1000 resultados para 167-1013A


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Integrating evidence from multiple domains is useful in prioritizing disease candidate genes for subsequent testing. We ranked all known human genes (n = 3819) under linkage peaks in the Irish Study of High-Density Schizophrenia Families using three different evidence domains: 1) a meta-analysis of microarray gene expression results using the Stanley Brain collection, 2) a schizophrenia protein-protein interaction network, and 3) a systematic literature search. Each gene was assigned a domain-specific p-value and ranked after evaluating the evidence within each domain. For comparison to this
ranking process, a large-scale candidate gene hypothesis was also tested by including genes with Gene Ontology terms related to neurodevelopment. Subsequently, genotypes of 3725 SNPs in 167 genes from a custom Illumina iSelect array were used to evaluate the top ranked vs. hypothesis selected genes. Seventy-three genes were both highly ranked and involved in neurodevelopment (category 1) while 42 and 52 genes were exclusive to neurodevelopment (category 2) or highly ranked (category 3), respectively. The most significant associations were observed in genes PRKG1, PRKCE, and CNTN4 but no individual SNPs were significant after correction for multiple testing. Comparison of the approaches showed an excess of significant tests using the hypothesis-driven neurodevelopment category. Random selection of similar sized genes from two independent genome-wide association studies (GWAS) of schizophrenia showed the excess was unlikely by chance. In a further meta-analysis of three GWAS datasets, four candidate SNPs reached nominal significance. Although gene ranking using integrated sources of prior information did not enrich for significant results in the current experiment, gene selection using an a priori hypothesis (neurodevelopment) was superior to random selection. As such, further development of gene ranking strategies using more carefully selected sources of information is warranted.

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Ce ms. a appartenu à l'église paroissiale de Chaumont-en-Bassigny (Haute-Marne), comme en témoigne la mention du XVe s. "Ce livre cy appartient a l'eglise de Chaumont" (f. 184). En-dessous de cette mention figure la signature "H. Vigniery" (XVIe s.). En 1655, Claude Joly, chantre de Notre-Dame de Paris, l'a acheté à cette église (cf. l'inscription au contreplat sup., datée d'octobre 1658). Il a ensuite appartenu à la bibliothèque du chapitre de Notre-Dame de Paris, dont il porte l'ex-libris "A la bibliotheque de l'Eglise de Paris", précédé de la cote L5 (XVIIe s., contreplat sup.). Notre-Dame.

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We present a new composite of geomagnetic activity which is designed to be as homogeneous in its construction as possible. This is done by only combining data that, by virtue of the locations of the source observatories used, have similar responses to solar wind and IMF (interplanetary magnetic field) variations. This will enable us (in Part 2, Lockwood et al., 2013a) to use the new index to reconstruct the interplanetary magnetic field, B, back to 1846 with a full analysis of errors. Allowance is made for the effects of secular change in the geomagnetic field. The composite uses interdiurnal variation data from Helsinki for 1845–1890 (inclusive) and 1893–1896 and from Eskdalemuir from 1911 to the present. The gaps are filled using data from the Potsdam (1891–1892 and 1897–1907) and the nearby Seddin observatories (1908–1910) and intercalibration achieved using the Potsdam–Seddin sequence. The new index is termed IDV(1d) because it employs many of the principles of the IDV index derived by Svalgaard and Cliver (2010), inspired by the u index of Bartels (1932); however, we revert to using one-day (1d) means, as employed by Bartels, because the use of near-midnight values in IDV introduces contamination by the substorm current wedge auroral electrojet, giving noise and a dependence on solar wind speed that varies with latitude. The composite is compared with independent, early data from European-sector stations, Greenwich, St Petersburg, Parc St Maur, and Ekaterinburg, as well as the composite u index, compiled from 2–6 stations by Bartels, and the IDV index of Svalgaard and Cliver. Agreement is found to be extremely good in all cases, except two. Firstly, the Greenwich data are shown to have gradually degraded in quality until new instrumentation was installed in 1915. Secondly, we infer that the Bartels u index is increasingly unreliable before about 1886 and overestimates the solar cycle amplitude between 1872 and 1883 and this is amplified in the proxy data used before 1872. This is therefore also true of the IDV index which makes direct use of the u index values.