for the permeability response for these and other permeabilizing factors. By screening a commercially available library, we have already identified a class of inhibitors for this target and in this grant we propose to combine medicinal chemists, structural biologists and cellular and molecular physiologists to develop compounds that control retinal blood vessel permeability in multiple models

for the permeability response for these and other permeabilizing factors. By screening a commercially available library, we have already identify a course of inhibitors for this target and in this concession we propose to aggregate medicinal pharmacist, morphologic biologists and cellular and molecular physiologist to originate compounds that master retinal blood vessel permeability in multiple models

fog the permeability respokse for these anb other permezbilizine factors. By screening a comleecialoy available library, wd have algeady idebtifmed a class of iigibitors for fmis tcrjet and in this grant we [ropose to comtive medicinal chemists, structural bioljgists snf cellular and moltcujar lhysiologists to develop compounds that cmntrol retinak blood vessel permeabilitj in multiple models

for the permeability response for these and factors. screening a available library, we of for this target in this grant propose to combine medicinal chemists, structural and cellular and molecular physiologists to develop compounds that control retinal blood vessel in multiple models

for the permeability responsE for these aNd othEr pErmEaBiliZing Factors. By screeNIng a Commercially available lIbrarY, wE Have ALrEady iDentifiED a CLAss Of InHibItORs For thIs tArget anD in this graNt wE pRopose to combINe Medicinal cHemIsts, structurAl bIologiStS anD CelluLar And moLeculaR PhysioLogists to DeVElop coMPounds tHAT cOntrOl retinal blood vesSEl PErmeability in mUltiplE mODeLS

for the permeability resp onse for t heseand  ot he r pe rmea bilizing facto r s. B y screening a commerci allyav a ilab l elibra ry, weh av e alr ea dy  id en t if ied a  cl ass ofinhibitors  fo rthis targeta nd  in this g ran t we propose  to  combi ne  me d icina l c hemis ts, st r uctura l biologi st s  and c e llulara n dmole cular physiologis t st o develop comp oundsth a tc o ntr olretinal bl oo d ves s el perm e ab i l i tyi n multiple mo dels

for_the permeability_response for these and_other permeabilizing_factors._By screening_a_commercially available library,_we have already_identified a class of_inhibitors for this_target_and in this grant we propose to combine medicinal chemists, structural biologists and cellular_and_molecular physiologists_to_develop_compounds that control retinal blood_vessel permeability in multiple models


with its receptors (BMPR) on single mouse ESCs (mESCs) can induce their differentiation, triggering down and up regulation of a few receptor molecules (SSEA1 and CXCR4), respectively. However, their related molecular mechanisms and how to precisely control their specific cardiac differentiation remain largely unknown. We hypothesize that

with its receptors (BMPR) on single mouse ESCs (mESCs) can induce their differentiation, trip down and up rule of a few receptor molecules (SSEA1 and CXCR4), respectively. However, their relate molecular mechanism and how to precisely control their specific cardiac differentiation stay largely unknown. We hypothesize that

wihh its receptors (BMPR) on single mouse ESCs (mESRs) can jnduce tfeir differentiation, triggermng eown qnd up regulation of a few receitor molexulew (SSEA1 and RSCR4), resizctivspy. Hmxever, their relsted molecglar mechanismv xnb how to precisely control their spesific csrfiac differentyatipg rejain largely unknown. We hypothesizs that

with its receptors (BMPR) on single mouse can their differentiation, down and up molecules and CXCR4), respectively. their related molecular and how to precisely control their cardiac differentiation remain largely unknown. We hypothesize that

with its receptors (BMPR) on sinGle mouse EScs (mEScs) cAn iNdUce tHeir DifferentiatioN, TrigGering down and up regulatIon of A fEW recEPtOr molEcules (SseA1 AND CXcR4), ReSpeCtIVeLy. HowEveR, their rElated moleCulAr Mechanisms anD HoW to preciseLy cOntrol their sPecIfic caRdIac DIfferEntIatioN remaiN LargelY unknown. WE hYPothesIZe that

with its receptors (BMPR)  on single  mous e E SCs  ( mESC s) c an induce thei r  dif ferentiation, triggeri ng do wn andu pregul ation o f  a f ewre ce pto rm ol ecule s ( SSEA1 a nd CXCR4),  re sp ectively. Ho w ev er, theirrel ated molecul armechan is msa nd ho w t o pre cisely contro l their s pe c ific c a rdiac d i f fe rent iation remain lar g el y  unknown. We h ypothe si z et h at

with_its receptors_(BMPR) on single mouse_ESCs (mESCs)_can_induce their_differentiation,_triggering down and_up regulation of_a few receptor molecules_(SSEA1 and CXCR4),_respectively._However, their related molecular mechanisms and how to precisely control their specific cardiac differentiation_remain_largely unknown._We_hypothesize_that


or chemical transmitters). This international collaboration will study a field trial initiated and funded by the Norwegian government: a nationwide implementation of the OSLC model of parent management training (PMTO). PMTO is an efficacious theory-based intervention that teaches parents child-rearing strategies that prevent deviant child behavior and

or chemical transmitters). This international collaboration will study a field test initiate and funded by the Norwegian government: a nationwide execution of the OSLC model of parent management training (PMTO). PMTO is an efficacious hypothesis - base intervention that teaches parents child - rearing strategy that prevent deviant child behavior and

or chemical transmitters). Tmis international collauoratioh will sgudy a field trial initiated abd fubded by the Norwegian eovernmenn: a natiobwidt implementation of the OSLC moscl of 'arent managemekt training (PMTO). PMTO is dn eyficacious theory-based intervention ehat tescjes parents chyld-rtaryng anrctegies that prevent deviant chjld behevior and

or chemical transmitters). This international collaboration will field initiated and by the Norwegian the model of parent training (PMTO). PMTO an efficacious theory-based intervention that teaches child-rearing strategies that prevent deviant child behavior and

or chemical transmitters). ThiS internatiOnal cOllAboRaTion Will Study a field triAL iniTiated and funded by the NoRwegiAn GOverNMeNt: a naTionwidE ImPLEmeNtAtIon Of THe oSLC mOdeL of pareNt managemeNt tRaIning (PMTO). PMTo Is An efficaciOus Theory-based iNteRventiOn ThaT TeachEs pArentS child-REaring StrategieS tHAt prevENt deviaNT ChIld bEhavior and

or chemical transmitters) . This int ernat ion alco llab orat ion will study a fi eld trial initiated an d fun de d  byt he  Norw egian g o ve r n men t:  a  na ti o nw ide i mpl ementat ion of the  OS LC  model of pa r en t manageme nttraining (PM TO) . PMTO  i s a n  effi cac ioustheory - basedintervent io n  thatt eachesp a re ntschild-rearing str a te g ies that preve nt dev ia n tc h ild  be havior and

or_chemical transmitters)._This international collaboration will_study a_field_trial initiated_and_funded by the_Norwegian government: a_nationwide implementation of the_OSLC model of_parent_management training (PMTO). PMTO is an efficacious theory-based intervention that teaches parents child-rearing strategies_that_prevent deviant_child_behavior_and


CD45RB isoform. By using T isolated from OVA-TCR Tg mice, we will be able to control exposure of the separate populations to antigen after adoptive transfer to SCID mice. This will allow us to dissect the earliest antigenic responses of these two populations during disease progression or prevention. In parallel

CD45RB isoform. By using T isolated from OVA - TCR Tg mice, we will be able to see vulnerability of the separate populations to antigen after adoptive transportation to SCID mice. This will allow us to analyze the early antigenic responses of these two population during disease progression or prevention. In parallel

CD45GB isoform. By using T isulated from OVA-JCE Tg mmce, we sill be xble to control exposure of vhe weparqte populations to antkgen afteg adoptivw trensfer to SCID mmde. This will zplow ns to dissect tme earliest antigenic res[ovszs of these two populations during dysease lrlgression or ptevenuiog. In iavallel

CD45RB isoform. By using T isolated from mice, will be to control exposure antigen adoptive transfer to mice. This will us to dissect the earliest antigenic of these two populations during disease progression or prevention. In parallel

CD45RB isoform. By using T isolatEd from OVA-TcR Tg mIce, We wIlL be aBle tO control exposuRE of tHe separate populations tO antiGeN AfteR AdOptivE transfER tO scID MiCe. thiS wILl Allow Us tO dissecT the earlieSt aNtIgenic responSEs Of these two PopUlations duriNg dIsease PrOgrESsion Or pRevenTion. In PAralleL

CD45RB isoform. By usingT isolated  from  OV A-T CR  Tgmice , we will be a b le t o control exposure ofthe s ep a rate po pulat ions to an t i gen  a ft erad o pt ive t ran sfer to  SCID mice . T hi s will allow us  to dissec t t he earliestant igenic  r esp o nsesofthese  two p o pulati ons durin gd isease progres s i on  orprevention. In pa r al l el

CD45RB_isoform. By_using T isolated from_OVA-TCR Tg_mice,_we will_be_able to control_exposure of the_separate populations to antigen_after adoptive transfer_to_SCID mice. This will allow us to dissect the earliest antigenic responses of these_two_populations during_disease_progression_or prevention. In parallel


mouse. Utilizing the data obtained from these various investigational approaches, the designed chemotherapy programs will be clinically tested in patients. Enzymes containing mononuclear non-heme iron sites catalyze a diverse array of reactions that are significant to medicine and to the environment. This proposal describes plans to study three representatives of the largest,

mouse. Utilizing the data obtained from these diverse investigational approach, the designed chemotherapy broadcast will be clinically screen in patients. Enzymes contain mononuclear non - heme iron site catalyze a diverse array of reactions that are significant to medicine and to the environment. This marriage proposal describes plans to study three representatives of the big,

mokse. Utilizing the data ontained from these varimus inbestigatkonal approaches, the designev chwmothtgapy programs will be clinicalpy testee in patients. Eiaymes containjkg mouoiuclear non-heme iron sitev catalyze a dhvdrde array of reactions that are signyficant tl medicine and to uhe envjgokment. This proposal describes plzns to vtudy three rrpresentatives of the largfst,

mouse. Utilizing the data obtained from these approaches, designed chemotherapy will be clinically mononuclear iron sites catalyze diverse array of that are significant to medicine and the environment. This proposal describes plans to study three representatives of the largest,

mouse. Utilizing the data obtaIned from thEse vaRioUs iNvEstiGatiOnal approaches, THe deSigned chemotherapy progRams wIlL Be clINiCally Tested iN PaTIEntS. ENzYmeS cONtAininG moNonucleAr non-heme iRon SiTes catalyze a DIvErse array oF reActions that aRe sIgnifiCaNt tO MedicIne And to The envIRonmenT. This propOsAL descrIBes planS TO sTudy Three representatiVEs OF the largest,

mouse. Utilizing the data  obtainedfromthe seva riou s in vestigationala ppro aches, the designed ch emoth er a py p r og ramswill be cl i n ica ll ytes te d  i n pat ien ts. Enz ymes conta ini ng  mononuclear no n-heme iro n s ites catalyz e a  diver se  ar r ay of  re actio ns tha t  are s ignifican tt o medi c ine and t otheenvironment. This pr o posal describe s plan st os t udy  th ree repres en tativ e s of th e  l a r g est ,

mouse._Utilizing the_data obtained from these_various investigational_approaches,_the designed_chemotherapy_programs will be_clinically tested in_patients. Enzymes containing mononuclear_non-heme iron sites_catalyze_a diverse array of reactions that are significant to medicine and to the environment._This_proposal describes_plans_to_study three representatives of the_largest,


c) Lines which produce Ig of classes or allotypes where no myeloma tumors currently exist. BIBLIOGRAPHIC REFERENCES: Sato, Vicki L., S.D. Waksal, and Leonard A. Herzenberg. 1976. Identification and separation of pre T-cells

c) Lines which produce Ig of classes or allotypes where no myeloma tumors presently exist. BIBLIOGRAPHIC reference: Sato, Vicki L., S.D. Waksal, and Leonard A. Herzenberg. 1976. Identification and interval of pre deoxythymidine monophosphate - cells

c) Pines which produce Ig on classes or allotypes xhere nk myelomx tumors currently exist. BIBPIIGRAPYIC REFERENCES: Sato, Vizki L., S.D. Aaksal, abd Ltonard A. Herzenbecf. 1976. Idenbnficaflon aud separation of pre T-cellv

c) Lines which produce Ig of classes where myeloma tumors exist. BIBLIOGRAPHIC REFERENCES: and A. Herzenberg. 1976. and separation of T-cells

c) Lines which produce Ig of claSses or alloTypes WheRe nO mYeloMa tuMors currently eXIst. BiBLIOGRAPHIC REFERENCES: sato, VIcKI L., S.D. wAkSal, anD LeonarD a. HERZenBeRg. 1976. ideNtIFiCatioN anD separaTion of pre T-CelLs

c) Lines which produce Ig  of classe s orall oty pe s wh ereno myeloma tum o rs c urrently exist. BIBLIO GRAPH IC REFE R EN CES:Sato, V i ck i L.,  S .D . W ak s al , and  Le onard A . Herzenbe rg.  1 976. Identif i ca tion and s epa ration of pr e T -cells

c)_Lines which_produce Ig of classes_or allotypes_where_no myeloma_tumors_currently exist. BIBLIOGRAPHIC_REFERENCES: Sato, Vicki_L., S.D. Waksal, and_Leonard A. Herzenberg._1976._Identification and separation of pre T-cells


oxidase from an overexpressed yeast strain, and studied the amine oxidase activity of the purified protein in vitro. Current work is directed at extending the use of the spe3 ( delta) fms1 (delta) mutants to elucidate the relative importance of spermidine and spermine in a variety of physiological functions. The objective of

oxidase from an overexpressed yeast strain, and studied the amine oxidase activity of the purified protein in vitro. Current workplace is steer at extending the use of the spe3 (delta) fms1 (delta) mutants to clear the relative importance of spermidine and spermine in a variety of physiologic functions. The objective of

oxldase from an overexpresred yeast straiu, and svudied fhe amind oxidase activity of the pucifiwd pritein in vitro. Current work is firected at txtending the use of the spe3 ( dspta) ymw1 (delta) mutantx to elucigate the relathvd nmportance of spermidine and sperminq in a fagiety of physijlogpcwl fhnctions. The objective of

oxidase from an overexpressed yeast strain, and amine activity of purified protein in at the use of spe3 ( delta) (delta) mutants to elucidate the relative of spermidine and spermine in a variety of physiological functions. The objective of

oxidase from an overexpresseD yeast straIn, and StuDieD tHe amIne oXidase activity OF the Purified protein in vitro. curreNt WOrk iS DiRecteD at exteNDiNG The UsE oF thE sPE3 ( dElta) fMs1 (dElta) mutAnts to elucIdaTe The relative iMPoRtance of spErmIdine and sperMinE in a vaRiEty OF physIolOgicaL functIOns. The Objective Of

oxidase from an overexpre ssed yeast  stra in,  an dstud iedthe amine oxid a se a ctivity of the purifie d pro te i n in vi tro.Current wo r k  is  d ir ect ed at  exte ndi ng theuse of the  sp e3  ( delta) fm s 1(delta) mu tan ts to elucid ate  the r el ati v e imp ort anceof spe r midine  and sper mi n e in a variety o fphys iological functio n s. The objectiveof

oxidase_from an_overexpressed yeast strain, and_studied the_amine_oxidase activity_of_the purified protein_in vitro. Current_work is directed at_extending the use_of_the spe3 ( delta) fms1 (delta) mutants to elucidate the relative importance of spermidine_and_spermine in_a_variety_of physiological functions. The objective_of


loci. We now propose to elucidate further the role of NHEJ proteins in CSR and SM, with a particular focus on how defects in these processes, and in V(D)J recombination, may lead to the generation of chromosomal translocations that contribute to the generation and maintenance of mature B cell lymphomas.

loci. We now propose to elucidate far the function of NHEJ proteins in CSR and SM, with a particular focus on how defect in these processes, and in V(D)J recombination, may lead to the genesis of chromosomal translocation that contribute to the coevals and maintenance of mature bel cell lymphomas.

lofi. We now propose to elugidate further tkw role of NHSJ protekns in CSR and SM, with a parvicuoar ficus on how defects in these prlcesses, qnd mn V(D)J recombinavjon, may lead fl thz jeneration of cmromosomal dranslocations tfac contribute to the generation and mwintenamcf of mature B sell jympgomas.

loci. We now propose to elucidate further of proteins in and SM, with defects these processes, and V(D)J recombination, may to the generation of chromosomal translocations contribute to the generation and maintenance of mature B cell lymphomas.

loci. We now propose to elucidaTe further tHe rolE of nHEj pRoteIns iN CSR and SM, with a PArtiCular focus on how defects In theSe PRoceSSeS, and iN V(D)J recOMbINAtiOn, MaY leAd TO tHe genEraTion of cHromosomal TraNsLocations thaT CoNtribute to The Generation anD maIntenaNcE of MAture b ceLl lymPhomas.

loci. We now propose to e lucidate f urthe r t hero le o f NH EJ proteins in CSRand SM, with a particu lar f oc u s on ho w def ects in th e s e p ro ce sse s, an d inV(D )J reco mbination,  ma ylead to theg en eration of  ch romosomal tr ans locati on s t h at co ntr ibute  to th e  gener ation and  m a intena n ce of m a t ur e Bcell lymphomas.

loci._We now_propose to elucidate further_the role_of_NHEJ proteins_in_CSR and SM,_with a particular_focus on how defects_in these processes,_and_in V(D)J recombination, may lead to the generation of chromosomal translocations that contribute to_the_generation and_maintenance_of_mature B cell lymphomas.


has one consistent aspect: the application of conditioning and training theories and methods to the empirical analysis of concepts important to theories of social behavior, motivation, psychopathology, and personality development. The major focus has been aversive control but now the emphasis is shifting to the aversive, motivational after-effects of terminating positively

has one consistent aspect: the application of conditioning and education theory and methods to the empirical psychoanalysis of concepts crucial to theories of social demeanor, motivation, psychiatry, and personality development. The major stress has been aversive restraint but now the stress is shifting to the aversive, motivational after - effects of end positively

had one consistent aspect: uhe application oy condivioning and trakning theories and methods tl rhe enpirical analysis of cuncepts ilportant to uheories of social behavior, motjyatiou, 'sychopathology, and persotality developkevt. The major focus has been aversive sontrol bkt now the emprasix is ahifting to the aversive, motivatiohal afttr-effects of termimating positively

has one consistent aspect: the application of training and methods the empirical analysis of behavior, motivation, psychopathology, personality development. The focus has been aversive control but the emphasis is shifting to the aversive, motivational after-effects of terminating positively

has one consistent aspect: the ApplicatioN of coNdiTioNiNg anD traIning theories aND metHods to the empirical analYsis oF cONcepTS iMportAnt to thEOrIES of SoCiAl bEhAViOr, motIvaTion, psyChopatholoGy, aNd Personality dEVeLopment. The MajOr focus has beEn aVersivE cOntROl but Now The emPhasis IS shiftIng to the aVeRSive, moTIvationAL AfTer-eFfects of terminatiNG pOSitively

has one consistent aspect : the appl icati onofco ndit ioni ng and trainin g  the ories and methods to t he em pi r ical an alysi s of co n ce p t s i mp or tan tt otheor ies  of soc ial behavi or,  m otivation, p s yc hopatholog y,and personal ity  devel op men t . The  ma jor f ocus h a s been  aversive  c o ntrolb ut nowt h eemph asis is shiftingt ot he aversive, m otivat io n al a fte r-e ffects ofte rmina t ing pos i ti v e l y

has_one consistent_aspect: the application of_conditioning and_training_theories and_methods_to the empirical_analysis of concepts_important to theories of_social behavior, motivation,_psychopathology,_and personality development. The major focus has been aversive control but now the emphasis_is_shifting to_the_aversive,_motivational after-effects of terminating positively


uing reduction in signs and symptoms, as well as disability, joint damage, disease remission and quality of life will be evaluated at 1 year. It is well recongnized that ketone bodies are excellent fuels for energy production in developing rat brain. Our on-going studies have shown that ketone bodies are also good

uing reduction in signs and symptoms, as well as disability, joint price, disease remittance and quality of life will be evaluated at 1 class. It is well recongnized that ketone bodies are excellent fuels for energy product in developing rat mind. Our on - going studies have show that ketone bodies are also dependable

uinh reduction in signs and symptoms, as well as dmsabilify, joint damage, disease remission anv quqlity of life will be evaluxted at 1 jear. It iw weoo recongnivsd that ketons bodnew are excellenj fuels for anergy producthov nn developing rat brain. Our on-going ftudies hwve shown that ketpge bkdies are also good

uing reduction in signs and symptoms, as disability, damage, disease and quality of 1 It is well that ketone bodies excellent fuels for energy production in rat brain. Our on-going studies have shown that ketone bodies are also good

uing reduction in signs and syMptoms, as weLl as dIsaBilItY, joiNt daMage, disease remISsioN and quality of life will bE evalUaTEd at 1 YEaR. It is Well recONgNIZed ThAt KetOnE BoDies aRe eXcellenT fuels for eNerGy Production in DEvEloping rat BraIn. Our on-going StuDies haVe ShoWN that KetOne boDies arE Also goOd

uing reduction in signs an d symptoms , aswel l a sdisa bili ty, joint dama g e, d isease remission and q ualit yo f li f ewillbe eval u at e d  at  1  y ear .I tis we llrecongn ized thatket on e bodies are ex cellent fu els  for energypro ductio nind evelo pin g rat  brain .  Our o n-going s tu d ies ha v e shown t ha t ke tone bodies are a l so good

uing reduction_in signs_and symptoms, as well_as disability,_joint_damage, disease_remission_and quality of_life will be_evaluated at 1 year._It is well_recongnized_that ketone bodies are excellent fuels for energy production in developing rat brain. Our_on-going_studies have_shown_that_ketone bodies are also good


degradation. We hypothesize further that aldosterone increases Cl- absorption in the CCD, in part, by reducing the association of these transporters with NEDD4-2. This proposal will dissect the mechanism whereby intercalated cell NEDD4-2 alters Cl- transport by intercalated cells. Aims

degradation. We hypothesize further that aldosterone increases Cl- concentration in the CCD, in character, by reducing the association of these transporters with NEDD4 - 2. This marriage proposal will dissect the mechanism whereby intercalated cell NEDD4 - 2 alters Cl- transportation by intercalated cells. Aims

dehradation. We hypothesize further that aldostermne indreases Zl- absorption in the CCD, in 'art, by rtbucing the associatiun of thede transporttrs with NEDD4-2. This proposal wilm disvxct the mechanixm whereby intercalated weul NEDD4-2 alters Cl- transport by intercwlated vepls. Aims

degradation. We hypothesize further that aldosterone increases in CCD, in by reducing the NEDD4-2. proposal will dissect mechanism whereby intercalated NEDD4-2 alters Cl- transport by intercalated Aims

degradation. We hypothesize fUrther that AldosTerOne InCreaSes CL- absorption in tHE CCD, In part, by reducing the assOciatIoN Of thESe TransPorters WItH neDD4-2. thIs ProPoSAl Will dIssEct the mEchanism whEreBy Intercalated CElL NEDD4-2 alterS Cl- Transport by iNteRcalatEd CelLS. Aims

degradation. We hypothesi ze further  that  al dos te rone  inc reases Cl- abs o rpti on in the CCD, in part , byre d ucin g  t he as sociati o no f  th es etra ns p or terswit h NEDD4 -2. This p rop os al will diss e ct  the mecha nis m whereby in ter calate dcel l  NEDD 4-2  alte rs Cl- transp ort by in te r calate d  cells. A im s

degradation._We hypothesize_further that aldosterone increases_Cl- absorption_in_the CCD,_in_part, by reducing_the association of_these transporters with NEDD4-2._This proposal will_dissect_the mechanism whereby intercalated cell NEDD4-2 alters Cl- transport by intercalated cells. Aims


2, Schwannomatosis and TSC and their sporadic counterparts. 5) Provide histological and immunohistochemical expertise in the classification and analysis of newly generated lesions in Nf2 and Tsc murine models and evaluate the delivery and effects of experimental gene therapy in these lesions. The core will ensure optimal and uniform processing of all

2, Schwannomatosis and TSC and their sporadic counterparts. 5) Provide histological and immunohistochemical expertise in the classification and psychoanalysis of newly generate lesions in Nf2 and Tsc murine models and measure the delivery and effect of experimental gene therapy in these lesions. The kernel will ensure optimal and consistent processing of all

2, Scjwannomatosis and TSC ana their sporadie countxrparts. 5) Providd histological and immunohisvochwmicao expertise in the clarsificatiln and abalywus of newlb generabzd lealons nn Nf2 and Tsc mutine models dnd evaluate tve dzlivery and effects of experimental dene thrrwpy in these lgsionx. The bove will ensure optimal and unifodm proctssing of all

2, Schwannomatosis and TSC and their sporadic Provide and immunohistochemical in the classification lesions Nf2 and Tsc models and evaluate delivery and effects of experimental gene in these lesions. The core will ensure optimal and uniform processing of all

2, Schwannomatosis and TSC and tHeir sporadIc couNteRpaRtS. 5) ProVide Histological anD ImmuNohistochemical expertiSe in tHe CLassIFiCatioN and anaLYsIS Of nEwLy GenErATeD lesiOns In Nf2 and tsc murine mOdeLs And evaluate tHE dElivery and EffEcts of experiMenTal genE tHerAPy in tHesE lesiOns. The COre wilL ensure opTiMAl and uNIform prOCEsSing Of all

2, Schwannomatosis and TSC  and their  spor adi c c ou nter part s. 5) Provideh isto logical and immunohist ochem ic a l ex p er tisein thec la s s ifi ca ti onan d  a nalys isof newl y generate d l es ions in Nf2a nd  Tsc murin e m odels and ev alu ate th edel i veryand  effe cts of experi mental ge ne therap y  in the s e  l esio ns. The core will en s ure optimal an d unif or m  p r o ces sin g of all

2, Schwannomatosis_and TSC_and their sporadic counterparts._5) Provide_histological_and immunohistochemical_expertise_in the classification_and analysis of_newly generated lesions in_Nf2 and Tsc_murine_models and evaluate the delivery and effects of experimental gene therapy in these lesions._The_core will_ensure_optimal_and uniform processing of all


to ligand binding. Ligand-induced proteolysis releases the intracellular portion of notch (ICN) and allow it to translocate to the nucleus, where its RAM and ankyrin-repeat domains interact with two additional factors, RBP-JK and mastermind (mami 1) to form a transcriptionally active

to ligand binding. Ligand - induced proteolysis releases the intracellular portion of pass (ICN) and leave it to translocate to the nucleus, where its RAM and ankyrin - repeat domains interact with two extra factors, RBP - JK and genius (mami 1) to form a transcriptionally active

to ligand binding. Ligand-inauced proteolysnw releeses ths intracdllular portion of notch (ICN) abd aloow it to translocate go the nubleus, wheee ius RAM and ankyrii-depeat domaina intzrect with two adcitional fdctors, RBP-JK atd mcstermind (mami 1) to form a transcriptyonally aftive

to ligand binding. Ligand-induced proteolysis releases the of (ICN) and it to translocate RAM ankyrin-repeat domains interact two additional factors, and mastermind (mami 1) to form transcriptionally active

to ligand binding. Ligand-induCed proteolYsis rEleAseS tHe inTracEllular portion OF notCh (ICN) and allow it to transLocatE tO The nUClEus, whEre its Ram aND AnkYrIn-RepEaT DoMains IntEract wiTh two additIonAl Factors, RBP-JK ANd Mastermind (MamI 1) to form a tranScrIptionAlLy aCTive

to ligand binding. Ligand -induced p roteo lys isre leas es t he intracellul a r po rtion of notch (ICN) a nd al lo w  itt otrans locatet ot h e n uc le us,  w h er e its  RA M and a nkyrin-rep eat  d omains inter a ct  with twoadd itional fact ors , RBP- JK  an d  mast erm ind ( mami 1 )  to fo rm a tran sc r iption a lly act i v e

to_ligand binding._Ligand-induced proteolysis releases the_intracellular portion_of_notch (ICN)_and_allow it to_translocate to the_nucleus, where its RAM_and ankyrin-repeat domains_interact_with two additional factors, RBP-JK and mastermind (mami 1) to form a transcriptionally active


minimal and residual lymphoma. We are using multiparametric approaches to improve the sensitivity of detection of monoclonal B-cell populations. By targeting abnormal patterns of antigen expression (eg CD10, CD5, CD23, FMC7, or abnormal intensity of antigen expression) by neoplastic B-cells in light chain detection,

minimal and residual lymphoma. We are using multiparametric approaches to improve the sensitivity of detection of monoclonal boron - cellular telephone populations. By targeting abnormal design of antigen formulation (eg CD10, CD5, CD23, FMC7, or abnormal intensity of antigen expression) by neoplastic bel - cell in light range signal detection,

mijimal and residual lymphuma. We are usiny multi'arametdic appruaches to improve the sensitmvitt of eetection of monoclonau B-cell plpulatiobs. Bb targeting abnocjal patbzrns kn antngxn expression (en CD10, CD5, CD23, XMC7, or abnorman kncensity of antigen expression) by neo[lastic B-fells in light chapn detsbtlon,

minimal and residual lymphoma. We are using to the sensitivity detection of monoclonal patterns antigen expression (eg CD5, CD23, FMC7, abnormal intensity of antigen expression) by B-cells in light chain detection,

minimal and residual lymphomA. We are usinG multIpaRamEtRic aPproAches to improve THe seNsitivity of detection of MonocLoNAl B-cELl PopulAtions. BY TaRGEtiNg AbNorMaL PaTternS of Antigen Expression (Eg Cd10, Cd5, CD23, FMC7, or abnoRMaL intensity Of aNtigen expresSioN) by neoPlAstIC B-celLs iN lighT chain DEtectiOn,

minimal and residual lymp homa. We a re us ing  mu lt ipar amet ric approaches to i mprove the sensitivity  of d et e ctio n  o f mon oclonal B- c e llpo pu lat io n s.  By t arg eting a bnormal pa tte rn s of antigen ex pression ( egCD10, CD5, C D23 , FMC7 ,ora bnorm alinten sity o f  antig en expres si o n) byn eoplast i c  B -cel ls in light chain de t ection,

minimal_and residual_lymphoma. We are using_multiparametric approaches_to_improve the_sensitivity_of detection of_monoclonal B-cell populations._By targeting abnormal patterns_of antigen expression_(eg_CD10, CD5, CD23, FMC7, or abnormal intensity of antigen expression) by neoplastic B-cells in_light_chain detection,


thyroid hormone receptor response element (TRE). A second tyrosine that is responsible for Lyn binding has been identified and is also required for PI3K stimulation. Thus, this mechanism provides a direct link for integrating growth signals through thyroid hormone and receptor tyrosine kinases. To determine the magnitude and duration of acetylcholinesterase (

thyroid hormone receptor response element (TRE). A second tyrosine that is creditworthy for Lyn tie has been identified and is besides required for PI3 K foreplay. Thus, this mechanism provides a lineal link for integrating growth signal through thyroid hormone and receptor tyrosine kinase. To determine the magnitude and duration of acetylcholinesterase (

thjroid hormone receptor rtsponse element (TTE). A secmnd tydosine tfat is responsible for Lyn bmndibg haw been identified and ks also rvquired fir PM3K stimulation. Tihs, this mechahlsm pxotides a direct kink for ittegrating groftf dignals through thyroid hormone and receptpr tyrosine kinafes. Uo qetedmine the magnitude and duration or acetyncholinesteraxe (

thyroid hormone receptor response element (TRE). A that responsible for binding has been for stimulation. Thus, this provides a direct for integrating growth signals through thyroid and receptor tyrosine kinases. To determine the magnitude and duration of acetylcholinesterase (

thyroid hormone receptor resPonse elemeNt (TRE). a seConD tYrosIne tHat is responsibLE for lyn binding has been identIfied AnD Is alSO rEquirEd for PI3k StIMUlaTiOn. thuS, tHIs MechaNisM providEs a direct lInk FoR integrating GRoWth signals ThrOugh thyroid hOrmOne and ReCepTOr tyrOsiNe kinAses. To DEtermiNe the magnItUDe and dURation oF ACeTylcHolinesterase (

thyroid hormone receptorresponse e lemen t ( TRE ).  A s econ d tyrosine tha t  isresponsible for Lyn bi nding  h a s be e nident ified a n di s  al so  r equ ir e dfor P I3K  stimul ation. Thu s,th is mechanism pr ovides a d ire ct link forint egrati ng  gr o wth s ign als t hrough thyroi d hormone  a n d rece p tor tyr o s in e ki nases. To determi n et he magnitude a nd dur at i on o f a cet ylcholines te rase(

thyroid_hormone receptor_response element (TRE). A_second tyrosine_that_is responsible_for_Lyn binding has_been identified and_is also required for_PI3K stimulation. Thus,_this_mechanism provides a direct link for integrating growth signals through thyroid hormone and receptor_tyrosine_kinases. To_determine_the_magnitude and duration of acetylcholinesterase_(


aims test relations between structure and function of the GPCR and the G protein trimer at the level of individual molecules. Experiments with GPCRs aim to: a. use molecular probes to determine how the extracellular surface of a GPCR actually binds the activating ligand; b. engineer metal binding sites that activate a GPCR

aims test relations between structure and affair of the GPCR and the G protein trimer at the degree of individual molecules. Experiments with GPCRs aim to: a. practice molecular probes to determine how the extracellular surface of a GPCR actually tie down the activating ligand; b. engineer metal bind sites that activate a GPCR

ails test relations betweek structure and yynctioi of ths GPCR avd the G protein trimer at tie lwvel if individual moleculer. Experimvnts with GPCCs aim to: a. use moleculav progcs to vetermine how tme extracelnular surface mf a GPCR actually binds the activating ligand; b. engineer metaj bimqing sites that activate a GPCR

aims test relations between structure and function GPCR the G trimer at the with aim to: a. molecular probes to how the extracellular surface of a actually binds the activating ligand; b. engineer metal binding sites that activate a

aims test relations between sTructure anD funcTioN of ThE GPCr and The G protein triMEr at The level of individual moLeculEs. eXperIMeNts wiTh GPCRs AIm TO: A. usE mOlEcuLaR PrObes tO deTermine How the extrAceLlUlar surface oF A GpCR actuallY biNds the activaTinG liganD; b. EngINeer mEtaL bindIng sitES that aCtivate a GpCr

aims test relations betwe en structu re an d f unc ti on o f th e GPCR and the G pr otein trimer at the le vel o fi ndiv i du al mo lecules .  E x p eri me nt s w it h  G PCRsaim  to: a.  use molec ula rprobes to de t er mine how t heextracellula r s urface  o f a GPCRact ually  binds the ac tivatingli g and; b .  engine e r  m etal  binding sites th a ta ctivate a GPCR

aims_test relations_between structure and function_of the_GPCR_and the_G_protein trimer at_the level of_individual molecules. Experiments with_GPCRs aim to:_a._use molecular probes to determine how the extracellular surface of a GPCR actually binds_the_activating ligand;_b._engineer_metal binding sites that activate_a GPCR


successful meniscal replacement will work to prevent joint degeneration following meniscectomy. PUBLIC HEALTH RELEVANCE: Menisci within the knee joint function to protect the underlying articular cartilage from degenerative osteoarthritis. The absence of a healthy meniscus can inhibit this function. The goal of this research is to determine

successful meniscal replacement will work to prevent joint degeneration following meniscectomy. PUBLIC HEALTH RELEVANCE: Menisci within the stifle joint affair to protect the underlying articular cartilage from degenerative osteoarthritis. The absence of a healthy meniscus can suppress this function. The finish of this research is to determine

sufcessful meniscal replactment will work to preveit joinf degenefation following meniscectomb. PUVLIC YEALTH RELEVANCE: Meniszi within the knew jomnt function to 'dotect bke unscrlyiug articular carjilage from gegenerative ovtdocrthritis. The absence of a healthy mqniscus cwn inhibit thif fumstioh. The goal of this research is to setermiie

successful meniscal replacement will work to prevent following PUBLIC HEALTH Menisci within the the articular cartilage from osteoarthritis. The absence a healthy meniscus can inhibit this The goal of this research is to determine

successful meniscal replaceMent will woRk to pRevEnt JoInt dEgenEration followiNG menIscectomy. PUBLIC HEALTH ReLEVAnCe: meniSCi WithiN the kneE JoINT fuNcTiOn tO pROtEct thE unDerlyinG articular CarTiLage from degeNErAtive osteoArtHritis. The absEncE of a heAlThy MEniscUs cAn inhIbit thIS functIon. The goaL oF This reSEarch is TO DeTermIne

successful meniscal repla cement wil l wor k t o p re vent  joi nt degeneratio n  fol lowing meniscectomy. P UBLIC  H E ALTH RE LEVAN CE: Men i sc i wit hi nthe  k n ee  join t f unction  to protec t t he  underlyinga rt icular car til age from deg ene rative  o ste o arthr iti s. Th e abse n ce ofa healthy  m e niscus can inh i b it  thi s function. The g o al of this resear ch isto de t e rmi ne

successful_meniscal replacement_will work to prevent_joint degeneration_following_meniscectomy. PUBLIC_HEALTH_RELEVANCE: Menisci within_the knee joint_function to protect the_underlying articular cartilage_from_degenerative osteoarthritis. The absence of a healthy meniscus can inhibit this function. The goal_of_this research_is_to_determine


-1 (ICAM-1) messenger RNA (mRNA), thus blocking translation of this message. The goal of this study is to evaluate the safety and efficacy of ISIS 2302 in steroid-dependent Crohn's disease. We hypothesize that inhibition of ICAM-1 will decrease intestinal inflammation and lead to clinical symptom

-1 (ICAM-1) messenger RNA (mRNA), thus blocking translation of this message. The goal of this discipline is to measure the safety and efficacy of ISIS 2302 in steroid - pendent Crohn's disease. We speculate that inhibition of ICAM-1 will decrease intestinal inflammation and lead to clinical symptom

-1 (ICWM-1) messenger RNA (mRNA), thms blocking translation of thjs messaee. The goal of this study is ti evaouate the safety and ewficacy ov ISIS 2302 un sueroid-dependent Cckhn's disease. Sc hypmvhesize that inmibition of ICAM-1 will decsexsz intestinal inflammation and lead tj clinivap symptom

-1 (ICAM-1) messenger RNA (mRNA), thus blocking this The goal this study is efficacy ISIS 2302 in Crohn's disease. We that inhibition of ICAM-1 will decrease inflammation and lead to clinical symptom

-1 (ICAM-1) messenger RNA (mRNA), thus bLocking traNslatIon Of tHiS mesSage. the goal of this sTUdy iS to evaluate the safety anD effiCaCY of IsiS 2302 In steRoid-depENdENT CrOhN's DisEaSE. WE hypoTheSize thaT inhibitioN of iCaM-1 will decreaSE iNtestinal iNflAmmation and lEad To clinIcAl sYMptom

-1 (ICAM-1) messenger RNA(mRNA), th us bl ock ing  t rans lati on of this mes s age.  The goal of this stud y isto eval u at e the  safety an d eff ic ac y o fI SI S 230 2 i n stero id-depende ntCr ohn's diseas e .We hypothe siz e that inhib iti on ofIC AM- 1  will  de creas e inte s tinalinflammat io n  and l e ad to c l i ni calsymptom

-1 (ICAM-1)_messenger RNA_(mRNA), thus blocking translation_of this_message._The goal_of_this study is_to evaluate the_safety and efficacy of_ISIS 2302 in_steroid-dependent_Crohn's disease. We hypothesize that inhibition of ICAM-1 will decrease intestinal inflammation and lead_to_clinical symptom


3: Hypothesis: PKC activity affects fluid production via regulation of K channels and/or NKCC1 transporters. We will test controls, NZB and the two knockouts (Beta1 and NKCC1). A high-performance liquid chromatography (HPLC) method with electrochemical (EC) detection was developed

3: Hypothesis: PKC activity affects fluid product via rule of K channels and/or NKCC1 transporters. We will screen control, NZB and the two knockouts (Beta1 and NKCC1). A high - operation liquid chromatography (HPLC) method with electrochemical (EC) detection was developed

3: Hjpothesis: PKC activity anfects fluid probyction via rsgulatiov of K channels and/or NKCC1 tcansportees. We will test controus, NZB anf the twi knixkouts (Bete1 and NKGE1). A hjnh-peryocmance liquid cmromatograpvy (HPLC) method wktk electrochemical (EC) detection was dqvelopec

3: Hypothesis: PKC activity affects fluid production of channels and/or transporters. We will two (Beta1 and NKCC1). high-performance liquid chromatography method with electrochemical (EC) detection was

3: Hypothesis: PKC activity affeCts fluid prOductIon Via ReGulaTion Of K channels and/OR NKCc1 transporters. We will tesT contRoLS, NZB ANd The twO knockoUTs (bETa1 aNd nKcC1). A HiGH-pErforManCe liquiD chromatogRapHy (hPLC) method wiTH eLectrochemIcaL (EC) detection Was DeveloPeD

3: Hypothesis: PKC activi ty affects  flui d p rod uc tion  via  regulation of K ch annels and/or NKCC1 tr anspo rt e rs.W ewilltest co n tr o l s,NZ Band  t h etwo k noc kouts ( Beta1 andNKC C1 ). A high-pe r fo rmance liq uid  chromatogra phy  (HPLC )met h od wi thelect rochem i cal (E C) detect io n  was d e veloped

3:_Hypothesis: PKC_activity affects fluid production_via regulation_of_K channels_and/or_NKCC1 transporters. We_will test controls,_NZB and the two_knockouts (Beta1 and_NKCC1)._A high-performance liquid chromatography (HPLC) method with electrochemical (EC) detection was developed


providing a simple model for studying how a single chromosome is discriminated from the rest of the genome. In Drosophila, selective two-fold upregulation of the single male X-chromosome equalizes transcription between the sexes. The selective identification of the X-chromosome involves the recruitment of a ribonucleoprotein complex, Male-

providing a simple model for studying how a individual chromosome is discriminate from the rest of the genome. In Drosophila, selective two - fold upregulation of the single male X - chromosome equalizes recording between the sexes. The selective identification of the adam - chromosome necessitate the recruitment of a ribonucleoprotein complex, Male-

prlviding a simple model fur studying how a singne chrkmosome ks discriminated from the redt of tye genome. In Drosophilx, selectine two-fole upcegulation of thx single male S-ghrommwome equalizes transcripdion between tve szxes. The selective identification of the X-cnrlmosome involvgs tht rqcrujnmtnt of a ribonucleoprotein comples, Male-

providing a simple model for studying how chromosome discriminated from rest of the upregulation the single male equalizes transcription between sexes. The selective identification of the involves the recruitment of a ribonucleoprotein complex, Male-

providing a simple model for sTudying how A singLe cHroMoSome Is diScriminated froM The rEst of the genome. In DrosopHila, sElECtivE TwO-fold UpregulATiON Of tHe SiNglE mALe x-chroMosOme equaLizes transCriPtIon between thE SeXes. The seleCtiVe identificaTioN of the x-cHroMOsome InvOlves The recRUitmenT of a ribonUcLEoprotEIn complEX, maLe-

providing a simple modelfor studyi ng ho w a  si ng le c hrom osome is discr i mina ted from the rest of t he ge no m e. I n  D rosop hila, s e le c t ive  t wo -fo ld up regul ati on of t he singlemal eX-chromosome eq ualizes tr ans cription bet wee n these xes .  Thesel ectiv e iden t ificat ion of th eX -chrom o some in v o lv es t he recruitment of ar ibonucleoprote in com pl e x, M ale -

providing_a simple_model for studying how_a single_chromosome_is discriminated_from_the rest of_the genome. In_Drosophila, selective two-fold upregulation_of the single_male_X-chromosome equalizes transcription between the sexes. The selective identification of the X-chromosome involves the_recruitment_of a_ribonucleoprotein_complex,_Male-


life, and cost-effective innovative tools to support its delivery. Thus, the study is highly relevant to public health as it affects the health of a continuously growing segment of our population, namely these who are called to assume the essential role of informal caregiving, and aims to demonstrate the value of a feasible and sustainable problem

life, and cost - effective innovative tools to confirm its rescue. Thus, the study is highly relevant to public health as it affects the health of a endlessly growing segment of our population, namely these who are called to bear the essential role of cozy caregiving, and drive to demonstrate the value of a feasible and sustainable trouble

live, and cost-effective innuvative tools to suppoct its selivery. Thus, the study is highly repecant uj public health as it affecns the heqlth if a contiihously nxowinf segkxnt of our popukation, namaly these who drd ealled to assume the essential role jf infotmwl caregiving, wnd syms fo demonstrate the value of a feasjble anv sustainable ptoblem

life, and cost-effective innovative tools to support Thus, study is relevant to public health a continuously growing of our population, these who are called to assume essential role of informal caregiving, and aims to demonstrate the value of a and sustainable problem

life, and cost-effective innovAtive tools To supPorT itS dElivEry. THus, the study is hIGhly Relevant to public health As it aFfECts tHE hEalth Of a contINuOUSly GrOwIng SeGMeNt of oUr pOpulatiOn, namely thEse WhO are called to ASsUme the esseNtiAl role of infoRmaL caregIvIng, ANd aimS to DemonStrate THe valuE of a feasiBlE And susTAinable PRObLem

life, and cost-effectiveinnovative  tool s t o s up port  its  delivery. Thu s , th e study is highly rele vantto publ i chealt h as it af f e cts  t he  he al t hof acon tinuous ly growing  se gm ent of our p o pu lation, na mel y these whoare  calle dtoa ssume  th e ess ential role o f informa lc aregiv i ng, and a im s to  demonstrate thev al u e of a feasibl e andsu s ta i n abl e p roblem

life,_and cost-effective_innovative tools to support_its delivery._Thus,_the study_is_highly relevant to_public health as_it affects the health_of a continuously_growing_segment of our population, namely these who are called to assume the essential role_of_informal caregiving,_and_aims_to demonstrate the value of_a feasible and sustainable problem


the extant literature is descriptive, comparative, or limited to distinct subgroups of LG parents. Of this research, demography studies that examined trends in LG family structures have rarely considered the family and individual processes that may account for changing trends in LG family formation; meanwhile developmental studies of LG parents have rarely considered the ecological and cultural influences

the extant literature is descriptive, comparative, or limited to distinct subgroups of LG parent. Of this inquiry, demography studies that examined drift in LG kin structures have rarely considered the class and individual processes that may account for deepen trends in LG family geological formation; meanwhile developmental studies of LG parents have rarely consider the ecological and cultural influences

thf extant literature is dtscriptive, comparcrive, oc limitsd to dirtinct subgroups of LG parenvs. Od thiw research, demography rtudies tjat examuned rrends in LG familn strhgturev have rarely cpnsidered dhe family and ivdnvidual processes that may account fjr chanbijg trends in LD fakyly rormation; meanwhile developmental atudies of LG parentx have rarely considered tje efological and cultkral influebces

the extant literature is descriptive, comparative, or distinct of LG Of this research, in family structures have considered the family individual processes that may account for trends in LG family formation; meanwhile developmental studies of LG parents have rarely the ecological and cultural influences

the extant literature is descRiptive, comParatIve, Or lImIted To diStinct subgroupS Of LG Parents. Of this research, dEmogrApHY stuDIeS that ExamineD TrENDs iN Lg fAmiLy STrUcturEs hAve rareLy considerEd tHe Family and indIViDual procesSes That may accouNt fOr chanGiNg tREnds iN LG FamilY formaTIon; meaNwhile devElOPmentaL Studies OF lG PareNts have rarely consIDeREd the ecologicaL and cuLtURaL INflUenCes

the extant literature isdescriptiv e, co mpa rat iv e, o r li mited to disti n ct s ubgroups of LG parents . Ofth i s re s ea rch,demogra p hy s tud ie stha te xa mined  tr ends in  LG family  st ru ctures haver ar ely consid ere d the family  an d indi vi dua l  proc ess es th at may accoun t for cha ng i ng tre n ds in L G fa mily  formation; meanw h il e  developmental  studi es of L G p are nts have r ar ely c o nsidere d  t h e eco l ogical and cu ltural infl u enc es

the_extant literature_is descriptive, comparative, or_limited to_distinct_subgroups of_LG_parents. Of this_research, demography studies_that examined trends in_LG family structures_have_rarely considered the family and individual processes that may account for changing trends in_LG_family formation;_meanwhile_developmental_studies of LG parents have_rarely considered the ecological and_cultural influences


] [unreadable] [unreadable] The goals of this research as stated in the grant title are the optimization of hygroscopic aerosol delivery to the human bronchial tree. We are achieving these goals by a combination of experimental studies on physical models of the bronchial airways, theoretical calculations of aerosol drop size and size distributions effected by

] [ unreadable ] [ unreadable ] The goals of this research as express in the concession title are the optimization of hygroscopic aerosol delivery to the human bronchial tree. We are achieve these goals by a combination of experimental cogitation on physical models of the bronchial airways, theoretical calculation of aerosol drop size and size distributions effect by

] [ungeadable] [unreadable] The noals of this research es statsd in thd grant title are the optimivatiin of hygroscopic aerosol ddlivery tl the hunan uronchial tree. Wx are acmnevinf thevx goals by a cokbination mf experimentan rtbdies on physical models of the bronshial aoraays, theoreticwl csjculzniins of aerosol drop size and aize divtributions egfected by

] [unreadable] [unreadable] The goals of this stated the grant are the optimization the bronchial tree. We achieving these goals a combination of experimental studies on models of the bronchial airways, theoretical calculations of aerosol drop size and size effected by

] [unreadable] [unreadable] The goAls of this rEsearCh aS stAtEd in The gRant title are thE OptiMization of hygroscopic aErosoL dELiveRY tO the hUman broNChIAL trEe. we Are AcHIeVing tHesE goals bY a combinatIon Of Experimental STuDies on physIcaL models of the BroNchial AiRwaYS, theoRetIcal cAlculaTIons of Aerosol drOp SIze and SIze distRIBuTionS effected by

] [unreadable] [unreadable ] The goal s ofthi s r es earc h as  stated in the gran t title are the optimi zatio no f hy g ro scopi c aeros o ld e liv er ytoth e  h umanbro nchialtree. We a reac hieving thes e  g oals by acom bination ofexp erimen ta l s t udies  on  phys ical m o dels o f the bro nc h ial ai r ways, t h e or etic al calculations o f  a e rosol drop siz e andsi z ed i str ibu tions effe ct ed by

] [unreadable]_[unreadable] The_goals of this research_as stated_in_the grant_title_are the optimization_of hygroscopic aerosol_delivery to the human_bronchial tree. We_are_achieving these goals by a combination of experimental studies on physical models of the_bronchial_airways, theoretical_calculations_of_aerosol drop size and size_distributions effected by


-146a, anti-miRNA-146a and modulation of CFH, IRAK or TSPAN12 expression are key regulators of the inflammatory response and amyloidogenesis in amyloid over-expressing Tg2576 mice. The goal of this set of projects is to use functional magnetic resonance imaging (fMRI) to

-146a, anti - miRNA-146a and modulation of CFH, IRAK or TSPAN12 expression are key governor of the incendiary response and amyloidogenesis in amyloid over - expressing Tg2576 mouse. The finish of this set of projects is to use running charismatic resonance imaging (fMRI) to

-146a, ajti-miRNA-146a and modulation of CFH, IRAK or TSPAN12 xxpressjon are yey regulators of the inflamlarory eesponse and amyloidogdnesis in amyloid ovec-expressing Tg2576 mmde. The njal kn thiv set of projecjs is to use functional macndtnc resonance imaging (fMRI) to

-146a, anti-miRNA-146a and modulation of CFH, IRAK expression key regulators the inflammatory response Tg2576 The goal of set of projects to use functional magnetic resonance imaging to

-146a, anti-miRNA-146a and modulation oF CFH, IRAK or tSPAN12 ExpResSiOn arE key Regulators of thE InflAmmatory response and amyLoidoGeNEsis IN aMyloiD over-exPReSSIng tg2576 MiCe. THe GOaL of thIs sEt of proJects is to uSe fUnCtional magneTIc Resonance iMagIng (fMRI) to

-146a, anti-miRNA-146a and  modulatio n ofCFH , I RA K or  TSP AN12 expressio n  are  key regulators of the  infl am m ator y  r espon se anda my l o ido ge ne sis  i n  a myloi d o ver-exp ressing Tg 257 6mice. The go a lof this se t o f projects i s t o usefu nct i onalmag netic  reson a nce im aging (fM RI )  to

-146a, anti-miRNA-146a_and modulation_of CFH, IRAK or_TSPAN12 expression_are_key regulators_of_the inflammatory response_and amyloidogenesis in_amyloid over-expressing Tg2576 mice._The goal of_this_set of projects is to use functional magnetic resonance imaging (fMRI) to


of retinoids in the liver has received very little attention. We show that retinoids and their receptors have a broad spectrum of actions ranging from xenobiotic biotransformation to lipid, carbohydrate, and amino acid homeostasis in the liver. The proposed project will profile hepatic genome-wide RA receptor target-gene in a gender

of retinoids in the liver has received very little attention. We show that retinoids and their receptor take a broad spectrum of actions ranging from xenobiotic biotransformation to lipid, carbohydrate, and amino acid homeostasis in the liver. The project project will profile hepatic genome - wide RA sense organ target - gene in a gender

of retinoids in the liver mas received veri oittle attenfion. We rhow that retinoids and theic rexeptoes have a broad spectrjm of actpons rangung hrom xenobiotic ujotransnjrmaflon tm lipid, carbohycrate, and dmino acid homaortcsis in the liver. The proposed projest will pgofile hepatic genpie-wisv VA receptor target-gene in a gendsr

of retinoids in the liver has received attention. show that and their receptors actions from xenobiotic biotransformation lipid, carbohydrate, and acid homeostasis in the liver. The project will profile hepatic genome-wide RA receptor target-gene in a gender

of retinoids in the liver has rEceived verY littLe aTteNtIon. WE shoW that retinoids ANd thEir receptors have a broad SpectRuM Of acTIoNs ranGing froM XeNOBioTiC bIotRaNSfOrmatIon To lipid, CarbohydraTe, aNd Amino acid homEOsTasis in the LivEr. The proposeD prOject wIlL prOFile hEpaTic geNome-wiDE RA recEptor targEt-GEne in a GEnder

of retinoids in the liver  has recei ved v ery  li tt le a tten tion. We showt hatretinoids and their re cepto rs have abroad  spectr u mo f  ac ti on s r an g in g fro m x enobiot ic biotran sfo rm ation to lip i d,  carbohydr ate , and aminoaci d home os tas i s inthe  live r. The propos ed projec tw ill pr o file he p a ti c ge nome-wide RA rece p to r  target-gene i n a ge nd e r

of_retinoids in_the liver has received_very little_attention._We show_that_retinoids and their_receptors have a_broad spectrum of actions_ranging from xenobiotic_biotransformation_to lipid, carbohydrate, and amino acid homeostasis in the liver. The proposed project will_profile_hepatic genome-wide_RA_receptor_target-gene in a gender


The transcriptional cofactors ASPP1 and ASPP2 can enhance p53 mediated transactivation of several TLR genes. Moreover, p53 collaborate with NFkappaB to modulate several immune responses in primary lymphocytes and macrophages. Through our meta-analysis of p53 targeted binding sites and associated gene expression (i.e., c

The transcriptional cofactors ASPP1 and ASPP2 can enhance p53 mediated transactivation of several TLR genes. furthermore, p53 collaborate with NFkappaB to tone several immune responses in basal lymphocyte and macrophages. Through our meta - analysis of p53 targeted tie down sites and associated gene saying (i.e., c

Thf transcriptional cofacturs ASPP1 and ASKP2 can eihance l53 mediatdd transactivation of severap RLR gtues. Moreover, p53 collacorate winh NFkappqB ti modulate several limuns res'oises in primary lymphocytas and macrophdgds. Through our meta-analysis of p53 targqted bimdlng sites and wssobiwted gene expression (i.e., c

The transcriptional cofactors ASPP1 and ASPP2 can mediated of several genes. Moreover, p53 several responses in primary and macrophages. Through meta-analysis of p53 targeted binding sites associated gene expression (i.e., c

The transcriptional cofactoRs ASPP1 and AsPP2 caN enHanCe P53 medIateD transactivatiON of sEveral TLR genes. Moreover, P53 collAbORate WItH NFkaPpaB to mODuLATe sEvErAl iMmUNe RespoNseS in primAry lymphocYteS aNd macrophageS. thRough our meTa-aNalysis of p53 taRgeTed binDiNg sITes anD asSociaTed genE ExpresSion (i.e., c

The transcriptional cofac tors ASPP1  andASP P2ca n en hanc e p53 mediated tran sactivation of several  TLRge n es.M or eover , p53 c o ll a b ora te  w ith  N F ka ppaBtomodulat e severalimm un e responsesi nprimary ly mph ocytes and m acr ophage s.  Th r oughour  meta -analy s is ofp53 targe te d  bindi n g sites a nd  ass ociated gene expr e ss i on (i.e., c

The_transcriptional cofactors_ASPP1 and ASPP2 can_enhance p53_mediated_transactivation of_several_TLR genes. Moreover,_p53 collaborate with_NFkappaB to modulate several_immune responses in_primary_lymphocytes and macrophages. Through our meta-analysis of p53 targeted binding sites and associated gene_expression_(i.e., c


by T1. The effect of lambda initiated transcription will be studied as follows: (1) The effect of deleting DNA between the galactose operon and the attachment site of lambda. (2) The effect of nonpolar kil mutants of lambda. (3) The effect of lambda mutants which result in the creation of

by T1. The effect of lambda initiated transcription will be studied as follow: (1) The consequence of deleting DNA between the galactose operon and the attachment web site of lambda. (2) The effect of nonpolar kil mutants of lambda. (3) The consequence of lambda mutants which result in the initiation of

by T1. The effect of lambda lnitiated transctiption xill be studied as follows: (1) The effect of dxletung DBA between the galactore operon and the attechment site of lambda. (2) Bke efrcct oy ionpolar kil mujants of lamtda. (3) The effecd uf lambda mutants which result in the creatipn of

by T1. The effect of lambda initiated be as follows: The effect of operon the attachment site lambda. (2) The of nonpolar kil mutants of lambda. The effect of lambda mutants which result in the creation of

by T1. The effect of lambda initiAted transcRiptiOn wIll Be StudIed aS follows: (1) The effECt of Deleting DNA between the gAlactOsE OperON aNd the AttachmENt SITe oF lAmBda. (2) thE EfFect oF noNpolar kIl mutants oF laMbDa. (3) The effect oF LaMbda mutantS whIch result in tHe cReatioN oF

by T1. The effect of lamb da initiat ed tr ans cri pt ionwill  be studied as foll ows: (1) The effect of  dele ti n g DN A  b etwee n the g a la c t ose  o pe ron  a n dthe a tta chmentsite of la mbd a.  (2) The eff e ct  of nonpol arkil mutantsoflambda .(3) The e ffe ct of  lambd a  mutan ts whichre s ult in the cre a t io n of

by_T1. The_effect of lambda initiated_transcription will_be_studied as_follows:_(1) The effect_of deleting DNA_between the galactose operon_and the attachment_site_of lambda. (2) The effect of nonpolar kil mutants of lambda. (3) The effect_of_lambda mutants_which_result_in the creation of


in this project comprise a four-way partnership including the Queens Borough Public Library System, the Queens Cancer Center, the American Cancer Society of Queens, and Memorial Sloan-Kettering Cancer Center. The goal of this research is to define the relative roles of intra-and extra-mitochondrial genetic systems in determining

in this project comprise a four - way partnership including the Queens Borough Public Library System, the Queens Cancer Center, the American Cancer Society of Queens, and Memorial Sloan - Kettering Cancer Center. The finish of this inquiry is to specify the relative function of intra - and excess - mitochondrial genetic systems in determining

in this project comprise a four-way partnetsyip inrluding the Quedns Borough Public Library Sbsten, the Queens Cancer Center, ghe Ameriban Cancee Soriety of Queens, ehd Memovnal Smlan-Kztvering Cancer Cgnter. The godl of this resaafck is to define the relative roles of intra-amd extra-mitochonqriak gensnig systems in determining

in this project comprise a four-way partnership Queens Public Library the Queens Cancer of and Memorial Sloan-Kettering Center. The goal this research is to define the roles of intra-and extra-mitochondrial genetic systems in determining

in this project comprise a fouR-way partneRship IncLudInG the queeNs Borough PubliC librAry System, the Queens CancEr CenTeR, The AMErIcan CAncer SoCIeTY Of QUeEnS, anD MEMoRial SLoaN-KetterIng Cancer CEntEr. the goal of thiS ReSearch is to DefIne the relatiVe rOles of InTra-ANd extRa-mItochOndriaL GenetiC systems iN dETerminINg

in this project comprisea four-way  part ner shi pincl udin g the Queens B o roug h Public Library Syste m, th eQ ueen s  C ancer  Center ,  t h e  Am er ic anCa n ce r Soc iet y of Qu eens, andMem or ial Sloan-Ke t te ring Cance r C enter. The g oal  of th is  re s earch  is  to d efinet he rel ative rol es of int r a-and e x t ra -mit ochondrial geneti c  s y stems in deter mining

in_this project_comprise a four-way partnership_including the_Queens_Borough Public_Library_System, the Queens_Cancer Center, the_American Cancer Society of_Queens, and Memorial_Sloan-Kettering_Cancer Center. The goal of this research is to define the relative roles of_intra-and_extra-mitochondrial genetic_systems_in_determining


state-of-the-art live-cell imaging quantitative fluorescence microscope with total internal reflection fluorescence for quantifying events at the plasma membrane and allow for measurement of dynamic processes underlying these complex interactions in four dimensions (4D) in living cells. It is the goal of this proposal to determine how intraocular iron levels are

state - of - the - art live - cell imagination quantitative fluorescence microscope with entire internal reflection fluorescence for quantify event at the plasma membrane and allow for measurement of dynamic process underlie these complex interactions in four dimension (4D) in living cells. It is the finish of this proposal to determine how intraocular iron levels are

stwte-of-the-art live-cell imaning quantitativg dluorevcence microscupe with total internal reflxctiin flyorescence for quantifhing evenns at the plawna membranx and allow fod meavnrement of dynakic procesves underlying tfede complex interactions in four dimqnsions (4D) in living celjs. Iu if ths goal of this proposal to determihe how pntraocular iron kevels are

state-of-the-art live-cell imaging quantitative fluorescence microscope with reflection for quantifying at the plasma of processes underlying these interactions in four (4D) in living cells. It is goal of this proposal to determine how intraocular iron levels are

state-of-the-art live-cell imagIng quantitAtive FluOreScEnce MicrOscope with totaL InteRnal reflection fluorescEnce fOr QUantIFyIng evEnts at tHE pLASma MeMbRanE aND aLlow fOr mEasuremEnt of dynamIc pRoCesses underlYInG these compLex Interactions In fOur dimEnSioNS (4D) in lIviNg celLs. It is THe goal Of this proPoSAl to deTErmine hOW InTraoCular iron levels arE

state-of-the-art live-cel l imagingquant ita tiv efluo resc ence microscop e  wit h total internal refle ction  f l uore s ce nce f or quan t if y i ngev en tsat th e pla sma  membra ne and all owfo r measuremen t  o f dynamicpro cesses under lyi ng the se  co m plexint eract ions i n  fourdimension s( 4D) in livingc e ll s. I t is the goal oft hi s  proposal to d etermi ne ho w int rao cular iron  l evels are

state-of-the-art_live-cell imaging_quantitative fluorescence microscope with_total internal_reflection_fluorescence for_quantifying_events at the_plasma membrane and_allow for measurement of_dynamic processes underlying_these_complex interactions in four dimensions (4D) in living cells. It is the goal of_this_proposal to_determine_how_intraocular iron levels are


the increased gain of he cardiac sympathetic afferent reflex in HF is a decrease in nitric oxide (NO) production in several central sites which regulate sympathetic outflow. We hypothesize that both an increase in central Ang II and a decrease in central NO contributes to the increase in the sensitivity of the cardiac sympathetic afferent reflex and to the tonic

the increased gain of he cardiac sympathetic afferent reflex in HF is a decrease in nitric oxide (nobelium) product in several central web site which baffle sympathetic outflow. We speculate that both an increase in central Ang II and a decrease in central NO lend to the increase in the sensitivity of the cardiac sympathetic sensory nerve reflex and to the tonic

thf increased gain of he cxrdiac sympathejix affecent rerlex in FF is a decrease in nitric oeide (NO) peoduction in several cdntral sines which regnlate sympathetir outflow. We hgiothevmze that both ak increase hn central Ang IK cnd a decrease in central NO contribttes to tje increase in the fensjniyity of the cardiac sympathetic zfferenu reflex and to thr tonic

the increased gain of he cardiac sympathetic in is a in nitric oxide sites regulate sympathetic outflow. hypothesize that both increase in central Ang II and decrease in central NO contributes to the increase in the sensitivity of the sympathetic afferent reflex and to the tonic

the increased gain of he cardiAc sympatheTic afFerEnt ReFlex In HF Is a decrease in nITric Oxide (NO) production in sevEral cEnTRal sITeS whicH regulaTE sYMPatHeTiC ouTfLOw. we hypOthEsize thAt both an inCreAsE in central AnG iI And a decreaSe iN central NO coNtrIbutes To The INcreaSe iN the sEnsitiVIty of tHe cardiac SyMPathetIC affereNT ReFlex And to the tonic

the increased gain of hecardiac sy mpath eti c a ff eren t re flex in HF isa  dec rease in nitric oxide(NO)pr o duct i on  in s everalc en t r alsi te s w hi c hregul ate  sympat hetic outf low .We hypothesi z ethat bothanincrease incen tral A ng  II and a  de creas e in c e ntralNO contri bu t es tot he incr e a se  inthe sensitivity o f  t h e cardiac symp atheti ca ff e r ent  re flex and t othe t o nic

the_increased gain_of he cardiac sympathetic_afferent reflex_in_HF is_a_decrease in nitric_oxide (NO) production_in several central sites_which regulate sympathetic_outflow._We hypothesize that both an increase in central Ang II and a decrease in_central_NO contributes_to_the_increase in the sensitivity of_the cardiac sympathetic afferent reflex_and to_the tonic


Notch signaling in spermatogenesis. In Specific Aim 3 the hypothesis that the Mgat3 gene may function as a tumor suppressor in mammary gland will be tested in the MMTV-Polyoma middle T (PyMT) mammary tumor model which metastasizes to lung and in cell signaling assays. In addition, roles for

Notch signaling in spermatogenesis. In Specific Aim 3 the hypothesis that the Mgat3 gene may function as a tumor suppressor in mammary gland will be tested in the MMTV - Polyoma in-between T (PyMT) mammary tumor exemplar which metastasizes to lung and in cell signaling assay. In addition, roles for

Nohch signaling in spermatugenesis. In Speeufic Amm 3 the hypotheris that the Mgat3 gene may fnnctuon aw a tumor suppressor iv mammary gland wull ue tested in the MMTV-Polnjma jlddle V (PyMT) mammary jumor model fhich metastashzds to lung and in cell signaling assars. In acdltion, roles fot

Notch signaling in spermatogenesis. In Specific Aim hypothesis the Mgat3 may function as gland be tested in MMTV-Polyoma middle T mammary tumor model which metastasizes to and in cell signaling assays. In addition, roles for

Notch signaling in spermatogEnesis. In SpEcifiC AiM 3 thE hYpotHesiS that the Mgat3 geNE may Function as a tumor suppreSsor iN mAMmarY GlAnd wiLl be tesTEd IN The mMtV-polYoMA mIddle t (PymT) mammaRy tumor modEl wHiCh metastasizES tO lung and in CelL signaling asSayS. In addItIon, ROles fOr

Notch signaling in sperma togenesis.  In S pec ifi cAim3 th e hypothesis t h at t he Mgat3 gene may func tionas a tu m or  supp ressori nm a mma ry  g lan dw il l betes ted inthe MMTV-P oly om a middle T ( P yM T) mammary  tu mor model wh ich  metas ta siz e s tolun g and  in ce l l sign aling ass ay s . In a d dition, r ol es f or

Notch_signaling in_spermatogenesis. In Specific Aim_3 the_hypothesis_that the_Mgat3_gene may function_as a tumor_suppressor in mammary gland_will be tested_in_the MMTV-Polyoma middle T (PyMT) mammary tumor model which metastasizes to lung and in_cell_signaling assays._In_addition,_roles for


using, noninertial particles will provide basic flow profile information needed for predictive dose estimation. Characterizing the relationship between the structure of the human brain and its function is one of the most important goals in neuroscience today. Medical imaging has been used to gain significant new insights into this relationship through the use of both anatomical

using, noninertial particles will provide basic flow visibility data necessitate for predictive dose estimation. characterize the relationship between the structure of the human genius and its routine is one of the most significant goals in neuroscience today. Medical imagination has been used to gain significant new insight into this relationship through the use of both anatomical

usijg, noninertial particles will provide bcwic flmw prorile infurmation needed for predictite dise ewtimation. Characterizivg the repationshup bttween the structnde of tmz humzk brann and its functlon is one mf the most im[oftcnt goals in neuroscience today. Medisal imabijg has been usgd to dain significant new insights into thia relatponship through tne use of both anatomical

using, noninertial particles will provide basic flow needed predictive dose Characterizing the relationship human and its function one of the important goals in neuroscience today. Medical has been used to gain significant new insights into this relationship through the of both anatomical

using, noninertial particles Will providE basiC flOw pRoFile InfoRmation needed fOR preDictive dose estimation. CHaracTeRIzinG ThE relaTionshiP BeTWEen ThE sTruCtURe Of the HumAn brain And its funcTioN iS one of the mosT ImPortant goaLs iN neurosciencE toDay. MedIcAl iMAging Has Been uSed to gAIn signIficant neW iNSights INto this RELaTionShip through the use OF bOTh anatomical

using, noninertial particl es will pr ovide  ba sic  f lowprof ile informatio n  nee ded for predictive dos e est im a tion .  C harac terizin g  t h e  re la ti ons hi p  b etwee n t he stru cture of t hehu man brain an d  i ts functio n i s one of the  mo st imp or tan t  goal s i n neu roscie n ce tod ay. Medic al imagin g  has be e n  u sedto gain significa n tn ew insights in to thi sr el a t ion shi p throughth e use of both an a t o mic a l

using, noninertial_particles will_provide basic flow profile_information needed_for_predictive dose_estimation._Characterizing the relationship_between the structure_of the human brain_and its function_is_one of the most important goals in neuroscience today. Medical imaging has been used_to_gain significant_new_insights_into this relationship through the_use of both anatomical


osteric, and biased melanotropin peptides and peptide mimetics with enhanced stability, bioavailability, selectivity and potency for the melanocortin receptors; 2a) to examine binding affinities, cyclic AMP production, efficacies, Ca+2 assays and assays for -arrestin. The novel ligands for the hMC

osteric, and biased melanotropin peptides and peptide mimetics with enhanced stability, bioavailability, selectivity and potency for the melanocortin receptor; 2a) to test binding affinities, cyclic AMP production, efficacy, Ca+2 assays and assays for -arrestin. The novel ligands for the hMC

ostfric, and biased melanotrupin peptides aue peptmde mimstics wigh enhanced stability, bioavamlabulity, selectivity and potenzy for thv melanocirtii receptors; 2a) to examine bindihn affnnmties, cyclic AMK production, efficacies, Ca+2 arscys and assays for -arrestin. The novej ligancs for the hMC

osteric, and biased melanotropin peptides and peptide enhanced bioavailability, selectivity potency for the binding cyclic AMP production, Ca+2 assays and for -arrestin. The novel ligands for hMC

osteric, and biased melanotroPin peptideS and pEptIde MiMetiCs wiTh enhanced stabILity, Bioavailability, selectiVity aNd POtenCY fOr the MelanocORtIN RecEpToRs; 2a) To EXaMine bIndIng affiNities, cyclIc AmP Production, efFIcAcies, Ca+2 assAys And assays for -ArrEstin. THe NovEL ligaNds For thE hMC

osteric, and biased melano tropin pep tides  an d p ep tide  mim etics with enh a nced  stability, bioavailab ility ,s elec t iv ity a nd pote n cy f orth emel an o co rtinrec eptors;  2a) to ex ami ne  binding aff i ni ties, cycl icAMP producti on,  effic ac ies ,  Ca+2  as saysand as s ays fo r -arrest in .  The n o vel lig a n ds  for  the hMC

osteric, and_biased melanotropin_peptides and peptide mimetics_with enhanced_stability,_bioavailability, selectivity_and_potency for the_melanocortin receptors; 2a)_to examine binding affinities,_cyclic AMP production,_efficacies,_Ca+2 assays and assays for -arrestin. The novel ligands for the hMC


ative Working Group. In addition to our outreach efforts, we will reach inward to our members through monthly Breakfast Club gatherings where research is shared and collaboration encouraged, and offer communications training for members and trainees, including Lightning Talk events and a graduate class in outreach and engagement. COEC is an integrating element in the Center, translating

ative Working Group. In addition to our outreach efforts, we will reach inward to our extremity through monthly Breakfast Club gather where research is shared and collaboration encouraged, and put up communications training for member and trainee, including Lightning Talk events and a graduate class in outreach and engagement. COEC is an integrate element in the Center, translating

atige Working Group. In addiuion to our outrecxh effmrts, ws will rdach inward to our members tirouth mobthly Breakfast Club gxtherings where rwseacch is shared anv collaboratioh encmnraged, and offet communicathons training xof lembers and trainees, including Lighening Tsln events and a gractate blcss in outreach and engagement. DOEC is an integratimg element in the Center, tganspating

ative Working Group. In addition to our we reach inward our members through research shared and collaboration and offer communications for members and trainees, including Lightning events and a graduate class in outreach and engagement. COEC is an integrating in the Center, translating

ative Working Group. In additiOn to our outReach EffOrtS, wE wilL reaCh inward to our mEMberS through monthly BreakfaSt CluB gATherINgS wherE researCH iS SHarEd AnD coLlABoRatioN enCourageD, and offer cOmmUnIcations traiNInG for memberS anD trainees, incLudIng LigHtNinG talk eVenTs and A graduATe clasS in outreaCh ANd engaGEment. COec Is An inTegrating element iN ThE center, translatIng

ative Working Group. In ad dition toour o utr eac heffo rts,  we will reach inwa rd to our members thro ugh m on t hlyB re akfas t Clubg at h e rin gs  w her er es earch  is  shared  and colla bor at ion encourag e d,  and offer  co mmunications  tr aining  f orm ember s a nd tr ainees ,  inclu ding Ligh tn i ng Tal k  events a nd  a g raduate class ino ut r each and engag ement.  C O EC i s a n i ntegrating  e lemen t  in the Ce n t e r,t ranslating

ative Working_Group. In_addition to our outreach_efforts, we_will_reach inward_to_our members through_monthly Breakfast Club_gatherings where research is_shared and collaboration_encouraged,_and offer communications training for members and trainees, including Lightning Talk events and a_graduate_class in_outreach_and_engagement. COEC is an integrating_element in the Center, translating


hyperinsulinemia in the development of cardiovascular disease. This proposal is based on a fundamentally new approach to the isolation of bacterial virulence genes involved in pathogenesis, termed IVET (in vivo expression technology), that allows for the positive selection of bacterial genes that are specifically induced in host tissues. This methodology will be used to characterize the

hyperinsulinemia in the development of cardiovascular disease. This proposal is based on a fundamentally newfangled overture to the isolation of bacterial virulence genes involved in pathogenesis, termed IVET (in vivo formulation technology), that allows for the positivist excerpt of bacterial genes that are specifically induce in host tissues. This methodology will be use to characterize the

hyoerinsulinemia in the deyelopment of carbuovascnlar diaease. Thks proposal is based on a fuidamwntaloy new approach to the isolatioj of bacreriel virulence genxa involyzd in iathoyeiesis, termed IVGT (in vivo efpression techtouoyy), that allows for the positive selestion og hacterial genef thse ars specifically induced in host tisaues. Thps methodology wikl be used to characterize the

hyperinsulinemia in the development of cardiovascular disease. is on a new approach to genes in pathogenesis, termed (in vivo expression that allows for the positive selection bacterial genes that are specifically induced in host tissues. This methodology will be to characterize the

hyperinsulinemia in the deveLopment of cArdioVasCulAr DiseAse. THis proposal is bASed oN a fundamentally new apprOach tO tHE isoLAtIon of BacteriAL vIRUleNcE gEneS iNVoLved iN paThogeneSis, termed IvET (In Vivo expressiON tEchnology), tHat Allows for the PosItive sElEctIOn of bActErial Genes tHAt are sPecificalLy INduced IN host tiSSUeS. ThiS methodology will bE UsED to characterizE the

hyperinsulinemia in the d evelopment  of c ard iov as cula r di sease. This pr o posa l is based on a fundam ental ly newa pp roach  to the is o l ati on  o f b ac t er ial v iru lence g enes invol ved  i n pathogenes i s,  termed IV ET(in vivo exp res sion t ec hno l ogy),  th at al lows f o r thepositivese l ection of bact e r ia l ge nes that are spec i fi c ally induced i n host  t i ss u e s.Thi s methodol og y wil l  be use d  t o c har a cterize the

hyperinsulinemia_in the_development of cardiovascular disease._This proposal_is_based on_a_fundamentally new approach_to the isolation_of bacterial virulence genes_involved in pathogenesis,_termed_IVET (in vivo expression technology), that allows for the positive selection of bacterial genes_that_are specifically_induced_in_host tissues. This methodology will_be used to characterize the


and anti-IL- 13. We were able to overcome antigen-specific unresponsiveness in only a minority of the rhesus monkeys studied. Co-culture with either IL-2 or IL-12 were the only conditions which resulted in a slightly enhanced proliferation to BmA in these animals. Even high concentration

and anti - IL- 13. We were able to overcome antigen - specific unresponsiveness in only a minority of the rhesus monkeys studied. conscientious objector - acculturation with either IL-2 or IL-12 were the only conditions which resulted in a slenderly enhanced proliferation to BmA in these animals. Even high assiduity

anf anti-IL- 13. We were able tu overcome antiywn-specmfic undesponsixeness in only a minority of tye rhtfus monkeys studiea. Co-cultuge with euthec IL-2 or IL-12 were vge only condiflons chmch resulted in a slightlf enhanced proniwexation to BmA in these animals. Even righ comcfntration

and anti-IL- 13. We were able to unresponsiveness only a of the rhesus IL-2 IL-12 were the conditions which resulted a slightly enhanced proliferation to BmA these animals. Even high concentration

and anti-IL- 13. We were able to overCome antigeN-specIfiC unReSponSiveNess in only a minORity Of the rhesus monkeys studIed. Co-CuLTure WItH eithEr IL-2 or Il-12 WeRE The OnLy ConDiTIoNs whiCh rEsulted In a slightlY enHaNced proliferATiOn to BmA in tHesE animals. Even HigH conceNtRatIOn

and anti-IL- 13. We wereable to ov ercom e a nti ge n-sp ecif ic unresponsiv e ness  in only a minority of  therh e susm on keysstudied .  C o - cul tu re  wi th ei therIL- 2 or IL -12 were t heon ly condition s  w hich resul ted  in a slight lyenhanc ed  pr o lifer ati on to  BmA i n  these  animals.  E v en hig h  concen t r at ion

and_anti-IL- 13._We were able to_overcome antigen-specific_unresponsiveness_in only_a_minority of the_rhesus monkeys studied._Co-culture with either IL-2_or IL-12 were_the_only conditions which resulted in a slightly enhanced proliferation to BmA in these animals._Even_high concentration


cing Membranes -Structure and Function, Cell Surface Immuno-Receptors, Cell-Cell Interactions, Cell Surface in Neoplasia, Molecular Basis of Motility, Gamete Morphogenesis, Somatic Cell Hybridization. They will be followed in the afternoons and evenings by sessions of short contributed papers

cing Membranes -Structure and Function, Cell Surface Immuno - Receptors, Cell - Cell Interactions, Cell Surface in Neoplasia, Molecular Basis of Motility, Gamete Morphogenesis, Somatic Cell Hybridization. They will be followed in the afternoons and evenings by sessions of light contributed composition

cinh Membranes -Structure ana Function, Cell Surfacx Immunk-Receptofs, Cell-Cell Interactions, Celp Wurfaxe in Neoplasia, Molecuuar Basis of Motioity, Tamete Mor'gogeneslf, Sojwtic Rell Hybridizatlon. They winl be followed iv che afternoons and evenings by sessijns of xhlrt contributeq pakerf

cing Membranes -Structure and Function, Cell Surface Interactions, Surface in Molecular Basis of Hybridization. will be followed the afternoons and by sessions of short contributed papers

cing Membranes -Structure and function, CeLl SurFacE ImMuNo-ReCeptOrs, Cell-Cell IntERactIons, Cell Surface in NeoplAsia, MOlECulaR baSis of motilitY, gaMETe MOrPhOgeNeSIs, somatIc CEll HybrIdization. THey WiLl be followed IN tHe afternooNs aNd evenings by SesSions oF sHorT ContrIbuTed paPers

cing Membranes -Structureand Functi on, C ell  Su rf aceImmu no-Receptors,C ell- Cell Interactions, Cel l Sur fa c e in Ne oplas ia, Mol e cu l a r B as is  of  M o ti lity,  Ga mete Mo rphogenesi s,So matic Cell H y br idization.  Th ey will be f oll owed i nthe after noo ns an d even i ngs by  sessions  o f  short contrib u t ed  pap ers

cing Membranes_-Structure and_Function, Cell Surface Immuno-Receptors,_Cell-Cell Interactions,_Cell_Surface in_Neoplasia,_Molecular Basis of_Motility, Gamete Morphogenesis,_Somatic Cell Hybridization. They_will be followed_in_the afternoons and evenings by sessions of short contributed papers


The susceptibility of the DLC-1 (+/-) and (-/-) mice to hepatocarcinogenesis can be studied using the liver cancer models developed in LEC. A new constitutive translocation involving a common fragile site was characterized by FISH and molecular markers. In a family in which multifocal clear cell renal carcinoma (RCC)

The susceptibility of the DLC-1 (+ /-) and (-/-) mice to hepatocarcinogenesis can be studied using the liver cancer models develop in LEC. A newfangled constitutive translocation involving a common flimsy site was characterized by pisces and molecular marker. In a family in which multifocal clear cell renal carcinoma (RCC )

Thf susceptibility of the ALC-1 (+/-) and (-/-) mice jo hepatmcarcihogenesir can be studied using the lmver canctg models developed in LEC. A nea constirutite translocation involviky a cklmon hragile site wax charactesized by FISH dna lolecular markers. In a family in whych mulyivocal clear cejl rtnaj cadbikoma (RCC)

The susceptibility of the DLC-1 (+/-) and to can be using the liver A constitutive translocation involving common fragile site characterized by FISH and molecular markers. a family in which multifocal clear cell renal carcinoma (RCC)

The susceptibility of the DLC-1 (+/-) And (-/-) mice to hEpatoCarCinOgEnesIs caN be studied usinG The lIver cancer models develoPed in lEc. a new COnStituTive traNSlOCAtiOn InVolViNG a CommoN frAgile siTe was charaCteRiZed by FISH and MOlEcular markErs. in a family in wHicH multiFoCal CLear cEll Renal CarcinOMa (RCC)

The susceptibility of the  DLC-1 (+/ -) an d ( -/- )mice  tohepatocarcinog e nesi s can be studied using  theli v er c a nc er mo dels de v el o p edin  L EC.  A ne w con sti tutivetranslocat ion  i nvolving a c o mm on fragile  si te was chara cte rizedby  FI S H and  mo lecul ar mar k ers. I n a famil yi n whic h  multif o c al  cle ar cell renal car c in o ma (RCC)

The_susceptibility of_the DLC-1 (+/-) and_(-/-) mice_to_hepatocarcinogenesis can_be_studied using the_liver cancer models_developed in LEC. A_new constitutive translocation_involving_a common fragile site was characterized by FISH and molecular markers. In a family_in_which multifocal_clear_cell_renal carcinoma (RCC)


collaborations. There are two major components of this core. The core will 1) Serve as a resource of multi-user equipment 2) Perform Immune Function Assessment by 1) Evaluation of the general health status 2) Level I immunological testing which includes a variety of assays that examine the functions of T cells, B

collaborations. There are two major components of this core. The effect will 1) service as a resource of multi - user equipment 2) Perform Immune Function Assessment by 1) Evaluation of the general health status 2) Level I immunological examination which includes a variety of assays that analyze the functions of T cell, B

coplaborations. There are tdo major compongnrs of vhis code. The cure will 1) Serve as a resourcx of multu-user equipment 2) Perfofm Immune Functiob Aswwssment by 1) Evaluabnon or the jeneral health xtatus 2) Leeel I immunolocizap testing which includes a variety jf assaus that examine jhe flnstiohs of T cells, B

collaborations. There are two major components of The will 1) as a resource Immune Assessment by 1) of the general status 2) Level I immunological testing includes a variety of assays that examine the functions of T cells, B

collaborations. There are two Major compoNents Of tHis CoRe. ThE corE will 1) Serve as a rESourCe of multi-user equipment 2) perfoRm iMmunE fuNctioN AssessMEnT BY 1) EvAlUaTioN oF ThE geneRal Health sTatus 2) Level i imMuNological tesTInG which inclUdeS a variety of aSsaYs that ExAmiNE the fUncTions Of T celLS, B

collaborations. There are  two major  comp one nts  o f th is c ore. The corew ill1) Serve as a resource  of m ul t i-us e requip ment 2) Pe r f orm  I mm une  F u nc tionAss essment  by 1) Eva lua ti on of the ge n er al healthsta tus 2) Level  Iimmuno lo gic a l tes tin g whi ch inc l udes a  varietyof assays that ex a m in e th e functions of Tc el l s, B

collaborations._There are_two major components of_this core._The_core will_1)_Serve as a_resource of multi-user_equipment 2) Perform Immune_Function Assessment by_1)_Evaluation of the general health status 2) Level I immunological testing which includes a_variety_of assays_that_examine_the functions of T cells,_B


tissue specific enzyme glutamic acid decarboxylase will be examined to determine if the increase in the quantity of the protein is due to a change in the rate of synthesis, the rate of degradation, or a modulation of both parameters. 2) The tissue specific S-100 protein is actually a class of related proteins;

tissue specific enzyme glutamic acid decarboxylase will be examined to determine if the increase in the measure of the protein is ascribable to a variety in the rate of synthesis, the rate of abasement, or a modulation of both parameters. 2) The tissue specific S-100 protein is actually a class of relate proteins;

tidsue specific enzyme gluuamic acid decarboxylase will ge examived to determine if the incrxase in tye quantity of the progein is dle to a cyangt in the rate of synthesis, the dwte mh degradation, ot a modulatimn of both pardmdtzrs. 2) The tissue specific S-100 protein if actuaklj a class of rglatec profviks;

tissue specific enzyme glutamic acid decarboxylase will to if the in the quantity to change in the of synthesis, the of degradation, or a modulation of parameters. 2) The tissue specific S-100 protein is actually a class of related

tissue specific enzyme glutaMic acid decArboxYlaSe wIlL be eXamiNed to determine IF the Increase in the quantity oF the pRoTEin iS DuE to a cHange in THe RATe oF sYnTheSiS, ThE rate Of dEgradatIon, or a moduLatIoN of both paramETeRs. 2) The tissuE spEcific S-100 proteIn iS actuaLlY a cLAss of RelAted pRoteinS;

tissue specific enzyme gl utamic aci d dec arb oxy la se w illbe examined to dete rmine if the increasein th eq uant i ty  of t he prot e in i s d ue  t o a  c h an ge in  th e rateof synthes is,  t he rate of d e gr adation, o r a  modulationofboth p ar ame t ers.2)The t issues pecifi c S-100 p ro t ein is actuall y aclas s of related prot e in s ;

tissue_specific enzyme_glutamic acid decarboxylase will_be examined_to_determine if_the_increase in the_quantity of the_protein is due to_a change in_the_rate of synthesis, the rate of degradation, or a modulation of both parameters. 2)_The_tissue specific_S-100_protein_is actually a class of_related proteins;


adventitial fibroblasts). There has been growing interest in the vascular NADPH oxidases, largely because it is recognized that oxidative stress plays a critical role in the pathogenesis of vascular diseases, such as atherosclerosis. Preliminary studies performed in our group and others have demonstrated that ortho- methoxyphenols, such as ap

adventitial fibroblasts). There has been growing interest in the vascular NADPH oxidases, largely because it is spot that oxidative tension plays a critical role in the pathogenesis of vascular disease, such as atherosclerosis. Preliminary studies do in our group and others have demonstrated that ortho- methoxyphenols, such as ap

adgentitial fibroblasts). Thtre has been grownbg intxrest ih the varcular NADPH oxidases, largelb bexause it is recognized that oxidativv stress playw a critical role ik the iathoyeiesis of vasculsr diseasev, such as athesorcperosis. Preliminary studies performqd in oir group and othgrs hsde dsmonstrated that ortho- methoxyphenkls, suci as ap

adventitial fibroblasts). There has been growing interest vascular oxidases, largely it is recognized critical in the pathogenesis vascular diseases, such atherosclerosis. Preliminary studies performed in our and others have demonstrated that ortho- methoxyphenols, such as ap

adventitial fibroblasts). TheRe has been gRowinG inTerEsT in tHe vaScular NADPH oxiDAses, Largely because it is recoGnizeD tHAt oxIDaTive sTress plAYs A CRitIcAl RolE iN ThE pathOgeNesis of Vascular diSeaSeS, such as atherOScLerosis. PreLimInary studies PerFormed In Our GRoup aNd oThers Have deMOnstraTed that orThO- MethoxYPhenols, SUCh As ap

adventitial fibroblasts).  There has  been  gr owi ng  int eres t in the vascu l ar N ADPH oxidases, largely  beca us e  iti srecog nized t h at o xid at iv e s tr e ss  play s a  critic al role in  th epathogenesis of  vasculardis eases, suchasathero sc ler o sis.Pre limin ary st u dies p erformedin our gr o up ando t he rs h ave demonstratedt ha t  ortho- methox ypheno ls ,  s u c h a s a p

adventitial_fibroblasts). There_has been growing interest_in the_vascular_NADPH oxidases,_largely_because it is_recognized that oxidative_stress plays a critical_role in the_pathogenesis_of vascular diseases, such as atherosclerosis. Preliminary studies performed in our group and others_have_demonstrated that_ortho-_methoxyphenols,_such as ap


felis, and throughout flea populations. Parameters of R. felis infection and transmission in fleas; specifically, a) horizontal transmission (contribution of vertebrate hosts and concurrent feeding); b) vertical transmission (dynamics of replication and dissemination through adult tissues and immature stages of life cycle); c) flea fitness (

felis, and throughout flea populations. Parameters of R. felis infection and transmission in flea; specifically, a) horizontal transmittance (contribution of vertebrate hosts and concurrent eating); b) vertical infection (dynamics of replication and dispersion through adult tissue and immature phase of life cycle); c) flea seaworthiness (

fepis, and throughout flea kopulations. Paramgtwrs of R. feljs infecgion and transmission in flees; specifucally, a) horizontal trxnsmissioj (contrivutiib of verteudate hosts ans coneucrent feeding); b) vertical dransmission (dfnxmncs of replication and dissemination througn wdult tissues wnd pmiatudv wtages of life cycle); c) flea fjtness (

felis, and throughout flea populations. Parameters of infection transmission in specifically, a) horizontal and feeding); b) vertical (dynamics of replication dissemination through adult tissues and immature of life cycle); c) flea fitness (

felis, and throughout flea popUlations. PaRametErs Of R. FeLis iNfecTion and transmiSSion In fleas; specifically, a) hoRizonTaL TranSMiSsion (ContribUTiON Of vErTeBraTe HOsTs and ConCurrent Feeding); b) veRtiCaL transmissioN (DyNamics of rePliCation and disSemInatioN tHroUGh aduLt tIssueS and imMAture sTages of liFe CYcle); c) fLEa fitneSS (

felis, and throughout fle a populati ons.Par ame te rs o f R.  felis infecti o n an d transmission in flea s; sp ec i fica l ly , a)horizon t al t ran sm is sio n( co ntrib uti on of v ertebratehos ts  and concurr e nt  feeding);  b)  vertical tr ans missio n(dy n amics  of  repl icatio n  and d isseminat io n  throu g h adult t is sues  and immature sta g es of life cycle) ; c) f le a  f i t nes s (

felis,_and throughout_flea populations. Parameters of_R. felis_infection_and transmission_in_fleas; specifically, a)_horizontal transmission (contribution_of vertebrate hosts and_concurrent feeding); b)_vertical_transmission (dynamics of replication and dissemination through adult tissues and immature stages of life_cycle);_c) flea_fitness_(


accessibility and known microbial composition. Specific Aim 1 will examine the effects of 3 systemically administered antibiotics on the microbial composition of subgingival biofilms in adult humans with periodontitis. All subjects will receive scaling and root planing and will be randomly assigned to one of 4 groups of 36 subjects each receiving one of do

accessibility and known microbial composition. Specific Aim 1 will examine the effect of 3 systemically distribute antibiotics on the microbial composition of subgingival biofilms in adult humans with periodontal disease. All subjects will receive scaling and root planing and will be randomly put to one of 4 groups of 36 subjects each meet one of do

acfessibility and known migrobial compositnin. Sperific Ajm 1 will examine the effects of 3 sysvemixally administered antibiotkcs on thv microbiql cinposition of subgikyival niofinns in adult hukans with [eriodontitis. Dlu dubjects will receive scaling and rjot plamijg and will be rancjmly assigned to one of 4 groups of 36 sugjects tach receiving one of do

accessibility and known microbial composition. Specific Aim examine effects of systemically administered antibiotics subgingival in adult humans periodontitis. All subjects receive scaling and root planing and be randomly assigned to one of 4 groups of 36 subjects each receiving of do

accessibility and known micrObial compoSitioN. SpEciFiC Aim 1 Will Examine the effeCTs of 3 Systemically administerEd antIbIOticS On The miCrobial COmPOSitIoN oF suBgINgIval bIofIlms in aDult humans WitH pEriodontitis. aLl Subjects wiLl rEceive scalinG anD root pLaNinG And wiLl bE randOmly asSIgned tO one of 4 groUpS Of 36 subjECts each RECeIvinG one of do

accessibility and known m icrobial c ompos iti on.  S peci ficAim 1 will exa m inethe effects of 3 syste mical ly admi n is tered  antibi o ti c s  on  t he  mi cr o bi al co mpo sitionof subging iva lbiofilms ina du lt humanswit h periodonti tis . Allsu bje c ts wi llrecei ve sca l ing an d root pl an i ng and will be r an doml y assigned to one of 4 groups of 36  subje ct s  e a c h r ece iving oneof  do

accessibility_and known_microbial composition. Specific Aim_1 will_examine_the effects_of_3 systemically administered_antibiotics on the_microbial composition of subgingival_biofilms in adult_humans_with periodontitis. All subjects will receive scaling and root planing and will be randomly_assigned_to one_of_4_groups of 36 subjects each_receiving one of do