簡(jiǎn)介：BIODRUGS20082213744NOVELTHERAPEUTICSTRATEGIES11738804/08/00010037/4800/0?2008ADISDATAINFORMATIONBVALLRIGHTSRESERVEDFIBROBLASTGROWTHFACTOR21ASATHERAPEUTICAGENTFORMETABOLICDISEASESALEXEIKHARITONENKOVANDARMENBSHANAFELTBIOTECHOLOGYDISCOVERYRESEARCH,LILLYRESEARCHLABORATORIES,LILLYCORPORATECENTER,INDIANAPOLIS,INDIANA,USACONTENTSABSTRACT371THEROLEOFFIBROBLASTGROWTHFACTORSFGFSINTHEREGULATIONOFMETABOLICPROCESSES372OVERVIEWOFFGF21ANDITSINVITROEFFECTS383FGF21INVIVOPHARMACOLOGY394INSIGHTSINTOFGF21MECHANISMOFACTION405CONCLUSION43FIBROBLASTGROWTHFACTORFGF21ISAUNIQUEMEMBEROFTHEFGFFAMILY,WITHSEVERALMOLECULARCHARACTERISABSTRACTTICSTHATDIFFERFROMCLASSICALFGFSANDEXHIBITINGAPHARMACOLOGICPROFILETHATINCLUDESAVARIETYOFMETABOLICRESPONSESINVITROANDWHENTESTEDINVIVOINANIMALMODELSFGF21REPRESENTSANOVELANDATTRACTIVETHERAPEUTICAGENTFORTYPE2DIABETESMELLITUS,BECAUSEOFITSABILITYTOMODULATEDISEASEPHENOTYPEINPRECLINICALSETTINGSWITHOUTINDUCINGANYAPPARENTADVERSEEFFECTSALTHOUGHFGF21WASDISCOVEREDRELATIVELYRECENTLY,THEUNDERSTANDINGOFITSBIOLOGYANDTHERAPEUTICUTILITYISRAPIDLYEVOLVINGANUMBEROFKEYMETABOLICALLYLINKEDMOLECULESANDPATHWAYSHAVEBEENSUGGESTEDTOBEINVOLVEDINTHEMECHANISMOFACTIONOFFGF21,DEPENDINGONTHESPECIFICTARGETTISSUE/ORGANFURTHERRESEARCHINTOTHESEMECHANISMSSHOULDLEADTOIMPORTANTADVANCESINTHEUNDERSTANDINGOFFGF21BIOLOGYANDPAVETHEWAYFORNOVELTHERAPEUTICSTRATEGIESTHESPECIFICSOFFGF21ACTIVITIESBOTHINCELLCULTUREANDINVIVO,ITSPOTENTIALASATARGETFORDIABETES,ANDINSIGHTSINTOTHEMOLECULARMECHANISMSOFFGF21METABOLICACTIONSWILLBEDISCUSSEDINTHISREVIEW1THEROLEOFFIBROBLASTGROWTHFACTORSFGFSINRODENTS,RESPECTIVELY8,9WHENTESTEDINMICE,FGF19PROVIDESTHEREGULATIONOFMETABOLICPROCESSESRESISTANCETOOBESITYANDINSULINDESENSITIZATION10,11ANOTHERMEMBEROFTHEFGFFAMILY,FGF23,ISAKEYPLAYERINTHEREGULAFIBROBLASTGROWTHFACTORSFGFSANDTHEIRCORRESPONDINGRETIONOFPHOSPHATEANDCALCIUMMETABOLISM12,13LIKEWISE,THECEPTORSFGFRSHAVEBEENPRIMARILYASSOCIATEDWITHTHEPROCESSESOFDEVELOPMENT,TRANSFORMATION,ANDANGIOGENESIS14HOWOVEREXPRESSIONOFADOMINANTNEGATIVEFORMOFFGFR1INPANCREEVER,OVERTHELASTDECADE,NEWDATAHAVEEMERGEDSHOWINGTHATATICΒCELLSLEADSTODIABETESMELLITUSINMICE14FGFR2APPEARSTOFGF/FGFRMEDIATEDPATHWAYSMAYPLAYIMPORTANTROLESINDEFINBEAKEYMOLECULEINTHEPROCESSOFPANCREATICDEVELOPMENT1517INGANDREGULATINGFUNCTIONSOFENDOCRINERELEVANTTISSUESANDFGFR3ISACRITICALPLAYERINBONE,18WHEREASFGFR4HASBEENORGANS,ASWELLASMODULATINGVARIOUSMETABOLICPROCESSESFORIMPLICATEDINCHOLESTEROLMETABOLISMANDBILEACIDSYNTHESIS19EXAMPLE,FGF10ANDFGF16PLAYIMPORTANTROLESINADIPOCYTEANDTHEMETABOLICROLESOFFGF/FGFRARESTILLNOTPRECISELYDEFINEDPANCREATICBIOLOGY,57ANDFGF19ANDITSMOUSEORTHOLOGFGF15,REGULATECHOLESTEROLANDBILEACIDMETABOLISMINHUMANSANDANDARECURRENTLYUNDERINTENSEINVESTIGATIONFGF21ANDMETABOLICDISEASES39INDUCESUPREGULATIONOFPPARΓPROTEINALTHOUGHITISCURRENTLYINCIDENCEOFHEPATOCELLULARCARCINOMASINFGF21TRANSGENICMICEUNCLEARWHATPARTICULARIMPACTEACHOFTHESEEFFECTSHASONGLUCOSEAT12MONTHSOFAGEWASSIMILARTOTHATINCONTROLANIMALSTHUS,IFTRANSPORT,THESEDATAREVEALPOTENTIALSYNERGYINTHEACTIONSBEFGF21NEGATIVELYREGULATESCHEMICALLYINDUCEDHEPATOCARCITWEENTHESETWOREGULATORSOFGLUCOSEHOMEOSTASIS,FGF21ANDNOGENESIS,ITISLIKELYTOINTERFEREWITHDISEASEPROGRESSIONATITSPPARΓ31EARLYSTAGES24RECENTLY,ANOTHERLINEOFFGF21TRANSGENICMICEONAC57BL/6JBACKGROUNDHASBEENDESCRIBED26THESEANIMALSHAD50–1503FGF21INVIVOPHARMACOLOGYTIMESHIGHERLEVELSOFFGF21MRNAINTHELIVERTHANCONTROLANIMALS,ANDHADLOWEREDLEVELSOFSERUMCHOLESTEROL,TRITHEINVIVOBIOACTIVITYOFFGF21HASBEENOBSERVEDUSINGGLYCERIDES,GLUCOSEANDINSULININDICATIVEOFTHEIMPROVEDLIPIDNUMEROUSBIOMARKERSTHATILLUSTRATETHEEFFECTSOFFGF21ACTIONSANDGLYCEMICMETABOLISM,ANDAMELIORATEDINSULINRESISTANCE,INABROADRANGEOFANIMALSTUDIESCOVERINGAVARIETYOFDISEASECONSISTENTWITHPREVIOUSLYPUBLISHEDDATA20FGF21TRANSGENICMODELS20,2326,35MICEWEREALSOFOUNDTOHAVEELEVATEDSERUMLEVELSOFΒHYDROXYTHECONSEQUENCESOFENFORCEDEXPRESSIONOFHUMAN20ANDBUTYRATE,SUGGESTINGTHEINDUCTIONOFKETOGENESIS,ASWELLASHAVMOUSEFGF2123,26HAVEBEENEVALUATEDINTRANSGENICMICE20,24,26INGADIPOCYTESOFSMALLERSIZE,INCREASEDLIPASEEXPRESSIONINWHITEFGF21TRANSGENICANIMALSAPPEARVIABLE,NORMALATBIRTH,ANDADIPOSETISSUEANDELEVATEDSERUMLEVELSOFFREEFATTYACIDS,ALLESSENTIALLYINDISTINGUISHABLEFROMTHEIRWILDTYPELITTERMATESNOEVOCATIVEOFTHEINDUCTIONOFLYPOLYSIS26IMPORTANTLY,ASURINETICEABLY,THEYDONOTPOSSESSSIGNSOFNEOPLASIA,TUMORS,ORANYCONCENTRATIONSOFADRENALINEANDNORADRENALINEWEREREDUCEDINOTHEROVERTABNORMALITIESTHROUGHOUTTHEIRLIFESPAN,ASDEMONSTRAFGF21TRANSGENICANIMALS,FGF21DOESNOTAPPEARTOSTIMULATETEDBYEXTENSIVEMORPHOLOGICANDHISTOLOGICANALYSES20,23THUS,LIPOLYSISTHROUGHASYSTEMICINCREASEINCATECHOLAMINES26SURPROLONGEDEXPOSUREOFMICETOFGF21DOESNOTLEADTOCARCINOGENPRISINGLY,THESEFGF21TRANSGENICMICEWEREALSOREPORTEDTOHAVEICEVENTSNEVERTHELESS,ASPECIFICPHENOTYPEOFFGF21TRANSGENIC1–2oCLOWERCOREBODYTEMPERATURES,REDUCEDLOCOMOTORACTIVITY,MICEWASREVEALEDUPONAVARIETYOFCHALLENGESANDENHANCEDTORPORDURING24HOURFASTINGCOMPAREDWITHTHEIRC57BL/6MICEOVEREXPRESSINGHUMANFGF21FROMTHELIVERCONTROLLITTERMATES26ALTHOUGHINTRIGUING,THELATTEROBSERVATIONSCIRCULATINGLEVELSOF70–150N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簡(jiǎn)介：THEMEDSECTIONVECTORDESIGNANDDRUGDELIVERYREVIEWTWENTYYEARSOFCELLPENETRATINGPEPTIDESFROMMOLECULARMECHANISMSTOTHERAPEUTICSFREDERICHEITZ,MAYCATHERINEMORRISANDGILLESDIVITACENTREDERECHERCHESDEBIOCHIMIEMACROMOLéCULAIRE,UMR5237,CNRS,UM1,UM2,CRBMDEPARTMENTOFMOLECULARBIOPHYSICSANDTHERAPEUTICS,1919ROUTEDEMENDE,MONTPELLIER,FRANCETHERECENTDISCOVERYOFNEWPOTENTTHERAPEUTICMOLECULESTHATDONOTREACHTHECLINICDUETOPOORDELIVERYANDLOWBIOAVAILABILITYHAVEMADEOFDELIVERYAKEYSTONEINTHERAPEUTICDEVELOPMENTSEVERALTECHNOLOGIESHAVEBEENDESIGNEDTOIMPROVECELLULARUPTAKEOFTHERAPEUTICMOLECULES,INCLUDINGCELLPENETRATINGPEPTIDESCPPSCPPSWEREFIRSTDISCOVEREDBASEDONTHEPOTENCYOFSEVERALPROTEINSTOENTERCELLSNUMEROUSCPPSHAVEBEENDESCRIBEDSOFAR,WHICHCANBEGROUPEDINTOTWOMAJORCLASSES,THEFIRSTREQUIRINGCHEMICALLINKAGEWITHTHEDRUGFORCELLULARINTERNALIZATIONANDTHESECONDINVOLVINGFORMATIONOFSTABLE,NONCOVALENTCOMPLEXESWITHDRUGSNOWADAYS,CPPSCONSTITUTEVERYPROMISINGTOOLSFORNONINVASIVECELLULARIMPORTOFCARGOANDHAVEBEENSUCCESSFULLYAPPLIEDFORINVITROANDINVIVODELIVERYOFTHERAPEUTICMOLECULESVARYINGFROMSMALLCHEMICALMOLECULE,NUCLEICACIDS,PROTEINS,PEPTIDES,LIPOSOMESANDPARTICLESTHISREVIEWWILLFOCUSONTHESTRUCTURE/FUNCTIONANDCELLULARUPTAKEMECHANISMOFCPPSINTHEGENERALCONTEXTOFDRUGDELIVERYWEWILLALSOHIGHLIGHTTHEAPPLICATIONOFPEPTIDECARRIERSFORTHEDELIVERYOFTHERAPEUTICMOLECULESANDPROVIDEANUPDATEOFTHEIRCLINICALEVALUATIONBRITISHJOURNALOFPHARMACOLOGY2009157,195–206DOI101111/J14765381200800057XPUBLISHEDONLINE20MARCH2009THISARTICLEISPARTOFATHEMEDSECTIONONVECTORDESIGNANDDRUGDELIVERYFORALISTOFALLARTICLESINTHISSECTIONSEETHEENDOFTHISPAPER,ORVISITHTTP//WWW3INTERSCIENCEWILEYCOM/JOURNAL/121548564/ISSUEYEARYEAR2009KEYWORDSCELLPENETRATINGPEPTIDENONCOVALENTDELIVERYSYSTEMSIRNANANOPARTICLEDRUGDELIVERYMOLECULARMECHANISMSTHERAPEUTICSABBREVIATIONSCPP,CELLPENETRATINGPEPTIDEGAG,GLUCOSAMINOGLYCANNLS,NUCLEARLOCALIZATIONSEQUENCEPMO,PHOSPHORODIAMIDATEMORPHOLINOOLIGOMERPNA,PEPTIDENUCLEICACIDPTD,PROTEINTRANSDUCTIONDOMAINSINTRODUCTIONCHALLENGESINDRUGDELIVERYOVERTHEPAST10YEARS,INORDERTOCIRCUMVENTLIMITATIONSOFSMALLMOLECULEANDGENEBASEDTHERAPIES,WEHAVEWITNESSEDADRAMATICACCELERATIONINTHEPRODUCTIONOFNEWLARGETHERAPEUTICMOLECULES,WHICHDONOTFOLLOWLIPINSKI’SRULES,SUCHASPROTEINS,PEPTIDESANDNUCLEICACIDTHERAPEUTICSHOWEVER,THEIRDEVELOPMENTISRESTRICTEDBYVERYSPECIFICISSUESINCLUDINGPOORSTABILITYINVIVO,LACKOFCELLULARUPTAKEANDINSUFFICIENTCAPABILITYTOREACHTARGETSTHISISASSOCIATEDWITHTHECOMPLETELOSSOFPHARMACEUTICALPOTENCYORATLEASTWITHTHEREQUIREMENTFORHIGHDOSESANDRISKOFMAJORSIDEEFFECTSTHEREFORE,DELIVERYCONSTITUTESAMAJORPIECEOFTHETHERAPEUTICPUZZLE,ANDTHEREISAREALDEMANDFORNEWANDMOREEFFICIENTDRUGDELIVERYSYSTEMSMAJORRULESHAVETOBESATISFIED,INPARTICULARIDELIVERYEFFICIENCYINDIFFERENTANDCHALLENGINGCELLLINESIIRAPIDENDOSOMALRELEASEIIIABILITYTOREACHTHETARGETIVACTIVITYATLOWDOSESVLACKOFTOXICITYANDVIFACILITYOFTHERAPEUTICAPPLICATIONSUBSTANTIALPROGRESSHASBEENMADEINTHEDESIGNOFNEWTECHNOLOGIESTOIMPROVECELLULARUPTAKEOFTHERAPEUTICCOMPOUNDSOPALINSKAANDGEWIRTZ,2002J?RVERANDLANGEL,2004GLOVERETAL,2005TORCHILIN,2005DEFOUGEROLLESETAL,2007KONGANDMOONEY,2007ANUMBEROFNONVIRALSTRATEGIESHAVEBEENPROPOSEDINCLUDINGLIPID,POLYCATIONIC,NANOPARTICLEANDPEPTIDEBASEDFORMULATIONSASREPORTEDINTHISSPECIALISSUEMORRISETAL,2000OGRISANDWAGNER,2002J?RVERANDLANGEL,2004TORCHILIN,2005,BUTONLYASUBSETOFTHESETECHNOLOGIESAREEFFICIENTLYAPPLIEDINVIVOATEITHERPRECLINICALORCLINICALLEVELSPROTEINTRANSDUCTIONDOMAINSPTDSORCELLPENETRATINGPEPTIDESCPPSCORRESPONDTOSHORT30RESIDUESYNTHETICPEPTIDESANDAREPARTOFTHEMOSTPROMISINGSTRATEGYTOOVERCOMEBOTHEXTRACELLULARANDINTRACELLULARLIMITATIONSOFVARIOUSBIOMOLECULESOFINCLUDINGPLASMIDDNA,CORRESPONDENCEGILLESDIVITA,CENTREDERECHERCHESDEBIOCHIMIEMACROMOLéCULAIRE,UMR5237,CNRS,UM1,UM2,CRBMDEPARTMENTOFMOLECULARBIOPHYSICSANDTHERAPEUTICS,1919ROUTEDEMENDE,34293MONTPELLIER,FRANCEEMAILGILLESDIVITACRBMCNRSFRRECEIVED14JULY2008REVISED7OCTOBER2008ACCEPTED20OCTOBER2008BRITISHJOURNALOFPHARMACOLOGY2009,157,195–206?2009THEAUTHORSJOURNALCOMPILATION?2009THEBRITISHPHARMACOLOGICALSOCIETYALLRIGHTSRESERVED00071188/09WWWBRJPHARMACOLORGCOVALENTSTRATEGYCELLPENETRATINGPEPTIDEBASEDTECHNOLOGIESDESCRIBEDSOFARMAINLYINVOLVETHEFORMATIONOFACOVALENTCONJUGATEBETWEENTHECARGOANDTHECARRIERPEPTIDE,WHICHISACHIEVEDBYCHEMICALCROSSLINKINGORBYCLONINGFOLLOWEDBYEXPRESSIONOFACPPFUSIONPROTEINNAGAHARAETAL,1998GAIT,2003MOULTONANDMOULTON,2004ZATSEPINETAL,2005MOSTOFTHEWORKHASBEENREPORTEDFORPEPTIDESDERIVEDFROMTATFAWELLETAL,1994VIVESETAL,1997FRANKELANDPABO,1988,PENETRATINDEROSSIETAL,1994,POLYARGININEPEPTIDEARG8SEQUENCEWENDERETAL,2000FUTAKIETAL,2001ANDTRANSPORTAN,POOGAETAL,1998OTHERPROTEINDERIVEDPEPTIDESSUCHASVP22PROTEINFROMHERPESSIMPLEXVIRUSELLIOTTANDO’HARE,1997,PVECELMQUISTETAL,2001,CALCITONINDERIVEDPEPTIDESSCHMIDTETAL,1998KRAUSSETAL,2004,ANTIMICROBIALPEPTIDESBUFORINIANDSYNBPARKETAL,1998PARKETAL,2000,ASWELLASPOLYPROLINESWEETARROWPEPTIDEPUJALSETAL,2006HAVEALSOBEENSUCCESSFULLYUSEDTOIMPROVETHEDELIVERYOFCOVALENTLYLINKEDCARGOSJOLIOTANDPROCHIANTZ,2004ELANDALOUSSIETAL,2005MURRIELANDDOWDY,2006MORERECENTLY,NEWGENERATIONSOFCPPS,COMBININ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簡(jiǎn)介：1ABSTRACTTHECOMBUSTIONSYSTEMOFCIRCULATINGFLUIDIZEDBEDBOILERCFBBISACOMPLEXOBJECTWITHMULTIVARIABLE,LARGEDELAY,TIGHTLYCOUPLING,NONLINEARANDSLOWTIMEVARYINGITISDIFFICULTTOBUILDTHEPRECISEMATHEMATICMODELOFTHEOBJECTANDTOACCURATELYCONTROLTHEOBJECTWITHTHETRADITIONALCONTROLMETHODSINTHISPAPER,THEOBJECTISDYNAMICALLYDECOUPLEDBYAFEEDFORWARDCOMPENSATORTHEN,THEOBJECTISRESPECTIVELYCONTROLLEDBYTHREECONTROLLERS,PIDCONTROLLER,FUZZYCONTROLLERANDSELFTUNINGPARAMETERFUZZY–PIDCONTROLLERTHESIMULATIONEXPERIMENTSARECARRIEDOUTTHROUGHCONTRASTWITHFORMERCONTROLLERSINMATLABSIMULATIONENVIRONMENTTHESIMULATIONRESULTSSHOWTHATTHESELFTUNINGPARAMETERFUZZYPIDCONTROLLERISSUPERIORTOTHEGENERALPIDCONTROLLERANDTHEGENERALFUZZYCONTROLLERINSPEEDINESS,STABILITY,ADAPTABILITY,ROBUSTNESSANDABILITYOFANTIDISTURBANCEINDEXTERMSCIRCULATINGFLUIDIZEDBEDBOILERDECOUPLINGFUZZYCONTROLMULTIVARIABLESELFTUNINGPARAMETERFUZZYPIDCONTROLI．INTRODUCTIONHECIRCULATINGFLUIDIZEDBEDBOILERCFBBHASBEENWIDELYUSEDASACLEANCOALCOMBUSTIONTECHNIQUEFORITSHIGHCOMBUSTIONEFFICIENCY,WIDEADAPTABILITYTOCOALRANKS,LOADADJUSTINGPERFORMANCEANDLOWPOLLUTION14HOWEVER,DUETOITSSPECIALSTRUCTUREANDTHECOMPLEXITYOFCOMBUSTIONMECHANISM,THECOMBUSTIONPROCESSHASCOMPLEXFEATURES,SUCHASHIGHLYNONLINEAR,TIMEVARYING,LARGEDELAYANDMULTIVARIABLEDECOUPLING,ETCITISVERYDIFFICULTTOESTABLISHITSPRECISEMATHEMATICALMODEL58,ANDTOCONTROLTHEOBJECTWITHTHETRADITIONALCONTROLMETHODSATPRESENT,THECOMMONCONTROLMETHODISTHATTHEMAINSTEAMPRESSUREISFOCALLYCONTROLLED,MEANWHILE,THEPRIMARYAIRFLOWISADJUSTEDACCORDINGTOTHEBESTAIRCOALRATIO,ANDTHEBEDTEMPERATUREISCONTROLLEDINTHEREQUIREDRANGE9THEMETHODCAN’TMAINTAINTHEBEDTEMPERATUREINTHEBESTRANGEWHILEKEEPINGTHEMAINSTEAMPRESSUREINTHISPAPER,ONTHEBASISOFDECOUPLINGMODELOFTHEMAINSTEAMPRESSUREANDTHEBEDTEMPERATURE10,THESELFTUNINGFUZZYPIDCONTROLLER1118WHICHHASBETTERADAPTABILITYANDTHISWORKWASSUPPORTEDBYLEADINGACADEMICDISCIPLINEPROJECTOFSHANGHAIMUNICIPALEDUCATIONCOMMISSIONPROJECTNUMBERJ51301ANDNATURESCIENCEKEYFOUNDATIONOFSHANGHAIMUNICIPALEDUCATIONCOMMISSIONPROJECTNUMBER06ZZ69ALLOFTHEAUTHORSAREWITHCOLLEGEOFELECTRICPOWERANDAUTOMATION,SHANGHAIUNIVERSITYOFELECTRICPOWER,YANGPUDISTRICT,SHANGHAI,200090,CHINAEMAILCHENGQIMINGSINACOMBETTERROBUSTNESS,ISUSEDTOCONTROLTHESTEAMPRESSUREANDTHEBEDTEMPERATURETOGETTHEBETTERCONTROLEFFECTSII．THECHARACTERISTICSOFCFBBANDTHESTRUCTUREOFTHEDECOUPLEDCONTROLSYSTEMOFCFBBTHEKEYREASONSTHATCFBBCOMBUSTIONSYSTEMISDIFFICULTTOCONTROL,ARETHESTRONGCOUPLINGRELATIONSBETWEENMULTIINPUTSCOAL,PRIMARYAIR,SECONDARYAIR,DRAWINGWIND,RECYCLEMATERIALANDMULTIOUTPUTSBEDTEMPERATURE,MAINSTEAMPRESSURE,THEFURNACENEGATIVEPRESSURE,OXYGENCONTENT,THEMOSTIMPORTANTRELATIONINTHESECOUPLINGRELATIONSISTHECOUPLINGRELATIONBETWEENBEDTEMPERATUREANDMAINSTEAMPRESSURE56INCHINA,CFBBAREUSUALLYDESIGNEDWITHOUTEXTERNALHEATEXCHANGERTOENSURESIMPLESTRUCTUREANDLOWCOSTTHEMAINSTEAMPRESSUREANDTHEBEDTEMPERATUREWITHSTRONGLYCOUPLEDRELATIONARECONTROLLEDBYREGULATINGTHECOALAMOUNTANDTHEPRIMARYAIRAMOUNTTHISCONTROLMETHODISWIDELYUSEDTOTHEACTUALCONTROLOFCFBBCOMBUSTIONSYSTEMINCHINA12THEREFORE,INTHISPAPER,THEBEDTEMPERATUREISCONTROLLEDBYTHEPRIMARYAIRAMOUNT,ANDTHEMAINSTEAMPRESSUREISREGULATEDBYTHECOALAMOUNTINTHISPAPER,THEDOMESTIC75T/HCFBBISSELECTEDASTHEOBJECTOFSIMULATIONEXPERIMENTSTHETRANSFERFUNCTIONMATRIXOFTHESYSTEMATTHELOADRANGEOF70TO100ISGOTTEN16???????????????????????????????????????12602230212221121101160036012600066011638767811803860QBSESSESQBSGSGSGSGPTSSB1WHERETB,P0ARERESPECTIVELYBEDTEMPERATUREANDMAINSTEAMPRESSUREB,Q1ARERESPECTIVELYCOALAMOUNTANDPRIMARYAIRAMOUNTG11,G12G21,G22ARERESPECTIVELYINPUTOUTPUTTRANSFERFUNCTIONSOFBTB,BP0,Q1TBANDQ1P0FROMEQ1TOSEE,THATTIMEDELAYSEXISTINBOTHCOALMAINSTEAMPRESSURELOOPANDCOALBEDTEMPERATURELOOPANDTHEREARESERIOUSLYCOUPLINGRELATIONSINCFBBSYSTEMTHEREFORE,DYNAMICFEEDFORWARDCOMPENSATIONISNEEDEDFORDYNAMICDECOUPLINGSYSTEMTOCONTROLTHESYSTEMBETTERDYNAMICFEEDFORWARDCOMPENSATIONISCOMMONLYUSEDFORSYSTEMDECOUPLING10FIG1ISTHESTRUCTUREOFTHERESEARCHONMULTIVARIABLEDECOUPLINGCONTROLSYSTEMFORCOMBUSTIONSYSTEMOFCIRCULATINGFLUIDIZEDBEDBOILERQIMINGCHENG,RUIQINGGUO,ANDXUFENGDUT3TRIALANDERRORMETHODIV．THEDESIGNOFSELFTUNINGFUZZYPIDCONTROLLERFORCOMBUSTIONCONTROLSYSTEMOFCFBBATHESTRUCTUREOFCONTROLSYSTEMTHEPIDCONTROLLERHASMANYADVANTAGES,SUCHASSIMPLESTRUCTURE,MATURETHEORETICALBASIS,WIDEAPPLICABILITY,CONVENIENTPARAMETERTUNING,MUCHENGINEERINGAPPLICATIONTHEREFORE,THEPIDCONTROLLEROCCUPIESADOMINANTPOSITIONINTHEACTUALCONTROLSYSTEMBUTTHELINEARCHARACTERISTICSOFTHECONVENTIONALPIDCONTROLLERWITHFIXEDCONTROLPARAMETERSHAVEGOODCONTROLPERFORMANCEONLYWHENWORKINGNEAROPERATINGPOINTWHENTHESYSTEMISFARTHEROUTOFTHEOPERATINGPOINT,NONLINEARCONTROLCHARACTERISTICSOFTHEOBJECTISDIFFICULTTOMAINTAINTHEDYNAMICQUALITYOFPIDCONTROLTHEREFORE,FUZZYREASONINGISINTRODUCEDTOSOLVEDTHEPROBLEM,THEPARAMETERSOFPIDCONTROLLERBASEDONTHEINITIALPIDCONTROLPARAMETERSARECORRECTEDWITHADDINGFUZZYREASONINGTOIMPROVETHESYSTEMDYNAMICPERFORMANCEINSELFTUNINGFUZZYPIDCONTROLLER1618,THECONDITIONSANDTHEOPERATIONSOFCONTROLRULESAREEXPRESSEDBYFUZZYSETONTHEBASISOFPIDCONTROL,ANDTHESEFUZZYCONTROLRULESASWELLASOTHERINFORMATIONARESTOREDINTOCOMPUTERKNOWLEDGEBASES,THEN,ACCORDINGTOACTUALRESPONSEOFTHECONTROLSYSTEM,FUZZYREASONINGISCARRIEDOUTBYCOMPUTERTOACHIEVEBESTADJUSTMENTOFPIDCONTROLTHESTRUCTUREOFSELFTUNINGPARAMETERFUZZYPIDCONTROLSYSTEMISSHOWNINFIG5FIRSTLY,THESELFTUNINGFUZZYPIDCONTROLLERISDESIGNEDTOFINDTHEFUZZYRELATIONSBETWEENTHETHREECONTROLPARAMETERSNAMELY,PROPORTIONALCOEFFICIENTKP,DIFFERENTIALCOEFFICIENTKDANDINTEGRALCOEFFICIENTKIANDTHETWOSYSTEMVARIABLESTHATIS,ERRORE,ERRORDEVIATIONECTHEN,ΔKP,ΔKI,ΔKD,THECHANGESOFKP,KI,KDPIDCONTROLPARAMETERSAREONLINEAMENDEDONFUZZYTHEORYWITHMEASURINGEANDECDURINGTHESYSTEMOPERATIONFINALLY,THECONTROLSYSTEMHASGOODDYNAMICANDSTATICPERFORMANCETHEDIGITALPIDCONTROLLERUSUALLYCANBEEXPRESSEDASUKKPEKKIΣEIKDECK（4）INFUZZYREASONING,THEINPUTVARIABLESAREEANDEC,ANDTHEOUTPUTVARIABLESAREΔKP,ΔKI,ΔKDTHEPIDCONTROLPARAMETERSAREGIVENASKPKP0ΔKP，KIKI0ΔKI，KDKD0ΔKD（5）WHERE,KP0,KI0,KD0ARETHEINITIALSETTINGVALUESOFKD,KI,KDPIDCONTROLPARAMETERSBTHERULETABLESOFFUZZYCONTROLFROMTHECHARACTERISTICSOFPIDCONTROLTOKNOW,THESTRONGINTEGRALACTIONILEADSTOBIGOVERSHOOT,FASTRESPONSETHESTRONGDERIVATIVEACTIONDHASGOODSTABILITY,SMALLOVERSHOOT,SMALLABILITYOFANTIINTERFERENCEACCORDINGTOEANDECATDIFFERENTSTAGES,THESETTINGPRINCIPLEOFPIDCONTROLPARAMETERSAREGIVEN11,181WHENTHECONTROLLEDVARIABLESARECLOSETOSETTINGVALUES,THEINTEGRALACTIONWITHTHESAMESIGNASECCANAVOIDSOVERSHOOTANDOSCILLATION,ANDISBENEFICIALTOTHECONTROLWHENTHECONTROLLEDVARIABLESAREFARFROMSETTINGVALUES,THEINTEGRALACTIONWITHTHEOPPOSITESIGNASECANREDUCEOVERSHOOTANDAVOIDOSCILLATION2ATINITIALSTAGEOFPIDPARAMETERADJUSTMENT,ITCANAVOIDOVERSHOOTANDINCREASERESPONSESPEEDTHATKPISPROPERLYLARGEANDKIISSMALLORZEROATMIDDLESTAGE,LETTHEVALUESOFKPANDKIBEMODERATEWHILETAKINGACCOUNTTOSTABILITYANDCONTROLPRECISIONATLASTSTAGE,ITCANELIMINATETHEERRORSANDREDUCEOVERSHOOTTHATKPISREDUCEDANDKIISINCREASEDPROPERLY3DIFFERENTIALCOEFFICIENTKDCANINHIBITCHANGEOFCONTROLLEDVARIABLE,SHORTENSTEADYTIME,REDUCESTEADYSTATEERRORITISASUPPLEMENTTOKP,KITHEFUZZYSUBSETSOFINPUTANDOUTPUTVARIABLESOFFUZZYCONTROLLERARERESPECTIVELYE,EC,ΔKP,ΔKI,ΔKDTHELANGUAGEVALUESOFTHESEFUZZYVARIABLESAREIN{NB,NM,NS,ZO,PS,PM,PB},ANDTHEMEMBERSHIPFUNCTIONSOFTHESEFUZZYVARIABLESAREALLSENSITIVELYTRIGONOMETRICFUNCTIONSWITHTHEVALUEFIELDIN3,3BYFUZZYREASONINGANDTESTMODIFICATIONBASEDONTHEABOVESETTINGPRINCIPLE,THEFUZZYCONTROLRULESOFTHESELFTUNINGPARAMETERFUZZYPIDCONTROLSYSTEMAREOBTAINEDANDSHOWNINTABLEIIITALLEIIFUZZYCONTROLRULESOFBP0CONTROLLOOPFIG5THESTRUCTUREOFSELFTUNINGFUZZYPIDCONTROLLER

簡(jiǎn)介：INTERNATIONALJOURNALOFTHERMALSCIENCES482009781–794WWWELSEVIERCOM/LOCATE/IJTSHEATTRANSFERINAMECHANICALFACESEALNO?LBRUNETIèRE?,BENOITMODOLOUNIVERSITéDEPOITIERS,UMRCNRS6610,LABORATOIREDEMéCANIQUEDESSOLIDES,SP2MI,BP30179,86962FUTUROSCOPECHASSENEUILCEDEX,FRANCERECEIVED28AUGUST2007RECEIVEDINREVISEDFORM18MARCH2008ACCEPTED17MAY2008AVAILABLEONLINE20JUNE2008ABSTRACTTHISPAPERPRESENTSANUMERICALANALYSISOFHEATTRANSFERINANEXPERIMENTALINNERPRESSURIZEDMECHANICALFACESEAL,USINGCFDTHECONFIGURATIONISSIMILARTOTHELAMINARFLOWBETWEENASTATICANDAROTATINGDISCBOUNDEDBYACOROTATINGSIDEWALLASERIESOFSIMULATIONSALLOWTHEAUTHORSTOPROPOSEACORRELATIONFORTHEGLOBALNUSSELTNUMBERFORTHEROTATINGRINGANDTHESTATICDISCTHENUSSELTNUMBERISAFUNCTIONOFTHEREYNOLDSNUMBEROFTHEFLOWANDTHEPRANDTLNUMBER,ASWELLASOFTHERATIOOFTHEFLUIDANDMATERIALTHERMALCONDUCTIVITIESTHISLASTCONCLUSIONARISESFROMTHEFACTTHATTHEHEATSOURCEISLOCATEDINTHECONTACTBETWEENTHEROTORANDTHESTATORANDDEPENDSONTHETEMPERATUREDISTRIBUTIONINTHESOLIDSTHECOOLINGOILFLOWAPPEARSNOTTOAFFECTTHENUSSELTNUMBERTHENUMERICALRESULTSWEREVALIDATEDBYCOMPARISONWITHMEASUREMENTSCARRIEDOUTONTHEEXPERIMENTALSEALBYMEANSOFANINFRAREDCAMERA?2008ELSEVIERMASSONSASALLRIGHTSRESERVEDKEYWORDSCONVECTIVEHEATTRANSFERINFRAREDTHERMOGRAPHYROTOR–STATORMECHANICALFACESEALCFDCOMPUTATIONALFLUIDDYNAMIC1INTRODUCTIONMECHANICALFACESEALSAREUSEDTOSEALPRESSURIZEDFLUIDSINROTATINGMACHINESSUCHASPUMPS,COMPRESSORSANDAGITATORS,WHEREPRESSURE,TEMPERATUREANDVELOCITYCONDITIONSPREVENTTHEUSEOFELASTOMERICSEALSTHESESEALSAREBASICALLYCOMPOSEDOFAROTATINGPARTMOUNTEDONTOTHESHAFTANDASTATIONARYPARTFIXEDTOTHEHOUSINGTHETWOPARTSAREMAINTAINEDINCONTACTBYTHEACTIONOFSPRINGSANDOFTHEPRESSURIZEDFLUIDFIG1GOODOPERATINGCONDITIONSAREACHIEVEDWHENTHESEALFACESAREPARTIALLYSEPARATEDBYATHINLUBRICATINGFLUIDFILMAFRACTIONOFMICROMETER,AVOIDINGWEARONTHEFACESWHILELIMITINGLEAKAGERATETOANACCEPTABLEVALUEACCORDINGTOLEBECK1,THEBEHAVIOURANDPERFORMANCEOFAMECHANICALFACESEALAREINFLUENCEDASMUCHBYTHETHERMALBEHAVIOUROFTHESEALASBYANYOTHERFACTORINDEED,THEDISSIPATEDPOWERDUETOVISCOUSFRICTIONANDASPERITIESCONTACTSINTHESEALINGINTERFACELEADSTOASIGNIFICANTINCREASEINTEMCORRESPONDINGAUTHOREMAILADDRESSNOELBRUNETIERELMSUNIVPOITIERSFRNBRUNETIèREFIG1EXAMPLEOFMECHANICALFACESEALPERATUREINTHEFLUIDFILMANDINTHECONTIGUOUSSOLIDS2,3CONSEQUENTLY,THELUBRICATIONCONDITIONSAREMODIFIEDBECAUSEOFFLUIDVISCOSITYVARIATION,THERMALDISTORTIONSOFTHESEALRINGSANDPOSSIBLEPHASECHANGEAPOSSIBLEEFFECTOFTHESEVARIATIONSISADRASTICINCREASEINLEAKAGERATEORSEALFAILURETHISISWHYTHEREHAVEBEENMANYSTUDIESDEALINGWITHTHERMALEFFECTSINRECENTDECADESABRIEFREVIEWISPRESENTEDIN4THEMAIN12900729/–SEEFRONTMATTER?2008ELSEVIERMASSONSASALLRIGHTSRESERVEDDOI101016/JIJTHERMALSCI200805014NBRUNETIèRE,BMODOLO/INTERNATIONALJOURNALOFTHERMALSCIENCES482009781–794783INALLTHESTUDIESDEALINGWITHHEATTRANSFERAROUNDAMECHANICALFACESEAL,NOAUTHORSETOUTTODEVELOPANUSSELTNUMBERCORRELATIONMOREOVER,THEAUTHORSWERECOMPARINGTHEIRFINDINGSWITHEMPIRICALFORMULASOBTAINEDINFLOWINVOLVINGAUNIFORMLYHEATEDROTATINGCYLINDERTHEREISASIGNIFICANTDIFFERENCEHEREFROMMECHANICALFACESEALS,WHERETHEHEATSOURCEISLOCATEDINTHESEALINGINTERFACETHUSTHENUSSELTNUMBERALSODEPENDSONTHETEMPERATUREDISTRIBUTIONINTHESEALRINGS,THISBEINGAFUNCTIONOFTHEMATERIALPROPERTIESINADDITION,NOSTUDIESWERECARRIEDOUTONINNERPRESSURIZEDMECHANICALFACESEALS,ALESSWIDESPREADTECHNOLOGYWHERETHESEALEDFLUIDISLOCATEDBETWEENTHEROTATINGSHAFTANDTHESEALRINGSTHEAIMOFTHEPRESENTWORKISTOANALYZENUMERICALLYAND,TOALESSEREXTENT,EXPERIMENTALLYAMECHANICALFACESEALTHISEXPERIMENTALSEALWASESSENTIALLYDESIGNEDTOVALIDATENUMERICALMODELSOFTHECONTACTBEHAVIOURTHROUGHINFRAREDTEMPERATUREMEASUREMENTS3,4ANDISTHUSQUITEDIFFERENTFROMINDUSTRIALMECHANICALFACESEALSMOREPARTICULARLY,THESEALISINNERPRESSURIZEDANDOPERATESWITHAHIGHLYVISCOUSMINERALOILRESULTINGINLAMINARFLOWMOREOVER,THESHAFTDOESNOTPASSTROUGHTHESEALCHAMBERLEADINGTOAROTORSTATORLIKEFLOWTHATISALSOOFINTEREST18NUMERICALSIMULATIONSALLOWTHEAUTHORSTOPROPOSEACORRELATIONFORTHENUSSELTNUMBERSONTHEROTATINGANDSTATIONARYPARTSOFTHESEALTHATAREFUNCTIONOFTHEREYNOLDSNUMBEROFTHEFLOW,THEPRANDTLNUMBER,THERATIOOFTHEFLUIDANDTHEMATERIALTHERMALCONDUCTIVITYTHEINFLUENCEOFGEOMETRICALPARAMETERSHASNOTBEENANALYZEDTHENUMERICALANDEXPERIMENTALTEMPERATUREDISTRIBUTIONANDNUSSELTNUMBERAREINREASONABLEAGREEMENT2GEOMETRICALANDOPERATINGCONFIGURATION21EXPERIMENTALDEVICETHEEXPERIMENTALMECHANICALFACESEALISPRESENTEDINFIG2THECARBONROTORISFIXEDONTHESHAFTBYMEANSOFASUPPORTANDACONEEXPANDERTHESTATOR,MADEOFAFLUORSPARDISCCAF2,ISFIXEDONANANNULARPISTONWHICHENSURESTHREEDEGREESOFFREEDOMWITHRESPECTTOTHEFRAMETHISENABLESADYNAMICTRACKINGOFANYROTORMISALIGNMENTTHESTATORISPRESSEDAGAINSTTHEROTORBYPRESSURIZEDAIRACTINGONTHETOPSURFACEOFTHEANNULARPISTONTHETHERMALPROPERTIESOFTHEMATERIALSOFTHESEALCOMPONENTSAREGIVENINTABLE1HYDRAULICEQUIPMENTPROVIDESOILATCONTROLLEDPRESSUREANDTEMPERATURETHEOILISAMINERALISOVG46ITSCHARACTERISTICSAREPRESENTEDINTABLE2THETYPICALOPERATINGCONDITIONSANDTHEMAINDIMENSIONSOFTHEMECHANICALFACESEALAREDETAILEDINTABLE322PHYSICALBACKGROUNDTHEOILFLOWINTHEMECHANICALFACESEALISSIMILARTOTHEFLOWBETWEENASTATICANDA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簡(jiǎn)介：INTENSIVECAREMED2007331162–1167DOI101007/S0013400706752ORIGINALHKALLELLHERGAFIMBAHLOULAHAKIMHDAMMAKHCHELLYCBENHAMIDAACHAARINREKIKMBOUAZIZSAFETYANDEFFICACYOFCOLISTINCOMPAREDWITHIMIPENEMINTHETREATMENTOFVENTILATORASSOCIATEDPNEUMONIAAMATCHEDCASE–CONTROLSTUDYRECEIVED26JULY2006ACCEPTED23APRIL2007PUBLISHEDONLINE25MAY2007?SPRINGERVERLAG2007HKALLELULHERGAFIMBAHLOULHDAMMAKHCHELLYCBHAMIDAACHAARINREKIKMBOUAZIZCHUHABIBBOURGUIBA,SERVICEDERéANIMATIONMéDICALE,ROUTEELAINKM1,3029SFAX,TUNISIAEMAILKALLELHATYAHOOFRTEL21698415299FAX21674243427AHAKIMFACULTéDEMéDECINEDESFAX,LABORATOIREDEPHARMACOLOGIE,ROUTEELAINKM1,3029SFAX,TUNISIAABSTRACTOBJECTIVEOURSTUDYAIMEDTODETERMINETHEEFFICACYANDSAFETYOFCOLISTININTHETREATMENTOFVENTILATORASSOCIATEDPNEUMONIAVAPCAUSEDBYPANDRUGRESISTANTPSEUDOMONASAERUGINOSAORACINETOBACTERBAUMANIIDESIGNPAIRWISE,RETROSPECTIVEEXPOSED–UNEXPOSEDSTUDYSETTINGCOMBINEDMEDICALANDSURGICALINTENSIVECAREUNITOFHABIBBOURGUIBAUNIVERSITYHOSPITALSFAX,TUNISIAPATIENTSSIXTYPATIENTSWITHVAPCAUSEDBYPANDRUGRESISTANTABAUMANIIORPAERUGINOSAMATCHEDTO60CONTROLSWITHVAPCAUSEDBYABAUMANIIORPAERUGINOSASUSCEPTIBLETOIMIPENEMALLPATIENTSHADNORMALRENALFUNCTIONATTHEONSETOFANTIBIOTICTHERAPYINTERVENTIONSCASEPATIENTSWERETREATEDBYCOLISTININTRAVENOUSLYANDCONTROLPATIENTSWERETREATEDBYIMIPENEMINTRAVENOUSLYMEASUREMENTSANDRESULTSBASELINECHARACTERISTICSWERESIMILARBETWEENTHECOLISTINANDIMIPENEMGROUPSTHEMEANDURATIONOFANTIBIOTICTHERAPYFORVAPWAS95±38DAYSRANGE5–22DAYSWITHCOLISTINAND89±28DAYSRANGE5–20DAYSWITHIMIPENEMP032AFAVORABLECLINICALRESPONSETOANTIBIOTICTHERAPYFORVAPOCCURREDIN45PATIENTS75INTHECOLISTINGROUPANDIN43PATIENTS717INTHEIMIPENEMGROUPP068THETIMETORESOLUTIONOFINFECTIOUSPARAMETERSAFTERTHEINITIATIONOFANTIBIOTICTHERAPYWASNOTSTATISTICALLYDIFFERENTBETWEENTHETWOGROUPSDURINGTHEANTIBIOTICCOURSE,NONEOFTHEPATIENTSINEITHERGROUPDEVELOPEDRENALFAILURECONCLUSIONSWECONCLUDETHATCOLISTINCANBEASAFEANDEFFECTIVEOPTIONINTHETREATMENTSOFVAPCAUSEDBYPANDRUGRESISTANTPAERUGINOSAORABAUMANIIKEYWORDSCOLISTINVENTILATORASSOCIATEDPNEUMONIANEPHROTOXICITYIMIPENEMINTRODUCTIONPANDRUGRESISTANTPDRGRAMNEGATIVEBACTERIAAREANIMPORTANTPROBLEMWORLDWIDE,ESPECIALLYINTHEINTENSIVECAREUNITICU1,2MULTIPLEDRUGRESISTANCEMAKESDIFFICULTTHECHOICEOFTHEEMPIRICANTIMICROBIALMOLECULEANDISRESPONSIBLEFORDELAYEDADAPTEDANTIMICROBIALTREATMENT3INTHERECENTLYPUBLISHEDLITERATURE,PSEUDOMONASAERUGINOSAANDACINETOBACTERBAUMANIIARETHETWOMOSTWIDELYDESCRIBEDMICROORGANISMSTOBERESISTANTTOTHEMOSTOFAVAILABLEANTIBIOTICS4FORTHISREASON,COLISTINHASBEENRECENTLYCONSIDEREDASALASTTHERAPEUTICOPTIONFORTHETREATMENTOFPATIENTSWITHINFECTIONSCAUSEDBYTHESEMICROORGANISMS4COLISTINISANOLDANTIBIOTICWHICHWASUSEDUNTILTHEEARLY1980STOTREATINFECTIONSCAUSEDBYGRAMNEGATIVERODSWHENGENTAMICINANDSECONDANDTHIRDGENERATIONCEPHALOSPORINSBECAMEAVAILABLE,COLISTINWASDROPPED,MAINLYBECAUSEOFITSNEUROANDNEPHROTOXICITY5–8THEINCREASINGPREVALENCEOFPDRGRAMNEGATIVEORGANISMS,1164TREATMENTREGIMENINTHECOLISTINGROUP,PATIENTSWERETREATEDWITHCOLISTINSULFOMETHATESODIUMBELLONRH?NEPOULENCRORERADMINISTEREDINTRAVENOUSLYTHEDOSAGEWAS6MILLIONUNITS≈100,000U/KGOFCOLISTINDAILY,DIVIDEDINTOTHREEDOSESINTHEIMIPENEMGROUP,PATIENTSWERETREATEDWITHIMIPENEMIMIPENEM/CILASTATINMSDADMINISTEREDINTRAVENOUSLYTHEDOSAGEWAS2GOFIMIPENEMDAILY,DIVIDEDINTOFOURDOSESINTHISSTUDY,ALLPATIENTSRECEIVEDCOLISTINORIMIPENEMONANEMPIRICALBASIS,WHICHMADETHEINITIALANTIBIOTICTREATMENTAPPROPRIATEINALLCASESSTATISTICALANALYSISCATEGORICALVARIABLESWEREEXPRESSEDASPERCENTAGESANDCONTINUOUSVARIABLESASMEANVALUESSDPERCENTAGESWERECOMPAREDUSINGTHECHISQUARETESTANDMEANSWITHTHETTESTTHEWILCOXONMATCHEDPAIRSTESTWASUSEDTOCOMPARETHEMATCHINGCRITERIAAGE,SAPSII,ANDPAO2/FIO2KAPLAN–MEIERCURVESWEREUSEDTOASSESSDIFFERENCESBETWEENTHECOLISTINGROUPANDTHEIMIPENEMGROUPIN1RESOLUTIONOFINFECTIOUSPARAMETERSAFTERTHEINITIATIONOFANTIBIOTICTHERAPYAND2MORTALITYAT28DAYSAFTERTHEONSETOFCOLISTINORIMIPENEMTHERAPYFORVAPCURVESWERECOMPAREDUSINGTHELOGRANKTESTAPVALUE≤005INATWOTAILEDTESTWASCONSIDEREDTOINDICATESTATISTICALSIGNIFICANCERESULTSDURINGTHESTUDYPERIOD,1,208PATIENTSWEREADMITTEDTOTHEUNITONETHOUSANDANDSEVENTYSIXOFTHEM891RETABLE1MATCHINGCRITERIAOFTHESTUDYPOPULATIONCOLISTINGROUPN60IMIPENEMGROUPN60PEFFECTIVENESSOFMATCHINGAGEYEARS434±188414±167060100SAPS352±123332±108035100PAO2/FIO2ONDAYOFINITIATIONOFANTIBIOTICS213±79215±81087100TABLE2BASELINECHARACTERISTICSOFTHESTUDYPOPULATIONCOLISTINGROUPN60IMIPENEMGROUPN60PREASONFORADMISSIONNACUTERESPIRATORYFAILURE71178133078COMA8133466022MULTIPLETRAUMA42704880020POSTOPERATIVERESUSCITATION3500024SEXRATIOMALE/FEMALE65445045SHOCKN183014233040ANTIBIOTICSN467673965016PAO2/FIO2ATADMISSION311±82313±8409UREANITROGENMMOL/L59±1964±20018SERUMCREATININEΜMOL/L797±178820±154046CEIVEDMECHANICALVENTILATIONAND123114DEVELOPEDVAPIN78634OFTHESEPATIENTSTHEVAPCAUSEDBYPDRABAUMANIIORPAERUGINOSAANDWASTREATEDWITHCOLISTINOFTHESE78PATIENTSPOTENTIALLYELIGIBLEASCASES,12WEREEXCLUDEDBECAUSEOFRENALFAILUREATTHEONSETOFCOLISTINTHERAPYOFTHE66REMAININGCASEPATIENTSENROLLEDINTHESTUDY,MATCHINGWASPOSSIBLEFORONLY60909ALLPATIENTSWEREMATCHEDFORAGE,SAPSII,ANDPAO2/FIO2ATTHEONSETOFANTIBIOTICTHERAPY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簡(jiǎn)介：HITOSHIFUJIMOTODEPARTMENTOFENERGYSCIENCEANDTECHNOLOGY,GRADUATESCHOOLOFENERGYSCIENCE,KYOTOUNIVERSITY,KYOTO6068501,JAPANSATOSHIOGAWAGRADUATESTUDENTATKYOTOUNIVERSITYPRESENTLY,TOYOTAMOTORCORPHIROHIKOTAKUDADEPARTMENTOFENERGYSCIENCEANDTECHNOLOGY,GRADUATESCHOOLOFENERGYSCIENCE,KYOTOUNIVERSITY,KYOTO6068501,JAPANNATSUOHATTADEPARTMENTOFCIVILENGINEERING,NIPPONBUNRIUNIVERSITY,OITA,JAPANOPERATIONPERFORMANCEOFASMALLAIRLIFTPUMPFORCONVEYINGSOLIDPARTICLESTHEPUMPPERFORMANCEOFASMALLAIRLIFTSYSTEMFORCONVEYINGSOLIDPARTICLESISINVESTIGATEDEXPERIMENTALLYTHETOTALLENGTHOFTHEVERTICALLIFTINGPIPEIS3200MM,ANDTHEINNERDIAMETEROFTHEPIPEIS18MMTHEGASINJECTORISSETATACERTAINPOINTOFTHEPIPETHEFLOWSINTHELIFTINGPIPEAREWATER/SOLIDTWOPHASEMIXTURESBELOWTHEGASINJECTIONPOINT,ANDAIR/WATER/SOLIDTHREEPHASEMIXTURESABOVEITTHETIMEAVERAGEDCHARACTERISTICSOFTHEFLOWSAREEXAMINEDFORVARIOUSEXPERIMENTALCONDITIONSTHEEFFECTSOFPARTICLEDIAMETER,PARTICLEDENSITY,THEGASINJECTIONPOINT,ANDTHEVOLUMEFLUXOFAIRONTHEPUMPPERFORMANCEARESTUDIEDSYSTEMATICALLYTHECRITICALBOUNDARYATWHICHTHEPARTICLESCANBELIFTEDISDISCUSSEDINDETAILBASEDUPONONEDIMENSIONALMIXTUREMODEL?DOI101115/11514498?KEYWORDSAIRLIFTPUMP,GAS/LIQUID/SOLIDTHREEPHASEFLOW,PARTICLESIZE,GASINJECTIONPOINT,CRITICALBOUNDARYOFTRANSPORTOFSOLIDPARTICLES1INTRODUCTIONAIRLIFTPUMPSAREUTILIZEDTOTRANSPORTEXPLOSIVE/TOXICLIQUIDSINCHEMICALINDUSTRIES,ANDTOCONVEYSLURRIESINMININGINDUSTRIES?1?THEUTILIZATIONOFAIRLIFTPUMPSHASALSOBEENEMPLOYEDFORLIFTINGMARINEMINERALRESOURCESSUCHASMANGANESENODULESFROMTHEDEEPSEABEDTOTHESEASURFACE?2?THEAIRLIFTPUMPSCONSISTOFVERTICALLIFTINGPIPESANDGASINJECTORS?SEEFIG1?THEUPWARDFLOWOFMIXTURESINTHEVERTICALPIPESARISESFROMTHEBUOYANCYOFTHEINJECTEDGASINTHELIQUIDTHEFLOWOFTHEGASLIQUIDTWOPHASEORGASLIQUIDSOLIDTHREEPHASEMIXTURESINTHEPIPESISUNSTEADYANDCHAOTICINNATURETHUS,THETRANSPORTPHENOMENAAREVERYCOMPLICATEDDESPITETHESIMPLEPUMPMECHANISMTODATE,THEPERFORMANCEOFAIRLIFTPUMPSHASBEENSTUDIEDEXPERIMENTALLYASWELLASTHEORETICALLYSINCETHEPRESENTSTUDYTREATSTHEAIRLIFTPUMPFORCONVEYINGSOLIDPARTICLES,PRIOREXPERIMENTALSTUDIESCONCERNEDWITHTHISARECITEDBRIEFLYWEBERANDDEDEGIL?3?PERFORMEDEXPERIMENTSUSINGALARGESCALEDAIRLIFTPUMPWHOSELENGTHWASFROM50TO441MWITHADIAMETEROF300MMTHREEKINDSOFSOLIDPARTICLESWEREUSEDTHEYMEASUREDTHEVOLUMEOFDISCHARGEDPARTICLESFORDIFFERENTGASINJECTIONPOINTSSAITOETAL?4?STUDIEDTHEOPERATIONPERFORMANCEOFAIRLIFTPUMPSCHANGINGTHEPIPELENGTHFROM77MTO1966MTHEYALSOVARIEDTHEPIPEDIAMETERFROM467MMTO154MMKATOETAL?5?,YOSHINAGAETAL?6?,YOSHINAGAANDSATO?7?,ANDHATTAETAL?8?CARRIEDOUTTHEEXPERIMENTSUSINGRELATIVELYSMALLAIRLIFTPUMPSFORCONVEYINGSOLIDPARTICLESINORDERTOVALIDATETHEIRTHEORETICALMODELSFORPREDICTINGTHEOPERATINGPERFORMANCEOFTHEPUMPSTHETOTALPIPELENGTHWASLESSTHAN10MINTHEIREXPERIMENTSKAWASHIMAETAL?9?EXAMINEDTHERELATIONSHIPBETWEENTHEVOLUMETRICFLUXESOFSUPPLIEDAIRANDDISCHARGEDPARTICLESUNDERTHECONDITIONTHATTHELIFTINGPIPEWAS6MINLENGTHAND50MMINDIAMETER,ANDCRUSHEDROCKS?ABOUT17MMINDIAMETER?WEREUSEDASSOLIDPARTICLESTHEOPERATIONPERFORMANCEOFAIRLIFTPUMPSFORCONVEYINGSOLIDPARTICLESDEPENDSUPONMANYFACTORS,FOREXAMPLE,THESCALEOFLIFTINGPIPES,THEPHYSICALPROPERTIESOFLIQUIDANDSOLIDPHASES,THESIZEOFSOLIDPARTICLES,THEVOLUMEOFSUPPLIEDAIR,ANDTHESUBMERGENCERATIO?6,7?SINCETHEPUMPPOWEROFAIRLIFTSYSTEMSISSMALLCOMPAREDTOMECHANICALPUMPS,SUCHFACTORSCANAFFECTTHEPUMPOPERATIONDRASTICALLYTHUS,THEOPERATIONCONDITIONSOFTHEAIRLIFTPUMPSMUSTBECAREFULLYCHOSENTOSUITTHEIRACTUALUSEINORDERTODETERMINEPROPEROPERATINGCONDITIONS,SYSTEMATICEXPERIMENTSAREESSENTIALHOWEVER,THEREISSTILLINSUFFICIENTEXPERIMENTALDATAINTHELITERATURECONCERNINGTHEFLOWCHARACTERISTICSOFGASLIQUIDSOLIDMIXTURES,DESPITEMANYPRIORSTUDIESFURTHERMORE,INDESIGNINGAIRLIFTPUMPSFORCONVEYINGSOLIDPARTICLES,ONEOFTHEIMPORTANTREQUIREMENTSISTOESTIMATETHECRITICALBOUNDARYATWHICHTHESOLIDPARTICLESCANBETRANSPORTEDTHISHASNOTYETBEENINVESTIGATEDEXPERIMENTALLYINDETAILINTHEPRESENTSTUDY,THEOPERATIONPERFORMANCEOFARELATIVELYSMALLAIRLIFTPUMPFORCONVEYINGSOLIDPARTICLESISINVESTIGATEDTHETOTALLENGTHOFTHELIFTINGPIPEIS3200MMANDITSINNERDIAMETERIS18MMTHETIMEAVERAGEDCHARACTERISTICSOFTHEMIXTURESINTHEPIPEAREEXAMINEDUNDERSTABLEPUMPOPERATINGCONDITIONSEMPHASISISPLACEDONTHECRITICALBOUNDARYATWHICHTHESOLIDPARTICLESCANBELIFTEDALONGTHEPIPEWEALSOINTENDTOPROVIDEUSEFULEXPERIMENTALDATAFORTHEAIRLIFTPUMPSYSTEMINORDERTODOSO,THEPARTICLESIZE,THEPARTICLEDENSITY,THEGASINJECTIONPOINT,ANDTHESUPPLIEDGASFLUXONTHEPUMPPERFORMANCEARESYSTEMATICALLYCHANGEDASPARAMETERSTHETRANSPORTPHENOMENAOFGASLIQUIDSOLIDMIXTURESWILLBEDISCUSSEDFROMBOTHEXPERIMENTALANDTHEORETICALVIEWPOINTS2EXPERIMENTALMETHODFIGURE1?A?SHOWSASCHEMATICOFTHEEXPERIMENTALAPPARATUSTHEBODYOFTHEAIRLIFTPUMPCONSISTSOFALIFTINGPIPE,ARESERVOIR,ASUCTIONBOX,ACHAMBERTOINJECTAIRINTOTHELIFTINGPIPE?GASINJECTOR?,APARTICLEFEEDER,ANDANAIRSEPARATORTHETOTALLENGTH,L,OFTHELIFTINGPIPEMADEOFTRANSPARENTPLASTICIS3200MMTHEINNERDIAMETEROFTHEPIPE,D,IS18MMTHEGASINJECTORISSETATACERTAINPOINTOFTHEPIPETHEBOTTOMENDOFTHELIFTINGPIPEISCONNECTEDTOTHERESERVOIRTHROUGHASUFFICIENTLYLARGEPIPEOFDIAMETER146MMWATERISCONTINUOUSLYSUPPLIEDTOTHERESERVOIRATTHETOPENDDURINGEXPERIMENTSTHEWATERSURF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簡(jiǎn)介：畢業(yè)設(shè)計(jì)綜合文檔設(shè)計(jì)題目基于物聯(lián)網(wǎng)的室內(nèi)定位系統(tǒng)學(xué)生姓名XXX指導(dǎo)教師XXX班級(jí)13級(jí)物聯(lián)網(wǎng)班學(xué)號(hào)XXXXXX完成日期2017年04月1第一章第一章項(xiàng)目需求分析說(shuō)明書(shū)項(xiàng)目需求分析說(shuō)明書(shū)1引言引言11編寫(xiě)目的編寫(xiě)目的全球衛(wèi)星定位系統(tǒng)（GPS）的成功使人們對(duì)定位服務(wù)的需求日益增多，然而在室內(nèi)環(huán)境下，由于衛(wèi)星信號(hào)接收受到嚴(yán)重干擾，GPS無(wú)法滿足定位精度的要求?；谖锫?lián)網(wǎng)的室內(nèi)定位技術(shù)由于使用范圍廣,能夠以純軟件的方式實(shí)現(xiàn),定位系統(tǒng)成本低等優(yōu)點(diǎn),成為近年物聯(lián)網(wǎng)位置感知領(lǐng)域的一個(gè)研究熱點(diǎn)。本文對(duì)這一技術(shù)進(jìn)行了較深入、系統(tǒng)的研究,并針對(duì)定位準(zhǔn)確度、定位算法等方面存在的問(wèn)題,提出了相應(yīng)的解決方案。通過(guò)算法比較和實(shí)驗(yàn)分析,證明了方案的有效性和可行性。12背景背景1基于物聯(lián)網(wǎng)的定位系統(tǒng)開(kāi)發(fā)；2該項(xiàng)目是基于前人的一些半成熟的定位算法做的實(shí)驗(yàn)；3該定位系統(tǒng)采用的硬件系統(tǒng)是CC2530，軟件層面是采用VB語(yǔ)言，架構(gòu)層面采用的國(guó)際標(biāo)準(zhǔn)是IEEE802154。13定義ZIGBEE是基于IEEE802154標(biāo)準(zhǔn)的低功耗局域網(wǎng)協(xié)議。根據(jù)國(guó)際標(biāo)準(zhǔn)規(guī)定，ZIGBEE技術(shù)是一種短距離、低功耗的無(wú)線通信技術(shù)。這一名稱（又稱紫蜂協(xié)議）來(lái)源于蜜蜂的八字舞，由于蜜蜂BEE是靠飛翔和“嗡嗡”ZIG地抖動(dòng)翅膀的“舞蹈”來(lái)與同伴傳遞花粉所在方位信息，也就是說(shuō)蜜蜂依靠這樣的方式構(gòu)成了群體中的通信網(wǎng)絡(luò)。物聯(lián)網(wǎng)顧名思義，物聯(lián)網(wǎng)就是物物相連的互聯(lián)網(wǎng)。這有兩層意思其一，物聯(lián)網(wǎng)的核心和基礎(chǔ)仍然是互聯(lián)網(wǎng)，是在互聯(lián)網(wǎng)基礎(chǔ)上的延伸和擴(kuò)展的網(wǎng)絡(luò)；其二，其用戶端延伸和擴(kuò)展到了任何物品與物品之間，進(jìn)行信息交換和通信，也就是物物相息。