简介:Hereditaryfructoseintolerance(HFI)isanunderrecognized,preventablelife-threateningcondition.ItisanautosomalrecessivedisorderwithsubnormalactivityofaldolaseBintheliver,kidneyandsmallbowel.Symptomsarepresentonlyaftertheingestionoffructose,whichleadstobriskhypoglycemia,andanindividualwithcontinuedingestionwillexhibitvomiting,abdominalpain,failuretothrive,andrenalandliverfailure.AdiagnosisofHFIwasmadeina50-year-oldwomanonthebasisofmedicalhistory,responsetofructoseintolerancetest,demonstrationofaldolaseBactivityreductioninduodenalbiopsy,andmolecularanalysisofleukocyteDNAbyPCRshowedhomozygosityfortwodosesofmutantgene.HFImayremainundiagnoseduntiladultlifeandmayleadtodisastrouscomplicationsfollowinginadvertentfructoseorsorbitolinfusion.SeverallethalepisodesofHFIfollowingsorbitolandfructoseinfusionhavebeenreported.Thediagnosiscanonlybesuspectedbytakingacarefuldietaryhistory,andthiscanpresentseriouscomplications.
简介:Objectives:Auditoryneuropathy(AN)isasensorineuralhearingdisordercharacterizedbyabsentorabnormalauditorybrainstemresponses(ABRs)andnormalcochlearouterhaircellfunctionasmeasuredbyotoacousticemissions(OAEs).Manyriskfactorsarethoughttobeinvolvedinitsetiologyandpathophysiology.ThreeChinesepedigreeswithfamilialANarepresentedhereintodemonstrateinvolvementofgeneticfactorsinANetiology.Methods:Probandsoftheabove-mentionedpedigrees,whohadbeendiagnosedwithAN,wereevaluatedandfollowedupintheDepartmentofOtolaryngologyHeadandNeckSurgery,ChinaPLAGeneralHospital.Theirfamilymemberswerestudiedandthepedigreediagramswereestablished.Historyofillness,physicalexamination,puretoneaudiometry,acousticreflex,ABRsandtransientevokedanddistortion-productotoacousticemissions(TEOAEsandDPOAEs)wereobtainedfrommembersofthesefamilies.DPOAEchangesundertheinfluenceofcontralateralsoundstimuliwereobservedbypresentingasetofcontinuouswhitenoisetothenon-recordingeartoexamthefunctionofauditoryefferentsystem.Somesubjectsreceivedvestibularcalorictest,computedtomography(CT)scanofthetemporalboneandelectrocardiography(ECG)toexcludeotherpossibleneuropathydisorders.Results:Inmostaffectedsubjects,hearinglossofvariousdegreesandspeechdiscriminationdifficultiesstartedat10to16yearsofage.TheiraudiologicalevaluationshowedabsenceofacousticreflexandABRs.AsexpectedinAN,thesesubjectsexhibitednearnormalcochlearouterhaircellfunctionasshowninTEOAE&DPOAErecordings.Pure-toneaudiometryrevealedhearinglossrangingfrommildtosevereinthesepatients.Autosomalrecessiveinheritancepatternswereobservedinthethreefamilies.InPedigreeⅠandⅡ,twoaffectedbrotherswerefoundrespectively,whileinpedigreeⅢ,2sisterswereaffected.Allthepatientswereotherwisenormalwithoutevidenceofperipheralneuropathyatthetimeofth
简介:Inthispaper,weintroduceandstudyanewclassofquasivariationalinequalities.Using’essentiallytheprojectiontechniqueanditsvariantforms,weestablishtheequivalencebetweengeneralizednonlinearquasivariationalinequalitiesandthefixedpointproblems.Thisequivalenceisthenusedtosuggestandanalyzeanumberofnewiterativealgorithms.Thesenewresultsincludethecorrespondingknownresultsforgeneralizedquasivariationalinequalitiesasspecialcases.
简介:Thespectraldensityofthequasi-homogeneous(QH)lighthasbeenknownwhenitscattersonQHmediaorpropagatesinfreespace.ThecasethatQHsourcesaresurroundedbyQHmediaisproposedinthispaper.Undertheparaxialapproximation,thespectraldensityoftheQHlightpropagatingthroughQHmediaisderived.AmodifiedscalinglawforthepropagationoftheQHlightthroughQHmediaisalsoobtained.Thislawalsoholdstrueinthefarfieldbeyondtheparaxialapproximation.
简介:Inmedicallaboratoryanimals,thepigistheclosestspeciestohumaninevolution,exceptforprimates.Asananimalmodel,thepigishighlyconcernedbymanyscientists,includingcomparativebiology,developmentalbiology,medicalgenetics.Rodentsasanimalmodelforhumanhearingdefectshasarepoorproducibilityandreliability,duetodifferencesinanatomicalstructure,evolutionaryrateandmetabolicrate,butthesehappenstobetheadvantagesofthepigmodel.Inthispaper,wewillsummarizetheapplicationofminiaturepiginthestudyofhumanhereditarydeafness.
简介:Algorithmsusedindataminingandbioinformaticshavetodealwithhugeamountofdataefficiently.Inmanyapplications,thedataaresupposedtohaveexplicitorimplicitstructures.Todevelopefficientalgorithmsforsuchdata,wehavetoproposepossiblestructuremodelsandtestifthemodelsarefeasible.Hence,itisimportanttomakeacompactmodelforstructureddata,andenumerateallinstancesefficiently.Therearefewgraphclassesbesidestreesthatcanbeusedforamodel.Inthispaper,weinvestigatedistance-hereditarygraphs.Thisclassofgraphsconsistsofisometricgraphsandhencecontainstreesandcographs.First,acanonicalandcompacttreerepresentationoftheclassisproposed.Thetreerepresentationcanbeconstructedinlineartimebyusingprefixtrees.Usually,prefixtreesareusedtomaintainasetofstrings.Inouralgorithm,theprefixtreesareusedtomaintaintheneighborhoodofvertices,whichisanewapproachunlikethelexicographicallybreadth-firstsearchusedinotherstudies.Basedonthecanonicaltreerepresentation,efficientalgorithmsforthedistance-hereditarygraphsareproposed,includinglineartimealgorithmsforgraphrecognitionandgraphisomorphismandanefficientenumerationalgorithm.Anefficientcodingforthetreerepresentationisalsopresented;itrequires[3.59n]bitsforadistance-hereditarygraphofnverticesand3nbitsforacograph.Theresultsofcodingimprovepreviouslyknownupperbounds(bothare2~(O(nlogn)))ofthenumberofdistance-hereditarygraphsandcographsto2~([3.59n])and2~(3n),respectively.
简介:ObjectiveTounderstandthegeneticloadintheChinesepopulationforimprovementindiagnosis,preventionandrehabilitationofdeafness.MethodsDNAsamples,immortalizedcelllinesaswellasdetailedclinicalandaudiometricdatawerecollectedthroughanationalgeneticresourcescollectingnetwork.Twoconventionalgeneticapproacheswereusedinthestudies.LinkageanalysisinXchromosomeandautosomeswithmicrosatellitemarkerswereperformedinlargefamiliesforgenemappingandpositionalcloningofnovelgenes.CandidategeneapproachwasusedforscreeningthemtDNA12SrRNA,GJB2andSLC26A4mutationsinpopulation-basedsamples.ResultsAtotalof2,572Chinesehearinglossfamiliesorsporadiccaseswerecharacterizedinthereportedstudies,includingsevenX-linked,oneY-linked,28largeandmultiplexautosomaldominanthearinglossfamilies,607simplexautosomalrecessivehereditaryhearinglossfamilies,100mitochondrialinheritancefamilies,147GJB2inducedhearinglosscases,230caseswithenlargedvestibularaqueduct(EVA)syndrome,169sporadiccaseswithauditoryneuropathy,and1,283sporadicsensorineuralhearinglosscases.Throughlinkageanalysisorsequenceanalysis,twoX-linkedfamilieswerefoundtransmittingtwonovelmutationsinthePOU3F4gene,whileanotherX-linkedfamilywasmappedontoanovellocus,nominatedasAUNX1(auditoryneuropathy,X-linkedlocus1).TheonlyY-linkedfamilywasmappedontotheDFNY1locus(Y-linkedlocus1,DFNY1).Eightofthe28autosomaldominantfamilieswerelinkedtovariousautosomalloci.Inpopulationgeneticsstudies,2,567familialcasesandsporadicpatientsweresubjectedtomutationscreeningforthreecommonhearinglossgenes:mtDNA12SrRNA1555G,GJB2andSLC26A4.TheauditoryneuropathycasesinoursampleswerescreenedforOTOFgenemutations.ConclusionsThesedatashowthattheChinesepopulationhasageneticloadonhereditaryhearingloss.Establishingpersonalizedsurveillanceandpreventionmodelsforhearing
简介:Hearingloss(HL)isoneofthemostwidespreadsensorydisorders,affectingapproximately1in500newborns.HeritablediseasesoftheinnereararetheleadingcausesofprelingualHL.TreatingofhereditaryHLandunderstandingitsunderlyingmechanismsremaindifficultchallengestootolaryngologists.Asstemcellsarecapableofself-renewalanddifferentiation,theyareideallysuitedbothfordiseasemodelingandregenerativemedicine.Recently,descriptionofinducedpluripotentstemcells(iPSCs)hasallowedthefieldofdiseasemodelingandpersonalizedtherapytobecomefarmoreaccessibleandphysiologicallyrelevant,asiPSCscanbegeneratedfrompatientsofanygeneticbackground.ThisreviewbrieflydescribestheadvantagesofiPSCstechnologyanddiscussespotentialapplicationsofthispowerfulbiologicaltoolinstudyingandtreatinghereditaryHL.
简介:这份报纸建议一些整齐条件,它在伪可能性的导致存在,强壮的一致性和最大的伪可能性的评估者(MQLE)的asymptotic规度有随机的regressors的非线性的模型(QLNM)。有随机的regressors的概括线性模型(GLM)的asymptotic结果与随机的regressors被概括到QLNM。关键词Asymptotic规度-一致性-最大的伪可能性的评估者-伪可能性的有随机的regressors的非线性的模型2000苏布杰克特先生分类62F12-62J02由中国的国家自然科学基础支持了(号码10761011,10671139,10901135),云南省(号码2008CD081)的自然科学基础和为云南大学的中间、年轻的优秀教师的特殊基础。
简介:AbstractHereditary spastic paraplegia type 56 (SPG56-HSP) is a rare autosomal recessive disorder caused by loss of function mutations in CYP2U1, leading to an early-onset limbs spasticity, often complicated by additional neurological or extra-neurological manifestations. Given its low prevalence, the molecular bases underlying SPG56-HSP are still poorly understood, and effective treatment options are still lacking. Recently, through the generation and characterization of the SPG56-HSP mouse model, we were able to take few important steps forward in expanding our knowledge of the molecular background underlying this complex disease. Leveraging the Cyp2u1-/- mouse model we were able to identify several new diagnostics biomarkers (vitamin B2, coenzyme Q, neopterin, and interferon-alpha), as well as to highlight the key role played by the folate pathway in SPG56-HSP pathogenesis, providing a potential treatment option. In this review, we discuss the major role played by the Cyp2u1-/- model in dissecting clinical and biological aspects of the disease, opening the way to a series of new research paths ranging from clinical trials, biomarker testing, and to the expansion of the underlying genetic and molecular, emphasizing how basic mouse model characterization could contribute to advance research in the context of rare disorders.
简介:Theintroductionofnext-generationsequencing(NGS)technologyintestingforhereditarycancersusceptibilityallowstestingofmultiplecancersusceptibilitygenessimultaneously.Whiletherearemanypotentialbenefitstoutilizingthistechnologyinthehereditarycancerclinic,includingefficiencyoftimeandcost,therearealsoimportantlimitationsthatmustbeconsidered.Thebestpanelforthegivenclinicalsituationshouldbeselectedtominimizethenumberofvariantsofunknownsignificance.Theinclusioninpanelsoflowpenetranceornewlyidentifiedgeneswithoutspecificactionabilitycanbeproblematicforinterpretation.Geneticcounselorsareanessentialpartofthehereditarycancerriskassessmentteam,helpingthemedicalteamselectthemostappropriatetestandinterprettheoftencomplexresults.Geneticcounselorsobtainanextendedfamilyhistory,counselpatientsontheavailabletestsandthepotentialimplicationsofresultsforthemselvesandtheirfamilymembers(pre-testcounseling),explaintopatientstheimplicationsofthetestresults(post-testcounseling),andassistintestingfamilymembersatrisk.
简介:让G一张连接k的图,和T是V(G)的一个子集。如果G-T没被连接,那么,T被说是G的一个切割集合。G的k-cut-setT是有|T的G的一个切割集合|=k。让T是连接k的图G的k-cut-set。如果G-T能被划分成subgraphsG1和G2以便|G1|2,|G2|2,然后,我们把T称为G的重要k-cut-set。假定G是一(k-1)-connected图没有重要(k-1)-cut-set。然后,我们把G称为伪连接k的图。在这份报纸,我们为任何整数k证明那5,如果没有K4,,G是一张连接k的图,那么,G的每个顶点是有其收缩产出伪的一个边的事件连接k的图,因此有至少\(\frac{{|V(G)|}}{2}\)G的边以便他们的每个成员的收缩导致伪连接k的图。
简介:InthispaperweusethesimplexB-splinerepresentationofpolynomialsorpiecewisepolynomialsintermsoftheirpolarformstoconstructseveraldifferentialordiscretebivariatequasiinterpolantswhichhaveanoptimalapproximationorder.Thismethodprovidesanefficienttoolfordescribingmanyapproximationschemesinvolvingvaluesand(or)derivativesofagivenfunction.
简介:修改Ansari的方法,我们为quasi-Mazur空格的hypercyclicity给一些标准。他们能被用于判定hypercyclicity非完全并且non-metrizable局部地凸的空格。为一些特殊局部地凸的空格,例如K?(LF)定序空格和quasi-Mazur空格的可计算的引入的限制,我们调查他们的hypercyclicity。当我们看,围住的biorthogonal系统在Ansari的构造起一个重要作用。而且,我们分别地获得典型条件局部地凸的空格跳了有稠密的线性跨度并且为局部地凸的空格的序列跳了吸收集合,它在判定围住的biorthogonal系统的存在是有用的。
简介:Inthispaper,thetheoryofQuasi-steadyisappliedtothecalculationsofturbochargersmatchingtothedieselenginesandperformanceprediction.Theengineperformancepredictionprogramswritteninlanguaechavebeenusedforcalculationsofvariousturbochargeddieselengines.Ithasbeenconfirmedbythecomparisonswithexperimentaldatathattheresultsofthecalcuationarereasonable,reliableandsatisfiedfortheengineeringapplications.
简介:Objective:ToinvestigatethemembranelocalizationfunctionoftheCX26proteinwhenits86thaminoacidisThr,SerorArg,anditsrelationstodeafness.Methods:CX26-GFPproteinwitheitherThr,SerorArgasthe86thaminoacidwasexpressedinmouseSGNcellsviatheGFPfusiontypelentivirusexpressionsystem.Themembranelocalizationofthefusionproteinwasobservedunderafluorescencemicroscope.Results:ThemutatedproteinofCX26T86Swaslocalizedtocellmembraneandformgapconjunctionstructures,showingnodifferencetothewildtypeCX26protein(withThrasthe86thaminoacid).However,thegapconjunctionstructuredisappearedwhenthemutationwasCX26T86A.Conclusion:TheseresultsindicatethattheCX26T86Rmutationmaybeacauseofhearingloss,butCX26T86Sasanon-pathogenicpolymorphismmutationdoesnotaffectfunctionsoftheCX26protein.Theresultsareinaccordancewiththeresultsofclinicalscreening.
简介:Accordingtothetheoryoftestingasphericalsurfacebynormalaberrationcompensationmethod,thedesigningmethodofquasi-universalcompensatorisstudied.Onthebasisofthird-orderaberrationtheory,aftercalculatingandoptimizingwithanopticaldesignprogram,thestructureparametersofacompensatorareobtained.ThisnewcompensatorcouldbeusedinTwyman-Greeninterferometer,andinmeasurementofacertainrangeofparaboloidellipsoidandhyperboloid.Thecompensationaccuracyismorethan0.02λ.