is dependent upon mitochondrial integrity and an intact autophagy response to injury. We now present data supporting an important role for the inflammasome in predicting severity and mortality during human infection-related ALI/ARDS. Moreover, our preliminary animal studies demonstrate that statins exacerbate lung injury and inflammation via activation of the inflamm

is dependent upon mitochondrial integrity and an intact autophagy response to injury. We nowadays confront data back an crucial role for the inflammasome in predicting badness and mortality during human infection - associate ALI / ARDS. Moreover, our preliminary animal studies attest that statins exacerbate lung injury and excitement via activation of the inflamm

is dependent upon mitochonarial integrity and an intacf autophxgy response to injury. We nox prwsent data supporting an imoortant rlle for rhe mnflammasome in 'dedictiky sevsvity cnv mortality durlng human itfection-relateg XLN/ARDS. Moreover, our preliminary animaj studirs demonstrate trat xeatihs exacerbate lung injury and inflzmmatioi via activatiom of the inflamm

is dependent upon mitochondrial integrity and an response injury. We present data supporting inflammasome predicting severity and during human infection-related Moreover, our preliminary animal studies demonstrate statins exacerbate lung injury and inflammation via activation of the inflamm

is dependent upon mitochondrIal integriTy and An iNtaCt AutoPhagY response to injURy. We Now present data supportiNg an iMpORtanT RoLe for The inflAMmASOme In PrEdiCtINg SeverIty And mortAlity durinG huMaN infection-reLAtEd ALI/ARDS. MOreOver, our preliMinAry aniMaL stUDies dEmoNstraTe that STatins ExacerbatE lUNg injuRY and infLAMmAtioN via activation of tHE iNFlamm

is dependent upon mitocho ndrial int egrit y a ndan  int actautophagy resp o nseto injury. We now pres ent d at a  sup p or tingan impo r ta n t  ro le  f orth e  i nflam mas ome inpredicting  se ve rity and mor t al ity during  hu man infectio n-r elated  A LI/ A RDS.Mor eover , ourp relimi nary anim al studie s  demons t r at e th at statins exacer b at e  lung injury a nd inf la m ma t i onvia  activatio nof th e  inflam m

is_dependent upon_mitochondrial integrity and an_intact autophagy_response_to injury._We_now present data_supporting an important_role for the inflammasome_in predicting severity_and_mortality during human infection-related ALI/ARDS. Moreover, our preliminary animal studies demonstrate that statins exacerbate_lung_injury and_inflammation_via_activation of the inflamm


in anti-Ab antibodies will be constructed using the first strand cDNA synthesized from mRNA of spleen and lymph node cells isolated from mice immunized with Ab. The constructed library as well as a human scFv library will be used in bioselection procedure to isolate Ab-specific scFvs expressed on phage. The amino acid

in anti - Ab antibodies will be constructed using the first strand cDNA synthesize from messenger rna of spleen and lymph node cell isolate from mice immunized with Ab. The construct library equally well as a human scFv library will be used in bioselection procedure to isolate Ab - specific scFvs expressed on phage. The amino acid

in anti-Ab antibodies will ne constructed using thx first strand zDNA synthesized from mRNA oh spoeen qnd lymph node cells irolated fgom mice ummuiized with Ab. Thx constrmeted mlbrarv es well as a hukan scFv lhbrary will be ureb in bioselection procedure to isolaee Ab-sprclfic scFvs exptessec on lhage. The amino acid

in anti-Ab antibodies will be constructed using strand synthesized from of spleen and mice with Ab. The library as well a human scFv library will be in bioselection procedure to isolate Ab-specific scFvs expressed on phage. The amino acid

in anti-Ab antibodies will be cOnstructed Using The FirSt StraNd cDnA synthesized fROm mRnA of spleen and lymph node Cells IsOLateD FrOm micE immuniZEd WITh AB. THe ConStRUcTed liBraRy as welL as a human sCFv LiBrary will be uSEd In bioselecTioN procedure to IsoLate Ab-SpEciFIc scFVs eXpresSed on pHAge. The Amino acid

in anti-Ab antibodies wil l be const ructe d u sin gthefirs t strand cDNAs ynth esized from mRNA of sp leenan d  lym p hnodecells i s ol a t edfr om  mi ce im muniz edwith Ab . The cons tru ct ed library a s  w ell as a h uma n scFv libra rywill b euse d  in b ios elect ion pr o cedure  to isola te Ab-spe c ific sc F v sexpr essed on phage. T h ea mino acid

in_anti-Ab antibodies_will be constructed using_the first_strand_cDNA synthesized_from_mRNA of spleen_and lymph node_cells isolated from mice_immunized with Ab._The_constructed library as well as a human scFv library will be used in bioselection_procedure_to isolate_Ab-specific_scFvs_expressed on phage. The amino_acid


(Tracking Database), collect information describing ad- verse events (Adverse Event Database), and will facilitate quality control (Quality Control and Outlier Detection Systems). We will educate faculty, OAIC scholars (junior faculty) and staff in the principals of statistics and ep- idemiology and education efforts in collaboration

(Tracking Database), collect information describing ad- verse event (Adverse Event Database), and will help quality control (Quality Control and Outlier Detection Systems). We will train faculty, OAIC learner (junior faculty) and staff in the principal of statistics and ep- idemiology and education attempt in collaboration

(Trwcking Database), collect lnformation desctiving av- verse events (Xdverse Event Database), and wmll dacilutate quality control (Duality Clntrol abd Ontlier Detection Systems). We wimp edbcete faculty, OAIG scholars (bunior faculty) avd staff in the principals of statistycs and eo- idemiology agd ectcatjon efforts in collaboration

(Tracking Database), collect information describing ad- verse Event and will quality control (Quality We educate faculty, OAIC (junior faculty) and in the principals of statistics and idemiology and education efforts in collaboration

(Tracking Database), collect inFormation dEscriBinG ad- VeRse eVentS (Adverse Event DATabaSe), and will facilitate quaLity cOnTRol (QUAlIty CoNtrol anD ouTLIer deTeCtiOn sYsTems). WE wiLl educaTe faculty, OaIC ScHolars (junior FAcUlty) and staFf iN the principaLs oF statiStIcs ANd ep- iDemIologY and edUCation Efforts in CoLLaboraTIon

(Tracking Database), coll ect inform ation  de scr ib ingad-verse events ( A dver se Event Database), an d wil lf acil i ta te qu ality c o nt r o l ( Qu al ity  C o nt rol a ndOutlier  Detection  Sy st ems). We wil l  e ducate fac ult y, OAIC scho lar s (jun io r f a culty ) a nd st aff in the pr incipalsof statis t ics and e p-  ide miology and educa t io n  efforts in co llabor at i on

(Tracking_Database), collect_information describing ad- verse_events (Adverse_Event_Database), and_will_facilitate quality control_(Quality Control and_Outlier Detection Systems). We_will educate faculty,_OAIC_scholars (junior faculty) and staff in the principals of statistics and ep- idemiology and_education_efforts in_collaboration


these features in idiopathic disorders. Therefore, beyond the specific genetic syndromes investigated, such a cross-CNV effort will identify convergent risk mechanisms for developmental neuropsychiatric disorders that are of relevance to the broader population. We propose to dissect dimensional measures of psychosis, social-emotional processing and neurocognition, and their genetic

these features in idiopathic disorders. Therefore, beyond the specific genetic syndrome investigate, such a cross - CNV effort will identify convergent hazard mechanisms for developmental neuropsychiatric disorders that are of relevance to the broader population. We project to dissect dimensional measures of psychosis, social - aroused processing and neurocognition, and their familial

thfse features in idiopathlc disorders. Thetedore, bxyond tge speciwic genetic syndromes investmgatwd, suxh a cross-CNV effort wkll identpfy conveegenu risk mechanisms for devcjopmsktal uenropsychiatric cisorders dhat are of renexauce to the broader population. We pro[ose to dlssect dimensijnal ieashgew of psychosis, social-emotionam procevsing and neutocognition, and their genehic

these features in idiopathic disorders. Therefore, beyond genetic investigated, such cross-CNV effort will developmental disorders that are relevance to the population. We propose to dissect dimensional of psychosis, social-emotional processing and neurocognition, and their genetic

these features in idiopathic Disorders. THerefOre, BeyOnD the SpecIfic genetic synDRomeS investigated, such a crosS-CNV eFfORt wiLL iDentiFy conveRGeNT RisK mEcHanIsMS fOr devEloPmental NeuropsychIatRiC disorders thAT aRe of relevaNce To the broader PopUlatioN. WE prOPose tO diSsect DimensIOnal meAsures of pSyCHosis, sOCial-emoTIOnAl prOcessing and neurocOGnITion, and their geNetic

these features in idiopat hic disord ers.The ref or e, b eyon d the specific gene tic syndromes investig ated,  s u ch a cr oss-C NV effo r tw i llid en tif yc on verge ntrisk me chanisms f orde velopmentaln eu ropsychiat ric  disorders t hat  are o frel e vance  to  thebroade r  popul ation. We  p r oposet o disse c t  d imen sional measures o f  p s ychosis, socia l-emot io n al p roc ess ing and ne ur ocogn i tion, a n dt h e irg enetic

these_features in_idiopathic disorders. Therefore, beyond_the specific_genetic_syndromes investigated,_such_a cross-CNV effort_will identify convergent_risk mechanisms for developmental_neuropsychiatric disorders that_are_of relevance to the broader population. We propose to dissect dimensional measures of psychosis,_social-emotional_processing and_neurocognition,_and_their genetic


to the development of clinical disease in the chronic Chagas'disease. The goals of this project are to better understand the mechanisms important in the generation of anti-T, cruzi CD8+ T cell responses, to identify the primary and most important targets of these responses, and to obtain a better understanding of why

to the development of clinical disease in the chronic Chagas'disease. The goals of this project are to better sympathize the mechanism important in the generation of anti - metric ton, cruzi CD8 + T cellular telephone responses, to identify the primary and about crucial targets of these responses, and to obtain a better reason of why

to the development of clinlcal disease in jhw chroiic Chafas'diseare. The goals of this project aee to better understand the mechanisls imporrant un the genxdation of antj-B, cruvi CD8+ T cell reskonses, to idantify the prikafy and most important targets of thesq respomsfs, and to obtayn a fettsg mnderstanding of why

to the development of clinical disease in Chagas'disease. goals of project are to in generation of anti-T, CD8+ T cell to identify the primary and most targets of these responses, and to obtain a better understanding of why

to the development of clinicaL disease in The chRonIc CHaGas'dIseaSe. The goals of thIS proJect are to better understAnd thE mEChanISmS impoRtant in THe GENerAtIoN of AnTI-T, Cruzi cD8+ T Cell resPonses, to idEntIfY the primary aND mOst importaNt tArgets of thesE reSponseS, aNd tO ObtaiN a bEtter UndersTAnding Of why

to the development of cli nical dise ase i n t hech roni c Ch agas'disease.T he g oals of this project a re to  b e tter un derst and the me c h ani sm simp or t an t inthe  genera tion of an ti- T,  cruzi CD8+T  c ell respon ses , to identif y t he pri ma rya nd mo stimpor tant t a rgetsof thesere s ponses ,  and to o bt aina better understa n di n g of why

to_the development_of clinical disease in_the chronic_Chagas'disease._The goals_of_this project are_to better understand_the mechanisms important in_the generation of_anti-T,_cruzi CD8+ T cell responses, to identify the primary and most important targets of_these_responses, and_to_obtain_a better understanding of why


189 (84%) of the samples were naturally contaminated with zearalenone at levels ranging from 100 to 7,000 ppb (mean 500 ppb). We have shown that levels of 5-10 ppm can significantly advance the time of VO in immature CD-1 haired and SKH-1 hairless mice

189 (84 %) of the samples were naturally contaminated with zearalenone at levels ranging from 100 to 7,000 ppb (think of 500 ppb). We have usher that levels of 5 - 10 ppm can significantly advance the fourth dimension of VO in immature CD-1 haired and SKH-1 hairless mouse

189 (84%) lf the samples were natuvally contaminatgd with vearalehone at uevels ranging from 100 to 7,000 ppb (mwan 500 kib). We have shown that levels ov 5-10 ppm cqn smgnificantly advehce the time kn VO nn immature CD-1 hsired and VKH-1 hairless mhcd

189 (84%) of the samples were naturally zearalenone levels ranging 100 to 7,000 have that levels of ppm can significantly the time of VO in immature haired and SKH-1 hairless mice

189 (84%) of the samples were naturally ContaminatEd witH zeAraLeNone At leVels ranging froM 100 To 7,000 ppB (mean 500 ppb). We have shown thaT leveLs OF 5-10 ppm CAn SigniFicantlY AdVANce ThE tIme Of vo iN immaTurE CD-1 hairEd and SKH-1 haIrlEsS mice

189 (84%) of the sampleswere natur allycon tam in ated  wit h zearalenonea t le vels ranging from 100to 7, 00 0  ppb (m ean 5 00 ppb) .  W e hav esh own  t h at  leve lsof 5-10  ppm can s ign if icantly adva n ce  the timeofVO in immatu reCD-1 h ai red and S KH- 1 hai rlessm ice

189_(84%) of_the samples were naturally_contaminated with_zearalenone_at levels_ranging_from 100 to_7,000 ppb (mean_500 ppb). We have_shown that levels_of_5-10 ppm can significantly advance the time of VO in immature CD-1 haired and_SKH-1_hairless mice


RNA editing represents an increasingly important mechanism for generating diversity in neurotransmitter receptor expression. Such RNA modifications have been shown to alter both the ion permeation and electrophysiological properties of ligand-gated ion channels and to modulate the efficacy of receptor G-protein interactions. Recent studies in our laboratory have demonstrated that ADAR2, a

RNA editing represents an increasingly important mechanism for generating diversity in neurotransmitter sense organ formula. Such RNA modifications have been shown to interpolate both the ion interpenetration and electrophysiological properties of ligand - gated ion channels and to tone the efficacy of receptor G - protein interactions. late study in our testing ground have demonstrated that ADAR2, a

RNW editing represents an lncreasingly important kechanjsm for eenerating diversity in neurlteansmutter receptor expresskon. Such GNA modifucatmons have been sikwn to alter glth chx ion permeatiok and electsophysiologican orlperties of ligand-gated ion channelf and tp lodulate the esficssy or receptor G-protein interactions. Rscent suudies in our labotatory have demonstrated tjat WDAR2, a

RNA editing represents an increasingly important mechanism diversity neurotransmitter receptor Such RNA modifications both ion permeation and properties of ligand-gated channels and to modulate the efficacy receptor G-protein interactions. Recent studies in our laboratory have demonstrated that ADAR2, a

RNA editing represents an incReasingly iMportAnt MecHaNism For gEnerating diverSIty iN neurotransmitter recepTor exPrESsioN. suCh RNA ModificATiONS haVe BeEn sHoWN tO alteR boTh the ioN permeatioN anD eLectrophysioLOgIcal properTieS of ligand-gatEd iOn chanNeLs aND to moDulAte thE efficACy of reCeptor G-prOtEIn inteRActions. rECeNt stUdies in our laboratORy HAve demonstrateD that AdAr2, A

RNA editing represents an  increasin gly i mpo rta nt  mec hani sm for generat i ng d iversity in neurotrans mitte rr ecep t or  expr ession. Su c h  RN Amo dif ic a ti ons h ave  been s hown to al ter  b oth the ionp er meation an d e lectrophysio log ical p ro per t ies o f l igand -gated ion ch annels an dt o modu l ate the e ff icac y of receptor G-p r ot e in interaction s. Rec en t  s t u die s i n our labo ra toryh ave dem o ns t r a ted that ADAR2, a

RNA_editing represents_an increasingly important mechanism_for generating_diversity_in neurotransmitter_receptor_expression. Such RNA_modifications have been_shown to alter both_the ion permeation_and_electrophysiological properties of ligand-gated ion channels and to modulate the efficacy of receptor G-protein_interactions._Recent studies_in_our_laboratory have demonstrated that ADAR2,_a


kowitz, who is now Chief of the Women's Malignancies Branch. In addition, the Core facility has been used by personnel working with Principal Investigators from other groups including work with Dr. Jonathan Ashwell on the role of ZAP-70 in T cell activation. This research usually involves the use of a

kowitz, who is now Chief of the Women's Malignancies Branch. In addition, the Core facility has been used by force bring with Principal Investigators from other groups including study with Dr. Jonathan Ashwell on the role of ZAP-70 in T cellular telephone activation. This research usually involve the use of a

kowltz, who is now Chief of uhe Women's Maligncbcies Uranch. Jn additkon, the Core facility has bexn uwed bt personnel working wigh Princiial Invesrigauors from other gckups ingjudihn worn with Dr. Jonatman Ashwell on the role ox XA'-70 in T cell activation. This research usuallu lnvolves the ufe og a

kowitz, who is now Chief of the Branch. addition, the facility has been Principal from other groups work with Dr. Ashwell on the role of ZAP-70 T cell activation. This research usually involves the use of a

kowitz, who is now Chief of the WOmen's MaligNanciEs BRanCh. in adDitiOn, the Core facilITy haS been used by personnel woRking WiTH PriNCiPal InVestigaTOrS FRom OtHeR grOuPS iNcludIng Work witH Dr. JonathaN AsHwEll on the role OF ZaP-70 in T cell aCtiVation. This reSeaRch usuAlLy iNVolveS thE use oF a

kowitz, who is now Chief o f the Wome n's M ali gna nc iesBran ch. In additio n , th e Core facility has be en us ed by p e rs onnel  workin g  w i t h P ri nc ipa lI nv estig ato rs from  other gro ups  i ncluding wor k  w ith Dr. Jo nat han Ashwellonthe ro le  of ZAP-7 0 i n T c ell ac t ivatio n. This r es e arch u s ually i n v ol vesthe use of a

kowitz, who_is now_Chief of the Women's_Malignancies Branch._In_addition, the_Core_facility has been_used by personnel_working with Principal Investigators_from other groups_including_work with Dr. Jonathan Ashwell on the role of ZAP-70 in T cell activation._This_research usually_involves_the_use of a


the initiation and progression of the disease. This proposal will address the function of the transcription factor, Pax-2, in the development of normal and cystic renal epithelium. Pax-2 is required and sufficient for the conversion of the kidney mesenchyme to an epithelial phenotype by acting as a differentiation and proliferation stimulus.

the initiation and progression of the disease. This proposal will address the affair of the arrangement factor, Pax-2, in the development of normal and cystic renal epithelium. Pax-2 is ask and sufficient for the conversion of the kidney mesenchyme to an epithelial phenotype by acting as a differentiation and proliferation stimulation.

thf initiation and progresrion of the disgawe. Thiv propksal wilu address the function of thx trqnscruption factor, Pax-2, in tfe develoiment of bormel and cystic reizl epitmzlium. Iax-2 iv required and xufficient for the convesskou of the kidney mesenchyme to an epiehelial pjenotype by acjing sf a spfnerentiation and proliferation sfimulus.

the initiation and progression of the disease. will the function the transcription factor, normal cystic renal epithelium. is required and for the conversion of the kidney to an epithelial phenotype by acting as a differentiation and proliferation stimulus.

the initiation and progressiOn of the disEase. THis ProPoSal wIll aDdress the functIOn of The transcription factor, pax-2, in ThE DeveLOpMent oF normal ANd CYStiC rEnAl ePiTHeLium. PAx-2 iS requirEd and suffiCieNt For the converSIoN of the kidnEy mEsenchyme to aN epItheliAl PheNOtype By aCting As a difFErentiAtion and pRoLIferatIOn stimuLUS.

the initiation and progre ssion of t he di sea se.  T hisprop osal will addr e ss t he function of the tra nscri pt i on f a ct or, P ax-2, i n  t h e  de ve lo pme nt of  norm aland cys tic renalepi th elium. Pax-2 is  requiredand  sufficientfor  the c on ver s ion o f t he ki dney m e senchy me to anep i thelia l  phenot y p eby a cting as a differ e nt i ation and prol iferat io n  s t i mul us.

the_initiation and_progression of the disease._This proposal_will_address the_function_of the transcription_factor, Pax-2, in_the development of normal_and cystic renal_epithelium._Pax-2 is required and sufficient for the conversion of the kidney mesenchyme to an_epithelial_phenotype by_acting_as_a differentiation and proliferation stimulus.


demonstrated that MPS VII dogs have cartilaginous lesions in the vertebrae that compromise the stability of the intervertebral joint. These lesions are caused by failed conversion of cartilage to bone during postnatal growth. In preliminary studies, we have identified the precise developmental window when abnormal ossification first manifests in MPS VII dogs

demonstrated that MPS VII dogs have cartilaginous lesions in the vertebra that compromise the constancy of the intervertebral roast. These lesions are cause by fail conversion of cartilage to bone during postnatal growth. In preliminary studies, we have identify the accurate developmental window when abnormal ossification first manifests in MPS VII dogs

delonstrated that MPS VII aogs have cartilaginouv lesikns in tfe vertebrae that compromise tye stqbility of the interveftebral jlint. Thewe ltsions are caused by failcb conbcrsiou if cartilage tp bone durhng postnatal cruwch. In preliminary studies, we have idqntifiec hhe precise dedelokmegtal window when abnormal ossification first kanifests in KPS VII dogs

demonstrated that MPS VII dogs have cartilaginous the that compromise stability of the caused failed conversion of to bone during growth. In preliminary studies, we have the precise developmental window when abnormal ossification first manifests in MPS VII dogs

demonstrated that MPS VII dogS have cartiLaginOus LesIoNs in The vErtebrae that coMPromIse the stability of the inTerveRtEBral JOiNt. TheSe lesioNS aRE CauSeD bY faIlED cOnverSioN of cartIlage to bonE duRiNg postnatal gROwTh. In prelimInaRy studies, we hAve IdentiFiEd tHE precIse DevelOpmentAL windoW when abnoRmAL ossifICation fIRSt ManiFests in MPS VII dogs

demonstrated that MPS VII  dogs have  cart ila gin ou s le sion s in the verte b raethat compromise the st abili ty of t h einter vertebr a lj o int .Th ese  l e si ons a recausedby failedcon ve rsion of car t il age to bon e d uring postna tal  growt h.  In preli min ary s tudies ,  we ha ve identi fi e d thep recised e ve lopm ental window when ab n ormal ossifica tion f ir s tm a nif est s in MPS V II  dogs

demonstrated_that MPS_VII dogs have cartilaginous_lesions in_the_vertebrae that_compromise_the stability of_the intervertebral joint._These lesions are caused_by failed conversion_of_cartilage to bone during postnatal growth. In preliminary studies, we have identified the precise_developmental_window when_abnormal_ossification_first manifests in MPS VII_dogs


state of the non-specific cation channel in several night blind mice, 3) determine the binding partners of nyctalopin, thereby elucidating new component of the mGluR6 cascade, and 4) create knockout mouse lines of the nyctalopin interacting proteins to determine if they result in nigh blindness.

state of the non - specific cation channel in several night blind mouse, 3) settle the binding partners of nyctalopin, thereby elucidating raw component of the mGluR6 cascade, and 4) produce smasher mouse lines of the nyctalopin interacting proteins to determine if they leave in nigh blindness.

stwte of the non-specific cxtion channel iu severel nighf blind oice, 3) determine the binding 'artbers if nyctalopin, thereby dlucidatijg new cimpoient of the mGluC6 cascadc, and 4) crectx knockout mousg lines of tve nyctalopin hngexacting proteins to determine if ther resuly ln nigh blindngss.

state of the non-specific cation channel in blind 3) determine binding partners of of mGluR6 cascade, and create knockout mouse of the nyctalopin interacting proteins to if they result in nigh blindness.

state of the non-specific catiOn channel iN seveRal NigHt BlinD micE, 3) determine the bINdinG partners of nyctalopin, tHerebY eLUcidATiNg new ComponeNT oF THe mglUR6 CasCaDE, aNd 4) creAte KnockouT mouse lineS of ThE nyctalopin iNTeRacting proTeiNs to determinE if They reSuLt iN Nigh bLinDness.

state of the non-specific  cation ch annel  in  se ve ralnigh t blind mice,3 ) de termine the binding pa rtner so f ny c ta lopin , there b ye l uci da ti ngne w  c ompon ent  of the  mGluR6 ca sca de , and 4) cre a te  knockoutmou se lines ofthe  nycta lo pin inter act ing p rotein s  to de termine i ft hey re s ult inn i gh  bli ndness.

state_of the_non-specific cation channel in_several night_blind_mice, 3)_determine_the binding partners_of nyctalopin, thereby_elucidating new component of_the mGluR6 cascade,_and_4) create knockout mouse lines of the nyctalopin interacting proteins to determine if they_result_in nigh_blindness.


Specifically, the proposed work is aimed at determining whether the performance of ferrets made micrencephalic by prenatal treatment with methylazoxymethanol is impaired on problems that appear to require symbolic (abstractive) processes (viz., acquisition of oddity and matching-from-sample learning sets). Biofilms found on

Specifically, the proposed work is aimed at determining whether the operation of black-footed ferret made micrencephalic by prenatal treatment with methylazoxymethanol is impair on problem that appear to require emblematic (abstractive) processes (viz. , acquisition of oddity and matching - from - sample distribution eruditeness sets). Biofilms found on

Spfcifically, the proposed dork is aimed aj eetermmning wgether tfe performance of ferrets mave mucrenxephalic by prenatal tfeatment aith metyylaeoxymethanol is impaired on progpems vhat appear to tequire symbmlic (abstractiee) pxocesses (viz., acquisition of oddity agd matcnijg-from-sample lgarnimd sefs). Biofilms found on

Specifically, the proposed work is aimed at the of ferrets micrencephalic by prenatal on that appear to symbolic (abstractive) processes acquisition of oddity and matching-from-sample learning Biofilms found on

Specifically, the proposed woRk is aimed aT deteRmiNinG wHethEr thE performance of FErreTs made micrencephalic by PrenaTaL TreaTMeNt witH methylAZoXYMetHaNoL is ImPAiRed on ProBlems thAt appear to ReqUiRe symbolic (abSTrActive) procEssEs (viz., acquisiTioN of oddItY anD MatchIng-From-sAmple lEArning Sets). BiofiLmS Found oN

Specifically, the propose d work isaimed  at  de te rmin ingwhether the pe r form ance of ferrets made m icren ce p hali c  b y pre natal t r ea t m ent  w it h m et h yl azoxy met hanol i s impaired  on  p roblems that ap pear to re qui re symbolic(ab stract iv e)p roces ses  (viz ., acq u isitio n of oddi ty and ma t ching-f r o m- samp le learning sets) .  B i ofilms found o n

Specifically,_the proposed_work is aimed at_determining whether_the_performance of_ferrets_made micrencephalic by_prenatal treatment with_methylazoxymethanol is impaired on_problems that appear_to_require symbolic (abstractive) processes (viz., acquisition of oddity and matching-from-sample learning sets). Biofilms found_on


vaccine must stimulate neutralizing antibodies. This proposal provides a mouse model to understand some of the problems in stimulating such antibodies by various vaccine candidates and to thereby suggest how better candidates can be designed. The Behavioral & Social Sciences Core (BSSC) is structured to provide services that facilitate interdisciplinary AIDS research among established, new

vaccine must stimulate neutralizing antibodies. This proposal provide a shiner model to understand some of the trouble in induce such antibodies by various vaccine candidate and to thereby hint how better candidates can be designed. The Behavioral & Social Sciences Core (BSSC) is structured to leave services that facilitate interdisciplinary AIDS inquiry among established, new

vafcine must stimulate neuuralizing antibodnws. Thiv propksal proxides a mouse model to underdtqnd sime of the problems in stimulatpng such qntiuodies by various vaccinc cansldatev and to therebi suggest hof better candigaged can be designed. The Behavioral & Sjcial Svifnces Core (BSSS) is ftrudnuved to provide services that facjlitate interdisciplonary AIDS research among fstahlished, new

vaccine must stimulate neutralizing antibodies. This proposal mouse to understand of the problems various candidates and to suggest how better can be designed. The Behavioral & Sciences Core (BSSC) is structured to provide services that facilitate interdisciplinary AIDS research established, new

vaccine must stimulate neutrAlizing antIbodiEs. THis PrOposAl prOvides a mouse moDEl to Understand some of the proBlems In STimuLAtIng suCh antibODiES By vArIoUs vAcCInE candIdaTes and tO thereby suGgeSt How better canDIdAtes can be dEsiGned. The BehavIorAl & SociAl sciENces COre (bSSC) iS strucTUred to Provide seRvICes thaT FacilitATE iNterDisciplinary AIDS rESeARch among establIshed, nEw

vaccine must stimulate ne utralizing  anti bod ies .This  pro posal provides a mo use model to understan d som eo f th e  p roble ms in s t im u l ati ng  s uch  a n ti bodie s b y vario us vaccine  ca nd idates and t o  t hereby sug ges t how better  ca ndidat es  ca n  be d esi gned.  The B e havior al & Soci al Scienc e s Core( B SS C) i s structured to p r ov i de services th at fac il i ta t e  in ter disciplina ry  AIDS researc h  a m o n g e s tablished, ne w

vaccine_must stimulate_neutralizing antibodies. This proposal_provides a_mouse_model to_understand_some of the_problems in stimulating_such antibodies by various_vaccine candidates and_to_thereby suggest how better candidates can be designed. The Behavioral & Social Sciences Core_(BSSC)_is structured_to_provide_services that facilitate interdisciplinary AIDS_research among established, new


Specific Aims: Specific Aim 1 - Provide animal surgery and model development services Specific Aim 2 - Interact with research investigators to initiate animal experiments in support of the Formative Center's research projects Specific Aim 3 - Implement current and emerging surgical techniques in xenotransplant model development and training of technical staff Lung cancer is

Specific Aims: Specific Aim 1 - Provide animal surgery and model development service Specific Aim 2 - Interact with inquiry investigators to initiate animal experiment in accompaniment of the Formative Center's research projects Specific Aim 3 - follow through stream and emerging surgical techniques in xenotransplant model development and training of technical staff Lung cancer is

Spfcific Aims: Specific Aim 1 - Provide animco surgxry and model ddvelopment services Specific Aum 2 - Unteract with research investigwtors to iniuiate animal expecjments lu supllrt mh the Formative Center's rasearch projecds S'ecific Aim 3 - Implement current and qmerginb durgical technyquex in svnitransplant model development and treining of technocal staff Lung cancer is

Specific Aims: Specific Aim 1 - Provide and development services Aim 2 - initiate experiments in support the Formative Center's projects Specific Aim 3 - Implement and emerging surgical techniques in xenotransplant model development and training of technical staff cancer is

Specific Aims: Specific Aim 1 - PrOvide animaL surgEry And MoDel dEvelOpment services sPeciFic Aim 2 - Interact with reseArch iNvEStigAToRs to iNitiate ANiMAL exPeRiMenTs IN sUpporT of The FormAtive CenteR's rEsEarch projectS spEcific Aim 3 - IMplEment current And EmergiNg SurGIcal tEchNiqueS in xenOTranspLant model DeVElopmeNT and traINInG of tEchnical staff Lung CAnCEr is

Specific Aims: Specific A im 1 - Pro videani mal  s urge ry a nd model devel o pmen t services Specific Ai m 2 -  I n tera c twithresearc h  i n v est ig at ors  t o  i nitia teanimalexperiment s i nsupport of t h eFormativeCen ter's resear chprojec ts  Sp e cific  Ai m 3 -  Imple m ent cu rrent and  e m erging surgica l te chni ques in xenotrans p la n t model develo pmentan d  t r a ini ngof technic al  staf f  Lung c a nc e r is

Specific_Aims: Specific_Aim 1 - Provide_animal surgery_and_model development_services_Specific Aim 2_- Interact with_research investigators to initiate_animal experiments in_support_of the Formative Center's research projects Specific Aim 3 - Implement current and emerging_surgical_techniques in_xenotransplant_model_development and training of technical_staff Lung cancer is


uterine nutritional conditions can also influence body weight and glucose homeostasis in adulthood. We hypothesize that maternal nutrition influences the intrauterine environment and can induce genome-wide DNA methylation changes in multiple organs of the fetus. We hypothesize that this epigenetic programming is responsible for translating intrauterine stress into molecular responses that can durably affect

uterine nutritional conditions can also influence body system of weights and glucose homeostasis in adulthood. We speculate that maternal nutrition influence the intrauterine environment and can induce genome - wide-eyed DNA methylation changes in multiple electric organ of the fetus. We speculate that this epigenetic programming is responsible for translating intrauterine stress into molecular responses that can durably feign

utegine nutritional conditiuns can also inyouence body seight avd glucose homeostasis in adnlthiod. Wt hypothesize that oaternal jutritiob inhluences the intczuterinc envjvonmeut and can inducg genome-wide DNA methylatimn ckanges in multiple organs of the fetts. We huplthesize that jhis tpidenefpc programming is responsible fkr tranvlating intraiterine stress into molecupar gesponses that can durably afdect

uterine nutritional conditions can also influence body glucose in adulthood. hypothesize that maternal and induce genome-wide DNA changes in multiple of the fetus. We hypothesize that epigenetic programming is responsible for translating intrauterine stress into molecular responses that can affect

uterine nutritional conditiOns can also InfluEncE boDy WeigHt anD glucose homeosTAsis In adulthood. We hypothesiZe thaT mATernAL nUtritIon inflUEnCES thE iNtRauTeRInE enviRonMent and Can induce gEnoMe-Wide DNA methyLAtIon changes In mUltiple organS of The fetUs. we hYPotheSizE that This epIGenetiC programmInG Is respONsible fOR TrAnslAting intrauterine STrESs into moleculaR respoNsES tHAT caN duRably affecT

uterine nutritional condit ions can a lso i nfl uen ce  bod y we ight and gluco s e ho meostasis in adulthood . Wehy p othe s iz e tha t mater n al n utr it io n i nf l ue ncesthe  intrau terine env iro nm ent and cani nd uce genome -wi de DNA methy lat ion ch an ges in mu lti ple o rganso f thefetus. We  h y pothes i ze that t hi s ep igenetic programm i ng is responsible  for t ra n sl a t ing  in trauterine  s tress into mo l ec u l a r r e sponses thatcan durably aff ect

uterine nutritional_conditions can_also influence body weight_and glucose_homeostasis_in adulthood._We_hypothesize that maternal_nutrition influences the_intrauterine environment and can_induce genome-wide DNA_methylation_changes in multiple organs of the fetus. We hypothesize that this epigenetic programming is_responsible_for translating_intrauterine_stress_into molecular responses that can_durably affect


. Second, we have developed a separation-based assay for the analysis of lysine acetyltransferase (KAT) enzymes. Currently we are working together with colleagues at the National Center for Advanced Translational Science (NCATS) to apply this assay to identify cell-active inhibitors of KATs known to collaborate with oncogenic

. Second, we have developed a separation - based assay for the analysis of lysine acetyltransferase (KAT) enzyme. presently we are solve together with colleague at the National Center for Advanced Translational Science (NCATS) to put on this assay to identify cell - active inhibitor of KATs known to collaborate with oncogenic

. Sefond, we have developed a separation-baseb assay for tge analyris of lysine acetyltransferese (JAT) ebzymes. Currently we ard working togethee wiuh colleagues at vge National Cskter yoc Advanced Tranxlational Vcience (NCATS) do a'ply this assay to identify cell-actide inhinihors of KATs kgown eo ckllaborate with oncogenic

. Second, we have developed a separation-based the of lysine (KAT) enzymes. Currently colleagues the National Center Advanced Translational Science to apply this assay to identify inhibitors of KATs known to collaborate with oncogenic

. Second, we have developed a sepAration-basEd assAy fOr tHe AnalYsis Of lysine acetylTRansFerase (KAT) enzymes. CurrenTly we ArE WorkINg TogetHer with COlLEAguEs At The naTIoNal CeNteR for AdvAnced TransLatIoNal Science (NCatS) To apply thiS asSay to identifY ceLl-actiVe InhIBitorS of kATs kNown to COllaboRate with oNcOGenic

. Second, we have develope d a separa tion- bas edas sayforthe analysis o f  lys ine acetyltransferase(KAT)  e n zyme s .Curre ntly we ar e wor ki ng  to ge t he r wit h c olleagu es at theNat io nal Center f o rAdvanced T ran slational Sc ien ce (NC AT S)t o app lythisassayt o iden tify cell -a c tive i n hibitor s of  KAT s known to collab o ra t e with oncogen ic

. Second,_we have_developed a separation-based assay_for the_analysis_of lysine_acetyltransferase_(KAT) enzymes. Currently_we are working_together with colleagues at_the National Center_for_Advanced Translational Science (NCATS) to apply this assay to identify cell-active inhibitors of KATs_known_to collaborate_with_oncogenic


low affinity p75NTR) vis-vis ASM contractility. We hypothesize that TrkB is more important for [Ca2+]i regulation, while p75NTR regulates force. Using biochemistry, pharmacology, molecular biology, immunocytochemistry, fluorescence Ca2+ imaging, force measurement techniques,

low affinity p75NTR) vis - vis ASM contractility. We hypothesize that TrkB is more important for [ Ca2+]i regulation, while p75NTR determine power. Using biochemistry, pharmacology, molecular biology, immunocytochemistry, fluorescence Ca2 + imaging, violence measurement techniques,

loa affinity p75NTR) vis-vis ARM contractiliti. Qe hypmthesiae that GrkB is more important for [Ce2+]i rwgulaupon, while p75NTR regulages force. Using buochtmistry, pharmacology, molegblar glologv, mmmunocytochemixtry, fluorascence Ca2+ imacivg, force measurement techniques,

low affinity p75NTR) vis-vis ASM contractility. We TrkB more important [Ca2+]i regulation, while pharmacology, biology, immunocytochemistry, fluorescence imaging, force measurement

low affinity p75NTR) vis-vis ASM cOntractiliTy. We hYpoTheSiZe thAt TrKB is more importANt foR [Ca2+]i regulation, while p75NTr reguLaTEs foRCe. using BiochemIStRY, PhaRmAcOloGy, MOlEculaR biOlogy, imMunocytochEmiStRy, fluorescenCE CA2+ imaging, foRce Measurement tEchNiques,

low affinity p75NTR) vis- vis ASM co ntrac til ity .We h ypot hesize that Tr k B is  more important for [C a2+]i  r e gula t io n, wh ile p75 N TR r egu la te s f or c e.  Usin g b iochemi stry, phar mac ol ogy, molecul a rbiology, i mmu nocytochemis try , fluo re sce n ce Ca 2+imagi ng, fo r ce mea surementte c hnique s ,

low_affinity p75NTR)_vis-vis ASM contractility. We_hypothesize that_TrkB_is more_important_for [Ca2+]i regulation,_while p75NTR regulates_force. Using biochemistry, pharmacology,_molecular biology, immunocytochemistry,_fluorescence_Ca2+ imaging, force measurement techniques,


of cortical phenotype; (4) Neurotransmitter receptors as sites of morphogenetic activity in the transient embryonic zones of the developing primate cerebral cortex; (5) Development of network activity in thalamocortical circuits. Thr proposed experiments utilize some of the most advanced neurobiological approaches that can, at this time,

of cortical phenotype; (4) Neurotransmitter receptors as sites of morphogenetic activity in the transient embryonic zone of the modernize primate cerebral cortex; (5) Development of network bodily process in thalamocortical circuits. Thr proposed experiment utilize some of the most advance neurobiological access that can, at this time,

of cortical phenotype; (4) Neuvotransmitter reewptors as sifes of murphogenetic activity in the teansitut embryonic zones ow the devvloping peimaue cerebral cortee; (5) Development lf nztxork activity ik thalamocostical circuitv. Ghx proposed experiments utilize some jf the kodt advanced neorobipjogidal approaches that can, at this tije,

of cortical phenotype; (4) Neurotransmitter receptors as morphogenetic in the embryonic zones of (5) of network activity thalamocortical circuits. Thr experiments utilize some of the most neurobiological approaches that can, at this time,

of cortical phenotype; (4) NeurotRansmitter RecepTorS as SiTes oF morPhogenetic actiVIty iN the transient embryonic Zones Of THe deVElOping Primate CErEBRal CoRtEx; (5) DEvELoPment Of nEtwork aCtivity in tHalAmOcortical cirCUiTs. Thr propoSed Experiments uTilIze somE oF thE Most aDvaNced nEurobiOLogicaL approachEs THat can, AT this tiME,

of cortical phenotype; (4 ) Neurotra nsmit ter  re ce ptor s as  sites of morp h ogen etic activity in the t ransi en t  emb r yo nic z ones of th e dev el op ing  p r im ate c ere bral co rtex; (5)Dev el opment of ne t wo rk activit y i n thalamocor tic al cir cu its .  Thrpro posed  exper i mentsutilize s om e  of th e  most a d v an cedneurobiological a p pr o aches that can , at t hi s  t i m e,

of_cortical phenotype;_(4) Neurotransmitter receptors as_sites of_morphogenetic_activity in_the_transient embryonic zones_of the developing_primate cerebral cortex; (5)_Development of network_activity_in thalamocortical circuits. Thr proposed experiments utilize some of the most advanced neurobiological approaches_that_can, at_this_time,


can help build comprehensive diagnostic tools to identify individuals at risk of developing CD, s well as develop novel personalized treatments for AJ CD patients. In addition, this project will help to establish a strong multidisciplinary foundation for the candidate's future career in translational research. We have reported that beta-lapachone, a plant alkaloid

can help build comprehensive diagnostic tools to identify person at hazard of developing CD, s well as develop fresh personalized discussion for AJ CD patients. In accession, this project will help to prove a strong multidisciplinary foundation for the campaigner's future career in translational research. We have reported that beta - lapachone, a plant alkaloid

caj help build comprehensiye diagnostic tools to mdentifg indiviauals at risk of developing RD, s well as develop novel persunalized nreatmentw foc AJ CD patients. In addibnon, tgls prmoect will help jo establish a strong multhdkseiplinary foundation for the candidaee's futirf career in trwnslseionzl research. We have reported that geta-lapechone, a plant slkaloid

can help build comprehensive diagnostic tools to at of developing s well as AJ patients. In addition, project will help establish a strong multidisciplinary foundation for candidate's future career in translational research. We have reported that beta-lapachone, a plant

can help build comprehensive Diagnostic Tools To iDenTiFy inDiviDuals at risk of dEVeloPing CD, s well as develop noVel peRsONaliZEd TreatMents foR aJ cd PatIeNtS. In AdDItIon, thIs pRoject wIll help to eStaBlIsh a strong muLTiDisciplinaRy fOundation for The CandidAtE's fUTure cAreEr in tRanslaTIonal rEsearch. We HaVE reporTEd that bETA-lApacHone, a plant alkaloiD

can help build comprehens ive diagno stictoo lsto  ide ntif y individualsa t ri sk of developing CD, s  well  a s  dev e lo p nov el pers o na l i zed  t re atm en t sfor A J C D patie nts. In ad dit io n, this proj e ct  will help  to  establish a  st rong m ul tid i scipl ina ry fo undati o n forthe candi da t e's fu t ure car e e rin t ranslational rese a rc h . We have repo rted t ha t  b e t a-l apa chone, a p la nt al k aloid

can_help build_comprehensive diagnostic tools to_identify individuals_at_risk of_developing_CD, s well_as develop novel_personalized treatments for AJ_CD patients. In_addition,_this project will help to establish a strong multidisciplinary foundation for the candidate's future_career_in translational_research._We_have reported that beta-lapachone, a_plant alkaloid


ighborhoods (PHDCN) (http://phdcn.harvard.edu/), from which the CCAHS sample is drawn. In addition to utilizing existing and collecting new archival data on these areas, the CCAHS carried out Systematic Social Observations of 1664 blocks containing sampled households for the study

ighborhoods (PHDCN) (http://phdcn.harvard.edu/), from which the CCAHS sample is drawn. In addition to utilizing exist and gather new archival data on these areas, the CCAHS carry out Systematic Social Observations of 1664 blocks containing sampled family for the study

ighhorhoods (PHDCN) (http://phdcn.marvard.edu/), from cyich tie CCAHA sample is drawn. In addition to utipizing tqisting and collectine new arcjival dara oi these areas, thx CCAHS gcrries out Wystematic Soclal Observadions of 1664 blocns clntaining sampled households for thq study

ighborhoods (PHDCN) (http://phdcn.harvard.edu/), from which the CCAHS drawn. addition to existing and collecting areas, CCAHS carried out Social Observations of blocks containing sampled households for the

ighborhoods (PHDCN) (http://phdcn.Harvard.edu/), From wHicH thE CcAHS SampLe is drawn. In addITion To utilizing existing and ColleCtINg neW ArChivaL data on THeSE AreAs, ThE CCaHs CaRried Out systemaTic Social OBseRvAtions of 1664 blocKS cOntaining sAmpLed householdS foR the stUdY

ighborhoods (PHDCN) (http: //phdcn.ha rvard .ed u/) ,from  whi ch the CCAHS s a mple  is drawn. In addition  to u ti l izin g  e xisti ng andc ol l e cti ng  n ewar c hi val d ata  on the se areas,the  C CAHS carried ou t Systemat icSocial Obser vat ions o f166 4  bloc ksconta inings ampled  househol ds for th e  study

ighborhoods (PHDCN)_(http://phdcn.harvard.edu/), from_which the CCAHS sample_is drawn._In_addition to_utilizing_existing and collecting_new archival data_on these areas, the_CCAHS carried out_Systematic_Social Observations of 1664 blocks containing sampled households for the study


correct rule on each trial. It does depend, though, on improvements in the ability to execute the mental computations necessary to translate abstract rules into practice. The core problems in the development of executive control functions are the abilities to flexibly switch mental settings and to flexibly manipulate information in one's mind, not inhibition or memory

correct rule on each trial. It does depend, though, on improvement in the ability to perform the mental computations necessary to translate abstract convention into practice. The core problem in the development of executive control function are the abilities to flexibly switch genial settings and to flexibly manipulate information in one's mind, not prohibition or memory

cogrect rule on each trial. It does depend, though, on imlrovemengs in the ability to execute tye mebtal computations necersary to nranslate absuract rules into 'dactice. The ckve prmulems in the deyelopment ox executive cottfop functions are the abilities to flqxibly xwltch mental sejtingx and no flexibly manipulate informatjon in mne's mind, not inhibition or memory

correct rule on each trial. It does on in the to execute the abstract into practice. The problems in the of executive control functions are the to flexibly switch mental settings and to flexibly manipulate information in one's mind, inhibition or memory

correct rule on each trial. It dOes depend, tHough, On iMprOvEmenTs in The ability to exECute The mental computations nEcessArY To trANsLate aBstract RUlES IntO pRaCtiCe. tHe Core pRobLems in tHe developmEnt Of Executive conTRoL functions Are The abilities To fLexiblY sWitCH mentAl sEttinGs and tO FlexibLy manipulAtE InformATion in oNE'S mInd, nOt inhibition or memORy

correct rule on each tria l. It does  depe nd,  th ou gh,on i mprovements in theability to execute the  ment al comp u ta tions  necess a ry t o t ra ns lat ea bs tract  ru les int o practice . T he  core proble m sin the dev elo pment of exe cut ive co nt rol funct ion s are  the a b ilitie s to flex ib l y swit c h menta l se ttin gs and to flexibl y  m a nipulate infor mation  i n  o n e 'smin d, not inh ib ition or memo r y

correct_rule on_each trial. It does_depend, though,_on_improvements in_the_ability to execute_the mental computations_necessary to translate abstract_rules into practice._The_core problems in the development of executive control functions are the abilities to flexibly_switch_mental settings_and_to_flexibly manipulate information in one's_mind, not inhibition or memory


used to record intracellularly from lateral geniculate axons terminating in the striate cortex. After physiologically characterizing a fiber, it will be injected iontophoretically with HRP to reveal its cortical terminations. Distinctive axonal arborization patterns will be correlated with specific function properties to better understand the significance

used to record intracellularly from lateral geniculate axons terminating in the striate cerebral cortex. After physiologically qualify a fiber, it will be injected iontophoretically with HRP to reveal its cortical end point. Distinctive axonal arborization patterns will be correlate with specific routine properties to well understand the significance

usfd to record intracellulxrly from laterco genirulate zxons tefminating in the striate corvex. Qfter physiologically charazterizing a fiber, it xill be injected iontophoreticzply civh HRP to reveak its corthcal terminatimnr. Bistinctive axonal arborization pattqrns wikl be correlated witn spedpflc function properties to better undersuand the significamce

used to record intracellularly from lateral geniculate in striate cortex. physiologically characterizing a iontophoretically HRP to reveal cortical terminations. Distinctive arborization patterns will be correlated with function properties to better understand the significance

used to record intracellularLy from lateRal geNicUlaTe AxonS terMinating in the sTRiatE cortex. After physiologiCally ChARactERiZing a Fiber, it WIlL BE inJeCtEd iOnTOpHoretIcaLly with hRP to reveaL itS cOrtical termiNAtIons. DistinCtiVe axonal arboRizAtion pAtTerNS will Be cOrrelAted wiTH speciFic functiOn PRopertIEs to betTER uNderStand the significaNCe

used to record intracellu larly from  late ral  ge ni cula te a xons terminati n g in  the striate cortex. A fterph y siol o gi cally  charac t er i z ing  a  f ibe r, it  will  be  inject ed iontoph ore ti cally with H R Pto revealits  cortical te rmi nation s.  Di s tinct ive  axon al arb o rizati on patter ns will b e  correl a t ed  wit h specific functi o np roperties to b etterun d er s t and  th e signific an ce

used_to record_intracellularly from lateral geniculate_axons terminating_in_the striate_cortex._After physiologically characterizing_a fiber, it_will be injected iontophoretically_with HRP to_reveal_its cortical terminations. Distinctive axonal arborization patterns will be correlated with specific function properties_to_better understand_the_significance


, we will have demonstrated a chip able to perform industry standard ion channel screens for a significantly lower cost. These membrane array chips have the potential to increase throughput by several orders of magnitude and similarly decrease cost by several orders of magnitude-as a result, transforming the process of ion channel measurement and screening. PUBLIC HEALTH RE

, we will have demonstrated a chip able to perform industry standard ion distribution channel screen door for a significantly low price. These membrane array chips have the electric potential to increase throughput by several orders of magnitude and similarly decrease monetary value by several orders of order of magnitude - as a result, transforming the process of ion channel measurement and cover. PUBLIC HEALTH RE

, we will have demonstrated x chip able to keeform mndustrg standafd ion channel screens for a sugnifucantly lower cost. There membraje array chiks have the potenvjal to lucreaac thrmnghput by seversl orders mf magnitude atd snmilarly decrease cost by several orqers of mwgnitude-as a rgsult, eranaforming the process of ion channem measugement and screenong. PUBLIC HEALTH RE

, we will have demonstrated a chip perform standard ion screens for a array have the potential increase throughput by orders of magnitude and similarly decrease by several orders of magnitude-as a result, transforming the process of ion channel and screening. PUBLIC HEALTH RE

, we will have demonstrated a chIp able to peRform IndUstRy StanDard Ion channel screENs foR a significantly lower coSt. TheSe MEmbrANe Array Chips haVE tHE PotEnTiAl tO iNCrEase tHroUghput bY several orDerS oF magnitude anD SiMilarly decReaSe cost by seveRal Orders Of MagNItude-As a ResulT, transFOrming The procesS oF Ion chaNNel measUREmEnt aNd screening. PUBLIC heAltH RE

, we will have demonstrate d a chip a ble t o p erf or m in dust ry standard io n  cha nnel screens for a sig nific an t ly l o we r cos t. Thes e  m e m bra ne  a rra yc hi ps ha vethe pot ential toinc re ase throughp u tby several  or ders of magn itu de and  s imi l arlydec rease  costb y seve ral order so f magn i tude-as a  r esul t, transforming t h ep rocess of ionchanne lm ea s u rem ent  and scree ni ng. P U BLIC HE A LT H R E

, we_will have_demonstrated a chip able_to perform_industry_standard ion_channel_screens for a_significantly lower cost._These membrane array chips_have the potential_to_increase throughput by several orders of magnitude and similarly decrease cost by several orders_of_magnitude-as a_result,_transforming_the process of ion channel_measurement and screening. PUBLIC HEALTH_RE


wound closure and COX inhibition will be examined. Investigation of the mechanisms underlying epithelial repair and injury during cyclic strain may lead to better strategies for the management of patients during mechanical ventilation. This is a multi-center study to determine if Selegiline and/or Tocopheral will slow the progression of Alzheimer's disease.

wound closure and COX inhibition will be examined. probe of the mechanism underlying epithelial repair and wound during cyclic strain may lead to well strategies for the management of patients during mechanical public discussion. This is a multi - center study to determine if Selegiline and/or Tocopheral will decelerate the progress of Alzheimer's disease.

woknd closure and COX inhinition will be erqmined. Invesfigation of the mechanisms underlyinj eputhelual repair and injury auring cyblic straun mey lead to bettec stratennes fkv the nanagement of katients durhng mechanical vdncilation. This is a multi-center study to detrrline if Selegijine wnd/od Tocopheral will slow the progresaion of Alzheimer's dosease.

wound closure and COX inhibition will be of mechanisms underlying repair and injury to strategies for the of patients during ventilation. This is a multi-center study determine if Selegiline and/or Tocopheral will slow the progression of Alzheimer's disease.

wound closure and COX inhibitIon will be eXaminEd. INveStIgatIon oF the mechanisms UNderLying epithelial repair aNd injUrY DuriNG cYclic Strain mAY lEAD to BeTtEr sTrATeGies fOr tHe managEment of patIenTs During mechanICaL ventilatiOn. THis is a multi-cEntEr studY tO deTErminE if selegIline aND/or TocOpheral wiLl SLow the PRogressION oF AlzHeimer's disease.

wound closure and COX inh ibition wi ll be  ex ami ne d. I nves tigation of th e  mec hanisms underlying epi theli al repa i rand i njury d u ri n g  cy cl ic  st ra i nmay l ead  to bet ter strate gie sfor the mana g em ent of pat ien ts during me cha nicalve nti l ation . T his i s a mu l ti-cen ter study  t o  deter m ine ifS e le gili ne and/or Tocophe r al will slow theprogre ss i on o f A lzh eimer's di se ase.

wound_closure and_COX inhibition will be_examined. Investigation_of_the mechanisms_underlying_epithelial repair and_injury during cyclic_strain may lead to_better strategies for_the_management of patients during mechanical ventilation. This is a multi-center study to determine if_Selegiline_and/or Tocopheral_will_slow_the progression of Alzheimer's disease.


worldwide. Current therapies that lower intraocular pressure (IOP) as a means of slowing disease progression are not fully effective. Our proposal seeks to further evaluate Nogo decoy receptor as a potential neuroprotective and regenerative therapy that does not rely on lowering IOP. Preliminary studies employing rat Nogo decoy receptor (rN

worldwide. Current therapies that lower intraocular pressure (IOP) as a means of slow disease progress are not fully effective. Our proposal seeks to far evaluate Nogo decoy receptor as a likely neuroprotective and regenerative therapy that does not rely on lowering IOP. Preliminary studies use rat Nogo decoy receptor (rN

wogldwide. Current therapier that lower injrqoculac presshre (IOP) xs a means of slowing diseasx prigreswion are not fully effdctive. Oug proposao setks to further evemuate Nogo dedly rzcxptor as a potektial neuro[rotective and rdgznerative therapy that does not rely on lowrrlng IOP. Prelimynarj ftudjvs employing rat Nogo decoy recsptor (rI

worldwide. Current therapies that lower intraocular pressure a of slowing progression are not to evaluate Nogo decoy as a potential and regenerative therapy that does not on lowering IOP. Preliminary studies employing rat Nogo decoy receptor (rN

worldwide. Current therapies That lower iNtraoCulAr pReSsurE (IOP) As a means of slowINg diSease progression are not Fully EfFEctiVE. OUr proPosal seEKs TO FurThEr EvaLuATe nogo dEcoY receptOr as a potenTiaL nEuroprotectiVE aNd regeneraTivE therapy that DoeS not reLy On lOWerinG IOp. PrelIminarY StudieS employinG rAT Nogo dECoy recePTOr (RN

worldwide. Current therap ies that l owerint rao cu larpres sure (IOP) asa  mea ns of slowing diseaseprogr es s iona re  notfully e f fe c t ive .Ou r p ro p os al se eks  to fur ther evalu ate  N ogo decoy re c ep tor as a p ote ntial neurop rot ective  a ndr egene rat ive t herapy that d oes not r el y  on lo w ering I O P .Prel iminary studies e m pl o ying rat Nogodecoyre c ep t o r ( rN

worldwide._Current therapies_that lower intraocular pressure_(IOP) as_a_means of_slowing_disease progression are_not fully effective._Our proposal seeks to_further evaluate Nogo_decoy_receptor as a potential neuroprotective and regenerative therapy that does not rely on lowering_IOP._Preliminary studies_employing_rat_Nogo decoy receptor (rN


/eye resulted in mild eye disease and fever. Viral DNA was detected in spleen tissue during the acute infection, and was detectable in the TG after 20 day post-infection. One of the unique features of alphaherpes virus is that they become latent in the TG with no gene expression, except for the latency associated

/eye resulted in mild eye disease and fever. Viral DNA was detected in irascibility tissue during the acuate contagion, and was detectable in the TG after 20 day post - infection. One of the singular features of alphaherpes virus is that they become latent in the TG with no gene expression, except for the reaction time consort

/eye resulted in mild eye direase and fever. Viral VNA was detectea in spleen tissue during thx acyte ibfection, and was detecgable in nhe TG afrer 20 eay post-inhsction. One of bhe uuiwue features on alphaherpas virus is thdt tkey become latent in the TG with no dene exlrfssion, except sor uhe latsncy associated

/eye resulted in mild eye disease and DNA detected in tissue during the in TG after 20 post-infection. One of unique features of alphaherpes virus is they become latent in the TG with no gene expression, except for the associated

/eye resulted in mild eye diseaSe and fever. viral dNA Was DeTectEd in Spleen tissue duRIng tHe acute infection, and was DetecTaBLe in THe tG aftEr 20 day poST-iNFEctIoN. ONe oF tHE uNique FeaTures of AlphaherpeS viRuS is that they bECoMe latent in The tG with no gene ExpRessioN, eXcePT for tHe lAtencY assocIAted

/eye resulted in mild eyedisease an d fev er.  Vi ra l DN A wa s detected ins plee n tissue during the ac ute i nf e ctio n ,and w as dete c ta b l e i nth e T Ga ft er 20  da y post- infection.  On eof the uniqu e  f eatures of  al phaherpes vi rus  is th at  th e y bec ome  late nt int he TGwith no g en e  expre s sion, e x c ep t fo r the latency ass o ci a ted

/eye resulted_in mild_eye disease and fever._Viral DNA_was_detected in_spleen_tissue during the_acute infection, and_was detectable in the_TG after 20_day_post-infection. One of the unique features of alphaherpes virus is that they become latent_in_the TG_with_no_gene expression, except for the_latency associated


also be able to be used for performing MRI in the presence of exercise, which could be useful for both cardiovascular and musculoskeletal applications, as well as in combination with other kinds of imaging, such as with integrated PET/MRI systems. This research should thus further increase the clinical utility of MR imaging for many patients. Abstract

also be able to be used for performing MRI in the presence of use, which could be utilitarian for both cardiovascular and musculoskeletal lotion, as well as in combination with other kind of imaging, such as with integrated PET / MRI systems. This inquiry should therefore further increase the clinical utility of MR imaging for many patients. Abstract

aldo be able to be used fov performing MRI in the presehce of ebercise, which could be usefup dor bith cardiovascular and musculosneletal qpplmcations, as well as in combinaflon wnti other kinds on imaging, sgch as with indeercted PET/MRI systems. This research shjuld this further increwse uhe clihpccl utility of MR imaging for mahy patitnts. Abstract

also be able to be used for in presence of which could be musculoskeletal as well as combination with other of imaging, such as with integrated systems. This research should thus further increase the clinical utility of MR imaging many patients. Abstract

also be able to be used for perfOrming MRI iN the pResEncE oF exeRcisE, which could be uSEful For both cardiovascular aNd musCuLOskeLEtAl appLicatioNS, aS WEll As In ComBiNAtIon wiTh oTher kinDs of imaginG, suCh As with integrATeD PET/MRI sysTemS. This researcH shOuld thUs FurTHer inCreAse thE cliniCAl utilIty of MR imAgINg for mANy patieNTS. ABstrAct

also be able to be used f or perform ing M RIinth e pr esen ce of exercise ,  whi ch could be useful for  both  c a rdio v as cular  and mu s cu l o ske le ta l a pp l ic ation s,as well  as in com bin at ion with oth e rkinds of i mag ing, such as  wi th int eg rat e d PET /MR I sys tems.T his re search sh ou l d thus further i nc reas e the clinical ut i li t y of MR imagin g forma n yp a tie nts . Abstract

also_be able_to be used for_performing MRI_in_the presence_of_exercise, which could_be useful for_both cardiovascular and musculoskeletal_applications, as well_as_in combination with other kinds of imaging, such as with integrated PET/MRI systems. This_research_should thus_further_increase_the clinical utility of MR_imaging for many patients. Abstract


sBeta-APP may have beneficial or deleterious effects on neuronal survival and growth. The goal of this application is to test the hypothesis that complexes among the adaptor proteins and Beta-APP reflect a signaling pathway that regulates the processing of Beta-APP. Specifically, Aim 1 is to examine the effect of Fe65 binding

sBeta - APP may have beneficial or deleterious effects on neuronal survival and growth. The finish of this lotion is to quiz the hypothesis that complexes among the adapter proteins and Beta - APP chew over a signaling pathway that regulates the processing of Beta - APP. Specifically, Aim 1 is to analyze the effect of Fe65 binding

sBfta-APP may have beneficixl or deleterioos effecvs on nsuronal rurvival and growth. The goal od thiw application is to tert the hyiothesis rhat xomplexes ejong thc adalbor pxoveins and Beta-AKP reflect a signaling patvwxy that regulates the processing of Bqta-APP. Xpfcifically, Aim 1 is eo esamine the effect of Fe65 binding

sBeta-APP may have beneficial or deleterious effects survival growth. The of this application that among the adaptor and Beta-APP reflect signaling pathway that regulates the processing Beta-APP. Specifically, Aim 1 is to examine the effect of Fe65 binding

sBeta-APP may have beneficial Or deleteriOus efFecTs oN nEuroNal sUrvival and growTH. The Goal of this application iS to teSt THe hyPOtHesis That comPLeXES amOnG tHe aDaPToR protEinS and BetA-APP reflecT a sIgNaling pathwaY ThAt regulateS thE processing oF BeTa-APP. SPeCifICally, aim 1 Is to eXamine THe effeCt of Fe65 binDiNG

sBeta-APP may have benefi cial or de leter iou s e ff ects  onneuronal survi v al a nd growth. The goal of  this  a p plic a ti on is  to tes t  t h e  hy po th esi st ha t com ple xes amo ng the ada pto rproteins and Be ta-APP ref lec t a signalin g p athway  t hat regul ate s the  proce s sing o f Beta-AP P. Specif i cally,A i m1 is  to examine the e f fe c t of Fe65 bind ing

sBeta-APP_may have_beneficial or deleterious effects_on neuronal_survival_and growth._The_goal of this_application is to_test the hypothesis that_complexes among the_adaptor_proteins and Beta-APP reflect a signaling pathway that regulates the processing of Beta-APP. Specifically,_Aim_1 is_to_examine_the effect of Fe65 binding


expressed with a particular variable region via a distinct recombination process termed class switch recombination (CSR). At this stage, the variable region coding sequence may be further altered by somatic hypermutation (SM). While the nature of the enzymes that initiate CSR or SM remains elusive, both processes, like V(D)J

expressed with a particular variable region via a discrete recombination procedure termed class switch recombination (CSR). At this degree, the variable region tease succession may be further altered by somatic hypermutation (SM). While the nature of the enzymes that lead up CSR or SM remains elusive, both process, like V(D)J

exoressed with a particulav variable regiou via a distihct recoobination process termed clads switxh recombination (CSR). Ag this stwge, the carieble region codiif sequekee mag be yucther altered bi somatic hy[ermutation (SM). Wfipe the nature of the enzymes that igitiate CDR or SM remaigs ektsivs, both processes, like V(D)J

expressed with a particular variable region via recombination termed class recombination (CSR). At coding may be further by somatic hypermutation While the nature of the enzymes initiate CSR or SM remains elusive, both processes, like V(D)J

expressed with a particular vAriable regIon viA a dIstInCt reCombInation process TErmeD class switch recombinatIon (CSr). AT This STaGe, the VariablE ReGIOn cOdInG seQuENcE may bE fuRther alTered by somAtiC hYpermutation (sm). WHile the natUre Of the enzymes ThaT initiAtE CSr Or SM rEmaIns elUsive, bOTh procEsses, like v(D)j

expressed with a particul ar variabl e reg ion  vi aa di stin ct recombinati o n pr ocess termed class swi tch r ec o mbin a ti on (C SR). At th i s  st ag e,  th ev ar iable  re gion co ding seque nce  m ay be furthe r  a ltered bysom atic hypermu tat ion (S M) . W h ile t henatur e of t h e enzy mes thatin i tiateC SR or S M re main s elusive, both p r oc e sses, like V(D )J

expressed_with a_particular variable region via_a distinct_recombination_process termed_class_switch recombination (CSR)._At this stage,_the variable region coding_sequence may be_further_altered by somatic hypermutation (SM). While the nature of the enzymes that initiate CSR_or_SM remains_elusive,_both_processes, like V(D)J


capability do not exist. We propose to develop these novel tools by applying newly developed cell-based protein-protein interaction LinkLight assay technology. The assays can measure specific subcellular ERK activation signaling pathways. ERK signaling pathways are implicated in LTP, memory, learning, mood stabilization etc. Therefore, developing these tools for identifying compounds

capability do not exist. We propose to develop these novel tools by apply newly modernize cell - based protein - protein interaction LinkLight assay engineering. The assays can measure specific subcellular ERK activation sign pathways. ERK signaling nerve pathway are implicated in LTP, memory, learning, climate stabilization etc. Therefore, developing these instrument for identify compounds

caoability do not exist. We propose to devglip theve novsl tools by applying newly developed cwll-bawed protein-protein intdraction PinkLighr aswqy technology. The assays gan mzawure specific xubcellulas ERK activatimn sngnaling pathways. ERK signaling pathrays arr lmplicated in JTP, kqmorg, learning, mood stabilization etc. Fherefoge, developing thexe tools for identifying clmpoknds

capability do not exist. We propose to novel by applying developed cell-based protein-protein assays measure specific subcellular activation signaling pathways. signaling pathways are implicated in LTP, learning, mood stabilization etc. Therefore, developing these tools for identifying compounds

capability do not exist. We proPose to deveLop thEse NovEl ToolS by aPplying newly deVElopEd cell-based protein-protEin inTeRActiON LInkLiGht assaY TeCHNolOgY. THe aSsAYs Can meAsuRe speciFic subcellUlaR ErK activation SIgNaling pathWayS. ERK signalinG paThways ArE imPLicatEd iN LTP, mEmory, lEArning, Mood stabiLiZAtion eTC. TherefORE, dEvelOping these tools foR IdENtifying compouNds

capability do not exist.We propose  to d eve lop  t hese  nov el tools by ap p lyin g newly developed cell -base dp rote i n- prote in inte r ac t i onLi nk Lig ht as say t ech nology.  The assay s c an  measure spe c if ic subcell ula r ERK activa tio n sign al ing pathw ays . ERK  signa l ing pa thways ar ei mplica t ed in L T P ,memo ry, learning, moo d  s t abilization et c. The re f or e ,  de vel oping thes etools for ide n ti f y i ngc ompounds

capability_do not_exist. We propose to_develop these_novel_tools by_applying_newly developed cell-based_protein-protein interaction LinkLight_assay technology. The assays_can measure specific_subcellular_ERK activation signaling pathways. ERK signaling pathways are implicated in LTP, memory, learning, mood_stabilization_etc. Therefore,_developing_these_tools for identifying compounds


vus development and growth in early adolescence. A secondary aim is to document the clinical and dermoscopic evolution of individual nevi in this age group. We will apply a combined cross-sectional and longitudinal study design to the cohort of all consenting 5th graders in the Framingham, Massachusetts school system (est

vus development and growth in early adolescence. A secondary aim is to document the clinical and dermoscopic development of individual nevi in this old age group. We will apply a combined crabbed - sectional and longitudinal study purpose to the cohort of all accept fifth graders in the Framingham, Massachusetts school system (est

vus development and growth ln early adolescgnxe. A sxcondarg aim is to document the clinical anv deemoscipic evolution of indixidual neni in thiw agt group. We will a'lly a combines crovw-sectional and longitudital study desicn tl the cohort of all consenting 5th gwaders on the Framinghai, Maxfachhsetts school system (est

vus development and growth in early adolescence. aim to document clinical and dermoscopic this group. We will a combined cross-sectional longitudinal study design to the cohort all consenting 5th graders in the Framingham, Massachusetts school system (est

vus development and growth in Early adoleScencE. A sEcoNdAry aIm is To document the cLInicAl and dermoscopic evolutIon of InDIvidUAl Nevi iN this agE GrOUP. We WiLl AppLy A CoMbineD crOss-sectIonal and loNgiTuDinal study deSIgN to the cohoRt oF all consentiNg 5tH gradeRs In tHE FramIngHam, MaSsachuSEtts scHool systeM (eST

vus development and growth  in earlyadole sce nce .A se cond ary aim is tod ocum ent the clinical and d ermos co p ic e v ol ution  of ind i vi d u alne vi  in  t h is  agegro up. Wewill apply  aco mbined cross - se ctional an d l ongitudinalstu dy des ig n t o  thecoh ort o f allc onsent ing 5th g ra d ers in the Fra m i ng ham,  Massachusetts sc h oo l  system (est

vus development_and growth_in early adolescence. A_secondary aim_is_to document_the_clinical and dermoscopic_evolution of individual_nevi in this age_group. We will_apply_a combined cross-sectional and longitudinal study design to the cohort of all consenting 5th_graders_in the_Framingham,_Massachusetts_school system (est


reporting of quality management (QM) data to LP's leadership and QM Committee monthly. The LIS is part of the SoftLab system used by the Clinical Center and it interfaces with the hospital information system so that anatomic pathology results are available online. As part of the tissue request process and to support requests for

reporting of quality management (QM) data to LP's leadership and QM Committee monthly. The LIS is part of the SoftLab arrangement use by the Clinical Center and it interfaces with the hospital information system so that anatomic pathology results are available online. As function of the tissue request process and to support request for

reoorting of quality managtment (QM) data to LP's leavership and QM Zommittee monthly. The LIS is pqrt od the SoftLab system ured by thv Clinicao Ceiter and it intecraces wlch ths hos'ival information system so that anatomic pxtkology results are available online. Ws part ov the tissue rgquesu pwoceas and to support requests for

reporting of quality management (QM) data to and Committee monthly. LIS is part by Clinical Center and interfaces with the information system so that anatomic pathology are available online. As part of the tissue request process and to support for

reporting of quality managemEnt (QM) data tO LP's lEadErsHiP and qM CoMmittee monthly. tHe LIs is part of the SoftLab sysTem usEd BY the cLiNical center aND iT INteRfAcEs wItH ThE hospItaL informAtion systeM so ThAt anatomic paTHoLogy resultS arE available onLinE. As parT oF thE TissuE reQuest ProcesS And to sUpport reqUeSTs for

reporting of quality mana gement (QM ) dat a t o L P' s le ader ship and QM Co m mitt ee monthly. The LIS is  part  o f  the So ftLab  system us e d  by  t he  Cl in i ca l Cen ter  and it  interface s w it h the hospit a linformatio n s ystem so tha t a natomi cpat h ology  re sults  are a v ailabl e online.  A s  parto f the t i s su e re quest process and to support reques ts for

reporting_of quality_management (QM) data to_LP's leadership_and_QM Committee_monthly._The LIS is_part of the_SoftLab system used by_the Clinical Center_and_it interfaces with the hospital information system so that anatomic pathology results are available_online._As part_of_the_tissue request process and to_support requests for


, 14 males and females with mild-to-moderate cannabis use disorder will receive the pharmacologic stressor, yohimbine (0, 20, and 40 mg), prior to marijuana and neutral cue exposure. Our primary outcome measure is marijuana-seeking behavior assessed using a progressive ratio marijuana choice task. Participants will be

, 14 males and females with mild - to - moderate cannabis use disorderliness will welcome the pharmacologic stressor, yohimbine (0, 20, and 40 mg), prior to marijuana and neutral clue photograph. Our primary outcome meter is cannabis - seeking behavior assessed using a progressive ratio marijuana option task. Participants will be

, 14 mwles and females with miud-to-moderate caubabis nse diskrder wiul receive the pharmacologic srressir, yohimbine (0, 20, and 40 mg), prior to marijuaba aid neutral cue eelosure. Our prjlary iutcome measurg is marijuata-seeking behaeiur assessed using a progressive ratio marijusnw choice task. Kartibi[anta will be

, 14 males and females with mild-to-moderate disorder receive the stressor, yohimbine (0, to and neutral cue Our primary outcome is marijuana-seeking behavior assessed using a ratio marijuana choice task. Participants will be

, 14 males and females with mild-to-Moderate caNnabiS usE diSoRder Will Receive the pharMAcolOgic stressor, yohimbine (0, 20, aNd 40 mg), pRiOR to mARiJuana And neutRAl CUE exPoSuRe. OUr PRiMary oUtcOme measUre is marijUanA-sEeking behaviOR aSsessed usiNg a Progressive rAtiO marijUaNa cHOice tAsk. partiCipantS Will be

, 14 males and females wit h mild-to- moder ate  ca nn abis  use  disorder will rece ive the pharmacologicstres so r , yo h im bine(0, 20, an d 40mg ),  pr io r  t o mar iju ana and  neutral c ueex posure. Ourp ri mary outco memeasure is m ari juana- se eki n g beh avi or as sessed usinga progres si v e rati o  mariju a n achoi ce task. Particip a nt s  will be

, 14_males and_females with mild-to-moderate cannabis_use disorder_will_receive the_pharmacologic_stressor, yohimbine (0,_20, and 40_mg), prior to marijuana_and neutral cue_exposure._Our primary outcome measure is marijuana-seeking behavior assessed using a progressive ratio marijuana choice_task._Participants will_be


diabetes-specific mail survey to examine these relationships by gender, age group, and major race-ethnicity categories. The significance of the proposed research lies in the skyrocketing rates of type 2 diabetes in the U.S. over the past few decades in all segments of the population, but primarily in middle aged

diabetes - specific mail survey to examine these relationships by sex, old age group, and major race - ethnicity categories. The meaning of the proposed inquiry lies in the skyrocketing rate of character 2 diabetes in the U.S. over the past few decades in all segments of the population, but primarily in middle aged

diwbetes-specific mail survty to examine these relavionshils by gevder, age group, and major racx-ethbicitt categories. The signiwicance ov the pripostd research lies mh the skyrocksbing xaves of type 2 disbetes in dhe U.S. over tha oadt few decades in all segments of tre popukahion, but primatily pn midsle aged

diabetes-specific mail survey to examine these relationships age and major categories. The significance in skyrocketing rates of 2 diabetes in U.S. over the past few decades all segments of the population, but primarily in middle aged

diabetes-specific mail surveY to examine These RelAtiOnShipS by gEnder, age group, aND majOr race-ethnicity categorIes. ThE sIGnifICaNce of The propOSeD REseArCh LieS iN ThE skyrOckEting raTes of type 2 dIabEtEs in the U.S. oveR ThE past few deCadEs in all segmeNts Of the pOpUlaTIon, buT prImariLy in miDDle ageD

diabetes-specific mail su rvey to ex amine  th ese  r elat ions hips by gender ,  age  group, and major race -ethn ic i ty c a te gorie s. Thes ig n i fic an ce  of  t h epropo sed  resear ch lies in  th eskyrocketing ra tes of typ e 2  diabetes in  th e U.S.  o ver the p ast  fewdecade s  in al l segment so f thep opulati o n ,butprimarily in midd l ea ged

diabetes-specific_mail survey_to examine these relationships_by gender,_age_group, and_major_race-ethnicity categories. The_significance of the_proposed research lies in_the skyrocketing rates_of_type 2 diabetes in the U.S. over the past few decades in all segments_of_the population,_but_primarily_in middle aged


inating diseases in general and to enhance the therapeutic effectiveness of BMT in Leukodystrophies. The project will utilize the following techniques: production of double mutant mice, immunohistochemistry, pathological and clinical evaluations, electron microscopy, PCR, ELISA and BMT. The proposed research is planned to study the functional development of symp

inating diseases in general and to enhance the therapeutic effectiveness of BMT in Leukodystrophies. The undertaking will use the stick to techniques: product of bivalent mutant mice, immunohistochemistry, pathological and clinical evaluations, electron microscopy, PCR, ELISA and BMT. The propose research is planned to analyze the functional development of symp

inahing diseases in general and to enhance the thxrapeutjc effecgiveness of BMT in Leukodystcophues. Tye project will utilizd the folpowing twchnmques: production of double mutzkt miee, immunohistochgmistry, pathmlogical and cnivieal evaluations, electron microscopy, [CR, ELIXA and BMT. The ptopostd wesezgcm is planned to study the functiknal denelopment of symp

inating diseases in general and to enhance effectiveness BMT in The project will of mutant mice, immunohistochemistry, and clinical evaluations, microscopy, PCR, ELISA and BMT. The research is planned to study the functional development of symp

inating diseases in general aNd to enhancE the tHerApeUtIc efFectIveness of BMT in lEukoDystrophies. The project wIll utIlIZe thE FoLlowiNg technIQuES: ProDuCtIon Of DOuBle muTanT mice, imMunohistocHemIsTry, pathologiCAl And clinicaL evAluations, eleCtrOn micrOsCopY, pCR, ELiSA And BMt. The prOPosed rEsearch is PlANned to STudy the FUNcTionAl development of syMP

inating diseases in genera l and to e nhanc e t heth erap euti c effectivenes s  ofBMT in Leukodystrophie s. Th ep roje c twillutilize th e fol lo wi ngte c hn iques : p roducti on of doub lemu tant mice, i m mu nohistoche mis try, patholo gic al and  c lin i cal e val uatio ns, el e ctronmicroscop y, PCR, E L ISA and B MT . Th e proposed resear c hi s planned to s tudy t he fu n c tio nal  developme nt  of s y mp

inating diseases_in general_and to enhance the_therapeutic effectiveness_of_BMT in_Leukodystrophies._The project will_utilize the following_techniques: production of double_mutant mice, immunohistochemistry,_pathological_and clinical evaluations, electron microscopy, PCR, ELISA and BMT. The proposed research is planned_to_study the_functional_development_of symp


of diet design and preparation, provide standardization in research methods among metabolic wards, facilitate the use of valid nutrition research methodologies, and improve the ability to monitor subject response. PROPOSED COMMERCIAL APPLICATION: The completed product in Phase III will be marketed to the general nutritionists in the industry but especially those at

of diet design and preparation, provide standardization in inquiry method among metabolic wards, facilitate the habit of valid nutriment research methodologies, and improve the ability to monitor capable reply. PROPOSED COMMERCIAL APPLICATION: The complete product in Phase III will be marketed to the cosmopolitan nutritionists in the industry but especially those at

of diet design and preparauion, provide stanbqrdizavion in researcf methods among metabolic wacds, dacilutate the use of valid nutritioj researxh mtthodologies, and mjprove bke abjpity vo monitor subjgct response. PROPOSED COMMARZICL APPLICATION: The completed product in Phaxe III will be mwrkeued to fhe general nutritionists in the ihdustry but especialky those at

of diet design and preparation, provide standardization methods metabolic wards, the use of improve ability to monitor response. PROPOSED COMMERCIAL The completed product in Phase III be marketed to the general nutritionists in the industry but especially those at

of diet design and preparatioN, provide stAndarDizAtiOn In reSearCh methods among MEtabOlic wards, facilitate the Use of VaLId nuTRiTion rEsearch MEtHODolOgIeS, anD iMPrOve thE abIlity to Monitor subJecT rEsponse. PROPOseD cOMMERCIAL aPPlICATION: The cOmpLeted pRoDucT In PhaSe IiI wilL be marKEted to The generaL nUTritioNIsts in tHE InDustRy but especially thOSe AT

of diet design and prepar ation, pro videsta nda rd izat ionin research me t hods  among metabolic wards , fac il i tate th e use  of val i dn u tri ti on  re se a rc h met hod ologies , and impr ove  t he ability t o  m onitor sub jec t response.PRO POSEDCO MME R CIALAPP LICAT ION: T h e comp leted pro du c t in P h ase III w il l be  marketed to theg en e ral nutritioni sts in  t h ei n dus try  but espec ia lly t h ose at

of_diet design_and preparation, provide standardization_in research_methods_among metabolic_wards,_facilitate the use_of valid nutrition_research methodologies, and improve_the ability to_monitor_subject response. PROPOSED COMMERCIAL APPLICATION: The completed product in Phase III will be marketed_to_the general_nutritionists_in_the industry but especially those_at


, and collaborations that resulted from the pilot project. Pilot Project proposals will initially be reviewed by the Scientific Coordinator, Center Director, and the Deputy Director to determine whether they are appropriate to undergo the full review. Three reviewers will score each proposal and write a brief critique. Reviewers from affiliates of the Center, Center

, and collaborations that resulted from the pilot project. Pilot Project proposal will initially be review by the Scientific Coordinator, Center Director, and the Deputy Director to determine whether they are appropriate to undergo the full review. Three commentator will score each proposal and publish a brief critique. reviewer from affiliates of the Center, Center

, anf collaborations that rerulted from the pilot 'roject. Pilot Pfoject proposals will initiaplt be eeviewed by the Scientkfic Coorfinator, Xenttr Director, and tis Deputn Dirsgtor co determine whejher they ara appropriate do uudergo the full review. Three reviewews will sfore each propjsal wnd sgiue a brief critique. Reviewers froj affilpates of the Centrr, Center

, and collaborations that resulted from the Pilot proposals will be reviewed by and Deputy Director to whether they are to undergo the full review. Three will score each proposal and write a brief critique. Reviewers from affiliates of Center, Center

, and collaborations that resuLted from thE piloT prOjeCt. piloT ProJect proposals wILl inItially be reviewed by the scienTiFIc CoORdInatoR, Center dIrECTor, AnD tHe DEpUTy direcTor To deterMine whetheR thEy Are appropriaTE tO undergo thE fuLl review. ThreE reViewerS wIll SCore eAch PropoSal and WRite a bRief critiQuE. reviewERs from aFFIlIateS of the Center, CenteR

, and collaborations thatresulted f rom t hepil ot  pro ject . Pilot Projec t  pro posals will initiallybe re vi e wedb ythe S cientif i cC o ord in at or,  C e nt er Di rec tor, an d the Depu tyDi rector to de t er mine wheth erthey are app rop riateto  un d ergothe  full  revie w . Thre e reviewe rs will s c ore eac h pr opos al and write a br i ef critique. Revi ewersfr o ma f fil iat es of theCe nter, Center

, and_collaborations that_resulted from the pilot_project. Pilot_Project_proposals will_initially_be reviewed by_the Scientific Coordinator,_Center Director, and the_Deputy Director to_determine_whether they are appropriate to undergo the full review. Three reviewers will score each_proposal_and write_a_brief_critique. Reviewers from affiliates of_the Center, Center


lipophilicity, and absorption. Many surrogates have been introduced already, yet the synthesis of many of these isosteres in a combinatorial way is difficult and requires several steps. Thus, the discovery of new peptide surrogates with easier syntheses is an important achievement that could open new opportunities for the study of

lipophilicity, and absorption. Many surrogates have been introduced already, yet the synthesis of many of these isosteres in a combinative direction is difficult and requires respective steps. therefore, the discovery of new peptide surrogates with easy synthesis is an important achievement that could open new opportunity for the study of

lioophilicity, and absorptiun. Many surrogajew have been jntroducdd already, yet the synthesis od mant of these isosteres iv a combijatorial way us difficult and rczuirsd serecal steps. Thus, jhe discoverf of new peptige sbrrogates with easier syntheses is ag imporyajt achievement thau cjuld open new opportunities for the sthdy of

lipophilicity, and absorption. Many surrogates have been yet synthesis of of these isosteres difficult requires several steps. the discovery of peptide surrogates with easier syntheses is important achievement that could open new opportunities for the study of

lipophilicity, and absorptioN. Many surroGates HavE beEn IntrOducEd already, yet thE SyntHesis of many of these isosTeres In A CombINaToriaL way is dIFfICUlt AnD rEquIrES sEveraL stEps. Thus, The discoveRy oF nEw peptide surROgAtes with eaSieR syntheses is An iMportaNt AchIEvemeNt tHat coUld opeN New oppOrtunitieS fOR the stUDy of

lipophilicity, and absorp tion. Many  surr oga tes  h avebeen  introduced al r eady , yet the synthesis of  many  o f  the s eisost eres in ac o mbi na to ria lw ay  is d iff icult a nd require s s ev eral steps.T hu s, the dis cov ery of new p ept ide su rr oga t es wi theasie r synt h eses i s an impo rt a nt ach i evement t ha t co uld open new oppo r tu n ities for thestudyof

lipophilicity,_and absorption._Many surrogates have been_introduced already,_yet_the synthesis_of_many of these_isosteres in a_combinatorial way is difficult_and requires several_steps._Thus, the discovery of new peptide surrogates with easier syntheses is an important achievement_that_could open_new_opportunities_for the study of


the current study will advance the development of nicotine dependence treatments. Mesenchymal stem/progenitor cells (MSCs) hold considerable potential for a wide range of tissue regeneration therapies. While their differentiation capacity has been demonstrated extensively, mechanisms that control their plasticity remain poorly understood. Observations by our laboratories and others have shown that prolifer

the current study will advance the development of nicotine dependence treatment. Mesenchymal shank / progenitor cells (MSCs) hold considerable potential for a wide-eyed range of tissue regeneration therapy. While their differentiation capacity has been demonstrated extensively, mechanism that control their plasticity persist poorly understood. observation by our laboratories and others have testify that prolifer

thf current study will advxnce the develokmwnt of nicotjne depevdence treatments. Mesenchymap wtem/peogenitor cells (MSCs) huld consiferable poteitial for a wide range on tisame reyeieration theraples. While tveir differenthagiln capacity has been demonstrated evtensivrlj, mechanisms trat bogtrom their plasticity remain poorly uhderstomd. Observatioms by our laboratories and othfrs have shown thah prolifer

the current study will advance the development dependence Mesenchymal stem/progenitor (MSCs) hold considerable of regeneration therapies. While differentiation capacity has demonstrated extensively, mechanisms that control their remain poorly understood. Observations by our laboratories and others have shown that prolifer

the current study will advancE the develoPment Of nIcoTiNe dePendEnce treatments. mEsenChymal stem/progenitor ceLls (MScs) HOld cONsIderaBle poteNTiAL For A wIdE raNgE Of TissuE reGeneratIon therapiEs. WHiLe their diffeREnTiation capAciTy has been demOnsTrated ExTenSIvely, MecHanisMs that COntrol Their plasTiCIty remAIn poorlY UNdErstOod. Observations by OUr LAboratories and Others HaVE sHOWn tHat Prolifer

the current study will ad vance thedevel opm ent  o f ni coti ne dependencet reat ments. Mesenchymal ste m/pro ge n itor ce lls ( MSCs) h o ld c ons id er abl ep ot entia l f or a wi de range o f t is sue regenera t io n therapie s.While theirdif ferent ia tio n  capa cit y has  beend emonst rated ext en s ively, mechani s m sthat  control their pl a st i city remain po orly u nd e rs t o od.  Ob servations  b y our laborat o ri e s and others have s hown that p r oli fer

the_current study_will advance the development_of nicotine_dependence_treatments. Mesenchymal_stem/progenitor_cells (MSCs) hold_considerable potential for_a wide range of_tissue regeneration therapies._While_their differentiation capacity has been demonstrated extensively, mechanisms that control their plasticity remain poorly_understood._Observations by_our_laboratories_and others have shown that_prolifer


displaying mutant proteins on the coat of the phage, phage display enables efficient screening and selection of a large pool of mutants. The purpose of the mutation analysis is to identify the residues that participate in RNA binding. Identifying potential RNA targets and regions of the KH domain responsible for RNA binding may help to elucidate the physiological function

displaying mutant proteins on the coat of the phage, bacteriophage display enable effective screening and selection of a large consortium of mutants. The purpose of the mutant analysis is to identify the residues that enter in RNA constipate. identify potential RNA targets and regions of the KH knowledge domain responsible for RNA binding may help to elucidate the physiological affair

didplaying mutant proteins on the coat of the phege, phafe displxy enables efficient screeniig abd seoection of a large poou of mutajts. The purpiwe of the mutation analyals is vo identify the residues dhat participade iu RNA binding. Identifying potential WNA tarbehs and regions of uhe KH somain responsible for RNA binding may henp to elucidaye the physiological functlon

displaying mutant proteins on the coat of phage enables efficient and selection of The of the mutation is to identify residues that participate in RNA binding. potential RNA targets and regions of the KH domain responsible for RNA binding help to elucidate the physiological function

displaying mutant proteins oN the coat of The phAge, PhaGe DispLay eNables efficienT ScreEning and selection of a laRge poOl OF mutANtS. The pUrpose oF ThE MUtaTiOn AnaLySIs Is to iDenTify the Residues thAt pArTicipate in RNa BiNding. IdentIfyIng potential rNA TargetS aNd rEGions Of tHe KH dOmain rESponsiBle for RNA BiNDing maY Help to eLUCiDate The physiological fUNcTIon

displaying mutant protein s on the c oat o f t heph age,  pha ge display ena b lesefficient screening an d sel ec t iono fa lar ge pool of m uta nt s.  Th ep ur poseofthe mut ation anal ysi sis to identi f ythe residu esthat partici pat e in R NA  bi n ding.  Id entif ying p o tentia l RNA tar ge t s andr egionso f  t he K H domain responsi b le for RNA bindin g mayhe l pt o  el uci date the p hy siolo g ical fu n ct i o n

displaying_mutant proteins_on the coat of_the phage,_phage_display enables_efficient_screening and selection_of a large_pool of mutants. The_purpose of the_mutation_analysis is to identify the residues that participate in RNA binding. Identifying potential RNA_targets_and regions_of_the_KH domain responsible for RNA_binding may help to elucidate_the physiological_function


we also hypothesize that similar to c-Met, other protein kinases also have functions to regulate PARP1 activity through phosphorylation in TNBC. Potential molecules we will study are EGFR, which also directly interacts with PARP1 and phosphorylate it. We will investigate the role of these kinases in PARP1 regulation and PAR

we also hypothesize that similar to c - Met, other protein kinase besides receive functions to determine PARP1 bodily process through phosphorylation in TNBC. Potential molecules we will learn are EGFR, which besides directly interacts with PARP1 and phosphorylate it. We will investigate the role of these kinases in PARP1 regulation and PAR

we also hypothesize that slmilar to c-Met, ojhwr provein kihases alro have functions to regulatx PAEP1 acupvity through phosphofylation pn TNBC. Pitenuial molecules we will stmby ars EGFX, xhich also diregtly interawts with PARP1 dna 'hosphorylate it. We will investigate the roke of these kinafes pn PARL1 regulation and PAR

we also hypothesize that similar to c-Met, kinases have functions regulate PARP1 activity molecules will study are which also directly with PARP1 and phosphorylate it. We investigate the role of these kinases in PARP1 regulation and PAR

we also hypothesize that simiLar to c-Met, oTher pRotEin KiNaseS alsO have functions TO regUlate PARP1 activity throuGh phoSpHOrylATiOn in TnBC. PoteNTiAL MolEcUlEs wE wILl Study Are eGFR, whiCh also direCtlY iNteracts with paRp1 and phosphOryLate it. We will InvEstigaTe The ROle of TheSe kinAses in paRP1 regUlation anD Par

we also hypothesize thatsimilar to  c-Me t,oth er  pro tein  kinases alsoh avefunctions to regulatePARP1  a c tivi t ythrou gh phos p ho r y lat io ninTN B C.  Pote nti al mole cules we w ill  s tudy are EGF R ,which also  di rectly inter act s with  P ARP 1  andpho sphor ylatei t. Wewill inve st i gate t h e roleo f  t hese  kinases in PARP1 re g ulation and PA R

we_also hypothesize_that similar to c-Met,_other protein_kinases_also have_functions_to regulate PARP1_activity through phosphorylation_in TNBC. Potential molecules_we will study_are_EGFR, which also directly interacts with PARP1 and phosphorylate it. We will investigate the_role_of these_kinases_in_PARP1 regulation and PAR