65 research outputs found

    A genome-wide screen for variants influencing certolizumab pegol response in a moderate to severe rheumatoid arthritis population

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    Certolizumab pegol (CZP) is a PEGylated Fc-free tumor necrosis factor (TNF) inhibitor antibody approved for use in the treatment of rheumatoid arthritis (RA), Crohn's disease, psoriatic arthritis, axial spondyloarthritis and psoriasis. In a clinical trial of patients with severe RA, CZP improved disease symptoms in approximately half of patients. However, variability in CZP efficacy remains a problem for clinicians, thus, the aim of this study was to identify genetic variants predictive of CZP response. We performed a genome-wide association study (GWAS) of 302 RA patients treated with CZP in the REALISTIC trial to identify common single nucleotide polymorphisms (SNPs) associated with treatment response. Wholeexome sequencing was also performed for 74 CZP extreme responders and non-responders within the same population, as well as 1546 population controls. No common SNPs or rare functional variants were significantly associated with CZP response, though a non-significant enrichment in the RA-implicated KCNK5 gene was observed. Two SNPs near spondin- 1 and semaphorin-4G approached genome-wide significance. The results of the current study did not provide an unambiguous predictor of CZP response

    Origins of the Ambient Solar Wind: Implications for Space Weather

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    The Sun's outer atmosphere is heated to temperatures of millions of degrees, and solar plasma flows out into interplanetary space at supersonic speeds. This paper reviews our current understanding of these interrelated problems: coronal heating and the acceleration of the ambient solar wind. We also discuss where the community stands in its ability to forecast how variations in the solar wind (i.e., fast and slow wind streams) impact the Earth. Although the last few decades have seen significant progress in observations and modeling, we still do not have a complete understanding of the relevant physical processes, nor do we have a quantitatively precise census of which coronal structures contribute to specific types of solar wind. Fast streams are known to be connected to the central regions of large coronal holes. Slow streams, however, appear to come from a wide range of sources, including streamers, pseudostreamers, coronal loops, active regions, and coronal hole boundaries. Complicating our understanding even more is the fact that processes such as turbulence, stream-stream interactions, and Coulomb collisions can make it difficult to unambiguously map a parcel measured at 1 AU back down to its coronal source. We also review recent progress -- in theoretical modeling, observational data analysis, and forecasting techniques that sit at the interface between data and theory -- that gives us hope that the above problems are indeed solvable.Comment: Accepted for publication in Space Science Reviews. Special issue connected with a 2016 ISSI workshop on "The Scientific Foundations of Space Weather." 44 pages, 9 figure

    Charge Transfer Reactions

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    Examining the Expert Gap in Parallel Programming

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    Abstract. Parallel programming is often regarded as one of the hardest programming disciplines. On the one hand, parallel programs are notoriously prone to concurrency errors; and, while trying to avoid such errors, achieving program performance becomes a significant challenge. As a result of the multicore revolution, parallel programming has however ceased to be a task for domain experts only. And for this reason, a large variety of languages and libraries have been proposed that promise to ease this task. This paper presents a study to investigate whether such approaches succeed in closing the gap between domain experts and mainstream developers. Four approaches are studied: Chapel, Cilk, Go, and Threading Building Blocks (TBB). Each approach is used to implement a suite of benchmark programs, which are then reviewed by notable experts in the language. By comparing original and revised versions with respect to source code size, coding time, execution time, and speedup, we gain insights into the importance of expert knowledge when using modern parallel programming approaches.
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