FP and sarin SE. Aim 5. Evaluate whether AT plus LV can reduce the development of cognitive impairment, the development of AE and mossy fiber sprouting following POX, DFP and sarin SE. The PR demonstrate the feasibility of these studies and underscore the potential significance of conducting this research. AT

FP and sarin SE. Aim 5. Evaluate whether AT plus LV can reduce the development of cognitive disability, the growth of AE and mossy fiber sprouting postdate POX, DFP and sarin SE. The PR demonstrate the feasibility of these study and underscore the potential meaning of behave this research. AT

FP wnd sarin SE. Aim 5. Evaluaue whether AT plus LV cai reducs the dexelopment of cognitive impaicmenr, the development of AE and mossy fiher sproytinj following POX, VRP and sarin AC. The 'R demonstrate jhe feasibilhty of these sduaizs and underscore the potential signyficancr lf conducting jhis gefeardh. AT

FP and sarin SE. Aim 5. Evaluate plus can reduce development of cognitive and fiber sprouting following DFP and sarin The PR demonstrate the feasibility of studies and underscore the potential significance of conducting this research. AT

FP and sarin SE. Aim 5. Evaluate whEther AT pluS LV caN reDucE tHe deVeloPment of cognitiVE impAirment, the development oF AE anD mOSsy fIBeR sproUting foLLoWINg PoX, dFp anD sARiN SE. ThE PR DemonstRate the feaSibIlIty of these stUDiEs and underScoRe the potentiAl sIgnifiCaNce OF condUctIng thIs reseARch. AT

FP and sarin SE. Aim 5. Ev aluate whe therATplu sLV c an r educe the deve l opme nt of cognitive impair ment,  t h e de v el opmen t of AE an d mos sy  f ibe rs pr outin g f ollowin g POX, DFP  an dsarin SE. Th e  P R demonstr ate  the feasibi lit y of t he ses tudie s a nd un dersco r e thepotential  s i gnific a nce ofc o nd ucti ng this research. AT

FP and_sarin SE._Aim 5. Evaluate whether_AT plus_LV_can reduce_the_development of cognitive_impairment, the development_of AE and mossy_fiber sprouting following_POX,_DFP and sarin SE. The PR demonstrate the feasibility of these studies and underscore_the_potential significance_of_conducting_this research. AT


correlated with a decrease in the amplitude of the first wave of the auditory brainstem response (ABR). Age-related reduction in the amplitude of wave I has been demonstrated in humans (Konrad-Martin et al. 2012) and is consistent with temporal bone studies showing auditory neuronal loss with age (Makary

correlated with a decrease in the amplitude of the first wave of the auditory brainstem response (ABR). Age - relate decrease in the amplitude of wave I has been demonstrated in humans (Konrad - Martin et al. 2012) and is reproducible with worldly bone studies showing auditory neuronal personnel casualty with age (Makary

cogrelated with a decrease in the amplitubw of tie firsf wave ow the auditory brainstem res'onsw (ABR). Age-related reduction kn the amilitude od wate I has been demonstratcb in gmmans (Jonrad-Martin ej al. 2012) and is consistent widh tzmporal bone studies showing auditorr neuromap loss with agg (Makswy

correlated with a decrease in the amplitude first of the brainstem response (ABR). of I has been in humans (Konrad-Martin al. 2012) and is consistent with bone studies showing auditory neuronal loss with age (Makary

correlated with a decrease in The amplituDe of tHe fIrsT wAve oF the Auditory brainsTEm reSponse (ABR). Age-related redUctioN iN The aMPlItude Of wave I HAs BEEn dEmOnStrAtED iN humaNs (KOnrad-MaRtin et al. 2012) anD is CoNsistent with TEmPoral bone sTudIes showing auDitOry neuRoNal LOss wiTh aGe (MakAry

correlated with a decreas e in the a mplit ude  of  t he f irst  wave of the a u dito ry brainstem response(ABR) .A ge-r e la ted r eductio n  i n the  a mp lit ud e  o f wav e I  has be en demonst rat ed  in humans ( K on rad-Martin  et  al. 2012) a ndis con si ste n t wit h t empor al bon e  studi es showin ga uditor y  neuron a l  l osswith age (Makary

correlated_with a_decrease in the amplitude_of the_first_wave of_the_auditory brainstem response_(ABR). Age-related reduction_in the amplitude of_wave I has_been_demonstrated in humans (Konrad-Martin et al. 2012) and is consistent with temporal bone studies_showing_auditory neuronal_loss_with_age (Makary


with each individual supported for a maximum of three years. Trainees undertake interdisciplinary studies with advanced courses in mathematics, quantum mechanics, statistical thermodynamics, biochemistry, molecular and cell biology, computation and instrumentation, and other special topics. In addition, students participate in multiple program functions including a weekly Biophysics Collo

with each individual supported for a maximum of three years. trainee contract interdisciplinary cogitation with advanced course in mathematics, quantum machinist, statistical thermodynamics, biochemistry, molecular and cell biology, calculation and orchestration, and other particular topics. In addition, scholar participate in multiple program affair include a weekly Biophysics Collo

wihh each individual suppovted for a maximom of thcee yeads. Traindes undertake interdisciplinery wtuditf with advanced cojrses in lathematucs, wyantum meciznics, sbctistjgal tkecmodynamics, bioghemistry, mmlecular and calu yiology, computation and instrumentatyon, and ohher special tjpicx. In zddition, students participate in mhltiple program funcyions including a weekly Blophjsics Collo

with each individual supported for a maximum years. undertake interdisciplinary with advanced courses thermodynamics, molecular and cell computation and instrumentation, other special topics. In addition, students in multiple program functions including a weekly Biophysics Collo

with each individual supportEd for a maxiMum of ThrEe yEaRs. TrAineEs undertake intERdisCiplinary studies with adVanceD cOUrseS In MatheMatics, qUAnTUM meChAnIcs, StATiSticaL thErmodynAmics, biochEmiStRy, molecular aND cEll biology, ComPutation and iNstRumentAtIon, ANd othEr sPeciaL topicS. in addiTion, studeNtS ParticIPate in mULTiPle pRogram functions inCLuDIng a weekly BiopHysics coLLo

with each individual supp orted fora max imu m o fthre e ye ars. Traineesu nder take interdisciplinary  stud ie s  wit h  a dvanc ed cour s es i n m at he mat ic s ,quant ummechani cs, statis tic al  thermodynam i cs , biochemi str y, molecular  an d cell  b iol o gy, c omp utati on and instru mentation ,a nd oth e r speci a l  t opic s. In addition, s t ud e nts participat e in m ul t ip l e  pr ogr am functio ns  incl u ding aw ee k l y  Bi o physics Collo

with_each individual_supported for a maximum_of three_years._Trainees undertake_interdisciplinary_studies with advanced_courses in mathematics,_quantum mechanics, statistical thermodynamics,_biochemistry, molecular and_cell_biology, computation and instrumentation, and other special topics. In addition, students participate in multiple_program_functions including_a_weekly_Biophysics Collo


gut-derived signals in response to a lack of luminal nutrient delivery, as occurring with TPN therapy drives such injury. Our lab has been investigating the role of such signaling. Using a novel ambulatory TPN piglet model, developed at our lab which recapitulates human TPN delivery; we have published significant alterations

gut - derived signals in response to a lack of luminal alimentary rescue, as occurring with TPN therapy drives such wound. Our lab has been investigating the character of such signaling. practice a novel ambulatory TPN piglet exemplar, developed at our lab which recapitulates human TPN rescue; we have published significant revision

guh-derived signals in respunse to a lack of lumiial nutdient deuivery, as occurring with TPN tyerapt drives such injury. Ojr lab had been ibvesuigating the role of such signamlng. Uvmng a novel ambolatory TPN [iglet model, davdllped at our lab which recapitulates human YPJ delivery; we rave [ubljshed significant alterations

gut-derived signals in response to a lack nutrient as occurring TPN therapy drives been the role of signaling. Using a ambulatory TPN piglet model, developed at lab which recapitulates human TPN delivery; we have published significant alterations

gut-derived signals in responSe to a lack oF lumiNal NutRiEnt dElivEry, as occurring WIth TpN therapy drives such injUry. OuR lAB has BEeN inveStigatiNG tHE RolE oF sUch SiGNaLing. USinG a novel Ambulatory tPN PiGlet model, devELoPed at our laB whIch recapitulAteS human tPn deLIvery; We hAve puBlisheD SignifIcant alteRaTIons

gut-derived signals in re sponse toa lac k o f l um inal  nut rient delivery ,  asoccurring with TPN the rapydr i vess uc h inj ury. Ou r  l a b  ha sbe enin v es tigat ing  the ro le of such  si gn aling. Using anovel ambu lat ory TPN pigl etmodel,  d eve l opedatour l ab whi c h reca pitulates  h u man TP N  delive r y ;we h ave published sig n if i cant alteratio ns

gut-derived_signals in_response to a lack_of luminal_nutrient_delivery, as_occurring_with TPN therapy_drives such injury._Our lab has been_investigating the role_of_such signaling. Using a novel ambulatory TPN piglet model, developed at our lab which_recapitulates_human TPN_delivery;_we_have published significant alterations


from insects to mammals. PGRPs bind PGNs with high affinity and are important contributors to host defense against bacterial infections. Insects PGRPs, of which there are at least 19, are involved in activating signaling pathways that induce expression of anti-microbial peptides. By contrast, mammalian PGRPs, of

from insects to mammals. PGRPs bind PGNs with high affinity and are authoritative subscriber to host defense against bacterial infections. Insects PGRPs, of which there be at least 19, are involved in activating bespeak pathway that induce expression of anti - microbial peptide. By line, mammalian PGRPs, of

frlm insects to mammals. PGVPs bind PGNs wijh high effinitg and ard important contributors to iost defebse against bacterial knfectiond. Insectw PGCPs, of which thecs are ab leaab 19, arz mnvolved in actlvating sigtaling pathwayv ghct induce expression of anti-microbiaj pepticed. By contrast, iammsjian IGVPs, of

from insects to mammals. PGRPs bind PGNs affinity are important to host defense of there are at 19, are involved activating signaling pathways that induce expression anti-microbial peptides. By contrast, mammalian PGRPs, of

from insects to mammals. PGRPs Bind PGNs wiTh higH afFinItY and Are iMportant contriBUtorS to host defense against bActerIaL InfeCTiOns. InSects PGrps, OF WhiCh ThEre ArE At Least 19, Are InvolveD in activatIng SiGnaling pathwAYs That induce ExpRession of antI-miCrobiaL pEptIDes. By ConTrast, MammalIAn PGRPS, of

from insects to mammals.PGRPs bind  PGNs  wi thhi gh a ffin ity and are im p orta nt contributors to hos t def en s e ag a in st ba cterial in f e cti on s.  In se c ts  PGRP s,of whic h there ar e a tleast 19, ar e  i nvolved in  ac tivating sig nal ing pa th way s  that  in duceexpres s ion of  anti-mic ro b ial pe p tides.B y  c ontr ast, mammalian PG R Ps ,  of

from_insects to_mammals. PGRPs bind PGNs_with high_affinity_and are_important_contributors to host_defense against bacterial_infections. Insects PGRPs, of_which there are_at_least 19, are involved in activating signaling pathways that induce expression of anti-microbial peptides._By_contrast, mammalian_PGRPs,_of


undergraduates to research on cancer in a form that is easy to understand (the on-off type roles of signaling pathways) and also expose them to tissue culture as well as basic cell/molecular biology techniques. An exciting, new investigative theme in airway physiology and pathophysiology is neurotrophins (NTs): growth

undergraduates to research on cancer in a form that is easy to understand (the on - off type function of sign pathways) and also expose them to weave culture as well as basic cell / molecular biota proficiency. An exciting, new fact-finding root in airway physiology and pathophysiology is neurotrophins (NTs ): emergence

unfergraduates to research on cancer in a form tiat is sasy to jnderstand (the on-off type ropew of wignaling pathways) and also explse them to uissue culture as well as basic gell/mmoecular biologi techniques. An exciting, naw iuvestigative theme in airway physioljgy and pwthophysiology is mqurofgokhins (NTs): growth

undergraduates to research on cancer in a is to understand on-off type roles expose to tissue culture well as basic biology techniques. An exciting, new investigative in airway physiology and pathophysiology is neurotrophins (NTs): growth

undergraduates to research oN cancer in a Form tHat Is eAsY to uNderStand (the on-off tYPe roLes of signaling pathways) And alSo EXposE ThEm to tIssue cuLTuRE As wElL aS baSiC CeLl/molEcuLar biolOgy techniqUes. an Exciting, new iNVeStigative tHemE in airway phySioLogy anD pAthOPhysiOloGy is nEurotrOPhins (Nts): growth

undergraduates to researc h on cance r ina f orm  t hatis e asy to underst a nd ( the on-off type rolesof si gn a ling pa thway s) anda ls o exp os ethe mt otissu e c ultureas well as  ba si c cell/molec u la r biologytec hniques. Anexc iting,  n ewi nvest iga tivethemei n airw ay physio lo g y andp athophy s i ol ogyis neurotrophins( NT s ): growth

undergraduates_to research_on cancer in a_form that_is_easy to_understand_(the on-off type_roles of signaling_pathways) and also expose_them to tissue_culture_as well as basic cell/molecular biology techniques. An exciting, new investigative theme in airway_physiology_and pathophysiology_is_neurotrophins_(NTs): growth


to origins and travel times and estimate the proportion who are incubating disease. It would also assess the positive predictive value of a short screening questionnaire. 3. Seasonal influenza hospitalizations and housing conditions - This component would measure rates of hospitalization with influenza in an established cohort of 225,000 people living in public housing in New

to origins and travel times and estimate the symmetry who are incubate disease. It would also assess the incontrovertible predictive value of a unretentive screening questionnaire. 3. Seasonal influenza hospitalizations and caparison conditions - This component would measure rate of hospitalization with influenza in an established age group of 225,000 people living in public housing in New

to origins and travel timer and estimate jhw propmrtion who are incubating disease. It would aoso awsess the positive preaictive vwlue of q shiet screeniif questljnnajve. 3. Szawonal influenzs hospitalhzations and hmuriug conditions - This component would ieasure rwtes of hospitwlizseion with influenza in an established dohort mf 225,000 people lifing in public housing in Jew

to origins and travel times and estimate who incubating disease. would also assess a screening questionnaire. 3. influenza hospitalizations and conditions - This component would measure of hospitalization with influenza in an established cohort of 225,000 people living in housing in New

to origins and travel times anD estimate tHe proPorTioN wHo arE incUbating disease. iT wouLd also assess the positivE predIcTIve vALuE of a sHort scrEEnING quEsTiOnnAiRE. 3. SEasonAl iNfluenzA hospitaliZatIoNs and housing COnDitions - ThiS coMponent would MeaSure raTeS of HOspitAliZatioN with iNFluenzA in an estaBlIShed coHOrt of 225,000 peOPLe LiviNg in public housing IN NEW

to origins and travel tim es and est imate  th e p ro port ionwho are incuba t ingdisease. It would also  asse ss thep os itive  predic t iv e val ue  o f a  s h or t scr een ing que stionnaire . 3 .Seasonal inf l ue nza hospit ali zations andhou sing c on dit i ons -  Th is co mponen t  would  measurera t es ofh ospital i z at ionwith influenza in an established co hort o f2 25 , 0 00peo ple living  i n pub l ic hous i ng i n  Ne w

to_origins and_travel times and estimate_the proportion_who_are incubating_disease._It would also_assess the positive_predictive value of a_short screening questionnaire._3._Seasonal influenza hospitalizations and housing conditions - This component would measure rates of hospitalization_with_influenza in_an_established_cohort of 225,000 people living_in public housing in New


of STDs and HIV infection. Natural products are extremely important sources of bioactive compounds for agricultural and pharmaceutical applications. Enzymes involved in secondary metabolism hold great potential as biocatalysts that may be used in the efficient synthesis of fine chemicals and high value pharmaceuticals. In this collaborative work between a metabolic engineering group and

of STDs and HIV infection. Natural products are extremely authoritative reservoir of bioactive compounds for agrarian and pharmaceutical applications. enzyme involved in secondary metamorphosis hold great potential as biocatalyst that may be use in the efficient deduction of fine chemicals and high value pharmaceuticals. In this collaborative workplace between a metabolic engineering group and

of STDs and HIV infection. Katural products are exvremely importavt sources of bioactive complubds fir agricultural and phxrmaceutibal applixatiibs. Enzymes involved in ssgondaxy metabolism hokd great pmtential as bimcxtclysts that may be used in the efficyent symtjesis of fine shempcwls znd high value pharmaceuticals. In fhis conlaborative wprk between a metabolic enhinefring group and

of STDs and HIV infection. Natural products important of bioactive for agricultural and secondary hold great potential biocatalysts that may used in the efficient synthesis of chemicals and high value pharmaceuticals. In this collaborative work between a metabolic engineering and

of STDs and HIV infection. NatuRal productS are eXtrEmeLy ImpoRtanT sources of bioaCTive Compounds for agriculturAl and PhARmacEUtIcal aPplicatIOnS. eNzyMeS iNvoLvED iN secoNdaRy metabOlism hold gReaT pOtential as biOCaTalysts thaT maY be used in the EffIcient SyNthESis of FinE chemIcals aND high vAlue pharmAcEUticalS. in this cOLLaBoraTive work between a mETaBOlic engineerinG group AnD

of STDs and HIV infection . Naturalprodu cts  ar eextr emel y important so u rces  of bioactive compound s for  a g ricu l tu ral a nd phar m ac e u tic al  a ppl ic a ti ons.Enz ymes in volved insec on dary metabol i sm  hold grea t p otential asbio cataly st s t h at ma y b e use d in t h e effi cient syn th e sis of fine ch e m ic alsand high value ph a rm a ceuticals. Inthis c ol l ab o r ati vework betwe en  a me t abolice ng i n e eri n g group and

of_STDs and_HIV infection. Natural products_are extremely_important_sources of_bioactive_compounds for agricultural_and pharmaceutical applications._Enzymes involved in secondary_metabolism hold great_potential_as biocatalysts that may be used in the efficient synthesis of fine chemicals and_high_value pharmaceuticals._In_this_collaborative work between a metabolic_engineering group and


are affected. We also hypothesize that stress will exacerbate the immunosuppressive effects of prenatal ethanol, and based on our previous data, that males will be more affected than females by exposure to prenatal ethanol and stress. This approach will increase our understanding of two fundamentally important issues: the nature of the immunoteratogenic effects of ethanol

are affected. We also hypothesize that stress will worsen the immunosuppressive effect of prenatal ethanol, and based on our former data, that male will be more affected than female by exposure to prenatal ethanol and tension. This overture will increase our understanding of two basically important issues: the nature of the immunoteratogenic effects of ethanol

arf affected. We also hypotmesize that stress will exacedbate thd immunosuppressive effects lf prenqtal ethanol, and based on our pgevious dqta, uhat males will bx more anyectes thau hemales by expoxure to pranatal ethanol avd stress. This approach will increase our uncegstanding of tro flnqamehnaoly important issues: the natude of tie immunoteratobenic effects of ethanol

are affected. We also hypothesize that stress the effects of ethanol, and based males be more affected females by exposure prenatal ethanol and stress. This approach increase our understanding of two fundamentally important issues: the nature of the immunoteratogenic of ethanol

are affected. We also hypothesIze that strEss wiLl eXacErBate The iMmunosuppressiVE effEcts of prenatal ethanol, aNd basEd ON our PReVious Data, thaT MaLES wiLl Be MorE aFFeCted tHan Females By exposure To pReNatal ethanol ANd Stress. This AppRoach will incReaSe our uNdErsTAndinG of Two fuNdamenTAlly imPortant isSuES: the naTUre of thE IMmUnotEratogenic effects OF eTHanol

are affected. We also hyp othesize t hat s tre sswi ll e xace rbate the immu n osup pressive effects of pr enata le than o l,  andbased o n  o u r  pr ev io usda t a,  that  ma les wil l be moreaff ec ted than fem a le s by expos ure  to prenatal  et hanolan d s t ress.  Th is ap proach will i ncrease o ur unders t andingo f  t wo f undamentally impo r ta n t issues: thenature  o f  t h e  im mun oteratogen ic  effe c ts of e t ha n o l

are_affected. We_also hypothesize that stress_will exacerbate_the_immunosuppressive effects_of_prenatal ethanol, and_based on our_previous data, that males_will be more_affected_than females by exposure to prenatal ethanol and stress. This approach will increase our_understanding_of two_fundamentally_important_issues: the nature of the_immunoteratogenic effects of ethanol


users to HIV infection, and potentially facilitating the penetration of virus across the blood brain barrier (BBB) into the brain. In this proposal we will dissect mechanisms by which Meth can induce and modulate free radical production, causing an aggravation on the severity of damage associated with virus presence in the brain tissue, and consequently

users to HIV infection, and potentially facilitating the penetration of virus across the blood mind barrier (BBB) into the mind. In this proposal we will dissect mechanisms by which Meth can induce and regulate free radical output, induce an aggravation on the severity of price associated with virus presence in the genius tissue, and consequently

usfrs to HIV infection, and potentially faeulitatmng the penetragion of virus across the blold braib barrier (BBB) into the brain. In this priposel we will disserf mechaknsms gn whieh Meth can induge and modunate free radiwau 'roduction, causing an aggravation on the sefegity of damage asspsiatsd with virus presence in the braih tissut, and consequently

users to HIV infection, and potentially facilitating of across the brain barrier (BBB) proposal will dissect mechanisms which Meth can and modulate free radical production, causing aggravation on the severity of damage associated with virus presence in the brain and consequently

users to HIV infection, and potEntially faCilitAtiNg tHe PeneTratIon of virus acroSS the Blood brain barrier (BBB) inTo the BrAIn. In THiS propOsal we wILl DISseCt MeChaNiSMs By whiCh MEth can iNduce and moDulAtE free radical PRoDuction, cauSinG an aggravatiOn oN the seVeRitY Of damAge AssocIated wITh viruS presence In THe braiN Tissue, aND CoNseqUently

users to HIV infection, a nd potenti allyfac ili ta ting  the  penetration o f  vir us across the blood br ain b ar r ier( BB B) in to theb ra i n . I nth ispr o po sal w e w ill dis sect mecha nis ms  by which Me t hcan induce  an d modulate f ree  radic al  pr o ducti on,  caus ing an aggrav ation onth e  sever i ty of d a m ag e as sociated with vir u sp resence in the  brain  t i ss u e , a ndconsequent ly

users_to HIV_infection, and potentially facilitating_the penetration_of_virus across_the_blood brain barrier_(BBB) into the_brain. In this proposal_we will dissect_mechanisms_by which Meth can induce and modulate free radical production, causing an aggravation on_the_severity of_damage_associated_with virus presence in the_brain tissue, and consequently


cortical cells and connections, regardless of the etiology. A common neuroanatomic denominator for dementia would greatly facilitate attempts to understand the cellular basis of dementing illnesses, and in turn, aid in directing therapeutic and preventative efforts to the appropriate cell class. These studies will involve detailed quantitative neuroanatomic analyses of non-

cortical cells and connections, regardless of the etiology. A common neuroanatomic denominator for dementia would greatly facilitate attempt to sympathize the cellular basis of dementing illnesses, and in twist, care in directing therapeutic and preventative attempt to the appropriate cell class. These study will involve detailed quantitative neuroanatomic analyses of non-

cogtical cells and connectlons, regardless of the xtiologg. A commun neuroanatomic denominator fir denentia would greatly fxcilitate attemptw to ynderstand the cellular gwsis if dementing iklnesses, atd in turn, aid iv birecting therapeutic and preventatide effottd to the approkriatt cqll dlass. These studies will involve dstailed quantitative neuroanatomic analyses of non-

cortical cells and connections, regardless of the common denominator for would greatly facilitate basis dementing illnesses, and turn, aid in therapeutic and preventative efforts to the cell class. These studies will involve detailed quantitative neuroanatomic analyses of non-

cortical cells and connectioNs, regardleSs of tHe eTioLoGy. A cOmmoN neuroanatomic DEnomInator for dementia would GreatLy FAcilITaTe attEmpts to UNdERStaNd ThE ceLlULaR basiS of DementiNg illnesseS, anD iN turn, aid in diREcTing therapEutIc and preventAtiVe effoRtS to THe appRopRiate Cell clASs. ThesE studies wIlL InvolvE DetaileD QUaNtitAtive neuroanatomiC AnALyses of non-

cortical cells and connec tions, reg ardle ssofth e et iolo gy. A common n e uroa natomic denominator fo r dem en t ia w o ul d gre atly fa c il i t ate  a tt emp ts to  unde rst and the  cellularbas is  of dementin g  i llnesses,and  in turn, ai d i n dire ct ing thera peu tic a nd pre v entati ve effort st o thea ppropri a t ecell  class. These stu d ie s  will involvedetail ed qu a n tit ati ve neuroan at omica nalyses of n o n-

cortical_cells and_connections, regardless of the_etiology. A_common_neuroanatomic denominator_for_dementia would greatly_facilitate attempts to_understand the cellular basis_of dementing illnesses,_and_in turn, aid in directing therapeutic and preventative efforts to the appropriate cell class._These_studies will_involve_detailed_quantitative neuroanatomic analyses of non-


dose for two weeks. The target AUC is considered to have been achieved if the dose was tolerated and at least 4 of 6 subjects reached the target AUC. Enrollment of subjects will be ongoing and those begun on a given starting dose will continue on that dose until individual subject dose adjustments are needed according to their individual pharmac

dose for two weeks. The target AUC is consider to have been achieve if the dose was tolerated and at least 4 of 6 discipline reach the target AUC. registration of topic will be ongoing and those begun on a contribute starting dose will cover on that dose until individual subject acid adaptation are needed harmonize to their individual pharmac

dode for two weeks. The tarnet AUC is consibwred tm have been acfieved if the dose was tolereted and qt least 4 of 6 subjects reached nhe targer AUR. Enrollment of subjects will gc ongmmng and those bggun on a gieen starting dmsd cill continue on that dose until indyvidual skbject dose adtustkqnts are needed according to their indjvidual pharmac

dose for two weeks. The target AUC to been achieved the dose was of subjects reached the AUC. Enrollment of will be ongoing and those begun a given starting dose will continue on that dose until individual subject dose are needed according to their individual pharmac

dose for two weeks. The target AuC is considEred tO haVe bEeN achIeveD if the dose was tOLeraTed and at least 4 of 6 subjectS reacHeD The tARgEt AUC. enrollmENt OF SubJeCtS wiLl BE oNgoinG anD those bEgun on a givEn sTaRting dose wilL CoNtinue on thAt dOse until indiVidUal subJeCt dOSe adjUstMents Are neeDEd accoRding to thEiR IndiviDUal pharMAC

dose for two weeks. The t arget AUCis co nsi der ed  tohave  been achieved if t he dose was toleratedand a tl east 4of 6subject s  r e a che dth e t ar g et  AUC.  En rollmen t of subje cts  w ill be ongoi n gand thosebeg un on a give n s tartin gdos e  will  co ntinu e on t h at dos e until i nd i vidual subject d os e ad justments are nee d ed according to t heir i nd i vi d u alpha rmac

dose_for two_weeks. The target AUC_is considered_to_have been_achieved_if the dose_was tolerated and_at least 4 of_6 subjects reached_the_target AUC. Enrollment of subjects will be ongoing and those begun on a given_starting_dose will_continue_on_that dose until individual subject_dose adjustments are needed according_to their_individual pharmac


high-level, long-term expression of a number of therapeutic proteins without eliciting a clinically significant immune reaction. The investigators have recently demonstrated high-efficacy gene transfer of GAA into embryonic tissues, cultured adult and neonatal rat cardiomyocytes, as well as, adult rat heart, and murine skeletal muscle in vivo using this

high - level, long - term formula of a numeral of therapeutic proteins without eliciting a clinically meaning immune reaction. The investigators have recently demonstrated eminent - efficacy gene transfer of GAA into embryonic tissues, civilized adult and neonatal informer cardiomyocytes, as well as, adult informer heart, and murine skeletal muscleman in vivo using this

hihh-level, long-term expresslon of a number of therepeutic proteinr without eliciting a clinicelly signuficant immune reactiov. The invvstigatorw hate recently demoiatrated high-ernicacv jene transfer on GAA into ambryonic tissger, eultured adult and neonatal rat cardyomyocyyed, as well as, aqult wat gvavt, and murine skeletal muscle in vivo uving this

high-level, long-term expression of a number of without a clinically immune reaction. The gene of GAA into tissues, cultured adult neonatal rat cardiomyocytes, as well as, rat heart, and murine skeletal muscle in vivo using this

high-level, long-term expressiOn of a numbeR of thEraPeuTiC proTeinS without elicitINg a cLinically significant imMune rEaCTion. tHe InvesTigatorS HaVE RecEnTlY deMoNStRated HigH-efficaCy gene tranSfeR oF GAA into embrYOnIc tissues, cUltUred adult and NeoNatal rAt CarDIomyoCytEs, as wEll as, aDUlt rat Heart, and mUrINe skelETal muscLE In Vivo Using this

high-level, long-term exp ression of  a nu mbe r o fther apeu tic proteins w i thou t eliciting a clinical ly si gn i fica n timmun e react i on . The  i nv est ig a to rs ha verecentl y demonstr ate dhigh-efficac y  g ene transf erof GAA intoemb ryonic  t iss u es, c ult uredadulta nd neo natal rat  c a rdiomy o cytes,a s  w ellas, adult rat hea r t, and murine ske letalmu s cl e inviv o using th is

high-level,_long-term expression_of a number of_therapeutic proteins_without_eliciting a_clinically_significant immune reaction._The investigators have_recently demonstrated high-efficacy gene_transfer of GAA_into_embryonic tissues, cultured adult and neonatal rat cardiomyocytes, as well as, adult rat heart,_and_murine skeletal_muscle_in_vivo using this


analysis of LDZ spheres at G1-G4 confirmed that a common LDZ signature was characterized by genes associated with oncogenic signaling pathways including tumor initiation, metastasis, and vasculogenesis and was able to predict clinical outcome of liver cancer patients. We conclude that epigenetic reprogramming of liver cancer cell lines induced by a combined

analysis of LDZ spheres at G1 - G4 confirmed that a common LDZ signature was qualify by gene associated with oncogenic signaling pathways include tumor trigger, metastasis, and vasculogenesis and was able to predict clinical outcome of liver cancer affected role. We reason that epigenetic reprogramming of liver cancer cell lines induced by a combined

anwlysis of LDZ spheres at G1-G4 confirmed tkqt a cmmmon MDZ signxture was characterized by gxnes assoxiated with oncogenic rignaling pathwayw inrluding tumor inmfiation, metasfwsis, end vasculogenexis and wav able to predhcg elinical outcome of liver cancer patyents. Wr fonclude that gpigemqtic gekrogramming of liver cancer cell mines iiduced by a comnined

analysis of LDZ spheres at G1-G4 confirmed common signature was by genes associated tumor metastasis, and vasculogenesis was able to clinical outcome of liver cancer patients. conclude that epigenetic reprogramming of liver cancer cell lines induced by a combined

analysis of LDZ spheres at G1-G4 cOnfirmed thAt a coMmoN LDz sIgnaTure Was characterizED by gEnes associated with oncoGenic SiGNaliNG pAthwaYs incluDInG TUmoR iNiTiaTiON, mEtastAsiS, and vasCulogenesiS anD wAs able to predICt Clinical ouTcoMe of liver canCer PatienTs. we cONcludE thAt epiGenetiC ReprogRamming of LiVEr cancER cell liNES iNducEd by a combined

analysis of LDZ spheres a t G1-G4 co nfirm edtha ta co mmon  LDZ signature wascharacterized by genes  asso ci a tedw it h onc ogenics ig n a lin gpa thw ay s  i nclud ing  tumorinitiation , m et astasis, and va sculogenes isand was able  to  predi ct  cl i nical  ou tcome  of li v er can cer patie nt s . We c o ncludet h at  epi genetic reprogram m in g  of liver canc er cel ll in e s  in duc ed by a co mb ined

analysis_of LDZ_spheres at G1-G4 confirmed_that a_common_LDZ signature_was_characterized by genes_associated with oncogenic_signaling pathways including tumor_initiation, metastasis, and_vasculogenesis_and was able to predict clinical outcome of liver cancer patients. We conclude that_epigenetic_reprogramming of_liver_cancer_cell lines induced by a_combined


in particular. Recent discoveries in molecular genetics have lead to the identification of functional variations in several candidate genes for susceptibility to obesity, insulin resistance, and/or diabetes. These include genes which code for beta-2and beta-3 adrenergic receptors, insulin receptor substrate 1, fatty acid binding protein 2, fratax

in particular. Recent discoveries in molecular genetics have lead to the designation of running variations in several campaigner genes for susceptibility to fleshiness, insulin resistance, and/or diabetes. These include gene which code for beta-2and beta-3 adrenergic receptors, insulin receptor substrate 1, fatty acid bind protein 2, fratax

in particular. Recent discoyeries in molecular genxtics hzve lead to the identification of fuictiinal cariations in several zandidate genes fir snsceptibility to obesity, insuljk resnsvance, and/or dianetes. These include genes wfieh code for beta-2and beta-3 adrenergic weceptots, insulin recepjor slbftrafv 1, fatty acid binding protein 2, rratax

in particular. Recent discoveries in molecular genetics to identification of variations in several obesity, resistance, and/or diabetes. include genes which for beta-2and beta-3 adrenergic receptors, insulin substrate 1, fatty acid binding protein 2, fratax

in particular. Recent discoveRies in moleCular GenEtiCs Have Lead To the identificATion Of functional variations In sevErAL canDIdAte geNes for sUScEPTibIlItY to ObESiTy, insUliN resistAnce, and/or dIabEtEs. These incluDE gEnes which cOde For beta-2and beTa-3 aDrenerGiC reCEptorS, inSulin ReceptOR substRate 1, fatty AcID bindiNG proteiN 2, FRaTax

in particular. Recent dis coveries i n mol ecu lar  g enet icshave lead to t h e id entification of functi onalva r iati o ns  in s everalc an d i dat ege nes  f o rsusce pti bilityto obesity , i ns ulin resista n ce , and/or d iab etes. Theseinc lude g en esw hichcod e for  beta- 2 and be ta-3 adre ne r gic re c eptors, i ns ulin  receptor substra t e1 , fatty acid b inding  p r ot e i n 2 , f ratax

in_particular. Recent_discoveries in molecular genetics_have lead_to_the identification_of_functional variations in_several candidate genes_for susceptibility to obesity,_insulin resistance, and/or_diabetes._These include genes which code for beta-2and beta-3 adrenergic receptors, insulin receptor substrate 1,_fatty_acid binding_protein_2,_fratax


the gain in some frequency channels has been permanently decreased. The data will be analyzed within a well-established physiologically-based model of the peripheral auditory system, to determine whether temporal effects are consistent with a decrease in gain within the auditory channel which is stimulated. This research is important to our understanding of basic auditory processing in

the gain in some frequency channels has been permanently decreased. The data will be analyze within a well - prove physiologically - based model of the peripheral auditory system, to decide whether temporal effects are coherent with a decrease in profit within the auditory channel which is stimulated. This research is important to our reason of basic auditory processing in

thf gain in some frequency channels has bgeb permenently decreasdd. The data will be analyzed wuthin a well-established phyriologicaply-based modtl of the peripheczl audibjry anstem, vo determine whgther tempordl effects are cundistent with a decrease in gain witrin the akditory channej whpcr is stimulated. This research is imporfant to our understamding of basic auditory prlcesding in

the gain in some frequency channels has decreased. data will analyzed within a peripheral system, to determine temporal effects are with a decrease in gain within auditory channel which is stimulated. This research is important to our understanding of auditory processing in

the gain in some frequency chaNnels has beEn perManEntLy DecrEaseD. The data will be ANalyZed within a well-establisHed phYsIOlogICaLly-baSed modeL Of THE peRiPhEraL aUDiTory sYstEm, to detErmine whetHer TeMporal effectS ArE consistenT wiTh a decrease iN gaIn withIn The AUditoRy cHanneL which IS stimuLated. This ReSEarch iS ImportaNT To Our uNderstanding of basIC aUDitory processiNg in

the gain in some frequenc y channels  hasbee n p er mane ntly  decreased. Th e  dat a will be analyzed wit hin a  w e ll-e s ta blish ed phys i ol o g ica ll y- bas ed mo del o f t he peri pheral aud ito ry  system, tod et ermine whe the r temporal e ffe cts ar econ s isten t w ith a  decre a se ingain with in the au d itory c h a nn el w hich is stimulate d .T his research i s impo rt a nt t o o urunderstand in g ofb asic au d it o r y  pr o cessing in

the_gain in_some frequency channels has_been permanently_decreased._The data_will_be analyzed within_a well-established physiologically-based_model of the peripheral_auditory system, to_determine_whether temporal effects are consistent with a decrease in gain within the auditory channel_which_is stimulated._This_research_is important to our understanding_of basic auditory processing in


SH, the adenylyl cyclase enzyme exhibits a transient attenuation response. In specific aim one, we will investigate possible mechanisms responsible for the transient attenuation of the granulosa cell adenylate cyclase enzyme. cAMP Induces all of the differentiation-associated effects in immature granulosa cells attributed to FSH; thus

SH, the adenylyl cyclase enzyme exhibits a transient attenuation response. In specific aim one, we will investigate potential mechanism responsible for the transient attenuation of the granulosa cellular telephone adenylate cyclase enzyme. cAMP induce all of the differentiation - associate effects in immature granulosa cell attributed to FSH; therefore

SH, hhe adenylyl cyclase enznme exhibits a ttabsient attenhation rdsponse. In specific aim one, xe wull ibvestigate possible mezhanisms gesponsiboe fie the transient atbznuatjln oy vhe granulosa cgll adenylata cyclase enzyke. cCMP Induces all of the differentiatijn-assocoahed effects in immseure granulosa cells attributed to FSH; thus

SH, the adenylyl cyclase enzyme exhibits a response. specific aim we will investigate transient of the granulosa adenylate cyclase enzyme. Induces all of the differentiation-associated effects immature granulosa cells attributed to FSH; thus

SH, the adenylyl cyclase enzymE exhibits a TransIenT atTeNuatIon rEsponse. In speciFIc aiM one, we will investigate pOssibLe MEchaNIsMs resPonsiblE FoR THe tRaNsIenT aTTeNuatiOn oF the graNulosa cell AdeNyLate cyclase eNZyMe. cAMP InduCes All of the diffEreNtiatiOn-AssOCiateD efFects In immaTUre graNulosa celLs ATtribuTEd to FSH; THUs

SH, the adenylyl cyclase e nzyme exhi bitsa t ran si entatte nuation respon s e. I n specific aim one, we  will  i n vest i ga te po ssiblem ec h a nis ms  r esp on s ib le fo r t he tran sient atte nua ti on of the gr a nu losa cellade nylate cycla seenzyme .cAM P  Indu ces  allof the differ entiation -a s sociat e d effec t s  i n im mature granulosac el l s attributed t o FSH;  t h us

SH, the_adenylyl cyclase_enzyme exhibits a transient_attenuation response._In_specific aim_one,_we will investigate_possible mechanisms responsible_for the transient attenuation_of the granulosa_cell_adenylate cyclase enzyme. cAMP Induces all of the differentiation-associated effects in immature granulosa cells_attributed_to FSH;_thus


to address these impediments by developing a 3D geometric hand model, to be integrated into the current CAD design software products used by design engineers (e.g., SolidWorks, ProE) to evaluate the interaction between the hand and a new product. The proposed Phase 1 research will result in a virtual hand model that

to address these impediments by developing a 3D geometric hand exemplar, to be integrate into the current CAD design software products used by purpose engineers (e.g., SolidWorks, ProE) to measure the interaction between the hand and a new product. The propose Phase 1 research will result in a virtual bridge player model that

to address these impedimenus by developing c 3D geoketric hand moael, to be integrated into thx cuerent CAD design software pfoducts uded by dwsigi engineers (e.g., SolidWorks, ProE) bo evclnate the interagtion betwean the hand ang x uew product. The proposed Phase 1 resewrch wikl result in a vyrtusj hahd model that

to address these impediments by developing a hand to be into the current by engineers (e.g., SolidWorks, to evaluate the between the hand and a new The proposed Phase 1 research will result in a virtual hand model that

to address these impediments By developiNg a 3D gEomEtrIc Hand ModeL, to be integrateD Into The current CAD design sofTware PrODuctS UsEd by dEsign enGInEERs (e.G., SOlIdWOrKS, PRoE) to EvaLuate thE interactiOn bEtWeen the hand aND a New product. the Proposed PhasE 1 reSearch WiLl rESult iN a vIrtuaL hand mODel thaT

to address these impedime nts by dev elopi nga 3 Dgeom etri c hand model,t o be  integrated into the c urren tC AD d e si gn so ftwarep ro d u cts  u se d b yd es ign e ngi neers ( e.g., Soli dWo rk s, ProE) toe va luate theint eraction bet wee n theha nda nd anew  prod uct. T h e prop osed Phas e1  resea r ch will r es ultin a virtual hand mo d el that

to_address these_impediments by developing a_3D geometric_hand_model, to_be_integrated into the_current CAD design_software products used by_design engineers (e.g.,_SolidWorks,_ProE) to evaluate the interaction between the hand and a new product. The proposed_Phase_1 research_will_result_in a virtual hand model_that


for natural blinking and tearing. Associated studies will be performed to quantify the surface-chemical events associated with tear spreading, and the effectiveness of commercially available artificial tear preparations in duplicating the wetting and spreading properties of natural tears will be investigated. The mission of the Analytical Laboratory for Pharmacogenetics, Pharmacodynamics and

for natural blinking and tearing. Associated studies will be perform to quantify the open - chemical events associated with tear dissemination, and the effectiveness of commercially available artificial tear preparations in double the leak and spreading properties of natural tears will be investigated. The deputation of the Analytical Laboratory for Pharmacogenetics, Pharmacodynamics and

fog natural blinking and ttaring. Associated studiev will be perfurmed to quantify the surfacx-chenical events associated witf tear spgeading, abd tie effectiveness of commcxcialmn avanleble artificial tear prepdrations in du[lkccting the wetting and spreading propqrties pf natural tears wilk be jnvestigated. The mission of the Anzlytican Laboratory gor Pharmacogenetics, Pharmwcodjnamics and

for natural blinking and tearing. Associated studies performed quantify the events associated with of available artificial tear in duplicating the and spreading properties of natural tears be investigated. The mission of the Analytical Laboratory for Pharmacogenetics, Pharmacodynamics and

for natural blinking and tearIng. AssociaTed stUdiEs wIlL be pErfoRmed to quantify THe suRface-chemical events assOciatEd WIth tEAr SpreaDing, and THe EFFecTiVeNesS oF CoMmercIalLy availAble artifiCiaL tEar preparatiONs In duplicatIng The wetting anD spReadinG pRopERties Of nAturaL tears WIll be iNvestigatEd. tHe missIOn of the aNAlYticAl Laboratory for PhARmACogenetics, PharMacodyNaMIcS ANd

for natural blinking andtearing. A ssoci ate d s tu dies  wil l be performed to q uantify the surface-ch emica le vent s  a ssoci ated wi t ht e arsp re adi ng ,  a nd th e e ffectiv eness of c omm er cially avail a bl e artifici altear prepara tio ns indu pli c ating  th e wet ting a n d spre ading pro pe r ties o f  natura l te arswill be investiga t ed .  The mission o f theAn a ly t i cal  La boratory f or  Phar m acogene t ic s , Pha r macodynamicsand

for_natural blinking_and tearing. Associated studies_will be_performed_to quantify_the_surface-chemical events associated_with tear spreading,_and the effectiveness of_commercially available artificial_tear_preparations in duplicating the wetting and spreading properties of natural tears will be investigated._The_mission of_the_Analytical_Laboratory for Pharmacogenetics, Pharmacodynamics and


uncover the primary mode of action of NGF by studying the ability of various chemical substances to mimic, enchance, or inhibit the effect of NGF on cultured sympathetic neurons. (3) Creation and characterization of dividing cell lines with neuronal properties. We shall use somatic cell hybridization and suitable selection techniques to fuse primary sympathetic

uncover the primary mode of action of NGF by studying the ability of diverse chemical meaning to mimic, enchance, or inhibit the effect of NGF on cultured harmonic neurons. (3) Creation and portrayal of separate cell credit line with neuronal properties. We shall practice somatic cell hybridization and suitable selection technique to fuse primary sympathetic

unfover the primary mode on action of NGF yt studbing ths abilith of various chemical substaices to mumic, enchance, or inhibkt the efvect of BGF ib cultured sympathccic nsmrons. (3) Creation and gharacterizdtion of dividhne eell lines with neuronal properties. Re shalk kse somatic cejl hjbwidiaation and suitable selection techhiques uo fuse primary sykpathetic

uncover the primary mode of action of studying ability of chemical substances to effect NGF on cultured neurons. (3) Creation characterization of dividing cell lines with properties. We shall use somatic cell hybridization and suitable selection techniques to fuse sympathetic

uncover the primary mode of acTion of NGF bY studYinG thE aBiliTy of Various chemicaL SubsTances to mimic, enchance, oR inhiBiT The eFFeCt of NgF on culTUrED SymPaThEtiC nEUrOns. (3) CrEatIon and cHaracterizAtiOn Of dividing ceLL lInes with neUroNal propertieS. We Shall uSe SomATic ceLl hYbridIzatioN And suiTable seleCtIOn techNIques to FUSe PrimAry sympathetic

uncover the primary modeof actionof NG F b y s tu dyin g th e ability of v a riou s chemical substancesto mi mi c , en c ha nce,or inhi b it t heef fe ctof NG F oncul tured s ympathetic  ne ur ons. (3) Cre a ti on and cha rac terization o f d ividin gcel l  line s w ith n eurona l  prope rties. We  s h all us e  somati c ce ll h ybridization ands ui t able selection  techn iq u es t o f use  primary s ym pathe t ic

uncover_the primary_mode of action of_NGF by_studying_the ability_of_various chemical substances_to mimic, enchance,_or inhibit the effect_of NGF on_cultured_sympathetic neurons. (3) Creation and characterization of dividing cell lines with neuronal properties. We_shall_use somatic_cell_hybridization_and suitable selection techniques to_fuse primary sympathetic


Aims are: 1. Structural studies of MsbA with anti-cancer compounds and nucleotide analogs. 2. Functional studies of MsbA and the detection of inhibitors. 3. Structural studies of MsbA with compounds that occupy the "ON" and "OFF" sites of MsbA (Class I Ms

Aims are: 1. Structural studies of MsbA with anti - cancer compounds and nucleotide analogue. 2. running cogitation of MsbA and the detection of inhibitor. 3. Structural cogitation of MsbA with compounds that occupy the " ON " and " OFF " site of MsbA (Class I Ms

Ails are: 1. Structural studits of MsbA with auri-cancxr compkunds ana nucleotide analogs. 2. Functilnql stydies of MsbA and the aetection of inhivitocs. 3. Structural svhdies on MsbZ witk rompounds that pccupy the "ON" and "OFF" sider lf MsbA (Class I Ms

Aims are: 1. Structural studies of MsbA compounds nucleotide analogs. Functional studies of inhibitors. Structural studies of with compounds that the "ON" and "OFF" sites of (Class I Ms

Aims are: 1. Structural studies oF MsbA with aNti-caNceR coMpOundS and Nucleotide analOGs. 2. FuNctional studies of MsbA aNd the DeTEctiON oF inhiBitors. 3. STRuCTUraL sTuDieS oF msBA witH coMpounds That occupy The "oN" And "OFF" sites oF msBA (Class I Ms

Aims are: 1. Structural s tudies ofMsbAwit h a nt i-ca ncer  compounds and nucl eotide analogs. 2. Fun ction al stud i es  of M sbA and th e det ec ti onof in hibit ors . 3. St ructural s tud ie s of MsbA wi t hcompoundstha t occupy the  "O N" and  " OFF "  site s o f Msb A (Cla s s I Ms

Aims_are: 1._Structural studies of MsbA_with anti-cancer_compounds_and nucleotide_analogs._2. Functional studies_of MsbA and_the detection of inhibitors._3. Structural studies_of_MsbA with compounds that occupy the "ON" and "OFF" sites of MsbA (Class I_Ms


Aguayo, 1981; Bently and Aguayo, 1982; Guth et al., 1981; Silver and Ogawa, 1983; Goldberg et al., 1986). These findings have renewed interest in regeneration of central nervous system neurons with much of the attention focused on inducing regeneration in species that under normal conditions exhibit little

Aguayo, 1981; Bently and Aguayo, 1982; Guth et al. , 1981; Silver and Ogawa, 1983; Goldberg et al. , 1986). These findings have renewed interest in regeneration of cardinal skittish system neurons with much of the care focused on induce regeneration in coinage that under normal conditions exhibit little

Agkayo, 1981; Bently and Aguayo, 1982; Guth et al., 1981; Silver anv Ogawa, 1983; Goldbefg et al., 1986). These findings havx rebewed interest in regeneratkon of cejtral neevouw system nendons wibk mucg of chx attention focosed on induwing regenerathov nn species that under normal conditijns exhoblt little

Aguayo, 1981; Bently and Aguayo, 1982; Guth 1981; and Ogawa, Goldberg et al., interest regeneration of central system neurons with of the attention focused on inducing in species that under normal conditions exhibit little

Aguayo, 1981; Bently and Aguayo, 1982; Guth Et al., 1981; Silver And OgAwa, 1983; golDbErg eT al., 1986). THese findings haVE renEwed interest in regeneraTion oF cENtraL NeRvous System nEUrONS wiTh MuCh oF tHE aTtentIon Focused On inducing RegEnEration in speCIeS that under NorMal conditionS exHibit lItTle

Aguayo, 1981; Bently andAguayo, 19 82; G uth  et  a l.,1981 ; Silver and O g awa,  1983; Goldberg et al. , 198 6) .  The s efindi ngs hav e  r e n ewe din ter es t  i n reg ene rationof central  ne rv ous system n e ur ons with m uch  of the atte nti on foc us edo n ind uci ng re genera t ion in  speciesth a t unde r  normal c on diti ons exhibit littl e

Aguayo,_1981; Bently_and Aguayo, 1982; Guth_et al.,_1981;_Silver and_Ogawa,_1983; Goldberg et_al., 1986). These_findings have renewed interest_in regeneration of_central_nervous system neurons with much of the attention focused on inducing regeneration in species_that_under normal_conditions_exhibit_little


aspects of cooperative group activities, including accrual, administrative and scientific input and data quality, the specific aims of the proposal for the next six years are to: 1. continue to enhance accrual in all disease site and modalities, beyong our current particpation, particularly in breast and lung cancers. 2.

aspects of cooperative group activities, including accrual, administrative and scientific stimulation and datum quality, the specific aims of the marriage proposal for the next six year are to: 1. continue to enhance accrual in all disease web site and modalities, beyong our current particpation, particularly in breast and lung cancers. 2.

asoects of cooperative gromp activities, ineouding accruzl, adminkstrative and scientific inpnt abd dauc quality, the specifkc aims ov the priposel for the next six years are fl: 1. cmitinue to enhange accrual hn all disease sktz and modalities, beyong our current [articpstlon, particularjy im brezst and lung cancers. 2.

aspects of cooperative group activities, including accrual, scientific and data the specific aims next years are to: continue to enhance in all disease site and modalities, our current particpation, particularly in breast and lung cancers. 2.

aspects of cooperative group Activities, IncluDinG acCrUal, aDminIstrative and scIEntiFic input and data quality, The spEcIFic aIMs Of the ProposaL FoR THe nExT sIx yEaRS aRe to: 1. cOntInue to eNhance accrUal In All disease siTE aNd modalitiEs, bEyong our currEnt ParticPaTioN, PartiCulArly iN breasT And lunG cancers. 2.

aspects of cooperative gr oup activi ties,  in clu di ng a ccru al, administra t iveand scientific input a nd da ta qual i ty , the  specif i ca i msof  t hepr o po sal f orthe nex t six year s a re  to: 1. cont i nu e to enhan ceaccrual in a lldiseas esit e  andmod aliti es, be y ong ou r current  p a rticpa t ion, pa r t ic ular ly in breast andl un g  cancers. 2.

aspects_of cooperative_group activities, including accrual,_administrative and_scientific_input and_data_quality, the specific_aims of the_proposal for the next_six years are_to:_1. continue to enhance accrual in all disease site and modalities, beyong our current_particpation,_particularly in_breast_and_lung cancers. 2.


orphic structures in the cortex and the behavior(s) mediated by this brain region. Our results will provide new important information on the functional link between alternative splicing and brain sexual differentiation. Successful completion of this project will also help the PI establish a new line of research in neuroendocrinology with the enhanced competitiveness

orphic structures in the cortex and the behavior(s) mediated by this mind area. Our results will provide newfangled crucial information on the functional radio link between alternate splicing and brain sexual differentiation. Successful completion of this project will besides help the PI establish a new line of inquiry in neuroendocrinology with the enhanced competitiveness

orpjic structures in the covtex and the behccior(s) kediatsd by thks brain region. Our results xill provude new important infofmation oj the fubctiibal link bxfween alternaflve s'lmcing and brain sexual dixferentiation. Vuzczssful completion of this project wijl also hflp the PI estwblixr a hvw line of research in neuroendkcrinolmgy with the rnhanced competitiveness

orphic structures in the cortex and the by brain region. results will provide functional between alternative splicing brain sexual differentiation. completion of this project will also the PI establish a new line of research in neuroendocrinology with the enhanced

orphic structures in the cortEx and the beHavioR(s) mEdiAtEd by This Brain region. Our REsulTs will provide new importAnt inFoRMatiON oN the fUnctionAL lINK beTwEeN alTeRNaTive sPliCing and Brain sexuaL diFfErentiation. SUCcEssful compLetIon of this proJecT will aLsO heLP the Pi esTabliSh a new LIne of rEsearch in NeURoendoCRinologY WItH the Enhanced competitiVEnESs

orphic structures in the c ortex andthe b eha vio r( s) m edia ted by this br a in r egion. Our results wil l pro vi d e ne w  i mport ant inf o rm a t ion  o nthe  f u nc tiona l l ink bet ween alter nat iv e splicing a n dbrain sexu aldifferentiat ion . Succ es sfu l  comp let ion o f this projec t will al so help t h e PI es t a bl isha new line of res e ar c h in neuroendo crinol og y  w i t h t heenhanced c om petit i veness

orphic structures_in the_cortex and the behavior(s)_mediated by_this_brain region._Our_results will provide_new important information_on the functional link_between alternative splicing_and_brain sexual differentiation. Successful completion of this project will also help the PI establish_a_new line_of_research_in neuroendocrinology with the enhanced_competitiveness


(T-cell intrinsic vs. T-cell extrinsic), de?ne the role of T cells, speci?c to irrelevant antigens, in the formation of clusters, and quantify the impact of T cell cluster size on the ef?ciency at which liver stages are eliminated. In speci?c Aim 2

(T - cell intrinsic vs. T - cell extrinsic), de?ne the role of metric ton cell, speci?c to irrelevant antigens, in the formation of clusters, and quantify the shock of T cell bunch size on the ef?ciency at which liver stages are eliminated. In speci?c Aim 2

(T-cfll intrinsic vs. T-cell ewtrinsic), de?ne thg eole oh T celms, speci?z to irrelevant antigens, in vhe dormaupon of clusters, and qjantify tje impacr of R cell cluster sizc on fme ef?eixncy at which llver stages are eliminateg. Kn speci?c Aim 2

(T-cell intrinsic vs. T-cell extrinsic), de?ne the T speci?c to antigens, in the the of T cell size on the at which liver stages are eliminated. speci?c Aim 2

(T-cell intrinsic vs. T-cell extrInsic), de?ne tHe rolE of t ceLlS, speCi?c tO irrelevant antIGens, In the formation of clusteRs, and QuANtifY ThE impaCt of T ceLL cLUSteR sIzE on ThE Ef?CiencY at Which liVer stages aRe eLiMinated. In speCI?c aim 2

(T-cell intrinsic vs. T-c ell extrin sic),  de ?ne  t he r oleof T cells, sp e ci?c  to irrelevant antigen s, in  t h e fo r ma tionof clus t er s ,  an dqu ant if y  t he im pac t of Tcell clust ersi ze on the ef ? ci ency at wh ich  liver stage s a re eli mi nat e d. In  sp eci?c  Aim 2

(T-cell_intrinsic vs._T-cell extrinsic), de?ne the_role of_T_cells, speci?c_to_irrelevant antigens, in_the formation of_clusters, and quantify the_impact of T_cell_cluster size on the ef?ciency at which liver stages are eliminated. In speci?c Aim_2


by passive immunization with xenoantisera, whereas evasion-negative tumors are rejected by some immunized mice and growth is markedly suppressed in others. Evasion-positive and -negative variants of FLC745 and RBL-5 lymphomas are being studied to establish the relationship between antigen evasion and tumor escape. X

by passive immunization with xenoantisera, whereas evasion - negative tumors are rejected by some immunized mouse and increase is markedly suppressed in others. Evasion - positive and -negative variants of FLC745 and RBL-5 lymphoma are being studied to establish the relationship between antigen evasion and tumor evasion. X

by passive immunization wiuh xenoantisera, wkwreas xvasion-hegative tumors are rejected by some inmunievd mice and growth is markedly suppreswed mn others. Evasioi-lositivc and -kegatnvx variants of FKC745 and RBL-5 lymphomas are bdiug studied to establish the relationfhip beywfen antigen evwsiom and nunor escape. X

by passive immunization with xenoantisera, whereas evasion-negative rejected some immunized and growth is and variants of FLC745 RBL-5 lymphomas are studied to establish the relationship between evasion and tumor escape. X

by passive immunization with XenoantiseRa, wheReaS evAsIon-nEgatIve tumors are reJEcteD by some immunized mice anD growTh IS marKEdLy supPressed IN oTHErs. evAsIon-PoSItIve anD -neGative vAriants of FlC745 aNd rBL-5 lymphomas ARe Being studiEd tO establish thE reLationShIp bETween AntIgen eVasion ANd tumoR escape. X

by passive immunization w ith xenoan tiser a,whe re as e vasi on-negative tu m orsare rejected by some i mmuni ze d  mic e  a nd gr owth is ma r k edl ysu ppr es s ed  in o the rs. Eva sion-posit ive  a nd -negative va riants ofFLC 745 and RBL- 5 l ymphom as  ar e  bein g s tudie d to e s tablis h the rel at i onship between a nt igen  evasion and tumo r  e s cape. X

by_passive immunization_with xenoantisera, whereas evasion-negative_tumors are_rejected_by some_immunized_mice and growth_is markedly suppressed_in others. Evasion-positive and_-negative variants of_FLC745_and RBL-5 lymphomas are being studied to establish the relationship between antigen evasion and_tumor_escape. X


validated on a number of well characterized performance and seroconversion panels for all five viruses and on large numbers (>1,000) of blood samples from normal blood donors. This test will provide a highly sensitive, cost-effective direct measure of infectious virus in blood and help further reduce the antibody-negative "window" period

validated on a number of well characterized performance and seroconversion panel for all five virus and on large numbers (> 1,000) of blood sample distribution from normal blood donors. This examination will put up a highly sensitive, cost - effective direct measure of infectious virus in lineage and help further dilute the antibody - damaging " window " period

vapidated on a number of wtll characterized perforkance znd serozonversion panels for all fite vurusew and on large numbers (>1,000) of bloof samplew frin normal blood donors. Thjd tevv will provide s highly sansitive, cost-exfdccive direct measure of infectious viwus in nllod and help fortheg wedudv uhe antibody-negative "window" perios

validated on a number of well characterized seroconversion for all viruses and on samples normal blood donors. test will provide highly sensitive, cost-effective direct measure of virus in blood and help further reduce the antibody-negative "window" period

validated on a number of well cHaracterizEd perForManCe And sErocOnversion panelS For aLl five viruses and on largE numbErS (>1,000) Of blOOd SamplEs from nORmAL BloOd DoNorS. THIs Test wIll Provide A highly senSitIvE, cost-effectiVE dIrect measuRe oF infectious vIruS in bloOd And HElp fuRthEr redUce the ANtibodY-negative "WiNDow" perIOd

validated on a number ofwell chara cteri zed  pe rf orma nceand seroconver s ionpanels for all five vi ruses  a n d on la rge n umbers( >1 , 0 00)  o fblo od sa mples  fr om norm al blood d ono rs . This testw il l providea h ighly sensit ive , cost -e ffe c tivedir ect m easure of inf ectious v ir u s in b l ood and h el p fu rther reduce thea nt i body-negative"windo w" pe r i od

validated_on a_number of well characterized_performance and_seroconversion_panels for_all_five viruses and_on large numbers_(>1,000) of blood samples_from normal blood_donors._This test will provide a highly sensitive, cost-effective direct measure of infectious virus in_blood_and help_further_reduce_the antibody-negative "window" period


expression, promoting insulin resistance, and modulating ER stress-induced cell death in specific tissues. This hypothesis will be tested by three complementary Aims. In Aim 1 biochemical and molecular biological methods will be used to delineate the pathway(s) required for MLK3 activation by FFA. In Aim 2 biochemical and molecular

expression, promoting insulin resistance, and modulating ER tension - induce cell death in specific tissue. This guess will be tested by three complementary Aims. In Aim 1 biochemical and molecular biological method will be used to delineate the pathway(s) necessitate for MLK3 activation by FFA. In Aim 2 biochemical and molecular

exoression, promoting insulln resistance, anb moduleting ED stress-knduced cell death in specifmc tussuew. This hypothesis will be testef by thrwe cinplementarb Aims. Ik Aim 1 bioehxmical and molegular biolocical methods fiul be used to delineate the pathway(s) wequirec vor MLK3 activajion nr FFZ. In Aim 2 biochemical and moleculad

expression, promoting insulin resistance, and modulating ER death specific tissues. hypothesis will be In 1 biochemical and biological methods will used to delineate the pathway(s) required MLK3 activation by FFA. In Aim 2 biochemical and molecular

expression, promoting insuliN resistancE, and mOduLatInG ER sTresS-induced cell deATh in Specific tissues. This hypOthesIs WIll bE TeSted bY three cOMpLEMenTaRy aimS. IN aiM 1 biocHemIcal and Molecular bIolOgIcal methods wILl Be used to deLinEate the pathwAy(s) RequirEd For mlK3 actIvaTion bY FFA. In aIm 2 biocHemical anD mOLeculaR

expression, promoting ins ulin resis tance , a ndmo dula ting  ER stress-ind u cedcell death in specific  tiss ue s . Th i shypot hesis w i ll b e t es te d b yt hr ee co mpl ementar y Aims. In  Ai m1 biochemica l  a nd molecul arbiological m eth ods wi ll  be usedtodelin eate t h e path way(s) re qu i red fo r  MLK3 a c t iv atio n by FFA. In Aim2  b i ochemical andmolecu la r

expression,_promoting insulin_resistance, and modulating ER_stress-induced cell_death_in specific_tissues._This hypothesis will_be tested by_three complementary Aims. In_Aim 1 biochemical_and_molecular biological methods will be used to delineate the pathway(s) required for MLK3 activation_by_FFA. In_Aim_2_biochemical and molecular


other reports in the literature demonstrating upregulation of NF-kappaB and AP-1 as well as identify other important transcription factors not reported in the literature. These and other experiments, as well as published reports lead us to modify our hypothesis that increased expression of MAP3K8 occur in lung cancer and contribute to disease progression.

other reports in the literature demonstrating upregulation of NF - kappaB and AP-1 as well as identify early authoritative transcription factors not report in the literature. These and early experiments, as well as published report card lead us to modify our guess that increase expression of MAP3K8 happen in lung cancer and contribute to disease progression.

otjer reports in the literxture demonstrajibg uprxgulatikn of NF-yappaB and AP-1 as well as ideitift othtg important transcripgion factlrs not eepocted in the liteczture. Tmzse ahf otkec experiments, ax well as [ublished repostr pead us to modify our hypothesis thwt incrraded expression of KWP3K8 kbcmr in lung cancer and contribute to distase progression.

other reports in the literature demonstrating upregulation and as well identify other important the These and other as well as reports lead us to modify our that increased expression of MAP3K8 occur in lung cancer and contribute to disease

other reports in the literatuRe demonstrAting UprEguLaTion Of NF-KappaB and AP-1 as wELl as Identify other important TransCrIPtioN FaCtors Not repoRTeD IN thE lItEraTuRE. THese aNd oTher expEriments, as WelL aS published rePOrTs lead us to ModIfy our hypothEsiS that iNcReaSEd expResSion oF MAP3K8 oCCur in lUng cancer AnD ContriBUte to diSEAsE proGression.

other reports in the lite rature dem onstr ati ngup regu lati on of NF-kappa B  and  AP-1 as well as ident ify o th e r im p or tanttranscr i pt i o n f ac to rsno t  r eport edin theliterature . T he se and other ex periments,  as  well as pub lis hed re po rts leadusto mo dify o u r hypo thesis th at increa s ed expr e s si on o f MAP3K8 occur in lu n g cancer and c ontrib ut e  t o dis eas e progress io n.

other_reports in_the literature demonstrating upregulation_of NF-kappaB_and_AP-1 as_well_as identify other_important transcription factors_not reported in the_literature. These and_other_experiments, as well as published reports lead us to modify our hypothesis that increased_expression_of MAP3K8_occur_in_lung cancer and contribute to_disease progression.


41 but retains gliding function. Insertions in the P65 gene result in the dragging of surface adhesin P30 from the terminal organelle to the trailing end, where it detaches to leave a trail behind the gliding cell. In the absence of P41, P24 foci appear to move along the long

41 but retains gliding function. Insertions in the P65 gene leave in the dragging of open adhesin P30 from the terminal organelle to the trailing end, where it detach to entrust a trail behind the gliding cellular telephone. In the absence of P41, P24 foci appear to move along the retentive

41 buh retains gliding functiun. Insertions iu the P65 gene desult iv the dragging of surface adiesib P30 feom the terminal organdlle to tje trailung tnd, where it detarges to leave z tranl behind the gllding cell. Hn the absence ow '41, P24 foci appear to move along the logg

41 but retains gliding function. Insertions in gene in the of surface adhesin to trailing end, where detaches to leave trail behind the gliding cell. In absence of P41, P24 foci appear to move along the long

41 but retains gliding function. insertions In the p65 geNe rEsUlt iN the Dragging of surfACe adHesin P30 from the terminal oRganeLlE To thE TrAilinG end, wheRE iT DEtaChEs To lEaVE a Trail BehInd the gLiding cell. in tHe Absence of P41, P24 fOCi Appear to moVe aLong the long

41 but retains gliding fun ction. Ins ertio nsinth e P6 5 ge ne result in t h e dr agging of surface adhe sin P 30 from th e ter minal o r ga n e lle  t othe  t r ai lingend , where  it detach esto  leave a tra i lbehind the  gl iding cell.Inthe ab se nce of P4 1,P24 f oci ap p ear to  move alo ng the lo n g

41 but_retains gliding_function. Insertions in the_P65 gene_result_in the_dragging_of surface adhesin_P30 from the_terminal organelle to the_trailing end, where_it_detaches to leave a trail behind the gliding cell. In the absence of P41,_P24_foci appear_to_move_along the long


, as cone photoreceptors are responsible for bright and color vision. At present, the mechanisms governing diabetes-induced photoreceptor degeneration are largely unexplored. Recent studies suggest that vascular endothelial growth factor (VEGF), a major angiogenic factor that is up-regulated under hypoxic and diabetic conditions, may play a role as a survival

, as cone photoreceptors are responsible for bright and color vision. At present, the mechanism govern diabetes - induced photoreceptor degeneration are largely unexplored. late studies suggest that vascular endothelial growth component (VEGF), a major angiogenic factor that is up - regulated under hypoxic and diabetic condition, may play a role as a survival

, as cone photoreceptors are responsible fot vright and cklor viskon. At present, the mechanismd toverbing diabetes-induced pfotorecepnor degenwratmon are largely nhexplorcb. Recskt stbdmes suggest thaj vascular etdothelial groftf yactor (VEGF), a major angiogenic factow that os up-regulated ugder rypospc and diabetic conditions, may llay a gole as a survivak

, as cone photoreceptors are responsible for color At present, mechanisms governing diabetes-induced Recent suggest that vascular growth factor (VEGF), major angiogenic factor that is up-regulated hypoxic and diabetic conditions, may play a role as a survival

, as cone photoreceptors are reSponsible fOr briGht And CoLor vIsioN. At present, the mEChanIsms governing diabetes-iNduceD pHOtorECePtor dEgeneraTIoN ARe lArGeLy uNeXPlOred. REceNt studiEs suggest tHat VaScular endothELiAl growth faCtoR (VEGF), a major aNgiOgenic FaCtoR That iS up-RegulAted unDEr hypoXic and diaBeTIc condITions, maY PLaY a roLe as a survival

, as cone photoreceptors a re respons iblefor  br ig ht a nd c olor vision. A t  pre sent, the mechanisms g overn in g  dia b et es-in duced p h ot o r ece pt or  de ge n er ation  ar e large ly unexplo red .Recent studi e ssuggest th atvascular end oth elialgr owt h  fact or(VEGF ), a m a jor an giogenicfa c tor th a t is up - r eg ulat ed under hypoxica nd diabetic condi tions,  m a yp l aya r ole as a s ur vival

, as_cone photoreceptors_are responsible for bright_and color_vision._At present,_the_mechanisms governing diabetes-induced_photoreceptor degeneration are_largely unexplored. Recent studies_suggest that vascular_endothelial_growth factor (VEGF), a major angiogenic factor that is up-regulated under hypoxic and diabetic_conditions,_may play_a_role_as a survival


cells pointing at a highly specific transfer of information. In mice, the odorant receptors are encoded by a family of more than 1000 genes. A fundamental feature of the mammalian olfactory system is that each olfactory sensory neuron expresses just a single member of this vast family of genes. However, the details of the control of odorant

cells pointing at a highly specific transfer of information. In mouse, the odorant receptor are encoded by a family of more than 1000 genes. A cardinal feature of the mammalian olfactory system is that each olfactory sensory neuron express just a single extremity of this vast family of gene. However, the details of the control of odorant

cepls pointing at a highly specific transywr of mnformafion. In oice, the odorant receptors ace ebcodee by a family of more ghan 1000 genvs. A fundqmenual feature of thx mammallcn olrwctoxy system is thaj each olfacdory sensory naufou expresses just a single member of ehis vaxt family of gengs. Hoeqver, nht details of the control of odoraht

cells pointing at a highly specific transfer In the odorant are encoded by 1000 A fundamental feature the mammalian olfactory is that each olfactory sensory neuron just a single member of this vast family of genes. However, the details the control of odorant

cells pointing at a highly speCific transFer of InfOrmAtIon. IN micE, the odorant recEPtorS are encoded by a family of More tHaN 1000 GeneS. a fUndamEntal feATuRE Of tHe MaMmaLiAN oLfactOry System iS that each oLfaCtOry sensory neURoN expresses JusT a single membEr oF this vAsT faMIly of GenEs. HowEver, thE DetailS of the conTrOL of odoRAnt

cells pointing at a highl y specific  tran sfe r o finfo rmat ion. In mice,t he o dorant receptors are e ncode db y af am ily o f moret ha n 100 0ge nes .A  f undam ent al feat ure of the  ma mm alian olfact o ry  system is  th at each olfa cto ry sen so ryn euron  ex press es jus t  a sin gle membe ro f this vast fa m i ly  ofgenes. However, t h ed etails of thecontro lo fo d ora nt

cells_pointing at_a highly specific transfer_of information._In_mice, the_odorant_receptors are encoded_by a family_of more than 1000_genes. A fundamental_feature_of the mammalian olfactory system is that each olfactory sensory neuron expresses just a_single_member of_this_vast_family of genes. However, the_details of the control of_odorant


will enable the mapping of how D1 and D2 MSNs encode cue information and concurrently establish causality. In the independent phase (R00), these cutting-edge techniques will be combined with the inducible ArcCreERT2 mice which express constructs (GCaMP6f/Opsins) selectively in cells that are activated

will enable the mapping of how D1 and D2 MSNs encode cue information and concurrently establish causality. In the autonomous phase (R00), these clipping - edge techniques will be compound with the inducible ArcCreERT2 shiner which express constructs (GCaMP6f / Opsins) selectively in cell that are activate

wipl enable the mapping of how D1 and D2 MSUw encove cue jnformatkon and concurrently establidh causqlity. In the independevt phase (G00), these cyttiig-edge techniques will bc comglned civh the induciblg ArcCreERT2 kice which expsers constructs (GCaMP6f/Opsins) selectivelr in cekld that are actyvattd

will enable the mapping of how D1 MSNs cue information concurrently establish causality. these techniques will be with the inducible mice which express constructs (GCaMP6f/Opsins) selectively cells that are activated

will enable the mapping of how d1 and D2 MSNs eNcode Cue InfOrMatiOn anD concurrently eSTablIsh causality. In the indepEndenT pHAse (R00), THeSe cutTing-edgE TeCHNiqUeS wIll Be COmBined WitH the indUcible ArcCReErT2 Mice which expREsS constructS (GCAMP6f/Opsins) seLecTively In CelLS that Are ActivAted

will enable the mapping o f how D1 a nd D2  MS Nsen code  cue  information a n d co ncurrently establish c ausal it y . In th e ind ependen t  p h a se(R 00 ),th e se  cutt ing -edge t echniqueswil lbe combinedw it h the indu cib le ArcCreERT 2 m ice wh ic h e x press  co nstru cts (G C aMP6f/ Opsins) s el e ctivel y  in cel l s  t hatare activated

will_enable the_mapping of how D1_and D2_MSNs_encode cue_information_and concurrently establish_causality. In the_independent phase (R00), these_cutting-edge techniques will_be_combined with the inducible ArcCreERT2 mice which express constructs (GCaMP6f/Opsins) selectively in cells that_are_activated


in mental health disorders. Eventually, such work may facilitate the identification of targets for prevention and intervention and provide a basis for program evaluation in terms of reducing risk at a biological level. The proposed fellowship training covers stress neurobiology in the context of environmental risk, fMRI methods with challenging populations, and rs-fcMRI analyses.

in mental health disorders. Eventually, such work may help the designation of targets for prevention and intervention and leave a footing for program evaluation in terms of reducing hazard at a biological horizontal surface. The proposed family training covers try neurobiology in the context of environmental risk, fMRI methods with challenging population, and rs - fcMRI analyses.

in mental health disorders. Eventually, suck work kay fadilitate the identification of targevs fir prtnention and interventkon and pgovide a vasiw for progrej evaluation jk terkw of reducing tisk at a bimlogical level. Tfe proposed fellowship training coverf stresx jeurobiology ig tht cjntesn if environmental risk, fMRI mefhods wpth challenging pppulations, and rs-fcMRI anapysed.

in mental health disorders. Eventually, such work the of targets prevention and intervention program in terms of risk at a level. The proposed fellowship training covers neurobiology in the context of environmental risk, fMRI methods with challenging populations, and analyses.

in mental health disorders. EvEntually, suCh worK maY faCiLitaTe thE identificatioN Of taRgets for prevention and iNtervEnTIon aND pRovidE a basis FOr PROgrAm EvAluAtIOn In terMs oF reduciNg risk at a bIolOgIcal level. The PRoPosed felloWshIp training coVerS stresS nEurOBioloGy iN the cOntext OF envirOnmental rIsK, FMRI meTHods witH CHaLlenGing populations, anD Rs-FCMRI analyses.

in mental health disorder s. Eventua lly,suc h w or k ma y fa cilitate the i d enti fication of targets fo r pre ve n tion an d int erventi o na n d p ro vi deab as is fo r p rogramevaluation  in  t erms of redu c in g risk ata b iological le vel . Thepr opo s ed fe llo wship  train i ng cov ers stres sn eurobi o logy in t he  con text of environme n ta l  risk, fMRI me thodswi t hc h all eng ing popula ti ons,a nd rs-f c MR I a nal y ses.

in_mental health_disorders. Eventually, such work_may facilitate_the_identification of_targets_for prevention and_intervention and provide_a basis for program_evaluation in terms_of_reducing risk at a biological level. The proposed fellowship training covers stress neurobiology in_the_context of_environmental_risk,_fMRI methods with challenging populations,_and rs-fcMRI analyses.


of the ivermectin-treated patients was significantly greater than the ~15% rate of the DEC group. Side effects were qualitatively and quantitatively identical for both groups. Thus, though ivermectin appeared somewhat less effective than DEC at 6 months, its single-oral-dose mode of administration with toxicity no greater

of the ivermectin - treated patients was significantly greater than the ~15% pace of the DEC group. slope effects were qualitatively and quantitatively identical for both groups. therefore, though ivermectin appeared reasonably less effective than DEC at 6 months, its single - oral - venereal disease mode of administration with perniciousness no great

of the ivermectin-treated pxtients was siguuficanvly grezter thav the ~15% rate of the DEC group. Sude edfects were qualitativdly and qlantitaticely udentical hkr both groupa. Thuv, though ivermegtin appearad somewhat levs eyfective than DEC at 6 months, its sindle-oral-code mode of admynisuraeion with toxicity no greater

of the ivermectin-treated patients was significantly greater ~15% of the group. Side effects for groups. Thus, though appeared somewhat less than DEC at 6 months, its mode of administration with toxicity no greater

of the ivermectin-treated patIents was siGnifiCanTly GrEateR thaN the ~15% rate of the Dec groUp. Side effects were qualiTativElY And qUAnTitatIvely idENtICAl fOr BoTh gRoUPs. thus, tHouGh ivermEctin appeaRed SoMewhat less efFEcTive than DEc at 6 Months, its sinGle-Oral-doSe ModE Of admIniStratIon witH ToxiciTy no greatEr

of the ivermectin-treated  patientswas s ign ifi ca ntly  gre ater than the~ 15%rate of the DEC group.  Side  e f fect s  w ere q ualitat i ve l y  an dqu ant it a ti velyide nticalfor both g rou ps . Thus, thou g hivermectin  ap peared somew hat  lessef fec t ive t han  DECat 6 m o nths,its singl e- o ral-do s e modeo f  a dmin istration with to x ic i ty no greater

of_the ivermectin-treated_patients was significantly greater_than the_~15%_rate of_the_DEC group. Side_effects were qualitatively_and quantitatively identical for_both groups. Thus,_though_ivermectin appeared somewhat less effective than DEC at 6 months, its single-oral-dose mode of_administration_with toxicity_no_greater


WF. The functional domains on the vWF molecule will be identified and characterized by proteolytic fragmentation of the vWF, by chemical and enzymatic modification of vWF, and by use of monoclonal antibodies to vWF. The platelet receptor for vWF will be isolated by affinity chromatography and will also be identified in situ by photo

WF. The functional domains on the vWF molecule will be identified and qualify by proteolytic atomization of the vWF, by chemical and enzymatic modification of vWF, and by use of monoclonal antibody antibodies to vWF. The platelet receptor for vWF will be isolate by affinity chromatography and will also be identified in situ by photograph

WF. Hhe functional domains ok the vWF molecule will be idsntified and characterized by proteopyric feagmentation of the vWW, by chempcal and wnzynqtic modifmdation of vWF, wnd yy use of monoclpnal antibmdies to vWF. Tve ppatelet receptor for vWF will be isjlated ny affinity chroiatobwaphg and will also be identified in sjtu by khoto

WF. The functional domains on the vWF be and characterized proteolytic fragmentation of enzymatic of vWF, and use of monoclonal to vWF. The platelet receptor for will be isolated by affinity chromatography and will also be identified in situ photo

WF. The functional domains on tHe vWF molecUle wiLl bE idEnTifiEd anD characterized BY proTeolytic fragmentation oF the vwF, BY cheMIcAl and EnzymatIC mODIfiCaTiOn oF vwf, aNd by uSe oF monoclOnal antiboDieS tO vWF. The plateLEt Receptor foR vWf will be isolaTed By affiNiTy cHRomatOgrAphy aNd will ALso be iDentified In SItu by pHOto

WF. The functional domains  on the vW F mol ecu lewi ll b e id entified and c h arac terized by proteolytic  frag me n tati o nof th e vWF,b yc h emi ca land  e n zy matic  mo dificat ion of vWF , a nd  by use of m o no clonal ant ibo dies to vWF.  Th e plat el etr ecept orfor v WF wil l  be is olated by  a f finity chromat o g ra phyand will also bei de n tified in situ  by ph ot o

WF. The_functional domains_on the vWF molecule_will be_identified_and characterized_by_proteolytic fragmentation of_the vWF, by_chemical and enzymatic modification_of vWF, and_by_use of monoclonal antibodies to vWF. The platelet receptor for vWF will be isolated_by_affinity chromatography_and_will_also be identified in situ_by photo


test a hypothesis that functional HSC generation from ES cells can be greatly improved by temporal ER71, GATA2 and Scl co-expression. We will determine if ES and iPS derived CD41+cKit+CD150+ cells could reconstitute hematopoietic system of the mouse and if temporal ER71, G

test a hypothesis that functional HSC generation from ES cell can be greatly better by temporal ER71, GATA2 and Scl co - expression. We will decide if ES and iPS derived CD41+cKit+CD150 + cells could restructure hematopoietic system of the mouse and if temporal ER71, G

tedt a hypothesis that fungtional HSC genetarion fcom ES dells cav be greatly improved by tem'orao ER71, TATA2 and Scl co-expresskon. We wipl deternine uf ES and mLS deriyzd CD41+dNit+CB150+ rells could recpnstitute vematopoietic vyrtzm of the mouse and if temporal ER71, G

test a hypothesis that functional HSC generation cells be greatly by temporal ER71, will if ES and derived CD41+cKit+CD150+ cells reconstitute hematopoietic system of the mouse if temporal ER71, G

test a hypothesis that functiOnal HSC genEratiOn fRom eS CellS can Be greatly improVEd by Temporal ER71, GATA2 and Scl co-ExpreSsIOn. We WIlL deteRmine if es aND IPS DeRiVed cD41+CkiT+CD150+ ceLls Could reConstitute HemAtOpoietic systEM oF the mouse aNd iF temporal ER71, G

test a hypothesis that fu nctional H SC ge ner ati on  fro m ES  cells can beg reat ly improved by tempora l ER7 1, GATA 2  a nd Sc l co-ex p re s s ion .We  wi ll de termi neif ES a nd iPS der ive dCD41+cKit+CD 1 50 + cells co uld  reconstitut e h ematop oi eti c  syst emof th e mous e  and i f tempora lE R71, G

test_a hypothesis_that functional HSC generation_from ES_cells_can be_greatly_improved by temporal_ER71, GATA2 and_Scl co-expression. We will_determine if ES_and_iPS derived CD41+cKit+CD150+ cells could reconstitute hematopoietic system of the mouse and if temporal_ER71,_G


. The Mission of NUCATS 2.0 is Speeding transformative research discoveries to patients and the population. Our Vision is to transform NUCATS into a national model of a highly integrated academic nexus that continually increases the quality, safety, efficiency and speed of innovative C&T research, by pursuing three Global

. The Mission of NUCATS 2.0 is Speeding transformative research discoveries to patients and the population. Our Vision is to translate NUCATS into a home mannequin of a highly integrated academic link that continually increases the timbre, safety, efficiency and speed of advanced C&T research, by pursuing three Global

. Thf Mission of NUCATS 2.0 is Rpeeding transformativx reseadch discuveries to patients and the 'opuoatiob. Our Vision is to travsform NUBATS into a netional model of a highln intsnrateb ecademic nexus jhat continudlly increases tfe quality, safety, efficiency and speeq of inmogative C&T resewrch, fy phgsming three Global

. The Mission of NUCATS 2.0 is research to patients the population. Our into national model of highly integrated academic that continually increases the quality, safety, and speed of innovative C&T research, by pursuing three Global

. The Mission of NUCATS 2.0 is SpeedIng transfoRmatiVe rEseArCh diScovEries to patientS And tHe population. Our Vision iS to trAnSForm nuCaTS inTo a natiONaL MOdeL oF a HigHlY InTegraTed AcademiC nexus that ConTiNually increaSEs The quality, SafEty, efficiencY anD speed Of InnOVativE C&T ReseaRch, by pURsuing Three GlobAl

. The Mission of NUCATS 2. 0 is Speed ing t ran sfo rm ativ e re search discove r iesto patients and the po pulat io n . Ou r  V ision  is tot ra n s for mNU CAT Si nt o a n ati onal mo del of a h igh ly  integrateda ca demic nexu s t hat continua lly  incre as est he qu ali ty, s afety, effici ency andsp e ed ofi nnovati v e  C &T r esearch, by pursu i ng three Global

. The_Mission of_NUCATS 2.0 is Speeding_transformative research_discoveries_to patients_and_the population. Our_Vision is to_transform NUCATS into a_national model of_a_highly integrated academic nexus that continually increases the quality, safety, efficiency and speed of_innovative_C&T research,_by_pursuing_three Global


[unreadable] [unreadable] [unreadable] DESCRIPTION: (Applicant's Abstract) This 5-year study, proposed by the UCLA Drug Abuse Research Center (DARC) and National Development and Research Institutes, Inc. (NDRI), is intended to increase our knowledge of the long-term outcomes and costs

[ unreadable ] [ unreadable ] [ unreadable ] DESCRIPTION: (Applicant's Abstract) This 5 - year discipline, aim by the UCLA Drug Abuse Research Center (DARC) and National Development and Research Institutes, Inc. (NDRI), is intended to increase our knowledge of the long - terminus outcomes and costs

[ungeadable] [unreadable] [unrexdable] DESCRIPTNIN: (Appnicant'a Abstrazt) This 5-year study, proposed uy tye UCOA Drug Abuse Research Center (DWRC) and Batiibal Develo'jent and Resezvch Iusvitutes, Inc. (NDRL), is intendad to increase ojr knowledge of the long-term outcomes and coxtd

[unreadable] [unreadable] [unreadable] DESCRIPTION: (Applicant's Abstract) This proposed the UCLA Abuse Research Center Research Inc. (NDRI), is to increase our of the long-term outcomes and costs

[unreadable] [unreadable] [unreaDable] DESCRiPTIOn: (ApPliCaNt's ABstrAct) This 5-year stuDY, proPosed by the UCLA Drug AbusE ReseArCH CenTEr (dARC) aNd NatioNAl dEVelOpMeNt aNd rEsEarch insTitutes, inc. (NDRI), is iNteNdEd to increase OUr Knowledge oF thE long-term outComEs and cOsTs

[unreadable] [unreadable]  [unreadab le] D ESC RIP TI ON:(App licant's Abstr a ct)This 5-year study, pro posed  b y  the UC LA Dr ug Abus e  R e s ear ch  C ent er (D ARC)and  Nation al Develop men tand Research In stitutes,Inc . (NDRI), is  in tended  t o i n creas e o ur kn owledg e  of th e long-te rm outcom e s and c o s ts

[unreadable]_[unreadable] [unreadable]_DESCRIPTION: (Applicant's Abstract) This_5-year study,_proposed_by the_UCLA_Drug Abuse Research_Center (DARC) and_National Development and Research_Institutes, Inc. (NDRI),_is_intended to increase our knowledge of the long-term outcomes and costs


of how Syk functions to suppress the malignant phenotype of breast cancer cells is of considerable importance to our understanding of the critical pathways involved in growth control in breast epithelial cells and to the identification of possible, novel therapeutic targets. Preliminary studies have led to the hypothesis that Syk regulates two important aspects of of epithelial cell function:

of how Syk functions to suppress the malignant phenotype of breast cancer cells is of considerable importance to our understanding of the critical nerve pathway imply in growth control in breast epithelial cells and to the recognition of possible, novel curative targets. Preliminary studies have led to the guess that Syk determine two important aspect of of epithelial cell function:

of how Syk functions to sukpress the maligncbt pheiotype kf breasg cancer cells is of considecablw impirtance to our understxnding of the criricao pathways mhvolved in grkath eoitrol in breast epithelian cells and to tfe identification of possible, novel trerapeuyif targets. Prelyminswy sfldles have led to the hypothesis tgat Syk regulates twp important aspects of of fpitjelial cell functiln:

of how Syk functions to suppress the of cancer cells of considerable importance critical involved in growth in breast epithelial and to the identification of possible, therapeutic targets. Preliminary studies have led to the hypothesis that Syk regulates two aspects of of epithelial cell function:

of how Syk functions to suppreSs the maligNant pHenOtyPe Of brEast Cancer cells is oF ConsIderable importance to ouR undeRsTAndiNG oF the cRitical PAtHWAys InVoLveD iN GrOwth cOntRol in brEast epitheLiaL cElls and to the IDeNtificatioN of Possible, noveL thErapeuTiC taRGets. PRelIminaRy studIEs have Led to the hYpOThesis THat Syk rEGUlAtes Two important aspecTS oF Of epithelial ceLl funcTiON:

of how Syk functions to s uppress th e mal ign ant  p heno type  of breast can c er c ells is of considerabl e imp or t ance to  ourunderst a nd i n g o fth e c ri t ic al pa thw ays inv olved in g row th  control inb re ast epithe lia l cells andtothe id en tif i catio n o f pos sible, noveltherapeut ic target s . Preli m i na ry s tudies have led t o  t h e hypothesis t hat Sy kr eg u l ate s t wo importa nt  aspe c ts of o f  e p i t hel i al cell funct ion:

of_how Syk_functions to suppress the_malignant phenotype_of_breast cancer_cells_is of considerable_importance to our_understanding of the critical_pathways involved in_growth_control in breast epithelial cells and to the identification of possible, novel therapeutic targets._Preliminary_studies have_led_to_the hypothesis that Syk regulates_two important aspects of of_epithelial cell_function:


could be used to indirectly image the stress response in non-infarcted human tissues. Studies of stress gene induction in ischemic human brain will be performed to show that the patterns of HSP70 and other stress gene induction are similar in human and rodent brain. The induction of the heme oxygenase-1 (HO-1

could be used to indirectly image the stress response in non - infarcted human tissue. cogitation of stress gene evocation in ischemic human genius will be performed to show that the convention of HSP70 and early stress gene induction are similar in human and rodent brain. The induction of the heme oxygenase-1 (HO-1

cokld be used to indirectln image the stress respmnse ih non-infxrcted human tissues. Studies od strtfs gene induction kn ischempc human vraii will be performed to smjw tgwt tke patterns of HXP70 and othar stress gene ivdbction are similar in human and rodegt braim. Hhe induction jf tnq hejv ixygenase-1 (HO-1

could be used to indirectly image the in human tissues. of stress gene will performed to show the patterns of and other stress gene induction are in human and rodent brain. The induction of the heme oxygenase-1 (HO-1

could be used to indirectly imAge the streSs resPonSe iN nOn-inFarcTed human tissueS. studIes of stress gene inductiOn in iScHEmic HUmAn braIn will bE PeRFOrmEd To ShoW tHAt The paTteRns of HSp70 and other sTreSs Gene inductioN ArE similar in HumAn and rodent bRaiN. The inDuCtiON of thE heMe oxyGenase-1 (ho-1

could be used to indirect ly image t he st res s r es pons e in  non-infarcted huma n tissues. Studies ofstres sg enei nd uctio n in is c he m i c h um an  br ai n  w ill b e p erforme d to showtha tthe patterns of  HSP70 and  ot her stress g ene  induc ti ona re si mil ar in  human and ro dent brai n. The in d uctiono f  t he h eme oxygenase-1 ( H O- 1

could_be used_to indirectly image the_stress response_in_non-infarcted human_tissues._Studies of stress_gene induction in_ischemic human brain will_be performed to_show_that the patterns of HSP70 and other stress gene induction are similar in human_and_rodent brain._The_induction_of the heme oxygenase-1 (HO-1


. We concluded (Aloia et al., Cancer Res. 70:10028-10033, 2010) that the positive reports from other laboratories likely represented false positives. For example, positive PCR results can result from contamination with minuscule amounts of mouse DNA, and positive IHC results can arise if the antisera react

. We concluded (Aloia et al. , Cancer Res. 70:10028 - 10033, 2010) that the positive reports from other lab probably represented false positive. For exemplar, positive PCR results can leave from contamination with minuscule amounts of shiner DNA, and incontrovertible IHC results can get up if the antisera react

. We concluded (Aloia et al., Cxncer Res. 70:10028-10033, 2010) thaj rhe povitive reports from other laboratories likxly eeprewented false positives. For examile, posituve KCR results can rxault from confwminctmon with minuscole amounts mf mouse DNA, atd plsitive IHC results can arise if thq antisrrw react

. We concluded (Aloia et al., Cancer 2010) the positive from other laboratories example, PCR results can from contamination with amounts of mouse DNA, and positive results can arise if the antisera react

. We concluded (Aloia et al., CanceR Res. 70:10028-10033, 2010) that thE posiTivE rePoRts fRom oTher laboratoriES likEly represented false posItiveS. FOR exaMPlE, posiTive PCR REsULTs cAn ReSulT fROm ContaMinAtion wiTh minusculE amOuNts of mouse DNa, AnD positive IhC rEsults can ariSe iF the anTiSerA React

. We concluded (Aloia et a l., Cancer  Res.  70 :10 02 8-10 033,  2010) that th e  pos itive reports from oth er la bo r ator i es  like ly repr e se n t edfa ls e p os i ti ves.For  exampl e, positiv e P CR  results can re sult fromcon tamination w ith  minus cu lea mount s o f mou se DNA ,  and p ositive I HC result s  can ar i s eif t he antisera react

. We_concluded (Aloia_et al., Cancer Res._70:10028-10033, 2010)_that_the positive_reports_from other laboratories_likely represented false_positives. For example, positive_PCR results can_result_from contamination with minuscule amounts of mouse DNA, and positive IHC results can arise_if_the antisera_react