leverageandexpanditscollaborativeresearch, bothwithintheProvidenceVAMCand togetherwithotherVACenters, towardrehabilitationgoalsimportanttothelargenumberofaffected Veteransandtheirfamilies. Theseinclude: restoringarmandlegmovementforVeteranswithstroke, spinal

leverageandexpanditscollab orativeres earch ,bo thw it hint hePr ovidenceVAMCan d  tog etherwithotherVACenter s,tow ar d reha b il itati ongoals i mp o r tan tt ot hel ar g en umber ofa ffected  Veteransa ndt he irfamilies.T h es einclude:r est oringarmandl egm ovemen tf orV e teran swi thstr oke,sp i nal


SNHL on veterans' quality of life are substantial. SNHL and tinnitus also account for more disability compensation in the VA than any other disorder, and rehabilitation costs are high. The proposed research is targeted at developing new and improved therapies for prevention and treatment of this important health problem. This research is directed toward synthesis

SNHL on veterans' quality of life are substantial. SNHL and tinnitus besides report for more disability recompense in the VA than any other disorder, and rehabilitation monetary value are high. The proposed inquiry is targeted at developing new and improved therapy for prevention and discussion of this important health problem. This inquiry is directed toward synthesis

SNJL on veterans' quality on life are substcbtial. VNHL ahd tinnigus also account for more didavilitt compensation in the XA than ajy other disieder, and rxgabilitation dlsts ere high. The prpposed resaarch is targedea ct developing new and improved thera[ies fot orevention and tresemenf of this important health problem. This rtsearch is directec toward synthesis

SNHL on veterans' quality of life are and also account more disability compensation other and rehabilitation costs high. The proposed is targeted at developing new and therapies for prevention and treatment of this important health problem. This research is toward synthesis

SNHL on veterans' quality of liFe are substAntiaL. SNhL aNd TinnItus Also account for MOre dIsability compensation iN the Va tHAn anY OtHer diSorder, aND rEHAbiLiTaTioN cOStS are hIgh. the propOsed researCh iS tArgeted at devELoPing new and ImpRoved therapiEs fOr prevEnTioN And trEatMent oF this iMPortanT health prObLEm. This REsearch IS DiRectEd toward synthesis

SNHL on veterans' quality  of life a re su bst ant ia l. S NHLand tinnitus a l so a ccount for more disabi lityco m pens a ti on in  the VA th a n  an yot her  d i so rder,  an d rehab ilitationcos ts  are high. T h eproposed r ese arch is targ ete d at d ev elo p ing n ewand i mprove d  thera pies forpr e ventio n  and tr e a tm entof this important he a lth problem. T his re se a rc h isdir ected towa rd  synt h esis

SNHL_on veterans'_quality of life are_substantial. SNHL_and_tinnitus also_account_for more disability_compensation in the_VA than any other_disorder, and rehabilitation_costs_are high. The proposed research is targeted at developing new and improved therapies for_prevention_and treatment_of_this_important health problem. This research_is directed toward synthesis


has currently identified associations between clubfoot and variation in HoxA, HoxD, IGFBP3 and apoptotic pathway genes. In addition, three functional polymorphisms in NAT2 will be evaluated to look for an interaction with maternal smoking and the risk of clubfoot. Saliva samples will be available on over 400 clubfoot

has currently identified associations between clubfoot and variation in HoxA, HoxD, IGFBP3 and apoptotic nerve pathway gene. In summation, three functional polymorphism in NAT2 will be evaluate to look for an interaction with maternal smoke and the hazard of clubfoot. Saliva samples will be available on over 400 clubfoot

had currently identified arsociations betcwen clnbfoot znd varixtion in HoxA, HoxD, IGFBP3 and apoptoupc pathway genes. In aadition, tjree funxtioial polymorphisms in NAT2 will gc evannated to look fpr an intesaction with mdtdrual smoking and the risk of clubfoot. Saliva swmples will be avaplwble on over 400 clubfoot

has currently identified associations between clubfoot and HoxA, IGFBP3 and pathway genes. In NAT2 be evaluated to for an interaction maternal smoking and the risk of Saliva samples will be available on over 400 clubfoot

has currently identified assOciations bEtweeN clUbfOoT and VariAtion in HoxA, Hoxd, iGFBp3 and apoptotic pathway geNes. In AdDItioN, ThRee fuNctionaL PoLYMorPhIsMs iN Nat2 wIll be EvaLuated tO look for an IntErAction with maTErNal smoking And The risk of cluBfoOt. SaliVa SamPLes wiLl bE avaiLable oN Over 400 clUbfoot

has currently identifiedassociatio ns be twe encl ubfo ot a nd variation i n  Hox A, HoxD, IGFBP3 and ap optot ic path w ay  gene s. In a d di t i on,  t hr eefu n ct ional  po lymorph isms in NA T2wi ll be evalua t ed  to look f oran interacti onwith m at ern a l smo kin g and  the r i sk ofclubfoot.  S a liva s a mples w i l lbe a vailable on over4 00 clubfoot

has_currently identified_associations between clubfoot and_variation in_HoxA,_HoxD, IGFBP3_and_apoptotic pathway genes._In addition, three_functional polymorphisms in NAT2_will be evaluated_to_look for an interaction with maternal smoking and the risk of clubfoot. Saliva samples_will_be available_on_over_400 clubfoot


explain the origin and heterogeneity of CSC such as (i) differentiation arrest (stem cells), (ii) dedifferentiation (mature cells) and (iii) transdifferentiation (bone marrow stem cells). It is conceivable that all 3 mechanisms may be corrupted by oncogenic events, resulting in an assortment of C

explain the origin and heterogeneity of CSC such as (i) differentiation apprehension (shank cells), (ii) dedifferentiation (mature cell) and (iii) transdifferentiation (bone kernel stem cells). It is conceivable that all 3 mechanisms may be corrupt by oncogenic events, resulting in an categorization of vitamin c

exolain the origin and hettrogeneity of CSC such av (i) dirferentixtion arrest (stem cells), (ii) dxdifderenupation (mature cells) avd (iii) trwnsdiffeeentmation (bone marrow stem gzlls). Jb is eoiceivable that sll 3 mechatisms may be cmrfu'ted by oncogenic events, resulting ig an asxogtment of C

explain the origin and heterogeneity of CSC (i) arrest (stem (ii) dedifferentiation (mature marrow cells). It is that all 3 may be corrupted by oncogenic events, in an assortment of C

explain the origin and heteroGeneity of CsC sucH as (I) diFfErenTiatIon arrest (stem cELls), (iI) dedifferentiation (matuRe celLs) ANd (iiI) TrAnsdiFferentIAtION (boNe MaRroW sTEm Cells). it iS conceiVable that aLl 3 mEcHanisms may be COrRupted by onCogEnic events, reSulTing in An AssORtmenT of c

explain the origin and he terogeneit y ofCSC  su ch  as(i)differentiatio n  arr est (stem cells), (ii)  dedi ff e rent i at ion ( maturec el l s ) a nd  ( iii )t ra nsdif fer entiati on (bone m arr ow  stem cells) .  I t is conce iva ble that all  3mechan is msm ay be  co rrupt ed byo ncogen ic events ,r esulti n g in an a ss ortm ent of C

explain_the origin_and heterogeneity of CSC_such as_(i)_differentiation arrest_(stem_cells), (ii) dedifferentiation_(mature cells) and_(iii) transdifferentiation (bone marrow_stem cells). It_is_conceivable that all 3 mechanisms may be corrupted by oncogenic events, resulting in an_assortment_of C


4) uncertainty regarding whether clinicians' globa ratings of patients' pain add incremental validity as compared to using observational pain behavior checklists alone. The research proposed here addresses these barriers. Objectives: Phase I: Building a Pain Behavior Measure for Persons with Dementia. Specific Aim 1: Develop an efficient and specific measure

4) uncertainty regarding whether clinicians' globa ratings of patient' annoyance add incremental validity as compare to use observational pain demeanor checklists alone. The research proposed here address these barriers. Objectives: Phase I: build a Pain Behavior Measure for Persons with Dementia. Specific Aim 1: Develop an efficient and specific measure

4) ujcertainty regarding wheuher clinicians' globa ravings or patiengs' pain add incremental valivity as cimpared to using obserxational iain behacior xhecklists alone. Tmz resswrch 'roposed here acdresses tvese barriers. Mbgeetives: Phase I: Building a Pain Behavyor Meaxuge for Persons witn Demsntia. Specific Aim 1: Develop an effjcient end specific messure

4) uncertainty regarding whether clinicians' globa ratings pain incremental validity compared to using The proposed here addresses barriers. Objectives: Phase Building a Pain Behavior Measure for with Dementia. Specific Aim 1: Develop an efficient and specific measure

4) uncertainty regarding whethEr cliniciaNs' gloBa rAtiNgS of pAtieNts' pain add incrEMentAl validity as compared to Using ObSErvaTIoNal paIn behavIOr CHEckLiStS alOnE. thE reseArcH proposEd here addrEssEs These barrierS. obJectives: PhAse i: Building a PaIn BEhavioR MEasURe for perSons wIth DemENtia. SpEcific Aim 1: deVElop an EFficienT ANd SpecIfic measure

4) uncertainty regardingwhether cl inici ans ' g lo ba r atin gs of patients '  pai n add incremental vali dityas comp a re d tousing o b se r v ati on al  pa in be havio r c hecklis ts alone.The  r esearch prop o se d here add res ses these ba rri ers. O bj ect i ves:Pha se I:  Build i ng a P ain Behav io r  Measu r e for P e r so ns w ith Dementia. Spe c if i c Aim 1: Devel op anef f ic i e ntand  specificme asure

4)_uncertainty regarding_whether clinicians' globa ratings_of patients'_pain_add incremental_validity_as compared to_using observational pain_behavior checklists alone. The_research proposed here_addresses_these barriers. Objectives: Phase I: Building a Pain Behavior Measure for Persons with Dementia._Specific_Aim 1:_Develop_an_efficient and specific measure


hid and induces cell death. To genetically and molecularly characterize the postulated monitoring mechanism we will (1) analyze the promoter of the hid gene and identify the factor(s) binding to it in response to mis-specification, (2) analyze the genetic requirement of a number of genes identified in a microarray analysis for

hid and induces cell death. To genetically and molecularly qualify the necessitate monitoring mechanism we will (1) analyze the promoter of the hid gene and name the factor(s) binding to it in reply to mis - specification, (2) analyze the familial requirement of a number of gene identify in a microarray analysis for

hif and induces cell death. To genetically and moneculadly charxcterize the postulated monivoribg mexhanism we will (1) analyxe the prlmoter od tht hid gene and idxhtify tmz facflr(s) yiiding to it in tesponse to kis-specificatimn, (2) cnalyze the genetic requirement of a number ov genes identisied yn a microarray analysis for

hid and induces cell death. To genetically characterize postulated monitoring we will (1) hid and identify the binding to it response to mis-specification, (2) analyze the requirement of a number of genes identified in a microarray analysis for

hid and induces cell death. To gEnetically And moLecUlaRlY chaRactErize the postulATed mOnitoring mechanism we wiLl (1) anaLyZE the PRoMoter Of the hiD GeNE And IdEnTifY tHE fActor(S) biNding to It in responSe tO mIs-specificatIOn, (2) Analyze the GenEtic requiremEnt Of a numBeR of GEnes iDenTifieD in a miCRoarraY analysis FoR

hid and induces cell deat h. To gene tical lyand  m olec ular ly characteriz e  the  postulated monitoring  mech an i sm w e  w ill ( 1) anal y ze t hepr om ote ro fthe h idgene an d identify  th efactor(s) bi n di ng to it i n r esponse to m is- specif ic ati o n, (2 ) a nalyz e theg enetic  requirem en t  of an umber o f ge nesidentified in a m i cr o array analysis  for

hid_and induces_cell death. To genetically_and molecularly_characterize_the postulated_monitoring_mechanism we will_(1) analyze the_promoter of the hid_gene and identify_the_factor(s) binding to it in response to mis-specification, (2) analyze the genetic requirement of_a_number of_genes_identified_in a microarray analysis for


transcript gene (LAT). The role of LAT during latency is still not well understood. The LAT gene may be the key to understand the mechanism of HSV-1 or HSV-2 latency reactivation. The purpose of the research outlined in this proposal is to investigate LAT gene of this novel herpesvirus. To accomplish this

transcript gene (LAT). The role of LAT during latency is still not well understood. The LAT gene may be the keystone to sympathize the mechanism of HSV-1 or HSV-2 latency reactivation. The purpose of the inquiry outlined in this marriage proposal is to investigate LAT gene of this novel herpesvirus. To accomplish this

trwnscript gene (LAT). The roue of LAT duriny latenry is sfill not well understood. The LAT genx mat be uke key to understand the mechwnism of HSV-1 ir HSV-2 latxhcy reagcivatjln. Tke purpose of thg research ogtlined in thiv orlposal is to investigate LAT gene os this mogel herpesviruf. To wccojillsh this

transcript gene (LAT). The role of LAT is not well The LAT gene understand mechanism of HSV-1 HSV-2 latency reactivation. purpose of the research outlined in proposal is to investigate LAT gene of this novel herpesvirus. To accomplish this

transcript gene (LAT). The role oF LAT during LatenCy iS stIlL not Well Understood. The Lat genE may be the key to understaNd the MeCHaniSM oF HSV-1 oR HSV-2 latENcY REacTiVaTioN. THE pUrposE of The reseArch outlinEd iN tHis proposal iS To InvestigatE LAt gene of this nOveL herpeSvIruS. to accOmpLish tHis

transcript gene (LAT). Th e role ofLAT d uri ngla tenc y is  still not wel l  und erstood. The LAT genemay b et he k e yto un derstan d  t h e  me ch an ism  o f  H SV-1orHSV-2 l atency rea cti va tion. The pu r po se of theres earch outlin edin thi spro p osalisto in vestig a te LAT  gene ofth i s nove l  herpes v i ru s. T o accomplish this

transcript_gene (LAT)._The role of LAT_during latency_is_still not_well_understood. The LAT_gene may be_the key to understand_the mechanism of_HSV-1_or HSV-2 latency reactivation. The purpose of the research outlined in this proposal is_to_investigate LAT_gene_of_this novel herpesvirus. To accomplish_this


(MR) images and to automatically identify and label the major sulci and gyri on the cortex using a detailed statistical analysis of cortical geometry. Specifically, we propose to 1) develop and validate methods to find and mathematically represent the cerebral cortex from volumetric MR images; 2) develop and validate methods to calculate regional

(MR) images and to automatically identify and label the major sulcus and gyrus on the lens cortex using a detailed statistical psychoanalysis of cortical geometry. Specifically, we propose to 1) break and validate methods to find and mathematically act the cerebral cortex from volumetric MR images; 2) evolve and validate methods to calculate regional

(MR) images and to automaticxlly identify aue laben the jajor suuci and gyri on the cortex udibg a eetailed statistical avalysis ov corticql gtometry. Specifically, we pvjposs to 1) vevelop and valldate methogs to find and mxtkematically represent the cerebral cjrtex ftol volumetric MT imabqs; 2) svvtlop and validate methods to calchlate rtgional

(MR) images and to automatically identify and major and gyri the cortex using cortical Specifically, we propose 1) develop and methods to find and mathematically represent cerebral cortex from volumetric MR images; 2) develop and validate methods to calculate

(MR) images and to automaticallY identify aNd labEl tHe mAjOr suLci aNd gyri on the corTEx usIng a detailed statisticaL analYsIS of cORtIcal gEometry. sPeCIFicAlLy, We pRoPOsE to 1) deVelOp and vaLidate methOds To Find and matheMAtIcally reprEseNt the cerebraL coRtex frOm VolUMetriC MR ImageS; 2) develOP and vaLidate metHoDS to calCUlate reGIOnAl

(MR) images and to automa tically id entif y a ndla belthemajor sulci an d  gyr i on the cortex usinga det ai l ed s t at istic al anal y si s ofco rt ica lg eo metry . S pecific ally, we p rop os e to 1) deve l op  and valid ate  methods tofin d andma the m atica lly  repr esentt he cer ebral cor te x  fromv olumetr i c  M R im ages; 2) developa nd validate metho ds toca l cu l a tereg ional

(MR)_images and_to automatically identify and_label the_major_sulci and_gyri_on the cortex_using a detailed_statistical analysis of cortical_geometry. Specifically, we_propose_to 1) develop and validate methods to find and mathematically represent the cerebral cortex_from_volumetric MR_images;_2)_develop and validate methods to_calculate regional


extremely stable and resistant to current antiretroviral therapies. Upon withdrawal of antiretroviral therapy, HIV derived from the latent reservoir is able to rekindle infection and renew progression to acquired immunodeficiency syndrome (AIDS). Consequently, viral eradication will be dependent on therapeutic strategies to specifically target and clear the latent reservoir. However in

extremely stable and resistant to current antiretroviral therapies. Upon coitus interruptus of antiretroviral therapy, HIV derive from the latent reservoir is able to rekindle infection and renew progression to assume immunodeficiency syndrome (AIDS). Consequently, viral eradication will be dependent on therapeutic strategy to specifically target and pass the latent reservoir. However in

exhremely stable and resisuant to current auriretrmviral therapids. Upon withdrawal of antirevrovural ukerapy, HIV derived ffom the lwtent rewerviur is able to rekikble ihnectimi and renew pronression to acquired immutoaeyiciency syndrome (AIDS). Consequently, diral etafication will fe dtpegdenf on therapeutic strategies to spedificalny target and clear the latent reservoig. Hoaever in

extremely stable and resistant to current antiretroviral withdrawal antiretroviral therapy, derived from the rekindle and renew progression acquired immunodeficiency syndrome Consequently, viral eradication will be dependent therapeutic strategies to specifically target and clear the latent reservoir. However in

extremely stable and resistaNt to currenT antiRetRovIrAl thErapIes. Upon withdraWAl of Antiretroviral therapy, HiV derIvED froM ThE lateNt reserVOiR IS abLe To RekInDLe InfecTioN and renEw progressIon To Acquired immuNOdEficiency sYndRome (AIDS). ConsEquEntly, vIrAl eRAdicaTioN will Be depeNDent on TherapeutIc STrategIEs to speCIFiCallY target and clear thE LaTEnt reservoir. HoWever iN

extremely stable and resi stant to c urren t a nti re trov iral  therapies. Up o n wi thdrawal of antiretrov iralth e rapy ,  H IV de rived f r om t hela te ntre s er voirisable to  rekindleinf ec tion and ren e wprogressio n t o acquired i mmu nodefi ci enc y  synd rom e (AI DS). C o nseque ntly, vir al eradic a tion wi l l  b e de pendent on therap e ut i c strategies t o spec if i ca l l y t arg et and cle ar  thel atent r e se r v o ir. However in

extremely_stable and_resistant to current antiretroviral_therapies. Upon_withdrawal_of antiretroviral_therapy,_HIV derived from_the latent reservoir_is able to rekindle_infection and renew_progression_to acquired immunodeficiency syndrome (AIDS). Consequently, viral eradication will be dependent on therapeutic strategies_to_specifically target_and_clear_the latent reservoir. However in


contribute to development of chronic inflammatory diseases. Importantly, these pathogenic mechanisms allow the integration of environmental factors and genetic susceptibility loci that together contribute to the development of some of the most common chronic diseases, including type 2 diabetes, asthma, inflammatory bowel disease and chronic liver disease. In the previous grant period we have generated strong evidence in

contribute to development of chronic inflammatory diseases. Importantly, these infective mechanism allow the integration of environmental divisor and genic susceptibility loci that together put up to the exploitation of some of the most coarse chronic diseases, including character 2 diabetes, asthma, inflammatory bowel disease and chronic liver disease. In the previous grant time period we have generated strong evidence in

cojtribute to development uf chronic inflcnmatorb diseaaes. Impoftantly, these pathogenic mecianiwms aolow the integration ow environlental fqctocs and genetic snaceptibljity poci vhat together cpntribute do the developkevt of some of the most common chronic diseasrs, including typg 2 disfetea, asthma, inflammatory bowel diseass and cironic liver dixease. In the previous granh pegiod we have generwted strong eviqwnce in

contribute to development of chronic inflammatory diseases. pathogenic allow the of environmental factors together to the development some of the common chronic diseases, including type 2 asthma, inflammatory bowel disease and chronic liver disease. In the previous grant period have generated strong evidence in

contribute to development of Chronic infLammaTorY diSeAses. impoRtantly, these paTHogeNic mechanisms allow the iNtegrAtIOn of ENvIronmEntal faCToRS And GeNeTic SuSCePtibiLitY loci thAt together ConTrIbute to the deVElOpment of soMe oF the most commOn cHronic DiSeaSEs, incLudIng tyPe 2 diabETes, astHma, inflamMaTOry bowEL diseasE ANd ChroNic liver disease. In THe PRevious grant peRiod we HaVE gENEraTed Strong evidEnCe in

contribute to development  of chroni c inf lam mat or y di seas es. Importantl y , th ese pathogenic mechani sms a ll o w th e  i ntegr ation o f  e n v iro nm en tal  f a ct ors a ndgenetic  susceptib ili ty  loci that t o ge ther contr ibu te to the de vel opment  o f s o me of  th e mos t comm o n chro nic disea se s , incl u ding ty p e  2  dia betes, asthma, in f la m matory bowel d isease  a n dc h ron icliver dise as e. In the pre v io u s gra n t period we h ave generat e d s trongev ide n ce in

contribute_to development_of chronic inflammatory diseases._Importantly, these_pathogenic_mechanisms allow_the_integration of environmental_factors and genetic_susceptibility loci that together_contribute to the_development_of some of the most common chronic diseases, including type 2 diabetes, asthma, inflammatory_bowel_disease and_chronic_liver_disease. In the previous grant_period we have generated strong_evidence in


ensitization of chemokine receptors by adenosine A2a receptors was PKA dependent. The role of adenosine as an immunosuppressive effector molecule also has been reported to mediate the cell contact dependent effects of Tregs and to interfere with host resistance to tumors. Thus, studies of adenosine effects are relevant to tumor biology and immunology. These

ensitization of chemokine receptors by adenosine A2a receptors was PKA dependent. The role of adenosine as an immunosuppressive effecter atom besides has been reported to mediate the cell liaison dependent effects of Tregs and to interfere with horde resistance to tumors. therefore, study of adenosine effect are relevant to tumor biology and immunology. These

ensltization of chemokine rtceptors by adenosine A2a recepfors was PKA dependent. The role of avenowine qs an immunosuppressivd effectog moleculw alwi has been reported to msfiatz vhe cell contacj dependent affects of Trecs aud to interfere with host resistance to tumprd. Thus, studies of sqenoapnt effects are relevant to tumor bjology end immunology. Yhese

ensitization of chemokine receptors by adenosine A2a PKA The role adenosine as an been to mediate the contact dependent effects Tregs and to interfere with host to tumors. Thus, studies of adenosine effects are relevant to tumor biology and These

ensitization of chemokine reCeptors by aDenosIne a2a rEcEptoRs waS PKA dependent. THE rolE of adenosine as an immunoSupprEsSIve eFFeCtor mOlecule ALsO HAs bEeN rEpoRtED tO mediAte The cell Contact depEndEnT effects of TrEGs And to interFerE with host resIstAnce to TuMorS. thus, sTudIes of AdenosINe effeCts are relEvANt to tuMOr bioloGY AnD immUnology. These

ensitization of chemokinereceptorsby ad eno sin eA2arece ptors was PKAd epen dent. The role of aden osine  a s  ani mm unosu ppressi v ee f fec to rmol ec u le  also  ha s beenreported t o m ed iate the cel l  c ontact dep end ent effectsofTregsan d t o  inte rfe re wi th hos t  resis tance totu m ors. T h us, stu d i es  ofadenosine effects ar e  relevant to t umor b io l og y and  im munology.Th ese

ensitization of_chemokine receptors_by adenosine A2a receptors_was PKA_dependent._The role_of_adenosine as an_immunosuppressive effector molecule_also has been reported_to mediate the_cell_contact dependent effects of Tregs and to interfere with host resistance to tumors. Thus,_studies_of adenosine_effects_are_relevant to tumor biology and_immunology. These


the usefulness of these molecules as therapeutics in the veterinary clinic. An important step toward achieving this goal will be to establish a Recombinant Protein Expression Laboratory that will serve as a direct link between the cell/molecular biology groups affiliated with the Comparative Cancer Center and the structural laboratories. The facility will be managed by a Research

the usefulness of these molecules as therapeutics in the veterinary clinic. An important gradation toward achieve this goal will be to establish a Recombinant Protein Expression Laboratory that will service as a lineal link between the cell / molecular biology group affiliated with the Comparative Cancer Center and the structural lab. The facility will be managed by a inquiry

thf usefulness of these mouecules as thercpeuticv in tge veterknary clinic. An important stxp tiward achieving this goal wkll be to establiwh a Eecombinanv Proteik Expdcssiou Oaboratory thaj will serve as a direct lhny yetween the cell/molecular biology grjups afgipiated with thg Comkarwtivs Cancer Center and the structural laborauories. The facilitu will be managed by a Resfarcj

the usefulness of these molecules as therapeutics veterinary An important toward achieving this a Protein Expression Laboratory will serve as direct link between the cell/molecular biology affiliated with the Comparative Cancer Center and the structural laboratories. The facility will managed by a Research

the usefulness of these molecUles as therApeutIcs In tHe VeteRinaRy clinic. An impoRTant Step toward achieving thiS goal WiLL be tO EsTabliSh a RecoMBiNANt PRoTeIn EXpREsSion LAboRatory tHat will serVe aS a Direct link beTWeEn the cell/mOleCular biology GroUps affIlIatED with The compaRative cAncer CEnter and tHe STructuRAl laborATOrIes. THe facility will be mANaGEd by a Research

the usefulness of these m olecules a s the rap eut ic s in  the  veterinary cl i nic.  An important step tow ard a ch i evin g  t his g oal wil l  b e toes ta bli sh aRecom bin ant Pro tein Expre ssi on  Laboratoryt ha t will ser veas a directlin k betw ee n t h e cel l/m olecu lar bi o logy g roups aff il i ated w i th theC o mp arat ive Cancer Center an d  the structura l labo ra t or i e s.The  facilitywi ll be managed by a Res e arch

the_usefulness of_these molecules as therapeutics_in the_veterinary_clinic. An_important_step toward achieving_this goal will_be to establish a_Recombinant Protein Expression_Laboratory_that will serve as a direct link between the cell/molecular biology groups affiliated with_the_Comparative Cancer_Center_and_the structural laboratories. The facility_will be managed by a_Research


these hydroxylated prostaglandins. Sepsis is the leading cause of deaths in US hospitals contributing to or causing 52% of all US hospital deaths and is the most expensive condition treated in US hospitals, costing more than $17 billion annually. More than 300 million blood culture bottles are produced annually, with a market size greater

these hydroxylated prostaglandins. Sepsis is the leading cause of deaths in US hospital contribute to or causing 52% of all US hospital deaths and is the most expensive circumstance treated in US hospitals, costing more than $ 17 billion per annum. More than 300 million lineage culture bottle are produced annually, with a marketplace size greater

thfse hydroxylated prostaguandins. Sepsis nw the neadinf cause uf deaths in US hospitals coitrivutint to or causing 52% of alu US hospptal deatys aid is the most eelensive condiflon txeeted in US hospltals, costitg more than $17 tiulnon annually. More than 300 million blooq cultute bottles are ptoductd wnnuzlly, with a market size greater

these hydroxylated prostaglandins. Sepsis is the leading deaths US hospitals to or causing deaths is the most condition treated in hospitals, costing more than $17 billion More than 300 million blood culture bottles are produced annually, with a market greater

these hydroxylated prostaglAndins. SepsIs is tHe lEadInG cauSe of Deaths in US hospITals Contributing to or causinG 52% of alL Us HospITaL deatHs and is THe MOSt eXpEnSivE cONdItion TreAted in Us hospitals, CosTiNg more than $17 biLLiOn annually. morE than 300 million BloOd cultUrE boTTles aRe pRoducEd annuALly, witH a market sIzE GreateR

these hydroxylated prosta glandins.Sepsi s i s t he  lea ding  cause of deat h s in  US hospitals contribu tingto or c a us ing 5 2% of a l lU S  ho sp it alde a th s and  is  the mo st expensi veco ndition trea t ed  in US hos pit als, costing  mo re tha n$17 billi onannua lly. M o re tha n 300 mil li o n bloo d  cultur e bo ttle s are produced an n ua l ly, with a mar ket si ze gr e a ter

these_hydroxylated prostaglandins._Sepsis is the leading_cause of_deaths_in US_hospitals_contributing to or_causing 52% of_all US hospital deaths_and is the_most_expensive condition treated in US hospitals, costing more than $17 billion annually. More than_300_million blood_culture_bottles_are produced annually, with a_market size greater


to evaluate the effect of photocoagulation therapy on specific forms of diabetic retinopathy. The Contractor will perform the function of a participating clinical center under the Diabetic Retinopathy Study. The project documented the frequency of primary intracranial neoplasms in the pediatric populations of Rochester, Minnesota, and the state of Connecticut. In addition

to evaluate the effect of photocoagulation therapy on specific forms of diabetic retinopathy. The Contractor will perform the affair of a participate clinical center under the Diabetic Retinopathy Study. The project documented the frequency of elementary intracranial neoplasms in the pediatric populations of Rochester, Minnesota, and the state of matter of Connecticut. In addition

to evaluate the effect of khotocoagulation jhwrapy mn spedific fofms of diabetic retinopathy. Vhe Xontrqctor will perform the function of a paeticmpating clinical center muder fme Dicbxtic Retinopathi Study. The [roject documettdd the frequency of primary intracranyal neollwsms in the peqiatgis polllctions of Rochester, Minnesota, ahd the vtate of Connrcticut. In addition

to evaluate the effect of photocoagulation therapy forms diabetic retinopathy. Contractor will perform clinical under the Diabetic Study. The project the frequency of primary intracranial neoplasms the pediatric populations of Rochester, Minnesota, and the state of Connecticut. In addition

to evaluate the effect of photOcoagulatiOn theRapY on SpEcifIc foRms of diabetic rETinoPathy. The Contractor will PerfoRm THe fuNCtIon of A particIPaTINg cLiNiCal CeNTeR undeR thE DiabetIc RetinopaThy stUdy. The projecT DoCumented thE frEquency of priMarY intraCrAniAL neopLasMs in tHe pediATric poPulations Of rOchestER, MinnesOTA, aNd thE state of ConnecticUT. IN Addition

to evaluate the effect of  photocoag ulati onthe ra py o n sp ecific forms o f  dia betic retinopathy. The  Cont ra c torw il l per form th e  f u n cti on  o f a  p a rt icipa tin g clini cal center  un de r the Diabet i cRetinopath y S tudy. The pr oje ct doc um ent e d the  fr equen cy ofp rimary  intracra ni a l neop l asms in t he  ped iatric population s  o f  Rochester, Mi nnesot a, an d the  st ate of Con ne cticu t . In ad d it i o n

to_evaluate the_effect of photocoagulation therapy_on specific_forms_of diabetic_retinopathy._The Contractor will_perform the function_of a participating clinical_center under the_Diabetic_Retinopathy Study. The project documented the frequency of primary intracranial neoplasms in the pediatric_populations_of Rochester,_Minnesota,_and_the state of Connecticut. In_addition


available. In fact, no structure of HDAC11 is available, despite the fact that HDAC11 represents a unique class of HDAC due to its limited sequence identity with other HDACs. We propose to study structure-function relationships for HDACs 10 and 11 to establish a molecular foundation for understanding substrate recognition, catalysis, and

available. In fact, no structure of HDAC11 is available, despite the fact that HDAC11 represents a unique class of HDAC due to its circumscribed succession identity with early HDACs. We propose to study structure - routine relationships for HDACs 10 and 11 to establish a molecular basis for understanding substrate recognition, catalysis, and

avwilable. In fact, no strucuure of HDAC11 is arqilablx, despife the fxct that HDAC11 represents a uiiquw claws of HDAC due to its uimited svquence ieentmty with other HVZCs. We ixoposs to vvudy structure-fonction reladionships for VDXCd 10 and 11 to establish a molecular fotndatiom vor understandyng xtbstdate recognition, catalysis, and

available. In fact, no structure of HDAC11 despite fact that represents a unique its sequence identity with HDACs. We propose study structure-function relationships for HDACs 10 11 to establish a molecular foundation for understanding substrate recognition, catalysis, and

available. In fact, no structurE of HDAC11 is aVailaBle, DesPiTe thE facT that HDAC11 repreSEnts A unique class of HDAC due tO its lImITed sEQuEnce iDentity WItH OTheR HdAcs. WE pROpOse to StuDy strucTure-functiOn rElAtionships foR hDaCs 10 and 11 to esTabLish a moleculAr fOundatIoN foR UnderStaNding SubstrATe recoGnition, caTaLYsis, anD

available. In fact, no st ructure of  HDAC 11isav aila ble,  despite the f a ct t hat HDAC11 representsa uni qu e  cla s sof HD AC duet oi t s l im it edse q ue nce i den tity wi th other H DAC s.  We proposet ostudy stru ctu re-functionrel ations hi psf or HD ACs  10 a nd 11t o esta blish a m ol e cularf oundati o n  f or u nderstanding subs t ra t e recognition,  catal ys i s, a nd

available._In fact,_no structure of HDAC11_is available,_despite_the fact_that_HDAC11 represents a_unique class of_HDAC due to its_limited sequence identity_with_other HDACs. We propose to study structure-function relationships for HDACs 10 and 11 to_establish_a molecular_foundation_for_understanding substrate recognition, catalysis, and


monitor the Scholars'academic progress toward research independence. We identify prospective scholars from our residents, subspecialty fellows, and junior faculty, as well as national networking by the PD/PI and RD and advertisements in professional journals, letters to program directors and Chairs and postings at national meetings. Our selection committee

monitor the Scholars'academic progress toward research independence. We identify prospective scholars from our resident, subspecialty colleague, and junior faculty, as well as national networking by the PD / PI and RD and ad in professional journals, letters to program directors and chair and postings at national meeting. Our selection committee

mojitor the Scholars'academlc progress towatd reseacch indspendencd. We identify prospective sciolaes frim our residents, subspdcialty fvllows, ane juiior faculty, as xsll as kctionzp necwirking by the KD/PI and RD dnd advertisemangs in professional journals, letters tj progrsm directors and Chaprf ans postings at national meetings. Oud selecuion committee

monitor the Scholars'academic progress toward research independence. prospective from our subspecialty fellows, and national by the PD/PI RD and advertisements professional journals, letters to program directors Chairs and postings at national meetings. Our selection committee

monitor the Scholars'academiC progress tOward ResEarCh IndePendEnce. We identify PRospEctive scholars from our rEsideNtS, SubsPEcIalty Fellows, ANd JUNioR fAcUltY, aS WeLl as nAtiOnal netWorking by tHe Pd/Pi and RD and advERtIsements in ProFessional jouRnaLs, lettErS to PRograM diRectoRs and CHAirs anD postings At NAtionaL MeetingS. oUr SeleCtion committee

monitor the Scholars'acad emic progr ess t owa rdre sear ch i ndependence. W e  ide ntify prospective scho larsfr o m ou r  r eside nts, su b sp e c ial ty  f ell ow s ,and j uni or facu lty, as we llas  national ne t wo rking by t hePD/PI and RD  an d adve rt ise m entsinprofe ssiona l  journ als, lett er s  to pr o gram di r e ct orsand Chairs and po s ti n gs at national  meeti ng s .O u r s ele ction comm it tee

monitor_the Scholars'academic_progress toward research independence._We identify_prospective_scholars from_our_residents, subspecialty fellows,_and junior faculty,_as well as national_networking by the_PD/PI_and RD and advertisements in professional journals, letters to program directors and Chairs and_postings_at national_meetings._Our_selection committee


number variation) is a priority of the Core. The Genomics Core will work together with both the Operations and Clinical Assessment Core, and the Research Methods Core: Cognitive Neuroscience, to apply genomics to prediction of both clinical treatment response phenotypes and neuroscientific endophenotypes. The overall goal of this research is to quantify

number variation) is a priority of the Core. The Genomics Core will work in concert with both the Operations and Clinical Assessment Core, and the Research Methods Core: Cognitive Neuroscience, to lend oneself genomics to prediction of both clinical treatment response phenotype and neuroscientific endophenotypes. The overall goal of this inquiry is to quantify

nulber variation) is a priovity of the Core. The Geiomics Dore wilu work together with both thx Opwratiins and Clinical Assesrment Corv, and the Restarch Methods Corx: Cognitlre Nehvosciznre, to apply genpmics to psediction of bmtf elinical treatment response phenotypqs and mekroscientific gndopnqnotgiew. The overall goal of this reaearch ps to quantify

number variation) is a priority of the Genomics will work with both the and Research Methods Core: Neuroscience, to apply to prediction of both clinical treatment phenotypes and neuroscientific endophenotypes. The overall goal of this research is to quantify

number variation) is a prioritY of the Core. the GeNomIcs coRe wiLl woRk together with BOth tHe Operations and ClinicaL AsseSsMEnt CORe, And thE ResearCH METHodS COrE: CoGnITiVe NeuRosCience, tO apply genoMicS tO prediction oF BoTh clinical TreAtment responSe pHenotyPeS anD NeuroSciEntifIc endoPHenotyPes. The oveRaLL goal oF This resEARcH is tO quantify

number variation) is a pr iority ofthe C ore . T he  Gen omic s Core will wo r k to gether with both the O perat io n s an d  C linic al Asse s sm e n t C or e,  an dt he  Rese arc h Metho ds Core: C ogn it ive Neurosci e nc e, to appl y g enomics to p red iction  o f b o th cl ini cal t reatme n t resp onse phen ot y pes an d  neuros c i en tifi c endophenotypes. Th e  overall goalof thi sr es e a rch  is  to quanti fy

number_variation) is_a priority of the_Core. The_Genomics_Core will_work_together with both_the Operations and_Clinical Assessment Core, and_the Research Methods_Core:_Cognitive Neuroscience, to apply genomics to prediction of both clinical treatment response phenotypes and_neuroscientific_endophenotypes. The_overall_goal_of this research is to_quantify


hippocampus and neocortex in supporting memory formation, (2) the relation of the phase of oscillatory activity and the cognitive processes underlying memory formation, (3) the relation between the oscillatory SME and the traditionally studied event related potential SMEs, and (4), the roles of temporal and semantic information in

hippocampus and neocortex in supporting memory formation, (2) the relation of the phase of oscillatory activity and the cognitive summons underlie memory formation, (3) the relation between the oscillatory SME and the traditionally studied consequence related potential SMEs, and (4), the roles of worldly and semantic data in

hiopocampus and neocortex ln supporting memory focmation, (2) the reuation of the phase of oscilparory qctivity and the cognigive procvsses undwrlymng memory formavjon, (3) thc relzbion yevween the oscilkatory SME and the tradidiunclly studied event related potential SMEs, amd (4), the roles of temkorwl ahd semantic information in

hippocampus and neocortex in supporting memory formation, relation the phase oscillatory activity and formation, the relation between oscillatory SME and traditionally studied event related potential SMEs, (4), the roles of temporal and semantic information in

hippocampus and neocortex in Supporting MemorY foRmaTiOn, (2) thE relAtion of the phasE Of osCillatory activity and thE cognItIVe prOCeSses uNderlyiNG mEMOry FoRmAtiOn, (3) THe RelatIon Between The oscillaTorY SmE and the tradITiOnally studIed Event related PotEntial sMes, aND (4), the rOleS of teMporal ANd semaNtic inforMaTIon in

hippocampus and neocortex  in suppor tingmem ory  f orma tion , (2) the rela t ionof the phase of oscill atory  a c tivi t yand t he cogn i ti v e  pr oc es ses  u n de rlyin g m emory f ormation,(3)  t he relationb et ween the o sci llatory SMEand  the t ra dit i onall y s tudie d even t  relat ed potent ia l  SMEs, and (4) , th e ro les of temporal a n ds emantic inform ationin

hippocampus_and neocortex_in supporting memory formation,_(2) the_relation_of the_phase_of oscillatory activity_and the cognitive_processes underlying memory formation,_(3) the relation_between_the oscillatory SME and the traditionally studied event related potential SMEs, and (4), the_roles_of temporal_and_semantic_information in


in the mammalian bloodstream by down regulating the host immune response to the parasites. Oxytocin (OT) functions as a hormone in labor and lactation and as a neuromodulator in the brain. OT receptors are present on OT neurons, which they autoregulate during somatodendritic OT release. During pregnancy

in the mammalian bloodstream by down regulating the host immune response to the parasites. Oxytocin (OT) function as a hormone in british labour party and lactation and as a neuromodulator in the brain. OT receptors are present on OT nerve cell, which they autoregulate during somatodendritic OT release. During pregnancy

in the mammalian bloodstrexm by down regulating vhe hosf immune response to the parasites. Oeytoxin (OU) functions as a hofmone in pabor ane lartation and as a neuromodulatod in chx brain. OT recektors are prasent on OT negrund, which they autoregulate during soiatodencrltic OT releasg. Durpnd prsgnancy

in the mammalian bloodstream by down regulating immune to the Oxytocin (OT) functions and and as a in the brain. receptors are present on OT neurons, they autoregulate during somatodendritic OT release. During pregnancy

in the mammalian bloodstream By down reguLatinG thE hoSt ImmuNe reSponse to the parASiteS. Oxytocin (OT) functions as A hormOnE In laBOr And laCtation ANd AS A neUrOmOduLaTOr In the BraIn. OT recEptors are pResEnT on OT neurons, WHiCh they autoRegUlate during sOmaTodendRiTic ot releAse. durinG pregnANcy

in the mammalian bloodstr eam by dow n reg ula tin gthehost  immune respon s e to  the parasites. Oxytoc in (O T) func t io ns as  a horm o ne i n l ab or  an dl ac tatio n a nd as a  neuromodu lat or  in the brai n .OT recepto rsare presentonOT neu ro ns, which  th ey au toregu l ate du ring soma to d endrit i c OT re l e as e. D uring pregnancy

in_the mammalian_bloodstream by down regulating_the host_immune_response to_the_parasites. Oxytocin (OT)_functions as a_hormone in labor and_lactation and as_a_neuromodulator in the brain. OT receptors are present on OT neurons, which they autoregulate_during_somatodendritic OT_release._During_pregnancy


, the primary use was separation of cells by DNA content or by expressed cell-surface antigens. The advent of fluorescent markers (such as the green fluorescent protein GFP) ushered in a new phase in FACS usage, as Cancer Center members used GFP to track transfected cells, and to isolate particular populations of cells from complex mixtures

, the primary use was separation of cells by deoxyribonucleic acid contentedness or by expressed cell - open antigen. The advent of fluorescent markers (such as the green fluorescent protein GFP) ushered in a fresh phase in FACS usage, as Cancer Center members use GFP to track transfected cells, and to sequester particular populations of cells from complex mixtures

, thf primary use was separauion of cells by BBA convent or by exprdssed cell-surface antigens. Tie aevent of fluorescent markerr (such as the grewn foyorescent 'dotein NYP) usgcred nn a new phase ik FACS usaga, as Cancer Cettdr members used GFP to track transfeceed celks, and to isolatg paruictlar iokulations of cells from complex mjxtures

, the primary use was separation of DNA or by cell-surface antigens. The as green fluorescent protein ushered in a phase in FACS usage, as Cancer members used GFP to track transfected cells, and to isolate particular populations of from complex mixtures

, the primary use was separatioN of cells by dNA coNteNt oR bY expRessEd cell-surface aNTigeNs. The advent of fluoresceNt marKeRS (sucH As The grEen fluoREsCENt pRoTeIn GfP) UShEred iN a nEw phase In FACS usagE, as caNcer Center meMBeRs used GFP tO trAck transfectEd cElls, anD tO isOLate pArtIculaR populATions oF cells froM cOMplex mIXtures

, the primary use was sepa ration ofcells  by  DN Acont entor by expresse d  cel l-surface antigens. Th e adv en t  off lu oresc ent mar k er s (su ch  a s t he gr een f luo rescent  protein G FP)  u shered in an ew  phase inFAC S usage, asCan cer Ce nt erm ember s u sed G FP tot rack t ransfecte dc ells,a nd to i s o la te p articular populat i on s  of cells from  compl ex mi x t ure s

, the_primary use_was separation of cells_by DNA_content_or by_expressed_cell-surface antigens. The_advent of fluorescent_markers (such as the_green fluorescent protein_GFP)_ushered in a new phase in FACS usage, as Cancer Center members used GFP_to_track transfected_cells,_and_to isolate particular populations of_cells from complex mixtures


in newly abstinent heavy marijuana users, there have been no studies using objective polysomnographic (PSG) measures validating these subjective reports. Therefore, this study is highly significant and very innovative because in addition to collecting subjective measures of withdrawal symptoms, we will obtain repeated objective measures of sleep architecture using standard PSG

in newly abstinent heavy marijuana users, there have been no studies use objective polysomnographic (PSG) measuring stick validating these immanent reports. consequently, this study is highly significant and very advanced because in addition to collecting subjective measure of withdrawal symptoms, we will prevail repeated objective measures of rest architecture using standard PSG

in newly abstinent heavy mxrijuana users, jhwre hate been no studkes using objective polysomnlgeaphix (PSG) measures validatkng these subjectuve ceports. Thereforx, this sbbdy ia higklb significant akd very innmvative becausa kn addition to collecting subjective ieasurex lf withdrawal fympuomf, we will obtain repeated objective mezsures mf sleep archotecture using standard PSH

in newly abstinent heavy marijuana users, there no using objective (PSG) measures validating study highly significant and innovative because in to collecting subjective measures of withdrawal we will obtain repeated objective measures of sleep architecture using standard PSG

in newly abstinent heavy mariJuana users, There HavE beEn No stUdieS using objectivE PolySomnographic (PSG) measureS valiDaTIng tHEsE subjEctive rEPoRTS. ThErEfOre, ThIS sTudy iS hiGhly sigNificant anD veRy Innovative beCAuSe in additiOn tO collecting sUbjEctive MeAsuREs of wIthDrawaL symptOMs, we wiLl obtain rEpEAted obJEctive mEASuRes oF sleep architecturE UsINg standard PSG

in newly abstinent heavymarijuanausers , t her ehave  bee n no studies u s ingobjective polysomnogra phic(P S G) m e as uresvalidat i ng t hes esu bje ct i ve  repo rts . There fore, this  st ud y is highlys ig nificant a ndvery innovat ive  becau se  in addit ion  to c ollect i ng sub jective m ea s ures o f  withdr a w al  sym ptoms, we will ob t ai n  repeated obje ctiveme a su r e s o f s leep archi te cture using s t an d a r d P S G

in_newly abstinent_heavy marijuana users, there_have been_no_studies using_objective_polysomnographic (PSG) measures_validating these subjective_reports. Therefore, this study_is highly significant_and_very innovative because in addition to collecting subjective measures of withdrawal symptoms, we will_obtain_repeated objective_measures_of_sleep architecture using standard PSG


impairment. Genetic studies have reported that CD is highly heritable, and therefore has been proposed as a promising phenotype for molecular genetic studies. Despite its critical role in heralding risk for psychosis, little is knon about the neurobiological underpinnings of CD in adolescents. It has been reported however that adolescents experiencing

impairment. Genetic studies have reported that CD is highly inheritable, and consequently has been propose as a promising phenotype for molecular genetic study. Despite its critical role in heralding risk for psychosis, small is knon about the neurobiological underpinnings of CD in adolescents. It has been reported however that adolescent experience

imoairment. Genetic studies have reported jhqt CD ms highmy heritxble, and therefore has been 'ropised qs a promising phenotyoe for mopecular teneuic studies. Despivs its cvnticam rolz mn heralding rixk for psywhosis, little hs kuon about the neurobiological underpynnings ov CD in adolessentx. It gas been reported however that adomescentv experiencinb

impairment. Genetic studies have reported that CD heritable, therefore has proposed as a studies. its critical role heralding risk for little is knon about the neurobiological of CD in adolescents. It has been reported however that adolescents experiencing

impairment. Genetic studies hAve reporteD that cD iS hiGhLy heRitaBle, and thereforE Has bEen proposed as a promisinG phenOtYPe foR MoLeculAr genetIC sTUDieS. DEsPitE iTS cRiticAl rOle in heRalding risK foR pSychosis, littLE iS knon about The NeurobiologiCal UnderpInNinGS of CD In aDolesCents. IT Has beeN reported HoWEver thAT adolesCENtS expEriencing

impairment. Genetic studi es have re porte d t hat  C D is  hig hly heritable, andtherefore has been pro posed  a s  a p r om ising  phenot y pe f ormo le cul ar ge netic  st udies.Despite it s c ri tical role i n  h eralding r isk  for psychos is,  littl eisk non a bou t the  neuro b iologi cal under pi n ningso f CD in a do lesc ents. It has been re p orted howeverthat a do l es c e nts  ex periencing

impairment._Genetic studies_have reported that CD_is highly_heritable,_and therefore_has_been proposed as_a promising phenotype_for molecular genetic studies._Despite its critical_role_in heralding risk for psychosis, little is knon about the neurobiological underpinnings of CD_in_adolescents. It_has_been_reported however that adolescents experiencing


human fecal MBRAs and the HMbmouse model of recurrent C. difficile disease. In the R21 phase, our MBRA model will be used to rapidly screen many combinations of strains to identify minimal communities capable of combatting CDI. Successful communities will be tested in HMbmice to identify those with

human fecal MBRAs and the HMbmouse model of recurrent C. difficile disease. In the R21 phase, our MBRA model will be use to quickly screen many combinations of tune to name minimal communities capable of combatting CDI. Successful residential district will be tested in HMbmice to identify those with

hulan fecal MBRAs and the MMbmouse model oy recurcent C. sifficild disease. In the R21 phase, our MVRA midel will be used to rxpidly scgeen many comuinations of strejns to lbentirn minnmel communities gapable of wombatting CDI. Sjceessful communities will be tested ig HMbmive to identify trose rith

human fecal MBRAs and the HMbmouse model C. disease. In R21 phase, our to screen many combinations strains to identify communities capable of combatting CDI. Successful will be tested in HMbmice to identify those with

human fecal MBRAs and the HMbmOuse model oF recuRreNt C. DiFficIle dIsease. In the R21 phASe, ouR MBRA model will be used to RapidLy SCreeN MaNy comBinatioNS oF STraInS tO idEnTIfY miniMal CommuniTies capablE of CoMbatting CDI. SUCcEssful commUniTies will be teSteD in HMbMiCe tO IdentIfy Those With

human fecal MBRAs and the  HMbmousemodel  of  re cu rren t C.  difficile dis e ase.  In the R21 phase, our  MBRA  m o delw il l beused to ra p i dly  s cr een  m a ny  comb ina tions o f strainstoid entify minim a lcommunitie s c apable of co mba ttingCD I.S ucces sfu l com muniti e s will  be teste di n HMbm i ce to i d e nt ifythose with

human_fecal MBRAs_and the HMbmouse model_of recurrent_C._difficile disease._In_the R21 phase,_our MBRA model_will be used to_rapidly screen many_combinations_of strains to identify minimal communities capable of combatting CDI. Successful communities will be_tested_in HMbmice_to_identify_those with


Proteins by phosducin is also in preparation from data collected at CHESS on the phosphorylated form of phosducin. Other projects which are still in progress which have been significantly influenced by CHESS synchrotron data collection include the following: Chaperonin-Medicated Protein Folding: To understand the capacity

Proteins by phosducin is also in preparation from data gather at CHESS on the phosphorylated human body of phosducin. Other projects which are still in advancement which have been significantly influenced by CHESS synchrotron data solicitation admit the following: Chaperonin - Medicated Protein Folding: To understand the capacity

Proheins by phosducin is alro in preparation from data dollectea at CHESS on the phosphoryleted form of phosducin. Other prujects whpch are srill un progress which mcve bscn siynmficantly influgnced by CHEVS synchrotron dxtc collection include the following: Craperonon-Ledicated Protgin Fpjdinf: To understand the capacity

Proteins by phosducin is also in preparation collected CHESS on phosphorylated form of still progress which have significantly influenced by synchrotron data collection include the following: Protein Folding: To understand the capacity

Proteins by phosducin is also In preparatIon frOm dAta CoLlecTed aT CHESS on the phoSPhorYlated form of phosducin. OTher pRoJEcts WHiCh are Still in PRoGREss WhIcH haVe BEeN signIfiCantly iNfluenced bY CHeSs synchrotron DAtA collectioN inClude the follOwiNg: ChapErOniN-medicAteD ProtEin FolDIng: To uNderstand ThE CapaciTY

Proteins by phosducin is a lso in pre parat ion  fr om  dat a co llected at CHE S S on  the phosphorylated fo rm of  p h osdu c in . Oth er proj e ct s whi ch  a rest i ll  in p rog ress wh ich have b een  s ignificantly in fluenced b y C HESS synchro tro n data  c oll e ction  in clude  the f o llowin g: Chaper on i n-Medi c ated Pr o t ei n Fo lding: To underst a nd the capacity

Proteins by_phosducin is_also in preparation from_data collected_at_CHESS on_the_phosphorylated form of_phosducin. Other projects_which are still in_progress which have_been_significantly influenced by CHESS synchrotron data collection include the following: Chaperonin-Medicated Protein Folding: To_understand_the capacity


with breast cancer, survivorship, and support; and 2) create and pre-test culturally resonant outreach themes and channels based on core cultural values and existing community resources. The conceptual framework is drawn from theories of quality of life, social capital, and relational culture. The product of this study will be new, culturally appropriate

with breast cancer, survivorship, and support; and 2) create and pre - test culturally resonant outreach theme and groove based on core cultural values and existing residential district resources. The conceptual framework is drawn from theory of quality of life, social das kapital, and relational acculturation. The product of this sketch will be new, culturally appropriate

wihh breast cancer, survivovship, and supporj; qnd 2) cceate ahd pre-tert culturally resonant outreech rhemew and channels based ov core cuptural vqluew and existmhg commmuity dcsoureew. The conceptusl framewosk is drawn frmm tkeories of quality of life, social ca[ital, amd relational cujturt. Tre pdoduct of this study will be new, chlturalny appropriatr

with breast cancer, survivorship, and support; and and culturally resonant themes and channels and community resources. The framework is drawn theories of quality of life, social and relational culture. The product of this study will be new, culturally appropriate

with breast cancer, survivorsHip, and suppOrt; anD 2) crEatE aNd prE-tesT culturally resONant Outreach themes and channEls baSeD On coRE cUlturAl valueS AnD EXisTiNg ComMuNItY resoUrcEs. The coNceptual frAmeWoRk is drawn froM ThEories of quAliTy of life, sociAl cApital, AnD reLAtionAl cUlturE. The prODuct of This study WiLL be new, CUlturalLY ApPropRiate

with breast cancer, survi vorship, a nd su ppo rt;  a nd 2 ) cr eate and pre-t e st c ulturally resonant out reach  t h emes an d cha nnels b a se d onco re  cu lt u ra l val ues  and ex isting com mun it y resources. Th e conceptu alframework is  dr awn fr om  th e ories  of  qual ity of life,social ca pi t al, an d  relati o n al  cul ture. The product of this study wil l be n ew ,  c u l tur all y appropri at e

with_breast cancer,_survivorship, and support; and_2) create_and_pre-test culturally_resonant_outreach themes and_channels based on_core cultural values and_existing community resources._The_conceptual framework is drawn from theories of quality of life, social capital, and relational_culture._The product_of_this_study will be new, culturally_appropriate


.001) or similar relative (4.65+1.02 umol.min-1.kg LBM-1) (P<0.001) intensifies. Mean carbohydrate oxidation in the elderly group (86.2+6.7 umol.min-kg LBM-1) was

.001) or similar relative (4.65 + 1.02 umol.min-1.kg LBM-1) (P<0.001) intensifies. Mean carbohydrate oxidation in the elderly group (86.2 + 6.7 umol.min - kg LBM-1) was

.001) or similar relative (4.65+1.02 umol.mln-1.kg LBM-1) (P<0.001) intensifies. Kean czrbohydrxte oxidation in the elderly geoup (86.2+6.7 umol.min-kg LBM-1) was

.001) or similar relative (4.65+1.02 umol.min-1.kg LBM-1) Mean oxidation in elderly group (86.2+6.7

.001) or similar relative (4.65+1.02 umol.min-1.kG LBM-1) (P<0.001) intenSifieS. MeAn cArBohyDratE oxidation in thE EldeRly group (86.2+6.7 umol.min-kg LBM-1) waS

.001) or similar relative(4.65+1.02  umol .mi n-1 .k g LB M-1)  (P<0.001) int e nsif ies. Mean carbohydrate  oxid at i on i n  t he el derly g r ou p (86 .2 +6 .7um o l. min-k g L BM-1) w as

.001) or_similar relative_(4.65+1.02 umol.min-1.kg LBM-1) (P<0.001)_intensifies. Mean_carbohydrate_oxidation in_the_elderly group (86.2+6.7_umol.min-kg LBM-1) was


cascade. In the previous project period, we identified two novel dissociation paradigms in which similar visual stimuli produce different scleral responses due to the prior history of the eye (somewhat longer or shorter than normal, an eye-size factor). Specific Aims 1 and 2 will use these dissociative paradigms

cascade. In the previous project period, we identify two novel dissociation substitution class in which similar visual stimuli grow different scleral responses due to the anterior history of the eye (somewhat longer or shorter than normal, an center - size agent). Specific Aims 1 and 2 will use these dissociative paradigm

cadcade. In the previous pruject period, we identihied twk novel aissociation paradigms in whmch wimilqr visual stimuli prodjce diffegent scleeal cesponses due to the prior hisflry mh the eye (somewmat longer mr shorter that voxmal, an eye-size factor). Specific Aims 1 and 2 eipl use these dyssobiwtivs paradigms

cascade. In the previous project period, we novel paradigms in similar visual stimuli to prior history of eye (somewhat longer shorter than normal, an eye-size factor). Aims 1 and 2 will use these dissociative paradigms

cascade. In the previous projeCt period, we IdentIfiEd tWo NoveL disSociation paradIGms iN which similar visual stiMuli pRoDUce dIFfErent Scleral REsPONseS dUe To tHe PRiOr hisTorY of the eYe (somewhat LonGeR or shorter thAN nOrmal, an eye-SizE factor). SpeciFic aims 1 anD 2 wIll USe theSe dIssocIative PAradigMs

cascade. In the previousproject pe riod,  we  id en tifi ed t wo novel disso c iati on paradigms in whichsimil ar visu a lstimu li prod u ce d iff er en t s cl e ra l res pon ses due  to the pr ior  h istory of th e  e ye (somewh atlonger or sh ort er tha nnor m al, a n e ye-si ze fac t or). S pecific A im s  1 and 2 willu s ethes e dissociative pa r ad i gms

cascade._In the_previous project period, we_identified two_novel_dissociation paradigms_in_which similar visual_stimuli produce different_scleral responses due to_the prior history_of_the eye (somewhat longer or shorter than normal, an eye-size factor). Specific Aims 1_and_2 will_use_these_dissociative paradigms


a systemic disorder of connective tissue with autosomal dominant inheritance and a prevalence of at least 1 in 10,000 individuals. Cardinal manifestations involve the ocular, skeletal and cardiovascular systems. While all clinical features impair quality of life, cardiovascular features are uniquely associated with early mortality due to myocardial failure or aortic rupture. Variability in the age

a systemic disorder of connective tissue with autosomal dominant inheritance and a prevalence of at least 1 in 10,000 individuals. Cardinal materialization imply the ocular, skeletal and cardiovascular systems. While all clinical features mar quality of life, cardiovascular features are uniquely associate with early mortality due to myocardial failure or aortal rupture. unevenness in the age

a dystemic disorder of conkective tissue wnrh autmsomal dominang inheritance and a prevalenre od at oeast 1 in 10,000 individuals. Cardinal manifesratiibs involve the ocular, skspetan and cardiovasgular systeks. While all cnivieal features impair quality of life, sardiovssfular features are tniqhvln associated with early mortalitg due tm myocardial gailure or aortic rupture. Gariwbility in the age

a systemic disorder of connective tissue with inheritance a prevalence at least 1 involve ocular, skeletal and systems. While all features impair quality of life, cardiovascular are uniquely associated with early mortality due to myocardial failure or aortic rupture. in the age

a systemic disorder of connecTive tissue With aUtoSomAl DomiNant Inheritance and A PrevAlence of at least 1 in 10,000 indivIdualS. CARdinAL mAnifeStationS InVOLve ThE oCulAr, SKeLetal And CardiovAscular sysTemS. WHile all cliniCAl Features imPaiR quality of liFe, cArdiovAsCulAR featUreS are uNiquelY AssociAted with eArLY mortaLIty due tO MYoCardIal failure or aortiC RuPTure. VariabilitY in the AgE

a systemic disorder of co nnective t issue  wi thau toso maldominant inher i tanc e and a prevalence ofat le as t  1 i n  1 0,000  indivi d ua l s . C ar di nal  m a ni festa tio ns invo lve the oc ula r,  skeletal an d  c ardiovascu lar  systems. Wh ile  all c li nic a l fea tur es im pair q u alityof life,ca r diovas c ular fe a t ur es a re uniquely assoc i at e d with early m ortali ty du e tomyo cardial fa il ure o r  aortic ru p t u re. Variability i n the age

a_systemic disorder_of connective tissue with_autosomal dominant_inheritance_and a_prevalence_of at least_1 in 10,000_individuals. Cardinal manifestations involve_the ocular, skeletal_and_cardiovascular systems. While all clinical features impair quality of life, cardiovascular features are uniquely_associated_with early_mortality_due_to myocardial failure or aortic_rupture. Variability in the age


low urine output, dilutional hyponatremia and marked sodium retention, and a median survival time of less than 2 weeks. There is no available pharmacologic treatment for HRS type 1 in the U.S., therefore, there is a significant medical need for an effective and safe treatment. Terlipressin has

low urine output, dilutional hyponatremia and marked sodium retention, and a medial survival meter of less than 2 weeks. There is no available pharmacological treatment for HRS character 1 in the U.S., therefore, there is a meaning medical need for an effective and safe discussion. Terlipressin have

loa urine output, dilutionau hyponatremia cbd marned sosium retdntion, and a median survival tume od less than 2 weeks. Thefe is no wvailablw phermacologic treavjent fov HRS bype 1 mn the U.S., therenore, there hs a significatt mzdical need for an effective and safq treatkejt. Terlipressig hax

low urine output, dilutional hyponatremia and marked and median survival of less than available treatment for HRS 1 in the therefore, there is a significant medical for an effective and safe treatment. Terlipressin has

low urine output, dilutional hYponatremiA and mArkEd sOdIum rEtenTion, and a median SUrviVal time of less than 2 weeks. there Is NO avaILaBle phArmacolOGiC TReaTmEnT foR Hrs tYpe 1 in The u.S., thereFore, there iS a sIgNificant mediCAl Need for an eFfeCtive and safe TreAtment. teRliPRessiN haS

low urine output, dilutio nal hypona tremi a a ndma rked  sod ium retention, anda median survival time  of l es s  tha n  2  week s. Ther e  i s noav ai lab le ph armac olo gic tre atment for  HR Stype 1 in th e  U .S., there for e, there isa s ignifi ca ntm edica l n eed f or ane ffecti ve and sa fe treatm e nt. Ter l i pr essi n has

low_urine output,_dilutional hyponatremia and marked_sodium retention,_and_a median_survival_time of less_than 2 weeks._There is no available_pharmacologic treatment for_HRS_type 1 in the U.S., therefore, there is a significant medical need for an_effective_and safe_treatment._Terlipressin_has


enzymes involved. The enzyme proteins involved in each reaction will be purified and the substrate affinities and substrate range will be studied for each step. Physiologic and pharmacologic controls of conjugation will be studied by assaying the individual reactions. Initial work will be performed in animal models as a prerequisite for future study in human tissue.

enzymes involved. The enzyme proteins involved in each chemical reaction will be purify and the substrate affinities and substrate range will be study for each footstep. Physiologic and pharmacologic controls of junction will be studied by assaying the individual chemical reaction. Initial work will be performed in animal model as a prerequisite for future study in human tissue.

enxymes involved. The enzymt proteins involvgd in earh reacfion wilu be purified and the substrete qffinuties and substrate ravge will he studiwd fie each ste'. Physiologic zkd phcrnacologic conttols of conjggation will ba rtbdied by assaying the individual reastions. Onltial work wilj be [erfkgmtd in animal models as a prerequiaite fog future study in human tissue.

enzymes involved. The enzyme proteins involved in will purified and substrate affinities and for step. Physiologic and controls of conjugation be studied by assaying the individual Initial work will be performed in animal models as a prerequisite for future in human tissue.

enzymes involved. The enzyme pRoteins invOlved In eAch ReActiOn wiLl be purified anD The sUbstrate affinities and sUbstrAtE RangE WiLl be sTudied fOR eACH stEp. phYsiOlOGiC and pHarMacologIc controls Of cOnJugation will BE sTudied by asSayIng the indiviDuaL reactIoNs. INItial WorK will Be perfORmed in Animal modElS As a preREquisitE FOr FutuRe study in human tisSUe.

enzymes involved. The enz yme protei ns in vol ved  i n ea ch r eaction will b e  pur ified and the substrat e aff in i ties an d sub strater an g e  wi ll  b e s tu d ie d for  ea ch step . Physiolo gic  a nd pharmacol o gi c controls  of  conjugation  wi ll best udi e d byass aying  the i n dividu al reacti on s . Init i al work w il l be  performed in ani m al models as a pr erequi si t ef o r f utu re study i nhuman tissue.

enzymes_involved. The_enzyme proteins involved in_each reaction_will_be purified_and_the substrate affinities_and substrate range_will be studied for_each step. Physiologic_and_pharmacologic controls of conjugation will be studied by assaying the individual reactions. Initial work_will_be performed_in_animal_models as a prerequisite for_future study in human tissue.


better understanding of the pathologies involved in glaucoma and cataract. Differentiating cultures of embryonic skeletal muscle are being studied from two points of view. (1) A protein factor in embryo extract that is required for differentiation is being purified and characterized by standard biochemical methodology. (2) It has been found that the permeability of myoblasts

better understanding of the pathologies involved in glaucoma and cataract. differentiate acculturation of embryonic skeletal muscle are being studied from two point of view. (1) A protein factor in embryo excerpt that is want for differentiation is being purify and characterized by standard biochemical methodology. (2) It has been found that the permeability of myoblasts

behter understanding of tht pathologies involved ii glauckma and zataract. Differentiating culvurew of tibryonic skeletal ouscle arv being sruditd from two points of view. (1) A pdlteiu hactor in embryp extract dhat is requirad flr differentiation is being purifieq and cnagacterized by ftancwrd gpoghemical methodology. (2) It has beeh found that the perkeability of myoblasts

better understanding of the pathologies involved in cataract. cultures of skeletal muscle are of (1) A protein in embryo extract is required for differentiation is being and characterized by standard biochemical methodology. (2) It has been found that the of myoblasts

better understanding of the pAthologies InvolVed In gLaUcomA and Cataract. DifferENtiaTing cultures of embryoniC skelEtAL musCLe Are beIng studIEd FROm tWo PoIntS oF ViEw. (1) A prOteIn factoR in embryo eXtrAcT that is requiREd For differeNtiAtion is being PurIfied aNd ChaRActerIzeD by stAndard BIochemIcal methoDoLOgy. (2) It hAS been foUND tHat tHe permeability of mYObLAsts

better understanding of t he patholo giesinv olv ed  inglau coma and catar a ct.Differentiating cultur es of  e m bryo n ic  skel etal mu s cl e are  b ei ngst u di ed fr omtwo poi nts of vie w.(1 ) A proteinf ac tor in emb ryo  extract tha t i s requ ir edf or di ffe renti ationi s bein g purifie da nd cha r acteriz e d  b y st andard biochemica l  m e thodology. (2)  It ha sb ee n fou ndthat the p er meabi l ity ofm yo b l a sts

better_understanding of_the pathologies involved in_glaucoma and_cataract._Differentiating cultures_of_embryonic skeletal muscle_are being studied_from two points of_view. (1) A_protein_factor in embryo extract that is required for differentiation is being purified and characterized_by_standard biochemical_methodology._(2)_It has been found that_the permeability of myoblasts


and its receptors) in lung endothelial and epithelial cells, and fetal lung explants, even in extreme hyperoxia. We hypothesize that PHDi can decrease PHNby restoring the fetal VEGF/eNOS axis and improving perinatal surfactant homeostasis. We propose to examine effects of PHDi delivered antenatally or postnat

and its receptors) in lung endothelial and epithelial cells, and fetal lung explants, even in extreme hyperoxia. We hypothesize that PHDi can decrease PHNby restoring the fetal VEGF / eNOS bloc and better perinatal surfactant homeostasis. We propose to test impression of PHDi delivered antenatally or postnat

anf its receptors) in lung tndothelial and ekirhelian cella, and fegal lung explants, even in exvremw hyptgoxia. We hypothesize ghat PHDi can deceeast PHNby restoring the fetal VEGR/cNOS cxms and improvinn perinatal surfactant hokeuscasis. We propose to examine effects jf PHDi dflivered antenwtalkr or iowtnat

and its receptors) in lung endothelial and and lung explants, in extreme hyperoxia. decrease restoring the fetal axis and improving surfactant homeostasis. We propose to examine of PHDi delivered antenatally or postnat

and its receptors) in lung endoThelial and EpithEliAl cElLs, anD fetAl lung explants, EVen iN extreme hyperoxia. We hypOthesIzE That phDI can dEcrease phNBY ResToRiNg tHe FEtAl VEGf/eNoS axis aNd improvinG peRiNatal surfactANt HomeostasiS. We Propose to exaMinE effecTs Of Phdi delIveRed anTenataLLy or poStnat

and its receptors) in lun g endothel ial a ndepi th elia l ce lls, and fetal lung  explants, even in ext remehy p erox i a.  We h ypothes i ze t hat  P HD i c an de creas e P HNby re storing th e f et al VEGF/eNOS ax is and imp rov ing perinata l s urfact an t h o meost asi s. We  propo s e to e xamine ef fe c ts ofP HDi del i v er ed a ntenatally or pos t na t

and_its receptors)_in lung endothelial and_epithelial cells,_and_fetal lung_explants,_even in extreme_hyperoxia. We hypothesize_that PHDi can decrease_PHNby restoring the_fetal_VEGF/eNOS axis and improving perinatal surfactant homeostasis. We propose to examine effects of PHDi_delivered_antenatally or_postnat


process that are subject to physiological regulation, and that will b amenable to experimental and therapeutic manipulations to control substrate polysialylation and function during development, repair, and disease. PUBLIC HEALTH RELEVANCE: Polysialic acid is a developmentally regulated sugar polymer found on a small group of adhesive and signaling proteins.

process that are subject to physiological regulation, and that will b amenable to experimental and curative manipulation to control substrate polysialylation and function during growth, haunt, and disease. PUBLIC HEALTH RELEVANCE: Polysialic acid is a developmentally regulated sugar polymer found on a little group of adhesive and signaling proteins.

prlcess that are subject tu physiological regulavion, ans that wkll b amenable to experimentel abd thtgapeutic manipulationr to contgol substeate polysialylefion and funcflon dbrmng development, repair, ang disease. PUBLHC HZALTH RELEVANCE: Polysialic acid is a develolmfntally regulajed slgwr pklymer found on a small group of ashesive and signalinb proteins.

process that are subject to physiological regulation, will amenable to and therapeutic manipulations function development, repair, and PUBLIC HEALTH RELEVANCE: acid is a developmentally regulated sugar found on a small group of adhesive and signaling proteins.

process that are subject to phYsiologicaL reguLatIon, AnD thaT wilL b amenable to exPErimEntal and therapeutic manIpulaTiONs to COnTrol sUbstratE PoLYSiaLyLaTioN aND fUnctiOn dUring deVelopment, rEpaIr, And disease. PUblIc HEALTH RELeVAnCE: PolysialiC acId is a dEvEloPMentaLly RegulAted suGAr polyMer found oN a SMall grOUp of adhESIvE and Signaling proteins.

process that are subjectto physiol ogica l r egu la tion , an d that will ba mena ble to experimental an d the ra p euti c  m anipu lations to c ont ro lsub st r at e pol ysi alylati on and fun cti on  during deve l op ment, repa ir,  and disease . P UBLICHE ALT H  RELE VAN CE: P olysia l ic aci d is a de ve l opment a lly reg u l at ed s ugar polymer foun d  o n  a small group  of ad he s iv e and  si gnaling pr ot eins.

process_that are_subject to physiological regulation,_and that_will_b amenable_to_experimental and therapeutic_manipulations to control_substrate polysialylation and function_during development, repair,_and_disease. PUBLIC HEALTH RELEVANCE: Polysialic acid is a developmentally regulated sugar polymer found on_a_small group_of_adhesive_and signaling proteins.


of the developed system by assessing a sample of new patients, providing the information to their mental health-care providers, surveying the clinicians for the usefulness and acceptability of the diagnostic system, and examining its predictive validity over 6 months post-intake. We expect that the newly developed system will have high predictive validity and

of the developed system by assessing a sample of newfangled patient, providing the information to their mental health - concern providers, surveying the clinician for the usefulness and acceptability of the diagnostic system, and examining its predictive cogency over 6 months post - intake. We expect that the newly develop system will get high predictive validity and

of the developed system by assessing a sample of new pztients, oroviding the information to tyeir nental health-care provkders, surneying thw clmnicians for the usefulncfs ahf acee'tability of thg diagnostic system, and exdmknnng its predictive validity over 6 mogths poxt-lntake. We expest tnwt tgv kewly developed system will have high pgedictive validitu and

of the developed system by assessing a new providing the to their mental for usefulness and acceptability the diagnostic system, examining its predictive validity over 6 post-intake. We expect that the newly developed system will have high predictive validity

of the developed system by assEssing a samPle of New PatIeNts, pRoviDing the informaTIon tO their mental health-care ProviDeRS, surVEyIng thE clinicIAnS FOr tHe UsEfuLnESs And acCepTabilitY of the diagNosTiC system, and exAMiNing its preDicTive validity OveR 6 monthS pOst-INtake. we eXpect That thE Newly dEveloped sYsTEm will HAve high PREdIctiVe validity and

of the developed system b y assessin g a s amp leof  new  pat ients, providi n g th e information to their  ment al heal t h- careprovide r s, s urv ey in g t he cl inici ans  for th e usefulne ssan d acceptabil i ty  of the di agn ostic system , a nd exa mi nin g  itspre dicti ve val i dity o ver 6 mon th s  post- i ntake.W e  e xpec t that the newlyd ev e loped system w ill ha ve hi g h  pr edi ctive vali di ty an d

of_the developed_system by assessing a_sample of_new_patients, providing_the_information to their_mental health-care providers,_surveying the clinicians for_the usefulness and_acceptability_of the diagnostic system, and examining its predictive validity over 6 months post-intake. We_expect_that the_newly_developed_system will have high predictive_validity and


is required for definitive HSC specification during embryogenesis and regulates adult HSC homeostasis. I recently performed a chemical genetic screen for modifiers of runx1+ HSC formation in zebrafish and identified the prostaglandin pathway as a conserved vertebrate regulator of HSCs. A stable prostaglandin E2 (PGE2) derivative

is required for definitive HSC specification during embryogenesis and regulates adult HSC homeostasis. I recently perform a chemical familial screen for modifiers of runx1 + HSC formation in zebrafish and name the prostaglandin pathway as a conserved vertebrate governor of HSCs. A stable prostaglandin E2 (PGE2) derivative

is required for definitive HSC specificatnin durmng embdyogenesks and regulates adult HSC hlmwostawis. I recently performdd a chempcal generic wxreen for modifiers of rhkx1+ HSE hormation in zenrafish and identified tha orlstaglandin pathway as a conserved dertebrstf regulator of HSCx. A sfable prostaglandin E2 (PGE2) derivatibe

is required for definitive HSC specification during regulates HSC homeostasis. recently performed a of HSC formation in and identified the pathway as a conserved vertebrate regulator HSCs. A stable prostaglandin E2 (PGE2) derivative

is required for definitive HSc specificaTion dUriNg eMbRyogEnesIs and regulates ADult hSC homeostasis. I recentlY perfOrMEd a cHEmIcal gEnetic sCReEN For MoDiFieRs OF rUnx1+ HSc foRmation In zebrafisH anD iDentified the PRoStaglandin PatHway as a conseRveD verteBrAte REgulaTor Of HSCS. A stabLE prostAglandin E2 (pGe2) DerivaTIve

is required for definitiv e HSC spec ifica tio n d ur ingembr yogenesis andr egul ates adult HSC homeost asis.  I rece n tl y per formeda  c h e mic al  g ene ti c  s creen  fo r modif iers of ru nx1 +HSC formatio n  i n zebrafis h a nd identifie d t he pro st agl a ndinpat hwayas a c o nserve d vertebr at e  regul a tor ofH S Cs . Astable prostaglan d in E2 (PGE2) deri vative

is_required for_definitive HSC specification during_embryogenesis and_regulates_adult HSC_homeostasis._I recently performed_a chemical genetic_screen for modifiers of_runx1+ HSC formation_in_zebrafish and identified the prostaglandin pathway as a conserved vertebrate regulator of HSCs. A_stable_prostaglandin E2_(PGE2)_derivative


function in animals with downregulated adrenal steroid receptors secondary to chronic steroid exposure or aging. Taken together, these studies, which are a major component of the PI's RSDA, are designed to provide a foundation for understanding the role of neuroendocrine function in immune-related diseases such as AIDS. Umbilical cord

function in animals with downregulated adrenal steroid receptors junior-grade to chronic steroid hormone photograph or aging. lead in concert, these studies, which are a major component of the PI's RSDA, are designed to supply a foundation for understanding the function of neuroendocrine function in immune - related disease such as AIDS. Umbilical cord

fujction in animals with duwnregulated adtebal stxroid rsceptors secondary to chronic steroiv exposurt or aging. Taken toeether, thvse studiws, wiich are a major componekc of fme PI'v RSDA, are desinned to proeide a foundathov yor understanding the role of neuroegdocrinr vunction in imiune-gejates diseases such as AIDS. Umbilical dord

function in animals with downregulated adrenal steroid to steroid exposure aging. Taken together, major of the PI's are designed to a foundation for understanding the role neuroendocrine function in immune-related diseases such as AIDS. Umbilical cord

function in animals with downRegulated aDrenaL stEroId RecePtorS secondary to chROnic Steroid exposure or aging. taken ToGEtheR, ThEse stUdies, whICh ARE a mAjOr ComPoNEnT of thE PI'S RSDA, arE designed tO prOvIde a foundatiON fOr understaNdiNg the role of nEurOendocRiNe fUNctioN in ImmunE-relatED diseaSes such as aIds. UmbilICal cord

function in animals withdownregula ted a dre nal  s tero id r eceptors secon d aryto chronic steroid exp osure  o r  agi n g.  Take n toget h er , the se  s tud ie s ,which  ar e a maj or compone ntof  the PI's RS D A,  are desig ned  to providea f oundat io n f o r und ers tandi ng the role o f neuroen do c rine f u nctioni n  i mmun e-related disease s  s u ch as AIDS. Um bilica lc or d

function_in animals_with downregulated adrenal steroid_receptors secondary_to_chronic steroid_exposure_or aging. Taken_together, these studies,_which are a major_component of the_PI's_RSDA, are designed to provide a foundation for understanding the role of neuroendocrine function_in_immune-related diseases_such_as_AIDS. Umbilical cord


through which community-level factors shape individual risk and community rates of psychopathology and adverse behavioral outcomes after disasters. Our broad aim is to demonstrate the utility of an ecological conceptualization of disaster recovery, focusing on individuals' health outcomes such as the occurrence/severity of posttraumatic stress disorder (PTSD), depressive symptoms,

through which community - level factors shape individual hazard and residential district rate of psychopathology and adverse behavioral result after calamity. Our broad aim is to show the utility of an ecological conceptualization of disaster convalescence, concenter on individuals' health consequence such as the occurrence / severity of posttraumatic tension disorder (PTSD), depressive symptoms,

thgough which community-levtl factors shape nbdividnal risi and coomunity rates of psychopathopoty ane adverse behavioral ojtcomes avter disqstecs. Our broad aim is to dcionsfvate chx utility of an ecologican conceptualizdtkou of disaster recovery, focusing on igdividusld' health outcoies xtch zs the occurrence/severity of posttdaumatib stress disorder (PTSD), depressive symptoms,

through which community-level factors shape individual risk rates psychopathology and behavioral outcomes after to the utility of ecological conceptualization of recovery, focusing on individuals' health outcomes as the occurrence/severity of posttraumatic stress disorder (PTSD), depressive symptoms,

through which community-leveL factors shApe inDivIduAl Risk And cOmmunity rates oF PsycHopathology and adverse bEhaviOrAL outCOmEs aftEr disasTErS. oUr bRoAd Aim Is TO dEmonsTraTe the utIlity of an eColOgIcal conceptuALiZation of diSasTer recovery, fOcuSing on InDivIDuals' HeaLth ouTcomes SUch as tHe occurreNcE/SeveriTY of postTRAuMatiC stress disorder (PTsd), dEPressive symptoMs,

through which community-l evel facto rs sh ape  in di vidu al r isk and commun i ty r ates of psychopatholog y and  a d vers e  b ehavi oral ou t co m e s a ft er  di sa s te rs. O urbroad a im is to d emo ns trate the ut i li ty of an e col ogical conce ptu alizat io n o f  disa ste r rec overy, focusi ng on ind iv i duals' healtho u tc omes  such as the occu r re n ce/severity of  postt ra u ma t i c s tre ss disorde r(PTSD ) , depre s si v e sym p toms,

through_which community-level_factors shape individual risk_and community_rates_of psychopathology_and_adverse behavioral outcomes_after disasters. Our_broad aim is to_demonstrate the utility_of_an ecological conceptualization of disaster recovery, focusing on individuals' health outcomes such as the_occurrence/severity_of posttraumatic_stress_disorder_(PTSD), depressive symptoms,


interventions designed to enhance nutritive flow. Nonetheless, the use of PET has been limited by the availability of cyclotron-produced flow tracers. Accordingly, development of generator- produced, positron-emitting flow tracers is highly desirable. In the initial two years of this award, we developed and implemented approaches

interventions designed to enhance nutritive flow. however, the habit of PET has been limited by the availability of cyclotron - produce stream tracers. Accordingly, exploitation of generator- produce, positron - emitting stream tracers is highly desirable. In the initial two years of this prize, we developed and implemented approaches

inherventions designed to tnhance nutritive flow. Nmnethemess, the use of PET has been limited bt the availability of cyclogron-produbed flow rractrs. Accordingly, dxbelopmekc of fcneracoc- produced, posijron-emitting flow tracers hs hnghly desirable. In the initial two yqars of tjis award, we dgveloked and pmklemented approaches

interventions designed to enhance nutritive flow. Nonetheless, of has been by the availability development generator- produced, positron-emitting tracers is highly In the initial two years of award, we developed and implemented approaches

interventions designed to enHance nutriTive fLow. nonEtHeleSs, thE use of PET has beEN limIted by the availability oF cyclOtROn-prODuCed flOw traceRS. ACCOrdInGlY, deVeLOpMent oF geNerator- Produced, poSitRoN-emitting floW TrAcers is higHly Desirable. In tHe iNitial TwO yeARs of tHis Award, We deveLOped anD implemenTeD ApproaCHes

interventions designed to  enhance n utrit ive  fl ow . No neth eless, the use of P ET has been limited by  theav a ilab i li ty of  cyclot r on - p rod uc ed  fl ow tr acers . A ccordin gly, devel opm en t of generat o r-  produced,  po sitron-emitt ing  flowtr ace r s ishig hly d esirab l e. Inthe initi al two ye a rs of t h i sawar d, we developed a n di mplemented app roache s

interventions_designed to_enhance nutritive flow. Nonetheless,_the use_of_PET has_been_limited by the_availability of cyclotron-produced_flow tracers. Accordingly, development_of generator- produced,_positron-emitting_flow tracers is highly desirable. In the initial two years of this award, we_developed_and implemented_approaches


Duncan at Yale University will develop methods for segmentation, shape tracking, dense displacement integration and strain computation. A cardiology/physiology group under Dr. Albert Sinusas at Yale will perform the acute and chronic canine studies and the human stress echo studies. A consultant from Philips Medical Systems will work with the entire team

Duncan at Yale University will develop methods for segmentation, shape trailing, dense displacement consolidation and tenor computation. A cardiology / physiology group under Dr. Albert Sinusas at Yale will perform the acuate and chronic canine studies and the human stress echo studies. A adviser from Philips Medical Systems will sour with the entire team

Dujcan at Yale University dill develop mejhids foc segmehtation, rhape tracking, dense displacxmenr inttyration and strain cumputatioj. A carduolojy/physiology gronl under Dr. Algcrt Snnnsas at Yale wikl perform the acute and cfrlnic canine studies and the human seress evhl studies. A cogsuluane frkm Philips Medical Systems will wodk with the entire tram

Duncan at Yale University will develop methods shape dense displacement and strain computation. Albert at Yale will the acute and canine studies and the human stress studies. A consultant from Philips Medical Systems will work with the entire team

Duncan at Yale University wilL develop meThods For SegMeNtatIon, sHape tracking, deNSe diSplacement integration aNd strAiN CompUTaTion. A CardiolOGy/PHYsiOlOgY grOuP UnDer Dr. albErt SinuSas at Yale wIll PeRform the acutE AnD chronic caNinE studies and tHe hUman stReSs eCHo stuDieS. A conSultanT From PhIlips MediCaL systemS Will worK WItH the Entire team

Duncan at Yale University  will deve lop m eth ods  f or s egme ntation, shape trac king, dense displaceme nt in te g rati o nand s train c o mp u t ati on .A c ar d io logy/ phy siology  group und erDr . Albert Sin u sa s at Yalewil l perform th e a cute a nd  ch r oniccan ine s tudies and th e human s tr e ss ech o  studie s .  A  con sultant from Phil i ps Medical System s will  w o rk w ith  th e entire t ea m

Duncan_at Yale_University will develop methods_for segmentation,_shape_tracking, dense_displacement_integration and strain_computation. A cardiology/physiology_group under Dr. Albert_Sinusas at Yale_will_perform the acute and chronic canine studies and the human stress echo studies. A_consultant_from Philips_Medical_Systems_will work with the entire_team


and interviewing techniques in order to develop the best and most cost-effective techniques for obtaining quantifiable data on the addict's daily income, expenditures, crime and drug use. This methodological experimentation will continue in the second year. A sample of street-level addicts selected to represent differing economic lifestyles, ethnicities and

and interviewing techniques in order to develop the good and most monetary value - effective techniques for obtaining quantifiable data on the addict's casual income, expenditures, crime and drug use. This methodological experimentation will proceed in the second year. A sample of street - degree addicts selected to defend differing economic lifestyles, ethnicity and

anf interviewing techniquer in order to dgvwlop tie best and mosg cost-effective techniques flr obtauning quantifiable datx on the wddict's eailb income, expendivhres, crlie ahf drbg use. This methpdological experimentatimn wnll continue in the second year. A saiple of shreet-level addycts feledneb to represent differing economjc lifevtyles, ethnicoties and

and interviewing techniques in order to develop and cost-effective techniques obtaining quantifiable data expenditures, and drug use. methodological experimentation will in the second year. A sample street-level addicts selected to represent differing economic lifestyles, ethnicities and

and interviewing techniques In order to dEveloP thE beSt And mOst cOst-effective teCHniqUes for obtaining quantifIable DaTA on tHE aDdict'S daily iNCoME, ExpEnDiTurEs, CRiMe and DruG use. ThiS methodoloGicAl ExperimentatIOn Will continUe iN the second yeAr. A Sample Of StrEEt-levEl aDdictS selecTEd to rePresent diFfERing ecONomic liFEStYles, Ethnicities and

and interviewing techniqu es in orde r todev elo pthebest  and most cost - effe ctive techniques for o btain in g  qua n ti fiabl e datao nt h e a dd ic t's  d a il y inc ome , expen ditures, c rim eand drug use .  T his method olo gical experi men tation  w ill conti nue  in t he sec o nd yea r. A samp le of str e et-leve l ad dict s selected to rep r es e nt differing e conomi cl if e s tyl es,  ethniciti es  and

and_interviewing techniques_in order to develop_the best_and_most cost-effective_techniques_for obtaining quantifiable_data on the_addict's daily income, expenditures,_crime and drug_use._This methodological experimentation will continue in the second year. A sample of street-level addicts_selected_to represent_differing_economic_lifestyles, ethnicities and


and therapeutic manipulation of immune system disorders including immunodeficiency as well as hypersensitivity disease states. The PI for this project, Dr. E. P. Greenberg has worked on quorum sensing for over 25 years. His long-term goals are to investigate the molecular mechanisms of social activity in bacteria, and to learn about why,

and therapeutic manipulation of immune system disorders include immunodeficiency equally well as hypersensitivity disease states. The PI for this project, Dr. E. P. Greenberg has work on quorum sense for over 25 years. His long - terminus goal are to investigate the molecular mechanisms of social action in bacteria, and to learn about why,

anf therapeutic manipulatiun of immune system divordera includkng immunodeficiency as well aw hyptgsensitivity disease rtates. Thv PI for rhis project, Dr. E. P. Grecuberg mas wmcked on quorum xensing fos over 25 years. Vir pong-term goals are to investigate tre molevupar mechanisms of xjciam activity in bacteria, and to learh about why,

and therapeutic manipulation of immune system disorders as as hypersensitivity states. The PI P. has worked on sensing for over years. His long-term goals are to the molecular mechanisms of social activity in bacteria, and to learn about why,

and therapeutic manipulatioN of immune sYstem DisOrdErS incLudiNg immunodeficiENcy aS well as hypersensitivitY diseAsE StatES. THe PI fOr this pROjECT, Dr. e. P. grEenBeRG hAs worKed On quoruM sensing foR ovEr 25 Years. His long-TErM goals are tO inVestigate the MolEcular MeChaNIsms oF soCial aCtivitY In bactEria, and to LeARn abouT Why,

and therapeutic manipulat ion of imm une s yst emdi sord ersincluding immu n odef iciency as well as hyp ersen si t ivit y  d iseas e state s .T h e P Ifo r t hi s  p rojec t,Dr. E.P. Greenbe rgha s worked onq uo rum sensin g f or over 25 y ear s. His  l ong - termgoa ls ar e to i n vestig ate the m ol e cularm echanis m s  o f so cial activity inb ac t eria, and to l earn a bo u tw h y,

and_therapeutic manipulation_of immune system disorders_including immunodeficiency_as_well as_hypersensitivity_disease states. The_PI for this_project, Dr. E. P._Greenberg has worked_on_quorum sensing for over 25 years. His long-term goals are to investigate the molecular_mechanisms_of social_activity_in_bacteria, and to learn about_why,


of the multiple forms of cytochrome P-450. Also, other compounds, i.e., medicarpin and maackiain, are being studied and their structural and inhibitory effects on cytochrome P-450 are being determined using microsomes and purified cytochromes P-450. New, powerful interventions such

of the multiple forms of cytochrome P-450. Also, other compounds, i.e., medicarpin and maackiain, are being study and their geomorphologic and inhibitory effects on cytochrome P-450 are being determined using microsome and purified cytochromes P-450. New, powerful treatment such

of the multiple forms of cntochrome P-450. Also, other rompounss, i.e., meaicarpin and maackiain, are bxing studued and their structurxl and injibitory efftcts on cytochromx P-450 are nzing sctermnnxd using microspmes and pgrified cytochsooed P-450. New, powerful interventions such

of the multiple forms of cytochrome P-450. compounds, medicarpin and are being studied effects cytochrome P-450 are determined using microsomes purified cytochromes P-450. New, powerful interventions

of the multiple forms of cytocHrome P-450. Also, Other ComPouNdS, i.e., mEdicArpin and maackiAIn, arE being studied and their sTructUrAL and INhIbitoRy effecTS oN CYtoChRoMe P-450 ArE BeIng deTerMined usIng microsoMes AnD purified cytOChRomes P-450. New, pOweRful intervenTioNs such

of the multiple forms ofcytochrome  P-45 0.Als o,  oth er c ompounds, i.e. ,  med icarpin and maackiain,  arebe i ng s t ud ied a nd thei r  s t r uct ur al  an di nh ibito ryeffects  on cytoch rom eP-450 are be i ng  determine d u sing microso mes  and p ur ifi e d cyt och romes  P-450 .  New,powerfulin t ervent i ons suc h

of_the multiple_forms of cytochrome P-450._Also, other_compounds,_i.e., medicarpin_and_maackiain, are being_studied and their_structural and inhibitory effects_on cytochrome P-450_are_being determined using microsomes and purified cytochromes P-450. New, powerful interventions such