简介:AbstractDrug resistance via drug-resistant mutations in the human immunodeficiency virus (HIV) genome is the primary cause of antiviral therapy failure. Consequently, HIV drug resistance genotyping has become a critical approach in HIV prevention and control. Compared to the Sanger sequencing technology, high-throughput sequencing (HTS) technology has superior sensitivity and timeliness, with strong detection capabilities for low-frequency mutations. With the continued advancement of HTS technologies, their prominence in HIV drug resistance detection techniques has increased accordingly. This article will review the latest developments in HTS technology and its applications in HIV drug resistance testing.
简介:螺旋体serovars引起的威胁生活的感染为设计反细螺旋体病药要求需要。现在的学习包含对螺旋体的phosphoheptoseisomerase(GmhA)探索禁止者,它为lipopolysaccharide(LPS)是重要的生合成并且通过减少性的genomic途径作为一个普通的药目标被识别。GmhA模型在Modeller9v7被造。预言的模型的结构的精炼和精力最小化用艺术大师9.0被执行。精制模型可靠性通过Procheck,ProSA,ProQ和侧面3D被估计。基于底层虚拟高产量的屏蔽(VHTS)在Ligand。信息元数据库工具产生了354底层的一个内部图书馆结构的类似物。而且,从有每ligand的不同符合构造的内部图书馆的基于结构的VHTS提供了14个新奇竞争禁止者。和从VHTS获得的卓见的模型将是为开发反细螺旋体病的一个有希望的起点竞争禁止者指向LPS生合成小径。
简介:Objective:Hepatocellularcarcinoma(HCC)isaleadingcauseofcancer-relateddeaths.NovelserumbiomarkersarerequiredtoincreasethesensitivityandspecificityofserumscreeningforearlyHCCdiagnosis.ThisstudyemployedaquantitativeproteomicstrategytoanalyzethedifferentialexpressionofserumglycoproteinsbetweenHCCandnormalcontrolserumsamples.Methods:Lectinaffinitychromatography(LAC)wasusedtoenrichglycoproteinsfromtheserumsamples.Quantitativemassspectrometricanalysiscombinedwithstableisotopedimethyllabelingand2Dliquidchromatography(LC)separationswereperformedtoexaminethedifferentiallevelsofthedetectedproteinsbetweenHCCandcontrolserumsamples.Westernblotwasusedtoanalyzethedifferentialexpressionlevelsofthethreeserumproteins.Results:Atotalof2,280proteingroupswereidentifiedintheserumsamplesfromHCCpatientsbyusingthe2DLC-MS/MSmethod.Upto36proteinswereup-regulatedintheHCCserum,whereas19proteinsweredown-regulated.Threedifferentialglycoproteins,namely,fibrinogengammachain(FGG),FOS-likeantigen2(FOSL2),andα-1,6-mannosylglycoprotein6-β-N-acetylglucosaminyltransferaseB(MGAT5B)werevalidatedbyWesternblot.Allthesethreeproteinswereup-regulatedintheHCCserumsamples.Conclusion:AquantitativeglycoproteomicmethodwasestablishedandprovenusefultodeterminepotentialnovelbiomarkersforHCC.
简介:Hearingloss(HL)isthemostcommonsensorydisorder,affectingallagegroups,ethnicities,andgen-ders.AccordingtoWorldHealthOrganization(WHO)estimatesin2005,278millionpeopleworldwidehavemoderatetoprofoundHLinbothears.Resultsofthe2002NationalHealthInterviewSurveyindicatethatnearly31millionofallnon-institutionalizedadults(aged18andover)intheUnitedStateshavetroublehearing.Epidemiologicalstudieshaveestimatedthatapproximately50%ofprofoundHLcanbeattributedtogeneticcauses.Withover60genesimplicatedinnonsyndromichearingloss,itisalsoanextremelyhet-erogeneoustrait.Recentprogressinidentifyinggenesresponsibleforhearinglossenablesotolaryngologistsandotherclinicianstoapplymoleculardiagnosisbygenetictesting.Theadventofthe$1000genomehasthepotentialtorevolutionizetheidentificationofgenesandtheirmutationsunderlyinggeneticdisorders.ThisisespeciallytrueforextremelyheterogeneousMendelianconditionssuchasdeafness,wherethemuta-tion,andindeedthegene,maybeprivate.Therecenttechnologicaladvancesintarget-enrichmentmethodsandnextgenerationsequencingofferauniqueopportunitytobreakthroughthebarriersoflimitationsim-posedbygenearrays.Theseapproachesnowallowforthecompleteanalysisofallknowndeafness-causinggenesandwillresultinanewwaveofdiscoveriesoftheremaininggenesforMendeliandisorders.Thisre-viewfocusesondescribinggenotype-phenotypecorrelationsofthemostfrequentgenesincludingGJB2,whichisresponsibleformorethanhalfofcases,followedbyothercommongenesandondiscussingtheim-pactofgenomicadvancesforcomprehensivegenetictestingandgenediscoveryinhereditaryhearingloss.
简介:AbstractBackground:Infectious disease diagnostics often requires sensitive molecular assays that identify at both genus and species levels. For large scale screening, such as malaria screening for elimination, diagnostic assay can be a challenge, as both the throughput and cost of the assay must be considered. The requirement of nucleic acid extraction hampers the throughput of most molecular assays. Co-amplification of multiple species or multiplex identification either can result in missed diagnosis or are too costly for large-scale screening. A genus-and species-specific diagnostic assay with simplified procedure, high sensitivity and throughput is still needed. This study aimed to develop a sensitive and high-throughput approach for large-scale infectious disease screening.Methods:We developed multi-section Capture and Ligation Probe PCR (mCLIP-PCR) for the direct detection of RNA without extraction and reverse transcription. Multiple tailed sandwich hybridization probes were used to bind at genus-and species-specific sections of the target RNA to cooperatively capture the target onto a 96-well plate. After enzymatic ligation of the bound probes, a single-stranded DNA formed at each section with distinct tail sequence at the ends. They were separately PCR-amplified with primers corresponding to tail sequences for genus or species identification. We applied the method to the active screening of Plasmodium infections of 4,580 asymptomatic dried blood spot samples collected in malaria endemic areas and compared the results with standard qPCR using linear regression.Results:With multi-section cooperative capture but separate amplification strategy, we accurately identified genus Plasmodium and species P. falciparum and P. vivax without RNA extraction, with favorable sensitivities among the published reports. In the active screening, our method identified all 53 positive infections including two mixed infections, and two P. vivax infections that were missed by standard qPCR.Conclusions:mCLIP-PCR provides a sensitive and high-throughput approach to large-scale infectious disease screening with low cost and labor, making it a valuable tool for malaria elimination in endemic region.
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简介:Noise-inducedhearinglossisacommoncauseofacquiredhearinglossintheadultpopulation.Acousticoverstimulationcausescochleardamagethroughmechanicalstresstothetissue.Consequently,complexmolec-ularchangesareinitiated,andthesechangesleadtomorphologicalandbiologicalalterationsinthecochlea,whichinturncompromisethecochlearfunctionandcausehearingloss.Inthepast10years,therehavebeensignificantadvancesinourunderstandingofthemolecularmechanismsofnoise-inducedhearingloss.Theseadvancesareattributed,inpart,tothedevelopmentofhigh-throughputtechnologiesfortheglobalanalysesofmolecularchanges.Inthisreview,webrieflydescribethenewlydevelopedmethodsforinvestigatingthemo-lecularresponsesofthecochleatoacoustictraumaandtheknowledgegeneratedfromthesestudies.Wealsodiscussthestrengthsandlimitationsofeachtechniqueandthemajorchallengestoinvestigatecochleardegen-erationfollowingacousticinjury.
简介:High-throughputSNPgenotypingplatformsuseautomatedgenotypecallingalgo-rithmstoassigngenotypes.Whilethesealgorithmsworkefficientlyforindividualplatforms,theyarenotcompatiblewithotherplatforms,andhaveindividualbiasesthatresultinmissedgenotypecalls.HerewepresentdataontheuseofasecondcomplementarySNPgenotypeclusteringalgorithm.ThealgorithmwasoriginallydesignedforindividualfluorescentSNPgenotypingassays,andhasbeenopti-mizedtopermittheclusteringoflargedatasetsgeneratedfromcustom-designedAffymetrixSNPpanels.Inananalysisofdatafroma3Karraygenotypedon1,560samples,theadditionalanalysisincreasedtheoverallnumberofgenotypesbyover45,000,significantlyimprovingthecompletenessoftheexperimentaldata.Thisanalysissuggeststhattheuseofmultiplegenotypecallingalgorithmsmaybead-visableinhigh-throughputSNPgenotypingexperiments.ThesoftwareiswritteninPerlandisavailablefromthecorrespondingauthor.
简介:Saccharina是最重要的无热水设备生活水兵褐之一海藻的类。在这研究,我们分析了S的transcriptome。装饰用的梨树,它属于1000植物(OneKP)工程,由使用定序技术的下一代的高产量的DNA。未加工的数据的大约5.16GB被产生,并且有454bp的平均长度的65536脚手架与肥皂denovo汇编方法被装配。总共,19040unigenes被强风识别;25734脚手架被聚类进37基因本体论功能的组;6760脚手架被分类进25个轮牙范畴,以及被分到306条KEGG小径的2665脚手架。unigenes的多数比另外的cyanobacteria,海洋的硅藻,和植物包括棕色的水藻和硅藻展出了更多的类似到水藻。Saccharina装饰用的梨树有突出的能力积累象Br那样的卤素,我从海水经由halogenation处理。我们在S获得了42不同钒依赖者haloperoxidases(vHPO)。装饰用的梨树transcriptome数据,包括钒依赖者iodoperoxidase(vIPO)的5个片断和钒依赖者bromoperoxidase(vBPO)的37个片断。识别fulllengthS的复杂分析。装饰用的梨树vBPO1和S。装饰用的梨树vBPO2在在海洋的海藻的vBPOs和vIPOs之间的棕色的水藻和强壮的关系的种类之中揭示了vBPO的重要性。这研究将提高我们生物特征的理解和S的经济价值。装饰用的梨树种类。
简介:一个新奇高产量的系统,为分离和反应(4SR)叫了叠的片胶化系统,为DNA/RNA和蛋白质/肽的分析被开发。系统提供利用叠的片胶化的性质的一条新奇三维的胶化电气泳动途径。它同时允许多重样品反应以及被分开,出现一二维(mxn)样品装载系统。为这个目的,包含井(在这篇论文的100口井)的可变数字的高产量的多微的容器(MMV)被使用了,它用25公里做的是方形尺寸的polyacrylamide胶化。在electrophoretic分离以后,而且,包含一件需要的样品的片胶化能容易被移开并且继续到下一步。不同生物反应以及产品的连续分离有效地被执行处理DNA/RNA和蛋白质/肽。它证明这个系统有多种潜力被发展。
简介:Afterlessthanayearofoperation,theBaBarexperimentatSLAChascollectedalmost100millionparticlecollisioneventsinadatabaseapproaching165TB.Around20TBofdatahasbeenexportedviatheInternettotheBaBarregionalcenteratIN2P3inLyon,France,andaround40TBofsimulateddatahasbeenimportedfromtheLawrenceLivermoreNationalLaboratory(LLNL),BaBarCollaboratorsplantodoubledatacollectioneachyearandexportathirdofthedatatoIN2P3.SowithinafewyearstheSLACOC3(155Mbps)connectionwillbefullyutilizedbyfiletransfertoFrancealone.Upgradestoinfrastructureisessentialanddetailedunderstandingofperformanceissuesandtherequirementsforreliablehighthroughputtransfersiscritical.Inthistalkresultsfromactiveandpassivemonitoringanddirectmeasurementsofthroughputwillbereviewed.Methodsforachievingtheambitiousrequirementswillbediscussed.
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简介:Thereappeartobethreeprincipleforcesdrivingthefutureofnewdrugdevelopment:under-standingthegenome-transcrip-tome-protemecorrelations,under-standingandmappingproteinposttrans-lationalmodification(PTM)pathways,andintegrationofmassspectrometry(MS)techniquesintoroutineproteinidentificationandcharacterization.
简介:以便更精确地在粗野货物产量检验发展中的趋势,我们为货物产量的概率分发建模。等到在港口和处理设备的操作效率乘货物轮船花了,粗野货物产量被决定。粗野货物产量是为到达港口的每艘货物轮船决定货物产量的每个方面的所有复合变量的和。概率分发用Wald方程被决定。结果证明粗野货物产量的可变性首先取决于到达港口的不同货物轮船要求的不同时间。这个模型克服以前的模型的缺点:精确地决定未来的特定的价值的概率的无能粗野货物产量。我们货物产量的建议模型取决于在到达港口和在港口处理设备的运作的能力的一艘货物轮船要求的时间之间的关系。同时,影响粗野货物产量的关键因素被分析。为了测试模型,的效率,在山东省的一个端口的货物卷被用作一个例子。在案例研究,实际结果匹配我们的理论分析。
简介:WhiletheNetworkCodingcooperativerelaying(NC-relaying)hasthemeritofhighspectralefficiency,SuperpositionCodingrelaying(SC-relaying)hasthemeritofhighthroughput.Inthispaper,anovelconcept,codedcooperativerelaying,ispresented,whichisaunifiedschemeoftheNC-relayingandSC-relaying.FortheSC-relayingstrategywhichcanbeconsideredone-waycodedrelayingschemewithmulti-accesschannel,theclose-formsolutionoftheoutageprobabilitiesofthebasicsignalandadditionalsignalareobtainedfirstly.Secondly,theDiversity-and-MultiplexingTradeoff(DMT)characteristicsofbasicsignalandadditionalsignalareinvestigatedentirelyaswellastheoptimalclose-formsolutions.Thecomparednumericalanalysisshowstheevaluationerrorofthroughputbasedontheclose-formsolutionisabout0.15nats,whichiswithintheacceptableerrorrange.Duetothemutualeffectbetweenthebothsourcesignals,theavailablemaximalvaluesofthetwomultiplexinggainsarelessthan1.
简介:无线网络在更宽的光谱利用的时尚下面被开发(例如,认知无线电)并且多跳跃通讯(例如,无线网孔网络)。在这些范例,怎么有效地与最小化的相互的干扰分配光谱到不同传播连接成为关键担心。在这份报纸,我们在认知收音机网络(CRN)经由光谱分配学习产量优化。以前的研究合并冲突图或SINR模型描绘干扰关系。然而,以前的模型忽视积聚的干扰效果并且导致讨厌的干扰和非最优的结果,当工作在所有潜在的连接之中在估计的RSS(收到的信号力量)的精确性上基于后者模型忽视它的重信赖时。两个是不适当的描绘在干扰和产量之间的复杂关系。到这个目的,由考虑CR的特征,象光谱差异和间断OFDM一样,我们建议一个帮助测量的基于SINR的跨层的产量优化答案。我们的工作在不同的层使特征担心:在物理层,我们在场改进SINR模型的精确性的一个有效RSS评价算法;在上面的层,流动水平为WMN的基于SINR的产量优化问题作为一个混合整数被建模被证明NP难的非线性的编程问题。解决这个问题,一集中(1)最佳的算法和一个有效分布式的算法被提供。评估算法表演,真实世界的踪迹被用来说明我们的计划的有效性。