1,664 research outputs found

    COMPLEMENT-MEDIATED ADIPOCYTE LYSIS BY NEPHRITIC FACTOR SERA

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    Recent data indicate a previously unsuspected link between the complement system and adipocyte biology. Murine adipocytes produce key components of the alternative pathway of complement and are able to activate this pathway. This suggested to us an explanation for adipose tissue loss in partial lipodystrophy, a rare human condition usually associated with the immunoglobulin G(IgG) autoantibody nephritic factor (NeF) which leads to enhanced alternative pathway activation in vivo. We hypothesized that in the presence of NeF, there is dysregulated complement activation at the membrane of the adipocyte, leading to adipocyte lysis. Here we show that adipocytes explanted from rat epididymal fat pads are lysed by NeF-containing sera but not by control sera. A similar pattern is seen with IgG fractions of these sera. Adipocyte lysis in the presence of NeF is associated with the generation of fluid-phase terminal complement complexes, the level of which correlates closely with the level of lactate dehydrogenase, a marker of cell lysis. Lysis is abolished by ethylenediaminetetraacetic acid, which chelates divalent cations and prevents complement activation, and reduced by an antibody to factor D, a key component of the alternative pathway. These data provide an explanation for the previously obscure link between NeF and fat cell damage

    The impact of poor asthma control among asthma patients treated with inhaled corticosteroids plus long-acting Ī²2-agonists in the United Kingdom : a cross-sectional analysis

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    This study was sponsored by Boehringer Ingelheim Ltd UK, which was involved in all stages of the study conduct and analysis and also funded all costs associated with the development of the manuscript. The authors acknowledge Kantar Health and Errol J Philip for providing medical writing support. Editorial assistance and medical writing support was also provided by Michelle Rebello, PhD, and Suchita Nath-Sain, PhD, of Cactus Communications. This study was sponsored by Boehringer Ingelheim Ltd., UK, which also funded all costs associated with the development of the manuscript. Author Correction, npj Primary Care Respiratory Medicine 27, Article number: 65 (2017) doi:10.1038/s41533-017-0063-5, 05 December 2017 Correction to:npj Primary Care Respiratory Medicine (2017); doi:10.1038/s41533-017-0014-1; Published 09 March 2017Peer reviewedPublisher PD

    Syntax error based quantification of the learning progress of the novice programmer

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    Ā© 2018 Association for Computing Machinery. Recent data-driven research has produced metrics for quantifying a novice programmerā€™s error profile, such as Jadudā€™s error quotient. However, these metrics tend to be context dependent and contain free parameters. This paper reviews the caveats of such metrics and proposes a more general approach to developing a metric. The online implementation of the proposed metric is publicly available at http://online-analysis-demo.herokuapp.com/

    ArAl: An Online Tool for Source Code Snapshot Metadata Analysis

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    Ā© 2019 Association for Computing Machinery. Several systems that collect data from students' problem solving processes exist. Within computing education research, such data has been used for multiple purposes, ranging from assessing students' problem solving strategies to detecting struggling students. To date, however, the majority of the analysis has been conducted by individual researchers or research groups using case by case methodologies. Our belief is that with increasing possibilities for data collection from students' learning process, researchers and instructors will benefit from ready-made analysis tools. In this study, we present ArAl, an online machine learning based platform for analyzing programming source code snapshot data. The benefit of ArAl is two-fold. The computing education researcher can use ArAl to analyze the source code snapshot data collected from their own institute. Also, the website provides a collection of well-documented machine learning and statistics based tools to investigate possible correlation between different variables. The presented web-portal is available at online-analysisdemo. herokuapp.com. This tool could be applied in many different subject areas given appropriate performance data

    Unveiling Clusters of RNA Transcript Pairs Associated with Markers of Alzheimer's Disease Progression

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    Background: One primary goal of transcriptomic studies is identifying gene expression patterns correlating with disease progression. This is usually achieved by considering transcripts that independently pass an arbitrary threshold (e.g. p<0.05). In diseases involving severe perturbations of multiple molecular systems, such as Alzheimer's disease (AD), this univariate approach often results in a large list of seemingly unrelated transcripts. We utilised a powerful multivariate clustering approach to identify clusters of RNA biomarkers strongly associated with markers of AD progression. We discuss the value of considering pairs of transcripts which, in contrast to individual transcripts, helps avoid natural human transcriptome variation that can overshadow disease-related changes. Methodology/Principal Findings: We re-analysed a dataset of hippocampal transcript levels in nine controls and 22 patients with varying degrees of AD. A large-scale clustering approach determined groups of transcript probe sets that correlate strongly with measures of AD progression, including both clinical and neuropathological measures and quantifiers of the characteristic transcriptome shift from control to severe AD. This enabled identification of restricted groups of highly correlated probe sets from an initial list of 1,372 previously published by our group. We repeated this analysis on an expanded dataset that included all pair-wise combinations of the 1,372 probe sets. As clustering of this massive dataset is unfeasible using standard computational tools, we adapted and re-implemented a clustering algorithm that uses external memory algorithmic approach. This identified various pairs that strongly correlated with markers of AD progression and highlighted important biological pathways potentially involved in AD pathogenesis. Conclusions/Significance: Our analyses demonstrate that, although there exists a relatively large molecular signature of AD progression, only a small number of transcripts recurrently cluster with different markers of AD progression. Furthermore, considering the relationship between two transcripts can highlight important biological relationships that are missed when considering either transcript in isolation. Ā© 2012 Arefin et al

    Post-16 maths for all: the role of Core Maths

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    Core Maths qualifications were introduced in 2014 to increase post-16 maths participation in England, which is low compared to international competitors. This policy note summarises a three-year study investigating the adoption of Core Maths in schools and colleges. It highlights that Core Maths is well received by teachers and students, but national uptake remains low compared to the governmentā€™s initial hopes, and further support for Core Maths is needed
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