26 research outputs found

    Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps

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    We expanded GWAS discovery for type 2 diabetes (T2D) by combining data from 898,130 European-descent individuals (9% cases), after imputation to high-density reference panels. With these data, we (i) extend the inventory of T2D-risk variants (243 loci,135 newly implicated in T2D predisposition, comprising 403 distinct association signals); (ii) enrich discovery of lower-frequency risk alleles (80 index variants with minor allele frequency 2); (iii) substantially improve fine-mapping of causal variants (at 51 signals, one variant accounted for >80% posterior probability of association (PPA)); (iv) extend fine-mapping through integration of tissue-specific epigenomic information (islet regulatory annotations extend the number of variants with PPA >80% to 73); (v) highlight validated therapeutic targets (18 genes with associations attributable to coding variants); and (vi) demonstrate enhanced potential for clinical translation (genome-wide chip heritability explains 18% of T2D risk; individuals in the extremes of a T2D polygenic risk score differ more than ninefold in prevalence).Peer reviewe

    A comparison of two hypermixing fuel injectors in a supersonic combustor

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    Photoinduced axial quantization in chalcogenide microfiber resonators

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    We investigate axial quantization in chalcogenide (As2S3) whispering gallery mode microfiber resonators. A microcavity is fabricated using a positive photoinduced index perturbation in the microfiber, and the modes are excited through evanescent field coupling with a tapered silica fiber. We show that the modes of the unperturbed fiber split into ladders of modes due to the confinement along the axial direction of the fiber. The axial quantization of the modes is reproduced with a combination of numerical models. Due to the high nonlinearity and photosensitive properties of chalcogenide glasses, microcavities in these materials offer unique potential in nonlinear optics and sensing applications. © 2013 Optical Society of America
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