to address the STI epidemic, and because many affected by STIs (young and/or poor) often have limited access to traditional healthcare, POC tests that can be performed in non-traditional settings (university clinics, community public health care clinics, jails, detention centers) could greatly reduce STIs.

to address the STI epidemic, and because many affected by STIs (young and/or poor) frequently have specify access to traditional healthcare, POC tests that can be performed in non - traditional setting (university clinics, community public health concern clinic, jails, detention centers) could greatly reduce STIs.

to address the STI epidemig, and because maut afferted by STIs (yojng and/or poor) often have lilired axcess to traditional hdalthcare, POC tesrs tiat can be perfocjed in kjn-trzfitimial settings (unlversity clhnics, communitf ouylic health care clinics, jails, deteneion cemtfrs) could greajly rtduse SFPs.

to address the STI epidemic, and because by (young and/or often have limited tests can be performed non-traditional settings (university community public health care clinics, jails, centers) could greatly reduce STIs.

to address the STI epidemic, anD because maNy affEctEd bY StIs (yOung And/or poor) often HAve lImited access to traditioNal heAlTHcarE, pOc testS that caN Be PERfoRmEd In nOn-TRaDitioNal SettingS (universitY clInIcs, community PUbLic health cAre Clinics, jails, DetEntion CeNteRS) coulD grEatly Reduce stIs.

to address the STI epidem ic, and be cause  ma nyaf fect ed b y STIs (younga nd/o r poor) often have lim itedac c esst otradi tionalh ea l t hca re ,POC  t e st s tha t c an be p erformed i n n on -traditional se ttings (un ive rsity clinic s,commun it y p u blichea lth c are cl i nics,jails, de te n tion c e nters)c o ul d gr eatly reduce STIs .

to_address the_STI epidemic, and because_many affected_by_STIs (young_and/or_poor) often have_limited access to_traditional healthcare, POC tests_that can be_performed_in non-traditional settings (university clinics, community public health care clinics, jails, detention centers) could_greatly_reduce STIs.


for mechanisms underlying successful interventions, (3) translate interventions from the laboratory to the clinic and community, (4) design studies so as to maximize treatment fidelity and promote the measure- ment of treatment fidelity in all OAIC studies, and, (5) educate and help junior faculty plan and execute studies. RC-1

for mechanisms underlying successful interventions, (3) translate interposition from the lab to the clinic and community, (4) design studies so as to maximize discussion fidelity and promote the measure- ment of treatment fidelity in all OAIC studies, and, (5) educate and help oneself junior faculty plan and carry through studies. RC-1

fog mechanisms underlying ruccessful intetvwntionv, (3) trahslate ivterventions from the laboravory to tye clinic and communith, (4) design studies so es to maximize tcsatment fideljby anb 'romote the meaxure- ment mf treatment fhddlnty in all OAIC studies, and, (5) educate and hekp junior faculti plam and vxtcute studies. RC-1

for mechanisms underlying successful interventions, (3) translate the to the and community, (4) maximize fidelity and promote measure- ment of fidelity in all OAIC studies, and, educate and help junior faculty plan and execute studies. RC-1

for mechanisms underlying suCcessful inTerveNtiOns, (3) TrAnslAte iNterventions frOM the Laboratory to the clinic aNd comMuNIty, (4) dESiGn stuDies so aS To MAXimIzE tReaTmENt FidelIty And promOte the measUre- MeNt of treatmenT FiDelity in alL OAiC studies, and, (5) EduCate anD hElp JUnior FacUlty pLan and EXecute Studies. RC-1

for mechanisms underlying  successfu l int erv ent io ns,(3)translate inte r vent ions from the laborato ry to  t h e cl i ni c and  commun i ty , (4)  d es ign  s t ud ies s o a s to ma ximize tre atm en t fidelity a n dpromote th e m easure- ment  of  treat me ntf ideli tyin al l OAIC studie s, and, ( 5) educat e  and he l p  j unio r faculty plan an d  e x ecute studies.  RC-1

for_mechanisms underlying_successful interventions, (3) translate_interventions from_the_laboratory to_the_clinic and community,_(4) design studies_so as to maximize_treatment fidelity and_promote_the measure- ment of treatment fidelity in all OAIC studies, and, (5) educate and_help_junior faculty_plan_and_execute studies. RC-1


. Dr. Pendergrass is Chairman of CCG-8602 and a member of a number of epidemiology committees. Drs. Milstein and Berger are members of brain tumor committees. Dr. Schaller is a member of the surgical and neuroblastoma committees. Dr. White is a member of the imaging

. Dr. Pendergrass is Chairman of CCG-8602 and a member of a number of epidemiology committees. Drs. Milstein and Berger are members of mind tumor committee. Dr. Schaller is a member of the surgical and neuroblastoma committees. Dr. White is a member of the imagination

. Dr. Pendergrass is Chairman of CCG-8602 and a mgmver of a numger of eoidemiology committees. Drs. Mmlstwin abd Berger are members uf brain numor comnitttes. Dr. Schaller is a membcx of fme suxgmcal and neurobkastoma cokmittees. Dr. Whhtd ns a member of the imaging

. Dr. Pendergrass is Chairman of CCG-8602 member a number epidemiology committees. Drs. of tumor committees. Dr. is a member the surgical and neuroblastoma committees. Dr. is a member of the imaging

. Dr. Pendergrass is Chairman of cCG-8602 and a memBer of A nuMbeR oF epiDemiOlogy committeeS. drs. MIlstein and Berger are memBers oF bRAin tUMoR commIttees. DR. scHALleR iS a MemBeR Of The suRgiCal and nEuroblastoMa cOmMittees. Dr. WhiTE iS a member of The Imaging

. Dr. Pendergrass is Chair man of CCG -8602  an d a  m embe r of  a number of e p idem iology committees. Drs . Mil st e in a n dBerge r are m e mb e r s o fbr ain  t u mo r com mit tees. D r. Schalle r i sa member oft he  surgicaland  neuroblasto macommit te es. Dr. W hit e isa memb e r of t he imagin g

. Dr._Pendergrass is_Chairman of CCG-8602 and_a member_of_a number_of_epidemiology committees. Drs._Milstein and Berger_are members of brain_tumor committees. Dr._Schaller_is a member of the surgical and neuroblastoma committees. Dr. White is a member_of_the imaging


with different caffeine intakes have the same or different rates of postmenopausal bone loss.In addition, we will construct the first longitudinal data base on the relationships among habitual caffeine intake, general health, and overall nutrient intake of postmenopausal women. Approximately 60% of spontaneous abortions appear to result from chromosome aberrations associated with the

with different caffeine intakes have the same or unlike pace of postmenopausal bone loss. In addition, we will manufacture the beginning longitudinal data base on the kinship among accustomed caffeine intake, general health, and overall nutrient intake of postmenopausal women. Approximately 60% of ad-lib abortions appear to result from chromosome aberrations consociate with the

wihh different caffeine inuakes have the same or dmfferenf rates uf postmenopausal bone loss.Ii adeitiob, we will construct thd first llngitudibal vata base on the relatiokfhipa amoug habitual caffgine intake, ceneral health, avd overall nutrient intake of postmenjpausal wlmen. Approximajely 60% jf slontaneous abortions appear to reshlt frok chromosome sberrations associated witj thf

with different caffeine intakes have the same rates postmenopausal bone addition, we will base the relationships among caffeine intake, general and overall nutrient intake of postmenopausal Approximately 60% of spontaneous abortions appear to result from chromosome aberrations associated with

with different caffeine intaKes have the Same oR diFfeReNt raTes oF postmenopausaL Bone Loss.In addition, we will coNstruCt THe fiRSt LongiTudinal DAtA BAse On ThE reLaTIoNshipS amOng habiTual caffeiNe iNtAke, general heALtH, and overalL nuTrient intake Of pOstmenOpAusAL womeN. ApProxiMately 60% OF spontAneous aboRtIOns appEAr to resULT fRom cHromosome aberratiONs ASsociated with tHe

with different caffeine i ntakes hav e the  sa meor  dif fere nt rates of po s tmen opausal bone loss.In a dditi on ,  wew il l con structt he f irs tlo ngi tu d in al da tabase on  the relat ion sh ips among ha b it ual caffei neintake, gene ral  healt h,  an d  over all  nutr ient i n take o f postmen op a usal w o men. Ap p r ox imat ely 60% of sponta n eo u s abortions ap pear t or es u l t f rom  chromosom eaberr a tions a s so c i a ted with the

with_different caffeine_intakes have the same_or different_rates_of postmenopausal_bone_loss.In addition, we_will construct the_first longitudinal data base_on the relationships_among_habitual caffeine intake, general health, and overall nutrient intake of postmenopausal women. Approximately 60%_of_spontaneous abortions_appear_to_result from chromosome aberrations associated_with the


groups in a dose-dependent manner; b) Isolated control of muscles opposing spastic agonists during movement tasks and gait will be conversely improved in a dose-dependent manner; c) Functional gains, including changes in gait temporal-spatial parameters and the Global Function Scale of the PODCI, will not be

groups in a dose - dependent manner; b) Isolated restraint of muscleman opposing spastic agonists during motion tasks and gait will be conversely better in a drug - dependent manner; c) Functional gains, including changes in gait worldly - spatial parameters and the Global Function Scale of the PODCI, will not be

grlups in a dose-dependent oanner; b) Isolatgd contrml of juscles upposing spastic agonists ducing movenent tasks and gait wiul be connersely inproted in a dose-depxhdent manner; d) Funetmonal gains, inckuding chatges in gait tamooxal-spatial parameters and the Global Functipn Scale of the KODCI, rill not be

groups in a dose-dependent manner; b) Isolated muscles spastic agonists movement tasks and in dose-dependent manner; c) gains, including changes gait temporal-spatial parameters and the Global Scale of the PODCI, will not be

groups in a dose-dependent manNer; b) IsolatEd conTroL of MuScleS oppOsing spastic agONistS during movement tasks anD gait WiLL be cONvErselY improvED iN A DosE-dEpEndEnT MaNner; c) funCtional Gains, incluDinG cHanges in gait TEmPoral-spatiAl pArameters and The global fuNctIOn ScaLe oF the PoDCI, wiLL not be

groups in a dose-dependen t manner;b) Is ola ted  c ontr ol o f muscles oppo s ingspastic agonists durin g mov em e nt t a sk s and  gait w i ll b e c on ve rse ly im prove d i n a dos e-dependen t m an ner; c) Func t io nal gains,  in cluding chan ges  in ga it  te m poral -sp atial  param e ters a nd the Gl ob a l Func t ion Sca l e  o f th e PODCI, will not be

groups_in a_dose-dependent manner; b) Isolated_control of_muscles_opposing spastic_agonists_during movement tasks_and gait will_be conversely improved in_a dose-dependent manner;_c)_Functional gains, including changes in gait temporal-spatial parameters and the Global Function Scale of_the_PODCI, will_not_be


genes implicated in presenilin-related pathways will be derived from three different pools: Pool 1. Positional candidate genes mapping to established AD genetic linkage peaks, including UBQLN1, VPS26A, VPS35, VDAC1, VDAC2, NCSTN, PSEN1 and

genes implicated in presenilin - related pathways will be derive from three unlike pools: Pool 1. Positional campaigner genes map to established AD genic linkage peak, including UBQLN1, VPS26A, VPS35, VDAC1, VDAC2, NCSTN, PSEN1 and

gejes implicated in presenllin-related pathcqys winl be serived wrom three different pools: Ploo 1. Powitional candidate gends mappinh to estqbliwyed AD genxfic linkage pswks, nnrluding UBQLN1, VKS26A, VPS35, VDAC1, VDAC2, NCSTN, PSAN1 aud

genes implicated in presenilin-related pathways will be three pools: Pool Positional candidate genes linkage including UBQLN1, VPS26A, VDAC1, VDAC2, NCSTN, and

genes implicated in presenilIn-related pAthwaYs wIll Be DeriVed fRom three differENt poOls: Pool 1. Positional candiDate gEnES mapPInG to esTablishED Ad GEneTiC lInkAgE PeAks, inCluDing UBQlN1, VPS26A, VPS35, VdAC1, vDaC2, NCSTN, PSEN1 aND

genes implicated in prese nilin-rela ted p ath way swill  bederived from t h reedifferent pools: Pool1. Po si t iona l  c andid ate gen e sm a ppi ng  t o e st a bl ished  AD  geneti c linkagepea ks , includingU BQ LN1, VPS26 A,VPS35, VDAC1 , V DAC2,NC STN ,  PSEN 1 a nd

genes_implicated in_presenilin-related pathways will be_derived from_three_different pools:_Pool_1. Positional candidate_genes mapping to_established AD genetic linkage_peaks, including UBQLN1,_VPS26A,_VPS35, VDAC1, VDAC2, NCSTN, PSEN1 and


the superficial dorsal horn under normal conditions and in an animal model of neuropathic pain, and the role of inhibitory interactions in shaping these patterns of functional connectivity. These studies are motivated by the PI's recent discovery of a novel class of polymodal nociceptors with large, thickly myelinated (A[unreadable])

the superficial dorsal horn under normal conditions and in an animal model of neuropathic pain, and the function of inhibitory interaction in shaping these patterns of functional connectivity. These study are motivated by the PI's recent discovery of a fresh class of polymodal nociceptors with large, thickly myelinated (A[unreadable ] )

thf superficial dorsal hork under normal conditiois and jn an ankmal model of neuropathic pamn, abd tht role of inhibitorh interacnions in whapmng these patteria of fuketionzp counxctivity. These xtudies ara motivated by tfe PI's recent discovery of a novel clwss of lopymodal nocicektors rith large, thickly myelinated (A[unreadagle])

the superficial dorsal horn under normal conditions an model of pain, and the shaping patterns of functional These studies are by the PI's recent discovery of novel class of polymodal nociceptors with large, thickly myelinated (A[unreadable])

the superficial dorsal horn uNder normal CondiTioNs aNd In an AnimAl model of neuroPAthiC pain, and the role of inhibItory InTEracTIoNs in sHaping tHEsE PAttErNs Of fUnCTiOnal cOnnEctivitY. These studIes ArE motivated by THe pI's recent dIscOvery of a noveL clAss of pOlYmoDAl nocIcePtors With laRGe, thicKly myelinAtED (A[unreADable])

the superficial dorsal ho rn under n ormal  co ndi ti onsandin an animal m o delof neuropathic pain, a nd th er oleo finhib itory i n te r a cti on sinsh a pi ng th ese  patter ns of func tio na l connectivi t y.  These stu die s are motiva ted  by th ePI' s  rece ntdisco very o f  a nov el classof polymo d al noci c e pt orswith large, thick l ym yelinated (A[u nreada bl e ])

the_superficial dorsal_horn under normal conditions_and in_an_animal model_of_neuropathic pain, and_the role of_inhibitory interactions in shaping_these patterns of_functional_connectivity. These studies are motivated by the PI's recent discovery of a novel class_of_polymodal nociceptors_with_large,_thickly myelinated (A[unreadable])


the strongest genetic control by gene(s) within the major histocompatibility complex so far described for such a disease. Preliminary experiments suggested that monoclonal anti-Ia antibodies given before immunization of mice with mouse thyroglobulin emulsified in complete Freund's adjuvant, completely prevented the development of thyroiditis. These

the strongest genetic control by gene(s) within the major histocompatibility complex therefore far trace for such a disease. Preliminary experiments suggested that monoclonal anti - Ia antibodies yield before immunization of mice with mouse thyroglobulin emulsified in arrant Freund's accessory, completely prevented the development of thyroiditis. These

thf strongest genetic contvol by gene(s) witkun the major histocoopatibility complex so far dxscrubed dor such a disease. Preuiminary vxperimenrs snggested that moikclonal anti-Iz antnbidies given benore immunisation of mice wktk mouse thyroglobulin emulsified in sompletr Vreund's adjuvagt, cpiplefvln prevented the development of tgyroidiuis. These

the strongest genetic control by gene(s) within histocompatibility so far for such a monoclonal antibodies given before of mice with thyroglobulin emulsified in complete Freund's adjuvant, prevented the development of thyroiditis. These

the strongest genetic controL by gene(s) wiThin tHe mAjoR hIstoCompAtibility complEX so fAr described for such a disEase. PReLIminARy ExperIments sUGgESTed ThAt MonOcLOnAl antI-Ia AntibodIes given beForE iMmunization oF MiCe with mousE thYroglobulin eMulSified In ComPLete FReuNd's adJuvant, COmpletEly prevenTeD The devELopment OF ThYroiDitis. These

the strongest genetic con trol by ge ne(s)  wi thi nthemajo r histocompati b ilit y complex so far descr ibedfo r  suc h  a  dise ase. Pr e li m i nar yex per im e nt s sug ges ted tha t monoclon alan ti-Ia antibo d ie s given be for e immunizati onof mic ewit h  mous e t hyrog lobuli n  emuls ified inco m pleteF reund's a dj uvan t, completely pre v en t ed the develop ment o ft hy r o idi tis . These

the_strongest genetic_control by gene(s) within_the major_histocompatibility_complex so_far_described for such_a disease. Preliminary_experiments suggested that monoclonal_anti-Ia antibodies given_before_immunization of mice with mouse thyroglobulin emulsified in complete Freund's adjuvant, completely prevented the_development_of thyroiditis._These


can modify EIB, clarify the components and operations in some of the mechanisms for EIB, and evaluate plus develop non-pharmacological methods such as physical conditioning for the prevention and therapy of EIB. The research proposed is the first stage of a program focused on the development and critical evaluation of quantitative predictive models for

can modify EIB, clarify the components and operations in some of the mechanism for exabyte, and evaluate plus develop non - pharmacological method such as forcible conditioning for the prevention and therapy of EIB. The research proposed is the inaugural stage of a program concentrate on the development and critical evaluation of quantitative predictive models for

caj modify EIB, clarify the components and operatmons in some of the mechanisms for EIB, and xvalyate kjus develop non-phafmacologibal methoes snch as physical rknditioknng fkv the 'revention and jherapy of EHB. The researcv orlposed is the first stage of a progwam focisfd on the devejopmtnt and brltical evaluation of quantitativs predibtive models for

can modify EIB, clarify the components and some the mechanisms EIB, and evaluate as conditioning for the and therapy of The research proposed is the first of a program focused on the development and critical evaluation of quantitative predictive for

can modify EIB, clarify the comPonents and OperaTioNs iN sOme oF the Mechanisms for Eib, and Evaluate plus develop non-PharmAcOLogiCAl MethoDs such aS PhYSIcaL cOnDitIoNInG for tHe pReventiOn and theraPy oF EiB. The researcH PrOposed is thE fiRst stage of a pRogRam focUsEd oN The deVelOpmenT and crITical eValuation Of QUantitATive preDICtIve mOdels for

can modify EIB, clarify t he compone nts a ndope ra tion s in  some of the m e chan isms for EIB, and eval uatepl u s de v el op no n-pharm a co l o gic al  m eth od s  s uch a s p hysical  condition ing  f or the preve n ti on and the rap y of EIB. Th e r esearc hpro p osedisthe f irst s t age of  a progra mf ocused on thed e ve lopm ent and criticale va l uation of quan titati ve pr e d ict ive  models fo r

can_modify EIB,_clarify the components and_operations in_some_of the_mechanisms_for EIB, and_evaluate plus develop_non-pharmacological methods such as_physical conditioning for_the_prevention and therapy of EIB. The research proposed is the first stage of a_program_focused on_the_development_and critical evaluation of quantitative_predictive models for


or the inv mutant. The rovA virulence defect is characterized by reduced systemic dissemination and an increased LD50 after oral infection. Infection using the i.p. route abrogates the rovA defect, suggesting RovA is required for events occurring either in/from the intestine/colon or in the P

or the inv mutant. The rovA virulence defect is characterized by reduced systemic dissemination and an increase LD50 after oral contagion. Infection using the i.p. path abrogate the rovA defect, suggesting RovA is required for event occurring either in / from the intestine / colon or in the P

or the inv mutant. The rovA virulence defeer is ciaractedized by reduced systemic disseminatmon qnd ab increased LD50 after ofal infecnion. Infextioi using the i.p. route abrogates bhe rmtA defect, suggexting RovA is required fmr erents occurring either in/from the ineestine/vopon or in the K

or the inv mutant. The rovA virulence characterized reduced systemic and an increased using i.p. route abrogates rovA defect, suggesting is required for events occurring either the intestine/colon or in the P

or the inv mutant. The rovA viruLence defecT is chAraCteRiZed bY redUced systemic diSSemiNation and an increased LD50 After OrAL infECtIon. InFection USiNG The I.p. RoUte AbROgAtes tHe rOvA defeCt, suggestiNg ROva is required fOR eVents occurRinG either in/froM thE intesTiNe/cOLon or In tHe P

or the inv mutant. The ro vA virulen ce de fec t i schar acte rized by reduc e d sy stemic dissemination a nd an  i n crea s ed  LD50  aftero ra l inf ec ti on.  I n fe ction  us ing the  i.p. rout e a br ogates the r o vA  defect, s ugg esting RovAisrequir ed  fo r  even tsoccur ring e i ther i n/from th ei ntesti n e/colon o rin t he P

or_the inv_mutant. The rovA virulence_defect is_characterized_by reduced_systemic_dissemination and an_increased LD50 after_oral infection. Infection using_the i.p. route_abrogates_the rovA defect, suggesting RovA is required for events occurring either in/from the intestine/colon_or_in the_P


and BMP7 delivery (either i.c.v. or systemically via adenovirus) produces an anorexigenic effect, at least in part through the hypothalamic mTOR pathway and activation of the melanocortin system. However, much is still unknown about the metabolic and physiological roles of BMP signaling in

and BMP7 delivery (either i.c.v. or systemically via adenovirus) produces an anorexigenic effect, at least in character through the hypothalamic mTOR nerve pathway and activation of the melanocortin system. However, much is however obscure about the metabolic and physiological roles of BMP bespeak in

anf BMP7 delivery (either i.c.y. or systemicalli cia adxnovirua) producds an anorexigenic effect, at lwast un part through the hyoothalamib mTOR parhwab and activation of the melanodlrtiu wystem. However, much is sdill unknown atojt the metabolic and physiological rojes of NMO signaling in

and BMP7 delivery (either i.c.v. or systemically produces anorexigenic effect, least in part and of the melanocortin However, much is unknown about the metabolic and physiological of BMP signaling in

and BMP7 delivery (either i.c.v. or SystemicalLy via AdeNovIrUs) prOducEs an anorexigenIC effEct, at least in part througH the hYpOThalAMiC mTOR Pathway ANd ACTivAtIoN of ThE MeLanocOrtIn systeM. However, muCh iS sTill unknown aBOuT the metaboLic And physiologIcaL roles Of bMP SIgnalIng In

and BMP7 delivery (either  i.c.v. or  syst emi cal ly  via  ade novirus) produ c es a n anorexigenic effect,  at l ea s t in pa rt th rough t h eh y pot ha la mic  m T OR  path way  and ac tivation o f t he  melanocorti n  s ystem. How eve r, much is s til l unkn ow n a b out t hemetab olic a n d phys iological  r o les of BMP sig n a li ng i n

and_BMP7 delivery_(either i.c.v. or systemically_via adenovirus)_produces_an anorexigenic_effect,_at least in_part through the_hypothalamic mTOR pathway and_activation of the_melanocortin_system. However, much is still unknown about the metabolic and physiological roles of BMP_signaling_in


) To increase, through iterative optimizations selectivity, potency and drug-likeness of selected LF inhibitors. (II) To perform in vitro and in cell toxicity studies to refine hits and identify drug-like inhibitor(s) of LF for subsequent in vivo studies. (Ill) To perform in vivo efficacy evaluations and

) To increase, through iterative optimizations selectivity, potency and drug - likeness of selected LF inhibitors. (II) To do in vitro and in cellular telephone perniciousness studies to refine hits and name drug - like inhibitor(s) of LF for subsequent in vivo studies. (Ill) To perform in vivo efficacy evaluations and

) To increase, through iteratlve optimizations selecvivity, lotency xnd drug-likeness of selected LD inhubitors. (II) To perform kn vitro wnd in cwll uoxicity studies vk refinc hita and mdentify drug-lile inhibitmr(s) of LF for vucszquent in vivo studies. (Ill) To perfori in vifo efficacy evaloatiomf ans

) To increase, through iterative optimizations selectivity, drug-likeness selected LF (II) To perform toxicity to refine hits identify drug-like inhibitor(s) LF for subsequent in vivo studies. To perform in vivo efficacy evaluations and

) To increase, through iterativE optimizatIons sEleCtiViTy, poTencY and drug-likeneSS of sElected LF inhibitors. (II) TO perfOrM In viTRo And in Cell toxICiTY StuDiEs To rEfINe Hits aNd iDentify Drug-like inHibItOr(s) of LF for suBSeQuent in vivO stUdies. (Ill) To peRfoRm in viVo EffICacy eValUatioNs and

) To increase, through ite rative opt imiza tio nsse lect ivit y, potency and drug -likeness of selectedLF in hi b itor s .(II)To perf o rm i n v it ro  an di ncelltox icity s tudies toref in e hits and i d en tify drug- lik e inhibitor( s)of LFfo r s u bsequ ent  in v ivo st u dies.(Ill) Tope r form i n  vivo e f f ic acyevaluations and

) To_increase, through_iterative optimizations selectivity, potency_and drug-likeness_of_selected LF_inhibitors._(II) To perform_in vitro and_in cell toxicity studies_to refine hits_and_identify drug-like inhibitor(s) of LF for subsequent in vivo studies. (Ill) To perform in_vivo_efficacy evaluations_and


of physical function and inflammation. Specifically, this project will (1) determine whether the presence and severity (number of components) of MetS is associated with lower physical function at baseline and with a decline in physical function over time in older adults; (2) determine whether the presence and severity of MetS is associated with

of physical function and inflammation. Specifically, this project will (1) settle whether the bearing and severity (number of component) of MetS is consort with lower physical routine at service line and with a decline in physical function over time in older adult; (2) determine whether the presence and asperity of MetS is consociate with

of physical function and ikflammation. Specndicallb, this lroject dill (1) determine whether the 'reswnce qnd severity (number of componenns) of MetW is qssociated with lower phgdican function at bsseline ang with a declite iu physical function over time in oldqr adulys; (2) determine whgther ehe lgewence and severity of MetS is associeted with

of physical function and inflammation. Specifically, this (1) whether the and severity (number associated lower physical function baseline and with decline in physical function over time older adults; (2) determine whether the presence and severity of MetS is associated

of physical function and inflAmmation. SpEcifiCalLy, tHiS proJect Will (1) determine wHEtheR the presence and severitY (numbEr OF comPOnEnts) oF MetS is ASsOCIatEd WiTh lOwER pHysicAl fUnction At baseline And WiTh a decline in PHySical functIon Over time in olDer Adults; (2) DeTerMIne whEthEr the PresenCE and seVerity of MEts Is assoCIated wiTH

of physical function andinflammati on. S pec ifi ca lly,  thi s project will (1)determine whether theprese nc e  and se verit y (numb e ro f  co mp on ent s) of  MetS  is  associ ated withlow er  physical fu n ct ion at bas eli ne and witha d ecline  i n p h ysica l f uncti on ove r  timein olderad u lts; ( 2 ) deter m i ne  whe ther the presence an d  severity of M etS is  a s so c i ate d w ith

of_physical function_and inflammation. Specifically, this_project will_(1)_determine whether_the_presence and severity_(number of components)_of MetS is associated_with lower physical_function_at baseline and with a decline in physical function over time in older adults;_(2)_determine whether_the_presence_and severity of MetS is_associated with


prostasin in chronic infection. Epithelial integrity and hydrafion is essenfial for defense against microbes and toxins. Failure of barrier funcfion leads to chronic infection and remodeling, as in cystic fibrosis. Aim 1 studies test the hypothesis that prostasin support of ainway ion flux and integrity is

prostasin in chronic infection. Epithelial integrity and hydrafion is essenfial for defense against microbes and toxins. bankruptcy of barrier funcfion go to chronic infection and remodeling, as in cystic fibrosis. Aim 1 report quiz the hypothesis that prostasin support of ainway ion flux density and integrity is

prlstasin in chronic infecuion. Epithelial iuregritb and hgdrafion is essenfial for defense ageinsr miceobes and toxins. Failufe of bargier funcdion oeads to cidonic ikyectikk and cemodeling, as ik cystic fitrosis. Aim 1 stgdked test the hypothesis that prostasig suppott of ainway ion fluq wnd jntegrity is

prostasin in chronic infection. Epithelial integrity and essenfial defense against and toxins. Failure chronic and remodeling, as cystic fibrosis. Aim studies test the hypothesis that prostasin of ainway ion flux and integrity is

prostasin in chronic infectiOn. EpitheliAl intEgrIty AnD hydRafiOn is essenfial fOR defEnse against microbes and ToxinS. FAIlurE Of BarriEr funcfIOn LEAds To ChRonIc INfEctioN anD remodeLing, as in cyStiC fIbrosis. Aim 1 stUDiEs test the hYpoThesis that prOstAsin suPpOrt OF ainwAy iOn fluX and inTEgrity Is

prostasin in chronic infe ction. Epi theli alint eg rity  and  hydrafion ise ssen fial for defense again st mi cr o besa nd  toxi ns. Fai l ur e ofba rr ier  f u nc fionlea ds to c hronic inf ect io n and remode l in g, as in c yst ic fibrosis.  Ai m 1 st ud ies testthe  hypo thesis that p rostasinsu p port o f  ainway i on  flu x and integrity i s

prostasin_in chronic_infection. Epithelial integrity and_hydrafion is_essenfial_for defense_against_microbes and toxins._Failure of barrier_funcfion leads to chronic_infection and remodeling,_as_in cystic fibrosis. Aim 1 studies test the hypothesis that prostasin support of ainway_ion_flux and_integrity_is


analyzing interactions between persisting antigen, antibody and the various cell types involved in the immune response in vivo, in vitro model systems have been developed which are amenable to manipulation and yet accurately reproduce phenomena observed in vivo. The aggregated human serum albumin (HSA) antigen used in this system appears to persist in rabbits for at least

analyzing interactions between persisting antigen, antibody and the various cellular telephone type involved in the immune response in vivo, in vitro exemplar system have been developed which are amenable to manipulation and however accurately regurgitate phenomena observed in vivo. The aggregated human serum albumin (HSA) antigen used in this system appear to persist in rabbits for at least

anwlyzing interactions betdeen persisting antigei, antibkdy and ghe various cell types involted un tht immune response iv vivo, in vitro midel wystems hats been develolcd whnci are amenable jo manipulathon and yet acwufacely reproduce phenomena observed in vivo. Tne aggregated huian xqrum albumin (HSA) antigen used in this aystem eppears to persost in rabbits for at leash

analyzing interactions between persisting antigen, antibody and cell involved in immune response in have developed which are to manipulation and accurately reproduce phenomena observed in vivo. aggregated human serum albumin (HSA) antigen used in this system appears to persist rabbits for at least

analyzing interactions betwEen persistIng anTigEn, aNtIbodY and The various cell TYpes Involved in the immune resPonse In VIvo, iN ViTro moDel systEMs HAVe bEeN dEveLoPEd Which Are AmenablE to manipulAtiOn And yet accuraTElY reproduce PheNomena observEd iN vivo. THe AggREgateD huMan seRum albUMin (HSA) Antigen usEd IN this sYStem appEARs To peRsist in rabbits for AT lEAst

analyzing interactions be tween pers istin g a nti ge n, a ntib ody and the va r ious  cell types involved i n the  i m mune re spons e in vi v o, i n v it ro  mo de l  s ystem s h ave bee n develope d w hi ch are amena b le  to manipu lat ion and yetacc uratel yrep r oduce  ph enome na obs e rved i n vivo. T he aggreg a ted hum a n  s erum  albumin (HSA) an t ig e n used in this  syste ma pp e a rstopersist in  r abbit s  for at le a s t

analyzing_interactions between_persisting antigen, antibody and_the various_cell_types involved_in_the immune response_in vivo, in_vitro model systems have_been developed which_are_amenable to manipulation and yet accurately reproduce phenomena observed in vivo. The aggregated human_serum_albumin (HSA)_antigen_used_in this system appears to_persist in rabbits for at_least


marriage) and self-efficacy influence good diabetes management in middle-aged and older adults living with diabetes may be key to developing and testing interventions that provide more effective supports, and all the more important to married couples because spouses may be at higher risk for developing diabetes themselves if their partner has diabetes.! Project Summary Exposure to

marriage) and self - efficacy influence good diabetes management in middle - aged and older adults living with diabetes may be cardinal to modernize and testing interventions that leave more effective support, and all the more important to married couple because spouse may be at higher risk for developing diabetes themselves if their partner has diabetes. ! Project Summary Exposure to

magriage) and self-efficacy lnfluence good dnqbetes managsment in middle-aged and older adults luving with diabetes may be yey to deneloping qnd uesting interventmkns thab problde mmce effective sukports, and anl the more im[oftcnt to married couples because spousqs may ne at higher rish fog qevemoping diabetes themselves if theid partntr has diabetes.! Prpject Summary Exposure to

marriage) and self-efficacy influence good diabetes management and adults living diabetes may be interventions provide more effective and all the important to married couples because spouses be at higher risk for developing diabetes themselves if their partner has diabetes.! Summary Exposure to

marriage) and self-efficacy inFluence gooD diabEteS maNaGemeNt in Middle-aged and oLDer aDults living with diabeteS may bE kEY to dEVeLopinG and tesTInG INteRvEnTioNs THaT provIde More effEctive suppOrtS, aNd all the more IMpOrtant to maRriEd couples becAusE spousEs May BE at hiGheR risk For devELoping Diabetes tHeMSelves IF their pARTnEr haS diabetes.! Project SUMmARy Exposure to

marriage) and self-effica cy influen ce go oddia be tesmana gement in midd l e-ag ed and older adults li vingwi t h di a be tes m ay be k e yt o  de ve lo pin ga nd  test ing  interv entions th atpr ovide more e f fe ctive supp ort s, and all t hemore i mp ort a nt to  ma rried  coupl e s beca use spous es may be at high e r  r iskfor developing di a be t es themselvesif the ir pa r t ner  ha s diabetes .!  Proj e ct Summ a ry E x pos u re to

marriage)_and self-efficacy_influence good diabetes management_in middle-aged_and_older adults_living_with diabetes may_be key to_developing and testing interventions_that provide more_effective_supports, and all the more important to married couples because spouses may be at_higher_risk for_developing_diabetes_themselves if their partner has_diabetes.! Project Summary Exposure to


Project 4 takes advantage of the advances in optical imaging to develop quantitative tools to monitor molecular features of tumors and their response to treatment, and to integrate them for the development of molecular-based combination therapies for standard clinical procedures. The proposed program will feature three cores that will provide support in three areas: Core A, through administration

Project 4 takes advantage of the advances in optical imaging to originate quantitative creature to monitor molecular features of tumors and their response to discussion, and to integrate them for the development of molecular - based combination therapy for standard clinical procedure. The proposed plan will feature three cores that will leave support in three areas: Core A, through presidency

Prlject 4 takes advantage on the advances iu opticel imagjng to ddvelop quantitative tools to minitoe molecular features ow tumors wnd theie rewponse to tcsatment, and tk intzgcate them for tme developmant of moleculdr-caded combination therapies for standwrd climifal procedures. The [ropksed program will feature three codes thau will provide suplort in three areas: Core A, thrlugh administratioj

Project 4 takes advantage of the advances imaging develop quantitative to monitor molecular response treatment, and to them for the of molecular-based combination therapies for standard procedures. The proposed program will feature three cores that will provide support in areas: Core A, through administration

Project 4 takes advantage of thE advances iN optiCal ImaGiNg to DeveLop quantitativE ToolS to monitor molecular feaTures Of TUmorS AnD theiR responSE tO TReaTmEnT, anD tO InTegraTe tHem for tHe developmEnt Of Molecular-basED cOmbination TheRapies for staNdaRd clinIcAl pROceduRes. the prOposed PRogram Will featuRe THree coREs that wILL pRoviDe support in three aREaS: core A, through adMinistRaTIoN

Project 4 takes advantage  of the ad vance s i n o pt ical  ima ging to develo p  qua ntitative tools to mon itormo l ecul a rfeatu res oft um o r s a nd  t hei rr es ponse  to  treatm ent, and t o i nt egrate themf or  the devel opm ent of molec ula r-base dcom b inati onthera pies f o r stan dard clin ic a l proc e dures.T h eprop osed program will fe a ture three cor es tha tw il l pro vid e supportin  thre e  areas: Co r e A,t hrough admini stration

Project_4 takes_advantage of the advances_in optical_imaging_to develop_quantitative_tools to monitor_molecular features of_tumors and their response_to treatment, and_to_integrate them for the development of molecular-based combination therapies for standard clinical procedures. The_proposed_program will_feature_three_cores that will provide support_in three areas: Core A,_through administration


;(ii) fiscal oversight (budgeting, purchasing);(iii) communication and coordination of data flow;(iv) seminar series coordination and travel arrangements;and (v)preparation of manuscripts and reports. The second purpose of this core component is to closely monitor the activities of the Cox-7 Animal Col

; (ii) fiscal oversight (budgeting, purchasing);(iii) communication and coordination of data flow;(iv) seminar series coordination and travel arrangements;and (v)preparation of manuscript and report. The second purpose of this core component is to close monitor the activities of the Cox-7 Animal Col

;(ii) viscal oversight (budgetikg, purchasing);(iii) communmcation and coofdination of data flow;(iv) semmnar seritf coordination and travel agrangemenrs;anv (v)preparation oh manuscvnpts zkd re'octs. The second kurpose of tvis core compotevt is to closely monitor the activitiqs of tne Cox-7 Animal Coj

;(ii) fiscal oversight (budgeting, purchasing);(iii) communication and data seminar series and travel arrangements;and The purpose of this component is to monitor the activities of the Cox-7 Col

;(ii) fiscal oversight (budgetinG, purchasinG);(iii) cOmmUniCaTion And cOordination of dATa flOw;(iv) seminar series coordInatiOn ANd trAVeL arraNgementS;AnD (V)PrePaRaTioN oF MaNuscrIptS and repOrts. The secOnd PuRpose of this cORe Component iS to Closely monitOr tHe actiViTieS Of the cox-7 animaL Col

;(ii) fiscal oversight (bu dgeting, p urcha sin g); (i ii)comm unication andc oord ination of data flow;( iv) s em i nars er ies c oordina t io n and  t ra vel  a r ra ngeme nts ;and (v )preparati onof  manuscripts an d reports.  Th e second pur pos e of t hi s c o re co mpo nentis toc losely  monitorth e  activ i ties of t he  Cox -7 Animal Col

;(ii) fiscal_oversight (budgeting,_purchasing);(iii) communication and coordination_of data_flow;(iv)_seminar series_coordination_and travel arrangements;and_(v)preparation of manuscripts_and reports. The second_purpose of this_core_component is to closely monitor the activities of the Cox-7 Animal Col


and evaluation of the intervention with regard to changes in knowledge, attitudes, and behavior. PROPOSED COMMERCIAL APPLICATIONS With the phenomenal growth of home computer purchases, potential markets of the proposed software include families with adolescents as well as schools. In a school environment, the program could be integrated with existing school sexuality

and evaluation of the intervention with regard to changes in knowledge, attitude, and demeanor. PROPOSED COMMERCIAL APPLICATIONS With the phenomenal growth of base calculator purchases, potential markets of the propose software include families with adolescent equally well as schools. In a school environment, the program could be integrate with existing school sexuality

anf evaluation of the intevvention with reyqrd to changss in knuwledge, attitudes, and behavilr. PROPISED COMMERCIAL APPLICXTIONS Winh the phwnomtnal growth of home compubzr pudghasev, potential marlets of tha proposed sofdwxrz include families with adolescents ws well ad schools. In a schpjl ehnivonment, the program could be intsgrated with existinb school sexuality

and evaluation of the intervention with regard in attitudes, and PROPOSED COMMERCIAL APPLICATIONS home purchases, potential markets the proposed software families with adolescents as well as In a school environment, the program could be integrated with existing school sexuality

and evaluation of the interveNtion with rEgard To cHanGeS in kNowlEdge, attitudes, aND behAvior. PROPOSED COMMERCIAl APPLiCatIONs wiTh the PhenomeNAl GROwtH oF hOme CoMPuTer puRchAses, potEntial markEts Of The proposed sOFtWare includE faMilies with adOleScents As WelL As schOolS. In a sChool eNVironmEnt, the proGrAM could BE integrATEd With Existing school sexUAlITy

and evaluation of the int erventionwithreg ard  t o ch ange s in knowledge ,  att itudes, and behavior.PROPO SE D  COM M ER CIALAPPLICA T IO N S  Wi th  t heph e no menal  gr owth of  home comp ute rpurchases, p o te ntial mark ets  of the prop ose d soft wa rei nclud e f amili es wit h  adole scents as  w e ll ass chools. I na sc hool environment, th e  program could  be in te g ra t e d w ith  existingsc hools exualit y

and_evaluation of_the intervention with regard_to changes_in_knowledge, attitudes,_and_behavior. PROPOSED COMMERCIAL_APPLICATIONS With the_phenomenal growth of home_computer purchases, potential_markets_of the proposed software include families with adolescents as well as schools. In a_school_environment, the_program_could_be integrated with existing school_sexuality


mainstream of the nation's scientific community. To this end, the Program will continue to recruit highly talented students and provide them with a mentored intramural research experience that includes a well-defined project that leads to results which will be presented at scientific meetings or published and which will be described in a tesina. Em

mainstream of the nation's scientific community. To this end, the Program will continue to enroll highly talented student and provide them with a mentored intramural research experience that include a well - define project that leads to resultant role which will be present at scientific meetings or print and which will be described in a tesina. Em

malnstream of the nation's rcientific commonuty. To this snd, the Orogram will continue to reccuit highoy talented students avd providv them wirh a nentored iiframural resezvch erpxrience that ingludes a wenl-defined projacg chat leads to results which will be [resentrd at scientific meeuinds od published and which will be descdibed ii a tesina. Em

mainstream of the nation's scientific community. To the will continue recruit highly talented a intramural research experience includes a well-defined that leads to results which will presented at scientific meetings or published and which will be described in a Em

mainstream of the nation's sciEntific comMunitY. To ThiS eNd, thE ProGram will continUE to rEcruit highly talented stUdentS aND proVIdE them With a meNToRED inTrAmUraL rESeArch eXpeRience tHat includeS a wElL-defined projECt That leads tO reSults which wiLl bE preseNtEd aT ScienTifIc meeTings oR PublisHed and whiCh WIll be dEScribed IN A tEsinA. Em

mainstream of the nation' s scientif ic co mmu nit y.  Tothis  end, the Prog r am w ill continue to recrui t hig hl y  tal e nt ed st udentsa nd p rov id ethe mw it h a m ent ored in tramural r ese ar ch experienc e  t hat includ esa well-defin edprojec ttha t  lead s t o res ults w h ich wi ll be pre se n ted at scienti f i cmeet ings or published an d  which will be  descr ib e di n  ates ina. Em

mainstream_of the_nation's scientific community. To_this end,_the_Program will_continue_to recruit highly_talented students and_provide them with a_mentored intramural research_experience_that includes a well-defined project that leads to results which will be presented at_scientific_meetings or_published_and_which will be described in_a tesina. Em


. This aim will test the hypothesis that actin is the major component influencing anisotropic cellular response to 3D confinement. Biochemical inhibitors and siRNA will be used to target specific cytoskeletal functions. The spatial organization and anisotropy of cytoskeletal assembly and matrix deposition will be evaluated for each treatment group using pairs of 3D shapes that have

. This aim will test the hypothesis that actin is the major component charm anisotropic cellular reception to 3D confinement. Biochemical inhibitors and siRNA will be used to target specific cytoskeletal function. The spatial organization and anisotropy of cytoskeletal assembly and matrix deposit will be evaluated for each treatment group using pair of 3D shapes that have

. Thls aim will test the hyputhesis that acjib is tie majod compondnt influencing anisotropic rellylar eesponse to 3D confinemdnt. Biochvmical inyibiuors and siRNA will be uscb to fwrgec wpecific cytosleletal futctions. The spdtkap organization and anisotropy of cyeoskeleyap assembly and matgiv delosition will be evaluated for eacg treatkent group usong pairs of 3D shapes that havf

. This aim will test the hypothesis is major component anisotropic cellular response and will be used target specific cytoskeletal The spatial organization and anisotropy of assembly and matrix deposition will be evaluated for each treatment group using pairs 3D shapes that have

. This aim will test the hypotheSis that actIn is tHe mAjoR cOmpoNent Influencing aniSOtroPic cellular response to 3D ConfiNeMEnt. BIOcHemicAl inhibIToRS And SirNa wiLl BE uSed to TarGet specIfic cytoskEleTaL functions. ThE SpAtial organIzaTion and anisoTroPy of cyToSkeLEtal aSseMbly aNd matrIX deposItion will Be EValuatED for eacH TReAtmeNt group using pairs OF 3D SHapes that have

. This aim will test the h ypothesisthatact inis  the  maj or component i n flue ncing anisotropic cell ularre s pons e  t o 3Dconfine m en t .  Bi oc he mic al in hibit ors  and si RNA will b e u se d to targets pe cific cyto ske letal functi ons . Thesp ati a l org ani zatio n anda nisotr opy of cy to s keleta l  assemb l y  a nd m atrix depositionw il l  be evaluatedfor ea ch tr e a tme ntgroup usin gpairs of 3D s h ap e s tha t  have

. This_aim will_test the hypothesis that_actin is_the_major component_influencing_anisotropic cellular response_to 3D confinement._Biochemical inhibitors and siRNA_will be used_to_target specific cytoskeletal functions. The spatial organization and anisotropy of cytoskeletal assembly and matrix_deposition_will be_evaluated_for_each treatment group using pairs_of 3D shapes that have


than 04) on the Behavior Checklist. Further analysis will establish the predictive accuracy of the screening procedure as it relates to measures of the child's functioning at follow-up. Recommendations for screening policy, as well as for providing identified service needs, will be made after the data is analyzed. The Howard University Graduate School

than 04) on the Behavior Checklist. Further analysis will establish the predictive accuracy of the screening procedure as it relate to measuring stick of the child's functioning at follow - up. recommendation for screen policy, as well as for providing identify serve needs, will be make after the data is analyzed. The Howard University Graduate School

thwn 04) on the Behavior Checylist. Further auqlysis will sstablisf the predictive accuracy of tye sceeening procedure as ig relates to measyres if the child's funcbnoninf at yoolow-up. Recommekdations fos screening ponizy, as well as for providing identifieq servive needs, will be madt aster nht data is analyzed. The Howard Unibersity Graduate Schpol

than 04) on the Behavior Checklist. Further establish predictive accuracy the screening procedure of child's functioning at Recommendations for screening as well as for providing identified needs, will be made after the data is analyzed. The Howard University Graduate

than 04) on the Behavior ChecklisT. Further anAlysiS wiLl eStAbliSh thE predictive accURacy Of the screening procedurE as it ReLAtes TO mEasurEs of the CHiLD'S fuNcTiOniNg AT fOllow-Up. REcommenDations for ScrEeNing policy, as WElL as for provIdiNg identified SerVice neEdS, wiLL be maDe aFter tHe data IS analyZed. The HowArD univerSIty GradUATe schoOl

than 04) on the BehaviorChecklist.  Furt her  an al ysis  wil l establish th e  pre dictive accuracy of th e scr ee n ingp ro cedur e as it re l a tes  t omea su r es  of t hechild's  functioni ngat  follow-up.R ec ommendatio nsfor screenin g p olicy,  a s w e ll as  fo r pro viding identi fied serv ic e  needs ,  will b e ma de a fter the data isa na l yzed. The Howa rd Uni ve r si t y  Gr adu ate School

than_04) on_the Behavior Checklist. Further_analysis will_establish_the predictive_accuracy_of the screening_procedure as it_relates to measures of_the child's functioning_at_follow-up. Recommendations for screening policy, as well as for providing identified service needs, will_be_made after_the_data_is analyzed. The Howard University_Graduate School


-based set of strategies, the Healthy Eating and Physical Activity (HEPA) Strategies, to optimize the implementation of the Standards. Our objective here is to evaluate the impact of HEPA Strategies on achieving the Healthy Eating and Physical Activity Standards and the associated costs with using the HEPA Strategies. To accomplish this

-based set of strategies, the Healthy Eating and Physical Activity (HEPA) Strategies, to optimize the implementation of the Standards. Our aim here is to measure the shock of HEPA Strategies on achieve the Healthy Eating and Physical Activity Standards and the associated monetary value with using the HEPA Strategies. To carry through this

-basfd set of strategies, the Healthy Eating and Phbsical Zctivity (HEPA) Strategies, to optimize tye imkjementation of the Standardd. Our obhectmve here is to etzluate bke imlwct mh HEPA Strategigs on achievhng the Healthf Dacing and Physical Activity Standards and thr wssociated cosjs wiuh tsinf the HEPA Strategies. To accomplisg this

-based set of strategies, the Healthy Eating Activity Strategies, to the implementation of is evaluate the impact HEPA Strategies on the Healthy Eating and Physical Activity and the associated costs with using the HEPA Strategies. To accomplish this

-based set of strategies, the HeAlthy EatinG and PHysIcaL ACtivIty (HePA) Strategies, tO OptiMize the implementation oF the STaNDardS. ouR objeCtive heRE iS TO evAlUaTe tHe IMpAct of hEPa StrateGies on achiEviNg The Healthy EaTInG and PhysicAl ACtivity StandArdS and thE aSsoCIated CosTs witH using THe HEPA strategieS. TO AccompLIsh this

-based set of strategies,the Health y Eat ing  an dPhys ical  Activity (HEP A ) St rategies, to optimizethe i mp l emen t at ion o f the S t an d a rds .Ou r o bj e ct ive h ere  is toevaluate t heim pact of HEPA St rategies o n a chieving the  He althyEa tin g  andPhy sical  Activ i ty Sta ndards an dt he ass o ciatedc o st s wi th using the HEPA St r ategies. To ac compli sh th i s

-based set_of strategies,_the Healthy Eating and_Physical Activity_(HEPA)_Strategies, to_optimize_the implementation of_the Standards. Our_objective here is to_evaluate the impact_of_HEPA Strategies on achieving the Healthy Eating and Physical Activity Standards and the associated_costs_with using_the_HEPA_Strategies. To accomplish this


in the U.S., >6,000 of which are caused by multidrug resistant strains. To identify Pseudomonas T3SS inhibitors and potential future therapeutics, we will carry out the following aims. In Aim 1, we will implement our primary screen and counterscreens to identify natural product fractions and synthetic compounds with

in the U.S., > 6,000 of which are caused by multidrug resistant strains. To identify Pseudomonas T3SS inhibitor and likely future remedy, we will carry out the following aims. In Aim 1, we will follow through our primary screen and counterscreens to name natural product fractions and man-made compounds with

in the U.S., >6,000 of which are camsed by multidruy resisvant stdains. To identify Pseudomonas T3SS iniibirors qnd potential future tferapeutibs, we wilo cacry out the following aims. In Zlm 1, wz xill implement pur primarf screen and cmuvtzrscreens to identify natural produce fractoojs and synthetyc cpipouhds with

in the U.S., >6,000 of which are multidrug strains. To Pseudomonas T3SS inhibitors will out the following In Aim 1, will implement our primary screen and to identify natural product fractions and synthetic compounds with

in the U.S., >6,000 of which are caused by Multidrug rEsistAnt StrAiNs. To IdenTify PseudomonaS t3SS iNhibitors and potential fUture ThERapeUTiCs, we wIll carrY OuT THe fOlLoWinG aIMs. in Aim 1, We wIll implEment our prImaRy Screen and couNTeRscreens to IdeNtify natural ProDuct frAcTioNS and sYntHetic CompouNDs with

in the U.S., >6,000 of wh ich are ca usedbymul ti drug  res istant strains .  Toidentify Pseudomonas T 3SS i nh i bito r sand p otentia l  f u t ure  t he rap eu t ic s, we  wi ll carr y out thefol lo wing aims. I n  A im 1, we w ill  implement o urprimar yscr e en an d c ounte rscree n s to i dentify n at u ral pr o duct fr a c ti onsand synthetic com p ou n ds with

in_the U.S.,_>6,000 of which are_caused by_multidrug_resistant strains._To_identify Pseudomonas T3SS_inhibitors and potential_future therapeutics, we will_carry out the_following_aims. In Aim 1, we will implement our primary screen and counterscreens to identify_natural_product fractions_and_synthetic_compounds with


due to the fact that they are rapidly metabolized. Within a few hours after administration most of the dose retained by the body was in the form of metabolites. These compounds were eliminated in both urine and feces, p-nitroaniline primarily in urine, and whole body half-lives for both compounds were less

due to the fact that they are rapidly metabolized. Within a few hours after administration most of the venereal disease retain by the body was in the form of metabolites. These compound were eliminated in both urine and feces, phosphorus - nitroaniline primarily in urine, and whole body half - liveliness for both compounds were less

duf to the fact that they xre rapidly metcvolizev. Withih a few fours after administration mlsr of uke dose retained by ghe body aas in tye fiem of metauklites. Bkese dlmpobnvs were eliminajed in both grine and fecev, o-nntroaniline primarily in urine, and wrole bocy half-lives for botn comlounds were less

due to the fact that they are Within few hours administration most of body in the form metabolites. These compounds eliminated in both urine and feces, primarily in urine, and whole body half-lives for both compounds were less

due to the fact that they are raPidly metabOlizeD. WiThiN a Few hOurs After administrATion Most of the dose retained bY the bOdY Was iN ThE form Of metabOLiTES. ThEsE cOmpOuNDs Were eLimInated iN both urine And FeCes, p-nitroaniLInE primarily In uRine, and whole BodY half-lIvEs fOR both ComPoundS were lESs

due to the fact that they  are rapid ly me tab oli ze d. W ithi n a few hoursa fter  administration most o f the  d o se r e ta inedby theb od y was  i nthe  f o rm  of m eta bolites . These co mpo un ds were elim i na ted in bot h u rine and fec es,  p-nit ro ani l ine p rim arily  in ur i ne, an d whole b od y  half- l ives fo r bo th c ompounds were les s

due_to the_fact that they are_rapidly metabolized._Within_a few_hours_after administration most_of the dose_retained by the body_was in the_form_of metabolites. These compounds were eliminated in both urine and feces, p-nitroaniline primarily in_urine,_and whole_body_half-lives_for both compounds were less


PPIB function in a collaboration with investigators at Hebrew University in Jerusalem. CyPB was shown to be critical to the folding of presenilin-1, a protein linked to familial Alzheimers Disease. Some substitutions in presenilin-1 make it resistant to folding properly by CyPB. Conversely, the brains

PPIB function in a collaboration with investigators at Hebrew University in Jerusalem. CyPB was shown to be critical to the folding of presenilin-1, a protein connect to familial Alzheimers Disease. Some substitution in presenilin-1 make it resistant to folding by rights by CyPB. Conversely, the brains

PPLB function in a collabovation with investigatocs at Hsbrew Unkversity in Jerusalem. CyPB wes syown uj be critical to tfe foldinh of prewenioun-1, a protemh linked to fzlilicl Alzheimers Dixease. Some substitutions iv 'resenilin-1 make it resistant to foldyng prolegly by CyPB. Cogverxqly, fhe brains

PPIB function in a collaboration with investigators University Jerusalem. CyPB shown to be presenilin-1, protein linked to Alzheimers Disease. Some in presenilin-1 make it resistant to properly by CyPB. Conversely, the brains

PPIB function in a collaboratIon with invEstigAtoRs aT HEbreW UniVersity in JerusALem. CYPB was shown to be criticaL to thE fOLdinG Of PreseNilin-1, a pROtEIN liNkEd To fAmILiAl AlzHeiMers DisEase. Some suBstItUtions in presENiLin-1 make it rEsiStant to foldiNg pRoperlY bY Cypb. ConvErsEly, thE brainS

PPIB function in a collab oration wi th in ves tig at orsat H ebrew Universi t y in  Jerusalem. CyPB was s hownto be c r it icalto thef ol d i ngof  p res en i li n-1,a p roteinlinked tofam il ial Alzheime r sDisease. S ome  substitutio nsin pre se nil i n-1 m ake  it r esista n t to f olding pr op e rly by CyPB. C o n ve rsel y, the brains

PPIB_function in_a collaboration with investigators_at Hebrew_University_in Jerusalem._CyPB_was shown to_be critical to_the folding of presenilin-1,_a protein linked_to_familial Alzheimers Disease. Some substitutions in presenilin-1 make it resistant to folding properly by_CyPB._Conversely, the_brains


accharides architectures and their interactions with solvent and solute molecules as well as the synergistic interactions in mixed polysaccharide systems. In this ongoing study, we chose a number of biologically important and industrial useful polysaccharides, such as specimens from algal (iota-, kappa- and lambda-carrageenans);bacterial

accharides architectures and their interactions with solvent and solute molecules equally well as the synergetic interaction in mixed polysaccharide system. In this ongoing report, we chose a number of biologically significant and industrial useful polysaccharides, such as specimen from algal (iota-, kappa- and lambda - carrageenans);bacterial

accjarides architectures ana their interacjiins wivh solvsnt and rolute molecules as well as vhe wynertistic interactions in mixed popysacchaeide wystems. In this onnjing dtudv, xe chose a numbgr of biologhcally importatt aud industrial useful polysaccharides, such ax dpecimens from algsj (iofa-, kappa- and lambda-carrageenans);bacferial

accharides architectures and their interactions with solvent molecules well as synergistic interactions in ongoing we chose a of biologically important industrial useful polysaccharides, such as specimens algal (iota-, kappa- and lambda-carrageenans);bacterial

accharides architectures anD their inteRactiOns WitH sOlveNt anD solute moleculES as wEll as the synergistic intEractIoNS in mIXeD polySaccharIDe SYSteMs. in ThiS oNGoIng stUdy, We chose A number of bIolOgIcally importANt And industrIal Useful polysaCchArides, SuCh aS SpeciMenS from Algal (iOTa-, kappA- and lambdA-cARrageeNAns);bactERIaL

accharides architectures a nd their i ntera cti ons  w ithsolv ent and solute mole cules as well as the s ynerg is t ic i n te racti ons inm ix e d  po ly sa cch ar i de  syst ems . In th is ongoing  st ud y, we chosea  n umber of b iol ogically imp ort ant an dind u stria l u seful  polys a cchari des, such  a s  speci m ens fro m al gal(iota-, kappa- an d  l a mbda-carrageen ans);b ac t er i a l

accharides architectures_and their_interactions with solvent and_solute molecules_as_well as_the_synergistic interactions in_mixed polysaccharide systems._In this ongoing study,_we chose a_number_of biologically important and industrial useful polysaccharides, such as specimens from algal (iota-, kappa-_and_lambda-carrageenans);bacterial


spectra. Based on the Time-Averaged SC-IVR implementation of Kaledin and Miller, we calculate the power spectra from a single trajectory obtained via Born-Oppenheimer Molecular Dynamics. My job is to perform BOMD calculations with Q-Chem. Other than positions, energy and momenta, SC

spectra. Based on the Time - Averaged SC - IVR implementation of Kaledin and Miller, we calculate the power spectrum from a individual trajectory obtained via Born - Oppenheimer Molecular Dynamics. My job is to perform BOMD calculation with Q - Chem. Other than positions, department of energy and momenta, SC

spfctra. Based on the Time-Ayeraged SC-IVR imklwmentavion of Kaledin and Miller, we calculate the piwer wpectra from a single grajectorj obtainee vie Born-Oppenheimec Molecular Dyhwmicv. My job is to kerform BOMD calculations figh Q-Chem. Other than positions, energy wnd momrnha, SC

spectra. Based on the Time-Averaged SC-IVR implementation and we calculate power spectra from Born-Oppenheimer Dynamics. My job to perform BOMD with Q-Chem. Other than positions, energy momenta, SC

spectra. Based on the Time-AverAged SC-IVR iMplemEntAtiOn Of KaLediN and Miller, we caLCulaTe the power spectra from a SinglE tRAjecTOrY obtaIned via bOrN-oPpeNhEiMer moLEcUlar DYnaMics. My jOb is to perfOrm bOmD calculatioNS wIth Q-Chem. OtHer Than positionS, enErgy anD mOmeNTa, SC

spectra. Based on the Tim e-Averaged  SC-I VRimp le ment atio n of Kaledin a n d Mi ller, we calculate the  powe rs pect r afroma singl e  t r a jec to ry  ob ta i ne d via  Bo rn-Oppe nheimer Mo lec ul ar Dynamics. My  job is to  pe rform BOMD c alc ulatio ns  wi t h Q-C hem . Oth er tha n  posit ions, ene rg y  and m o menta,S C

spectra._Based on_the Time-Averaged SC-IVR implementation_of Kaledin_and_Miller, we_calculate_the power spectra_from a single_trajectory obtained via Born-Oppenheimer_Molecular Dynamics. My_job_is to perform BOMD calculations with Q-Chem. Other than positions, energy and momenta, SC


of the host. The long-term goal of our research program is to gain a detailed molecular understanding of regulation of lymphocyte trafficking in acute and chronic inflammation using viral infections as a model system. We have found that expression of a phospholipid receptor, sphingosine-1-phosphate receptor-1 (S1P1

of the host. The long - term goal of our inquiry platform is to gain a detailed molecular understanding of rule of lymphocyte trafficking in acute and chronic ignition using viral infections as a exemplar system. We have found that saying of a phospholipid receptor, sphingosine-1 - phosphate receptor-1 (S1P1

of the host. The long-term gual of our resecech prmgram js to gakn a detailed molecular undecstabding of regulation of lympfocyte trwffickint in qcute and rgronic luflamjwtiou nsing viral infgctions as a model system. Fe hcve found that expression of a phosprolipid rfceptor, sphingjsint-1-phjsphzne receptor-1 (S1P1

of the host. The long-term goal of program to gain detailed molecular understanding in and chronic inflammation viral infections as model system. We have found that of a phospholipid receptor, sphingosine-1-phosphate receptor-1 (S1P1

of the host. The long-term goal oF our researCh proGraM is To Gain A detAiled molecular UNderStanding of regulation of LymphOcYTe trAFfIckinG in acutE AnD CHroNiC iNflAmMAtIon usIng Viral inFections as A moDeL system. We havE FoUnd that expResSion of a phospHolIpid reCePtoR, SphinGosIne-1-phOsphatE ReceptOr-1 (S1P1

of the host. The long-ter m goal ofour r ese arc hprog ramis to gain a d e tail ed molecular understan dingof regu l at ion o f lymph o cy t e  tr af fi cki ng in  acut e a nd chro nic inflam mat io n using vira l  i nfectionsasa model syst em.  We ha ve  fo u nd th atexpre ssiono f a ph ospholipi dr ecepto r , sphin g o si ne-1 -phosphate recept o r- 1  (S1P1

of_the host._The long-term goal of_our research_program_is to_gain_a detailed molecular_understanding of regulation_of lymphocyte trafficking in_acute and chronic_inflammation_using viral infections as a model system. We have found that expression of a_phospholipid_receptor, sphingosine-1-phosphate_receptor-1_(S1P1


brain neurons. The assessment of receptor number and localization after lesioning of the fimbria-fornix and basal forebrain in rats will provide infomation about the pre- and postsynaptic localization of the subtypes and the cellular and molecular bases for changes induced by deafferentation. Lastly, muscarinic receptor proteins

brain neurons. The assessment of receptor numeral and localization of function after lesioning of the fimbria - fornix and basal forebrain in rats will provide infomation about the pre- and postsynaptic localization of function of the subtypes and the cellular and molecular bases for change induced by deafferentation. Lastly, muscarinic sense organ protein

braln neurons. The assessmenu of receptor numywr and localjzation xfter lesioning of the fimbrma-foenix qnd basal forebrain in rats wilp providw inhomation about tis pre- akb posfdyna'tmc localization of the suttypes and the cdlpular and molecular bases for changqs induvef by deafferenjatiom. Lasfly, muscarinic receptor proteins

brain neurons. The assessment of receptor number after of the and basal forebrain about pre- and postsynaptic of the subtypes the cellular and molecular bases for induced by deafferentation. Lastly, muscarinic receptor proteins

brain neurons. The assessment Of receptor NumbeR anD loCaLizaTion After lesioning OF the Fimbria-fornix and basal fOrebrAiN In raTS wIll prOvide inFOmATIon AbOuT thE pRE- aNd posTsyNaptic lOcalizatioN of ThE subtypes and THe Cellular anD moLecular bases For ChangeS iNduCEd by dEafFerenTation. lAstly, mUscarinic ReCEptor pROteins

brain neurons. The assessm ent of rec eptor  nu mbe randloca lization after lesi oning of the fimbria-f ornix  a n d ba s al  fore brain i n  r a t s w il lpro vi d einfom ati on abou t the pre-  an dpostsynaptic lo calization  of  the subtype s a nd the  c ell u lar a ndmolec ular b a ses fo r changes  i n ducedb y deaff e r en tati on. Lastly, musca r in i c receptor pro teins

brain neurons._The assessment_of receptor number and_localization after_lesioning_of the_fimbria-fornix_and basal forebrain_in rats will_provide infomation about the_pre- and postsynaptic_localization_of the subtypes and the cellular and molecular bases for changes induced by deafferentation._Lastly,_muscarinic receptor_proteins


, responsiveness of health systems and obstacles to care experienced by children with epilepsy and their families, (2) characterize risk factors, outcomes and comorbidities related to prevalent and new onset pediatric epilepsy, and (3) reassess population-based estimates of epilepsy incidence and prevalence over a 2-year period among children living in DC.

, responsiveness of health systems and obstacles to care experienced by child with epilepsy and their class, (2) characterize risk factors, consequence and comorbidities related to prevalent and modern onset pediatric epilepsy, and (3) reassess population - base estimates of epilepsy incidence and prevalence over a 2 - year period among child living in DC.

, redponsiveness of health snstems and obstaeoes to care sxperienzed by children with epilepsb ane theur families, (2) characterkze risk vactors, iutcines and comorbiditlzs remwted vo prevalent anc new onsed pediatric ephldpdy, and (3) reassess population-based eseimates ov epilepsy incydenbe and irtvalence over a 2-year period among childrtn living in DC.

, responsiveness of health systems and obstacles experienced children with and their families, and related to prevalent new onset pediatric and (3) reassess population-based estimates of incidence and prevalence over a 2-year period among children living in DC.

, responsiveness of health sysTems and obsTacleS to CarE eXperIencEd by children wiTH epiLepsy and their families, (2) cHaracTeRIze rISk FactoRs, outcoMEs AND coMoRbIdiTiES rElateD to PrevaleNt and new onSet PeDiatric epilePSy, And (3) reassesS poPulation-baseD esTimateS oF epILepsy IncIdencE and prEValencE over a 2-yeaR pERiod amONg childREN lIvinG in DC.

, responsiveness of health  systems a nd ob sta cle sto c areexperienced by chil dren with epilepsy and  thei rf amil i es , (2)  charac t er i z e r is kfac to r s,  outc ome s and c omorbiditi esre lated to pre v al ent and ne w o nset pediatr icepilep sy , a n d (3)  re asses s popu l ation- based est im a tes of epileps y in cide nce and prevalenc e  o v er a 2-year pe riod a mo n gc h ild ren  living in  D C.

, responsiveness_of health_systems and obstacles to_care experienced_by_children with_epilepsy_and their families,_(2) characterize risk_factors, outcomes and comorbidities_related to prevalent_and_new onset pediatric epilepsy, and (3) reassess population-based estimates of epilepsy incidence and prevalence_over_a 2-year_period_among_children living in DC.


methylation status of the allele in mice bred for Aims 1 and 2. The airway epithelium represents the first line of defense for the lungs against inhaled-pollutants and infectious agents. Injury to the airway epithelium occurs during mechanical ventilation and in inflammatory diseases such as asthma. Movement of air into and out of the lungs during

methylation status of the allele in mice bred for Aims 1 and 2. The respiratory tract epithelium stage the first line of defense for the lung against inhaled - pollutants and infectious agents. wound to the airline epithelium occurs during mechanical public discussion and in inflammatory diseases such as asthma. apparent motion of air into and out of the lungs during

mehhylation status of the xllele in mice yeed foc Aims 1 and 2. Thd airway epithelium represenvs tye fiest line of defense fof the lunhs againwt iihaled-pollutants and infcetioua ageutw. Injury to thg airway epidhelium occurs djrnng mechanical ventilation and in inslammatprj diseases sucr as wsthja. Movement of air into and out of the luigs during

methylation status of the allele in mice Aims and 2. airway epithelium represents for lungs against inhaled-pollutants infectious agents. Injury the airway epithelium occurs during mechanical and in inflammatory diseases such as asthma. Movement of air into and out the lungs during

methylation status of the allEle in mice bRed foR AiMs 1 aNd 2. the aIrwaY epithelium repREsenTs the first line of defensE for tHe LUngs AGaInst iNhaled-pOLlUTAntS aNd InfEcTIoUs ageNts. injury tO the airway EpiThElium occurs dURiNg mechanicAl vEntilation anD in InflamMaTorY DiseaSes Such aS asthmA. movemeNt of air inTo ANd out oF The lungS DUrIng

methylation status of the  allele in  mice  br edfo r Ai ms 1  and 2. The ai r wayepithelium representsthe f ir s t li n eof de fense f o rt h e l un gs  ag ai n st  inha led -pollut ants and i nfe ct ious agents. In jury to th e a irway epithe liu m occu rs  du r ing m ech anica l vent i lation  and in i nf l ammato r y disea s e ssuch  as asthma. Movem e nt of air into an d outof th e lun gsduring

methylation_status of_the allele in mice_bred for_Aims_1 and_2._The airway epithelium_represents the first_line of defense for_the lungs against_inhaled-pollutants_and infectious agents. Injury to the airway epithelium occurs during mechanical ventilation and in_inflammatory_diseases such_as_asthma._Movement of air into and_out of the lungs during


a preclinical murine model. The focus of Phase II will be the development of a commercial imaging platform that is optimized to monitor the in vivo effects of anti-metastatic therapies. When our system is benchmarked against the current standards of optical imaging, we expect to find a 10x increase in spatial resolution enabling detection of

a preclinical murine model. The focus of Phase II will be the development of a commercial imaging chopine that is optimize to monitor the in vivo effects of anti - metastatic therapies. When our arrangement is benchmarked against the current criterion of optical imaging, we have a bun in the oven to find oneself a 10x increase in spatial resolution enabling detection of

a oreclinical murine model. The focus of Pkqse II will ge the ddvelopment of a commercial ilating kjatform that is opgimized tl monitoe tht in vivo effects of anti-metastzbic tkecapies. When our system is benchmarked acakndt the current standards of optical imaginb, ae expect to fynd s 10x ihbrtase in spatial resolution enablihg detebtion of

a preclinical murine model. The focus of will the development a commercial imaging monitor in vivo effects anti-metastatic therapies. When system is benchmarked against the current of optical imaging, we expect to find a 10x increase in spatial resolution detection of

a preclinical murine model. ThE focus of PhAse II WilL be ThE devElopMent of a commercIAl imAging platform that is optImizeD tO MoniTOr The in Vivo effECtS OF anTi-MeTasTaTIc TheraPieS. When ouR system is bEncHmArked against THe Current staNdaRds of optical ImaGing, we ExPecT To finD a 10x IncreAse in sPAtial rEsolution EnABling dETection OF

a preclinical murine mode l. The foc us of  Ph ase  I I wi ll b e the developm e nt o f a commercial imaging  plat fo r m th a tis op timized to m oni to rthe  i n  v ivo e ffe cts ofanti-metas tat ic  therapies.W he n our syst emis benchmark edagains tthe curre ntstand ards o f  optic al imagin g, we exp e ct to f i n da 10 x increase in spa t ia l  resolution en abling  d e te c t ion  of

a_preclinical murine_model. The focus of_Phase II_will_be the_development_of a commercial_imaging platform that_is optimized to monitor_the in vivo_effects_of anti-metastatic therapies. When our system is benchmarked against the current standards of optical_imaging,_we expect_to_find_a 10x increase in spatial_resolution enabling detection of


this study may provide prognostic markers for this disease. We have refined methods for flow cytometric monitoring of patient specimens for apoptosis induced by chemotherapy and have been able to detect apoptosis in specific cell populations. This has allowed us to demonstrate different sensitivities of specific cell lineages to chemotherapeutic agents. We have initiated a study of clonal

this study may provide prognostic markers for this disease. We get refine methods for flow cytometric monitoring of patient specimens for apoptosis induce by chemotherapy and have been able to detect apoptosis in specific cell populations. This has leave us to demonstrate different sensitivity of specific cell lineages to chemotherapeutic agent. We have initiated a study of clonal

thls study may provide pronnostic markers yir thiv disezse. We hxve refined methods for flow cttomeugic monitoring of patkent specpmens for apoktosis induced by chemothcxapy zkd hare been able to cetect apo[tosis in spechfkc cell populations. This has allowed ts to drmlnstrate diffetent xqnsifpvlties of specific cell lineages fo chemmtherapeutic sgents. We have initiated a stufy of clonal

this study may provide prognostic markers for We refined methods flow cytometric monitoring induced chemotherapy and have able to detect in specific cell populations. This has us to demonstrate different sensitivities of specific cell lineages to chemotherapeutic agents. We initiated a study of clonal

this study may provide prognoStic markerS for tHis DisEaSe. We Have Refined methods FOr flOw cytometric monitoring Of patIeNT speCImEns foR apoptoSIs INDucEd By CheMoTHeRapy aNd hAve been Able to deteCt aPoPtosis in specIFiC cell populAtiOns. This has alLowEd us to DeMonSTrate DifFerenT sensiTIvitieS of specifIc CEll linEAges to cHEMoTherApeutic agents. We haVE iNItiated a study oF clonaL

this study may provide pr ognostic m arker s f orth is d isea se. We have re f ined  methods for flow cyto metri cm onit o ri ng of  patien t  s p e cim en sfor  a p op tosis  in duced b y chemothe rap yand have bee n  a ble to det ect  apoptosis i n s pecifi ccel l  popu lat ions.  Thish as all owed us t od emonst r ate dif f e re nt s ensitivities of s p ec i fic cell linea ges to  c h em o t her ape utic agent s.  We h a ve init i at e d a s t udy of clonal

this_study may_provide prognostic markers for_this disease._We_have refined_methods_for flow cytometric_monitoring of patient_specimens for apoptosis induced_by chemotherapy and_have_been able to detect apoptosis in specific cell populations. This has allowed us to_demonstrate_different sensitivities_of_specific_cell lineages to chemotherapeutic agents._We have initiated a study_of clonal


Ligand-mediated TCR degradation is inhibitable both by reagents that block vesicular acidification and by inhibitors of the ubiquitin/proteasome pathway, suggesting a complex pathway leading to TCR degradation. Our determination that the TCR is a substrate for ubiquitination has led us to evaluate ubiquitination in more detail. A family of human

Ligand - mediated TCR degradation is inhibitable both by reagents that block vesicular acidification and by inhibitor of the ubiquitin / proteasome nerve pathway, suggest a complex pathway leading to TCR abasement. Our determination that the TCR is a substrate for ubiquitination has led us to evaluate ubiquitination in more contingent. A kin of human

Lihand-mediated TCR degradauion is inhibitable both by rezgents tfat block vesicular acidificetiob and by inhibitors of the jbiquitin/iroteasomw pauhway, suggesting e complew patgaay nxading to TCR dggradation. Ogr determinatimn tkat the TCR is a substrate for ubiquytinatipn has led us to evaktate lblquitination in more detail. A fajily of human

Ligand-mediated TCR degradation is inhibitable both by block acidification and inhibitors of the pathway to TCR degradation. determination that the is a substrate for ubiquitination has us to evaluate ubiquitination in more detail. A family of human

Ligand-mediated TCR degradatIon is inhibItablE boTh bY rEageNts tHat block vesicuLAr acIdification and by inhibiTors oF tHE ubiQUiTin/prOteasomE PaTHWay, SuGgEstInG A cOmpleX paThway leAding to TCR DegRaDation. Our detERmInation thaT thE TCR is a substRatE for ubIqUitINatioN haS led uS to evaLUate ubIquitinatIoN In more DEtail. A fAMIlY of hUman

Ligand-mediated TCR degra dation isinhib ita ble  b othby r eagents that b l ockvesicular acidificatio n and  b y  inh i bi torsof theu bi q u iti n/ pr ote as o me  path way , sugge sting a co mpl ex  pathway lea d in g to TCR d egr adation. Our  de termin at ion thatthe  TCRis a s u bstrat e for ubi qu i tinati o n has l e d  u s to  evaluate ubiquit i na t ion in more de tail.Af am i l y o f h uman

Ligand-mediated_TCR degradation_is inhibitable both by_reagents that_block_vesicular acidification_and_by inhibitors of_the ubiquitin/proteasome pathway,_suggesting a complex pathway_leading to TCR_degradation._Our determination that the TCR is a substrate for ubiquitination has led us to_evaluate_ubiquitination in_more_detail._A family of human


distinguished Scientific Advisory Board, will answer three questions: (1) How do relevant stakeholder groups perceive different PEIs for the treatment of depression? That is, what are their ethical concerns and related beliefs and attitudes about the use of PEIs? (2) How do PEI characteristics and disease severity shape ethical concerns and

distinguished Scientific Advisory Board, will answer three questions: (1) How do relevant stakeholder groups perceive unlike pei for the discussion of depression? That is, what are their ethical concerns and related beliefs and position about the use of PEIs? (2) How do PEI characteristic and disease asperity shape ethical concerns and

didtinguished Scientific Aavisory Board, wnol ansxer thrse questkons: (1) How do relevant stakehlleer geoups perceive differevt PEIs flr the teeatnwnt of depcsssion? Bkat ia, whac ere their ethicsl concernv and related teuizfs and attitudes about the use of PQIs? (2) Hoe fo PEI charactgristpcf ans disease severity shape ethical ckncerns and

distinguished Scientific Advisory Board, will answer three How relevant stakeholder perceive different PEIs That what are their concerns and related and attitudes about the use of (2) How do PEI characteristics and disease severity shape ethical concerns and

distinguished Scientific AdVisory BoarD, will AnsWer ThRee qUestIons: (1) How do relevANt stAkeholder groups perceivE diffErENt PEiS fOr the TreatmeNT oF DEprEsSiOn? THaT Is, What aRe tHeir ethIcal concerNs aNd Related belieFS aNd attitudeS abOut the use of PeIs? (2) how do PeI ChaRActerIstIcs anD diseaSE severIty shape eThICal conCErns and

distinguished ScientificAdvisory B oard,  wi llan swer  thr ee questions:( 1) H ow do relevant stakeho ldergr o upsp er ceive  differ e nt P EIs  f or  th et re atmen t o f depre ssion? Tha t i s,  what are th e ir  ethical c onc erns and rel ate d beli ef s a n d att itu des a bout t h e useof PEIs?(2 )  How d o  PEI ch a r ac teri stics and disease se v erity shape et hicalco n ce r n s a nd

distinguished_Scientific Advisory_Board, will answer three_questions: (1)_How_do relevant_stakeholder_groups perceive different_PEIs for the_treatment of depression? That_is, what are_their_ethical concerns and related beliefs and attitudes about the use of PEIs? (2) How_do_PEI characteristics_and_disease_severity shape ethical concerns and


, we have shown that loss of MK-STYX increases ATP production. Therefore, we predict that the elevation in cellular ATP due to loss of MK-STYX is sufficient to inhibit apoptosome formation and entry into apoptosis. We have shown that MK-STYX interacts with two additional mitochondrial proteins and we

, we have shown that loss of MK - STYX increases ATP production. consequently, we bode that the acme in cellular ATP due to loss of MK - STYX is sufficient to inhibit apoptosome geological formation and entry into apoptosis. We have shown that MK - STYX interact with two additional mitochondrial proteins and we

, we have shown that loss of MK-STYX increasgs ATP pcoductikn. Therewore, we predict that the eletatiin in cellular ATP due to luss of MK-DTYX is wuffmcient to inhibiv apoptosome fkvmatimi and entry intp apoptosiv. We have showt ghct MK-STYX interacts with two additiogal mitpcjondrial proteyns sgd ws

, we have shown that loss of ATP Therefore, we that the elevation loss MK-STYX is sufficient inhibit apoptosome formation entry into apoptosis. We have shown MK-STYX interacts with two additional mitochondrial proteins and we

, we have shown that loss of MK-STyX increaseS ATP pRodUctIoN. TheRefoRe, we predict thaT The eLevation in cellular ATP dUe to lOsS Of MK-stYx is suFficienT To INHibIt ApOptOsOMe FormaTioN and entRy into apopTosIs. we have shown tHAt mK-STYX inteRacTs with two addItiOnal miToChoNDrial ProTeins And we

, we have shown that lossof MK-STYX  incr eas esAT P pr oduc tion. Therefor e , we  predict that the elev ation  i n  cel l ul ar AT P due t o  l o s s o fMK -ST YX is  suff ici ent toinhibit ap opt os ome formatio n  a nd entry i nto  apoptosis.Wehave s ho wnt hat M K-S TYX i nterac t s with  two addi ti o nal mi t ochondr i a lprot eins and we

, we_have shown_that loss of MK-STYX_increases ATP_production._Therefore, we_predict_that the elevation_in cellular ATP_due to loss of_MK-STYX is sufficient_to_inhibit apoptosome formation and entry into apoptosis. We have shown that MK-STYX interacts with_two_additional mitochondrial_proteins_and_we


AD is the most common dementia in the elderly population and one of the leading causes of death in the developed world. One of the main problems in AD is the lack of an early, sensitive and objective laboratory diagnosis to identify individuals that will develop the disease before substantial brain damage. Compelling evidences point that the hallmark event

AD is the most common dementia in the elderly population and one of the leading campaign of end in the developed world. One of the main trouble in AD is the lack of an early, sensible and objective laboratory diagnosis to identify individuals that will explicate the disease before substantial brain price. Compelling evidences point that the authentication event

AD is the most common demektia in the eldetlt popunation and one of the leading causes of deeth un tht developed world. Ove of the main priblenw in AD is the lack of ah earnb, sensitive and objective laboratory didgvodis to identify individuals that wijl devekoo the disease fefoge subanaktial brain damage. Compelling evjdences point that tne hallmark event

AD is the most common dementia in population one of leading causes of One the main problems AD is the of an early, sensitive and objective diagnosis to identify individuals that will develop the disease before substantial brain damage. evidences point that the hallmark event

AD is the most common dementia In the elderLy popUlaTioN aNd onE of tHe leading causeS Of deAth in the developed world. one of ThE Main PRoBlems In AD is tHE lACK of An EaRly, SeNSiTive aNd oBjectivE laboratorY diAgNosis to identIFy IndividualS thAt will develoP thE diseaSe BefORe subStaNtial Brain dAMage. CoMpelling eViDEnces pOInt that THE hAllmArk event

AD is the most common dem entia in t he el der lypo pula tion  and one of th e  lea ding causes of death i n the  d e velo p ed  worl d. Oneo ft h e m ai npro bl e ms  in A D i s the l ack of anear ly , sensitivea nd  objective  la boratory dia gno sis to  i den t ify i ndi vidua ls tha t  willdevelop t he diseas e  before s ub stan tial brain damage .  C o mpelling evide nces p oi n tt h atthe  hallmarkev ent

AD_is the_most common dementia in_the elderly_population_and one_of_the leading causes_of death in_the developed world. One_of the main_problems_in AD is the lack of an early, sensitive and objective laboratory diagnosis to_identify_individuals that_will_develop_the disease before substantial brain_damage. Compelling evidences point that_the hallmark_event


have continued to investigate the mechanism of PI3K stimulation by TRbeta and the consequences of PI3K signaling for the physiological effects of thyroid hormone. We have used a fluorescent PIP3 binding domain from the Akt protein kinase coupled with cyan and yellow fluorecent proteins to detect PIP3 production by fluorescence resonance energy transfer (

have continued to investigate the mechanism of PI3 K stimulation by TRbeta and the consequences of PI3 K signaling for the physiologic effect of thyroid hormone. We have used a fluorescent PIP3 bind world from the Akt protein kinase coupled with cyan and yellow fluorecent protein to detect PIP3 production by fluorescence resonance energy transportation (

hage continued to investigxte the mechanism of PM3K stimhlation cy TRbeta and the consequencxs od PI3K signaling for the phyriologicap effectw of rhyroid hocjone. We have hded c hluorescent PIP3 binding dmmain from the Ayt protein kinase coupled with cyan agd yellpw fluorecent prjteimf to detect PIP3 production by fluorescsnce revonance energu transfer (

have continued to investigate the mechanism of by and the of PI3K signaling thyroid We have used fluorescent PIP3 binding from the Akt protein kinase coupled cyan and yellow fluorecent proteins to detect PIP3 production by fluorescence resonance energy (

have continued to investigatE the mechanIsm of pI3K StiMuLatiOn by tRbeta and the coNSequEnces of PI3K signaling for The phYsIOlogICaL effeCts of thYRoID HorMoNe. we hAvE UsEd a flUorEscent PiP3 binding dOmaIn From the Akt prOTeIn kinase coUplEd with cyan anD yeLlow flUoRecENt proTeiNs to dEtect Pip3 produCtion by flUoREscencE ResonanCE EnErgy Transfer (

have continued to investi gate the m echan ism  of  P I3Kstim ulation by TRb e ta a nd the consequences of  PI3K  s i gnal i ng  forthe phy s io l o gic al  e ffe ct s  o f thy roi d hormo ne. We hav e u se d a fluoresc e nt  PIP3 bind ing  domain from  th e Aktpr ote i n kin ase  coup led wi t h cyan  and yell ow fluore c ent pro t e in s to  detect PIP3 prod u ct i on by fluoresc ence r es o na n c e e ner gy transfe r(

have_continued to_investigate the mechanism of_PI3K stimulation_by_TRbeta and_the_consequences of PI3K_signaling for the_physiological effects of thyroid_hormone. We have_used_a fluorescent PIP3 binding domain from the Akt protein kinase coupled with cyan and_yellow_fluorecent proteins_to_detect_PIP3 production by fluorescence resonance_energy transfer (


and in asthmatics for exacerbated disease. Project Narrative: The coordinated production of chemokines during pulmonary inflammation leads to the recruitment of various leukocytes into the lung interstitium and airway. Identifying chemokine mediators as well as the relevant receptor during allergic and viral disease may be important for identifying therapeutics targets for treating chronic

and in asthmatics for exacerbated disease. Project Narrative: The coordinated production of chemokines during pulmonary excitement go to the recruitment of various leukocytes into the lung interstitium and airway. name chemokine mediators as well as the relevant sense organ during allergic and viral disease may be important for identifying therapeutics target for treating chronic

anf in asthmatics for exactrbated disease. Ptohect Nerrativs: The courdinated production of chemlkunes euring pulmonary inflaomation lvads to tye rtcruitment of varmkus leukocytea intm the lung intetstitium and airway. Identixykny chemokine mediators as well as the relevamt receptor durigg akjergjb cnd viral disease may be importznt for identifying yherapeutics targets for tgeatlng chronic

and in asthmatics for exacerbated disease. Project coordinated of chemokines pulmonary inflammation leads leukocytes the lung interstitium airway. Identifying chemokine as well as the relevant receptor allergic and viral disease may be important for identifying therapeutics targets for treating

and in asthmatics for exacerbAted diseasE. ProjEct narRaTive: the cOordinated prodUCtioN of chemokines during pulMonarY iNFlamMAtIon leAds to thE ReCRUitMeNt Of vArIOuS leukOcyTes into The lung intErsTiTium and airwaY. idEntifying cHemOkine mediatoRs aS well aS tHe rELevanT reCeptoR durinG AllergIc and viraL dISease mAY be impoRTAnT for Identifying therapEUtICs targets for trEating ChROnIC

and in asthmatics for exa cerbated d iseas e.Pro je ct N arra tive: The coor d inat ed production of chemo kines  d u ring pu lmona ry infl a mm a t ion  l ea dsto th e rec rui tment o f variousleu ko cytes into t h elung inter sti tium and air way . Iden ti fyi n g che mok ine m ediato r s as w ell as th er elevan t  recept o r  d urin g allergic and vi r al disease may be  impor ta n tf o r i den tifying th er apeut i cs targ e ts f o r t r eating chroni c

and_in asthmatics_for exacerbated disease. Project_Narrative: The_coordinated_production of_chemokines_during pulmonary inflammation_leads to the_recruitment of various leukocytes_into the lung_interstitium_and airway. Identifying chemokine mediators as well as the relevant receptor during allergic and_viral_disease may_be_important_for identifying therapeutics targets for_treating chronic


ERATIONS 8 PROJECT 1: NLR in Host Response to Gamma-Herpesviruses 9 PROJECT 2: Regulators of Innate Immune Responses to Gamma-herpesviruses 17 PROJECT 3: Role of Non-Coding RNAs in Regulating Gamma-Herpesvirus-Host-Interactions 26 PRO

ERATIONS 8 PROJECT 1: NLR in Host Response to Gamma - Herpesviruses 9 PROJECT 2: Regulators of Innate Immune Responses to Gamma - herpesviruses 17 PROJECT 3: Role of Non - Coding RNAs in determine Gamma - Herpesvirus - Host - Interactions 26 professional

ERAHIONS 8 PROJECT 1: NLR in Hust Response to Gamma-Hxrpesviduses 9 PFOJECT 2: Regulators of Innate Inmune Responses to Gamma-heroesvirused 17 PROJEXT 3: Cole of Non-Codinj RNAs ik Reghpatiug Gamma-Herpesvitus-Host-Interdctions 26 PRO

ERATIONS 8 PROJECT 1: NLR in Host Gamma-Herpesviruses PROJECT 2: of Innate Immune 3: of Non-Coding RNAs Regulating Gamma-Herpesvirus-Host-Interactions 26

ERATIONS 8 PROJECT 1: NLR in Host REsponse to GAmma-HErpEsvIrUses 9 pROJeCT 2: Regulators oF innaTe Immune Responses to GamMa-herPeSViruSEs 17 pROJEcT 3: Role oF noN-cOdiNg rNas iN REGuLatinG GaMma-HerpEsvirus-HosT-InTeRactions 26 PRO

ERATIONS 8 PROJECT 1: NLRin Host Re spons e t o G am ma-H erpe sviruses 9 PRO J ECT2: Regulators of Innat e Imm un e  Res p on ses t o Gamma - he r p esv ir us es17 PR OJECT  3:  Role o f Non-Codi ngRN As in Regula t in g Gamma-He rpe svirus-Host- Int eracti on s 2 6  PRO

ERATIONS 8_PROJECT 1:_NLR in Host Response_to Gamma-Herpesviruses_9_PROJECT 2:_Regulators_of Innate Immune_Responses to Gamma-herpesviruses_17 PROJECT 3: Role_of Non-Coding RNAs_in_Regulating Gamma-Herpesvirus-Host-Interactions 26 PRO


test the hyposthesis that patients with chronic fatigue syndrome manifest a characteristic neuroendocrine defect, namely, a reduction in adrenal glucocorticoid secretion mediated by a failure in the central release of corticotropin-releasing hormone (CRH). Specifically, we will confirm and extend our preliminary findings of impaired activation of the H

test the hyposthesis that patients with chronic fatigue syndrome manifest a characteristic neuroendocrine blemish, namely, a decrease in adrenal glucocorticoid secretion mediate by a failure in the cardinal release of adrenocorticotropic hormone - releasing hormone (CRH). Specifically, we will confirm and extend our preliminary determination of impaired activation of the hydrogen

tedt the hyposthesis that katients with chronic favigue sgndrome oanifest a characteristic nenroebdocrune defect, namely, a reauction ij adrenao glncocorticoid seccstion mcbiates by c hailure in the gentral relaase of corticmtfo'in-releasing hormone (CRH). Specificallr, we wikl confirm and evtenc our irtliminary findings of impaired acfivatioi of the H

test the hyposthesis that patients with chronic manifest characteristic neuroendocrine namely, a reduction by failure in the release of corticotropin-releasing (CRH). Specifically, we will confirm and our preliminary findings of impaired activation of the H

test the hyposthesis that patIents with cHroniC faTigUe SyndRome Manifest a charaCTeriStic neuroendocrine defeCt, namElY, A redUCtIon in Adrenal GLuCOCorTiCoId sEcREtIon meDiaTed by a fAilure in thE ceNtRal release of COrTicotropin-RelEasing hormonE (CRh). SpeciFiCalLY, we wiLl cOnfirM and exTEnd our PreliminaRy FIndingS Of impaiRED aCtivAtion of the H

test the hyposthesis that  patientswithchr oni cfati guesyndrome manif e st a  characteristic neuroe ndocr in e  def e ct , nam ely, ar ed u c tio nin  ad re n al  gluc oco rticoid  secretion  me di ated by a fa i lu re in thecen tral release  of  corti co tro p in-re lea singhormon e  (CRH) . Specifi ca l ly, we will co n f ir m an d extend our prel i mi n ary findings o f impa ir e da c tiv ati on of theH

test_the hyposthesis_that patients with chronic_fatigue syndrome_manifest_a characteristic_neuroendocrine_defect, namely, a_reduction in adrenal_glucocorticoid secretion mediated by_a failure in_the_central release of corticotropin-releasing hormone (CRH). Specifically, we will confirm and extend our preliminary_findings_of impaired_activation_of_the H


prevent the development of CM in patients with sub-clinical infection, and antifungal therapy is required. Yet, the optimal pre-emptive anti-fungal treatment dose and duration necessary to prevent CM in patients with sub-clinical infection have yet to be established. We propose to investigate how practical and effective CRAG screening and

prevent the development of CM in patients with sub - clinical infection, and antifungal therapy is command. so far, the optimal pre - emptive anti - fungal treatment dose and duration necessary to prevent curium in patients with sub - clinical infection hold yet to be established. We project to investigate how practical and effective CRAG screening and

prfvent the development of CM in patients with snb-clinidal infeztion, and antifungal therapy iw reqyired. Yet, the optimal ore-emptivv anti-funtal ureatment dose anv duration necsdsarv vo prevent CM ik patients fith sub-clinicdl iufection have yet to be established. Re proppsf to investigaje hoe pradnigal and effective CRAG screening and

prevent the development of CM in patients infection, antifungal therapy required. Yet, the and necessary to prevent in patients with infection have yet to be established. propose to investigate how practical and effective CRAG screening and

prevent the development of CM In patients With sUb-cLinIcAl inFectIon, and antifungAL theRapy is required. Yet, the opTimal PrE-EmptIVe Anti-fUngal trEAtMENt dOsE aNd dUrATiOn necEssAry to prEvent CM in pAtiEnTs with sub-cliNIcAl infectioN haVe yet to be estAblIshed. WE pRopOSe to iNveStigaTe how pRActicaL and effecTiVE CRAG sCReening AND

prevent the development o f CM in pa tient s w ith  s ub-c lini cal infection, andantifungal therapy isrequi re d . Ye t ,the o ptimalp re - e mpt iv eant i- f un gal t rea tment d ose and du rat io n necessaryt oprevent CM  in  patients wi thsub-cl in ica l  infe cti on ha ve yet to beestablish ed .  We pr o pose to i nv esti gate how practica l  a n d effective CR AG scr ee n in g and

prevent_the development_of CM in patients_with sub-clinical_infection,_and antifungal_therapy_is required. Yet,_the optimal pre-emptive_anti-fungal treatment dose and_duration necessary to_prevent_CM in patients with sub-clinical infection have yet to be established. We propose to_investigate_how practical_and_effective_CRAG screening and