管理科学与信息

<正> 一、管理的地位与作用管理的含义,就是在一定的社会生产条件下,按照一定的原则、程序和方法,通过对管理对象的诸要素(人、财、物、信息等)及其运动过程实施各种管理职能(计划、组织、指挥和控制等)活动,使之达到预期的目的。管理总是相对于特定的管理对象而言的。从根本上说,任何事物都有自身的规律性,管理当然亦不例外,无论管理什     

Evidence of widespread selection on standing variation in Europe at height-associated SNPs

Strong signatures of positive selection at newly arising genetic variants are well documented in humans, but this form of selection may not be widespread in recent human evolution. Because many human traits are highly polygenic and partly determined by common, ancient genetic variation, an alternative model for rapid genetic adaptation has been proposed: weak selection acting on many pre-existing (standing) genetic variants, or polygenic adaptation. By studying height, a classic polygenic trait, we demonstrate the first human signature of widespread selection on standing variation. We show that frequencies of alleles associated with increased height, both at known loci and genome wide, are systematically elevated in Northern Europeans compared with Southern Europeans (P < 4.3 × 10(-4)). This pattern mirrors intra-European height differences and is not confounded by ancestry or other ascertainment biases. The systematic frequency differences are consistent with the presence of widespread weak selection (selection coefficients ～10(-3)-10(-5) per allele) rather than genetic drift alone (P < 10(-15)).     

Mutations in NMNAT1 cause Leber congenital amaurosis and identify a new disease pathway for retinal degeneration

Leber congenital amaurosis (LCA) is a blinding retinal disease that presents within the first year after birth. Using exome sequencing, we identified mutations in the nicotinamide adenine dinucleotide (NAD) synthase gene NMNAT1 encoding nicotinamide mononucleotide adenylyltransferase 1 in eight families with LCA, including the family in which LCA was originally linked to the LCA9 locus. Notably, all individuals with NMNAT1 mutations also have macular colobomas, which are severe degenerative entities of the central retina (fovea) devoid of tissue and photoreceptors. Functional assays of the proteins encoded by the mutant alleles identified in our study showed that the mutations reduce the enzymatic activity of NMNAT1 in NAD biosynthesis and affect protein folding. Of note, recent characterization of the slow Wallerian degeneration (Wld(s)) mouse model, in which prolonged axonal survival after injury is observed, identified NMNAT1 as a neuroprotective protein when ectopically expressed. Our findings identify a new disease mechanism underlying LCA and provide the first link between endogenous NMNAT1 dysfunction and a human nervous system disorder.     

Conditional and joint multiple-SNP analysis of GWAS summary statistics identifies additional variants influencing complex traits

We present an approximate conditional and joint association analysis that can use summary-level statistics from a meta-analysis of genome-wide association studies (GWAS) and estimated linkage disequilibrium (LD) from a reference sample with individual-level genotype data. Using this method, we analyzed meta-analysis summary data from the GIANT Consortium for height and body mass index (BMI), with the LD structure estimated from genotype data in two independent cohorts. We identified 36 loci with multiple associated variants for height (38 leading and 49 additional SNPs, 87 in total) via a genome-wide SNP selection procedure. The 49 new SNPs explain approximately 1.3% of variance, nearly doubling the heritability explained at the 36 loci. We did not find any locus showing multiple associated SNPs for BMI. The method we present is computationally fast and is also applicable to case-control data, which we demonstrate in an example from meta-analysis of type 2 diabetes by the DIAGRAM Consortium.     

A Sensitivity-Based Heuristic Search for Constrained Optimization in Complex Systems

1.INTRODUCTIONThealgorithmforconstrainedoptimizationincomplexsystemscanbedividedintotwoclasses:exactandheuristicmethods.Theexactmethods,whicharepartlysummarizedbyTitanetal.[1],havecomputationalrequiremeatsthatgrowexponentiajlywiththesizeoftheproblem.AlthoughheuristicmethodshavemodestcomputationalrequirementsandareeasytoAnplemellt,theyaregenerallyforredundancyallocation[2-4].2.S~EMENTOFProBLEM2.1NotationN:nUmberofcomponents;M:numberofconstraints;Rs:systemreliability;Rj:thereliabili…     

Analysis of Reliability for 3-State Device Network with Link-Capacities

1.INTRODUCTION2-statesystemreliabilityoftenassumesthatthesystemisrepresentedbyaprobabilisticgraphG=(V,E),withasetV~{yi,v2,'',}ofvenicesandasetE~{el,e2,'',}ofedges(orlinks,branches)containedinit.Thesystemisfunctioningifthereexistsapathfromtheinputnodetotheoutputnode.Thusthereliabilityisconsideredwithamatterofconnectivityonlyandthereliabilityanalysishasbeenprimarilyconcernedwiththeenumerationofpathesorcutsinthereferences[1-4].Butinmanyphysicalsystemsuchaspowertransmissionsystems,oilorwat…     

DIAGNOSTICS FOR EMPIRICAL BAYES MODELS

1.IntroductionInthelilleaxmodels,manykindsofBayesiandiagnosticshavebeenproposedtoassesstheinfluenceofeaChindividualobservationandthelocalinfluenceofminorperturbationsontheposteriordistributioll(see,[l--4])oronthepredictionoffutuxeobservation(see[5]).However,allthosediagnosticscannotbedirectlyappliedtotheempiricalBayes(EB)models(see[6]and[7]).Inthisarticle,westudythediagnosticproblemsinEBmodelssystematically.FirstlyjadeletiondiagllosticisobtainedtoexaminethesensitivityofeachcaseonEBestimate…