-funded studies have enabled us to develop large tissue banks with detailed clinical information on all patients. In this proposal, we intend to utilize these resources in order to generate molecular staging tools and to identify novel therapeutic targets to improve the treatment of esophageal adenocarcinoma patients. Specifically, we propose to examine the genome of EA using high density

-funded studies have enabled us to develop large tissue bank with detailed clinical data on all patients. In this proposal, we mean to use these resources in order to generate molecular theatrical production tools and to identify fresh curative targets to improve the discussion of esophageal adenocarcinoma patients. Specifically, we propose to probe the genome of EA use high concentration

-funfed studies have enabled us to develop large tmssue bznks witf detailed clinical informatmon in alo patients. In this prooosal, we pntend to utiouze these cssources in odfer co generate molegular stagitg tools and tm kdzntify novel therapeutic targets to ymprove tje treatment os esp[hagsal adenocarcinoma patients. Specifjcally, xe propose to ecamine the genome of EA uslng jigh density

-funded studies have enabled us to develop banks detailed clinical on all patients. to these resources in to generate molecular tools and to identify novel therapeutic to improve the treatment of esophageal adenocarcinoma patients. Specifically, we propose to examine genome of EA using high density

-funded studies have enabled uS to develop Large TisSue BaNks wIth dEtailed clinicaL InfoRmation on all patients. In This pRoPOsal, WE iNtend To utiliZE tHESe rEsOuRceS iN OrDer to GenErate moLecular staGinG tOols and to ideNTiFy novel theRapEutic targets To iMprove ThE trEAtmenT of EsophAgeal aDEnocarCinoma patIeNTs. SpecIFically, WE PrOposE to examine the genoME oF eA using high denSity

-funded studies have enabl ed us to d evelo p l arg etiss ue b anks with deta i ledclinical information o n all  p a tien t s.  In t his pro p os a l , w ein ten dt outili zethese r esources i n o rd er to genera t emolecularsta ging tools a ndto ide nt ify novel  th erape utic t a rgetsto improv et he tre a tment o f es opha geal adenocarcino m ap atients. Speci ficall y, we p rop ose  to examin ethe g e nome of EA u s ing high density

-funded studies_have enabled_us to develop large_tissue banks_with_detailed clinical_information_on all patients._In this proposal,_we intend to utilize_these resources in_order_to generate molecular staging tools and to identify novel therapeutic targets to improve the_treatment_of esophageal_adenocarcinoma_patients._Specifically, we propose to examine_the genome of EA using_high density


use Pharmacology in their careers as active research scientists in leadership roles. This is an interdisciplinary training program composed of students from an innovative triumvirate of Departments of Pharmacology and Cancer Biology, Chemistry and Biomedical Engineering. Leadership in the program is provided by a Director, Co- Director, Executive, Admissions

use Pharmacology in their careers as active research scientists in leadership function. This is an interdisciplinary education program composed of student from an advanced triumvirate of Departments of Pharmacology and Cancer Biology, Chemistry and Biomedical Engineering. Leadership in the program is provided by a Director, Co- Director, Executive, Admissions

usf Pharmacology in their gareers as activg eesearrh sciehtists iv leadership roles. This is ai inrerdiwciplinary training prugram comiosed of wtudtnts from an innotztive tvnumvidwte mh Departments on Pharmacolmgy and Cancer Bkopogy, Chemistry and Biomedical Enginqering. Kewdership in thg probwam js provided by a Director, Co- Direcfor, Exebutive, Admissions

use Pharmacology in their careers as active in roles. This an interdisciplinary training an triumvirate of Departments Pharmacology and Cancer Chemistry and Biomedical Engineering. Leadership in program is provided by a Director, Co- Director, Executive, Admissions

use Pharmacology in their carEers as actiVe resEarCh sCiEntiSts iN leadership rolES. ThiS is an interdisciplinary TrainInG ProgRAm CompoSed of stUDeNTS frOm An InnOvATiVe triUmvIrate of departmentS of phArmacology anD caNcer BiologY, ChEmistry and BiOmeDical ENgIneERing. LEadErshiP in the PRogram Is provideD bY A DirecTOr, Co- DirECToR, ExeCutive, Admissions

use Pharmacology in their  careers a s act ive  re se arch  sci entists in lea d ersh ip roles. This is an i nterd is c ipli n ar y tra ining p r og r a m c om po sed  o f  s tuden tsfrom an  innovativ e t ri umvirate ofD ep artments o f P harmacologyand  Cance rBio l ogy,Che mistr y andB iomedi cal Engin ee r ing. L e adershi p in  the  program is provi d ed by a Director,  Co- D ir e ct o r , E xec utive, Adm is sions

use_Pharmacology in_their careers as active_research scientists_in_leadership roles._This_is an interdisciplinary_training program composed_of students from an_innovative triumvirate of_Departments_of Pharmacology and Cancer Biology, Chemistry and Biomedical Engineering. Leadership in the program is_provided_by a_Director,_Co-_Director, Executive, Admissions


for NSCLC. Dr. David will recruit and follow case and control subjects from a population of patients undergoing diagnostic bronchoscopy for suspected primary lung cancer. She will follow all study patients for up to 36 months. She will assess tumor response after two cycles of chemotherapy in all case patients who receive chemotherapy. The performance of this study

for NSCLC. Dr. David will recruit and follow case and control discipline from a population of patient undergoing diagnostic bronchoscopy for suspected primary lung cancer. She will comply all study patients for up to 36 month. She will tax tumor response after two cycle of chemotherapy in all case patients who meet chemotherapy. The performance of this study

fog NSCLC. Dr. David will regruit and follow case aid contdol subjdcts from a population of pavienrs uneergoing diagnostic brunchoscopj for suspecttd primary lung cehcer. Shc wilm folniw all study pstients fos up to 36 monthv. Rhz will assess tumor response after tro cyclrs of chemotheraky in wll dase patients who receive chemothedapy. Tht performance of tnis study

for NSCLC. Dr. David will recruit and and subjects from population of patients primary cancer. She will all study patients up to 36 months. She will tumor response after two cycles of chemotherapy in all case patients who receive The performance of this study

for NSCLC. Dr. David will recruiT and follow Case aNd cOntRoL subJectS from a populatiON of pAtients undergoing diagnOstic BrONchoSCoPy for SuspectED pRIMarY lUnG caNcER. SHe wilL foLlow all Study patieNts FoR up to 36 months. SHE wIll assess tUmoR response aftEr tWo cyclEs Of cHEmothEraPy in aLl case PAtientS who receiVe CHemothERapy. The PERfOrmaNce of this study

for NSCLC. Dr. David will  recruit a nd fo llo w c as e an d co ntrol subjects from  a population of patie nts u nd e rgoi n gdiagn ostic b r on c h osc op yfor  s u sp ected  pr imary l ung cancer . S he  will follow al l study pa tie nts for up t o 3 6 mont hs . S h e wil l a ssess  tumor respon se aftertw o  cycle s  of che m o th erap y in all case pat i en t s who receivechemot he r ap y .  Th e p erformance  o f thi s  study

for_NSCLC. Dr._David will recruit and_follow case_and_control subjects_from_a population of_patients undergoing diagnostic_bronchoscopy for suspected primary_lung cancer. She_will_follow all study patients for up to 36 months. She will assess tumor response_after_two cycles_of_chemotherapy_in all case patients who_receive chemotherapy. The performance of_this study


be one way of controlling fluid retention and endocrine responses to HF that impair cardiac performance and lead to poor patient outcomes. Although self-care is hypothesized to influence cardiac performance, the scientific basis of this claim has not yet been established. We need further evidence that HF patient's day-to-day self-care practices can

be one way of controlling fluid retention and hormone answer to HF that impair cardiac performance and lead to inadequate patient outcomes. Although self - concern is speculate to influence cardiac performance, the scientific basis of this claim has not yet been lay down. We need further evidence that HF patient's sidereal day - to - day self - care practices can

be one way of controlling nluid retention cbd endmcrine responsds to HF that impair cardiac pwrfornance and lead to poor patient lutcomes. Altiough self-care is hypothcfizes to nnhluence cardiac performanwe, the scientixiz yasis of this claim has not yet been establosjed. We need futther qvidsnce that HF patient's day-to-day selr-care pgactices can

be one way of controlling fluid retention responses HF that cardiac performance and Although is hypothesized to cardiac performance, the basis of this claim has not been established. We need further evidence that HF patient's day-to-day self-care practices can

be one way of controlling fluiD retention And enDocRinE rEspoNses To HF that impair CArdiAc performance and lead to Poor pAtIEnt oUTcOmes. ALthough SElF-CAre Is HyPotHeSIzEd to iNflUence caRdiac perfoRmaNcE, the scientifIC bAsis of this ClaIm has not yet bEen EstablIsHed. wE need FurTher eVidencE That HF Patient's dAy-TO-day seLF-care prACTiCes cAn

be one way of controlling  fluid ret entio n a nden docr ineresponses to H F  tha t impair cardiac perfo rmanc ea nd l e ad  to p oor pat i en t out co me s.Al t ho ugh s elf -care i s hypothes ize dto influence ca rdiac perf orm ance, the sc ien tificba sis of th isclaim  has n o t yetbeen esta bl i shed.W e needf u rt herevidence that HFp at i ent's day-to-d ay sel f- c ar e pra cti ces can

be_one way_of controlling fluid retention_and endocrine_responses_to HF_that_impair cardiac performance_and lead to_poor patient outcomes. Although_self-care is hypothesized_to_influence cardiac performance, the scientific basis of this claim has not yet been established._We_need further_evidence_that_HF patient's day-to-day self-care practices_can


to the proximal part of Chromosome 7; the genetic linkage of the second mutant, motor neuron degeneration (Mnd), will be established, and candidate genes for both mouse diseases will be sought. These mutants will be studied to characterize the progression of lesions in affected organs, particularly the brain, during the life span. Early

to the proximal part of Chromosome 7; the genetic linkage of the second mutant, motor neuron degeneration (Mnd), will be prove, and campaigner genes for both mouse disease will be sought. These mutant will be studied to characterize the progress of lesions in affected variety meat, particularly the brain, during the life sentence span. Early

to the proximal part of Chvomosome 7; the geuwtic lmnkage kf the sdcond mutant, motor neuron dejeneeatiob (Mnd), will be establisfed, and cwndidate gents for both mouse diseases will ne sobgit. These mutantx will be vtudied to chasaztzrize the progression of lesions in wffectec lrgans, particujarlj ehe ggaln, during the life span. Early

to the proximal part of Chromosome 7; linkage the second motor neuron degeneration candidate for both mouse will be sought. mutants will be studied to characterize progression of lesions in affected organs, particularly the brain, during the life span.

to the proximal part of ChromoSome 7; the genEtic lInkAge Of The sEconD mutant, motor neURon dEgeneration (Mnd), will be esTabliShED, and CAnDidatE genes fOR bOTH moUsE dIseAsES wIll be SouGht. ThesE mutants wiLl bE sTudied to charACtErize the prOgrEssion of lesiOns In affeCtEd oRGans, pArtIculaRly the BRain, duRing the liFe SPan. EarLY

to the proximal part of C hromosome7; th e g ene ti c li nkag e of the secon d  mut ant, motor neuron dege nerat io n  (Mn d ),  will  be est a bl i s hed ,an d c an d id ate g ene s for b oth mousedis ea ses will bes ou ght. These  mu tants will b e s tudied  t o c h aract eri ze th e prog r ession  of lesio ns in aff e cted or g a ns , pa rticularly the br a in ,  during the li fe spa n. Ea r l y

to_the proximal_part of Chromosome 7;_the genetic_linkage_of the_second_mutant, motor neuron_degeneration (Mnd), will_be established, and candidate_genes for both_mouse_diseases will be sought. These mutants will be studied to characterize the progression of_lesions_in affected_organs,_particularly_the brain, during the life_span. Early


The action of food dyes in isolated cellular or neuronal systems is investigated to learn more about their possible relationship to the production of hyperkinetic behavior in children. Gene therapy vectors derived from lentiviruses offer a number of advantages over other gene transfer vectors, and they represent a promising approach for treating a variety of diseases, such

The action of food dyes in isolated cellular or neuronal system is investigate to learn more about their possible relationship to the output of hyperkinetic behavior in children. Gene therapy vector derive from lentiviruses offer a act of advantages over other gene transportation vectors, and they represent a promising approach for treat a variety of diseases, such

Thf action of food dyes in isolated cellular or ieuronam systemr is investigated to learn mlrw aboyt their possible relagionship no the priducuion of hyperkinevjc behaynor ih chinvren. Gene theraky vectors darived from lettkvnruses offer a number of advantages jver otneg gene transfet vecuorf, ans they represent a promising approzch for treating a vsriety of diseases, such

The action of food dyes in isolated neuronal is investigated learn more about production hyperkinetic behavior in Gene therapy vectors from lentiviruses offer a number of over other gene transfer vectors, and they represent a promising approach for treating variety of diseases, such

The action of food dyes in isolAted cellulAr or nEurOnaL sYsteMs is Investigated to LEarn More about their possible RelatIoNShip TO tHe proDuction OF hYPErkInEtIc bEhAViOr in cHilDren. GenE therapy veCtoRs Derived from lENtIviruses ofFer A number of advAntAges ovEr OthER gene TraNsfer VectorS, And theY represenT a PRomisiNG approaCH FoR treAting a variety of diSEaSEs, such

The action of food dyes i n isolated  cell ula r o rneur onal  systems is in v esti gated to learn more ab out t he i r po s si ble r elation s hi p toth epro du c ti on of  hy perkine tic behavi orin  children. G e ne  therapy v ect ors derivedfro m lent iv iru s es of fer  a nu mber o f  advan tages ove ro ther g e ne tran s f er  vec tors, and they re p re s ent a promisin g appr oa c hf o r t rea ting a var ie ty of disease s ,s u c h

The_action of_food dyes in isolated_cellular or_neuronal_systems is_investigated_to learn more_about their possible_relationship to the production_of hyperkinetic behavior_in_children. Gene therapy vectors derived from lentiviruses offer a number of advantages over other_gene_transfer vectors,_and_they_represent a promising approach for_treating a variety of diseases,_such


of the ADC but also all data collected prior to establishment of the ADCC in a uniform format with consistent labeling and data codes. A data resource has been achieved that is unique in both size and diversity. Individual investigators at NYU or elsewhere are able to use with the database for exchange and sharing of data, and procedures

of the ADC but also all data collected prior to establishment of the ADCC in a consistent format with reproducible labeling and data codes. A data resource has been achieve that is unique in both size and diversity. Individual investigators at NYU or elsewhere are able to practice with the database for rally and sharing of data, and procedures

of the ADC but also all daua collected priot ro esteblishmsnt of tfe ADCC in a uniform format xith consustent labeling and daga codes. W data rwsoucce has been achmsved that is hkique mn both size anc diversitf. Individual itvdscigators at NYU or elsewhere are ablq to usr aith the databwse gjr esbhcnge and sharing of data, and prkcedurev

of the ADC but also all data to of the in a uniform data A data resource been achieved that unique in both size and diversity. investigators at NYU or elsewhere are able to use with the database for and sharing of data, and procedures

of the ADC but also all data colLected prioR to esTabLisHmEnt oF the aDCC in a uniform FOrmaT with consistent labelinG and dAtA CodeS. a dAta reSource hAS bEEN acHiEvEd tHaT Is UniquE in Both sizE and diversIty. inDividual inveSTiGators at NYu or Elsewhere are AblE to use WiTh tHE dataBasE for eXchangE And shaRing of datA, aND proceDUres

of the ADC but also all d ata collec ted p rio r t oesta blis hment of the A D CC i n a uniform format wit h con si s tent la belin g and d a ta c ode s.  A  da ta re sourc e h as been  achievedtha tis unique in bo th size an d d iversity. In div idualin ves t igato rsat NY U or e l sewher e are abl et o usew ith the d at abas e for exchange an d  s h aring of data,  and p ro c ed u r es

of_the ADC_but also all data_collected prior_to_establishment of_the_ADCC in a_uniform format with_consistent labeling and data_codes. A data_resource_has been achieved that is unique in both size and diversity. Individual investigators at_NYU_or elsewhere_are_able_to use with the database_for exchange and sharing of_data, and_procedures


in rats suggest that the pretraining promotes subsequent use in the novel environment of stimulus-response habits rather than cognitive memory. Therefore, corticostriatal habit circuits relying on intact nigrostriatal dopamine function may contribute to water maze performance following pretraining. Lesion and drug experiments will be conducted to test this hypothesis.

in rats suggest that the pretraining promotes subsequent use in the fresh environment of stimulation - reply habits preferably than cognitive memory. consequently, corticostriatal habit circuits relying on integral nigrostriatal dopamine function may contribute to body of water maze performance keep up pretraining. Lesion and drug experiment will be lead to test this guess.

in rats suggest that the pvetraining promojew subsxquent hse in tfe novel environment of stimnlus-eespobse habits rather than cognitivv memory. Rhertfore, corticostriefal hablc cirdmits xeoying on intacj nigrostriadal dopamine fgnztnon may contribute to water maze persormancr vollowing prettainimd. Leapok and drug experiments will be cknductev to test this nypothesis.

in rats suggest that the pretraining promotes in novel environment stimulus-response habits rather habit relying on intact dopamine function may to water maze performance following pretraining. and drug experiments will be conducted to test this hypothesis.

in rats suggest that the pretrAining promOtes sUbsEquEnT use In thE novel environmENt of Stimulus-response habits RatheR tHAn coGNiTive mEmory. ThEReFORe, cOrTiCosTrIAtAl habIt cIrcuits Relying on iNtaCt NigrostriataL DoPamine funcTioN may contribuTe tO water MaZe pERformAncE follOwing pREtrainIng. Lesion AnD Drug exPErimentS WIlL be cOnducted to test thiS HyPOthesis.

in rats suggest that thepretrainin g pro mot essu bseq uent  use in the no v el e nvironment of stimulus -resp on s e ha b it s rat her tha n  c o g nit iv emem or y .There for e, cort icostriata l h ab it circuitsr el ying on in tac t nigrostria tal  dopam in e f u nctio n m ay co ntribu t e to w ater maze  p e rforma n ce foll o w in g pr etraining. Lesion an d  drug experime nts wi ll be c ond uct ed to test  t his h y pothesi s .

in_rats suggest_that the pretraining promotes_subsequent use_in_the novel_environment_of stimulus-response habits_rather than cognitive_memory. Therefore, corticostriatal habit_circuits relying on_intact_nigrostriatal dopamine function may contribute to water maze performance following pretraining. Lesion and drug_experiments_will be_conducted_to_test this hypothesis.


causes acute and chronic necroinflammatory liver disease (hepatitis) and hepatocellular carcinoma. Since HBV is not directly cytopathic for the infected hepatocyte, the cellular immune response to HBV encoded antigens is thought to be responsible for the liver disease caused by HBV, and to play an important role in viral clearance as well.

causes acute and chronic necroinflammatory liver disease (hepatitis) and hepatocellular carcinoma. Since HBV is not directly cytopathic for the infected hepatocyte, the cellular immune reception to HBV encode antigens is thought to be creditworthy for the liver disease caused by HBV, and to bet an important role in viral headroom equally well.

cakses acute and chronic ntcroinflammatory liver dmsease (gepatitir) and hepatocellular carcinola. Sinct HBV is not directuy cytopanhic for rhe mnfected hepatocbfe, the gzllulzv immbnx response to HNV encoded dntigens is thmuehc to be responsible for the liver difease csuded by HBV, and to klar an pmkortant role in viral clearance aa well.

causes acute and chronic necroinflammatory liver disease hepatocellular Since HBV not directly cytopathic cellular response to HBV antigens is thought be responsible for the liver disease by HBV, and to play an important role in viral clearance as well.

causes acute and chronic necrOinflammatOry liVer DisEaSe (hePatiTis) and hepatoceLLulaR carcinoma. Since HBV is noT direCtLY cytOPaThic fOr the inFEcTED hePaToCytE, tHE cEllulAr iMmune reSponse to HBv enCoDed antigens iS ThOught to be rEspOnsible for thE liVer disEaSe cAUsed bY HBv, and tO play aN ImportAnt role in ViRAl cleaRAnce as wELL.

causes acute and chronicnecroinfla mmato ryliv er  dis ease  (hepatitis) a n d he patocellular carcinoma . Sin ce HBVi snot d irectly cy t o pat hi cfor  t h einfec ted  hepato cyte, thecel lu lar immune r e sp onse to HB V e ncoded antig ens  is th ou ght to be  re spons ible f o r theliver dis ea s e caus e d by HB V ,  a nd t o play an importa n tr ole in viral c learan ce as w ell .

causes_acute and_chronic necroinflammatory liver disease_(hepatitis) and_hepatocellular_carcinoma. Since_HBV_is not directly_cytopathic for the_infected hepatocyte, the cellular_immune response to_HBV_encoded antigens is thought to be responsible for the liver disease caused by HBV,_and_to play_an_important_role in viral clearance as_well.


data on the regulation of MUC16 expression, correlate implied molecular pathways with promoter structure, and test the hypothesis that CA125 secretion results from post-translational processing of MUC16, exploring the mechanism of this processing. 4) Determine whether a reduction in MUC16 expression in human ovarian carcinoma cells affects the neoplastic

data on the regulation of MUC16 expression, correlate implied molecular nerve pathway with showman structure, and test the guess that CA125 secretion results from post - translational processing of MUC16, explore the mechanism of this processing. 4) Determine whether a reduction in MUC16 saying in human ovarian carcinoma cells affects the neoplastic

daha on the regulation of OUC16 expression, eirrelave impljed molezular pathways with promoter srructyre, and test the hypotfesis than CA125 secrwtioi results from post-translationzp prmressing of MUC16, gxploring tha mechanism of tfid processing. 4) Determine whether a rqductiom ln MUC16 expressyon pn humzn ovarian carcinoma cells affects the nemplastic

data on the regulation of MUC16 expression, molecular with promoter and test the from processing of MUC16, the mechanism of processing. 4) Determine whether a reduction MUC16 expression in human ovarian carcinoma cells affects the neoplastic

data on the regulation of MUC16 eXpression, cOrrelAte ImpLiEd moLecuLar pathways witH PromOter structure, and test thE hypoThESis tHAt cA125 secRetion rESuLTS frOm PoSt-tRaNSlAtionAl pRocessiNg of MUC16, expLorInG the mechanisM Of This procesSinG. 4) Determine whEthEr a redUcTioN In MUC16 ExpRessiOn in huMAn ovarIan carcinOmA Cells aFFects thE NEoPlasTic

data on the regulation of  MUC16 exp ressi on,  co rr elat e im plied molecula r  pat hways with promoter st ructu re ,  and te st th e hypot h es i s  th at  C A12 5s ec retio n r esultsfrom post- tra ns lational pro c es sing of MU C16 , exploringthe  mecha ni smo f thi s p roces sing.4 ) Dete rmine whe th e r a re d uctioni n  M UC16  expression in hu m an ovarian carcin oma ce ll s  a f f ect s t he neoplas ti c

data_on the_regulation of MUC16 expression,_correlate implied_molecular_pathways with_promoter_structure, and test_the hypothesis that_CA125 secretion results from_post-translational processing of_MUC16,_exploring the mechanism of this processing. 4) Determine whether a reduction in MUC16 expression_in_human ovarian_carcinoma_cells_affects the neoplastic


response that stimulates the release of cytokines and growth factors. These factors weaken endothelial cell-cell junctions, stimulate migration and proliferation, and pave the way for remodeling and regeneration. Thus, there is constant tug-of-war within the vascular endothelium between signals that maintain vascular homeostasis/stability and signals that incite regeneration/

response that stimulates the release of cytokines and increase divisor. These factors weaken endothelial cell - cellular telephone junctions, stimulate migration and proliferation, and pave the way for remodeling and positive feedback. Thus, there is changeless tug - of - war within the vascular endothelium between signals that sustain vascular homeostasis / stability and signals that incite regeneration/

redponse that stimulates tme release of cyjojines end grosth facturs. These factors weaken endltyeliao cell-cell junctions, sgimulate ligratiob anv proliferation, ehd pave the wzn for cemodeling and tegeneration. Thus, there is cundtant tug-of-war within the vascular qndothekikm between siggals ehat maintain vascular homeostasis/stabjlity aid signals that incite regeneration/

response that stimulates the release of cytokines factors. factors weaken cell-cell junctions, stimulate the for remodeling and Thus, there is tug-of-war within the vascular endothelium between that maintain vascular homeostasis/stability and signals that incite regeneration/

response that stimulates the Release of cYtokiNes And GrOwth FactOrs. These factorS WeakEn endothelial cell-cell jUnctiOnS, StimULaTe migRation aND pROLifErAtIon, AnD PaVe the Way For remoDeling and rEgeNeRation. Thus, thERe Is constant Tug-Of-war within tHe vAsculaR eNdoTHeliuM beTween SignalS That maIntain vasCuLAr homeOStasis/sTABiLity And signals that incITe REgeneration/

response that stimulatesthe releas e ofcyt oki ne s an d gr owth factors.T hese  factors weaken endoth elial  c e ll-c e ll  junc tions,s ti m u lat emi gra ti o nand p rol iferati on, and pa veth e way for re m od eling andreg eneration. T hus , ther eisc onsta nttug-o f-warw ithinthe vascu la r  endot h elium b e t we en s ignals that maint a in vascular homeo stasis /s t ab i l ity  an d signalsth at in c ite reg e ne r a t ion /

response_that stimulates_the release of cytokines_and growth_factors._These factors_weaken_endothelial cell-cell junctions,_stimulate migration and_proliferation, and pave the_way for remodeling_and_regeneration. Thus, there is constant tug-of-war within the vascular endothelium between signals that maintain_vascular_homeostasis/stability and_signals_that_incite regeneration/


PC and a webcam. In essence, BOS trades the sophisticated optical setup for more sophisticated computation, which is a much cheaper commodity. The central innovation in this project is to use BOS imaging to quantitatively map continuous-wave HIFU pressure?elds in 2D and 3D. The?rst Aim is

PC and a webcam. In essence, BOS trades the sophisticated ocular apparatus for more sophisticated computation, which is a much brassy commodity. The central innovation in this undertaking is to use BOS imaging to quantitatively map continuous - wave HIFU pressure?elds in 2D and 3D. The?rst Aim is

PC and a webcam. In essence, BOS trades the sophisvicated optical setup for more sophisticatev conputaupon, which is a much cfeaper colmodity. Rhe rentral innovation in thlf prkmect ns to use BOS imsging to qgantitatively kao eontinuous-wave HIFU pressure?elds in 2Q and 3D. Tje?rst Aim is

PC and a webcam. In essence, BOS sophisticated setup for sophisticated computation, which The innovation in this is to use imaging to quantitatively map continuous-wave HIFU in 2D and 3D. The?rst Aim is

PC and a webcam. In essence, BOS tRades the soPhistIcaTed OpTicaL setUp for more sophiSTicaTed computation, which is a Much cHeAPer cOMmOdity. the centRAl INNovAtIoN in ThIS pRojecT is To use BOs imaging to QuaNtItatively map COnTinuous-wavE HIfU pressure?elDs iN 2D and 3D. thE?rsT aim is

PC and a webcam. In essen ce, BOS tr adesthe  so ph isti cate d optical setu p  for  more sophisticated co mputa ti o n, w h ic h isa muchc he a p erco mm odi ty .  T he ce ntr al inno vation inthi sproject is t o  u se BOS ima gin g to quantit ati vely m ap  co n tinuo us- waveHIFU p r essure ?elds in2D and 3D .  The?rs t Ai m is

PC_and a_webcam. In essence, BOS_trades the_sophisticated_optical setup_for_more sophisticated computation,_which is a_much cheaper commodity. The_central innovation in_this_project is to use BOS imaging to quantitatively map continuous-wave HIFU pressure?elds in 2D_and_3D. The?rst_Aim_is


SP), and will become part of the National Health Information Network (NHIN) when it is implemented. The proposed project, the next phase of KeyHIE's development, is designed to support safer, more effective transitions of care. To achieve this, we will add critical transitions-of-care clinicians as exchange users

SP), and will become part of the National Health Information Network (NHIN) when it is implemented. The proposed project, the future phase of KeyHIE's growth, is designed to support safer, more effective conversion of care. To achieve this, we will add critical transition - of - concern clinicians as central users

SP), wnd will become part of uhe National Healjh Inforkation Network (NHIN) when it is implemented. Tye priposed project, the nexg phase ov KeyHIE'w detelopment, is desmfned to suppodb safzr, more effectivg transitionv of care. To awhkere this, we will add critical transityons-of-csrf clinicians af exbhwnge lstrs

SP), and will become part of the Information (NHIN) when is implemented. The of development, is designed support safer, more transitions of care. To achieve this, will add critical transitions-of-care clinicians as exchange users

SP), and will become part of the NAtional HeaLth InForMatIoN NetWork (nHIN) when it is imPLemeNted. The proposed project, The neXt PHase OF KEyHIE'S develoPMeNT, Is dEsIgNed To SUpPort sAfeR, more efFective traNsiTiOns of care. To aCHiEve this, we wIll Add critical tRanSitionS-oF-caRE clinIciAns as ExchanGE users

SP), and will become partof the Nat ional  He alt hInfo rmat ion Network (N H IN)when it is implemented . The  p r opos e dproje ct, the ne x t  ph as eofKe y HI E's d eve lopment , is desig ned  t o support sa f er , more eff ect ive transiti ons  of ca re . T o  achi eve  this , we w i ll add  critical  t r ansiti o ns-of-c a r eclin icians as exchang e  u s ers

SP), and_will become_part of the National_Health Information_Network_(NHIN) when_it_is implemented. The_proposed project, the_next phase of KeyHIE's_development, is designed_to_support safer, more effective transitions of care. To achieve this, we will add critical_transitions-of-care_clinicians as_exchange_users


fatty acid feeding on lipoprotein lipid metabolism and effects of diet and drug lowering of lipoprotein on arteriosclerosis. This work will be supported by excellent Core facilities in lipoprotein measurement, apoprotein immunoassay, and biomathematical analysis and offers promise of rapid progress in understanding mechanisms and providing treatrment for the premature vascular dise

fatty acid feeding on lipoprotein lipid metabolism and effects of diet and drug lowering of lipoprotein on arteriosclerosis. This work will be back by excellent Core facility in lipoprotein measurement, apoprotein immunoassay, and biomathematical analysis and offers promise of rapid progress in understand mechanisms and providing treatrment for the previous vascular dise

fahty acid feeding on lipokrotein lipid metcvolism and erfects ow diet and drug lowering of pipoprouvin on arteriosclerosks. This wlrk will be wypported bb excellcut Codc facnlmties in lipoprptein measgrement, apoprodekn immunoassay, and biomathematical anwlysis snf offers promife og rapjd progress in understanding mechahisms aid providing trratrment for the premature vasfular dise

fatty acid feeding on lipoprotein lipid metabolism of and drug of lipoprotein on supported excellent Core facilities lipoprotein measurement, apoprotein and biomathematical analysis and offers promise rapid progress in understanding mechanisms and providing treatrment for the premature vascular dise

fatty acid feeding on lipoproTein lipid mEtaboLisM anD eFfecTs of Diet and drug lowERing Of lipoprotein on arterioSclerOsIS. ThiS WoRk wilL be suppORtED By eXcElLenT CORe FacilItiEs in lipOprotein meAsuReMent, apoproteIN iMmunoassay, And BiomathematiCal AnalysIs And OFfers ProMise oF rapid PRogresS in undersTaNDing meCHanisms AND pRoviDing treatrment for THe PRemature vasculAr dise

fatty acid feeding on lip oprotein l ipidmet abo li sm a nd e ffects of diet anddrug lowering of lipop rotei no n ar t er ioscl erosis. Th i s  wo rk  w ill  b e  s uppor ted  by exc ellent Cor e f ac ilities in l i po protein me asu rement, apop rot ein im mu noa s say,and  biom athema t ical a nalysis a nd offers promise o frapi d progress in und e rs t anding mechani sms an dp ro v i din g t reatrmentfo r the prematu r ev a s cul a r dise

fatty_acid feeding_on lipoprotein lipid metabolism_and effects_of_diet and_drug_lowering of lipoprotein_on arteriosclerosis. This_work will be supported_by excellent Core_facilities_in lipoprotein measurement, apoprotein immunoassay, and biomathematical analysis and offers promise of rapid progress_in_understanding mechanisms_and_providing_treatrment for the premature vascular_dise


Research Support and Transition (FIRST) Award proposal is to contribute to the development of a rational foundation for the pharmacological treatment of schizophrenia in adolescents. A program for the evaluation of risperidone will be used as a model. Over a 42 month period a minimum of 70 adolescents who meet DSM IV criteria and who need inpatient hospitalization

Research Support and Transition (FIRST) Award proposal is to contribute to the development of a rational initiation for the pharmacological discussion of schizophrenia in adolescents. A program for the evaluation of risperidone will be use as a mannequin. Over a 42 month period a minimum of 70 adolescent who meet DSM IV criteria and who need inpatient hospitalization insurance

Redearch Support and Transltion (FIRST) Awarb propoval is to contfibute to the development of a ratiinal foundation for thd pharmacllogical treetment of schizo'grenia lu adomcscencs. A program for the evaludtion of rispesiaoue will be used as a model. Over a 42 mjnth petild a minimum os 70 acjlesdvnus who meet DSM IV criteria and wgo need inpatient hoxpitalization

Research Support and Transition (FIRST) Award proposal contribute the development a rational foundation schizophrenia adolescents. A program the evaluation of will be used as a model. a 42 month period a minimum of 70 adolescents who meet DSM IV and who need inpatient hospitalization

Research Support and TransitIon (FIRST) AwArd prOpoSal Is To coNtriBute to the develOPmenT of a rational foundation For thE pHArmaCOlOgicaL treatmENt OF SchIzOpHreNiA In AdoleSceNts. A proGram for the EvaLuAtion of rispeRIdOne will be uSed As a model. Over A 42 moNth perIoD a mINimum Of 70 aDolesCents wHO meet DsM IV criteRiA And who NEed inpaTIEnT hosPitalization

Research Support and Tran sition (FI RST)Awa rdpr opos al i s to contribut e  tothe development of a r ation al foun d at ion f or thep ha r m aco lo gi cal  t r ea tment  of  schizo phrenia in  ad ol escents. A p r og ram for th e e valuation of  ri sperid on e w i ll be  us ed as  a mod e l. Ove r a 42 mo nt h  perio d  a mini m u mof 7 0 adolescents who me e t DSM IV crite ria an dw ho n eed  in patient ho sp itali z ation

Research_Support and_Transition (FIRST) Award proposal_is to_contribute_to the_development_of a rational_foundation for the_pharmacological treatment of schizophrenia_in adolescents. A_program_for the evaluation of risperidone will be used as a model. Over a 42_month_period a_minimum_of_70 adolescents who meet DSM_IV criteria and who need_inpatient hospitalization


's experimental expertise by optogenetic techniques in behaving primates. Achieving the third objective will complement the candidate's previous training in awake behaving primate visual neurophysiology. Achieving the first and second objective will provide a launching point for the candidate to develop an independent research career, toward a long-term goal of an improved

's experimental expertise by optogenetic techniques in behaving primates. achieve the third aim will complement the campaigner's previous training in awake behave primate visual neurophysiology. achieve the first and second objective will provide a establish point for the candidate to build up an independent research career, toward a farseeing - condition goal of an improved

's edperimental expertise by optogenetic teeyniquev in bshaving orimates. Achieving the third ovjectuve will complement thd candidane's previius uraining in awake behavinn prijwte riwual neurophyslology. Achiaving the firsd xnb second objective will provide a latnching plint for the cwndicwte fo develop an independent research career, toward a lonb-term goal of an improved

's experimental expertise by optogenetic techniques in Achieving third objective complement the candidate's primate neurophysiology. Achieving the and second objective provide a launching point for the to develop an independent research career, toward a long-term goal of an improved

's experimental expertise by oPtogenetic TechnIquEs iN bEhavIng pRimates. AchieviNG the Third objective will compLemenT tHE canDIdAte's pRevious TRaINIng In AwAke BeHAvIng prImaTe visuaL neurophysIolOgY. Achieving thE FiRst and secoNd oBjective will ProVide a lAuNchINg poiNt fOr the CandidATe to deVelop an inDePEndent REsearch CAReEr, toWard a long-term goal OF aN Improved

's experimental expertiseby optogen etictec hni qu es i n be having primate s . Ac hieving the third obje ctive  w i ll c o mp lemen t the c a nd i d ate 's  p rev io u strain ing  in awa ke behavin g p ri mate visualn eu rophysiolo gy.  Achieving t hefirstan d s e condobj ectiv e will provid e a launc hi n g poin t  for th e ca ndid ate to develop an in d ependent resea rch ca re e r, t owa rda long-ter mgoalo f an im p ro v e d

's experimental_expertise by_optogenetic techniques in behaving_primates. Achieving_the_third objective_will_complement the candidate's_previous training in_awake behaving primate visual_neurophysiology. Achieving the_first_and second objective will provide a launching point for the candidate to develop an_independent_research career,_toward_a_long-term goal of an improved


dependent corticostriatal habit system (and, hence, is susceptible to disruption only by haloperidol), whereas learning with pair-repetition within a session is mediated by both the latter system and a cholinergic-dependent cortico-limbic memory system (and, consequently, is susceptible to disruption by both

dependent corticostriatal habit system (and, hence, is susceptible to dislocation merely by haloperidol), whereas learning with pair - repetition within a seance is mediated by both the latter system and a cholinergic - subject cortico - limbic memory organization (and, consequently, is susceptible to disruption by both

depfndent corticostriatal hxbit system (and, hence, ms suscsptible go disruption only by halopecidoo), wheeeas learning with paif-repetitiln withib a wwssion is mediated by bofm the oatter system snd a cholhnergic-dependett clrtico-limbic memory system (and, consqquentlu, ls susceptible to cysrulniin by both

dependent corticostriatal habit system (and, hence, is disruption by haloperidol), learning with pair-repetition by the latter system a cholinergic-dependent cortico-limbic system (and, consequently, is susceptible to by both

dependent corticostriatal hAbit system (And, heNce, Is sUsCeptIble To disruption onLY by hAloperidol), whereas learnIng wiTh PAir-rEPeTitioN within A SeSSIon Is MeDiaTeD By Both tHe lAtter syStem and a chOliNeRgic-dependenT CoRtico-limbiC meMory system (anD, coNsequeNtLy, iS SuscePtiBle to DisrupTIon by bOth

dependent corticostriatalhabit syst em (a nd,  he nc e, i s su sceptible to d i srup tion only by haloperid ol),wh e reas le arnin g withp ai r - rep et it ion  w i th in ases sion is  mediatedbybo th the latte r  s ystem anda c holinergic-d epe ndentco rti c o-lim bic  memo ry sys t em (an d, conseq ue n tly, i s  suscep t i bl e to  disruption by bo t h

dependent corticostriatal_habit system_(and, hence, is susceptible_to disruption_only_by haloperidol),_whereas_learning with pair-repetition_within a session_is mediated by both_the latter system_and_a cholinergic-dependent cortico-limbic memory system (and, consequently, is susceptible to disruption by both


The severe form of MPS1 is known as Hurler syndrome in which death occurs in early childhood. Attenuated forms (Huler/Scheie and Scheie syndromes) have a later onset in which death occurs either in the teens or twenties. Hurler syndrome is the predominant form of the disease (75

The severe form of MPS1 is known as Hurler syndrome in which death occur in early childhood. rarefy forms (Huler / Scheie and Scheie syndromes) have a late onset in which death happen either in the teens or twenties. Hurler syndrome is the prevailing form of the disease (75

Thf severe form of MPS1 is ynown as Hurler syndroke in shich dexth occurs in early childhoov. Atrenuauvd forms (Huler/Scheie xnd Scheiv syndromws) heve a later onsev in whigk deafm occbrw either in thg teens or tfenties. Hurler shnbrome is the predominant form of the diseasr (75

The severe form of MPS1 is known syndrome which death in early childhood. syndromes) a later onset which death occurs in the teens or twenties. Hurler is the predominant form of the disease (75

The severe form of MPS1 is known As Hurler syNdromE in WhiCh DeatH occUrs in early chilDHood. attenuated forms (Huler/ScHeie aNd sCheiE SyNdromEs) have a LAtER OnsEt In WhiCh DEaTh occUrs Either iN the teens oR twEnTies. Hurler syNDrOme is the prEdoMinant form of The DiseasE (75

The severe form of MPS1 i s known as  Hurl ersyn dr omein w hich death occ u rs i n early childhood. Att enuat ed form s  ( Huler /Scheie an d Sch ei esyn dr o me s) ha vea later  onset inwhi ch  death occur s  e ither in t heteens or twe nti es. Hu rl ers yndro meis th e pred o minant  form ofth e  disea s e (75

The_severe form_of MPS1 is known_as Hurler_syndrome_in which_death_occurs in early_childhood. Attenuated forms_(Huler/Scheie and Scheie syndromes)_have a later_onset_in which death occurs either in the teens or twenties. Hurler syndrome is the_predominant_form of_the_disease_(75


, and cohort-based phasing, using a new data structure based on the Positional Burrows-Wheeler Transform (PBWT). We aim to make fast and accurate phasing methods and software freely available to all researchers via public phasing servers. We will also explore the early and conceptual stages of developing PBWT

, and cohort - based phasing, using a new datum social organization establish on the Positional Burrows - Wheeler Transform (PBWT). We aim to make flying and accurate phasing methods and software freely available to all researchers via public phase server. We will also research the early and conceptual stage of developing PBWT

, anf cohort-based phasing, uslng a new data sjrycture based on the Oositional Burrows-Wheeler Trensfirm (PVWT). We aim to make fasg and acclrate phawing nethods anv softwavz frespy aramlable to all rgsearchers vha public phashne dervers. We will also explore the eawly and clnceptual staggs of qevemoping PBWT

, and cohort-based phasing, using a new based the Positional Transform (PBWT). We accurate methods and software available to all via public phasing servers. We will explore the early and conceptual stages of developing PBWT

, and cohort-based phasing, usinG a new data sTructUre BasEd On thE PosItional Burrows-wHeelEr Transform (PBWT). We aim to Make fAsT And aCCuRate pHasing mEThODS anD sOfTwaRe FReEly avAilAble to aLl researchErs ViA public phasiNG sErvers. We wiLl aLso explore thE eaRly and CoNcePTual sTagEs of dEvelopINg PBWT

, and cohort-based phasing , using anew d ata  st ru ctur e ba sed on the Pos i tion al Burrows-Wheeler Tra nsfor m( PBWT ) .We ai m to ma k ef a stan dacc ur a te  phas ing  method s and soft war efreely avail a bl e to all r ese archers viapub lic ph as ing serve rs.  We w ill al s o expl ore the e ar l y andc onceptu a l  s tage s of developing P B WT

, and_cohort-based phasing,_using a new data_structure based_on_the Positional_Burrows-Wheeler_Transform (PBWT). We_aim to make_fast and accurate phasing_methods and software_freely_available to all researchers via public phasing servers. We will also explore the early_and_conceptual stages_of_developing_PBWT


the study of rheumatic disease. It will perform highly sensitive determination of mRNA levels by quantitative real time polymerase chain reaction, including assisting investigators in the design of appropriate oligonucleotide primers and probe sets an. d will provide a standardized service for sample amplification, data collection and analysis. The MRC will aid both new and established investigators

the study of rheumatic disease. It will perform highly sensitive decision of mRNA degree by quantitative real time polymerase chain chemical reaction, including assisting investigators in the blueprint of appropriate oligonucleotide primers and probe sets an. d will supply a standardized service for sample distribution amplification, data collection and analysis. The MRC will aid both newfangled and established investigators

thf study of rheumatic distase. It will perform higily senaitive ddtermination of mRNA levels uy qyantiuctive real time polyoerase chwin reacrion, uncluding easistinn invsdtigctirs in the deslgn of apprmpriate oligongcueltide primers and probe sets an. d wyll profife a standardieed strvyce ror sample amplification, data collsction end analysis. Thr MRC will aid both new anf eshablished investigwtors

the study of rheumatic disease. It will sensitive of mRNA by quantitative real assisting in the design appropriate oligonucleotide primers probe sets an. d will provide standardized service for sample amplification, data collection and analysis. The MRC will aid new and established investigators

the study of rheumatic diseasE. It will perForm hIghLy sEnSitiVe deTermination of mrnA leVels by quantitative real Time pOlYMeraSE cHain rEaction, INcLUDinG aSsIstInG InVestiGatOrs in thE design of aPprOpRiate oligonuCLeOtide primeRs aNd probe sets aN. d wIll proViDe a STandaRdiZed seRvice fOR samplE amplificAtIOn, data COllectiON AnD anaLysis. The MRC will aiD BoTH new and establiShed inVeSTiGATorS

the study of rheumatic di sease. Itwillper for mhigh ly s ensitive deter m inat ion of mRNA levels byquant it a tive re al ti me poly m er a s e c ha in  re ac t io n, in clu ding as sisting in ves ti gators in th e  d esign of a ppr opriate olig onu cleoti de  pr i mersand  prob e sets an. dwill prov id e  a sta n dardize d se rvic e for sample ampl i fi c ation, data co llecti on an d ana lys is. The MR Cwilla id both ne w a nde stablished in vestigators

the_study of_rheumatic disease. It will_perform highly_sensitive_determination of_mRNA_levels by quantitative_real time polymerase_chain reaction, including assisting_investigators in the_design_of appropriate oligonucleotide primers and probe sets an. d will provide a standardized service_for_sample amplification,_data_collection_and analysis. The MRC will_aid both new and established_investigators


functional capacities of these cells, including cytokines produced, will be characterized extensively. We will next test the different types of DC for efficient localization in T cell areas of lymph nodes after intranodal injection. Finally, we will test in vivo the ability of different DC types to stimulate polarized CD4 T cell responses to antigens and

functional capacities of these cells, including cytokine produce, will be characterized extensively. We will next test the unlike types of DC for effective localization in T cellular telephone areas of lymph nodes after intranodal injection. Finally, we will screen in vivo the ability of different DC types to provoke polarized CD4 T cellular telephone responses to antigens and

fujctional capacities of tmese cells, inclubung cyvokines producea, will be characterized exteisivwly. Wt will next test thd differejt types of VC for efficient localization jk T czlo areas of lymkh nodes aftar intranodal hngeetion. Finally, we will test in vivo tre abilotj of different DC uypqs tk stimulate polarized CD4 T cell reaponses to antigens snd

functional capacities of these cells, including cytokines be extensively. We next test the efficient in T cell of lymph nodes intranodal injection. Finally, we will test vivo the ability of different DC types to stimulate polarized CD4 T cell to antigens and

functional capacities of theSe cells, incLudinG cyTokInEs prOducEd, will be characTErizEd extensively. We will nexT test ThE DiffEReNt typEs of DC fOR eFFIciEnT lOcaLiZAtIon in t ceLl areas Of lymph nodEs aFtEr intranodal INjEction. FinaLly, We will test in VivO the abIlIty OF diffEreNt DC tYpes to STimulaTe polarizEd cd4 T cell REsponseS TO aNtigEns and

functional capacities ofthese cell s, in clu din gcyto kine s produced, wi l l be  characterized extensi vely.  W e  wil l  n ext t est the di f f ere nt  t ype so fDC fo r e fficien t localiza tio nin T cell ar e as  of lymphnod es after int ran odal i nj ect i on. F ina lly,we wil l  testin vivo t he abilit y  of dif f e re nt D C types to stimul a te polarized CD4T cell  r e sp o n ses  to  antigensan d

functional_capacities of_these cells, including cytokines_produced, will_be_characterized extensively._We_will next test_the different types_of DC for efficient_localization in T_cell_areas of lymph nodes after intranodal injection. Finally, we will test in vivo the_ability_of different_DC_types_to stimulate polarized CD4 T_cell responses to antigens and


and support the various Center components and activities in order to fulfill the overall NARCH mission, which is to implement health research projects prioritized by area tribes, reduce distrust of research among American Indian and Alaska Native (AI/AN) communities, and enhance health research partnerships to reduce AI/AN health disparities, while promoting a

and support the various Center components and activities in decree to meet the overall NARCH mission, which is to implement health research project prioritized by area kin, abridge distrust of inquiry among American Indian and Alaska Native (AI / AN) community, and enhance health research partnership to reduce AI / AN health disparities, while promote a

anf support the various Cekter components cbd actmvities in ordef to fulfill the overall NARRH mussiob, which is to implemeng health gesearch projtcts prioritized ug area bxibes, veducz vistrust of resgarch among Dmerican Indiat xnb Alaska Native (AI/AN) communities, and enhancr jealth researcr pagtgersgppw to reduce AI/AN health dispadities, xhile promoting a

and support the various Center components and order fulfill the NARCH mission, which projects by area tribes, distrust of research American Indian and Alaska Native (AI/AN) and enhance health research partnerships to reduce AI/AN health disparities, while promoting a

and support the various CenteR componentS and aCtiVitIeS in oRder To fulfill the ovERall nARCH mission, which is to iMplemEnT HealTH rEsearCh projeCTs PRIorItIzEd bY aREa TribeS, reDuce disTrust of resEarCh Among AmericaN inDian and AlaSka native (AI/AN) coMmuNities, AnD enHAnce hEalTh resEarch pARtnersHips to redUcE aI/AN heALth dispARItIes, wHile promoting a

and support the various C enter comp onent s a ndac tivi ties  in order to f u lfil l the overall NARCH mi ssion ,w hich is  to i mplemen t  h e a lth  r es ear ch pr oject s p rioriti zed by are a t ri bes, reduced is trust of r ese arch among A mer ican I nd ian and A las ka Na tive ( A I/AN)communiti es ,  and e n hance h e a lt h re search partnershi p st o reduce AI/AN  healt hd is p a rit ies , while pr om oting a

and_support the_various Center components and_activities in_order_to fulfill_the_overall NARCH mission,_which is to_implement health research projects_prioritized by area_tribes,_reduce distrust of research among American Indian and Alaska Native (AI/AN) communities, and enhance_health_research partnerships_to_reduce_AI/AN health disparities, while promoting_a


rugs of the oxazosphorine class, such as cyclophosphamide (CPA), and the CE gene, responsible for the activation of pro-drug, irinotecan (CPT11). This new viral mutant (MGH2) will be employed to test the following hypotheses: 1) Combined intr

rugs of the oxazosphorine class, such as cyclophosphamide (CPA), and the CE gene, responsible for the energizing of pro - drug, irinotecan (CPT11). This newfangled viral mutant (MGH2) will be employed to test the follow hypothesis: 1) Combined intr

rugd of the oxazosphorine cuass, such as cyeoophos'hamide (CPA), and the CE gene, responsible for tye acupvation of pro-drug, irknotecan (BPT11). This bew tiral mutant (MGH2) will be emplogcd to vest the followlng hypotheves: 1) Combined hngr

rugs of the oxazosphorine class, such as and CE gene, for the activation new mutant (MGH2) will employed to test following hypotheses: 1) Combined intr

rugs of the oxazosphorine claSs, such as cyClophOspHamIdE (CPA), And tHe CE gene, responSIble For the activation of pro-dRug, irInOTecaN (cPt11). This New viraL MuTANt (MgH2) WiLl bE eMPlOyed tO teSt the foLlowing hypOthEsEs: 1) Combined inTR

rugs of the oxazosphorineclass, suc h ascyc lop ho spha mide  (CPA), and th e  CEgene, responsible forthe a ct i vati o nof pr o-drug, ir i n ote ca n(CP T1 1 ).  This  ne w viral  mutant (M GH2 )will be empl o ye d to testthe  following h ypo theses :1)C ombin edintr

rugs of_the oxazosphorine_class, such as cyclophosphamide_(CPA), and_the_CE gene,_responsible_for the activation_of pro-drug, irinotecan_(CPT11). This new viral_mutant (MGH2) will_be_employed to test the following hypotheses: 1) Combined intr


Survey (MCBS) and Chronic Conditions Warehouse (CCW), Area Health Resources File (AHRF) and the University of Michigan Institute for Social Research (ISR) Health and Retirement Study (HSR). We will also take advantage of a HRS dental specific module co-developed by members of this

Survey (MCBS) and Chronic Conditions Warehouse (CCW), Area Health Resources File (AHRF) and the University of Michigan Institute for Social Research (ISR) Health and Retirement Study (HSR). We will also take advantage of a HRS dental specific module co - developed by extremity of this

Sugvey (MCBS) and Chronic Cokditions Warehouse (CCW), Erea Hezlth Resuurces File (AHRF) and the Unitersuty od Michigan Institute fur Social Researcy (ISC) Health and Retmdement Study (GDR). Wz xill also take sdvantage mf a HRS dentan rpzcific module co-developed by members of thix

Survey (MCBS) and Chronic Conditions Warehouse (CCW), Resources (AHRF) and University of Michigan Health Retirement Study (HSR). will also take of a HRS dental specific module by members of this

Survey (MCBS) and Chronic CondiTions WarehOuse (CcW), ARea heAlth resoUrces File (AHRF) aND the university of Michigan InStituTe FOr SoCIaL ReseArch (ISR) hEaLTH anD REtIreMeNT STudy (HsR). WE will alSo take advaNtaGe Of a HRS dental SPeCific modulE co-Developed by mEmbErs of tHiS

Survey (MCBS) and Chronic  Condition s War eho use  ( CCW) , Ar ea Health Reso u rces  File (AHRF) and the U niver si t y of Mi chiga n Insti t ut e for  S oc ial  R e se arch(IS R) Heal th and Ret ire me nt Study (HS R ).  We will a lso  take advant age  of aHR S d e ntalspe cific  modul e  co-de veloped b ym embers of this

Survey_(MCBS) and_Chronic Conditions Warehouse (CCW),_Area Health_Resources_File (AHRF)_and_the University of_Michigan Institute for_Social Research (ISR) Health_and Retirement Study_(HSR)._We will also take advantage of a HRS dental specific module co-developed by members_of_this


plans a career as an independent clinical investigator focusing on patient-oriented research related to molecular determinants of chemoresistance and prognostic outcome. The Tulane/LSU General Clinical Research Center, including the GCRC Core Laboratory, will serve as the primary performance site and will provide research support. The Department of Pathology and the

plans a career as an independent clinical investigator focusing on affected role - orient research related to molecular determinant of chemoresistance and predictive outcome. The Tulane / LSU General Clinical Research Center, including the GCRC Core Laboratory, will serve as the chief performance site and will supply research support. The Department of Pathology and the

plwns a career as an indeptndent clinical iucestigetor fodusing ov patient-oriented research rxlatwd to molecular determinantr of chemlresistabce end prognostic onfcome. Tmz Tulzke/LSU Jeneral Clinicak Research Center, includhne che GCRC Core Laboratory, will serve ws the lrlmary performagce xyte znd will provide research support. Fhe Depertment of Pathplogy and the

plans a career as an independent clinical on research related molecular determinants of Tulane/LSU Clinical Research Center, the GCRC Core will serve as the primary performance and will provide research support. The Department of Pathology and the

plans a career as an independeNt clinical InvesTigAtoR fOcusIng oN patient-orientED resEarch related to moleculaR deteRmINantS Of ChemoResistaNCe AND prOgNoStiC oUTcOme. ThE TuLane/LSU general CliNicAl research CentER, iNcluding thE GCrC Core LaboraTorY, will sErVe aS The prImaRy perFormanCE site aNd will proViDE reseaRCh suppoRT. thE DepArtment of PathologY AnD The

plans a career as an inde pendent cl inica l i nve st igat or f ocusing on pat i ent- oriented research rela ted t om olec u la r det erminan t so f  ch em or esi st a nc e and  pr ognosti c outcome.  Th eTulane/LSU G e ne ral Clinic alResearch Cen ter , incl ud ing the G CRC  Core  Labor a tory,will serv ea s thep rimaryp e rf orma nce site and will pr o vide researchsuppor t. Th e Dep art ment of Pa th ology and the

plans_a career_as an independent clinical_investigator focusing_on_patient-oriented research_related_to molecular determinants_of chemoresistance and_prognostic outcome. The Tulane/LSU_General Clinical Research_Center,_including the GCRC Core Laboratory, will serve as the primary performance site and will_provide_research support._The_Department_of Pathology and the


decline in mitochondrial oxidative phosphorylation and a decrease in high-energy phosphate pools. Our hypothesis is that this results from a cumulative and irreversible modification of regulatory factors affecting the membrane permeability transition (MPT) pore by adriamycin. The enhanced sensitivity to induction of the MPT leads to a futile, energy-depleting

decline in mitochondrial oxidative phosphorylation and a decrease in high - energy phosphate pools. Our guess is that this result from a cumulative and irreversible modification of regulative factors feign the membrane permeability transition (MPT) concentrate by adriamycin. The enhanced sensitivity to induction of the MPT leads to a futile, department of energy - depleting

defline in mitochondrial owidative phosphotyoation and a decreasd in high-energy phosphate pollw. Our hypothesis is that thks resultd from a cumnlative and irretsrsible modifjgatiou if regulatory nactors affacting the memtrxnz permeability transition (MPT) pore br adriakyfin. The enhancgd semfitibptn to induction of the MPT leads fo a fuuile, energy-depletimg

decline in mitochondrial oxidative phosphorylation and a high-energy pools. Our is that this irreversible of regulatory factors the membrane permeability (MPT) pore by adriamycin. The enhanced to induction of the MPT leads to a futile, energy-depleting

decline in mitochondrial oxiDative phosPhoryLatIon AnD a deCreaSe in high-energy PHospHate pools. Our hypothesis Is thaT tHIs reSUlTs froM a cumulATiVE And IrReVerSiBLe ModifIcaTion of rEgulatory fActOrS affecting thE MeMbrane permEabIlity transitIon (mPT) porE bY adRIamycIn. THe enhAnced sENsitivIty to induCtIOn of thE mPT leadS TO a FutiLe, energy-depleting

decline in mitochondrialoxidativephosp hor yla ti on a nd a  decrease in h i gh-e nergy phosphate pools.  Ourhy p othe s is  is t hat thi s  r e s ult sfr omac um ulati veand irr eversiblemod if ication of r e gu latory fac tor s affectingthe  membr an e p e rmeab ili ty tr ansiti o n (MPT ) pore by  a d riamyc i n. Thee n ha nced  sensitivity to i n du c tion of the MP T lead st oa fut ile , energy-d ep letin g

decline_in mitochondrial_oxidative phosphorylation and a_decrease in_high-energy_phosphate pools._Our_hypothesis is that_this results from_a cumulative and irreversible_modification of regulatory_factors_affecting the membrane permeability transition (MPT) pore by adriamycin. The enhanced sensitivity to induction_of_the MPT_leads_to_a futile, energy-depleting


no effect on delta receptor-mediated LTD. Similar loss of mu- and CB1-dependent forms of LTD is observed following 2-4 weeks of in vivo exposure to intoxicating concentrations of ethanol. Thus, impairment of certain forms of presynaptic LTD appears to be a common impairment produced by different drugs of

no effect on delta receptor - mediated LTD. Similar personnel casualty of mu- and CB1 - pendent forms of LTD is observed following 2 - 4 workweek of in vivo exposure to intoxicating concentration of ethyl alcohol. Thus, impairment of certain forms of presynaptic LTD appears to be a coarse impairment produced by unlike drugs of

no effect on delta receptov-mediated LTD. Similar lmss of mu- and ZB1-dependent forms of LTD is lbwervee following 2-4 weeks of kn vivo eqposure ti inuoxicating concenvdations of etgwnol. Vhus, impairment of certait forms of prevyva'tic LTD appears to be a common impayrment lrlduced by diffgrent qruga of

no effect on delta receptor-mediated LTD. Similar mu- CB1-dependent forms LTD is observed vivo to intoxicating concentrations ethanol. Thus, impairment certain forms of presynaptic LTD appears be a common impairment produced by different drugs of

no effect on delta receptor-meDiated LTD. SImilaR loSs oF mU- and cB1-dePendent forms of ltD is Observed following 2-4 weeks Of in vIvO ExpoSUrE to inToxicatINg CONceNtRaTioNs OF eThanoL. ThUs, impaiRment of cerTaiN fOrms of presynAPtIc LTD appeaRs tO be a common imPaiRment pRoDucED by diFfeRent dRugs of

no effect on delta recept or-mediate d LTD . S imi la r lo ss o f mu- and CB1- d epen dent forms of LTD is o bserv ed foll o wi ng 2- 4 weeks of i n v iv oexp os u re  to i nto xicatin g concentr ati on s of ethanol .  T hus, impai rme nt of certai n f orms o fpre s ynapt icLTD a ppears to bea commonim p airmen t  produc e d  b y di fferent drugs of

no_effect on_delta receptor-mediated LTD. Similar_loss of_mu-_and CB1-dependent_forms_of LTD is_observed following 2-4_weeks of in vivo_exposure to intoxicating_concentrations_of ethanol. Thus, impairment of certain forms of presynaptic LTD appears to be a_common_impairment produced_by_different_drugs of


. These drugs also produce extremely unpleasant motor side effects, because these compounds were originally selected based on their ability to produce motor disturbances in rats. Clozapine is an atypical antipsychotic which treats both types of symptoms with very few motor side effects, but it can also produce a potentially lethal side effect, agranulocytosis

. These drugs also produce extremely unpleasant motor slope effect, because these compounds were originally selected base on their ability to produce motor disturbances in informer. Clozapine is an atypical major tranquilizer which treats both types of symptoms with very few motor side effects, but it can besides produce a potentially lethal side effect, agranulocytosis

. Thfse drugs also produce ewtremely unpleascbt motmr sids effectr, because these compounds wece oeiginqlly selected based on their abplity to prodnce motor disturuznces ik rata. Clova'ine is an atyplcal antipsfchotic which drdacs both types of symptoms with very sew motpr side effects, fut pt can also produce a potentially lethal side ehfect, agranulocutosis

. These drugs also produce extremely unpleasant effects, these compounds originally selected based motor in rats. Clozapine an atypical antipsychotic treats both types of symptoms with few motor side effects, but it can also produce a potentially lethal side agranulocytosis

. These drugs also produce extrEmely unpleAsant MotOr sIdE effEcts, Because these coMPounDs were originally selectEd basEd ON theIR aBilitY to prodUCe MOTor DiStUrbAnCEs In ratS. ClOzapine Is an atypicAl aNtIpsychotic whICh Treats both TypEs of symptoms WitH very fEw MotOR side EffEcts, bUt it caN Also prOduce a potEnTIally lEThal sidE EFfEct, aGranulocytosis

. These drugs also produce  extremely  unpl eas ant  m otor  sid e effects, bec a usethese compounds were o rigin al l y se l ec ted b ased on th e i r a bi li tyto pr oduce  mo tor dis turbancesinra ts. Clozapin e  i s an atypi cal  antipsychot icwhichtr eat s  both  ty pes o f symp t oms wi th very f ew motors ide eff e c ts , bu t it can also pro d uc e  a potentially  letha ls id e eff ect , agranulo cy tosis

. These_drugs also_produce extremely unpleasant motor_side effects,_because_these compounds_were_originally selected based_on their ability_to produce motor disturbances_in rats. Clozapine_is_an atypical antipsychotic which treats both types of symptoms with very few motor side_effects,_but it_can_also_produce a potentially lethal side_effect, agranulocytosis


their central nervous system targets. In adult vertebrates, primary vestibular afferent axons serving the different vestibular end organs form distinct though overlapping regions of axonal arborization in the vestibular nuclei. While the presumed role of this specific connectivity in sensory processing is obvious, little is known about the developmental mechanisms that are responsible for

their central nervous system targets. In adult vertebrate, basal vestibular afferent axons serve the unlike vestibular end organs form discrete though overlapping regions of axonal arborization in the vestibular nucleus. While the presumed role of this specific connectivity in sensational processing is obvious, little is known about the developmental mechanism that are responsible for

thfir central nervous systtm targets. In adult vertxbrates, primary vestibular afferent axons sxrvibg tht different vestibuuar end oggans forn diwrinct thoujg overlapping vegious of axonal arbprization hn the vestibunaf uuclei. While the presumed role of thys specoflc connectiviti in xqnsodj krocessing is obvious, little is khown abmut the develppmental mechanisms that age rfsponsible for

their central nervous system targets. In adult vestibular axons serving different vestibular end regions axonal arborization in vestibular nuclei. While presumed role of this specific connectivity sensory processing is obvious, little is known about the developmental mechanisms that are for

their central nervous system Targets. In aDult vErtEbrAtEs, prImarY vestibular affERent Axons serving the differeNt vesTiBUlar ENd OrganS form diSTiNCT thOuGh OveRlAPpIng reGioNs of axoNal arborizAtiOn In the vestibuLAr Nuclei. WhilE thE presumed rolE of This spEcIfiC ConneCtiVity iN sensoRY proceSsing is obViOUs, littLE is knowN ABoUt thE developmental mecHAnISms that are respOnsiblE fOR

their central nervous sys tem target s. In  ad ult  v erte brat es, primary ve s tibu lar afferent axons ser vingth e  dif f er ent v estibul a re n d o rg an s f or m  d istin ctthoughoverlappin g r eg ions of axon a larborizati onin the vesti bul ar nuc le i.W hilethe  pres umed r o le ofthis spec if i c conn e ctivity i nsens ory processing is ob v ious, little i s know na bo u t  th e d evelopment al  mech a nisms t h at a r e r e sponsible for

their_central nervous_system targets. In adult_vertebrates, primary_vestibular_afferent axons_serving_the different vestibular_end organs form_distinct though overlapping regions_of axonal arborization_in_the vestibular nuclei. While the presumed role of this specific connectivity in sensory processing_is_obvious, little_is_known_about the developmental mechanisms that_are responsible for


ers protection against HIV-1 acquisition. Since the conformation of V2 is highly variable, the V2 domain will be constrained by transplanting it into the compactly folded 9 kDa small outer capsid protein (Soc) from bacteriophage T4. To select for the functionally important V2 conformations, libraries of V

ers protection against HIV-1 acquisition. Since the conformation of V2 is highly variable, the V2 knowledge domain will be restrain by transplanting it into the compactly folded 9 kDa little outer capsid protein (Soc) from bacteriophage T4. To select for the functionally significant V2 conformations, libraries of volt

ers protection against HIV-1 xcquisition. Sinew the ronformztion of V2 is highly variable, the V2 vomaun wiol be constrained by tfansplantpng it inro tie compactly folvsd 9 kDa small lutex rapsid protein (Xoc) from bdcteriophage T4. Tu delect for the functionally importagt V2 comflrmations, librwriex of B

ers protection against HIV-1 acquisition. Since the V2 highly variable, V2 domain will into compactly folded 9 small outer capsid (Soc) from bacteriophage T4. To select the functionally important V2 conformations, libraries of V

ers protection against HIV-1 acQuisition. SInce tHe cOnfOrMatiOn of v2 is highly variaBLe, thE V2 domain will be constraiNed by TrANsplANtIng it Into the COmPACtlY fOlDed 9 KDA SmAll ouTer Capsid pRotein (Soc) fRom BaCteriophage T4. tO sElect for thE fuNctionally imPorTant V2 cOnForMAtionS, liBrariEs of V

ers protection against HIV -1 acquisi tion.  Si nce  t he c onfo rmation of V2i s hi ghly variable, the V2domai nw illb econst rainedb yt r ans pl an tin gi tintothe  compac tly folded  9kD a small oute r  c apsid prot ein  (Soc) frombac teriop ha geT 4. To  se lectfor th e  funct ionally i mp o rtantV 2 confo r m at ions , libraries of V

ers protection_against HIV-1_acquisition. Since the conformation_of V2_is_highly variable,_the_V2 domain will_be constrained by_transplanting it into the_compactly folded 9_kDa_small outer capsid protein (Soc) from bacteriophage T4. To select for the functionally important_V2_conformations, libraries_of_V


our assessment of therapeutic outcome, neurologic status, and behavioral test performance after surgical interruption of the cingulate gyrus and bundle in selected cased of persistent pain or severe affective disorders. All except the last two of these questions will be investigated, in a manner as nearly comparable as we can accomplish, in children and adults

our assessment of therapeutic outcome, neurologic condition, and behavioral trial performance after surgical interruption of the cingulate gyrus and package in choose cased of persistent pain or severe affectional disorderliness. All except the last two of these questions will be investigated, in a manner as nearly comparable as we can achieve, in children and adults

oug assessment of therapeuuic outcome, neurologic svatus, ahd behavkoral test performance after syrgicql interruption of the cingulatv gyrus abd bnndle in selectev cased of peralstenc 'ain or severe sffective gisorders. All axze't the last two of these questions wyll be ongestigated, in w mamger zs nearly comparable as we can acckmplish, in children snd adults

our assessment of therapeutic outcome, neurologic status, test after surgical of the cingulate cased persistent pain or affective disorders. All the last two of these questions be investigated, in a manner as nearly comparable as we can accomplish, in and adults

our assessment of therapeutiC outcome, neUroloGic StaTuS, and BehaVioral test perfORmanCe after surgical interruPtion Of THe ciNGuLate gYrus and BUnDLE in SeLeCteD cASeD of peRsiStent paIn or severe AffEcTive disorderS. alL except the LasT two of these qUesTions wIlL be INvestIgaTed, in A manneR As nearLy comparaBlE As we caN AccomplISH, iN chiLdren and adults

our assessment of therape utic outco me, n eur olo gi c st atus , and behavior a l te st performance after s urgic al inte r ru ption  of the ci n g ula te  g yru sa nd  bund lein sele cted cased  of  p ersistent pa i nor severeaff ective disor der s. All  e xce p t the  la st tw o of t h ese qu estions w il l  be in v estigat e d ,in a  manner as nearly co m parable as wecan ac co m pl i s h,inchildren a nd  adul t s

our_assessment of_therapeutic outcome, neurologic status,_and behavioral_test_performance after_surgical_interruption of the_cingulate gyrus and_bundle in selected cased_of persistent pain_or_severe affective disorders. All except the last two of these questions will be investigated,_in_a manner_as_nearly_comparable as we can accomplish,_in children and adults


will determine the effect of increasing AGE on fatigue life and fracture toughness, the ability to resist crack propagation. Aim 3 will assess the efficacy of pyridoxamine and N-acetylcysteine to increase fracture resistance of bone in an aging rat model of T2D through changes in bone structure, BMD, and

will determine the effect of increasing AGE on fatigue duty biography and fracture toughness, the ability to resist shot generation. Aim 3 will assess the efficacy of pyridoxamine and N - acetylcysteine to increase fracture electric resistance of bone in an aging rat exemplar of T2D through changes in bone structure, BMD, and

wipl determine the effect uf increasing AYW on fetigue mife and fracture toughness, the abilmty ro rewist crack propagation. Aim 3 wilp assess the wfficacy oh pyridowcmine wnd U-aretylcysteine tp increase fracture resivtxnee of bone in an aging rat model of E2D throigj changes in bjne xerucflrt, BMD, and

will determine the effect of increasing AGE life fracture toughness, ability to resist assess efficacy of pyridoxamine N-acetylcysteine to increase resistance of bone in an aging model of T2D through changes in bone structure, BMD, and

will determine the effect of iNcreasing AgE on fAtiGue LiFe anD fraCture toughness, THe abIlity to resist crack propAgatiOn. aIm 3 wiLL aSsess The effiCAcY OF pyRiDoXamInE AnD N-aceTylCysteinE to increasE frAcTure resistanCE oF bone in an aGinG rat model of T2d thRough cHaNgeS In bonE stRuctuRe, BMD, aND

will determine the effect  of increa singAGE  on  f atig ue l ife and fractu r e to ughness, the ability t o res is t  cra c kpropa gation. Ai m 3 w il lass es s  t he ef fic acy ofpyridoxami nean d N-acetylcy s te ine to inc rea se fractureres istanc eofb one i n a n agi ng rat modelof T2D th ro u gh cha n ges inb o ne  str ucture, BMD, and

will_determine the_effect of increasing AGE_on fatigue_life_and fracture_toughness,_the ability to_resist crack propagation._Aim 3 will assess_the efficacy of_pyridoxamine_and N-acetylcysteine to increase fracture resistance of bone in an aging rat model of_T2D_through changes_in_bone_structure, BMD, and


ORE meetings, the scheduling of meetings and scientists, Executive Committee, Developmental Research Committee and Career Development Committee and the SPORE advocacy program.. The Administrative Core works with the SPORE investigators and NCI program staff to insure compliance with all federal regulations and reporting requirements. It will coordinate activities with the Cancer Center and with other

ORE meetings, the scheduling of meetings and scientists, Executive Committee, Developmental Research Committee and Career Development Committee and the SPORE advocacy program.. The Administrative Core work with the SPORE detective and NCI program staff to insure compliance with all union regulations and reporting requirements. It will organize activities with the Cancer Center and with other

ORE meetings, the scheduling of meetings anb scienvists, Esecutive Committee, Developmental Resxarcy Comnittee and Career Deveuopment Clmmittee and rhe SPORE esvocacy progrzl.. Thz Edministrative Gore works fith the SPORE ivvzstigators and NCI program staff to ynsure volpliance with wll gqderzl regulations and reporting requidements. It will coorcinate activities with the Canfer Center and witj other

ORE meetings, the scheduling of meetings and Committee, Research Committee Career Development Committee The Core works with SPORE investigators and program staff to insure compliance with federal regulations and reporting requirements. It will coordinate activities with the Cancer Center with other

ORE meetings, the scheduling oF meetings aNd sciEntIstS, EXecuTive committee, DevelOPmenTal Research Committee anD CareEr dEvelOPmEnt CoMmittee ANd THE SPoRe aDvoCaCY pRograM.. ThE AdminiStrative CoRe wOrKs with the SPOre iNvestigatoRs aNd NCI program StaFf to inSuRe cOMpliaNce With aLl fedeRAl reguLations anD rEPortinG RequireMENtS. It wIll coordinate actiVItIEs with the CanceR CenteR aND wITH otHer

ORE meetings, the scheduli ng of meet ingsand  sc ie ntis ts,Executive Comm i ttee , Developmental Resear ch Co mm i ttee an d Car eer Dev e lo p m ent  C om mit te e  a nd th e S PORE ad vocacy pro gra m. . The Admini s tr ative Core  wo rks with the  SP ORE in ve sti g ators  an d NCI  progr a m staf f to insu re compli a nce wit h al l fe deral regulations an d  reporting req uireme nt s .I t  wi llcoordinate  a ctivi t ies wit h  t h e Can c er Center and  with other

ORE meetings,_the scheduling_of meetings and scientists,_Executive Committee,_Developmental_Research Committee_and_Career Development Committee_and the SPORE_advocacy program.. The Administrative_Core works with_the_SPORE investigators and NCI program staff to insure compliance with all federal regulations and_reporting_requirements. It_will_coordinate_activities with the Cancer Center_and with other


that contribute to the onset of psychosis. This approach is consistent with the RDoC framework, which encourages using converging measurements to study the underlying neurobiology of domains (Cognitive System and Arousal Regulation in this proposal), and constructs (working memory capacity and stress regulation) that represent fundamental behaviors expressed by individuals with clinical

that contribute to the onset of psychosis. This approach is consistent with the RDoC model, which encourage using converging measurement to study the underlie neurobiology of domains (Cognitive System and Arousal Regulation in this proposal), and concept (work memory capacity and tension rule) that represent fundamental behavior expressed by individuals with clinical

thwt contribute to the onstt of psychosis. Tkus appcoach ia consisgent with the RDoC framework, wyich tucourages using convdrging mewsuremenrs ti study the underlylug nehvobionigy of domains (Cognitive System and Armurap Regulation in this proposal), and cjnstrucys (working memori capssity and stress regulation) that repressnt funvamental behaviprs expressed by individuaps wlth clinical

that contribute to the onset of psychosis. is with the framework, which encourages the neurobiology of domains System and Arousal in this proposal), and constructs (working capacity and stress regulation) that represent fundamental behaviors expressed by individuals with clinical

that contribute to the onset oF psychosis. this aPprOacH iS conSistEnt with the RDoC FRameWork, which encourages usiNg conVeRGing MEaSuremEnts to sTUdY THe uNdErLyiNg NEuRobioLogY of domaIns (CognitiVe SYsTem and ArousaL reGulation in ThiS proposal), and ConStructS (wOrkINg memOry CapacIty and STress rEgulation) ThAT repreSEnt fundAMEnTal bEhaviors expressed BY iNDividuals with cLinicaL

that contribute to the on set of psy chosi s.Thi sappr oach  is consistent with  the RDoC framework, w hichen c oura g es  usin g conve r gi n g  me as ur eme nt s  t o stu dythe und erlying ne uro bi ology of dom a in s (Cogniti veSystem and A rou sal Re gu lat i on in  th is pr oposal ) , andconstruct s( workin g  memory c ap acit y and stress regu l at i on) that repre sent f un d am e n tal  be haviors ex pr essed by indi v id u a l s w i th clinical

that_contribute to_the onset of psychosis._This approach_is_consistent with_the_RDoC framework, which_encourages using converging_measurements to study the_underlying neurobiology of_domains_(Cognitive System and Arousal Regulation in this proposal), and constructs (working memory capacity and_stress_regulation) that_represent_fundamental_behaviors expressed by individuals with_clinical


netic'species pairs'have evolved, and similar changes in mating behavior have occurred independently in each lake. The aim of this study is to investigate the genetic underpinnings of behaviors involved in reproductive isolation between benthic and limnetic sticklebacks from two lakes (Priest and Paxton) using

netic'species pairs'have evolved, and similar changes in mating demeanor have occur independently in each lake. The aim of this study is to investigate the familial underpinnings of behavior involved in reproductive isolation between benthic and limnetic stickleback from two lakes (Priest and Paxton) using

netlc'species pairs'have evolyed, and similar eyanges in mafing behxvior have occurred independxntlt in tcch lake. The aim of ghis studj is to ibvesuigate the genetir underpluninga of yeiaviors involvec in reproguctive isolathov yetween benthic and limnetic sticklefacks ftol two lakes (Pryest wnd Laxton) using

netic'species pairs'have evolved, and similar changes in have independently in lake. The aim investigate genetic underpinnings of involved in reproductive between benthic and limnetic sticklebacks from lakes (Priest and Paxton) using

netic'species pairs'have evolVed, and simiLar chAngEs iN mAtinG behAvior have occurREd inDependently in each lake. THe aim Of THis sTUdY is to InvestiGAtE THe gEnEtIc uNdERpInninGs oF behaviOrs involveD in ReProductive isOLaTion betweeN beNthic and limnEtiC stickLeBacKS from Two Lakes (priest ANd PaxtOn) using

netic'species pairs'have e volved, an d sim ila r c ha nges  inmating behavio r  hav e occurred independent ly in  e a ch l a ke . The  aim of th i s  st ud yisto in vesti gat e the g enetic und erp in nings of beh a vi ors involv edin reproduct ive  isola ti onb etwee n b enthi c andl imneti c stickle ba c ks fro m  two la k e s(Pri est and Paxton) u s in g

netic'species pairs'have_evolved, and_similar changes in mating_behavior have_occurred_independently in_each_lake. The aim_of this study_is to investigate the_genetic underpinnings of_behaviors_involved in reproductive isolation between benthic and limnetic sticklebacks from two lakes (Priest and_Paxton)_using


evidence supports the role of the major CD susceptibility genes, NOD2/CARD15, IRGM and ATG16L1 in the processing of microbial antigens and innate immunity. Moreover, studies showed significant differences in microbiome profiles among ethnic groups. However, it is unclear whether carriage of the major genetic risk alleles correlates with

evidence supports the role of the major CD susceptibility genes, NOD2 / CARD15, IRGM and ATG16L1 in the processing of microbial antigen and innate unsusceptibility. Moreover, studies testify meaning differences in microbiome profiles among ethnic group. However, it is unclear whether carriage of the major familial risk alleles correlate with

evldence supports the role of the major CB susce'tibilify genes, NOD2/CARD15, IRGM and ATG16L1 in thx pricessung of microbial antigdns and ijnate imnuniuy. Moreover, studixa showed signjnicanc vifferences in kicrobiome profiles amonc dtknic groups. However, it is unclear whqther csrgiage of the mwjor denefpc risk alleles correlates with

evidence supports the role of the major genes, IRGM and in the processing immunity. studies showed significant in microbiome profiles ethnic groups. However, it is unclear carriage of the major genetic risk alleles correlates with

evidence supports the role of The major CD SuscePtiBilItY genEs, NOd2/CARD15, IRGM and ATg16l1 in tHe processing of microbiaL antiGeNS and INnAte imMunity. MOReOVEr, sTuDiEs sHoWEd SigniFicAnt diffErences in mIcrObIome profiles AMoNg ethnic grOupS. However, it is UncLear whEtHer CArriaGe oF the mAjor geNEtic riSk alleles CoRRelateS With

evidence supports the rol e of the m ajorCDsus ce ptib ilit y genes, NOD2/ C ARD1 5, IRGM and ATG16L1 in  thepr o cess i ng  of m icrobia l  a n t ige ns  a ndin n at e imm uni ty. Mor eover, stu die sshowed signi f ic ant differ enc es in microb iom e prof il esa mongeth nic g roups. Howeve r, it isun c lear w h ether c a r ri ageof the major gene t ic risk alleles c orrela te s  w i t h

evidence_supports the_role of the major_CD susceptibility_genes,_NOD2/CARD15, IRGM_and_ATG16L1 in the_processing of microbial_antigens and innate immunity._Moreover, studies showed_significant_differences in microbiome profiles among ethnic groups. However, it is unclear whether carriage of_the_major genetic_risk_alleles_correlates with


inflammation at baseline and with changes in inflammation over time in older adults; and (3) determine whether, and to what degree, inflammation reduces the effect of MetS on physical function. Statistical methods to be used include logistic regression and mixed effects modeling, as well as mediation analysis. This project will provide a practical opportunity for

inflammation at baseline and with changes in inflammation over meter in previous adults; and (3) determine whether, and to what degree, ignition reduces the effect of MetS on forcible function. Statistical methods to be used admit logistic arrested development and mixed effects model, as well as mediation analysis. This project will leave a practical opportunity for

invlammation at baseline akd with changes nb inflemmatioh over tkme in older adults; and (3) detxrmibe whtnher, and to what degrde, inflamlation rwducts the effect of MetS on ikysiczp fuucvion. Statisticak methods do be used incnuae logistic regression and mixed effests modrllng, as well as medpaeion analysis. This project will provids a prabtical opportunitu for

inflammation at baseline and with changes in time older adults; (3) determine whether, reduces effect of MetS physical function. Statistical to be used include logistic regression mixed effects modeling, as well as mediation analysis. This project will provide a opportunity for

inflammation at baseline and With changeS in inFlaMmaTiOn ovEr tiMe in older adultS; And (3) dEtermine whether, and to whAt degReE, InflAMmAtion Reduces THe EFFecT oF MEtS On PHySical FunCtion. StAtistical mEthOdS to be used incLUdE logistic rEgrEssion and mixEd eFfects MoDelINg, as wEll As medIation ANalysiS. This projEcT Will prOVide a prACTiCal oPportunity for

inflammation at baselineand with c hange s i n i nf lamm atio n over time in olde r adults; and (3) dete rmine  w h ethe r ,and t o whatd eg r e e,in fl amm at i on  redu ces  the ef fect of Me tSon  physical fu n ct ion. Stati sti cal methodstobe use dinc l ude l ogi sticregres s ion an d mixed e ff e cts mo d eling,a s  w ellas mediation anal y si s . This project  willpr o vi d e  apra ctical opp or tunit y  for

inflammation_at baseline_and with changes in_inflammation over_time_in older_adults;_and (3) determine_whether, and to_what degree, inflammation reduces_the effect of_MetS_on physical function. Statistical methods to be used include logistic regression and mixed effects_modeling,_as well_as_mediation_analysis. This project will provide_a practical opportunity for


recompute lung and esophagus dose-volume histograms using a novel Monte Carlo-based technique, to improve the consistency and accuracy of the database dose distributions. Under Specific Aim (SA) #1, Improvements in post-RT late pneumonitis/fibrosis NTCP models, we will: (a) expand

recompute lung and esophagus dose - volume histograms using a fresh Monte Carlo - free-base technique, to improve the consistency and accuracy of the database venereal disease distribution. Under Specific Aim (SA) # 1, Improvements in post - RT late pneumonitis / fibrosis NTCP exemplar, we will: (a) expand

refompute lung and esophagms dose-volume histogramv usinf a noveu Monte Carlo-based technique, ti impeove the consistency avd accuraby of the datebase dose distrmgutions. Under Dpecnfmc Aim (SA) #1, Imprpvements it post-RT late [ndulonitis/fibrosis NTCP models, we will: (a) expamd

recompute lung and esophagus dose-volume histograms using Monte technique, to the consistency and distributions. Specific Aim (SA) Improvements in post-RT pneumonitis/fibrosis NTCP models, we will: (a)

recompute lung and esophagus Dose-volume HistoGraMs uSiNg a nOvel monte Carlo-baseD TechNique, to improve the consiStencY aND accURaCy of tHe databASe DOSe dIsTrIbuTiONs. under speCific AiM (SA) #1, ImproveMenTs In post-RT late PNeUmonitis/fiBroSis NTCP modelS, we Will: (a) eXpAnd

recompute lung and esopha gus dose-v olume  hi sto gr amsusin g a novel Mont e  Car lo-based technique, to  impr ov e  the co nsist ency an d  a c c ura cy  o f t he da tabas e d ose dis tributions . U nd er SpecificA im  (SA) #1,Imp rovements in  po st-RTla tep neumo nit is/fi brosis NTCP m odels, we  w i ll: (a )  expand

recompute_lung and_esophagus dose-volume histograms using_a novel_Monte_Carlo-based technique,_to_improve the consistency_and accuracy of_the database dose distributions._Under Specific Aim_(SA)_#1, Improvements in post-RT late pneumonitis/fibrosis NTCP models, we will: (a) expand


18, we defined a role for RGS5 in neutrophil trafficking. RGS5 was expressed in both human and murine neutrophils. We detected significantly more neutrophils in the airways of Rgs5-/- mice than wild-type counterparts following acute respiratory virus infection and also in the peritoneum in response to injection of

18, we defined a role for RGS5 in neutrophil trafficking. RGS5 was expressed in both human and murine neutrophils. We detect importantly more neutrophil in the airways of Rgs5-/- mice than wild - character counterparts following acute respiratory virus contagion and besides in the peritoneum in response to injection of

18, we defined a role for RGS5 ln neutrophil trcdfickiig. RGS5 sas exprdssed in both human and muriie nwutrokkils. We detected sigvificantlj more neytrokhils in the airwegs of Rnf5-/- midc thau xild-type countetparts follofing acute res[ifacory virus infection and also in the peritomekm in response to pntectjon of

18, we defined a role for RGS5 trafficking. was expressed both human and more in the airways Rgs5-/- mice than counterparts following acute respiratory virus infection also in the peritoneum in response to injection of

18, we defined a role for RGS5 in neuTrophil traFfickIng. rGS5 WaS expRessEd in both human aND murIne neutrophils. We detectEd sigNiFIcanTLy More nEutrophILs IN The AiRwAys Of rGs5-/- Mice tHan Wild-typE counterpaRts FoLlowing acute REsPiratory viRus Infection and AlsO in the PeRitONeum iN reSponsE to injECtion oF

18, we defined a role forRGS5 in ne utrop hil  tr af fick ing.  RGS5 was expr e ssed  in both human and mur ine n eu t roph i ls . Wedetecte d  s i g nif ic an tly  m o re  neut rop hils in  the airwa ysof  Rgs5-/- mic e  t han wild-t ype  counterpart s f ollowi ng  ac u te re spi rator y viru s  infec tion andal s o in t h e perit o n eu m in  response to inje c ti o n of

18, we_defined a_role for RGS5 in_neutrophil trafficking._RGS5_was expressed_in_both human and_murine neutrophils. We_detected significantly more neutrophils_in the airways_of_Rgs5-/- mice than wild-type counterparts following acute respiratory virus infection and also in the_peritoneum_in response_to_injection_of


[unreadable] DESCRIPTION: (Applicant's Description) The capacity of memory T-cells to traffic preferentially to distinct epithelial tissues has only recently been appreciated. Evidence is accumulating that a skin homing memory T-cell population, identified by E/P selectin ligand expression (e.g., CLA/PS

[ unreadable ] DESCRIPTION: (Applicant's Description) The capacity of memory T - cells to dealings preferentially to discrete epithelial tissues has only recently been prize. Evidence is accumulate that a skin homing memory T - cellular telephone population, identified by E / P selectin ligand expression (e.g., CLA / PS

[ungeadable] DESCRIPTION: (Appuicant's Descripjiin) The capacjty of mdmory T-cells to traffic prefxrenriallt to distinct epithelixl tissued has onoy rtcently been apprxdiated. Cridendc is ccrumulating that a skin hoking memory T-calu 'opulation, identified by E/P selectin ligand edpression (e.g., CJA/PS

[unreadable] DESCRIPTION: (Applicant's Description) The capacity of to preferentially to epithelial tissues has is that a skin memory T-cell population, by E/P selectin ligand expression (e.g.,

[unreadable] DESCRIPTION: (ApplIcant's DescRiptiOn) THe cApAcitY of mEmory T-cells to tRAffiC preferentially to distiNct epItHEliaL TiSsues Has only REcENTly BeEn AppReCIaTed. EvIdeNce is acCumulating ThaT a Skin homing meMOrY T-cell popuLatIon, identifieD by e/P seleCtIn lIGand eXprEssioN (e.g., CLA/ps

[unreadable] DESCRIPTION:  (Applican t's D esc rip ti on)Thecapacity of me m oryT-cells to traffic pre feren ti a llyt odisti nct epi t he l i alti ss ues  h a sonlyrec ently b een apprec iat ed . Evidence i s  a ccumulatin g t hat a skin h omi ng mem or y T - cellpop ulati on, id e ntifie d by E/Pse l ectinl igand e x p re ssio n (e.g., CLA/PS

[unreadable]_DESCRIPTION: (Applicant's_Description) The capacity of_memory T-cells_to_traffic preferentially_to_distinct epithelial tissues_has only recently_been appreciated. Evidence is_accumulating that a_skin_homing memory T-cell population, identified by E/P selectin ligand expression (e.g., CLA/PS


of representative species from several medically important genera of enteric bacteria. Johnson C. Smith University recognizes the tremendous benefits of an active research program to our overall educational atmosphere; therefore, released time is requested for those faculty who conduct supported research. The training of students in research techniques and the methodology of research is also a major goal

of representative species from several medically important genera of intestinal bacteria. Johnson C. Smith University recognize the tremendous benefit of an active inquiry program to our overall educational atmosphere; therefore, exhaust time is requested for those staff who impart supported inquiry. The training of students in research techniques and the methodology of inquiry is also a major goal

of representative species nrom several mednxally mmportaht generx of enteric bacteria. Johnsoi C. Wmith University recognizes the tremvndous bebefius of an active rxaearch ixograj to mnr overall educstional atkosphere; therexofe, released time is requested for thofe facuktj who conduct fupppwted gewearch. The training of studenfs in rtsearch techniques and the methodology of redearfh is also a major goal

of representative species from several medically important enteric Johnson C. University recognizes the research to our overall atmosphere; therefore, released is requested for those faculty who supported research. The training of students in research techniques and the methodology of is also a major goal

of representative species frOm several mEdicaLly ImpOrTant GeneRa of enteric bacTEria. johnson C. Smith UniversitY recoGnIZes tHE tRemenDous benEFiTS Of aN aCtIve ReSEaRch prOgrAm to our Overall eduCatIoNal atmospherE; ThErefore, relEasEd time is requEstEd for tHoSe fACulty Who ConduCt suppORted reSearch. The TrAIning oF StudentS IN rEseaRch techniques and tHE mEThodology of resEarch iS aLSo A MAjoR goAl

of representative species  from seve ral m edi cal ly  imp orta nt genera of e n teri c bacteria. Johnson C.  Smit hU nive r si ty re cognize s  t h e  tr em en dou sb en efits  of  an act ive resear chpr ogram to our ov erall educ ati onal atmosph ere ; ther ef ore ,  rele ase d tim e is r e queste d for tho se facult y  who co n d uc t su pported research. Th e  training of s tudent si nr e sea rch  technique sand t h e metho d ol o g y  of research is a lso a major goa l

of_representative species_from several medically important_genera of_enteric_bacteria. Johnson_C._Smith University recognizes_the tremendous benefits_of an active research_program to our_overall_educational atmosphere; therefore, released time is requested for those faculty who conduct supported research._The_training of_students_in_research techniques and the methodology_of research is also a_major goal


by recent reviewers (Belenko & Logan, 2003; Cooper, 2002), juvenile drug courts began emerging in the 1980s to address these problems, and 268 juvenile drug courts were in operation by December, 2003 (Huddleston, Freeman-Wilson, & Boone, 2004). Although juvenile drug courts have continued to

by recent reviewers (Belenko & Logan, 2003; Cooper, 2002), juvenile drug courts begin emerge in the 1980s to address these problems, and 268 adolescent drug courts were in operation by December, 2003 (Huddleston, Freeman - Wilson, & Boone, 2004). Although juvenile drug court have continued to

by recent reviewers (Belenku & Logan, 2003; Coopet, 2002), juvenmle druf courts began emerging in the 1980s to eddrwss tyese problems, and 268 juvdnile druh courts wert in operation by Decembev, 2003 (Husflescoi, Freeman-Wilson, & Boone, 2004). Anthough juvenine dxug courts have continued to

by recent reviewers (Belenko & Logan, 2003; juvenile courts began in the 1980s 268 drug courts were operation by December, (Huddleston, Freeman-Wilson, & Boone, 2004). Although drug courts have continued to

by recent reviewers (Belenko & LOgan, 2003; Cooper, 2002), JuvenIle DruG cOurtS begAn emerging in thE 1980S to aDdress these problems, and 268 JuvenIlE Drug COuRts weRe in opeRAtION by deCeMbeR, 2003 (HUDdLestoN, FrEeman-WiLson, & Boone, 2004). ALthOuGh juvenile drUG cOurts have cOntInued to

by recent reviewers (Bele nko & Loga n, 20 03;  Co op er,2002 ), juvenile dr u g co urts began emerging in  the19 8 0s t o  a ddres s these pr o b lem s,  a nd26 8  j uveni ledrug co urts wereinop eration by D e ce mber, 2003  (H uddleston, F ree man-Wi ls on, & Boo ne,  2004 ). Alt h ough j uvenile d ru g  court s  have c o n ti nued  to

by_recent reviewers_(Belenko & Logan, 2003;_Cooper, 2002),_juvenile_drug courts_began_emerging in the_1980s to address_these problems, and 268_juvenile drug courts_were_in operation by December, 2003 (Huddleston, Freeman-Wilson, & Boone, 2004). Although juvenile drug courts_have_continued to