简介：IrecentlyreadaneditorialbyChrisO’ConnorinJACCheartfailureonthetopicofinstitutionalmemory[1].Thisstimulatedmetothinkaboutthecurrentstateofinstitutionalmemoryvsthatwhichweperceivedindaysgoneby.Inmycase,IamreferringtotheinstitutionalmemoryofJohnsHopkinsSchoolofMedicine(whereIwenttomedicalschool)andcomparingittotheinstitutionalmemoryattheUniversityofFlorida,CollegeofMedicine,(whereIhavebeenforthepast43years.)WhatfollowsaresomeofmymemoriesofmytimeatHopkins.

简介：Themulticoreevolutionhasstimulatedrenewedinterestsinscalingupapplicationsonshared-memorymultiprocessors,significantlyimprovingthescalabilityofmanyapplications.Butthescalabilityislimitedwithinasinglenode;thereforeprogrammersstillhavetoredesignapplicationstoscaleoutovermultiplenodes.Thispaperrevisitsthedesignandimplementationofdistributedsharedmemory(DSM)asawaytoscaleoutapplicationsoptimizedfornon-uniformmemoryaccess(NUMA)architectureoverawell-connectedcluster.ThispaperpresentsMAGI,anefficientDSMsystemthatprovidesatransparentsharedaddressspacewithscalableperformanceonaclusterwithfastnetworkinterfaces.MAGIisuniqueinthatitpresentsaNUMAabstractiontofullyharnessthemulticoreresourcesineachnodethroughhierarchicalsynchronizationandmemorymanagement.MAGIalsoexploitsthememoryaccesspatternsofbig-dataapplicationsandleveragesasetofoptimizationsforremotedirectmemoryaccess(RDMA)toreducethenumberofpagefaultsandthecostofthecoherenceprotocol.MAGIhasbeenimplementedasauser-spacelibrarywithpthread-compatibleinterfacesandcanrunexistingmultithreadedapplicationswithminimizedmodifications.WedeployedMAGIoveran8-nodeRDMA-enabledcluster.ExperimentalevaluationshowsthatMAGIachievesupto9.25:4speedupcomparedwithanunoptimizedimplementation,leadingtoasealableperformanceforlarge-scaledata-intensiveapplications.

简介：Newnon-volatilememory(NVM)technologiesareexpectedtoreplacemainmemoryDRAM(dynamicrandomaccessmemory)inthenearfuture.NANDflashtechnologicalbreakthroughshaveenabledwideadoptionofsolidstatedrives(SSDs)instoragesystems.However,flash-basedSSDs,bynature,cannotavoidlowenduranceproblemsbecauseeachcellonlyallowsalimitednumberoferasures.ThiscangiverisetocriticalSSDreliabilityissues.SincemanySSDwriteoperationseventuallycausemanySSDeraseoperations,reducingSSDwritetrafficplaysacrucialroleinSSDreliability.ThispaperproposestwoNVM-basedbuffercachepolicieswhichcanworktogetherindifferentlayerstomaximallyreduceSSDwritetraffic:amainmemorybuffercachedesignnamedHierarchicalAdaptiveReplacementCache(H-ARC)andaninternalSSDwritebufferdesignnamedWriteTrafficReductionBuffer(WRB).H-ARCconsidersfourfactors(dirty,clean,recency,andfrequency)toreducewritetrafficandimprovecachehitratiosinthehost.WRBreducesblockerasuresandwritetrafficfurtherinsideanSSDbyeffectivelyexploitingtemporalandspatiallocalities.ThesetwocomprehensiveschemessignificantlyreducetotalSSDwritetrafficateachdifferentlayer(i.e.,hostandSSD)byupto3x.Consequently,theyhelpextendSSDlifespanwithoutsystemperformancedegradation.

简介：Objective:MemorystemTcells(Tscm)haveattractedattentionbecauseoftheirenhancedself-renewal,multipotentcapacity,andanti-tumorcapacities.However,littleisknownaboutTscminpatientswithrenalclearcellcarcinoma(RCC)andtheroleofWntsignalinginthesecells.WeevaluatedTscmfromRCCpatientsconcerningtheiractivationofWntsignalinginvitroandexploredthemechanismofpreferentialsurvival.Methods:FlowcytometryidentifiedsurfacemarkersandcytokinesproducedfromaccumulatedTscminthepresenceoftheglycogensynthasekinasebetainhibitorTWS119.Apoptosiswasevaluatedafterinductionusingtumornecrosisfactor-alpha.ImmunofluorescenceandWesternblotanalyseswereusedtoinvestigatetheactivationofthenuclearfactor-kappaB(NF-КB)pathway.Results:RCCpatientshadasimilarpercentageofCD4~+andCD8~+Tscmashealthydonors.ActivationofWntsignalingbyTWS119resultedintheaccumulationofTscminactivatedTcells,butreversalofdifferentiatedTcellstoTscmwasnotachieved.PreferentialsurvivalofTscmwasassociatedwithincreasedanti-apoptoticabilitymediateddownstreamoftheNF-КBactivationpathway.Conclusions:ThefindingthatTscmcanaccumulatebyWntsignalinginvitroinbloodfromRCCpatientswillhelpindevisingnewcancertherapystrategiesofTscm-basedadoptiveimmunotherapy,suchasdendriticcell-stimulatedTscm,andTcellreceptororchimericantigenreceptor-engineeredTscm.