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排序方式: 共有185条查询结果,搜索用时 31 毫秒
51.
Fujimoto A Totoki Y Abe T Boroevich KA Hosoda F Nguyen HH Aoki M Hosono N Kubo M Miya F Arai Y Takahashi H Shirakihara T Nagasaki M Shibuya T Nakano K Watanabe-Makino K Tanaka H Nakamura H Kusuda J Ojima H Shimada K Okusaka T Ueno M Shigekawa Y Kawakami Y Arihiro K Ohdan H Gotoh K Ishikawa O Ariizumi S Yamamoto M Yamada T Chayama K Kosuge T Yamaue H Kamatani N Miyano S Nakagama H Nakamura Y Tsunoda T Shibata T Nakagawa H 《Nature genetics》2012,44(7):760-764
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. We sequenced and analyzed the whole genomes of 27 HCCs, 25 of which were associated with hepatitis B or C virus infections, including two sets of multicentric tumors. Although no common somatic mutations were identified in the multicentric tumor pairs, their whole-genome substitution patterns were similar, suggesting that these tumors developed from independent mutations, although their shared etiological backgrounds may have strongly influenced their somatic mutation patterns. Statistical and functional analyses yielded a list of recurrently mutated genes. Multiple chromatin regulators, including ARID1A, ARID1B, ARID2, MLL and MLL3, were mutated in ~50% of the tumors. Hepatitis B virus genome integration in the TERT locus was frequently observed in a high clonal proportion. Our whole-genome sequencing analysis of HCCs identified the influence of etiological background on somatic mutation patterns and subsequent carcinogenesis, as well as recurrent mutations in chromatin regulators in HCCs. 相似文献
52.
In this paper we compare the in‐sample fit and out‐of‐sample forecasting performance of no‐arbitrage quadratic, essentially affine and dynamic Nelson–Siegel term structure models. In total, 11 model variants are evaluated, comprising five quadratic, four affine and two Nelson–Siegel models. Recursive re‐estimation and out‐of‐sample 1‐, 6‐ and 12‐month‐ahead forecasts are generated and evaluated using monthly US data for yields observed at maturities of 1, 6, 12, 24, 60 and 120 months. Our results indicate that quadratic models provide the best in‐sample fit, while the best out‐of‐sample performance is generated by three‐factor affine models and the dynamic Nelson–Siegel model variants. Statistical tests fail to identify one single best forecasting model class. Copyright © 2011 John Wiley & Sons, Ltd. 相似文献
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Rivas MA Beaudoin M Gardet A Stevens C Sharma Y Zhang CK Boucher G Ripke S Ellinghaus D Burtt N Fennell T Kirby A Latiano A Goyette P Green T Halfvarson J Haritunians T Korn JM Kuruvilla F Lagacé C Neale B Lo KS Schumm P Törkvist L;National Institute of Diabetes Digestive Kidney Diseases Inflammatory Bowel Disease Genetics Consortium 《Nature genetics》2011,43(11):1066-1073
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
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提出了声景观图的概念,用来作为城市声景观的表述方法.声景观图由客观信息、主观信息、关系分析以及模拟信息等组成.同时,文中还提出了开发声景观图的方法,包括信息收集、数据处理、制图、分析和模拟等过程.然后以日本佐贺市作为案例制作和分析了该区域的声景观图.最后分析了声景观图的应用方法和前景.文中提出的声景观图是表述和分析城市声景观的有效方法. 相似文献
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This paper describes a form of management epistemology, and suggests that it be called Decision Research, since it is primarily based on what can be learned from how managers make decisions in practice. The paper proposes that Decision Research be founded on generic cognitive structures that show a high degree of stability from east to west, old to new. These are described by Nomology, the science of the laws of the mind, and so have a positivist flavor. The paper develops, through an understanding of settled practice, how these structures are used in different cultures and fields of management. The richness of diversity it reveals encourages an interpretivist approach. Its value to Systemic Practice comes from the way that it provides frameworks and maps to elucidate issues and resolve situations in management. 相似文献
58.
Curran JE Jowett JB Elliott KS Gao Y Gluschenko K Wang J Abel Azim DM Cai G Mahaney MC Comuzzie AG Dyer TD Walder KR Zimmet P MacCluer JW Collier GR Kissebah AH Blangero J 《Nature genetics》2005,37(11):1234-1241
Chronic inflammation has a pathological role in many common diseases and is influenced by both genetic and environmental factors. Here we assess the role of genetic variation in selenoprotein S (SEPS1, also called SELS or SELENOS), a gene involved in stress response in the endoplasmic reticulum and inflammation control. After resequencing SEPS1, we genotyped 13 SNPs in 522 individuals from 92 families. As inflammation biomarkers, we measured plasma levels of IL-6, IL-1beta and TNF-alpha. Bayesian quantitative trait nucleotide analysis identified associations between SEPS1 polymorphisms and all three proinflammatory cytokines. One promoter variant, -105G --> A, showed strong evidence for an association with each cytokine (multivariate P = 0.0000002). Functional analysis of this polymorphism showed that the A variant significantly impaired SEPS1 expression after exposure to endoplasmic reticulum stress agents (P = 0.00006). Furthermore, suppression of SEPS1 by short interfering RNA in macrophage cells increased the release of IL-6 and TNF-alpha. To investigate further the significance of the observed associations, we genotyped -105G --> A in 419 Mexican American individuals from 23 families for replication. This analysis confirmed a significant association with both TNF-alpha (P = 0.0049) and IL-1beta (P = 0.0101). These results provide a direct mechanistic link between SEPS1 and the production of inflammatory cytokines and suggest that SEPS1 has a role in mediating inflammation. 相似文献
59.
Second-generation shRNA libraries covering the mouse and human genomes 总被引:23,自引:0,他引:23
60.