109 research outputs found

    PM-Pendulum Model: Conservatives Edge Labour in Votes and Seats

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    Last week, a group of academics gathered at LSE to discuss a variety of forecasting models. In this post, Matthew Lebo and Helmut Norpoth, both professors of political science at Stony Brook University in New York, discuss their PM-and-Pendulum model. Their model favours the Conservatives in terms of parliamentary seats, though predicts that Cameron will not win a majority. Further, they suggest that the SNP is likely to win 41 of 59 Scottish seats

    Somatic, germline and sex hierarchy regulated gene expression during Drosophila metamorphosis

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    <p>Abstract</p> <p>Background</p> <p><it>Drosophila melanogaster </it>undergoes a complete metamorphosis, during which time the larval male and female forms transition into sexually dimorphic, reproductive adult forms. To understand this complex morphogenetic process at a molecular-genetic level, whole genome microarray analyses were performed.</p> <p>Results</p> <p>The temporal gene expression patterns during metamorphosis were determined for all predicted genes, in both somatic and germline tissues of males and females separately. Temporal changes in transcript abundance for genes of known functions were found to correlate with known developmental processes that occur during metamorphosis. We find that large numbers of genes are sex-differentially expressed in both male and female germline tissues, and relatively few are sex-differentially expressed in somatic tissues. The majority of genes with somatic, sex-differential expression were found to be expressed in a stage-specific manner, suggesting that they mediate discrete developmental events. The <it>Sex-lethal </it>paralog, <it>CG3056</it>, displays somatic, male-biased expression at several time points in metamorphosis. Gene expression downstream of the somatic, sex determination genes <it>transformer </it>and <it>doublesex (dsx) </it>was examined in two-day old pupae, which allowed for the identification of genes regulated as a consequence of the sex determination hierarchy. These include the homeotic gene <it>abdominal A</it>, which is more highly expressed in females as compared to males, as a consequence of <it>dsx</it>. For most genes regulated downstream of <it>dsx </it>during pupal development, the mode of regulation is distinct from that observed for the well-studied direct targets of DSX, <it>Yolk protein 1 </it>and <it>2</it>.</p> <p>Conclusion</p> <p>The data and analyses presented here provide a comprehensive assessment of gene expression during metamorphosis in each sex, in both somatic and germline tissues. Many of the genes that underlie critical developmental processes during metamorphosis, including sex-specific processes, have been identified. These results provide a framework for further functional studies on the regulation of sex-specific development.</p

    Marine Boundary Layer Clouds Associated with Coastally Trapped Disturbances: Observations and Model Simulations

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    This work has been accepted to Journal of Atmospheric Sciences. The AMS does not guarantee that the copy provided here is an accurate copy of the final published work.Modeling marine low clouds and fog in coastal environments remains an outstanding challenge due to the inherently complex ocean–land–atmosphere system. This is especially important in the context of global circulation models due to the profound radiative impact of these clouds. This study utilizes aircraft and satellite measurements, in addition to numerical simulations using the Weather Research and Forecasting (WRF) Model, to examine three well-observed coastally trapped disturbance (CTD) events from June 2006, July 2011, and July 2015. Cloud water-soluble ionic and elemental composition analyses conducted for two of the CTD cases indicate that anthropogenic aerosol sources may impact CTD cloud decks due to synoptic-scale patterns associated with CTD initiation. In general, the dynamics and thermodynamics of the CTD systems are well represented and are relatively insensitive to the choice of physics parameterizations; however, a set of WRF simulations suggests that the treatment of model physics strongly influences CTD cloud field evolution. Specifically, cloud liquid water path (LWP) is highly sensitive to the choice of the planetary boundary layer (PBL) scheme; in many instances, the PBL scheme affects cloud extent and LWP values as much as or more than the microphysics scheme. Results suggest that differences in the treatment of entrainment and vertical mixing in the Yonsei University (nonlocal) and Mellor–Yamada–Janjić (local) PBL schemes may play a significant role. The impact of using different driving models—namely, the North American Mesoscale Forecast System (NAM) 12-km analysis and the NCEP North American Regional Reanalysis (NARR) 32-km products—is also investigated

    Marine Boundary Layer Clouds Associated with Coastally Trapped Disturbances: Observations and Model Simulations

    Get PDF
    Modeling marine low clouds and fog in coastal environments remains an outstanding challenge due to the inherently complex ocean–land–atmosphere system. This is especially important in the context of global circulation models due to the profound radiative impact of these clouds. This study utilizes aircraft and satellite measurements, in addition to numerical simulations using the Weather Research and Forecasting (WRF) Model, to examine three well-observed coastally trapped disturbance (CTD) events from June 2006, July 2011, and July 2015. Cloud water-soluble ionic and elemental composition analyses conducted for two of the CTD cases indicate that anthropogenic aerosol sources may impact CTD cloud decks due to synoptic-scale patterns associated with CTD initiation. In general, the dynamics and thermodynamics of the CTD systems are well represented and are relatively insensitive to the choice of physics parameterizations; however, a set of WRF simulations suggests that the treatment of model physics strongly influences CTD cloud field evolution. Specifically, cloud liquid water path (LWP) is highly sensitive to the choice of the planetary boundary layer (PBL) scheme; in many instances, the PBL scheme affects cloud extent and LWP values as much as or more than the microphysics scheme. Results suggest that differences in the treatment of entrainment and vertical mixing in the Yonsei University (nonlocal) and Mellor–Yamada–Janjić (local) PBL schemes may play a significant role. The impact of using different driving models—namely, the North American Mesoscale Forecast System (NAM) 12-km analysis and the NCEP North American Regional Reanalysis (NARR) 32-km products—is also investigated

    Bioinformatics Workflow for Clinical Whole Genome Sequencing at Partners HealthCare Personalized Medicine

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    Effective implementation of precision medicine will be enhanced by a thorough understanding of each patient’s genetic composition to better treat his or her presenting symptoms or mitigate the onset of disease. This ideally includes the sequence information of a complete genome for each individual. At Partners HealthCare Personalized Medicine, we have developed a clinical process for whole genome sequencing (WGS) with application in both healthy individuals and those with disease. In this manuscript, we will describe our bioinformatics strategy to efficiently process and deliver genomic data to geneticists for clinical interpretation. We describe the handling of data from FASTQ to the final variant list for clinical review for the final report. We will also discuss our methodology for validating this workflow and the cost implications of running WGS

    Polygenic Prediction of Weight and Obesity Trajectories from Birth to Adulthood

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    Severe obesity is a rapidly growing global health threat. Although often attributed to unhealthy lifestyle choices or environmental factors, obesity is known to be heritable and highly polygenic; the majority of inherited susceptibility is related to the cumulative effect of many common DNA variants. Here we derive and validate a new polygenic predictor comprised of 2.1 million common variants to quantify this susceptibility and test this predictor in more than 300,000 individuals ranging from middle age to birth. Among middle-aged adults, we observe a 13-kg gradient in weight and a 25-fold gradient in risk of severe obesity across polygenic score deciles. In a longitudinal birth cohort, we note minimal differences in birthweight across score deciles, but a significant gradient emerged in early childhood and reached 12 kg by 18 years of age. This new approach to quantify inherited susceptibility to obesity affords new opportunities for clinical prevention and mechanistic assessment. © 2019 Author(s)National Human Genome Research Institute (1K08HG0101)Wellcome Trust (202802/Z/16/Z)University of Bristol NIHR Biomedical Research Centre (S- BRC-1215-20011)National Human Genome Research Institute (HG008895)National Heart, Lung, and Blood Institute (NHLBI) HHSN268201300025CNational Heart, Lung, and Blood Institute (NHLBI) HHSN268201300026CNational Heart, Lung, and Blood Institute (NHLBI) HHSN268201300027CNational Heart, Lung, and Blood Institute (NHLBI) HHSN268201300028CNational Heart, Lung, and Blood Institute (NHLBI) HHSN268201300029CNational Heart, Lung, and Blood Institute (NHLBI) HHSN268200900041CNational Institute on Aging (AG0005)NHLBI (AG0005)National Human Genome Research Institute (U01-HG004729)National Human Genome Research Institute (U01-HG04424)National Human Genome Research Institute (U01-HG004446)Wellcome (102215/2/13/2

    Performance of ACMG-AMP Variant-Interpretation Guidelines among Nine Laboratories in the Clinical Sequencing Exploratory Research Consortium

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    Evaluating the pathogenicity of a variant is challenging given the plethora of types of genetic evidence that laboratories consider. Deciding how to weigh each type of evidence is difficult, and standards have been needed. In 2015, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) published guidelines for the assessment of variants in genes associated with Mendelian diseases. Nine molecular diagnostic laboratories involved in the Clinical Sequencing Exploratory Research (CSER) consortium piloted these guidelines on 99 variants spanning all categories (pathogenic, likely pathogenic, uncertain significance, likely benign, and benign). Nine variants were distributed to all laboratories, and the remaining 90 were evaluated by three laboratories. The laboratories classified each variant by using both the laboratory's own method and the ACMG-AMP criteria. The agreement between the two methods used within laboratories was high (K-alpha = 0.91) with 79% concordance. However, there was only 34% concordance for either classification system across laboratories. After consensus discussions and detailed review of the ACMG-AMP criteria, concordance increased to 71%. Causes of initial discordance in ACMG-AMP classifications were identified, and recommendations on clarification and increased specification of the ACMG-AMP criteria were made. In summary, although an initial pilot of the ACMG-AMP guidelines did not lead to increased concordance in variant interpretation, comparing variant interpretations to identify differences and having a common framework to facilitate resolution of those differences were beneficial for improving agreement, allowing iterative movement toward increased reporting consistency for variants in genes associated with monogenic disease
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