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991.
Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes 总被引:1,自引:0,他引:1
Zeggini E Scott LJ Saxena R Voight BF Marchini JL Hu T de Bakker PI Abecasis GR Almgren P Andersen G Ardlie K Boström KB Bergman RN Bonnycastle LL Borch-Johnsen K Burtt NP Chen H Chines PS Daly MJ Deodhar P Ding CJ Doney AS Duren WL Elliott KS Erdos MR Frayling TM Freathy RM Gianniny L Grallert H Grarup N Groves CJ Guiducci C Hansen T Herder C Hitman GA Hughes TE Isomaa B Jackson AU Jørgensen T Kong A Kubalanza K Kuruvilla FG Kuusisto J Langenberg C Lango H Lauritzen T Li Y Lindgren CM 《Nature genetics》2008,40(5):638-645
Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and approximately 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P = 5.0 x 10(-14)), CDC123-CAMK1D (P = 1.2 x 10(-10)), TSPAN8-LGR5 (P = 1.1 x 10(-9)), THADA (P = 1.1 x 10(-9)), ADAMTS9 (P = 1.2 x 10(-8)) and NOTCH2 (P = 4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D. 相似文献
992.
van Es MA van Vught PW Blauw HM Franke L Saris CG Van den Bosch L de Jong SW de Jong V Baas F van't Slot R Lemmens R Schelhaas HJ Birve A Sleegers K Van Broeckhoven C Schymick JC Traynor BJ Wokke JH Wijmenga C Robberecht W Andersen PM Veldink JH Ophoff RA van den Berg LH 《Nature genetics》2008,40(1):29-31
We identified a SNP in the DPP6 gene that is consistently strongly associated with susceptibility to amyotrophic lateral sclerosis (ALS) in different populations of European ancestry, with an overall P value of 5.04 x 10(-8) in 1,767 cases and 1,916 healthy controls and with an odds ratio of 1.30 (95% confidence interval (CI) of 1.18-1.43). Our finding is the first report of a genome-wide significant association with sporadic ALS and may be a target for future functional studies. 相似文献
993.
Pravenec M Churchill PC Churchill MC Viklicky O Kazdova L Aitman TJ Petretto E Hubner N Wallace CA Zimdahl H Zidek V Landa V Dunbar J Bidani A Griffin K Qi N Maxova M Kren V Mlejnek P Wang J Kurtz TW 《Nature genetics》2008,40(8):952-954
To identify renally expressed genes that influence risk for hypertension, we integrated expression quantitative trait locus (QTL) analysis of the kidney with genome-wide correlation analysis of renal expression profiles and blood pressure in recombinant inbred strains derived from the spontaneously hypertensive rat (SHR). This strategy, together with renal transplantation studies in SHR progenitor, transgenic and congenic strains, identified deficient renal expression of Cd36 encoding fatty acid translocase as a genetically determined risk factor for spontaneous hypertension. 相似文献
994.
Vermulst M Wanagat J Kujoth GC Bielas JH Rabinovitch PS Prolla TA Loeb LA 《Nature genetics》2008,40(4):392-394
Mitochondrial DNA (mtDNA) mutations are thought to have a causal role in many age-related pathologies. Here we identify mtDNA deletions as a driving force behind the premature aging phenotype of mitochondrial mutator mice, and provide evidence for a homology-directed DNA repair mechanism in mitochondria that is directly linked to the formation of mtDNA deletions. In addition, our results demonstrate that the rate at which mtDNA mutations reach phenotypic expression differs markedly among tissues, which may be an important factor in determining the tolerance of a tissue to random mitochondrial mutagenesis. 相似文献
995.
Vitart V Rudan I Hayward C Gray NK Floyd J Palmer CN Knott SA Kolcic I Polasek O Graessler J Wilson JF Marinaki A Riches PL Shu X Janicijevic B Smolej-Narancic N Gorgoni B Morgan J Campbell S Biloglav Z Barac-Lauc L Pericic M Klaric IM Zgaga L Skaric-Juric T Wild SH Richardson WA Hohenstein P Kimber CH Tenesa A Donnelly LA Fairbanks LD Aringer M McKeigue PM Ralston SH Morris AD Rudan P Hastie ND Campbell H Wright AF 《Nature genetics》2008,40(4):437-442
Uric acid is the end product of purine metabolism in humans and great apes, which have lost hepatic uricase activity, leading to uniquely high serum uric acid concentrations (200-500 microM) compared with other mammals (3-120 microM). About 70% of daily urate disposal occurs via the kidneys, and in 5-25% of the human population, impaired renal excretion leads to hyperuricemia. About 10% of people with hyperuricemia develop gout, an inflammatory arthritis that results from deposition of monosodium urate crystals in the joint. We have identified genetic variants within a transporter gene, SLC2A9, that explain 1.7-5.3% of the variance in serum uric acid concentrations, following a genome-wide association scan in a Croatian population sample. SLC2A9 variants were also associated with low fractional excretion of uric acid and/or gout in UK, Croatian and German population samples. SLC2A9 is a known fructose transporter, and we now show that it has strong uric acid transport activity in Xenopus laevis oocytes. 相似文献
996.
COMPARISON OF TWO METHODS OF OPERATING THEATRE PLANNING: APPLICATION IN BELGIAN HOSPITAL 总被引:3,自引:0,他引:3
Sondes CHAABANE~ Nadine MESKENS~ Alain GUINET~ Marius LAURENT~ ~LAMIH laboratory Valenciennes University Valenciennes Cedex France ~MAAD Laboratory FUCAM Mons Belgium ~LIESP Laboratory INSA-Lyon France ~CHU de TIVOLI La Louvière Belgium 《系统科学与系统工程学报(英文版)》2008,17(2):171-186
Operating Theatre is the centre of the hospital management's efforts. It constitutes the most expensive sector with more than 10% of the intended operating budget of the hospital. To reduce the costs while maintaining a good quality of care, one of the solutions is to improve the existent planning and scheduling methods by improving the services and surgical specialty coordination or finding the best estimation of surgical case durations. The other solution is to construct an effective surgical case plan and schedule. The operating theatre planning and scheduling is the two important steps, which aim to make a surgical case programming with an objective of obtaining a realizable and efficient surgical case schedule. This paper focuses on the first step, the operating theatre planning problem. Two planning methods are introduced and compared. Real data of a Belgian university hospital "Tivoli" are used for the experiments. 相似文献
997.
An improved branch-and-bound algorithm to minimize the weighted flowtime on identical parallel machines with family setup times 总被引:1,自引:0,他引:1
Belgacem BETTAYEB Imed KACEM Kondo H.ADJALLAH LOSI-ICD CNRS FRE Universitéde technologie de Troyes France 《系统科学与系统工程学报(英文版)》2008,17(4):446-459
This article investigates identical parallel machines scheduling with family setup times. The objective function being the weighted sum of completion times, the problem is known to be strongly NP-hard. We propose a constructive heuristic algorithm and three complementary lower bounds. Two of these bounds proceed by elimination of setup times or by distributing each of them to jobs of the corresponding family, while the third one is based on a lagrangian relaxation. The bounds and the heuristic are incorporated into a branch-and-bound algorithm. Experimental results obtained outperform those of the methods presented in previous works, in term of size of solved problems. 相似文献
998.
Interval Time Series Analysis with an Application to the Sterling-Dollar Exchange Rate 总被引:2,自引:0,他引:2
Traditional econometrics has long employed "points" to measure time series data. In real life situations, however, it suffers the loss of volatility information, since many variables are bounded by intervals in a given period. To address this issue, this paper provides a new methodology for interval time series analysis. The concept of "interval stochastic process" is formally defined as a counterpart of "stochastic process" in point-based econometrics. The authors introduce the concepts of interval stationarity, interval statistics (including interval mean, interval variance, etc.) and propose an interval linear model to investigate the dynamic relationships between interval processes. A new interval-based optimization approach for estimation is proposed, and corresponding evaluation criteria are derived. To demonstrate that the new interval method provides valid results, an empirical example on the sterling-dollar exchange rate is presented. 相似文献
999.
In this study, a novel hybrid intelligent mining system integrating rough sets theory and support vector machines is developed to extract efficiently association rules from original information table for credit risk evaluation and analysis. In the proposed hybrid intelligent system, support vector machines are used as a tool to extract typical features and filter its noise, which are different from the previous studies where rough sets were only used as a preprocessor for support vector machines. Such an approach could reduce the information table and generate the final knowledge from the reduced information table by rough sets. Therefore, the proposed hybrid intelligent system overcomes the difficulty of extracting rules from a trained support vector machine classifier and possesses the robustness which is lacking for rough-set-based approaches. In addition, the effectiveness of the proposed hybrid intelligent system is illustrated with two real-world credit datasets. 相似文献
1000.
Joseph W. Dauben 《Archive for History of Exact Sciences》2008,62(2):91-178
In December and January of 1983–1984, archaeologists excavating the tomb of an ancient Chinese provincial bureaucrat at a
Western Han Dynasty site near Zhangjiashan, in Jiangling county, Hubei Province, discovered a number of books on bamboo strips,
including inter alia works on legal statutes, military practice, and medicine. Among these was a previously unknown mathematical work on some
200 bamboo strips, the
Suan shu shu, or Book of Numbers and Computations. Based upon other works found in the tomb, especially a copy of the
Er nian lü ling (Laws and Decrees of the Second Year (of the reign of empress Lü, i.e. Lü Hou)), archaeologists have dated the tomb to ca. 186 BCE (Lü Hou’s regency lasted from 188 to 180 BCE). The Suan shu shu, as the earliest yet discovered work devoted specifically to mathematics from ancient China, has stirred considerable interest
among Chinese historians of science. The translation and commentary offered here draw extensively on the works cited in Sect.
3 below. Several appendixes devoted to specific issues related to translating the Suan shu shu, including its title and the problem of determining English equivalents for various commodities that arise in the text, may
be found in Appendix II.
An erratum to this article can be found at 相似文献