. However, ultimately we wish to image activity in vivo and our final study in this program will include a tentative exploration of fMREIT in a live animal model as a precursor to further research in this area. In summary, this study will establish the basis for functional MREIT (fMREIT) techniques

. However, ultimately we wish to image activity in vivo and our final study in this platform will admit a tentative exploration of fMREIT in a live animal exemplar as a harbinger to further research in this area. In summary, this study will prove the basis for functional MREIT (fMREIT) technique

. Hoaever, ultimately we wish to image activnry in tivo ans our fival study in this program wipl inclyde a tentative explorxtion of vMREIT ib a ouve animal model as a prsgursox vo further resesrch in thhs area. In sumkafy, this study will establish the basif for finftional MREIT (sMREPT) tecgniques

. However, ultimately we wish to image vivo our final in this program of in a live model as a to further research in this area. summary, this study will establish the basis for functional MREIT (fMREIT) techniques

. However, ultimately we wish to Image activIty in VivO anD oUr fiNal sTudy in this progRAm wiLl include a tentative expLoratIoN Of fMreIt in a lIve animAL mODEl aS a PrEcuRsOR tO furtHer ResearcH in this areA. In SuMmary, this stuDY wIll establiSh tHe basis for fuNctIonal MrEiT (fmrEIT) tEchNiqueS

. However, ultimately we w ish to ima ge ac tiv ity  i n vi vo a nd our final s t udyin this program will i nclud ea  ten t at ive e xplorat i on o f f MR EI T i na  l ive a nim al mode l as a pre cur so r to further re search inthi s area. In s umm ary, t hi s s t udy w ill  esta blisht he bas is for fu nc t ionalM REIT (f M R EI T) t echniques

. However,_ultimately we_wish to image activity_in vivo_and_our final_study_in this program_will include a_tentative exploration of fMREIT_in a live_animal_model as a precursor to further research in this area. In summary, this study_will_establish the_basis_for_functional MREIT (fMREIT) techniques


is evident by the fact that bone marrow transplantation is not always fully successful because of host versus graft responses (HVGR) and graft versus host disease (GVHD). The role that bone marrow pre-T cells play in these problems is unclear. In vitro models of GVHD and HVGR using bone marrow cells could greatly

is evident by the fact that bone marrow transplantation is not always amply successful because of server versus graft responses (HVGR) and graft versus master of ceremonies disease (GVHD). The role that bone marrow pre - T cell act in these problem is unclear. In vitro models of GVHD and HVGR use bone marrow cells could greatly

is evident by the fact thau bone marrow trauwplantetion ia not aldays fully successful becausx of host versus graft responser (HVGR) anf graft cersns host disease (JBHD). The role fmat bmie marrow pre-T gells play hn these problamr ns unclear. In vitro models of GVHD agd HVGR uding bone marrjw ctllf cohld greatly

is evident by the fact that bone is always fully because of host graft host disease (GVHD). role that bone pre-T cells play in these problems unclear. In vitro models of GVHD and HVGR using bone marrow cells could

is evident by the fact that bonE marrow traNsplaNtaTioN iS not AlwaYs fully successFUl beCause of host versus graft RespoNsES (HVGr) AnD grafT versus HOsT DIseAsE (GvHD). thE RoLe thaT boNe marroW pre-T cells PlaY iN these probleMS iS unclear. In VitRo models of GVhD aNd HVGR UsIng BOne maRroW cellS could GReatly

is evident by the fact th at bone ma rrowtra nsp la ntat ionis not alwaysf ully  successful because of  host  v e rsus gr aft r esponse s  ( H V GR)  a nd  gr af t  v ersus  ho st dise ase (GVHD) . T he  role that b o ne  marrow pr e-T  cells playinthesepr obl e ms is  un clear . In v i tro mo dels of G VH D  and H V GR usin g bo ne m arrow cells could gr e atly

is_evident by_the fact that bone_marrow transplantation_is_not always_fully_successful because of_host versus graft_responses (HVGR) and graft_versus host disease_(GVHD)._The role that bone marrow pre-T cells play in these problems is unclear. In_vitro_models of_GVHD_and_HVGR using bone marrow cells_could greatly


type and SK1-/- mice revealed that deletion of SK1 reverses the effect of AngII on GFR. Based on our data we propose to elucidate the role of EGFR transactivation and SK1/S1P in AngII-dependent intracellular Ca2+ mobilization, vascular tone, and renal hemodynamics.

type and SK1-/- mice revealed that deletion of SK1 overrule the consequence of AngII on GFR. Based on our data we propose to clear the role of EGFR transactivation and SK1 / S1P in AngII - dependent intracellular Ca2 + mobilization, vascular note, and nephritic hemodynamics.

tyoe and SK1-/- mice revealed uhat deletion of SK1 revecses ths effect of AngII on GFR. Based on ouc dara we propose to elucidate ghe role lf EGFR rranwqctivation and SK1/S1I in ZkgII-dzpxndent intracelkular Ca2+ mmbilization, vavcjlcr tone, and renal hemodynamics.

type and SK1-/- mice revealed that deletion reverses effect of on GFR. Based to the role of transactivation and SK1/S1P AngII-dependent intracellular Ca2+ mobilization, vascular tone, renal hemodynamics.

type and SK1-/- mice revealed that Deletion of sK1 revErsEs tHe EffeCt of angII on GFR. BaseD On ouR data we propose to elucidAte thE rOLe of egFr tranSactivaTIoN ANd Sk1/S1p iN AnGIi-DePendeNt iNtracelLular Ca2+ mobIliZaTion, vascular TOnE, and renal hEmoDynamics.

type and SK1-/- mice reve aled thatdelet ion  of  S K1 r ever ses the effect of A ngII on GFR. Based onour d at a  wep ro poseto eluc i da t e  th ero leof EG FR tr ans activat ion and SK 1/S 1P  in AngII-de p en dent intra cel lular Ca2+ m obi lizati on , v a scula r t one,and re n al hem odynamics .

type_and SK1-/-_mice revealed that deletion_of SK1_reverses_the effect_of_AngII on GFR._Based on our_data we propose to_elucidate the role_of_EGFR transactivation and SK1/S1P in AngII-dependent intracellular Ca2+ mobilization, vascular tone, and renal hemodynamics.


should lead to a more logical approach to the most appropriate clinical transfusion protocol, principally an understanding of whether donor blood or non-specific is more effective. The underlying hypothesis of this study is that the complexity of cancer dictates that compared to single modalities, combination therapies that are mechanistically independent and which are directed at nonoverl

should lead to a more logical approach to the most appropriate clinical transfusion protocol, chiefly an reason of whether donor blood or non - specific is more effective. The underlying guess of this study is that the complexity of cancer dictate that compared to single modality, combination therapies that are mechanistically independent and which are direct at nonoverl

shluld lead to a more logigal approach to jhw most approlriate cuinical transfusion protocol, peincikclly an understandine of whetjer donoe bliid or non-s'scific lf modc effzcvive. The underliing hypothevis of this stgdh ns that the complexity of cancer diceates tnah compared to fingkq mosalities, combination therapies thaf are mtchanistically indrpendent and which are dirfctef at nonoverl

should lead to a more logical approach most clinical transfusion principally an understanding non-specific more effective. The hypothesis of this is that the complexity of cancer that compared to single modalities, combination therapies that are mechanistically independent and which directed at nonoverl

should lead to a more logical aPproach to tHe mosT apProPrIate ClinIcal transfusioN ProtOcol, principally an underStandInG Of whEThEr donOr blood OR nON-SpeCiFiC is MoRE eFfectIve. the undeRlying hypoTheSiS of this study IS tHat the compLexIty of cancer dIctAtes thAt ComPAred tO siNgle mOdalitIEs, combInation thErAPies thAT are mecHANiSticAlly independent anD WhICh are directed aT nonovErL

should lead to a more log ical appro ach t o t hemo st a ppro priate clinica l  tra nsfusion protocol, pri ncipa ll y  anu nd ersta nding o f  w h e the rdo nor  b l oo d ornon -specif ic is more  ef fe ctive. The u n de rlying hyp oth esis of this  st udy is  t hat the c omp lexit y of c a ncer d ictates t ha t  compa r ed to s i n gl e mo dalities, combina t io n  therapies tha t areme c ha n i sti cal ly indepen de nt an d  whicha re d i rec t ed at nonover l

should_lead to_a more logical approach_to the_most_appropriate clinical_transfusion_protocol, principally an_understanding of whether_donor blood or non-specific_is more effective._The_underlying hypothesis of this study is that the complexity of cancer dictates that compared_to_single modalities,_combination_therapies_that are mechanistically independent and_which are directed at nonoverl


/Th17 numbers, and CD4+CD25+-, CD4+CD25+IL-17+-, CD4+IL-17+-T cell suppressor capacity will be analyzed. Human GBM is a fatal type of glioma, which results in the infiltration of Tregs and Th17s, as well as

/Th17 numbers, and CD4+CD25 + -, CD4+CD25+IL-17 + -, CD4+IL-17 + -T cell suppressor capacity will be analyzed. Human GBM is a fateful character of glioma, which results in the infiltration of Tregs and Th17s, equally well as

/Th17 jumbers, and CD4+CD25+-, CD4+CD25+IL-17+-, GD4+IL-17+-T cell supprgswor ca'acity sill be xnalyzed. Human GBM is a fatap rype if glioma, which resultr in the pnfiltratuon id Tregs anv Th17s, as well zd

/Th17 numbers, and CD4+CD25+-, CD4+CD25+IL-17+-, CD4+IL-17+-T cell will analyzed. Human is a fatal in infiltration of Tregs Th17s, as well

/Th17 numbers, and CD4+CD25+-, CD4+CD25+IL-17+-, CD4+Il-17+-T cell suppRessoR caPacItY wilL be aNalyzed. Human GBm Is a fAtal type of glioma, which rEsultS iN The iNFiLtratIon of TrEGs AND Th17S, aS wEll As

/Th17 numbers, and CD4+CD2 5+-, CD4+C D25+I L-1 7+- ,CD4+ IL-1 7+-T cell supp r esso r capacity will be ana lyzed .H uman GB M isa fatal ty p e  of  g li oma ,w hi ch re sul ts in t he infiltr ati on  of Tregs an d  T h17s, as w ell  as

/Th17 numbers,_and CD4+CD25+-,_CD4+CD25+IL-17+-, CD4+IL-17+-T cell suppressor_capacity will_be_analyzed. Human_GBM_is a fatal_type of glioma,_which results in the_infiltration of Tregs_and_Th17s, as well as


high titer and were genetically stable. They were, however, unable to compete with wild-type virus in mixed infections, suggesting that the location and /or length of the engineered sequence duplication did not provide for preferential packaging of the segment. These results indicate that sequence duplication alone (or increased segment length) is not the

high titer and were genetically stable. They were, however, unable to compete with wild - character virus in assorted infections, suggesting that the placement and /or distance of the engineered sequence duplicate did not provide for preferential packaging of the section. These result indicate that succession duplication alone (or increased segment duration) is not the

hihh titer and were genetigally stable. Thei qere, hmwever, unable go compete with wild-type virns ib mixtb infections, suggestkng that nhe locatuon end /or length of the englueeres seqbeice duplication did not psovide for prexefeutial packaging of the segment. These resultx lndicate that fequtncq dullication alone (or increased segmeht lenguh) is not the

high titer and were genetically stable. They unable compete with virus in mixed and length of the sequence duplication did provide for preferential packaging of the These results indicate that sequence duplication alone (or increased segment length) is not

high titer and were geneticalLy stable. ThEy werE, hoWevEr, UnabLe to Compete with wilD-Type Virus in mixed infections, SuggeStINg thAT tHe locAtion anD /Or LENgtH oF tHe eNgINeEred sEquEnce dupLication diD noT pRovide for preFErEntial packAgiNg of the segmeNt. THese reSuLts INdicaTe tHat seQuence DUplicaTion alone (Or INcreasED segmenT LEnGth) iS not the

high titer and were genet ically sta ble.The y w er e, h owev er, unable toc ompe te with wild-type viru s inmi x ed i n fe ction s, sugg e st i n g t ha tthe  l o ca tionand  /or le ngth of th e e ng ineered sequ e nc e duplicat ion  did not pro vid e forpr efe r entia l p ackag ing of the se gment. Th es e  resul t s indic a t ethat  sequence duplica t io n  alone (or inc reased  s e gm e n t l eng th) is not  t he

high_titer and_were genetically stable. They_were, however,_unable_to compete_with_wild-type virus in_mixed infections, suggesting_that the location and_/or length of_the_engineered sequence duplication did not provide for preferential packaging of the segment. These results_indicate_that sequence_duplication_alone_(or increased segment length) is_not the


specific stages in their life cycles. The Biostatistics Core provides statistical expertise in study design, data analysis, and interpretation of the results of analysis of cancer research data. Core biostatisticians collaborate with Cancer Center investigators in framing testable questions, devising experimental plans that make efficient use of experimental materials, patient populations

specific stages in their life cycles. The Biostatistics Core provides statistical expertness in discipline design, data psychoanalysis, and interpretation of the resultant role of analysis of cancer research datum. congress of racial equality biostatisticians collaborate with Cancer Center investigators in framing testable questions, devising experimental plan that make efficient habit of experimental materials, patient populations

spfcific stages in their llfe cycles. The Bnistativtics Dore proxides statistical expertise mn srudy eesign, data analysis, avd interpgetation if tie results of anemysis on candcr revxarch data. Core biostatisdicians collabmrxtz with Cancer Center investigators ig framimg testable quesjions, qeviapnn experimental plans that make erficienu use of experimenyal materials, patient popupatilns

specific stages in their life cycles. The provides expertise in design, data analysis, of of cancer research Core biostatisticians collaborate Cancer Center investigators in framing testable devising experimental plans that make efficient use of experimental materials, patient populations

specific stages in their life Cycles. The BIostaTisTicS COre pRoviDes statistical EXperTise in study design, data aNalysIs, ANd inTErPretaTion of tHE rESUltS oF aNalYsIS oF cancEr rEsearch Data. Core biOstAtIsticians colLAbOrate with CAncEr Center inveStiGators In FraMIng teStaBle quEstionS, DevisiNg experimEnTAl planS That makE EFfIcieNt use of experimentAL mATerials, patient PopulaTiONs

specific stages in theirlife cycle s. Th e B ios ta tist icsCore providess tati stical expertise in st udy d es i gn,d at a ana lysis,a nd i nte rp re tat io n  o f the  re sults o f analysis  of  c ancer resear c hdata. Core  bi ostatisticia nscollab or ate withCan cer C enteri nvesti gators in  f r amingt estable q ue stio ns, devising expe r im e ntal plans tha t make  e f fi c i ent  us e of exper im ental materia l s, p a tie n t populations

specific_stages in_their life cycles. The_Biostatistics Core_provides_statistical expertise_in_study design, data_analysis, and interpretation_of the results of_analysis of cancer_research_data. Core biostatisticians collaborate with Cancer Center investigators in framing testable questions, devising experimental_plans_that make_efficient_use_of experimental materials, patient populations


K-region and non-K-region epoxides, dols, phenols and ketones derived from them which have been proposed as intermediates in the carcinogenic process. Molecular complexes of the hydrocarbons and acridines with more polar planar molecules, and covalent products of the action of activated carcinogenic hydrocarbons with

K - region and non - K - region epoxides, dol, phenol and ketones derived from them which have been proposed as intermediate in the carcinogenic process. Molecular complexes of the hydrocarbons and acridines with more diametric planar molecules, and covalent products of the military action of activated carcinogenic hydrocarbons with

K-rfgion and non-K-region epowides, dols, phenols and netonea derivea from them which have been 'ropised qs intermediates in thd carcinohenic pricesw. Molecular complexcf of bhe hvdcocarbons and agridines widh more polar [lxncr molecules, and covalent products os the avtlon of activatgd cagcynogsnic hydrocarbons with

K-region and non-K-region epoxides, dols, phenols and from which have proposed as intermediates complexes the hydrocarbons and with more polar molecules, and covalent products of the of activated carcinogenic hydrocarbons with

K-region and non-K-region epoxiDes, dols, pheNols aNd kEtoNeS derIved From them which hAVe beEn proposed as intermediaTes in ThE CarcINoGenic Process. mOlECUlaR cOmPleXeS Of The hyDroCarbons And acridinEs wItH more polar plANaR molecules, And Covalent prodUctS of the AcTioN Of actIvaTed caRcinogENic hydRocarbons WiTH

K-region and non-K-region  epoxides,  dols , p hen ol s an d ke tones derivedf romthem which have been p ropos ed as i n te rmedi ates in th e car ci no gen ic pr ocess . M olecula r complexe s o fthe hydrocar b on s and acri din es with more  po lar pl an arm olecu les , and  coval e nt pro ducts ofth e  actio n  of act i v at ed c arcinogenic hydro c ar b ons with

K-region_and non-K-region_epoxides, dols, phenols and_ketones derived_from_them which_have_been proposed as_intermediates in the_carcinogenic process. Molecular complexes_of the hydrocarbons_and_acridines with more polar planar molecules, and covalent products of the action of activated_carcinogenic_hydrocarbons with


the cancer field with over 40 GWAS-related manuscripts since 2010, leadership roles in several international genetics consortia, expansion of the genetics emphasis to study the biological implications of genetic inheritance through strategic recruitment, development of an integrative genomics theme to study the relationship between inherited and somatically acquired mutations in tumors, submission

the cancer field with over 40 GWAS - related manuscripts since 2010, leadership roles in respective external genetics consortium, expansion of the genetics emphasis to study the biological implications of genic inheritance through strategic recruitment, development of an integrative genomics subject to study the relationship between inherit and somatically acquired mutations in tumor, submission

thf cancer field with over 40 GWAS-related mcbuscri'ts sinde 2010, leaddrship roles in several intecnatuonal genetics consortia, exoansion ov the gebetirs emphasis to svhdy the bioloflcal nm'lications of ggnetic inherhtance through sgrctegic recruitment, development of an integrstlve genomics treme eo sfldn the relationship between inherjted anv somatically avquired mutations in tumord, suhmission

the cancer field with over 40 GWAS-related 2010, roles in international genetics consortia, to the biological implications genetic inheritance through recruitment, development of an integrative genomics to study the relationship between inherited and somatically acquired mutations in tumors, submission

the cancer field with over 40 GWAs-related maNuscrIptS siNcE 2010, leaDersHip roles in seveRAl inTernational genetics conSortiA, eXPansIOn Of the GeneticS EmPHAsiS tO sTudY tHE bIologIcaL implicAtions of geNetIc Inheritance tHRoUgh strategIc rEcruitment, deVelOpment Of An iNTegraTivE genoMics thEMe to stUdy the relAtIOnship BEtween iNHErIted And somatically acqUIrED mutations in tuMors, suBmISsION

the cancer field with ove r 40 GWAS- relat edman us crip ts s ince 2010, lea d ersh ip roles in several in terna ti o nalg en etics  consor t ia , exp an si onof th e gen eti cs emph asis to st udy  t he biologica l  i mplication s o f genetic in her itance  t hro u gh st rat egicrecrui t ment,developme nt of ani ntegrat i v egeno mics theme to stu d yt he relationshi p betw ee n  i n h eri ted  and somat ic allya cquired mu t a t ion s  in tumors, s ubmission

the_cancer field_with over 40 GWAS-related_manuscripts since_2010,_leadership roles_in_several international genetics_consortia, expansion of_the genetics emphasis to_study the biological_implications_of genetic inheritance through strategic recruitment, development of an integrative genomics theme to study_the_relationship between_inherited_and_somatically acquired mutations in tumors,_submission


. However, data from patients has suggested the opposite, that IDO activity may actually be associated with the development of disease symptoms. Consistent with this, inhibitors of IDO reduce autoantibody titers and alleviate arthritis symptoms in a B cell-mediated mouse model of RA. These data support a role for IDO in exacerb

. However, data from patients has suggested the opposite, that IDO natural process may actually be consociate with the development of disease symptoms. Consistent with this, inhibitor of IDO reduce autoantibody titers and alleviate arthritis symptoms in a B cellular telephone - mediate mouse exemplar of RA. These data support a function for IDO in exacerb

. Hoaever, data from patients has suggested jhw oppovite, tgat IDO xctivity may actually be asslcuated with the development uf diseasv symptomw. Coisistent with thma, inhiblcors kn IDO ceduce autoantinody titers and alleviate aftkritis symptoms in a B cell-mediated iouse mpdfl of RA. These dats suplort a role for IDO in exacerb

. However, data from patients has suggested that activity may be associated with Consistent this, inhibitors of reduce autoantibody titers alleviate arthritis symptoms in a B mouse model of RA. These data support a role for IDO in exacerb

. However, data from patients haS suggested The opPosIte, ThAt IDo actIvity may actualLY be aSsociated with the develoPment Of DIseaSE sYmptoMs. ConsiSTeNT WitH tHiS, inHiBItOrs of iDO Reduce aUtoantibodY tiTeRs and alleviaTE aRthritis syMptOms in a B cell-mEdiAted moUsE moDEl of Ra. ThEse daTa suppORt a rolE for IDO in ExACerb

. However, data from patie nts has su ggest edthe  o ppos ite,  that IDO acti v itymay actually be associ atedwi t h th e  d evelo pment o f  d i s eas esy mpt om s .Consi ste nt with  this, inh ibi to rs of IDO re d uc e autoanti bod y titers and  al leviat eart h ritis  sy mptom s in a B cell -mediated  m o use mo d el of R A .  T hese  data support a r o le for IDO in exa cerb

. However,_data from_patients has suggested the_opposite, that_IDO_activity may_actually_be associated with_the development of_disease symptoms. Consistent with_this, inhibitors of_IDO_reduce autoantibody titers and alleviate arthritis symptoms in a B cell-mediated mouse model of_RA._These data_support_a_role for IDO in exacerb


tissue monitoring during therapy, thereby maximizing benefits and minimizing risks of treatment. A population of diabetics, both juvenile-onset and adult-onset, either on diet, insulin or oral hypoglycemic agents, will be screened using the photon absorption technique to detect the incidence of low bone mass. The presence of abnormally low mass

tissue monitoring during therapy, thereby maximizing benefits and minimizing risks of discussion. A population of diabetic, both juvenile - attack and adult - onset, either on diet, insulin or oral hypoglycemic agents, will be screened use the photon absorption technique to detect the incidence of broken bone multitude. The presence of abnormally low mass

tidsue monitoring during tmerapy, thereby mczimiziig benerits and minimizing risks of treatmeit. A popuoation of diabetics, bogh juvenipe-onset qnd edult-onset, eithec on dieb, inshpin mc oral hypoglycgmic agents, fill be screenad uding the photon absorption techniquq to deyeft the incidense og low bone mass. The presence of abnormamly low mass

tissue monitoring during therapy, thereby maximizing benefits risks treatment. A of diabetics, both diet, or oral hypoglycemic will be screened the photon absorption technique to detect incidence of low bone mass. The presence of abnormally low mass

tissue monitoring during theRapy, therebY maxiMizIng BeNefiTs anD minimizing risKS of tReatment. A population of dIabetIcS, Both JUvEnile-Onset anD AdULT-onSeT, eIthEr ON dIet, inSulIn or oraL hypoglyceMic AgEnts, will be scREeNed using thE phOton absorptiOn tEchniqUe To dETect tHe iNcideNce of lOW bone mAss. The preSeNCe of abNOrmally LOW mAss

tissue monitoring duringtherapy, t hereb y m axi mi zing  ben efits and mini m izin g risks of treatment.A pop ul a tion of  diab etics,b ot h juv en il e-o ns e tand a dul t-onset , either o n d ie t, insulin o r  o ral hypogl yce mic agents,wil l be s cr een e d usi ngthe p hotona bsorpt ion techn iq u e to d e tect th e in cide nce of low bone m a ss .  The presenceof abn or m al l y  lo w m ass

tissue_monitoring during_therapy, thereby maximizing benefits_and minimizing_risks_of treatment._A_population of diabetics,_both juvenile-onset and_adult-onset, either on diet,_insulin or oral_hypoglycemic_agents, will be screened using the photon absorption technique to detect the incidence of_low_bone mass._The_presence_of abnormally low mass


B. They are the mammalian orthologues of SAD-1, a gene required for presynaptic differentiation in C. elegans. Because SADs are kinases, we hope they will provide a valuable starting point for elucidating regulatory mechanisms that govern assembly of nerve terminals. Unfortunately, initial genetic tests of this idea gave complex

B. They are the mammalian orthologues of SAD-1, a gene required for presynaptic differentiation in C. elegans. Because SADs are kinases, we hope they will provide a valuable start item for elucidating regulatory mechanism that regulate assembly of nerve terminals. Unfortunately, initial familial tests of this idea contribute complex

B. Tjey are the mammalian oruhologues of SAD-1, c gene cequires for prdsynaptic differentiation in C. elegqns. Because SADs are kknases, we hope thwy wmll provide a valuable sbcrtinf poiut for elucidatikg regulatosy mechanisms dhxt govern assembly of nerve terminals. Unfortinwtely, initial deneuic tesfs of this idea gave complex

B. They are the mammalian orthologues of gene for presynaptic in C. elegans. hope will provide a starting point for regulatory mechanisms that govern assembly of terminals. Unfortunately, initial genetic tests of this idea gave complex

B. They are the mammalian orthoLogues of SAd-1, a genE reQuiReD for PresYnaptic differeNTiatIon in C. elegans. Because SAds are KiNAses, WE hOpe thEy will pROvIDE a vAlUaBle StARtIng poInt For elucIdating regUlaToRy mechanisms THaT govern assEmbLy of nerve terMinAls. UnfOrTunATely, iNitIal geNetic tESts of tHis idea gaVe COmplex

B. They are the mammalianorthologue s ofSAD -1,  a  gen e re quired for pre s ynap tic differentiation in  C. e le g ans. Be cause  SADs a r ek i nas es ,weho p etheywil l provi de a valua ble  s tarting poin t  f or elucida tin g regulatory  me chanis ms  th a t gov ern  asse mbly o f  nerve  terminal s. Unfort u nately, i ni tial  genetic tests of th i s idea gave co mplex

B. They_are the_mammalian orthologues of SAD-1,_a gene_required_for presynaptic_differentiation_in C. elegans._Because SADs are_kinases, we hope they_will provide a_valuable_starting point for elucidating regulatory mechanisms that govern assembly of nerve terminals. Unfortunately, initial_genetic_tests of_this_idea_gave complex


of treatment on aerobic and hypoxic populations exposed simultaneously and to determine whether thermal enhancements are possible at MISO concentrations and pharmaco-kinetics achievable in the clinic. These later experiments will make use of a spheroid treatment device designed to permit pharmacokinetic modeling in vitro. Finally, the effect of heat on the chemopotent

of treatment on aerobic and hypoxic populations exposed simultaneously and to determine whether thermal enhancement are potential at MISO concentration and pharmaco - kinetics achievable in the clinic. These late experiments will make manipulation of a spheroid discussion device designed to permit pharmacokinetic modeling in vitro. Finally, the effect of heating system on the chemopotent

of treatment on aerobic ana hypoxic populcrions xxposed simultaveously and to determine whevher thernal enhancements are pussible an MISO cobcenurations and pharmaco-kinebncs admievaylx in the clinic. These latar experiments wklp make use of a spheroid treatment qevice cedigned to permyt pnwrmadokinetic modeling in vitro. Finallg, the ehfect of heat om the chemopotent

of treatment on aerobic and hypoxic populations and determine whether enhancements are possible achievable the clinic. These experiments will make of a spheroid treatment device designed permit pharmacokinetic modeling in vitro. Finally, the effect of heat on the chemopotent

of treatment on aerobic and hyPoxic populAtionS exPosEd SimuLtanEously and to detERminE whether thermal enhanceMents ArE PossIBlE at MIsO conceNTrATIonS aNd PhaRmACo-KinetIcs AchievaBle in the clIniC. THese later expERiMents will mAke Use of a spheroId tReatmeNt DevICe desIgnEd to pErmit pHArmacoKinetic moDeLIng in vITro. FinaLLY, tHe efFect of heat on the chEMoPOtent

of treatment on aerobic a nd hypoxic  popu lat ion sexpo sedsimultaneously andto determine whether t herma le nhan c em entsare pos s ib l e  at  M IS O c on c en trati ons  and ph armaco-kin eti cs  achievablei nthe clinic . T hese later e xpe riment swil l  make  us e ofa sphe r oid tr eatment d ev i ce des i gned to p er mitpharmacokinetic m o de l ing in vitro.Finall y, th e eff ect  of heat o nthe c h emopote n t

of_treatment on_aerobic and hypoxic populations_exposed simultaneously_and_to determine_whether_thermal enhancements are_possible at MISO_concentrations and pharmaco-kinetics achievable_in the clinic._These_later experiments will make use of a spheroid treatment device designed to permit pharmacokinetic_modeling_in vitro._Finally,_the_effect of heat on the_chemopotent


Research Core will also provide access to other Core Facilities located at the lead institutions, for example, DNA Sequencing and Flow Cytometry, for all researchers within the Arkansas INBRE. In addition, through the INBRE consortium, the Arkansas INBRE will network with other INBREs to obtain access to facilities that may

Research Core will also provide access to other Core Facilities locate at the lead institution, for example, DNA Sequencing and Flow Cytometry, for all research worker within the Arkansas INBRE. In addition, through the INBRE consortium, the Arkansas INBRE will network with other INBREs to obtain entree to facility that may

Redearch Core will also pruvide access to other Rore Fadilities located at the lead instituvionw, for example, DNA Sequencine and Floa Cytomerry, hor all researchxds withlu the Wrkauses INBRE. In addltion, throuch the INBRE cmnroxtium, the Arkansas INBRE will networh with ptjer INBREs to jbtapn accsss to facilities that may

Research Core will also provide access to Facilities at the institutions, for example, for researchers within the INBRE. In addition, the INBRE consortium, the Arkansas INBRE network with other INBREs to obtain access to facilities that may

Research Core will also proviDe access to Other corE FaCiLitiEs loCated at the lead INstiTutions, for example, DNA SeQuencInG And FLOw cytomEtry, for ALl RESeaRcHeRs wItHIn The ArKanSas INBRe. In additioN, thRoUgh the INBRE cONsOrtium, the ARkaNsas INBRE wilL neTwork wItH otHEr INBrEs To obtAin accESs to faCilities tHaT May

Research Core will also p rovide acc ess t o o the rCore  Fac ilities locate d  atthe lead institutions,  forex a mple ,  D NA Se quencin g  a n d  Fl ow  C yto me t ry , for  al l resea rchers wit hin  t he ArkansasI NB RE. In add iti on, throughthe  INBRE  c ons o rtium , t he Ar kansas INBREwill netw or k  witho ther IN B R Es  toobtain access tof ac i lities that ma y

Research_Core will_also provide access to_other Core_Facilities_located at_the_lead institutions, for_example, DNA Sequencing_and Flow Cytometry, for_all researchers within_the_Arkansas INBRE. In addition, through the INBRE consortium, the Arkansas INBRE will network with_other_INBREs to_obtain_access_to facilities that may


between initial sensitivity, allostasis development and N2O self-administration behavior will be investigated. SA 3 examines whether factors measured in the allostatic state (N2O concentration, core temperature, heat loss, heat production) can be used as predictors of motivated behavior. This work has practical and theoretical importance for understanding

between initial sensitivity, allostasis development and N2O self - administration behavior will be investigated. SA 3 probe whether divisor measured in the allostatic state (N2O concentration, congress of racial equality temperature, heat loss, hotness production) can be used as forecaster of motivated behavior. This work suffer practical and theoretical importance for sympathy

behween initial sensitivitn, allostasis devglipment and N2K self-adoinistration behavior will bx incestitated. SA 3 examines whegher factlrs measyred un the allostatic state (H2L coucxntration, core jemperature, veat loss, heat pfobuction) can be used as predictors of motivayef behavior. Thif wogk has ircctical and theoretical importahce for understandinb

between initial sensitivity, allostasis development and N2O will investigated. SA examines whether factors (N2O core temperature, heat heat production) can used as predictors of motivated behavior. work has practical and theoretical importance for understanding

between initial sensitivity, Allostasis DevelOpmEnt AnD N2O sElf-aDministration bEHaviOr will be investigated. SA 3 ExamiNeS WhetHEr FactoRs measuREd IN The AlLoStaTiC StAte (N2O ConCentratIon, core temPerAtUre, heat loss, hEAt Production) Can Be used as predIctOrs of mOtIvaTEd behAviOr. ThiS work hAS practIcal and thEoREtical IMportanCE FoR undErstanding

between initial sensitivi ty, allost asisdev elo pm entandN2O self-admin i stra tion behavior will beinves ti g ated .  S A 3 e xamines wh e t her  f ac tor sm ea sured  in  the al lostatic s tat e(N2O concent r at ion, coretem perature, he atloss,he atp roduc tio n) ca n be u s ed aspredictor so f moti v ated be h a vi or.This work has pra c ti c al and theoret ical i mp o rt a n cefor  understan di ng

between_initial sensitivity,_allostasis development and N2O_self-administration behavior_will_be investigated._SA_3 examines whether_factors measured in_the allostatic state (N2O_concentration, core temperature,_heat_loss, heat production) can be used as predictors of motivated behavior. This work has_practical_and theoretical_importance_for_understanding


in the brain requires differentiation of the sending and receiving elements -the nerve terminal and postsynaptic membrane, respectively- and their precise apposition to each other. Much has been learned about the signals that postsynaptic cells use to organize nerve terminals, but little is known about how the nerve terminals pattern their differentiation in response to the

in the brain requires differentiation of the sending and receiving chemical element -the heart terminal and postsynaptic membrane, respectively- and their precise apposition to each early. Much has been learned about the signals that postsynaptic cells practice to mastermind nerve terminals, but little is known about how the boldness terminals pattern their specialization in response to the

in the brain requires difftrentiation of thg wendinj and rsceiving elements -the nerve terminal abd powtsynaptic membrane, rerpectivelj- and theur pcecise appositioi to eacm othsv. Muck ias been learnec about tha signals that puscsynaptic cells use to organize nervq termimaps, but little ys kmjwn zbout how the nerve terminals pattsrn thepr differentiatiom in response to the

in the brain requires differentiation of the receiving -the nerve and postsynaptic membrane, to other. Much has learned about the that postsynaptic cells use to organize terminals, but little is known about how the nerve terminals pattern their differentiation response to the

in the brain requires differeNtiation of The seNdiNg aNd ReceIvinG elements -the neRVe teRminal and postsynaptic mEmbraNe, REspeCTiVely- aNd their PReCISe aPpOsItiOn TO eAch otHer. much has Been learneD abOuT the signals tHAt PostsynaptIc cElls use to orgAniZe nervE tErmINals, bUt lIttle Is knowN About hOw the nervE tERminalS Pattern THEiR difFerentiation in resPOnSE to the

in the brain requires dif ferentiati on of  th e s en ding  and  receiving ele m ents  -the nerve terminal a nd po st s ynap t ic  memb rane, r e sp e c tiv el y-  an dt he ir pr eci se appo sition toeac hother. Muchh as  been lear ned  about the s ign als th at  po s tsyna pti c cel ls use to org anize ner ve termin a ls, but l it tleis known about ho w  t h e nerve termin als pa tt e rn t hei r d ifferentia ti on in respons e  t o t he

in_the brain_requires differentiation of the_sending and_receiving_elements -the_nerve_terminal and postsynaptic_membrane, respectively- and_their precise apposition to_each other. Much_has_been learned about the signals that postsynaptic cells use to organize nerve terminals, but_little_is known_about_how_the nerve terminals pattern their_differentiation in response to the


and their physiological relevance in the testis. Intimal hyperplasia in arterialized vein bypass grafts is a significant cause of vein graft stenosis and delayed graft failure. Injury at the time of implantation or as a consequence of transplantation into the high pressure arterial system may contribute to these delayed events. Alterations in gene expression accompany implantation and

and their physiological relevance in the testis. Intimal hyperplasia in arterialized vein bypass grafts is a meaning lawsuit of vein graft stenosis and delayed bribery failure. wound at the time of implantation or as a consequence of transplantation into the gamey imperativeness arterial system may contribute to these delayed events. revision in gene expression accompany implantation and

anf their physiological reuevance in the jewtis. Iitimal gyperplaria in arterialized vein bypess traftw is a significant caure of veij graft wteniwis and delayed graft fajpure. Mnjury at the tlme of impldntation or as a clnsequence of transplantation into ehe hign oressure arteryal xrstej may contribute to these delayed svents. Elterations in bene expression accompany lmplwntation and

and their physiological relevance in the testis. in vein bypass is a significant and graft failure. Injury the time of or as a consequence of transplantation the high pressure arterial system may contribute to these delayed events. Alterations in expression accompany implantation and

and their physiological releVance in the TestiS. InTimAl HypeRplaSia in arterialiZEd veIn bypass grafts is a signiFicanT cAUse oF VeIn graFt stenoSIs AND deLaYeD grAfT FaIlure. injUry at thE time of impLanTaTion or as a conSEqUence of traNspLantation intO thE high pReSsuRE arteRiaL systEm may cONtribuTe to these DeLAyed evENts. AlteRATiOns iN gene expression acCOmPAny implantatioN and

and their physiological r elevance i n the  te sti s.  Int imal  hyperplasia i n  art erialized vein bypassgraft si s as ig nific ant cau s eo f  ve in  g raf ts te nosis  an d delay ed graft f ail ur e. Injury at th e time ofimp lantation or  as  a con se que n ce of  tr anspl antati o n into  the high  p r essure arteria l sy stem  may contribute t o  t h ese delayed ev ents.Al t er a t ion s i n gene exp re ssion accompa n yi m p lan t ation and

and_their physiological_relevance in the testis._Intimal hyperplasia_in_arterialized vein_bypass_grafts is a_significant cause of_vein graft stenosis and_delayed graft failure._Injury_at the time of implantation or as a consequence of transplantation into the high_pressure_arterial system_may_contribute_to these delayed events. Alterations_in gene expression accompany implantation_and


. These will include basic immunologic and cytogenetic studies of the evolving tumors, and multimodality therapeutic approaches involving radiation and medical oncology. The mucopolysaccharidoses (MPS) are a group of hereditary diseases characterized by defective metabolism of glycosaminoglycans (GAGs). The disorders are usually associated with

. These will include basic immunologic and cytogenetic studies of the evolving tumor, and multimodality curative approach involving radiation sickness and aesculapian oncology. The mucopolysaccharidoses (MPS) are a group of hereditary diseases characterized by bad metamorphosis of glycosaminoglycans (GAGs). The disorders are usually associated with

. Thfse will include basic iomunologic and ettogenxtic sthdies of the evolving tumors, and mulvimoealitt therapeutic approachds involvpng radiarion qnd medical oncolonv. The luco'ooysaccharidosex (MPS) are d group of heradktcry diseases characterized by defectyve metsbllism of glycofamimjglydans (GAGs). The disorders are usuallg assocpated with

. These will include basic immunologic and of evolving tumors, multimodality therapeutic approaches The (MPS) are a of hereditary diseases by defective metabolism of glycosaminoglycans (GAGs). disorders are usually associated with

. These will include basic immuNologic and CytogEneTic StUdieS of tHe evolving tumoRS, and Multimodality therapeutIc appRoAChes INvOlvinG radiatIOn AND meDiCaL onCoLOgY. The mUcoPolysacCharidoses (mPS) ArE a group of herEDiTary diseasEs cHaracterized By dEfectiVe MetABolisM of GlycoSaminoGLycans (gAGs). The diSoRDers arE Usually ASSoCiatEd with

. These will include basic  immunolog ic an d c yto ge neti c st udies of the e v olvi ng tumors, and multimo dalit yt hera p eu tic a pproach e si n vol vi ng  ra di a ti on an d m edicaloncology.The  m ucopolysacch a ri doses (MPS ) a re a group o f h eredit ar y d i sease s c harac terize d  by de fective m et a bolism of glyc o s am inog lycans (GAGs). Th e  d i sorders are us uallyas s oc i a ted  wi th

. These_will include_basic immunologic and cytogenetic_studies of_the_evolving tumors,_and_multimodality therapeutic approaches_involving radiation and_medical oncology. The mucopolysaccharidoses_(MPS) are a_group_of hereditary diseases characterized by defective metabolism of glycosaminoglycans (GAGs). The disorders are usually_associated_with


want to promote this alternative or supplementary therapy. This is vital to devising efficient antipseudomonal therapy and eradicating complications resulting from P. aeruginosa infections among patients with CF. This proposal requests support for a Keystone Symposia meeting entitled Neurodegenerative Diseases: The Molecular and Cellular Basis for Neurode

want to promote this alternative or supplementary therapy. This is critical to devise efficient antipseudomonal therapy and eradicating complications leave from P. aeruginosa infections among patients with CF. This marriage proposal requests support for a Keystone Symposia meeting entitle Neurodegenerative Diseases: The Molecular and Cellular Basis for Neurode

wajt to promote this alterkative or supplementary theraly. This ks vital to devising efficieit abtipstldomonal therapy and dradicatijg complucatmons resulting fckm P. aevbginoaw inyertions among pajients with WF. This proposdl rzquests support for a Keystone Sympofia meeyijg entitled Neorodebqnerzniye Diseases: The Molecular and Cemlular Uasis for Neuroce

want to promote this alternative or supplementary is to devising antipseudomonal therapy and aeruginosa among patients with This proposal requests for a Keystone Symposia meeting entitled Diseases: The Molecular and Cellular Basis for Neurode

want to promote this alternatIve or supplEmentAry TheRaPy. ThIs is Vital to devisinG EffiCient antipseudomonal thErapy AnD EradICaTing cOmplicaTIoNS ResUlTiNg fRoM p. aErugiNosA infectIons among pAtiEnTs with CF. This PRoPosal requeSts Support for a KEysTone SyMpOsiA MeetiNg eNtitlEd NeurODegeneRative DisEaSEs: The MOLecular AND CElluLar Basis for NeurodE

want to promote this alte rnative or  supp lem ent ar y th erap y. This is vit a l to  devising efficient an tipse ud o mona l  t herap y and e r ad i c ati ng  c omp li c at ionsres ultingfrom P. ae rug in osa infectio n samong pati ent s with CF. T his  propo sa l r e quest s s uppor t fora  Keyst one Sympo si a  meeti n g entit l e dNeur odegenerative Dis e as e s: The Molecul ar and  C e ll u l arBas is for Neu ro de

want_to promote_this alternative or supplementary_therapy. This_is_vital to_devising_efficient antipseudomonal therapy_and eradicating complications_resulting from P. aeruginosa_infections among patients_with_CF. This proposal requests support for a Keystone Symposia meeting entitled Neurodegenerative Diseases: The_Molecular_and Cellular_Basis_for_Neurode


a decline in oocyte and subsequent embryo quality. As women increasingly delay attempts at pregnancy into their 30s and beyond, any acceleration of reproductive aging has dire consequences for the possibility of successful pregnancy and the risk of birth defects. Furthermore, early reproductive senescence in women is associated with decreased lifespan and quality of life. Although the

a decline in oocyte and subsequent embryo quality. As women increasingly delay attempt at pregnancy into their thirty and beyond, any acceleration of reproductive aging experience awful consequences for the possibility of successful pregnancy and the hazard of birth defects. Furthermore, early reproductive aging in women is associated with decrease lifespan and quality of liveliness. Although the

a fecline in oocyte and sunsequent embryo quality. As wojen incrdasingly delay attempts at pcegnqncy unto their 30s and beyona, any accvleration of ceproductive agiif has dlxe cohdequznres for the posxibility ox successful pseencncy and the risk of birth defects. Ftrthermprf, early reprodoctivt sqnesdvnge in women is associated with dscreasev lifespan and auality of life. Although tje

a decline in oocyte and subsequent embryo women delay attempts pregnancy into their of aging has dire for the possibility successful pregnancy and the risk of defects. Furthermore, early reproductive senescence in women is associated with decreased lifespan and of life. Although the

a decline in oocyte and subseqUent embryo QualiTy. AS woMeN incReasIngly delay atteMPts aT pregnancy into their 30s anD beyoNd, ANy acCElEratiOn of repROdUCTivE aGiNg hAs DIrE consEquEnces foR the possibIliTy Of successful PReGnancy and tHe rIsk of birth deFecTs. FurtHeRmoRE, earlY reProduCtive sENescenCe in women Is ASsociaTEd with dECReAsed Lifespan and qualitY Of LIfe. Although the

a decline in oocyte and s ubsequentembry o q ual it y. A s wo men increasing l y de lay attempts at pregna ncy i nt o  the i r30s a nd beyo n d, a nyac ce ler at i on  of r epr oductiv e aging ha s d ir e consequenc e sfor the po ssi bility of su cce ssfulpr egn a ncy a ndthe r isk of birthdefects.Fu r thermo r e, earl y re prod uctive senescence in women is assoc iatedwi t hd e cre ase d lifespan  a nd qu a lity of li f e .  Al t hough the

a_decline in_oocyte and subsequent embryo_quality. As_women_increasingly delay_attempts_at pregnancy into_their 30s and_beyond, any acceleration of_reproductive aging has_dire_consequences for the possibility of successful pregnancy and the risk of birth defects. Furthermore,_early_reproductive senescence_in_women_is associated with decreased lifespan_and quality of life. Although_the


but development of novel therapies is hampered by limited insight into pathophysiological mechanisms as well as small patient groups and insufficiently developed animal models. Therefore the overall objective of this proposal is to increase our knowledge of the pathophysiology of FAO disorders by studying newly identified molecular mechanisms and metabolic pathways that contribute to the different disease presentations using well

but development of novel therapies is hampered by circumscribed penetration into pathophysiological mechanism as well as small patient group and insufficiently developed animal models. consequently the overall objective of this proposal is to increase our knowledge of the pathophysiology of FAO disorder by studying newly identified molecular mechanism and metabolic pathways that contribute to the unlike disease presentations using well

buh development of novel tmerapies is hampgrwd by nimites insighg into pathophysiological merhanusms qs well as small patievt groups and insyffiriently developev animal modela. Thexehore the overalk objectiva of this propmsxl is to increase our knowledge of thq patholhjsiology of FAJ dixjrdeds by studying newly identified momecular mechanisms amd metabolic pathways that conhribute to the difverent diseqse [eesentations using well

but development of novel therapies is hampered insight pathophysiological mechanisms well as small animal Therefore the overall of this proposal to increase our knowledge of the of FAO disorders by studying newly identified molecular mechanisms and metabolic pathways that to the different disease presentations using well

but development of novel therApies is hamPered By lImiTeD insIght Into pathophysiOLogiCal mechanisms as well as sMall pAtIEnt gROuPs and InsuffiCIeNTLy dEvElOpeD aNImAl modEls. therefoRe the overaLl oBjEctive of this PRoPosal is to iNcrEase our knowlEdgE of the PaThoPHysioLogY of FAo disorDErs by sTudying neWlY IdentiFIed moleCULaR mecHanisms and metabolIC pAThways that contRibute To THe DIFfeRenT disease prEsEntatIOns usinG WeLL

but development of noveltherapiesis ha mpe red  b y li mite d insight into path ophysiological mechani sms a sw ella ssmall  patien t  g r o ups  a nd  in su f fi cient lydevelop ed animalmod el s. Therefore th e overallobj ective of th ispropos al  is to in cre ase o ur kno w ledgeof the pa th o physio l ogy ofF A Odiso rders by studying ne w ly identifiedmolecu la r  m e c han ism s and meta bo lic p a thwayst ha t c ont r ibute to thedifferent d i sea se pre se nta t ions u singwe l l

but_development of_novel therapies is hampered_by limited_insight_into pathophysiological_mechanisms_as well as_small patient groups_and insufficiently developed animal_models. Therefore the_overall_objective of this proposal is to increase our knowledge of the pathophysiology of FAO_disorders_by studying_newly_identified_molecular mechanisms and metabolic pathways_that contribute to the different_disease presentations_using well


, and its relatively frequent abuse in the HIV infected population, this work is relevant to public health in the US. Knowledge about how METH is toxic to the brain in the setting of HIV infection will be useful not only in discouraging METH use, but in obtaining disease-specific markers that can be used for diagnosis

, and its relatively frequent abuse in the HIV infected population, this work is relevant to public health in the US. Knowledge about how METH is toxic to the mind in the place setting of HIV infection will be useful not only in discourage METH use, but in obtain disease - specific markers that can be used for diagnosis

, anf its relatively frequenu abuse in the HIR infecved pophlation, ghis work is relevant to pubpix heaoth in the US. Knowledgd about hlw METH us tizic to the brain ik the dettnnj of HIV infectlon will be useful not onny iu discouraging METH use, but in obtaiging dixewse-specific matkers ehat bak be used for diagnosis

, and its relatively frequent abuse in infected this work relevant to public about METH is toxic the brain in setting of HIV infection will be not only in discouraging METH use, but in obtaining disease-specific markers that can used for diagnosis

, and its relatively frequent aBuse in the HiV infEctEd pOpUlatIon, tHis work is relevANt to Public health in the US. KnoWledgE aBOut hOW MeTH is Toxic to THe BRAin In ThE seTtINg Of HIV InfEction wIll be usefuL noT oNly in discourAGiNg METH use, bUt iN obtaining diSeaSe-specIfIc mARkers ThaT can bE used fOR diagnOsis

, and its relatively frequ ent abusein th e H IVin fect ed p opulation, thi s  wor k is relevant to publi c hea lt h  int he  US.Knowled g ea b out  h ow  ME TH is  toxi c t o the b rain in th e s et ting of HIVi nf ection wil l b e useful not  on ly indi sco u ragin g M ETH u se, bu t  in ob taining d is e ase-sp e cific m a r ke rs t hat can be used f o rd iagnosis

, and_its relatively_frequent abuse in the_HIV infected_population,_this work_is_relevant to public_health in the_US. Knowledge about how_METH is toxic_to_the brain in the setting of HIV infection will be useful not only in_discouraging_METH use,_but_in_obtaining disease-specific markers that can_be used for diagnosis


atory oligodendrocytes possess OLG-growth cones that containmRNAs, the locally restricted translation of which is critical for the regulation of oligodendroglial process pathfinding and targeting, i.e. myelination. This hypothesis will be tested in two specific aims. 1) We will determine the role of locally

atory oligodendrocytes possess OLG - growth cones that containmRNAs, the locally restrict transformation of which is critical for the regulation of oligodendroglial process pathfinding and target, i.e. myelination. This hypothesis will be test in two specific aims. 1) We will specify the role of locally

atogy oligodendrocytes posstss OLG-growth congs that rontainjRNAs, thd locally restricted translavion of wyich is critical for tfe regulanion of ooigovendroglial procxas pathnnndinf and vargeting, i.e. myglination. Thhs hypothesis fiul be tested in two specific aims. 1) We will drtfrmine the rolg of kjcalmj

atory oligodendrocytes possess OLG-growth cones that containmRNAs, restricted of which critical for the and i.e. myelination. This will be tested two specific aims. 1) We will the role of locally

atory oligodendrocytes possEss OLG-growTh conEs tHat CoNtaiNmRNas, the locally reSTricTed translation of which iS critIcAL for THe RegulAtion of OLiGODenDrOgLiaL pROcEss paThfInding aNd targetinG, i.e. MyElination. ThiS HyPothesis wiLl bE tested in two SpeCific aImS. 1) We WIll deTerMine tHe role OF localLy

atory oligodendrocytes pos sess OLG-g rowth  co nes  t hatcont ainmRNAs, thel ocal ly restricted translat ion o fw hich is  crit ical fo r  t h e  re gu la tio no foligo den droglia l processpat hf inding and t a rg eting, i.e . m yelination.Thi s hypo th esi s  will  be  test ed int wo spe cific aim s. 1) Wew ill det e r mi ne t he role of locall y

atory oligodendrocytes_possess OLG-growth_cones that containmRNAs, the_locally restricted_translation_of which_is_critical for the_regulation of oligodendroglial_process pathfinding and targeting,_i.e. myelination. This_hypothesis_will be tested in two specific aims. 1) We will determine the role of_locally


autoimmune disorder of the central nervous system typified by axonal demyelination and neuronal death. To date, there is no effective treatment to cure the disease, and the available therapies do not alter the outcome of the disease. The development of better therapeutic options requires in-depth understanding of the molecular mechanisms leading to disease development and

autoimmune disorder of the central nervous system typify by axonal demyelination and neural death. To date, there is no effective discussion to cure the disease, and the available therapy do not alter the outcome of the disease. The exploitation of good therapeutic option requires in - depth reason of the molecular mechanisms leading to disease growth and

auhoimmune disorder of the central nervous systek typiried by xxonal demyelination and neuconao deauk. To date, there is nu effectine treatmwnt uo cure the disease, and tmz avajpablz vherapies do noj alter the mutcome of the dkszase. The development of better thera[eutic pphions requires in-dtptr unsvrwtanding of the molecular mecganisms leading to dosease development and

autoimmune disorder of the central nervous system axonal and neuronal To date, there cure disease, and the therapies do not the outcome of the disease. The of better therapeutic options requires in-depth understanding of the molecular mechanisms leading to development and

autoimmune disorder of the ceNtral nervoUs sysTem TypIfIed bY axoNal demyelinatiON and Neuronal death. To date, theRe is nO eFFectIVe TreatMent to cURe THE diSeAsE, anD tHE aVailaBle TherapiEs do not altEr tHe Outcome of the DIsEase. The devEloPment of betteR thErapeuTiC opTIons rEquIres iN-depth UNderstAnding of tHe MOleculAR mechanISMs LeadIng to disease develOPmENt and

autoimmune disorder of th e centralnervo ussys te m ty pifi ed by axonal d e myel ination and neuronal d eath.  T o  dat e ,there  is noe ff e c tiv etr eat me n tto cu rethe dis ease, andthe  a vailable the r ap ies do not  al ter the outc ome  of th edis e ase.The  deve lopmen t  of be tter ther ap e utic o p tions r e q ui resin-depth understa n di n g of the molec ular m ec h an i s mslea ding to di se ase d e velopme n ta n d

autoimmune_disorder of_the central nervous system_typified by_axonal_demyelination and_neuronal_death. To date,_there is no_effective treatment to cure_the disease, and_the_available therapies do not alter the outcome of the disease. The development of better_therapeutic_options requires_in-depth_understanding_of the molecular mechanisms leading_to disease development and


, the high molecular weight extrachromosomal DNA of C. difficile will be characterized. Preliminary work in our laboratory has demonstrated a large extrachromosomal DNA element in 16 out of 16 strains of C. difficile tested. Also bacteriophage particals were identified with electron microscopy to be associated with C. diff

, the high molecular weight extrachromosomal DNA of C. difficile will be characterized. Preliminary work in our lab has attest a large extrachromosomal DNA element in 16 out of 16 stress of C. difficile tested. Also bacteriophage particals were identify with electron microscopy to be consort with C. diff

, thf high molecular weight txtrachromosomal BBA of R. diffidile wilu be characterized. Preliminacy wirk ib our laboratory has ddmonstratvd a largw exurachromosomal DNE elemenb in 16 lut mh 16 strains of C. difficile tested. Also bdcgexiophage particals were identified wyth elevtgon microscopy to nq asaociated with C. diff

, the high molecular weight extrachromosomal DNA difficile be characterized. work in our extrachromosomal element in 16 of 16 strains C. difficile tested. Also bacteriophage particals identified with electron microscopy to be associated with C. diff

, the high molecular weight extRachromosoMal DNa of c. diFfIcilE wilL be characterizED. PreLiminary work in our laborAtory HaS DemoNStRated A large eXTrACHroMoSoMal dNa ElEment In 16 oUt of 16 strAins of C. difFicIlE tested. Also bACtEriophage pArtIcals were ideNtiFied wiTh EleCTron mIcrOscopY to be aSSociatEd with C. diFf

, the high molecular weigh t extrachr omoso mal  DN Aof C . di fficile will b e  cha racterized. Preliminar y wor ki n ou r  l abora tory ha s  d e m ons tr at edal ar ge ex tra chromos omal DNA e lem en t in 16 outo f16 strains  of  C. difficil e t ested.  A lso bacte rio phage  parti c als we re identi fi e d with electro n mi cros copy to be associ a te d  with C. diff

, the_high molecular_weight extrachromosomal DNA of_C. difficile_will_be characterized._Preliminary_work in our_laboratory has demonstrated_a large extrachromosomal DNA_element in 16_out_of 16 strains of C. difficile tested. Also bacteriophage particals were identified with electron_microscopy_to be_associated_with_C. diff


and advanced sequences, MRI shows potential for improved and non-invasive assessment of liver disease. Fast spin echo or single shot techniques, often combined with fat suppression, are the most common T2 weighted sequences used in liver MRI procedures. Liver MRI is highly dependent on the administration of contrast agents, especially when detection and characterization of

and advanced sequences, MRI shows potential for improved and non - incursive appraisal of liver disease. Fast spin echo or single stroke techniques, often combine with fatty suppression, are the most common T2 weighted sequences use in liver MRI procedures. Liver MRI is highly dependent on the government of line agents, especially when signal detection and characterization of

anf advanced sequences, MRI shows potential for ikproves and nov-invasive assessment of livec diwease. Fast spin echo or sinele shot nechniquew, ofuen combined with fat supixessikk, are vhe most common T2 weighteg sequences usad iu liver MRI procedures. Liver MRI is righly ceoendent on the admpnystrzniin of contrast agents, especiamly whei detection and characterization of

and advanced sequences, MRI shows potential for non-invasive of liver Fast spin echo combined fat suppression, are most common T2 sequences used in liver MRI procedures. MRI is highly dependent on the administration of contrast agents, especially when detection characterization of

and advanced sequences, MRI shOws potentiAl for ImpRovEd And nOn-inVasive assessmeNT of lIver disease. Fast spin echO or siNgLE shoT TeChniqUes, ofteN CoMBIneD wItH faT sUPpRessiOn, aRe the moSt common T2 wEigHtEd sequences uSEd In liver MRI ProCedures. Liver mRI Is highLy DepENdent On tHe admInistrATion of Contrast aGeNTs, espeCIally whEN DeTectIon and characterizATiON of

and advanced sequences, M RI shows p otent ial  fo rimpr oved  and non-invas i ve a ssessment of liver dis ease.  F a st s p in  echo  or sin g le s hot  t ec hni qu e s,  ofte n c ombined  with fatsup pr ession, aret he  most comm onT2 weightedseq uences  u sed in li ver  MRIproced u res. L iver MRIis highly depende n t  o n th e administrationo fc ontrast agents , espe ci a ll y whe n d etection a nd  char a cteriza t io n o f

and_advanced sequences,_MRI shows potential for_improved and_non-invasive_assessment of_liver_disease. Fast spin_echo or single_shot techniques, often combined_with fat suppression,_are_the most common T2 weighted sequences used in liver MRI procedures. Liver MRI is_highly_dependent on_the_administration_of contrast agents, especially when_detection and characterization of


immune response is specific, but productive intra-molecular cross-priming against other potential tumor-associated antigens is incomplete. We believe that productive extension of such secondary immune responses is hindered by the presence of regulatory T-cells (T ) which are disproportionately represented within the peripheral blood and tumors of Regs patients with

immune response is specific, but productive intra - molecular cross - priming against other likely tumor - consociate antigens is incomplete. We believe that generative reference of such secondary immune responses is impede by the presence of regulatory thymine - cells (T) which are disproportionately represent within the peripheral blood and tumors of Regs affected role with

imlune response is specifig, but productive intra-mmleculzr cross-oriming against other potentmal rumor-qssociated antigens is incomplene. We belueve rhat produrfive exbznsioh of vnch secondary ikmune respmnses is hindesea yy the presence of regulatory T-cells (T ) whivh are disproporjionauelr relgewented within the peripheral glood aid tumors of Rebs patients with

immune response is specific, but productive intra-molecular other tumor-associated antigens incomplete. We believe secondary responses is hindered the presence of T-cells (T ) which are disproportionately within the peripheral blood and tumors of Regs patients with

immune response is specific, bUt productiVe intRa-mOleCuLar cRoss-Priming against OTher Potential tumor-associatEd antIgENs is INcOmpleTe. We belIEvE THat PrOdUctIvE ExTensiOn oF such seCondary immUne ReSponses is hinDErEd by the preSenCe of regulatoRy T-Cells (T ) WhIch ARe disProPortiOnatelY RepresEnted withIn THe periPHeral blOOD aNd tuMors of Regs patientS WiTH

immune response is specif ic, but pr oduct ive  in tr a-mo lecu lar cross-prim i ng a gainst other potential  tumo r- a ssoc i at ed an tigensi si n com pl et e.We be lieve  th at prod uctive ext ens io n of such se c on dary immun e r esponses ishin deredby  th e  pres enc e ofregula t ory T- cells (T)w hich a r e dispr o p or tion ately represented wi t hin the periph eral b lo o da n d t umo rs of Regs  p atien t s with

immune_response is_specific, but productive intra-molecular_cross-priming against_other_potential tumor-associated_antigens_is incomplete. We_believe that productive_extension of such secondary_immune responses is_hindered_by the presence of regulatory T-cells (T ) which are disproportionately represented within the_peripheral_blood and_tumors_of_Regs patients with


we will systematically investigate this hypothesis via three specific aims. In Aim 1, we will perform experiments to establish the long-term stability of?-crystallin-client protein complexes under the conditions of the lens by employing fluorescence resonance energy transfer (FRET)- based assays. We will then determine whether?-crystallin-

we will systematically investigate this hypothesis via three specific aims. In Aim 1, we will perform experiments to install the retentive - term stability of?-crystallin - client protein complex under the conditions of the lens by employing fluorescence rapport department of energy transfer (FRET)- based assays. We will then determine whether?-crystallin-

we will systematically invtstigate this hypothesis via tgree spezific aims. In Aim 1, we will pxrfoem exkvriments to establish the long-nerm stabulitb of?-crystallin-clmsnt probzin cklplerew under the cokditions of the lens by ekpuoving fluorescence resonance energy twansfer (FGET)- based assais. We rill nhtn determine whether?-crystallin-

we will systematically investigate this hypothesis via aims. Aim 1, will perform experiments of?-crystallin-client complexes under the of the lens employing fluorescence resonance energy transfer (FRET)- assays. We will then determine whether?-crystallin-

we will systematically invesTigate this HypotHesIs vIa ThreE speCific aims. In Aim 1, WE wilL perform experiments to eStablIsH The lONg-Term sTabilitY Of?-CRYstAlLiN-clIeNT pRoteiN coMplexes Under the coNdiTiOns of the lens BY eMploying flUorEscence resonAncE energY tRanSFer (FReT)- bAsed aSsays. WE Will thEn determiNe WHether?-CRystallIN-

we will systematically in vestigatethishyp oth es is v ia t hree specifica ims.  In Aim 1, we will per formex p erim e nt s toestabli s ht h e l on g- ter ms ta bilit y o f?-crys tallin-cli ent  p rotein compl e xe s under th e c onditions of  th e lens  b y e m ployi ngfluor escenc e  reson ance ener gy transf e r (FRET ) -  b ased  assays. We willt he n  determine whe ther?- cr y st a l lin -

we_will systematically_investigate this hypothesis via_three specific_aims._In Aim_1,_we will perform_experiments to establish_the long-term stability of?-crystallin-client_protein complexes under_the_conditions of the lens by employing fluorescence resonance energy transfer (FRET)- based assays. We_will_then determine_whether?-crystallin-


constrain tropomyosin in the inhibitory "blocking" state characteristic of relaxed muscle;(C) we will test both the hypothesis that tropomyosin assumes the contours of the F-actin helix as a relatively stiff coiled coiled-coil and the alternative view that tropomyosin is flexible. (2) We

constrain tropomyosin in the inhibitory " blocking " state characteristic of relaxed muscle;(C) we will screen both the guess that tropomyosin assumes the contours of the F - actin coil as a relatively stiff handbuild coiled - coil and the alternate scene that tropomyosin is flexible. (2) We

cojstrain tropomyosin in tme inhibitory "blocking" vtate dharactefistic of relaxed muscle;(C) we wull ttft both the hypothdsis that tropomyisin qssumes thx contouvf of bhe F-ccvin helix as a telatively sdiff coiled cohldd-eoil and the alternative view that twopomyoxij is flexible. (2) We

constrain tropomyosin in the inhibitory "blocking" state relaxed we will both the hypothesis of F-actin helix as relatively stiff coiled and the alternative view that tropomyosin flexible. (2) We

constrain tropomyosin in the Inhibitory "BlockIng" StaTe CharActeRistic of relaxeD MuscLe;(C) we will test both the hyPotheSiS That TRoPomyoSin assuMEs THE coNtOuRs oF tHE F-Actin HelIx as a reLatively stIff CoIled coiled-coIL aNd the alterNatIve view that tRopOmyosiN iS flEXible. (2) we

constrain tropomyosin inthe inhibi tory"bl ock in g" s tate  characteristi c  ofrelaxed muscle;(C) wewillte s t bo t hthe h ypothes i st h attr op omy os i nassum esthe con tours of t heF- actin helixa sa relative lystiff coiled  co iled-c oi l a n d the  al terna tive v i ew tha t tropomy os i n is f l exible. ( 2)  We

constrain_tropomyosin in_the inhibitory "blocking" state_characteristic of_relaxed_muscle;(C) we_will_test both the_hypothesis that tropomyosin_assumes the contours of_the F-actin helix_as_a relatively stiff coiled coiled-coil and the alternative view that tropomyosin is flexible. (2)_We


which there are four, do not act through host signaling pathways, but are directly bactericidal against both Gram-positive and -negative bacteria (1). Indeed, these PGRPs are a new class of bactericidal proteins that have a different structure and mechanism of action than currently known mammalian antimicrobial peptides. Mammalian P

which there are four, do not act through host signaling nerve pathway, but are immediately bactericidal against both Gram - positive and -negative bacteria (1). Indeed, these PGRPs are a new course of bactericidal proteins that receive a different structure and mechanism of military action than currently known mammalian antimicrobial peptide. Mammalian phosphorus

whlch there are four, do nou act through hosj wignalmng patgways, bug are directly bactericidal egaibst bith Gram-positive and -ndgative bwcteria (1). Indted, these PGRPs acs a new class lf bccvericidal protelns that haee a different sgrbcture and mechanism of action than surrentky known mammaliwn ameimidgonial peptides. Mammalian P

which there are four, do not act signaling but are bactericidal against both Indeed, PGRPs are a class of bactericidal that have a different structure and of action than currently known mammalian antimicrobial peptides. Mammalian P

which there are four, do not act Through hosT signAliNg pAtHwayS, but Are directly bacTEricIdal against both Gram-posItive AnD -NegaTIvE bactEria (1). IndEEd, THEse pGrPS arE a NEw Class Of bActericIdal proteiNs tHaT have a differENt Structure aNd mEchanism of acTioN than cUrRenTLy knoWn mAmmalIan antIMicrobIal peptidEs. mAmmaliAN P

which there are four, donot act th rough  ho stsi gnal ingpathways, buta re d irectly bactericidal a gains tb othG ra m-pos itive a n d- n ega ti ve  ba ct e ri a (1) . I ndeed,these PGRP s a re  a new class of  bacterici dal  proteins th athave a  d iff e rentstr uctur e andm echani sm of act io n  thanc urrentl y kn ownmammalian antimic r ob i al peptides. M ammali an P

which_there are_four, do not act_through host_signaling_pathways, but_are_directly bactericidal against_both Gram-positive and_-negative bacteria (1). Indeed,_these PGRPs are_a_new class of bactericidal proteins that have a different structure and mechanism of action_than_currently known_mammalian_antimicrobial_peptides. Mammalian P


coordinated development and differentiation of neuronal cells throughout the brain. Over the past several years, it has become clear that the RhoGTPases and related molecules play an important role in neuronal cell development, including neurite outgrowth, differentiation, axon pathfinding, dendritic spine formation, as well as neuronal cell maintenance. Results from

coordinated development and differentiation of neuronal cell throughout the mind. Over the past several years, it has become clear that the RhoGTPases and related atom play an important function in neuronal cell growth, including neurite outgrowth, specialization, axon pathfinding, dendritic spine formation, as well as neuronal cell sustenance. Results from

colrdinated development ana differentiation of nxuronal cells tfroughout the brain. Over the pqst stneral years, it has bezome cleag that thw RhiTTPases anv related moledmles 'ley an important role in nauronal cell davdllpment, including neurite outgrowth, qifferemtlation, axon pajhfincyng, svnbritic spine formation, as well zs neurmnal cell maimtenance. Results from

coordinated development and differentiation of neuronal cells brain. the past years, it has and molecules play an role in neuronal development, including neurite outgrowth, differentiation, axon dendritic spine formation, as well as neuronal cell maintenance. Results from

coordinated development and DifferentiAtion Of nEurOnAl ceLls tHroughout the brAIn. OvEr the past several years, iT has bEcOMe clEAr That tHe RhoGTpAsES And ReLaTed MoLEcUles pLay An imporTant role in NeuRoNal cell develOPmEnt, includiNg nEurite outgroWth, DifferEnTiaTIon, axOn pAthfiNding, dENdritiC spine forMaTIon, as wELl as neuRONaL celL maintenance. ResulTS fROm

coordinated development a nd differe ntiat ion  of  n euro nalcells througho u t th e brain. Over the past  seve ra l  yea r s,  it h as beco m ec l ear  t ha t t he Rh oGTPa ses  and re lated mole cul es  play an imp o rt ant role i n n euronal cell  de velopm en t,i nclud ing  neur ite ou t growth , differe nt i ation, axon pa t h fi ndin g, dendritic spin e  f o rmation, as we ll asne u ro n a l c ell  maintenan ce . Res u lts fro m

coordinated_development and_differentiation of neuronal cells_throughout the_brain._Over the_past_several years, it_has become clear_that the RhoGTPases and_related molecules play_an_important role in neuronal cell development, including neurite outgrowth, differentiation, axon pathfinding, dendritic spine_formation,_as well_as_neuronal_cell maintenance. Results from


opiate addiction. We will evaluate the effect of the course on physicians' knowledge, attitude, behavior and satisfaction using assessment forms developed in Phase I. In Phase II we will create and evaluate the full suite of courses. Phase III work will involve modifying and expanding the courses to teach a full range of health professionals. PROP

opiate addiction. We will evaluate the effect of the course on physicians' cognition, position, demeanor and satisfaction using assessment kind developed in Phase I. In Phase II we will create and measure the full suite of courses. Phase III employment will involve modifying and boom the courses to teach a full image of health master. PROP

oplate addiction. We will eyaluate the effeer of tie courae on phhsicians' knowledge, attitude, uehacior qnd satisfaction using assessmejt forms devtloped in Phase I. In Phasc II sc wiln create and evsluate the full suite of cuuxses. Phase III work will involve modyfying snf expanding thg cougsqs tk teach a full range of health proressionels. PROP

opiate addiction. We will evaluate the effect course physicians' knowledge, behavior and satisfaction Phase In Phase II will create and the full suite of courses. Phase work will involve modifying and expanding the courses to teach a full range health professionals. PROP

opiate addiction. We will evalUate the effEct of The CouRsE on pHysiCians' knowledge, ATtitUde, behavior and satisfacTion uSiNG assESsMent fOrms devELoPED in phAsE I. IN PHAsE II we WilL create And evaluatE thE fUll suite of coURsEs. Phase III WorK will involve ModIfying AnD exPAndinG thE courSes to tEAch a fuLl range of HeALth proFEssionaLS. pRoP

opiate addiction. We will  evaluatethe e ffe ctof  the  cou rse on physici a ns'knowledge, attitude, b ehavi or ands at isfac tion us i ng a sse ss me ntfo r ms  deve lop ed in P hase I. In  Ph as e II we will cr eate and e val uate the ful l s uite o fcou r ses.Pha se II I work will i nvolve mo di f ying a n d expan d i ng  the  courses to teach af ull range of h ealthpr o fe s s ion als . PROP

opiate_addiction. We_will evaluate the effect_of the_course_on physicians'_knowledge,_attitude, behavior and_satisfaction using assessment_forms developed in Phase_I. In Phase_II_we will create and evaluate the full suite of courses. Phase III work will_involve_modifying and_expanding_the_courses to teach a full_range of health professionals. PROP


mortality rates >80%. Our long-term goals are to develop a vaccine and to provide better means for the early diagnosis and monitoring of aspergillosis. Our specific hypotheses are: 1) certain aspergillus antigens have an immunoprotective effect, and 2) some antigens may serve as indicators of early stages of

mortality rates > 80% . Our long - term goal are to originate a vaccine and to provide better means for the early diagnosis and monitoring of aspergillosis. Our specific hypothesis are: 1) certain aspergillus antigens hold an immunoprotective effect, and 2) some antigens may service as indicators of early stages of

mogtality rates >80%. Our long-ttrm goals are to bwvelop a vacdine and to provide better means for tye eaely diagnosis and monigoring of aspergiolosms. Our specific igpothescf ars: 1) cextein aspergillus antigens vave an immuno[rutzctive effect, and 2) some antigens may serve ss indicators of earkr stzges of

mortality rates >80%. Our long-term goals are a and to better means for of Our specific hypotheses 1) certain aspergillus have an immunoprotective effect, and 2) antigens may serve as indicators of early stages of

mortality rates >80%. Our long-term Goals are to DevelOp a VacCiNe anD to pRovide better meANs foR the early diagnosis and mOnitoRiNG of aSPeRgillOsis. Our SPeCIFic HyPoTheSeS ArE: 1) certAin AspergiLlus antigeNs hAvE an immunoproTEcTive effect, And 2) Some antigens May Serve aS iNdiCAtors Of eArly sTages oF

mortality rates >80%. Our  long-term  goal s a reto  dev elop  a vaccine and to p rovide better means fo r the  e a rlyd ia gnosi s and m o ni t o rin gof  as pe r gi llosi s.Our spe cific hypo the se s are: 1) ce r ta in aspergi llu s antigens h ave  an im mu nop r otect ive  effe ct, an d  2) so me antige ns may se r ve as i n d ic ator s of early stages of

mortality_rates >80%._Our long-term goals are_to develop_a_vaccine and_to_provide better means_for the early_diagnosis and monitoring of_aspergillosis. Our specific_hypotheses_are: 1) certain aspergillus antigens have an immunoprotective effect, and 2) some antigens may_serve_as indicators_of_early_stages of


to the renin-angiotensin system (RAS). Angiotensin (AngII), an important regulator of RAS, plays a critical role in regulation of blood pressure and volume homeostasis. These effects are mediated mainly via Ca2+ mobilization. Investigators reported the involvement of sphingosine kinase1 (SK1) in

to the renin - angiotensin system (RAS). Angiotensin (AngII), an important regulator of RAS, plays a critical function in rule of blood pressure and bulk homeostasis. These impression are mediated mainly via Ca2 + mobilization. research worker reported the involvement of sphingosine kinase1 (SK1) in

to the renin-angiotensin syrtem (RAS). Angiotgnwin (AnjII), an jmportang regulator of RAS, plays a ccitixal rile in regulation of buood presdure and volnme homeostasis. Vgese efnzcts zve mebieted mainly via Ca2+ mobilisation. Investicagoxs reported the involvement of sphindosine lijase1 (SK1) in

to the renin-angiotensin system (RAS). Angiotensin (AngII), regulator RAS, plays critical role in volume These effects are mainly via Ca2+ Investigators reported the involvement of sphingosine (SK1) in

to the renin-angiotensin systEm (RAS). AngioTensiN (AnGII), An ImpoRtanT regulator of RAs, PlayS a critical role in regulaTion oF bLOod pREsSure aNd volumE HoMEOstAsIs. theSe EFfEcts aRe mEdiated Mainly via CA2+ moBiLization. InveSTiGators repoRteD the involvemEnt Of sphiNgOsiNE kinaSe1 (Sk1) in

to the renin-angiotensinsystem (RA S). A ngi ote ns in ( AngI I), an importa n t re gulator of RAS, playsa cri ti c al r o le  in r egulati o no f  bl oo dpre ss u re  andvol ume hom eostasis.The se  effects are me diated mai nly  via Ca2+ mo bil izatio n.  In v estig ato rs re ported the in volvement  o f  sphin g osine k i n as e1 ( SK1) in

to_the renin-angiotensin_system (RAS). Angiotensin (AngII),_an important_regulator_of RAS,_plays_a critical role_in regulation of_blood pressure and volume_homeostasis. These effects_are_mediated mainly via Ca2+ mobilization. Investigators reported the involvement of sphingosine kinase1 (SK1) in


patients with status epilepticus. Genes regulated more than two fold on microarrays will be confirmed by quantitative RT-PCR for all of the aims. The goal is to objectively differentiate seizures, syncope, global cerebral ischemia, hypoglycemia, and transient ischemic attacks hours to days after they occur; and to begin to identify

patients with status epilepticus. Genes regulated more than two fold on microarrays will be confirm by quantitative RT - PCR for all of the aim. The goal is to objectively differentiate seizures, faint, global cerebral ischemia, hypoglycemia, and transient ischemic attacks hours to day after they occur; and to begin to name

pahients with status epilekticus. Genes regulated mmre thzn two fuld on microarrays will be clndirmee by quantitative RT-PCF for all of the qims. Rhe goal is to objcetivemn difyecentiate seizurgs, syncope, gnobal cerebral irckemia, hypoglycemia, and transient iscremic aytwcks hours to qays wfted they occur; and to begin to identjfy

patients with status epilepticus. Genes regulated more fold microarrays will confirmed by quantitative aims. goal is to differentiate seizures, syncope, cerebral ischemia, hypoglycemia, and transient ischemic hours to days after they occur; and to begin to identify

patients with status epileptIcus. Genes rEgulaTed MorE tHan tWo foLd on microarrayS Will Be confirmed by quantitatIve RT-pCr For aLL oF the aIms. The gOAl IS To oBjEcTivElY DiFfereNtiAte seizUres, syncopE, glObAl cerebral isCHeMia, hypoglyCemIa, and transieNt iSchemiC aTtaCKs houRs tO days After tHEy occuR; and to begIn TO identIFy

patients with status epil epticus. G enesreg ula te d mo re t han two fold o n  mic roarrays will be confi rmedby quan t it ative  RT-PCR fo r all  o fthe  a i ms . The  go al is t o objectiv ely  d ifferentiate se izures, sy nco pe, global c ere bral i sc hem i a, hy pog lycem ia, an d  trans ient isch em i c atta c ks hour s to  day s after they occu r ;a nd to begin to  ident if y

patients_with status_epilepticus. Genes regulated more_than two_fold_on microarrays_will_be confirmed by_quantitative RT-PCR for_all of the aims._The goal is_to_objectively differentiate seizures, syncope, global cerebral ischemia, hypoglycemia, and transient ischemic attacks hours to_days_after they_occur;_and_to begin to identify


reactive oxygen species. This hypothesis will be investigated by stretching both primary cultures of cat tracheal epithelial cells and human bronchial epithelial cells as well as lines of human bronchial epithelial cells grown on elastic membranes using a novel biaxial strain device. Preliminary results demonstrate that both cyclic mechanical elongation and compression delay wound closure by inhibiting cell

reactive oxygen species. This hypothesis will be investigated by stretching both basal acculturation of cat tracheal epithelial cells and human bronchial epithelial cells as well as line of human bronchial epithelial cells grown on elastic membrane use a novel biaxial stress device. Preliminary results demonstrate that both cyclic mechanical elongation and compaction delay wound closure by inhibiting cell

rewctive oxygen species. Thls hypothesis will be iivestigzted by rtretching both primary cultnres of cqt tracheal epithelial cells anf human vronrhial epithelial cells as well ws lnnxs of human brokchial epitvelial cells gsodn on elastic membranes using a novel biaxiak dtrain device. Krelikynarg results demonstrate that both cydlic mebhanical elongatipn and compression delay wlund closure by inhibihing cell

reactive oxygen species. This hypothesis will be stretching primary cultures cat tracheal epithelial cells well as lines human bronchial epithelial grown on elastic membranes using a biaxial strain device. Preliminary results demonstrate that both cyclic mechanical elongation and compression wound closure by inhibiting cell

reactive oxygen species. This Hypothesis Will bE inVesTiGateD by sTretching both pRImarY cultures of cat tracheal EpithElIAl ceLLs And huMan bronCHiAL EpiThElIal CeLLs As welL as Lines of Human broncHiaL ePithelial celLS gRown on elasTic Membranes usiNg a Novel bIaXiaL StraiN deVice. PRelimiNAry resUlts demonStRAte thaT Both cycLIC mEchaNical elongation anD CoMPression delay wOund clOsURe BY InhIbiTing cell

reactive oxygen species.This hypot hesis  wi llbe  inv esti gated by stret c hing  both primary cultures  of c at trac h ea l epi thelial ce l l s a nd  h uma nb ro nchia l e pitheli al cells a s w el l as lines o f  h uman bronc hia l epithelial  ce lls gr ow n o n  elas tic  memb ranesu sing a  novel bi ax i al str a in devi c e .Prel iminary results d e mo n strate that bo th cyc li c  m e c han ica l elongati on  andc ompress i on d e lay wound closure  by inhibit i ngcell

reactive_oxygen species._This hypothesis will be_investigated by_stretching_both primary_cultures_of cat tracheal_epithelial cells and_human bronchial epithelial cells_as well as_lines_of human bronchial epithelial cells grown on elastic membranes using a novel biaxial strain_device._Preliminary results_demonstrate_that_both cyclic mechanical elongation and_compression delay wound closure by_inhibiting cell


by PKA. Signaling by PKA is confined to specific locations in cells by virtue of a family of A-kinase anchoring proteins (AKAPs) that localize pools of PKA, their substrates, and interconnected signaling enzymes. This application focuses on the mechanisms by which PKA integrates transcriptional networks to imitate

by PKA. Signaling by PKA is confined to specific locations in cells by merit of a syndicate of A - kinase anchoring proteins (AKAPs) that place pond of PKA, their substrates, and interconnected signaling enzyme. This application focuses on the mechanisms by which PKA integrate transcriptional networks to imitate

by PKA. Signaling by PKA is confined to spgcufic lmcatiohs in ceuls by virtue of a family of A-jinast anchoring proteinr (AKAPs) tjat locaoize pools of PKA, their substdwtes, end interconnecjed signalinc enzymes. This aoppication focuses on the mechanisms fy whicn OKA integrates tramfcrilniinal networks to imitate

by PKA. Signaling by PKA is confined locations cells by of a family that pools of PKA, substrates, and interconnected enzymes. This application focuses on the by which PKA integrates transcriptional networks to imitate

by PKA. Signaling by PKA is confIned to specIfic lOcaTioNs In ceLls bY virtue of a famiLY of A-Kinase anchoring proteinS (AKAPS) tHAt loCAlIze poOls of PKa, ThEIR suBsTrAteS, aND iNtercOnnEcted siGnaling enzYmeS. THis applicatiON fOcuses on thE meChanisms by whIch pKA intEgRatES tranScrIptioNal netWOrks to Imitate

by PKA. Signaling by PKAis confine d tospe cif ic  loc atio ns in cells by virt ue of a family of A-ki nasean c hori n gprote ins (AK A Ps ) tha tlo cal iz e  p oolsofPKA, th eir substr ate s,  and interco n ne cted signa lin g enzymes. T his  appli ca tio n  focu ses  on t he mec h anisms  by which  P K A inte g rates t r a ns crip tional networks t o  i m itate

by_PKA. Signaling_by PKA is confined_to specific_locations_in cells_by_virtue of a_family of A-kinase_anchoring proteins (AKAPs) that_localize pools of_PKA,_their substrates, and interconnected signaling enzymes. This application focuses on the mechanisms by which_PKA_integrates transcriptional_networks_to_imitate


angiogenic activity in an animal model of human non-small cell lung cancer (NSCLC). They will demonstrate that underexpression of IP-10 imparts increased angiogenic activity to NSCLC cell lines. Next, they will reconstitute IP-10 production in NSCLC cell lines, thus restoring the angiostatic balance, using

angiogenic activity in an animal model of human non - small cell lung cancer (NSCLC). They will attest that underexpression of IP-10 imparts increase angiogenic activity to NSCLC cell lines. Next, they will restructure IP-10 production in NSCLC cell lines, therefore repair the angiostatic balance, use

anhiogenic activity in an xnimal model of human ion-smalm cell ljng cancer (NSCLC). They will dxmonwtratt that underexpresskon of IP-10 imparts incceased angiogenir activibv to HDCLC rell lines. Next, they will reconstitute HP-10 pxoduction in NSCLC cell lines, thus rqstorinb hhe angiostatis bakwnce, lslng

angiogenic activity in an animal model of cell cancer (NSCLC). will demonstrate that angiogenic to NSCLC cell Next, they will IP-10 production in NSCLC cell lines, restoring the angiostatic balance, using

angiogenic activity in an aniMal model of Human Non-SmaLl Cell Lung Cancer (NSCLC). TheY Will Demonstrate that underexPressIoN Of IP-10 IMpArts iNcreaseD AnGIOgeNiC aCtiViTY tO NSCLc ceLl lines. next, they wiLl rEcOnstitute IP-10 pROdUction in NScLC Cell lines, thuS reStorinG tHe aNGiostAtiC balaNce, usiNG

angiogenic activity in an  animal mo del o f h uma nnon- smal l cell lung ca n cer(NSCLC). They will dem onstr at e  tha t  u ndere xpressi o no f  IP -1 0imp ar t sincre ase d angio genic acti vit yto NSCLC cel l  l ines. Next , t hey will rec ons titute  I P-1 0  prod uct ion i n NSCL C  celllines, th us restor i ng thea n gi osta tic balance, usin g

angiogenic_activity in_an animal model of_human non-small_cell_lung cancer_(NSCLC)._They will demonstrate_that underexpression of_IP-10 imparts increased angiogenic_activity to NSCLC_cell_lines. Next, they will reconstitute IP-10 production in NSCLC cell lines, thus restoring the_angiostatic_balance, using


-fat diet reduces hepatic CEACAM1 levels by > 50% to cause hyperinsulinemia and insulin resistance. Conversely, Ceacam1 overexpression in liver protects mice against insulin resistance and visceral obesity. This suggests that hyperinsulinemia plays a detrimental role in the pathogenesis of diet-induced obesity and insulin resistance. We

-fat diet reduces hepatic CEACAM1 levels by > 50% to cause hyperinsulinemia and insulin resistance. Conversely, Ceacam1 overexpression in liver protect mouse against insulin resistance and visceral obesity. This hint that hyperinsulinemia plays a detrimental function in the pathogenesis of diet - induced obesity and insulin electric resistance. We

-fat diet reduces hepatic CEXCAM1 levels by > 50% to canse hypsrinsulivemia and insulin resistance. Cinverwely, Ceacam1 overexpresrion in lpver protwcts nice against insullu resjdtanee and visceral pbesity. Thhs suggests thdt hvperinsulinemia plays a detrimental wole in tje pathogenesif of qiet-jnduced obesity and insulin resistznce. We

-fat diet reduces hepatic CEACAM1 levels by to hyperinsulinemia and resistance. Conversely, Ceacam1 against resistance and visceral This suggests that plays a detrimental role in the of diet-induced obesity and insulin resistance. We

-fat diet reduces hepatic CEACaM1 levels by > 50% To cauSe hYpeRiNsulInemIa and insulin reSIstaNce. Conversely, Ceacam1 oveRexprEsSIon iN LiVer prOtects mICe AGAinSt InSulIn REsIstanCe aNd visceRal obesity. thiS sUggests that hYPeRinsulinemIa pLays a detrimeNtaL role iN tHe pAThogeNesIs of dIet-indUCed obeSity and inSuLIn resiSTance. We

-fat diet reduces hepaticCEACAM1 le velsby> 5 0%  tocaus e hyperinsulin e miaand insulin resistance . Con ve r sely ,  C eacam 1 overe x pr e s sio nin  li ve r  p rotec tsmice ag ainst insu lin  r esistance an d  v isceral ob esi ty. This sug ges ts tha thyp e rinsu lin emiaplaysa  detri mental ro le in the pathoge n e si s of  diet-induced obe s it y  and insulin r esista nc e .W e

-fat diet_reduces hepatic_CEACAM1 levels by >_50% to_cause_hyperinsulinemia and_insulin_resistance. Conversely, Ceacam1_overexpression in liver_protects mice against insulin_resistance and visceral_obesity._This suggests that hyperinsulinemia plays a detrimental role in the pathogenesis of diet-induced obesity_and_insulin resistance._We


ligands for Toll-like receptors (TLR) and transmit regenerative signals to ISCs. We thereby propose intestinal regenerative therapy with a combination of systemic administration of growth factors and cell replacement therapy to salvage Gl function post-radiation exposure. In order to develop an stem cell-based therapeutic strategy for RIGS,

ligands for Toll - like receptors (TLR) and air regenerative signal to ISCs. We thereby propose intestinal regenerative therapy with a combination of systemic administration of growth component and cell replacement therapy to salvage Gl routine post - radiation photograph. In order to evolve an stem cell - free-base therapeutic strategy for RIGS,

lihands for Toll-like recepuors (TLR) and transmit rejeneratjve signxls to ISCs. We thereby propode intewtinal regenerative thdrapy witj a combunatmon of systemic esministvction lf gxoxth factors and cell repldcement therapf go salvage Gl function post-radiation qxposurr. Ln order to dedelok ag stsm cell-based therapeutic strategy ror RIGV,

ligands for Toll-like receptors (TLR) and transmit to We thereby intestinal regenerative therapy administration growth factors and replacement therapy to Gl function post-radiation exposure. In order develop an stem cell-based therapeutic strategy for RIGS,

ligands for Toll-like receptoRs (TLR) and trAnsmiT reGenErAtivE sigNals to ISCs. We thEReby Propose intestinal regenEratiVe THeraPY wIth a cOmbinatIOn OF SysTeMiC adMiNIsTratiOn oF growth Factors and CelL rEplacement thERaPy to salvagE Gl Function post-RadIation ExPosURe. In oRdeR to deVelop aN Stem ceLl-based thErAPeutic STrategy FOR RiGS,

ligands for Toll-like rec eptors (TL R) an d t ran sm it r egen erative signal s  toISCs. We thereby propo se in te s tina l  r egene rativet he r a pywi th  aco m bi natio n o f syste mic admini str at ion of growt h  f actors and  ce ll replaceme nttherap ytos alvag e G l fun ctionp ost-ra diation e xp o sure.I n order t odeve lop an stem cell- b as e d therapeuticstrate gy fo r RIG S,

ligands_for Toll-like_receptors (TLR) and transmit_regenerative signals_to_ISCs. We_thereby_propose intestinal regenerative_therapy with a_combination of systemic administration_of growth factors_and_cell replacement therapy to salvage Gl function post-radiation exposure. In order to develop an_stem_cell-based therapeutic_strategy_for_RIGS,


ylaxis trial using weekly doses of DEC. In Gabon (where exposure to the parasite was heaviest) 30% of individuals in the placebo group developed overt clinical disease compared to none in the DEC-treated group (p<.02) and 50% became seropositive in the placebo group vs 13% in

ylaxis trial using weekly doses of DEC. In Gabon (where exposure to the leech was dense) 30% of individuals in the placebo group developed overt clinical disease compare to none in the DEC - process group (p<.02) and 50% became seropositive in the placebo group vs 13% in

yladis trial using weekly duses of DEC. In Yqbon (wiere exlosure tu the parasite was heaviest) 30% od induviduals in the placebu group dvveloped iveru clinical diseasx comparcb to hlne nn the DEC-treatec group (p<.02) dnd 50% became sesoooditive in the placebo group vs 13% in

ylaxis trial using weekly doses of DEC. (where to the was heaviest) 30% group overt clinical disease to none in DEC-treated group (p<.02) and 50% became in the placebo group vs 13% in

ylaxis trial using weekly dosEs of DEC. In GAbon (wHerE exPoSure To thE parasite was heAViesT) 30% of individuals in the plaCebo gRoUP devELoPed ovErt clinICaL DIseAsE cOmpArED tO none In tHe DEC-trEated group (P<.02) anD 50% bEcame seroposITiVe in the plaCebO group vs 13% in

ylaxis trial using weeklydoses of D EC. I n G abo n(whe re e xposure to the para site was heaviest) 30%  of i nd i vidu a ls  in t he plac e bo g rou pde vel op e dovert  cl inicaldisease co mpa re d to none in th e DEC-trea ted  group (p<.0 2)and 50 %bec a me se rop ositi ve int he pla cebo grou pv s 13%i n

ylaxis trial_using weekly_doses of DEC. In_Gabon (where_exposure_to the_parasite_was heaviest) 30%_of individuals in_the placebo group developed_overt clinical disease_compared_to none in the DEC-treated group (p<.02) and 50% became seropositive in the placebo_group_vs 13%_in


; the administration of hormones for experimental purposes; continuous, close-range observation of behavior; a simple social system focusing on peer relations; systematic comparison of behavior in this semi-natural habitat with behavior of chimpanzees in their fully natural habitat and with human adolescents in roughly similar situations. Hormone assays will be

; the administration of hormones for experimental purposes; continuous, close - compass notice of behavior; a simple social arrangement focus on peer relations; systematic comparison of demeanor in this semi - natural habitat with behavior of chimpanzees in their amply natural habitat and with human adolescents in approximately similar situations. Hormone assays will be

; thf administration of hormunes for experimental 'urposea; continjous, close-range observation lf behacior; a simple social shstem foclsing on peer eelations; systematle comlwrismi of behavior ik this semi-tatural habitad dich behavior of chimpanzees in their sully nstkral habitat agd wptr hujan adolescents in roughly similar situatpons. Hormone assaus will be

; the administration of hormones for experimental close-range of behavior; simple social system comparison behavior in this habitat with behavior chimpanzees in their fully natural habitat with human adolescents in roughly similar situations. Hormone assays will be

; the administration of hormonEs for experImentAl pUrpOsEs; coNtinUous, close-range OBserVation of behavior; a simplE sociAl SYsteM FoCusinG on peer RElATIonS; sYsTemAtIC cOmparIsoN of behaVior in this SemI-nAtural habitaT WiTh behavior Of cHimpanzees in TheIr fullY nAtuRAl habItaT and wIth humAN adoleScents in rOuGHly simILar situATIoNs. HoRmone assays will be

; the administration of ho rmones for  expe rim ent al  pur pose s; continuous, clos e-range observation of  beha vi o r; a si mplesocials ys t e m f oc us ing  o n  p eer r ela tions;systematic  co mp arison of be h av ior in thi s s emi-naturalhab itat w it h b e havio r o f chi mpanze e s in t heir full yn atural habitat a nd  wit h human adolescen t si n roughly simi lar si tu a ti o n s.Hor mone assay swillb e

; the_administration of_hormones for experimental purposes;_continuous, close-range_observation_of behavior;_a_simple social system_focusing on peer_relations; systematic comparison of_behavior in this_semi-natural_habitat with behavior of chimpanzees in their fully natural habitat and with human adolescents_in_roughly similar_situations._Hormone_assays will be