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More than 1,000 susceptibility loci have been identified through genome-wide association studies (GWAS) of common variants; however, the specific genes and full allelic spectrum of causal variants underlying these findings have not yet been defined. Here we used pooled next-generation sequencing to study 56 genes from regions associated with Crohn's disease in 350 cases and 350 controls. Through follow-up genotyping of 70 rare and low-frequency protein-altering variants in nine independent case-control series (16,054 Crohn's disease cases, 12,153 ulcerative colitis cases and 17,575 healthy controls), we identified four additional independent risk factors in NOD2, two additional protective variants in IL23R, a highly significant association with a protective splice variant in CARD9 (P < 1 × 10(-16), odds ratio ≈ 0.29) and additional associations with coding variants in IL18RAP, CUL2, C1orf106, PTPN22 and MUC19. We extend the results of successful GWAS by identifying new, rare and probably functional variants that could aid functional experiments and predictive models.  相似文献   
915.
Genome-wide association studies have identified 11 common variants convincingly associated with coronary artery disease (CAD)1??, a modest number considering the apparent heritability of CAD?. All of these variants have been discovered in European populations. We report a meta-analysis of four large genome-wide association studies of CAD, with ~575,000 genotyped SNPs in a discovery dataset comprising 15,420 individuals with CAD (cases) (8,424 Europeans and 6,996 South Asians) and 15,062 controls. There was little evidence for ancestry-specific associations, supporting the use of combined analyses. Replication in an independent sample of 21,408 cases and 19,185 controls identified five loci newly associated with CAD (P < 5 × 10?? in the combined discovery and replication analysis): LIPA on 10q23, PDGFD on 11q22, ADAMTS7-MORF4L1 on 15q25, a gene rich locus on 7q22 and KIAA1462 on 10p11. The CAD-associated SNP in the PDGFD locus showed tissue-specific cis expression quantitative trait locus effects. These findings implicate new pathways for CAD susceptibility.  相似文献   
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In the background of the green transformation of the economy and society, the ESG performance of enterprises has been paid more and more attention in the investment decision-making.However, previous studies have inadequately explored how the ESG performance affects corporate financing costs. Based on the information asymmetry theory, this paper analyzes the impact mechanism of ESG performance on corporate financing costs. Then, taking 1044 A-share listed companies in2016–2020 as a sample, throug...  相似文献   
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卷取机用途广泛,卷筒则是热轧卷取机的核心部件,从卷筒部件结构、工作原理和主要技术要求入手,深入开展了卷筒部件的制造工艺研究,重点分析了核心零件--芯轴的结构及加工工艺,对卷筒部件的卷曲圆采用“先组装后加工”的整体加工方案及芯轴加工采取“利用中心孔,配中心堵”的技术措施,卷简部件及其芯轴制造获得一次成功。  相似文献   
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To express human phospholipid hydroperoxide glutathione peroxidase (PHGPx) in eukaryotic cells and to study its antiviral effect against Coxsackievirus B3m (CVB3m) in vitro, PHGPx cDNA was amplified from a human testis library using specific primers and cloned into expression vector pcDNA3. I/His. Expression of PHGPx was performed in COS-1 cells. The antiviral effect was studied by the treatment of HeLa cells with the recombinant PHGPx. Results showed that the activity of PHGPx expressed in COS-1 cells was 5-fold higher than that in control group, and it inhibited the cytopathic effect on HeLa cells caused by CVB3m. It can be concluded that recombinant PHGPx expressed in COS-1 cells has antiviral effect against CVB3m in vitro.  相似文献   
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1.IntroductionLetRpbeapdimellsionalEuclideanspace,KanirreflekivebinaryrelationonRp.ForyEgr,thelowersection0fy(w.r-tK)istheset(`y)={y'ly'Ky}.TheinteriorrelationK'of`isdefinedasy,`"yifandonlyify'EIllt(Ky)(Int,Clmeaninteriorandclosure0faset).Letf:Rn- Rp,g:R"- RmbelocallyLipschitzvector-valuedfunctions(i.e.eachcomponelltofthemislocallyLipschitz),Kaclosedc0nvexpointedconewithnonemptyinieri0rinRm.SetX={xER"lg(x)E-K}.TheMultiobjectiveProgramming,withf,X,Kasobjectivefuncti0n,feasiblesetan…  相似文献   
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