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排序方式: 共有1247条查询结果,搜索用时 15 毫秒
981.
Painter JN Anderson CA Nyholt DR Macgregor S Lin J Lee SH Lambert A Zhao ZZ Roseman F Guo Q Gordon SD Wallace L Henders AK Visscher PM Kraft P Martin NG Morris AP Treloar SA Kennedy SH Missmer SA Montgomery GW Zondervan KT 《Nature genetics》2011,43(1):51-54
Endometriosis is a common gynecological disease associated with pelvic pain and subfertility. We conducted a genome-wide association study (GWAS) in 3,194 individuals with surgically confirmed endometriosis (cases) and 7,060 controls from Australia and the UK. Polygenic predictive modeling showed significantly increased genetic loading among 1,364 cases with moderate to severe endometriosis. The strongest association signal was on 7p15.2 (rs12700667) for 'all' endometriosis (P = 2.6 × 10??, odds ratio (OR) = 1.22, 95% CI 1.13-1.32) and for moderate to severe disease (P = 1.5 × 10??, OR = 1.38, 95% CI 1.24-1.53). We replicated rs12700667 in an independent cohort from the United States of 2,392 self-reported, surgically confirmed endometriosis cases and 2,271 controls (P = 1.2 × 10?3, OR = 1.17, 95% CI 1.06-1.28), resulting in a genome-wide significant P value of 1.4 × 10?? (OR = 1.20, 95% CI 1.13-1.27) for 'all' endometriosis in our combined datasets of 5,586 cases and 9,331 controls. rs12700667 is located in an intergenic region upstream of the plausible candidate genes NFE2L3 and HOXA10. 相似文献
982.
Hirota T Takahashi A Kubo M Tsunoda T Tomita K Doi S Fujita K Miyatake A Enomoto T Miyagawa T Adachi M Tanaka H Niimi A Matsumoto H Ito I Masuko H Sakamoto T Hizawa N Taniguchi M Lima JJ Irvin CG Peters SP Himes BE Litonjua AA Tantisira KG Weiss ST Kamatani N Nakamura Y Tamari M 《Nature genetics》2011,43(9):893-896
Bronchial asthma is a common inflammatory disease caused by the interaction of genetic and environmental factors. Through a genome-wide association study and a replication study consisting of a total of 7,171 individuals with adult asthma (cases) and 27,912 controls in the Japanese population, we identified five loci associated with susceptibility to adult asthma. In addition to the major histocompatibility complex and TSLP-WDR36 loci previously reported, we identified three additional loci: a USP38-GAB1 locus on chromosome 4q31 (combined P = 1.87 × 10(-12)), a locus on chromosome 10p14 (P = 1.79 × 10(-15)) and a gene-rich region on chromosome 12q13 (P = 2.33 × 10(-13)). We observed the most significant association with adult asthma at rs404860 in the major histocompatiblity complex region (P = 4.07 × 10(-23)), which is close to rs2070600, a SNP previously reported for association with FEV(1)/FVC in genome-wide association studies for lung function. Our findings offer a better understanding of the genetic contribution to asthma susceptibility. 相似文献
983.
984.
Edgar S 《Studies in history and philosophy of science》2008,39(1):54-65
This paper examines the anti-psychologism of Paul Natorp, a Marburg School Neo-Kantian. It identifies both Natorp’s principle argument against psychologism and the views underlying the argument that give it its force. Natorp’s argument depends for its success on his view that certain scientific laws constitute the intersubjective content of knowledge. That view in turn depends on Natorp’s conception of subjectivity, so it is only against the background of his conception of subjectivity that his reasons for rejecting psychologism make sense. This interpretation of Natorp suggests that attention paid to late nineteenth century theories of subjectivity and philosophy of psychology could improve our understanding of the emergence of anti-psychologism in that period. 相似文献
985.
针对D-S(Dempster-Shafer)证据理论中证据融合可能存在冲突的问题,通过考虑证据之间的关系及其本身的特性,提出一种基于Lance距离和信度熵的冲突证据融合方法。首先,利用Lance距离来度量证据之间的差异和冲突程度,并通过矩阵形式表示证据的可信度,再通过计算信度熵来度量证据的信息量,并以此表示证据的不确定度。其次,综合考虑证据的可信度和不确定度来衡量证据最终融合的折扣系数,并通过折扣系数修正原始证据。最后,采用Dempster合成规则进行证据融合得到最终结果。算例分析结果表明,所提方法较其他方法而言,收敛速度更快,融合结果更准确、可靠。 相似文献
986.
摘要:针对一代双动半膝关节定制化程度不高,缺少有效的韧带附丽系统等问题,设计出具有有效韧带附丽的二代双动半膝关节假体,并提出半膝关节韧带附丽概念。通过计算机软件技术设计路线,在一代双动半膝关节假体的原理和基础上进行韧带附丽装置设计和高度个体化仿生设计。利用快速成型技术制造的树脂假体模型进行在此韧带附丽装置下韧带附丽点的选择、韧带的走行与规律、及假体初始安装角度等探索性实验。二代双动半膝关节假体能够有效进行关节韧带重建,并保持良好的稳定性和运动功能。实验表明,选取接近生理状态下的韧带附丽点,并使用LARS韧带进行韧带重建时,双动半膝关节假体的最佳初始固定角度是关节屈曲105°的状态,此时胫骨前向松弛度为5.96±0.05mm,后向松弛度5.00±0.03mm二代双动半膝关节假体设计较一代更为合理有效。韧带附丽装置和附丽概念为膝关节韧带重建提供新的思路和方法。 相似文献
987.
基于遗传规划的相关关系预测方法研究 总被引:2,自引:0,他引:2
基于遗传规划的搜索寻优技术,给出了一种经济变量与其解释变量间相关关系的预测方法。该方法避开了统计中假设、变换的影响,可以获得显性预测函数表达式,能够处理回归分析法难以解决的非线性问题,比较适合经济变量间复杂关系的分析研究。计算过程中结合蒙特卡洛优化法改进了遗传规划的初始群体,从而提高了进化的全局收敛速度。同时,计算实例表明了预测结果的合理性。 相似文献
988.
Sansone SA Rocca-Serra P Field D Maguire E Taylor C Hofmann O Fang H Neumann S Tong W Amaral-Zettler L Begley K Booth T Bougueleret L Burns G Chapman B Clark T Coleman LA Copeland J Das S de Daruvar A de Matos P Dix I Edmunds S Evelo CT Forster MJ Gaudet P Gilbert J Goble C Griffin JL Jacob D Kleinjans J Harland L Haug K Hermjakob H Ho Sui SJ Laederach A Liang S Marshall S McGrath A Merrill E Reilly D Roux M Shamu CE Shang CA Steinbeck C Trefethen A Williams-Jones B Wolstencroft K Xenarios I 《Nature genetics》2012,44(2):121-126
To make full use of research data, the bioscience community needs to adopt technologies and reward mechanisms that support interoperability and promote the growth of an open 'data commoning' culture. Here we describe the prerequisites for data commoning and present an established and growing ecosystem of solutions using the shared 'Investigation-Study-Assay' framework to support that vision. 相似文献
989.
Lee JH Huynh M Silhavy JL Kim S Dixon-Salazar T Heiberg A Scott E Bafna V Hill KJ Collazo A Funari V Russ C Gabriel SB Mathern GW Gleeson JG 《Nature genetics》2012,44(8):941-945
De novo somatic mutations in focal areas are well documented in diseases such as neoplasia but are rarely reported in malformation of the developing brain. Hemimegalencephaly (HME) is characterized by overgrowth of either one of the two cerebral hemispheres. The molecular etiology of HME remains a mystery. The intractable epilepsy that is associated with HME can be relieved by the surgical treatment hemispherectomy, allowing sampling of diseased tissue. Exome sequencing and mass spectrometry analysis in paired brain-blood samples from individuals with HME (n = 20 cases) identified de novo somatic mutations in 30% of affected individuals in the PIK3CA, AKT3 and MTOR genes. A recurrent PIK3CA c.1633G>A mutation was found in four separate cases. Identified mutations were present in 8-40% of sequenced alleles in various brain regions and were associated with increased neuronal S6 protein phosphorylation in the brains of affected individuals, indicating aberrant activation of mammalian target of rapamycin (mTOR) signaling. Thus HME is probably a genetically mosaic disease caused by gain of function in phosphatidylinositol 3-kinase (PI3K)-AKT3-mTOR signaling. 相似文献
990.
Estrada K Styrkarsdottir U Evangelou E Hsu YH Duncan EL Ntzani EE Oei L Albagha OM Amin N Kemp JP Koller DL Li G Liu CT Minster RL Moayyeri A Vandenput L Willner D Xiao SM Yerges-Armstrong LM Zheng HF Alonso N Eriksson J Kammerer CM Kaptoge SK Leo PJ Thorleifsson G Wilson SG Wilson JF Aalto V Alen M Aragaki AK Aspelund T Center JR Dailiana Z Duggan DJ Garcia M Garcia-Giralt N Giroux S Hallmans G Hocking LJ Husted LB Jameson KA Khusainova R Kim GS Kooperberg C Koromila T Kruk M Laaksonen M 《Nature genetics》2012,44(5):491-501
Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility. 相似文献