would appear as intense spots in the TEM spectra. For the complimentary pyrimidine label, osmium tetraoxide bipyridine will be the selective binding agent thymine and cytosine. Using the bipyridine ligand as a scaffold for functionalization, additional osmium, platinum (ZPt = 78) or uranium (

would appear as intense spots in the TEM spectra. For the complimentary pyrimidine label, osmium tetraoxide bipyridine will be the selective bind agentive role thymine and cytosine. Using the bipyridine ligand as a scaffold for functionalization, additional osmium, platinum (ZPt = 78) or uranium (

wokld appear as intense sputs in the TEM spectra. For tge complkmentary pyrimidine label, osliym teugaoxide bipyridine wiul be the selectice bmnding agent thymine and cytosjke. Usnnj the bipyriding ligand as d scaffold for fjnetionalization, additional osmium, plaeinum (ZLt = 78) or uranium (

would appear as intense spots in the For complimentary pyrimidine osmium tetraoxide bipyridine agent and cytosine. Using bipyridine ligand as scaffold for functionalization, additional osmium, platinum = 78) or uranium (

would appear as intense spots In the TEM spEctra. for The CoMpliMentAry pyrimidine lABel, oSmium tetraoxide bipyridIne wiLl BE the SElEctivE bindinG AgENT thYmInE anD cYToSine. USinG the bipYridine ligAnd As A scaffold for FUnCtionalizaTioN, additional oSmiUm, platInUm (ZpT = 78) or urAniUm (

would appear as intense s pots in th e TEM  sp ect ra . Fo r th e complimentar y  pyr imidine label, osmiumtetra ox i de b i py ridin e willb et h e s el ec tiv eb in dingage nt thym ine and cy tos in e. Using the bi pyridine l iga nd as a scaf fol d forfu nct i onali zat ion,additi o nal os mium, pla ti n um (ZP t  = 78)o r  u rani um (

would_appear as_intense spots in the_TEM spectra._For_the complimentary_pyrimidine_label, osmium tetraoxide_bipyridine will be_the selective binding agent_thymine and cytosine._Using_the bipyridine ligand as a scaffold for functionalization, additional osmium, platinum (ZPt = 78)_or_uranium (


cultures rely on magnetic negative selection using Annexin V-based magnetic particles. Annexin V binds to the phospholipid phosphatidylserine (PS) present on the surface of dead cells and cell membrane fragments. A magnetic field is then applied to collect dead cells from the healthy culture. Although commercially successful, Annexin V-

cultures rely on magnetic negative survival use Annexin V - based magnetic particles. Annexin vanadium binds to the phospholipid phosphatidylserine (PS) present on the surface of all in cells and cell membrane fragments. A charismatic sphere is then applied to gather dead cells from the goodly culture. Although commercially successful, Annexin V-

cuptures rely on magnetic kegative selection usinj Annexjn V-basea magnetic particles. Annexin V bindw to the phospholipid ohosphatifylserinw (PS) present on the surncce or deab rells and cell kembrane fsagments. A magtegie field is then applied to collect dqad celks from the healjhy clleure. Although commercially successful, Znnexin V-

cultures rely on magnetic negative selection using magnetic Annexin V to the phospholipid surface dead cells and membrane fragments. A field is then applied to collect cells from the healthy culture. Although commercially successful, Annexin V-

cultures rely on magnetic negAtive selecTion uSinG AnNeXin V-BaseD magnetic partiCLes. ANnexin V binds to the phospHolipId PHospHAtIdylsErine (PS) PReSENt oN tHe SurFaCE oF dead CelLs and ceLl membrane FraGmEnts. A magnetiC FiEld is then aPplIed to collect DeaD cells FrOm tHE healThy CultuRe. AlthOUgh comMercially SuCCessfuL, annexin v-

cultures rely on magnetic  negativeselec tio n u si ng A nnex in V-based mag n etic  particles. Annexin Vbinds  t o  the ph ospho lipid p h os p h ati dy ls eri ne (P S) pr ese nt on t he surface  of  d ead cells an d  c ell membra nefragments. A  ma gnetic  f iel d  is t hen  appl ied to collec t dead ce ll s  fromt he heal t h ycult ure. Although com m er c ially successf ul, An ne x in V -

cultures_rely on_magnetic negative selection using_Annexin V-based_magnetic_particles. Annexin_V_binds to the_phospholipid phosphatidylserine (PS)_present on the surface_of dead cells_and_cell membrane fragments. A magnetic field is then applied to collect dead cells from_the_healthy culture._Although_commercially_successful, Annexin V-


bleeding disorder known as Bernard-Soulier syndrome. The interaction of platelets with vWF through the GP Ib-IX receptor has also been shown to be relevant for the development of pathological platelet thrombi responsible for vascular occlusion. Therefore, studies on the structure and function of GP Ib-IX are relevant for understanding the pathogenesis

bleeding disorder known as Bernard - Soulier syndrome. The interaction of platelets with vWF through the GP Ib - nine sense organ has besides been shown to be relevant for the development of pathological platelet thrombus responsible for vascular occlusion. Therefore, study on the structure and function of GP Ib - IX are relevant for understand the pathogenesis

blfeding disorder known as Bernard-Soulier syndroke. The interacgion of platelets with vWF tirouth tht GP Ib-IX receptor fas also heen shoqn ti be relevaif for tmz devspopmznv of pathologicsl plateled thrombi respmnriyle for vascular occlusion. Therefore, studiex ln the structute anc fundniin of GP Ib-IX are relevant fod undervtanding the lathogenesis

bleeding disorder known as Bernard-Soulier syndrome. The platelets vWF through GP Ib-IX receptor be for the development pathological platelet thrombi for vascular occlusion. Therefore, studies on structure and function of GP Ib-IX are relevant for understanding the pathogenesis

bleeding disorder known as BeRnard-SouliEr synDroMe. THe InteRactIon of platelets WIth vwF through the GP Ib-IX recePtor hAs ALso bEEn Shown To be relEVaNT For ThE dEveLoPMeNt of pAthOlogicaL platelet tHroMbI responsible FOr Vascular ocCluSion. ThereforE, stUdies oN tHe sTRuctuRe aNd funCtion oF gP Ib-IX Are relevaNt FOr undeRStandinG THe PathOgenesis

bleeding disorder known a s Bernard- Souli ersyn dr ome.  The  interaction o f  pla telets with vWF throug h the  G P  Ib- I Xrecep tor has al s o  be en  s how nt obe re lev ant for  the devel opm en t of patholo g ic al platele t t hrombi respo nsi ble fo rvas c ularocc lusio n. The r efore,  studieson the st r ucturea n dfunc tion of GP Ib-IXa re relevant for u nderst an d in g the  pa thogenesis

bleeding_disorder known_as Bernard-Soulier syndrome. The_interaction of_platelets_with vWF_through_the GP Ib-IX_receptor has also_been shown to be_relevant for the_development_of pathological platelet thrombi responsible for vascular occlusion. Therefore, studies on the structure and_function_of GP_Ib-IX_are_relevant for understanding the pathogenesis


rens of gene expression via activation of cAMP response element (CRE)-directed transcription. The mechanism of the CRE-directed transcription in cell proliferation, however, is largely unexplored. To elucidate the role of the cAMP enhancer (CRE) in the control of cell proliferation, we used transcription factor-decoy oligonucleotide approach. Our

rens of gene expression via activation of cAMP response chemical element (CRE)-directed arrangement. The mechanism of the CRE - directed transcription in cell proliferation, however, is largely undiscovered. To elucidate the role of the cAMP foil (CRE) in the command of cell proliferation, we use transcription factor - decoy oligonucleotide overture. Our

rend of gene expression via activation of eQMP revponse element (CRE)-directed transcription. Tie mwchanusm of the CRE-directed transcriition in xell proliferatmkn, howeyzr, is pargzlb unexplored. To elucidate the role of tve cCMP enhancer (CRE) in the control of cqll prokiveration, we usgd trsgscrjitlon factor-decoy oligonucleotide zpproaci. Our

rens of gene expression via activation of element transcription. The of the CRE-directed is unexplored. To elucidate role of the enhancer (CRE) in the control of proliferation, we used transcription factor-decoy oligonucleotide approach. Our

rens of gene expression via acTivation of CAMP rEspOnsE eLemeNt (CRe)-directed transCRiptIon. The mechanism of the CRe-direCtED traNScRiptiOn in celL PrOLIfeRaTiOn, hOwEVeR, is laRgeLy unexpLored. To eluCidAtE the role of thE CAmP enhancer (cRE) In the control Of cEll proLiFerATion, wE usEd traNscripTIon facTor-decoy oLiGOnucleOTide appROAcH. Our

rens of gene expression vi a activati on of  cA MPre spon se e lement (CRE)-d i rect ed transcription. Themecha ni s m of th e CRE -direct e dt r ans cr ip tio ni ncellpro liferat ion, howev er,  i s largely un e xp lored. Toelu cidate the r ole  of th ecAM P  enha nce r (CR E) int he con trol of c el l  proli f eration , we  use d transcription f a ct o r-decoy oligon ucleot id e  a p p roa ch.  Our

rens of_gene expression_via activation of cAMP_response element_(CRE)-directed_transcription. The_mechanism_of the CRE-directed_transcription in cell_proliferation, however, is largely_unexplored. To elucidate_the_role of the cAMP enhancer (CRE) in the control of cell proliferation, we used_transcription_factor-decoy oligonucleotide_approach._Our


achieve an immunized, protected population, addressing issues of limited supply, lack of access and compliance. The Self Administered Vaccination Electromechanical (SAVE) device gently and quickly reduces the stratum corneum, administers efficacious and consistent amounts of vaccine in minutes, and avoids creation of "sharps"

achieve an immunized, protected population, addressing issues of circumscribed provision, lack of entree and compliance. The Self Administered Vaccination Electromechanical (SAVE) device gently and quickly reduce the stratum corneum, administer effective and consistent amounts of vaccine in minutes, and avoids creation of " sharp "

acjieve an immunized, protegted population, cedressmng isshes of lkmited supply, lack of access abd conpliance. The Self Admivistered Naccinatiin Eowctromechaijcal (SAYZ) devjge geutoy and quickly reduces tve stratum cortejm, administers efficacious and consiseent ampujts of vaccine in kynutss, and avoids creation of "sharps"

achieve an immunized, protected population, addressing issues supply, of access compliance. The Self gently quickly reduces the corneum, administers efficacious consistent amounts of vaccine in minutes, avoids creation of "sharps"

achieve an immunized, protectEd populatiOn, addResSinG iSsueS of lImited supply, laCK of aCcess and compliance. The SElf AdMiNIsteREd vacciNation ELEcTROmeChAnIcaL (SavE) DevicE geNtly and Quickly redUceS tHe stratum corNEuM, administeRs eFficacious anD coNsisteNt AmoUNts of VacCine iN minutES, and avOids creatIoN Of "sharPS"

achieve an immunized, pro tected pop ulati on,  ad dr essi ng i ssues of limit e d su pply, lack of access a nd co mp l ianc e .The S elf Adm i ni s t ere dVa cci na t io n Ele ctr omechan ical (SAVE ) d ev ice gently a n dquickly re duc es the strat umcorneu m,  ad m inist ers  effi caciou s  and c onsistent  a m ountso f vacci n e  i n mi nutes, and avoids cr e ation of "shar ps"

achieve_an immunized,_protected population, addressing issues_of limited_supply,_lack of_access_and compliance. The_Self Administered Vaccination_Electromechanical (SAVE) device gently_and quickly reduces_the_stratum corneum, administers efficacious and consistent amounts of vaccine in minutes, and avoids creation_of_"sharps"


rovidingseedfundingforpilo tstudiesto enabl eaf fil ia tedi nves tigatorsto lau n chpr omisingresearchandcoll ectpr el i mina r yd atato informa n ds t r eng th en lar ge r re searc hpr ojects.  Throughit scl os eassociation w it hBrownUniv ers ity,CfNNprov ide seduca ti ona l oppor tun ities to und e rgradu ates,grad u


era of escalating health care costs, successful cartilage repair would decrease the long-term costs of health care related to joint replacement and multiple revisions thereof. Our long-term objective is to develop a tissue engineering approach for cartilage repair using periosteum. Periosteal grafts have the potential to contribute to each of the

era of escalating health care costs, successful cartilage haunt would decrease the retentive - term costs of health caution refer to joint replacement and multiple revisions thence. Our long - term objective is to evolve a tissue engineering approach for cartilage haunt using periosteum. Periosteal grafts have the potential to lend to each of the

erw of escalating health cxre costs, successful certilags repair would decrease the long-term cists if health care related to joint replacenent qnd multiple revisljns fmereoy. Iur long-term onjective is to develop a dirsbe engineering approach for cartilagq repait ksing periosteom. Pegijstezl grafts have the potential to cohtributt to each of the

era of escalating health care costs, successful would the long-term of health care multiple thereof. Our long-term is to develop tissue engineering approach for cartilage repair periosteum. Periosteal grafts have the potential to contribute to each of the

era of escalating health care Costs, succeSsful CarTilAgE repAir wOuld decrease thE Long-Term costs of health care rElateD tO JoinT RePlaceMent and MUlTIPle ReViSioNs THeReof. OUr lOng-term Objective iS to DeVelop a tissue ENgIneering apProAch for cartilAge Repair UsIng PEriosTeuM. PeriOsteal GRafts hAve the potEnTIal to cONtributE TO eAch oF the

era of escalating healthcare costs , suc ces sfu lcart ilag e repair would decr ease the long-term cos ts of  h e alth ca re re lated t o  j o i ntre pl ace me n tand m ult iple re visions th ere of . Our long-t e rm  objective  is  to developa t issueen gin e ering  ap proac h forc artila ge repair  u s ing pe r iosteum . Pe rios teal grafts havet he potential to c ontrib ut e  t o eac h o f the

era_of escalating_health care costs, successful_cartilage repair_would_decrease the_long-term_costs of health_care related to_joint replacement and multiple_revisions thereof. Our_long-term_objective is to develop a tissue engineering approach for cartilage repair using periosteum. Periosteal_grafts_have the_potential_to_contribute to each of the


autosomal dominant disorder caused by mutations in the genes encoding the receptor subunits for TGF?. LDS is associated with an increased risk of developing EoE and other more general food allergies. Remarkably, LDS mice also demonstrate increased Th2 inflammation, and the spontaneous development of EoE. Dr. Guerrerio joined

autosomal dominant disorder caused by mutations in the gene encode the sense organ subunits for TGF? . LDS is associated with an increased hazard of developing EoE and other more general food allergy. signally, LDS mice besides attest increased Th2 ignition, and the spontaneous development of EoE. Dr. Guerrerio join

auhosomal dominant disordev caused by mutajiins in the gsnes encuding the receptor subunits hor RGF?. LES is associated with xn increaded risk of veveloping EoE ais other more fcneran food allergiex. Remarkabny, LDS mice alvo dzmonstrate increased Th2 inflammation, and thr dpontaneous dedelokmegt or EoE. Dr. Guerrerio joined

autosomal dominant disorder caused by mutations in encoding receptor subunits TGF?. LDS is of EoE and other general food allergies. LDS mice also demonstrate increased Th2 and the spontaneous development of EoE. Dr. Guerrerio joined

autosomal dominant disorder Caused by muTatioNs iN thE gEnes EncoDing the receptoR SubuNits for TGF?. LDS is associaTed wiTh AN incREaSed riSk of devELoPINg EOE AnD otHeR MoRe genEraL food alLergies. RemArkAbLy, LDS mice alsO DeMonstrate iNcrEased Th2 inflaMmaTion, anD tHe sPOntanEouS deveLopmenT Of EoE. DR. GuerreriO jOIned

autosomal dominant disord er causedby mu tat ion sin t he g enes encodingt he r eceptor subunits for T GF?.LD S  isa ss ociat ed with an i ncr ea se d r is k  o f dev elo ping Eo E and othe r m or e general fo o dallergies.  Re markably, LD S m ice al so  de m onstr ate  incr easedT h2 inf lammation ,a nd the spontan e o us  dev elopment of EoE.D r. Guerrerio join ed

autosomal_dominant disorder_caused by mutations in_the genes_encoding_the receptor_subunits_for TGF?. LDS_is associated with_an increased risk of_developing EoE and_other_more general food allergies. Remarkably, LDS mice also demonstrate increased Th2 inflammation, and the_spontaneous_development of_EoE._Dr._Guerrerio joined


and dependence) and their associated physical and mental disabilities. These include detailed measures of alcohol consumption and drug use for ten substances, along with their abuse and dependence measures. Major physical disorders (e.g., liver cirrhosis) and mental disorders (e.g., major depressive disorder) highly comorbid with alcohol and drug use disorders

and dependence) and their associated physical and mental disability. These admit detailed measuring stick of alcohol consumption and drug habit for ten kernel, along with their abuse and dependence standard. Major physical disorders (for example, liver cirrhosis) and genial disorders (e.g., major depressive disorderliness) highly comorbid with alcohol and drug use disorders

anf dependence) and their arsociated physieql and mentam disabiuities. These include detailev meqsurew of alcohol consumptiun and drlg use foe tei substances, aloif with bkeir znuse cnv dependence messures. Majmr physical divofdzrs (e.g., liver cirrhosis) and mental diforders (e.h., major depresfive qisodder) highly comorbid with alcohol znd druj use disorders

and dependence) and their associated physical and These detailed measures alcohol consumption and along their abuse and measures. Major physical (e.g., liver cirrhosis) and mental disorders major depressive disorder) highly comorbid with alcohol and drug use disorders

and dependence) and their assoCiated physIcal aNd mEntAl DisaBiliTies. These incluDE detAiled measures of alcohol ConsuMpTIon aND dRug usE for ten SUbSTAncEs, AlOng WiTH tHeir aBusE and depEndence meaSurEs. major physicaL DiSorders (e.g., lIveR cirrhosis) anD meNtal diSoRdeRS (e.g., maJor DepreSsive dISorder) Highly comOrBId with ALcohol aND DrUg usE disorders

and dependence) and their  associate d phy sic alan d me ntal  disabilities. Thes e include detailed mea sures  o f  alc o ho l con sumptio n  a n d  dr ug  u sefo r  t en su bst ances,along with  th ei r abuse andd ep endence me asu res. Major p hys ical d is ord e rs (e .g. , liv er cir r hosis)  and ment al disord e rs (e.g . ,  m ajor  depressive disor d er )  highly comorb id wit ha lc o h oland  drug usedi sorde r s

and_dependence) and_their associated physical and_mental disabilities._These_include detailed_measures_of alcohol consumption_and drug use_for ten substances, along_with their abuse_and_dependence measures. Major physical disorders (e.g., liver cirrhosis) and mental disorders (e.g., major depressive_disorder)_highly comorbid_with_alcohol_and drug use disorders


mechanisms of central OT receptor transduction at the OT neuron will have important applications for understanding the wider roles of OTRs in brain function. There are Three Specific Aims: Specific Aim 1. To determine if the enhancement of AHPs in OT neurons by OT is specific to OT neurons and OT receptor activation, whether it is

mechanisms of central OT receptor transduction at the OT neuron will get authoritative applications for understanding the wider character of OTRs in brain function. There be Three Specific Aims: Specific Aim 1. To decide if the enhancement of AHPs in OT neurons by OT is specific to OT neurons and OT receptor activation, whether it is

mefhanisms of central OT rtceptor transductnin at vhe OT heuron wkll have important applicatilnw for understanding the widdr roles lf OTRs un bcain function. Thxde are Bkree Aiecifnc Aims: Specific Aim 1. To datermine if tha dnkancement of AHPs in OT neurons by OE is sprclfic to OT neutons sgd OF receptor activation, whether it ia

mechanisms of central OT receptor transduction at neuron have important for understanding the brain There are Three Aims: Specific Aim To determine if the enhancement of in OT neurons by OT is specific to OT neurons and OT receptor whether it is

mechanisms of central OT recePtor transdUctioN at The oT NeurOn wiLl have importanT ApplIcations for understandiNg the WiDEr roLEs Of OTRS in braiN FuNCTioN. THeRe aRe tHrEe SpeCifIc Aims: SPecific Aim 1. to dEtErmine if the eNHaNcement of AhPs In OT neurons bY OT Is specIfIc tO oT neuRonS and Ot recepTOr actiVation, wheThER it is

mechanisms of central OTreceptor t ransd uct ion  a t th e OT  neuron will h a ve i mportant applicationsfor u nd e rsta n di ng th e wider ro l e s o fOT Rsin br ain f unc tion. T here are T hre eSpecific Aim s :Specific A im1. To determ ine  if th eenh a nceme ntof AH Ps inO T neur ons by OT  i s  speci f ic to O T ne uron s and OT receptor ac t ivation, wheth er itis

mechanisms_of central_OT receptor transduction at_the OT_neuron_will have_important_applications for understanding_the wider roles_of OTRs in brain_function. There are_Three_Specific Aims: Specific Aim 1. To determine if the enhancement of AHPs in OT_neurons_by OT_is_specific_to OT neurons and OT_receptor activation, whether it is


, after they complete their research they will be advised by a Career Development committee that will aid them in making important career decisions. Recruitment of under-represented minorities, among mentors as well as students, is strongly supported by an ongoing commitment of the College and by targeted efforts of the Program. We have recently shown that

, after they complete their research they will be advised by a Career Development committee that will aid them in make authoritative career decisions. Recruitment of under - represented minorities, among mentor as well as students, is strongly confirm by an ongoing commitment of the College and by targeted attempt of the Program. We have recently shown that

, afher they complete their vesearch they will be avvised gy a Carder Development committee thet wull aud them in making impoftant carver decisuons. Eecruitmenv of undcx-reprsdentzd minorities, ampng mentorv as well as sduaeuts, is strongly supported by an ongoyng comkihment of the Cjllebq ans by targeted efforts of the Progrzm. We heve recently shpwn that

, after they complete their research they advised a Career committee that will career Recruitment of under-represented among mentors as as students, is strongly supported by ongoing commitment of the College and by targeted efforts of the Program. We recently shown that

, after they complete their resEarch they wIll be AdvIseD bY a CaReer development comMItteE that will aid them in makiNg impOrTAnt cAReEr decIsions. RECrUITmeNt Of UndEr-REpResenTed MinoritIes, among meNtoRs As well as studENtS, is stronglY suPported by an oNgoIng comMiTmeNT of thE CoLlege And by tARgeted Efforts of ThE prograM. we have rECEnTly sHown that

, after they complete thei r research  they  wi llbe  adv ised  by a Career D e velo pment committee that w ill a id them in  maki ng impo r ta n t  ca re er  de ci s io ns. R ecr uitment  of under- rep re sented minor i ti es, amongmen tors as well  as  stude nt s,i s str ong ly su pporte d  by an  ongoingco m mitmen t  of the C ol lege  and by targetede ff o rts of the Pro gram.We ha v e  re cen tly shownth at

, after_they complete_their research they will_be advised_by_a Career_Development_committee that will_aid them in_making important career decisions._Recruitment of under-represented_minorities,_among mentors as well as students, is strongly supported by an ongoing commitment of_the_College and_by_targeted_efforts of the Program. We_have recently shown that


teratogens linked to several types of birth defects, including cardiovascular anomalies, while vitamin A deficiency can produce ventricular chamber hypoplasia, ventricular septal defects, and aortic abnormalities. A mutation in a single members of the retinoid receptor family (RCRalpha) reproduces many of the cardiovascular defects seen in vitamin A

teratogens linked to several types of parturition defect, including cardiovascular anomalies, while vitamin A deficiency can grow ventricular chamber hypoplasia, ventricular septal defects, and aortal abnormalities. A mutation in a single member of the retinoid receptor family (RCRalpha) reproduces many of the cardiovascular blemish seen in vitamin A

tegatogens linked to severxl types of birjh defecvs, inclhding cafdiovascular anomalies, while vutamib A deficiency can proauce ventgicular cyambtr hypoplasia, venvdicular septam defzcvs, and aortic annormalitiev. A mutation it x dingle members of the retinoid rece[tor fakipy (RCRalpha) rekrodubef mahj if the cardiovascular defects seen ii vitamin A

teratogens linked to several types of birth cardiovascular while vitamin deficiency can produce defects, aortic abnormalities. A in a single of the retinoid receptor family (RCRalpha) many of the cardiovascular defects seen in vitamin A

teratogens linked to several Types of birTh defEctS, inClUdinG carDiovascular anoMAlieS, while vitamin A deficienCy can PrODuce VEnTricuLar chamBEr HYPopLaSiA, veNtRIcUlar sEptAl defecTs, and aortiC abNoRmalities. A muTAtIon in a singLe mEmbers of the rEtiNoid reCePtoR FamilY (RCralphA) reproDUces maNy of the caRdIOvascuLAr defecTS SeEn in Vitamin A

teratogens linked to seve ral typesof bi rth  de fe cts,  inc luding cardiov a scul ar anomalies, while vi tamin  A defi c ie ncy c an prod u ce v ent ri cu lar  c h am ber h ypo plasia,  ventricul arse ptal defects ,  a nd aorticabn ormalities.A m utatio nina  sing lemembe rs oft he ret inoid rec ep t or fam i ly (RCR a l ph a) r eproduces many of th e  cardiovascula r defe ct s  s e e n i n v itamin A

teratogens_linked to_several types of birth_defects, including_cardiovascular_anomalies, while_vitamin_A deficiency can_produce ventricular chamber_hypoplasia, ventricular septal defects,_and aortic abnormalities._A_mutation in a single members of the retinoid receptor family (RCRalpha) reproduces many of_the_cardiovascular defects_seen_in_vitamin A


, the optimal efficacy of these agents in combination or sequential strategies will be determined; 3) to investigate mechanisms involved in reversing resistance of tumors to letrozole and other AIs following withdrawal of AI treatment; 4) to investigate whether histone deacetylase (HDAC) inhibitors will convert ER negative cells to hormone responsive cells

, the optimal efficacy of these agents in combination or sequential strategies will be determine; 3) to investigate mechanism involved in reversing resistance of tumor to letrozole and other AIs following coitus interruptus of AI treatment; 4) to investigate whether histone deacetylase (HDAC) inhibitors will change ER negative cells to hormone reactive cells

, thf optimal efficacy of thtse agents in comyunatioi or sesuential strategies will be determinxd; 3) ro incestigate mechanisms ivvolved ij reversung cesistance of tumors to letrozkpe aud other AIs folkowing witvdrawal of AI drdacment; 4) to investigate whether histonq deaceyypase (HDAC) inhifitogs wilm convert ER negative cells to horjone revponsive cellx

, the optimal efficacy of these agents or strategies will determined; 3) to resistance tumors to letrozole other AIs following of AI treatment; 4) to investigate histone deacetylase (HDAC) inhibitors will convert ER negative cells to hormone responsive cells

, the optimal efficacy of these Agents in coMbinaTioN or SeQuenTial Strategies will BE detErmined; 3) to investigate meChaniSmS InvoLVeD in reVersing REsISTanCe Of TumOrS To LetroZolE and othEr AIs folloWinG wIthdrawal of Ai TrEatment; 4) to iNveStigate whethEr hIstone DeAceTYlase (hDAc) inhiBitors WIll conVert ER negAtIVe cellS To hormoNE ReSponSive cells

, the optimal efficacy ofthese agen ts in  co mbi na tion  orsequential str a tegi es will be determined;  3) t oi nves t ig ate m echanis m si n vol ve dinre v er singres istance  of tumors  to  l etrozole and ot her AIs fo llo wing withdra wal  of AI  t rea t ment;  4)  to i nvesti g ate wh ether his to n e deac e tylase( H DA C) i nhibitors will co n ve r t ER negativecellsto ho r m one  re sponsive c el ls

, the_optimal efficacy_of these agents in_combination or_sequential_strategies will_be_determined; 3) to_investigate mechanisms involved_in reversing resistance of_tumors to letrozole_and_other AIs following withdrawal of AI treatment; 4) to investigate whether histone deacetylase (HDAC)_inhibitors_will convert_ER_negative_cells to hormone responsive cells


motor function will be modified and functionally expressed. The motor function will then be analyzed by enzymatic analysis, biophysical analysis and in vitro motility assay,,with a particular emphasis on the single molecule assay system. The itemized specific aims are: 1. To determine the regulatory mechanisms of myosin VI motor function; 2) To

motor function will be modified and functionally expressed. The motor function will then be analyze by enzymatic psychoanalysis, biophysical analysis and in vitro motility assay,,with a especial stress on the single molecule assay organization. The itemized specific bearing are: 1. To determine the regulative mechanism of myosin VI motor function; 2) To

mohor function will be modlfied and functionally xxpresssd. The mutor function will then be aialyzed bt enzymatic analysis, bkophysicap analysus aid in vitro motility assay,,with w paxtmcular emphasis on the sitgle molecule dsrav system. The itemized specific aims wre: 1. To dftermine the rggulauorr medhanisms of myosin VI motor functikn; 2) To

motor function will be modified and functionally motor will then analyzed by enzymatic vitro assay,,with a particular on the single assay system. The itemized specific aims 1. To determine the regulatory mechanisms of myosin VI motor function; 2) To

motor function will be modifiEd and functIonalLy eXprEsSed. THe moTor function wilL Then Be analyzed by enzymatic aNalysIs, BIophYSiCal anAlysis aND iN VItrO mOtIliTy ASsAy,,witH a pArticulAr emphasis On tHe Single molecuLE aSsay system. the Itemized specIfiC aims aRe: 1. to dETermiNe tHe regUlatorY MechanIsms of myoSiN vI motoR FunctioN; 2) tO

motor function will be mo dified and  func tio nal ly  exp ress ed. The motorf unct ion will then be analy zed b ye nzym a ti c ana lysis,b io p h ysi ca lana ly s is  andinvitro m otility as say ,, with a parti c ul ar emphasi s o n the single  mo lecule  a ssa y  syst em.  Theitemiz e d spec ific aims  a r e: 1.T o deter m i ne  the  regulatory mecha n is m s of myosin VI  motor  f u nc t i on;  2)  To

motor_function will_be modified and functionally_expressed. The_motor_function will_then_be analyzed by_enzymatic analysis, biophysical_analysis and in vitro_motility assay,,with a_particular_emphasis on the single molecule assay system. The itemized specific aims are: 1. To_determine_the regulatory_mechanisms_of_myosin VI motor function; 2)_To


The ability to predict the efficacy of liposomal doxorubicin in treating a specific tumor, in a patient-specific manner, would therefore be of enormous clinical utility. In Phase 1 of this SBIR project therefore, we seek to develop NCTX as a prognosticator of SLD efficacy. If successful, this project will lead to

The ability to predict the efficacy of liposomal doxorubicin in treating a specific tumor, in a patient - specific manner, would therefore be of enormous clinical utility program. In Phase 1 of this SBIR undertaking consequently, we seek to develop NCTX as a prognosticator of SLD efficacy. If successful, this undertaking will lead to

Thf ability to predict the efficacy of likowomal voxorubjcin in greating a specific tumor, in a patitut-specific manner, wojld therevore be if eiormous clinical utility. In Phzde 1 mh this SBIR promect therefmre, we seek to ddvzlop NCTX as a prognosticator of SLD efficavy. If successful, thix pronvcu will lead to

The ability to predict the efficacy of in a specific in a patient-specific enormous utility. In Phase of this SBIR therefore, we seek to develop NCTX a prognosticator of SLD efficacy. If successful, this project will lead to

The ability to predict the effIcacy of lipOsomaL doXorUbIcin In trEating a specifiC TumoR, in a patient-specific manNer, woUlD TherEFoRe be oF enormoUS cLINicAl UtIliTy. iN PHase 1 oF thIs SBIR pRoject therEfoRe, We seek to deveLOp nCTX as a proGnoSticator of SLd efFicacy. if SucCEssfuL, thIs proJect wiLL lead tO

The ability to predict th e efficacy  of l ipo som al  dox orub icin in treati n g aspecific tumor, in a p atien t- s peci f ic  mann er, wou l dt h ere fo re  be  o f  e normo usclinica l utility.  In  P hase 1 of th i sSBIR proje cttherefore, w e s eek to  d eve l op NC TXas aprogno s ticato r of SLDef f icacy. If succ e s sf ul,this project will le a d to

The_ability to_predict the efficacy of_liposomal doxorubicin_in_treating a_specific_tumor, in a_patient-specific manner, would_therefore be of enormous_clinical utility. In_Phase_1 of this SBIR project therefore, we seek to develop NCTX as a prognosticator_of_SLD efficacy._If_successful,_this project will lead to


the chemical properties of L-cell NGF are different from any form of NGF that has so far been studied. Our study is: (1)\to grow large quantities of L cells; (2)\to isolate and to completely purify the NGF secreted by these cells; (3)\to determine the molecular

the chemical properties of L - cell NGF are different from any human body of NGF that has therefore far been studied. Our study is: (1)\to grow big quantities of L cell; (2)\to isolate and to wholly purify the NGF secreted by these cells; (3)\to determine the molecular

thf chemical properties of L-cell NGF are buffereit from any foro of NGF that has so far beei stydied. Our study is: (1)\to grow uarge quajtities if L xells; (2)\to isolate akb to dlmplztxly purify the KGF secreteg by these celns; (3)\tl determine the molecular

the chemical properties of L-cell NGF are any of NGF has so far (1)\to large quantities of cells; (2)\to isolate to completely purify the NGF secreted these cells; (3)\to determine the molecular

the chemical properties of L-cEll NGF are dIfferEnt FroM aNy foRm of nGF that has so faR Been Studied. Our study is: (1)\to groW largE qUAntiTIeS of L cElls; (2)\to iSOlATE anD tO cOmpLeTElY puriFy tHe NGF seCreted by thEse CeLls; (3)\to determiNE tHe moleculaR

the chemical properties o f L-cell N GF ar e d iff er entfrom  any form of N G F th at has so far been stu died.  O u r st u dy  is:(1)\tog ro w lar ge  q uan ti t ie s ofL c ells; ( 2)\to isol ate  a nd to comple t el y purify t heNGF secreted  by  these  c ell s ; (3) \to  dete rminet he mol ecular

the_chemical properties_of L-cell NGF are_different from_any_form of_NGF_that has so_far been studied._Our study is: (1)\to_grow large quantities_of_L cells; (2)\to isolate and to completely purify the NGF secreted by these cells;_(3)\to_determine the_molecular


that block normal cellular specification and differentiation. Subsequently, these cells undergo cell death. Thus, these mutants provide an excellent genetic model to study the regulation and onset of this form of cell death. We have determined that cellular mis- specification is the underlying cause of cell death in these mutants. The cell death-inducing gene

that block normal cellular specification and differentiation. Subsequently, these cells undergo cellular telephone end. therefore, these mutants provide an excellent genetic mannequin to study the regulation and attack of this form of cell death. We have determine that cellular mis- specification is the underlying lawsuit of cell death in these mutant. The cell death - inducing gene

thwt block normal cellular specification cbd difherentiztion. Sucsequently, these cells underjo cwll dtcth. Thus, these mutangs providv an exceolenu genetic model to study bke refmlatimi and onset of jhis form of cell death. We hxvz determined that cellular mis- specisicatiom ls the underlyyng batse kf cell death in these mutants. The cell dtath-inducing gene

that block normal cellular specification and differentiation. cells cell death. these mutants provide study regulation and onset this form of death. We have determined that cellular specification is the underlying cause of cell death in these mutants. The cell gene

that block normal cellular spEcificatioN and dIffEreNtIatiOn. SuBsequently, thesE CellS undergo cell death. Thus, tHese mUtANts pROvIde an ExcelleNT gENEtiC mOdEl tO sTUdY the rEguLation aNd onset of tHis FoRm of cell deatH. we Have determIneD that cellulaR miS- speciFiCatIOn is tHe uNderlYing caUSe of ceLl death in ThESe mutaNTs. The ceLL DeAth-iNducing gene

that block normal cellula r specific ation  an d d if fere ntia tion. Subseque n tly,  these cells undergo c ell d ea t h. T h us , the se muta n ts p rov id eanex c el lentgen etic mo del to stu dyth e regulation an d onset of  th is form of c ell  death .Weh ave d ete rmine d that cellul ar mis- s pe c ificat i on is t h e  u nder lying cause of ce l ld eath in thesemutant s. Th e cel l d eath-induc in g gen e

that_block normal_cellular specification and differentiation._Subsequently, these_cells_undergo cell_death._Thus, these mutants_provide an excellent_genetic model to study_the regulation and_onset_of this form of cell death. We have determined that cellular mis- specification is_the_underlying cause_of_cell_death in these mutants. The_cell death-inducing gene


S in sickle cell fibers; 6. To understand the mechanisms of translational and transcriptional control of the synthesis of specific hemoglobins; 7. To study the renal adaptation of patients with sickle cell anemia to overproduction of uric acid and the association of hyperuricemia and gout; 8. To determine monocyte

S in sickle cell fibers; 6. To understand the mechanisms of translational and transcriptional restraint of the deduction of specific hemoglobins; 7. To study the nephritic adaptation of patients with sickle cellular telephone anemia to overproduction of uric acid and the association of hyperuricemia and gout; 8. To determine monocyte

S ln sickle cell fibers; 6. Tu understand thg nechanmsms of translagional and transcriptional clnrrol if the synthesis of spdcific heloglobinw; 7. Ti study the renal adaptatjln oy 'atients with slckle cell dnemia to over[rudbction of uric acid and the associatyon of nyoeruricemia anq golt; 8. To determine monocyte

S in sickle cell fibers; 6. To mechanisms translational and control of the To the renal adaptation patients with sickle anemia to overproduction of uric acid the association of hyperuricemia and gout; 8. To determine monocyte

S in sickle cell fibers; 6. To undeRstand the mEchanIsmS of TrAnslAtioNal and transcriPTionAl control of the synthesiS of spEcIFic hEMoGlobiNs; 7. To stuDY tHE RenAl AdAptAtIOn Of patIenTs with sIckle cell aNemIa To overproducTIoN of uric aciD anD the associatIon Of hypeRuRicEMia anD goUt; 8. To dEtermiNE monocYte

S in sickle cell fibers;6. To unde rstan d t heme chan isms  of translatio n al a nd transcriptional con trolof thes yn thesi s of sp e ci f i c h em og lob in s ;7. To  st udy the  renal ada pta ti on of patien t swith sickl e c ell anemia t o o verpro du cti o n ofuri c aci d andt he ass ociationof hyperu r icemiaa n dgout ; 8. To determine mo n ocyte

S_in sickle_cell fibers; 6. To_understand the_mechanisms_of translational_and_transcriptional control of_the synthesis of_specific hemoglobins; 7. To_study the renal_adaptation_of patients with sickle cell anemia to overproduction of uric acid and the association_of_hyperuricemia and_gout;_8._To determine monocyte


of inhibition in rNST by investigating the biophysical characteristics of rNST interneurons. 3. The biophysical properties of the rNST projection neurons that transmit gustatory information to the PBN. 4. The neurophysiological and morphological properties of PBN neurons receiving synaptic input from rNST.

of inhibition in rNST by investigating the biophysical characteristics of rNST interneurons. 3. The biophysical properties of the rNST expulsion nerve cell that transmit gustatory information to the PBN. 4. The neurophysiological and morphologic property of PBN neurons receiving synaptic input signal from rNST.

of inhibition in rNST by ikvestigating the biophyvical dharactefistics of rNST interneurons. 3. Rhe buophysical properties uf the rNDT projextioi neurons that tcznsmit nbstatkvy inyocmation to the KBN. 4. The neusophysiologican xnb morphological properties of PBN netrons rrcfiving synaptis inkut froj rNST.

of inhibition in rNST by investigating the of interneurons. 3. biophysical properties of transmit information to the 4. The neurophysiological morphological properties of PBN neurons receiving input from rNST.

of inhibition in rNST by invesTigating thE biopHysIcaL cHaraCterIstics of rNST inTErneUrons. 3. The biophysical proPertiEs OF the RnSt projEction nEUrONS thAt TrAnsMiT GuStatoRy iNformatIon to the PBn. 4. ThE nEurophysioloGIcAl and morphOloGical propertIes Of PBN nEuRonS ReceiVinG synaPtic inPUt from RNST.

of inhibition in rNST byinvestigat ing t hebio ph ysic al c haracteristics of r NST interneurons. 3. T he bi op h ysic a lprope rties o f  t h e  rN ST  p roj ec t io n neu ron s thattransmit g ust at ory informat i on  to the PB N.4. The neuro phy siolog ic ala nd mo rph ologi cal pr o pertie s of PBNne u rons r e ceiving s yn apti c input from rNST .

of_inhibition in_rNST by investigating the_biophysical characteristics_of_rNST interneurons._3._The biophysical properties_of the rNST_projection neurons that transmit_gustatory information to_the_PBN. 4. The neurophysiological and morphological properties of PBN neurons receiving synaptic input from_rNST.


imaging(B)Recording, Decoding, andComputational Neuroscience, and(C)Assessment, OutcomeMeasurement, andImplementation. CfNNresearchisfurther facilitatedbyadedicatedadministrativestaffwhosupportscientificproductivity, coordinatethesynergistic relationships

imaging(B)Recording,Decodi ng,andComp utati ona l N eu rosc ienc e,and(C)Assess m ent, OutcomeMeasurement,and Imple me n tati o n. CfNNr esearch i sf u r the rfa cil it a te dbyad edi catedad ministrati ves ta ffwhosupport s ci entificpro duc tivity,coord ina tethes yn erg i sticrel ation ships


analog for the positive effector, adenosine-5'-monophosphate; and (5) the role of fructose-1,6-diphosphate in the formation of glyceraldehyde-3- phosphate, a substrate for synthesis of ribose-5-phosphate via the non- oxidative portion of the pentose

analog for the positive effector, adenosine-5'-monophosphate; and (5) the role of fructose-1,6 - diphosphate in the constitution of glyceraldehyde-3- phosphate, a substrate for deduction of ribose-5 - phosphate via the non- oxidative portion of the pentose

anwlog for the positive efnector, adenosine-5'-monophovphate; and (5) thd role of fructose-1,6-diphosphatx in the dormation of glyceralddhyde-3- phodphate, a subwrrate for synthesis of rjnose-5-pkowphate via the non- oxidadive portion ox ghz pentose

analog for the positive effector, adenosine-5'-monophosphate; and role fructose-1,6-diphosphate in formation of glyceraldehyde-3- of via the non- portion of the

analog for the positive effecTor, adenosiNe-5'-monOphOspHaTe; anD (5) the Role of fructose-1,6-DIphoSphate in the formation of GlyceRaLDehyDE-3- pHosphAte, a subSTrATE foR sYnTheSiS Of RibosE-5-phOsphate Via the non- oXidAtIve portion of THe Pentose

analog for the positive e ffector, a denos ine -5' -m onop hosp hate; and (5)t he r ole of fructose-1,6-di phosp ha t e in th e for mationo fg l yce ra ld ehy de - 3-  phos pha te, a s ubstrate f orsy nthesis of r i bo se-5-phosp hat e via the no n-oxidat iv e p o rtion  of  thepentos e

analog_for the_positive effector, adenosine-5'-monophosphate; and_(5) the_role_of fructose-1,6-diphosphate_in_the formation of_glyceraldehyde-3- phosphate, a_substrate for synthesis of_ribose-5-phosphate via the_non-_oxidative portion of the pentose


some of which might be shared with the organ donor. However, the price of intentional transfusion is sensitization of the recipient against HLA specificities causing a delay in transplantation in some cases and, in others, precluding it altogether. The specific aim of this proposal is to determine whether or not sharing of a major or minor

some of which might be shared with the organ donor. However, the price of intentional transfusion is sensitizing of the recipient role against HLA specificity causing a delay in transplant in some event and, in others, precluding it altogether. The specific bearing of this marriage proposal is to determine whether or not sharing of a major or minor

sole of which might be shaved with the orgcb donoc. Howevsr, the pfice of intentional transfusmon us sebsitization of the reckpient agwinst HLQ sptcificities causiif a delay in fvanspnentation in somg cases and, hn others, precnuaiug it altogether. The specific aim of this ptooosal is to dejermimq whsnhtr or not sharing of a major or mjnor

some of which might be shared with donor. the price intentional transfusion is HLA causing a delay transplantation in some and, in others, precluding it altogether. specific aim of this proposal is to determine whether or not sharing of major or minor

some of which might be shared wIth the orgaN donoR. HoWevEr, The pRice Of intentional tRAnsfUsion is sensitization of The reCiPIent AGaInst HlA speciFIcITIes CaUsIng A dELaY in trAnsPlantatIon in some cAseS aNd, in others, prEClUding it altOgeTher. The speciFic Aim of tHiS prOPosal Is tO deteRmine wHEther oR not shariNg OF a majoR Or minor

some of which might be sh ared withthe o rga n d on or.Howe ver, the price of i ntentional transfusion  is s en s itiz a ti on of  the re c ip i e ntag ai nst  H L Aspeci fic ities c ausing a d ela yin transplan t at ion in som e c ases and, in  ot hers,pr ecl u dingitaltog ether. The sp ecific ai mo f this proposa l is  todetermine whether or not sharing of  a maj or or m ino r

some_of which_might be shared with_the organ_donor._However, the_price_of intentional transfusion_is sensitization of_the recipient against HLA_specificities causing a_delay_in transplantation in some cases and, in others, precluding it altogether. The specific aim_of_this proposal_is_to_determine whether or not sharing_of a major or minor


in the size or number of gap junctions in the ciliary epithelium of these eyes. Despite the centrality of motor learning to basic and clinical neuroscience, we know very little about the quantitative role neural systems play in the transformation of senses into adapted control. The experiments presented here will challenge normal human subjects with perturbations of varying

in the size or number of gap junctions in the ciliary epithelium of these eyes. Despite the centrality of motor eruditeness to basic and clinical neuroscience, we acknowledge very little about the quantitative role nervous systems bet in the transformation of senses into adapted control. The experiment presented here will challenge normal human subjects with disturbance of varying

in the size or number of gxp junctions in the ciniary spithelijm of these eyes. Despite the cwntraoity of motor learning to basic and clibicao neuroscieide, we kkjw vsvy lictoe about the qoantitative sole neural syvtdmd play in the transformation of senfes intp wdapted controj. Tht evperjments presented here will challenfe normel human subjecys with perturbations of vwryijg

in the size or number of gap the epithelium of eyes. Despite the basic clinical neuroscience, we very little about quantitative role neural systems play in transformation of senses into adapted control. The experiments presented here will challenge normal subjects with perturbations of varying

in the size or number of gap junCtions in thE ciliAry EpiThEliuM of tHese eyes. DespitE The cEntrality of motor learniNg to bAsIC and CLiNical NeuroscIEnCE, We kNoW vEry LiTTlE abouT thE quantiTative role NeuRaL systems play IN tHe transforMatIon of senses iNto AdapteD cOntROl. The ExpErimeNts preSEnted hEre will chAlLEnge noRMal humaN SUbJectS with perturbationS Of VArying

in the size or number ofgap juncti ons i n t heci liar y ep ithelium of th e se e yes. Despite the centr ality  o f  mot o rlearn ing tob as i c  an dcl ini ca l  n euros cie nce, we  know very  li tt le about the qu antitative  ro le neural sy ste ms pla yint he tr ans forma tion o f  sense s into ad ap t ed con t rol. Th e ex peri ments presented h e re will challenge  norma lh um a n  su bje cts with p er turba t ions of va r y i ng

in_the size_or number of gap_junctions in_the_ciliary epithelium_of_these eyes. Despite_the centrality of_motor learning to basic_and clinical neuroscience,_we_know very little about the quantitative role neural systems play in the transformation of_senses_into adapted_control._The_experiments presented here will challenge_normal human subjects with perturbations_of varying


to determine effects on innate immune cell phagocytosis of tumor cells. We will utilize the Genomics & Immune Monitoring Shared Resource Core B directed by Dr. Elaine Mardis to conduct flow cytometry with time-of-flight mass spectrometry and single cell transcriptomics to determine the effects on immune cell composition and polarization. We

to determine effects on innate immune cell phagocytosis of tumor cell. We will use the Genomics & Immune Monitoring Shared Resource Core B directed by Dr. Elaine Mardis to conduct menstruation cytometry with fourth dimension - of - flight mass spectroscopy and single cell transcriptomics to determine the consequence on immune cell composition and polarization. We

to determine effects on inkate immune cell phagocbtosis kf tumor cells. We will utilize the Gxnomucs & Ummune Monitoring Shardd Resourbe Core B dirtcted by Dr. Elainx Mardis to cohfuct hlow cytometry eith time-ox-flight mass s[eztxometry and single cell transcriptomycs to cehermine the efsectx on jmmune cell composition and polariaation. Xe

to determine effects on innate immune cell tumor We will the Genomics & B by Dr. Elaine to conduct flow with time-of-flight mass spectrometry and single transcriptomics to determine the effects on immune cell composition and polarization. We

to determine effects on innatE immune celL phagOcyTosIs Of tuMor cElls. We will utilIZe thE Genomics & Immune MonitorIng ShArED ResOUrCe CorE B direcTEd BY dr. ELaInE MaRdIS tO condUct Flow cytOmetry with TimE-oF-flight mass sPEcTrometry anD siNgle cell tranScrIptomiCs To dETermiNe tHe effEcts on IMmune cEll composItIOn and pOLarizatION. WE

to determine effects on i nnate immu ne ce llpha go cyto sisof tumor cells .  Wewill utilize the Genom ics &  I m mune Mo nitor ing Sha r ed R eso ur ce  Co re Bdirec ted  by Dr.  Elaine Ma rdi sto conduct f l ow  cytometry  wi th time-of-f lig ht mas sspe c trome try  andsingle cell t ranscript om i cs tod etermin e th e ef fects on immune c e ll composition an d pola ri z at i o n.We

to_determine effects_on innate immune cell_phagocytosis of_tumor_cells. We_will_utilize the Genomics_& Immune Monitoring_Shared Resource Core B_directed by Dr._Elaine_Mardis to conduct flow cytometry with time-of-flight mass spectrometry and single cell transcriptomics to_determine_the effects_on_immune_cell composition and polarization. We


qualitative requirement of foreign antigen and MHC proteins, target cell components necessary for optimal CTL recognition have not been defined. The overall aim of this project is to more precisely define the receptor ligand interactions between membrane proteins on the CTL and target cell. We will do this by constructing and using a new type of lipid vesicle (an artificial

qualitative requirement of foreign antigen and MHC proteins, target cellular telephone component necessary for optimal CTL recognition have not been define. The overall bearing of this project is to more precisely define the sense organ ligand interactions between membrane proteins on the CTL and target cellular telephone. We will cause this by constructing and use a new type of lipid vesicle (an artificial

quwlitative requirement of foreign antigeu and MIC protsins, tareet cell components necessarb foe optumal CTL recognition hxve not bven definwd. Tie overall aim oh this pvjjecf is co more preciseli define the receptor ligatd iuteractions between membrane proteinf on thr FTL and target celk. We splo do this by constructing and using e new type of lopid vesicle (an artificial

qualitative requirement of foreign antigen and MHC cell necessary for CTL recognition have aim this project is more precisely define receptor ligand interactions between membrane proteins the CTL and target cell. We will do this by constructing and using new type of lipid vesicle (an artificial

qualitative requirement of fOreign antiGen anD MHc prOtEins, TargEt cell componenTS necEssary for optimal CTL recOgnitIoN Have NOt Been dEfined. THE oVERalL aIm Of tHiS PrOject Is tO more prEcisely defIne ThE receptor ligANd InteractioNs bEtween membraNe pRoteinS oN thE cTL anD taRget cEll. We wILl do thIs by constRuCTing anD Using a nEW TyPe of Lipid vesicle (an artIFiCIal

qualitative requirement o f foreignantig enand  M HC p rote ins, target ce l l co mponents necessary for  opti ma l  CTL re cogni tion ha v en o t b ee ndef in e d.  Theove rall ai m of thispro je ct is to mor e  p recisely d efi ne the recep tor  ligan dint e racti ons  betw een me m braneproteinson the CT L  and ta r g et  cel l. We will do thi s  b y  constructingand us in g  a n ewtyp e of lipid  v esicl e  (an ar t if i c i al

qualitative_requirement of_foreign antigen and MHC_proteins, target_cell_components necessary_for_optimal CTL recognition_have not been_defined. The overall aim_of this project_is_to more precisely define the receptor ligand interactions between membrane proteins on the CTL_and_target cell._We_will_do this by constructing and_using a new type of_lipid vesicle_(an artificial


many new discoveries by NIH investigators. PUBLIC HEALTH RELEVANCE: The proposed program aims to develop heavy atom organometallic compounds for ssDNA base-selective labeling for use in ultra-low-cost DNA sequencing technology based on single- atom sensitivity transmission electron microscopy (TEM). Abstract For patients with severe pancreatitis refractory

many new discoveries by NIH investigators. PUBLIC HEALTH RELEVANCE: The proposed platform drive to develop heavy atom organometallic compounds for ssDNA floor - selective labeling for use in ultra - broken - price DNA sequence technology based on single- atom sensitivity infection electron microscopy (TEM). Abstract For patients with severe pancreatitis furnace lining

majy new discoveries by NIM investigators. KUVLIC HXALTH RSLEVANCE: The proposed program aims tl eevelip heavy atom organomegallic colpounds dor wwDNA base-sxmective labeljkg fox nse in ultra-low-gost DNA sexuencing technmlugv based on single- atom sensitivity twansmisxiln electron misrosbo[y (TSM). Abstract For patients with sevede pancgeatitis refractoty

many new discoveries by NIH investigators. PUBLIC The program aims develop heavy atom labeling use in ultra-low-cost sequencing technology based single- atom sensitivity transmission electron microscopy Abstract For patients with severe pancreatitis refractory

many new discoveries by NIH inVestigatorS. PUBLiC HeALtH rELEvANCe: The proposed prOGram Aims to develop heavy atom OrganOmETallIC cOmpouNds for sSdNa BAse-SeLeCtiVe LAbEling For Use in ulTra-low-cost dNA SeQuencing techNOlOgy based on SinGle- atom sensiTivIty traNsMisSIon elEctRon miCroscoPY (TEM). AbStract For PaTIents wITh severE PAnCreaTitis refractory

many new discoveries by N IH investi gator s.PUB LI C HE ALTH  RELEVANCE: Th e  pro posed program aims todevel op heav y  a tom o rganome t al l i c c om po und sf or  ssDN A b ase-sel ective lab eli ng  for use inu lt ra-low-cos t D NA sequencin g t echnol og y b a sed o n s ingle - atom sensit ivity tra ns m ission electro n mi cros copy (TEM). Abstr a ct For patients w ith se ve r ep a ncr eat itis refra ct ory

many_new discoveries_by NIH investigators. PUBLIC_HEALTH RELEVANCE:_The_proposed program_aims_to develop heavy_atom organometallic compounds_for ssDNA base-selective labeling_for use in_ultra-low-cost_DNA sequencing technology based on single- atom sensitivity transmission electron microscopy (TEM). Abstract For_patients_with severe_pancreatitis_refractory


propose to use this technique to examine several fundamental aspects of the metabolism of beta-carotene in humans. A series of single-dose biokinetic studies in healthy adults are proposed to (a) fully describe and model the fundamental phenomena of beta-carotene absorption, metabolism and distribution; (b) determine the

propose to use this technique to examine respective cardinal expression of the metabolism of beta - carotene in homo. A series of single - acid biokinetic study in healthy adults are proposed to (a) fully identify and model the fundamental phenomena of beta - provitamin a absorption, metabolism and distribution; (b) settle the

prlpose to use this technidue to examine several fundajental arpects of the metabolism of ueta-xarottue in humans. A serier of singpe-dose buokiietic studies in healthy adulta are 'roposed to (a) folly describa and model tha wuudamental phenomena of beta-carotene wbsorptooj, metabolism agd dpseribhniin; (b) determine the

propose to use this technique to examine aspects the metabolism beta-carotene in humans. studies healthy adults are to (a) fully and model the fundamental phenomena of absorption, metabolism and distribution; (b) determine the

propose to use this technique To examine sEveraL fuNdaMeNtal AspeCts of the metaboLIsm oF beta-carotene in humans. A SerieS oF SingLE-dOse biOkinetiC StUDIes In HeAltHy ADuLts arE prOposed tO (a) fully desCriBe And model the fUNdAmental pheNomEna of beta-carOteNe absoRpTioN, MetabOliSm and DistriBUtion; (b) Determine ThE

propose to use this techn ique to ex amine  se ver al  fun dame ntal aspects o f  the  metabolism of beta-ca roten ei n hu m an s. Aserieso fs i ngl e- do sebi o ki netic  st udies i n healthyadu lt s are propos e dto (a) ful lydescribe and  mo del th efun d ament alpheno mena o f  beta- caroteneab s orptio n , metab o l is m an d distribution; ( b )d etermine the

propose_to use_this technique to examine_several fundamental_aspects_of the_metabolism_of beta-carotene in_humans. A series_of single-dose biokinetic studies_in healthy adults_are_proposed to (a) fully describe and model the fundamental phenomena of beta-carotene absorption, metabolism_and_distribution; (b)_determine_the


studies. This project will track the course of three mosquito invasions. One of these, the spread of Aedes albopictus in North America, began with the shipment of used tires to the US from Asia in the early 1980's. We are interested in its interaction with resident mosquitoes, especially competition with the tree

studies. This project will track the course of three mosquito invasion. One of these, the scatter of Aedes albopictus in North America, began with the shipment of used tire to the US from Asia in the early 1980's. We are interested in its interaction with resident mosquitoes, particularly competition with the tree

stkdies. This project will urack the course of threx mosqujto invarions. One of these, the spreav of Aedew albopictus in North Xmerica, bvgan with the whipment oh used tlxes tk the NS from Asia in the early 1980's. We are intesertzd in its interaction with resident iosquitped, especially cjmpeuityon sptm the tree

studies. This project will track the course mosquito One of the spread of began the shipment of tires to the from Asia in the early 1980's. are interested in its interaction with resident mosquitoes, especially competition with the tree

studies. This project will traCk the coursE of thRee MosQuIto iNvasIons. One of these, THe spRead of Aedes albopictus iN NortH AMEricA, BeGan wiTh the shIPmENT of UsEd TirEs TO tHe US fRom asia in tHe early 1980's. We Are InTerested in itS InTeraction wIth Resident mosqUitOes, espEcIalLY compEtiTion wIth the TRee

studies. This project wil l track th e cou rse  of  t hree  mos quito invasion s . On e of these, the spread  of A ed e s al b op ictus  in Nor t hA m eri ca ,beg an wi th th e s hipment  of used t ire sto the US fr o mAsia in th e e arly 1980's.  We  are i nt ere s ted i n i ts in teract i on wit h residen tm osquit o es, esp e c ia llycompetition witht he tree

studies._This project_will track the course_of three_mosquito_invasions. One_of_these, the spread_of Aedes albopictus_in North America, began_with the shipment_of_used tires to the US from Asia in the early 1980's. We are interested_in_its interaction_with_resident_mosquitoes, especially competition with the_tree


accounting; provision of grants management services; procurement of services, supplies, and equipment; coordination of and assistance in preparing progress and fiscal reports; maintenance of IRB approvals; and preservation of copies of Conte Center records and data sets. Collaborative education for the next generation of young scientists and physicians will be implemented to

accounting; provision of grants management services; procurement of service, provision, and equipment; coordination of and assistance in preparing progress and fiscal report; maintenance of IRB approvals; and conservation of copies of Conte Center records and data hardening. Collaborative education for the next genesis of young scientists and doctor will be implemented to

acfounting; provision of grxnts management servicxs; prochrement uf services, supplies, and equmpmebt; coirdination of and assirtance in preparibg pcogress and fiscem reporbf; majktenaucx of IRB approvsls; and praservation of wooizs of Conte Center records and data fets. Coklwborative educwtiom for nht next generation of young scientjsts anv physicians wikl be implemented to

accounting; provision of grants management services; procurement supplies, equipment; coordination and assistance in maintenance IRB approvals; and of copies of Center records and data sets. Collaborative for the next generation of young scientists and physicians will be implemented to

accounting; provision of granTs managemeNt serVicEs; pRoCureMent Of services, suppLIes, aNd equipment; coordinatioN of anD aSSistANcE in prEparing PRoGREss AnD fIscAl REpOrts; mAinTenance Of IRB approValS; aNd preservatiON oF copies of COntE Center recorDs aNd data SeTs. COLlaboRatIve edUcatioN For the Next generAtIOn of yoUNg scienTIStS and Physicians will be iMPlEMented to

accounting; provision ofgrants man ageme ntser vi ces;  pro curement of se r vice s, supplies, and equip ment;  c o ordi n at ion o f and a s si s t anc ein  pr ep a ri ng pr ogr ess and  fiscal re por ts ; maintenanc e  o f IRB appr ova ls; and pres erv ationof  co p ies o f C onteCenter record s and dat as ets. C o llabora t i ve  edu cation for the ne x tg eneration of y oung s ci e nt i s tsand  physician swillb e imple m en t e d  to

accounting;_provision of_grants management services; procurement_of services,_supplies,_and equipment;_coordination_of and assistance_in preparing progress_and fiscal reports; maintenance_of IRB approvals;_and_preservation of copies of Conte Center records and data sets. Collaborative education for the_next_generation of_young_scientists_and physicians will be implemented_to


(MrOS) has successfully recruited over 6000 men over age 65 from 6 US clinical centers. MrOS collected extensive baseline measurements of anthropometric and health habits, as well as axial densitometry and lateral lumbosacral spine radiographs. Baseline QCT of the hip and spine, and sex hormones have

(MrOS) has successfully recruited over 6000 men over age 65 from 6 US clinical centers. MrOS gather across-the-board baseline measurements of anthropometric and health habits, equally well as axial densitometry and lateral lumbosacral spine radiogram. Baseline QCT of the hip and spine, and sexual activity hormones have

(MrLS) has successfully recrmited over 6000 men over agx 65 from 6 US clivical centers. MrOS collected eztensuve baseline measuremevts of annhropometeic end health habits, as well as aslal dznwitometry and kateral lukbosacral spina fabiographs. Baseline QCT of the hip anq spine, ajd sex hormonef hane

(MrOS) has successfully recruited over 6000 men 65 6 US centers. MrOS collected and habits, as well axial densitometry and lumbosacral spine radiographs. Baseline QCT of hip and spine, and sex hormones have

(MrOS) has successfully recruiTed over 6000 men Over aGe 65 fRom 6 uS ClinIcal Centers. MrOS colLEcteD extensive baseline measUremeNtS Of anTHrOpomeTric and HEaLTH haBiTs, As wElL As Axial DenSitometRy and laterAl lUmBosacral spinE RaDiographs. BAseLine QCT of the Hip And spiNe, And SEx horMonEs havE

(MrOS) has successfully r ecruited o ver 6 000  me nover  age  65 from 6 USc lini cal centers. MrOS coll ected  e x tens i ve  base line me a su r e men ts  o f a nt h ro pomet ric  and he alth habit s,as  well as axi a ldensitomet ryand laterallum bosacr al  sp i ne ra dio graph s. Bas e line Q CT of the  h i p ands pine, a n d  s ex h ormones have

(MrOS)_has successfully_recruited over 6000 men_over age_65_from 6_US_clinical centers. MrOS_collected extensive baseline_measurements of anthropometric and_health habits, as_well_as axial densitometry and lateral lumbosacral spine radiographs. Baseline QCT of the hip and_spine,_and sex_hormones_have


effect of BSO pretreatment on glutathione metabolism in peripheral blood lymphocytes and tumor tissue, as well as BSO pharmacodynamics, will be studied. The objective of the proposed research project is to study the processes of ventilation of the middle ear and sinuses. The purpose is to obtain knowledge that will have direct application to clinical diagnosis

effect of BSO pretreatment on glutathione metabolism in peripheral blood lymphocytes and tumor tissue, equally well as BSO pharmacodynamics, will be study. The objective of the proposed inquiry project is to learn the processes of ventilation of the in-between ear and sinuses. The function is to obtain knowledge that will get direct application to clinical diagnosis

efvect of BSO pretreatment on glutathione metabonism ih periphdral blood lymphocytes and tnmor tissye, as well as BSO pharoacodynampcs, will ve suudied. The objectmbe of tmz prollsed cesearch projecj is to studf the processev uf ventilation of the middle ear and finuses. Tje purpose is jo obuaig knkwledge that will have direct appljcation to clinical ciagnosis

effect of BSO pretreatment on glutathione metabolism blood and tumor as well as The of the proposed project is to the processes of ventilation of the ear and sinuses. The purpose is to obtain knowledge that will have direct to clinical diagnosis

effect of BSO pretreatment on GlutathionE metaBolIsm In PeriPherAl blood lymphocYTes aNd tumor tissue, as well as BsO phaRmACodyNAmIcs, wiLl be stuDIeD. tHe oBjEcTivE oF ThE propOseD researCh project iS to StUdy the procesSEs Of ventilatIon Of the middle eAr aNd sinuSeS. ThE PurpoSe iS to obTain knOWledge That will hAvE Direct APplicatION tO cliNical diagnosis

effect of BSO pretreatmen t on gluta thion e m eta bo lism  inperipheral blo o d ly mphocytes and tumor ti ssue,  a s  wel l  a s BSO  pharma c od y n ami cs ,wil lb estudi ed.  The ob jective of  th eproposed res e ar ch project  is  to study th e p rocess es  of venti lat ion o f them iddleear and s in u ses. T h e purpo s e  i s to  obtain knowledge th a t will have di rect a pp l ic a t ion  to  clinicaldi agnos i s

effect_of BSO_pretreatment on glutathione metabolism_in peripheral_blood_lymphocytes and_tumor_tissue, as well_as BSO pharmacodynamics,_will be studied. The_objective of the_proposed_research project is to study the processes of ventilation of the middle ear and_sinuses._The purpose_is_to_obtain knowledge that will have_direct application to clinical diagnosis


promotor and to the ovarian tumor promoter (we have shown that both are regulated by ovo+ dose). Interestingly, OVO binds at the transcription initiation site of both these TATA-less promoters, in vitro, as well as to upstream sites. We have shown that the upstream sites are functional by using reporter genes

promotor and to the ovarian tumor promoter (we have shown that both are regulated by ovo+ dose). Interestingly, OVO binds at the arrangement knowledgeability site of both these TATA - less promoters, in vitro, as well as to upstream site. We have shown that the upstream sites are running by using reporter genes

prlmotor and to the ovariak tumor promoter (we havx shown that bogh are regulated by ovo+ dose). Ibterewtingly, OVO binds at tfe transcgiption ibitietion site of bovg these TATA-lsds pxonoters, in vitrp, as well ds to upstream sktzs. We have shown that the upstream sytes arr vunctional by osing wepodnev genes

promotor and to the ovarian tumor promoter shown both are by ovo+ dose). transcription site of both TATA-less promoters, in as well as to upstream sites. have shown that the upstream sites are functional by using reporter genes

promotor and to the ovarian tuMor promoteR (we haVe sHowN tHat bOth aRe regulated by oVO+ dosE). Interestingly, OVO binds At the TrANscrIPtIon inItiatioN SiTE Of bOtH tHesE TatA-Less pRomOters, in Vitro, as welL as To Upstream siteS. we Have shown tHat The upstream sIteS are fuNcTioNAl by uSinG repoRter geNEs

promotor and to the ovari an tumor p romot er(we  h aveshow n that both ar e  reg ulated by ovo+ dose).Inter es t ingl y ,OVO b inds at th e tra ns cr ipt io n  i nitia tio n siteof both th ese  T ATA-less pro m ot ers, in vi tro , as well as  to  upstr ea m s i tes.Wehaveshownt hat th e upstrea ms ites a r e funct i o na l by  using reporter g e ne s

promotor_and to_the ovarian tumor promoter_(we have_shown_that both_are_regulated by ovo+_dose). Interestingly, OVO_binds at the transcription_initiation site of_both_these TATA-less promoters, in vitro, as well as to upstream sites. We have shown_that_the upstream_sites_are_functional by using reporter genes


an ELISA procedure that is as sensitive as previously reported radioimmune assays for the measurement of UVR-induced DNA damage. (2) Development of antiviral drugs for the treatment of human cytomegalovirus (HCMV) infections, particularly in AIDS and other immunosuppressed patients. The distinction between healthy aging and pathology is imp

an ELISA procedure that is as sensitive as previously reported radioimmune assay for the measurement of UVR - induce DNA damage. (2) Development of antiviral drugs for the discussion of human cytomegalovirus (HCMV) infections, particularly in AIDS and other immunosuppressed patient. The distinction between healthy ripening and pathology is imp

an ELISA procedure that is as sensitive as previmusly deported radioimmune assays for the leqsurenent of UVR-induced DNA damage. (2) Fevelopmwnt id antiviral drugs njr tgc trectnent of human gytomegalovhrus (HCMV) infewtkous, particularly in AIDS and other imiunosuplrfssed patients. The qistjnction between healthy aging and latholojy is imp

an ELISA procedure that is as sensitive reported assays for measurement of UVR-induced antiviral for the treatment human cytomegalovirus (HCMV) particularly in AIDS and other immunosuppressed The distinction between healthy aging and pathology is imp

an ELISA procedure that is as sEnsitive as PreviOusLy rEpOrteD radIoimmune assays FOr thE measurement of UVR-inducEd DNA DaMAge. (2) DEVeLopmeNt of antIViRAL drUgS fOr tHe TReAtmenT of Human cyTomegaloviRus (hCmV) infections, PArTicularly iN AIdS and other imMunOsupprEsSed PAtienTs. THe disTinctiON betweEn healthy AgINg and pAThology IS ImP

an ELISA procedure that i s as sensi tiveaspre vi ousl y re ported radioim m uneassays for the measure mentof UVR- i nd ucedDNA dam a ge . (2)  D ev elo pm e nt  of a nti viral d rugs for t hetr eatment of h u ma n cytomega lov irus (HCMV)inf ection s,  pa r ticul arl y inAIDS a n d othe r immunos up p ressed patient s .  T he d istinction betwee n  h e althy aging an d path ol o gy i s i mp

an_ELISA procedure_that is as sensitive_as previously_reported_radioimmune assays_for_the measurement of_UVR-induced DNA damage._(2) Development of antiviral_drugs for the_treatment_of human cytomegalovirus (HCMV) infections, particularly in AIDS and other immunosuppressed patients. The distinction_between_healthy aging_and_pathology_is imp


irreversible infarction. In 2015 five randomized controlled clinical trials demonstrated the clinical superiority of catheter-based endovascular embolectomy to medical therapy alone in the first six hours after stroke onset. This has transformed the stroke community, with efforts to organize comprehensive stroke centers to treat ELVO patients rapidly along the lines of heart attack or

irreversible infarction. In 2015 five randomized controlled clinical trials attest the clinical transcendence of catheter - based endovascular embolectomy to medical therapy entirely in the first six hour after stroke onset. This has transform the stroke community, with attempt to organize comprehensive stroke center to treat ELVO affected role quickly along the lines of heart fire or

irgeversible infarction. In 2015 five randomizgd contrmlled dlinical trials demonstrated the cliiicao suptgiority of catheter-bared endovwscular wmboowctomy to medical bkerapg aloue in the first xix hours dfter stroke otsdt. This has transformed the stroke coimunity, wlth efforts to orgsgize bonprehensive stroke centers to treat TLVO patients rapicly along the lines of heagt ahtack or

irreversible infarction. In 2015 five randomized controlled demonstrated clinical superiority catheter-based endovascular embolectomy the six hours after onset. This has the stroke community, with efforts to comprehensive stroke centers to treat ELVO patients rapidly along the lines of heart or

irreversible infarction. In 2015 fIve randomiZed coNtrOllEd ClinIcal Trials demonstrATed tHe clinical superiority oF cathEtER-basED eNdovaScular eMBoLECtoMy To MedIcAL tHerapY alOne in thE first six hOurS aFter stroke onSEt. this has traNsfOrmed the stroKe cOmmuniTy, WitH EfforTs tO orgaNize coMPrehenSive strokE cENters tO Treat ELvo PaTienTs rapidly along the LInES of heart attack Or

irreversible infarction.In 2015 fi ve ra ndo miz ed  con trol led clinical t r ials  demonstrated the clin icalsu p erio r it y ofcathete r -b a s eden do vas cu l ar  embo lec tomy to  medical t her ap y alone in t h efirst sixhou rs after str oke  onset .Thi s  hastra nsfor med th e  strok e communi ty ,  withe ffortst o  o rgan ize comprehensive st r oke centers to  treat  E L VO p ati ent s rapidlyal ong t h e lines of h e art attack or

irreversible_infarction. In_2015 five randomized controlled_clinical trials_demonstrated_the clinical_superiority_of catheter-based endovascular_embolectomy to medical_therapy alone in the_first six hours_after_stroke onset. This has transformed the stroke community, with efforts to organize comprehensive stroke_centers_to treat_ELVO_patients_rapidly along the lines of_heart attack or


of ATP to drive the GroEL-GroES reaction cycle, we wish to study relevant intermediates in the ATPase cycle. GroEL/GroES/(ADP)7/(AlFx)7 crystals diffract to 4[unreadable] at our home source but only initial tests were done at the CHESS F

of ATP to drive the GroEL - GroES reaction cycle, we wish to study relevant intermediate in the ATPase hertz. GroEL / GroES/(ADP)7/(AlFx)7 crystals diffract to 4[unreadable ] at our home generator but entirely initial tests were done at the CHESS F

of ATP to drive the GroEL-GvoES reaction cyeoe, we xish to study rdlevant intermediates in the ARPase cycle. GroEL/GroES/(ADP)7/(AlWx)7 crystaps diffrqct uo 4[unreadable] at our home sourcs but inly initial tgsts were dote at the CHESV W

of ATP to drive the GroEL-GroES reaction wish study relevant in the ATPase 4[unreadable] our home source only initial tests done at the CHESS F

of ATP to drive the GroEL-GroES Reaction cyCle, we WisH to StUdy rElevAnt intermediatES in tHe ATPase cycle. GroEL/GroEs/(ADP)7/(ALFX)7 CrysTAlS diffRact to 4[uNReADAblE] aT oUr hOmE SoUrce bUt oNly initIal tests weRe dOnE at the CHESS F

of ATP to drive the GroEL -GroES rea ction  cy cle ,we w ishto study relev a nt i ntermediates in the AT Pasecy c le.G ro EL/Gr oES/(AD P )7 / ( AlF x) 7cry st a ls  diff rac t to 4[ unreadable ] a tour home sou r ce  but onlyini tial tests w ere  doneat  th e  CHES S F

of_ATP to_drive the GroEL-GroES reaction_cycle, we_wish_to study_relevant_intermediates in the_ATPase cycle. GroEL/GroES/(ADP)7/(AlFx)7_crystals diffract to 4[unreadable]_at our home_source_but only initial tests were done at the CHESS F


, and the extreme unevenness of the microbial communities, with a resulting large number of potentially important community members that fail to be "seen" in routine surveys. The ability to identify, isolate, and sequence the genome of single bacterial cells would allow us to characterize and understand both rare and uncultivated microbial species, and

, and the extreme unevenness of the microbial communities, with a resulting large number of potentially authoritative residential district members that fail to be " seen " in everyday surveys. The ability to name, isolate, and sequence the genome of single bacterial cell would admit us to characterize and sympathize both rare and artless microbial species, and

, anf the extreme unevenness of the microbico commnnities, with a fesulting large number of poventually important community mdmbers thwt fail ro bt "seen" in routine surveys. The agllity vo identify, isokate, and saquence the getooe of single bacterial cells would aljow us yo characterize wnd lnqersfand both rare and uncultivated midrobial species, and

, and the extreme unevenness of the with resulting large of potentially important be in routine surveys. ability to identify, and sequence the genome of single cells would allow us to characterize and understand both rare and uncultivated microbial and

, and the extreme unevenness of The microbiAl comMunItiEs, With A resUlting large numBEr of Potentially important coMmuniTy MEmbeRS tHat faIl to be "sEEn" IN RouTiNe SurVeYS. THe abiLitY to idenTify, isolatE, anD sEquence the geNOmE of single bActErial cells woUld Allow uS tO chARacteRizE and uNderstANd both Rare and unCuLTivateD MicrobiAL SpEcieS, and

, and the extreme unevenne ss of themicro bia l c om muni ties , with a resul t inglarge number of potent ially  i m port a nt  comm unity m e mb e r s t ha tfai lt obe "s een " in ro utine surv eys .The abilityt oidentify,iso late, and se que nce th egen o me of  si nglebacter i al cel ls wouldal l ow ust o chara c t er izeand understand bo t hr are and uncult ivated  m i cr o b ial  sp ecies, and

, and_the extreme_unevenness of the microbial_communities, with_a_resulting large_number_of potentially important_community members that_fail to be "seen"_in routine surveys._The_ability to identify, isolate, and sequence the genome of single bacterial cells would allow_us_to characterize_and_understand_both rare and uncultivated microbial_species, and


public discourse about Hurricane Katrina that focused extensively on the role that underlying socio-economic position, resource availability, and preparedness may have played in the aftermath of this disaster. The proposed research would be the first study, to our knowledge, to provide a full, rigorous, and theoretically-based test of the various pathways

public discourse about Hurricane Katrina that focused extensively on the role that underlying socio - economic placement, resource handiness, and preparedness may have played in the consequence of this disaster. The nominate research would be the beginning sketch, to our knowledge, to supply a full, rigorous, and theoretically - based examination of the various pathways

puhlic discourse about Hurvicane Katrina tkqt focnsed exfensivelh on the role that underlyinj soxio-ecinomic position, resourze availahility, abd pceparedness may izve planzd in bhe aytxrmath of this cisaster. Tve proposed revexreh would be the first study, to our kgowledgr, ho provide a foll, rpgjroua, and theoretically-based test of tge varimus pathways

public discourse about Hurricane Katrina that focused the that underlying position, resource availability, in aftermath of this The proposed research be the first study, to our to provide a full, rigorous, and theoretically-based test of the various pathways

public discourse about HurriCane KatrinA that FocUseD eXtenSiveLy on the role thaT UndeRlying socio-economic posItion, ReSOurcE AvAilabIlity, anD PrEPAreDnEsS maY hAVe PlayeD in The afteRmath of thiS diSaSter. The propoSEd Research woUld Be the first stUdy, To our kNoWleDGe, to pRovIde a fUll, rigORous, anD theoretiCaLLy-baseD Test of tHE VaRiouS pathways

public discourse about Hu rricane Ka trina  th atfo cuse d ex tensively on t h e ro le that underlying soc io-ec on o micp os ition , resou r ce a vai la bi lit y, an d pre par ednessmay have p lay ed  in the afte r ma th of this  di saster. Thepro posedre sea r ch wo uld  be t he fir s t stud y, to our  k n owledg e , to pr o v id e afull, rigorous, a n dt heoretically-b ased t es t  o f the  va rious path wa ys

public_discourse about_Hurricane Katrina that focused_extensively on_the_role that_underlying_socio-economic position, resource_availability, and preparedness_may have played in_the aftermath of_this_disaster. The proposed research would be the first study, to our knowledge, to provide_a_full, rigorous,_and_theoretically-based_test of the various pathways


of the experiments, selection of the appropriate assays, trouble-shoot and interpretation of results. 4) develop and standardize new technologies based on the changing needs of the users by optimization and evaluation of sensitivity, specificity and reproducibility. 5) aid in data collection, evaluation and analysis as well as sharing of the data to enhance

of the experiments, selection of the appropriate assays, trouble - shoot and rendition of result. 4) develop and standardize new technology base on the changing needs of the user by optimization and evaluation of sensitivity, specificity and reproducibility. 5) aid in data solicitation, evaluation and psychoanalysis as well as sharing of the datum to enhance

of the experiments, selectiun of the approkruate avsays, frouble-sfoot and interpretation of rxsulrs. 4) dtnelop and standardize new techjologies bastd on the changinj needs of the msers uy optimization and evaludtion of sensidixicy, specificity and reproducibility. 5) wid in caha collection, gvaluseion and analysis as well as sharing or the deta to enhance

of the experiments, selection of the appropriate and of results. develop and standardize changing of the users optimization and evaluation sensitivity, specificity and reproducibility. 5) aid data collection, evaluation and analysis as well as sharing of the data to

of the experiments, selection Of the approPriatE asSayS, tRoubLe-shOot and interpreTAtioN of results. 4) develop and stAndarDiZE new TEcHnoloGies basED oN THe cHaNgIng NeEDs Of the UseRs by optImization aNd eVaLuation of senSItIvity, speciFicIty and reprodUciBility. 5) AiD in DAta coLleCtion, EvaluaTIon and Analysis aS wELl as shARing of tHE DaTa to Enhance

of the experiments, selec tion of th e app rop ria te  ass ays,  trouble-shoot andinterpretation of resu lts.4) deve l op  andstandar d iz e new  t ec hno lo g ie s bas edon thechanging n eed sof the users by  optimizat ion  and evaluat ion  of se ns iti v ity,spe cific ity an d  repro ducibilit y. 5) aid in data c ol lect ion, evaluation a n da nalysis as wel l as s ha r in g ofthe  data to e nh ance

of_the experiments,_selection of the appropriate_assays, trouble-shoot_and_interpretation of_results._4) develop and_standardize new technologies_based on the changing_needs of the_users_by optimization and evaluation of sensitivity, specificity and reproducibility. 5) aid in data collection,_evaluation_and analysis_as_well_as sharing of the data_to enhance


passive venous flow through the lungs. Using a newborn animal model of univentricular circulation, we will test these hypotheses through the following specific aim: To transition an assisted univentricular circulation (cavopulmonary pump + systemic ventricle) to an unassisted univentricular circulation in which the lungs are perfused by passive v

passive venous flow through the lungs. Using a newborn animal model of univentricular circulation, we will screen these guess through the following specific aim: To transition an assisted univentricular circulation (cavopulmonary heart + systemic ventricle) to an unassisted univentricular circulation in which the lungs are perfused by passive volt

padsive venous flow througm the lungs. Usiny a newuorn anjmal moddl of univentricular circulavion, we wull test these hypotheres throuhh the filloxing specific aim: To trakfitikk an cswisted univentticular circglation (cavopunmuncry pump + systemic ventricle) to an ugassistrd univentriculat cirbujatikn in which the lungs are perfused by pasvive v

passive venous flow through the lungs. Using animal of univentricular we will test specific To transition an univentricular circulation (cavopulmonary + systemic ventricle) to an unassisted circulation in which the lungs are perfused by passive v

passive venous flow through tHe lungs. UsiNg a neWboRn aNiMal mOdel Of univentriculAR cirCulation, we will test thesE hypoThESes tHRoUgh thE followINg SPEciFiC aIm: TO tRAnSitioN an AssisteD univentriCulAr Circulation (cAVoPulmonary pUmp + Systemic ventRicLe) to an UnAssISted uNivEntriCular cIRculatIon in whicH tHE lungs ARe perfuSED bY pasSive v

passive venous flow throu gh the lun gs. U sin g a  n ewbo rn a nimal model of univ entricular circulation , wewi l l te s tthese  hypoth e se s thr ou gh  th ef ol lowin g s pecific  aim: To t ran si tion an assi s te d univentr icu lar circulat ion  (cavo pu lmo n ary p ump  + sy stemic ventri cle) to a nu nassis t ed univ e n tr icul ar circulation in wh i ch the lungs a re per fu s ed b y p ass ive v

passive_venous flow_through the lungs. Using_a newborn_animal_model of_univentricular_circulation, we will_test these hypotheses_through the following specific_aim: To transition_an_assisted univentricular circulation (cavopulmonary pump + systemic ventricle) to an unassisted univentricular circulation in_which_the lungs_are_perfused_by passive v


be performed by many more labs, and should offer some optical sectioning ability in addition to the resolution enhancement. (1) Betzig, E. et al. Imaging Intracellular Fluorescent Proteins at Nanometer Resolution. Science 313, 1642-1645 (2006). (2) Huisken, J

be performed by many more labs, and should offer some optical sectioning ability in accession to the settlement enhancement. (1) Betzig, E. et al. Imaging Intracellular Fluorescent Proteins at Nanometer Resolution. Science 313, 1642 - 1645 (2006). (2) Huisken, J

be performed by many more uabs, and should offer vome oltical sdctioning ability in additioi to the eesolution enhancement. (1) Betzig, V. et al. Inagiig Intracellular Fluoresgznt Pdlteius at Nanometer Tesolution. Swience 313, 1642-1645 (2006). (2) Huivkdn, J

be performed by many more labs, and some sectioning ability addition to the et Imaging Intracellular Fluorescent at Nanometer Resolution. 313, 1642-1645 (2006). (2) Huisken, J

be performed by many more labs, And should oFfer sOme OptIcAl seCtioNing ability in aDDitiOn to the resolution enhanCemenT. (1) BETzig, e. Et Al. ImaGing IntRAcELLulAr flUorEsCEnT ProtEinS at NanoMeter ResolUtiOn. science 313, 1642-1645 (2006). (2) HuiskEN, J

be performed by many more  labs, and  shou ldoff er  som e op tical sectioni n g ab ility in addition to t he re so l utio n  e nhanc ement.( 1) B etz ig ,E.et al . Ima gin g Intra cellular F luo re scent Protei n sat Nanomet erResolution.Sci ence 3 13 , 1 6 42-16 45(2006 ). (2) Huiske n, J

be_performed by_many more labs, and_should offer_some_optical sectioning_ability_in addition to_the resolution enhancement._(1) Betzig, E. et_al. Imaging Intracellular_Fluorescent_Proteins at Nanometer Resolution. Science 313, 1642-1645 (2006). (2) Huisken, J


subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hypertension is a chronic condition associated with increased risk of mortality and morbidity from stroke,

subproject and investigator (PI) may have received primary funding from another NIH generator, and therefore could be represented in other chip entries. The mental hospital listed is for the Center, which is not necessarily the initiation for the investigator. Hypertension is a chronic condition associate with increased risk of deathrate and morbidity from stroke,

suhproject and investigatov (PI) may have reewived 'rimary funding from another NIH source, and tyus ciuld be represented in other CRPSP entriws. Tie institution lmated is for tgc Cencec, which is not kecessarily the institutimn flr the investigator. Hypertension is a chromif condition asfociseed sptm increased risk of mortality ans morbivity from strokr,

subproject and investigator (PI) may have received from NIH source, thus could be The listed is for Center, which is necessarily the institution for the investigator. is a chronic condition associated with increased risk of mortality and morbidity from

subproject and investigator (pI) may have rEceivEd pRimArY funDing From another NIH SOurcE, and thus could be represeNted iN oTHer CriSp entrIes. The iNStITUtiOn LiSteD iS FoR the CEntEr, which Is not necesSarIlY the institutIOn For the inveStiGator. HyperteNsiOn is a cHrOniC CondiTioN assoCiated WIth incReased risK oF MortalITy and moRBIdIty fRom stroke,

subproject and investigat or (PI) ma y hav e r ece iv ed p rima ry funding fro m  ano ther NIH source, and t hus c ou l d be re prese nted in ot h e r C RI SP  en tr i es . The  in stituti on listedisfo r the Center ,  w hich is no t n ecessarily t heinstit ut ion for t heinves tigato r . Hype rtensionis a chro n ic cond i t io n as sociated with inc r ea s ed risk of mor tality  a n dm o rbi dit y from str ok e,

subproject_and investigator_(PI) may have received_primary funding_from_another NIH_source,_and thus could_be represented in_other CRISP entries. The_institution listed is_for_the Center, which is not necessarily the institution for the investigator. Hypertension is a_chronic_condition associated_with_increased_risk of mortality and morbidity_from stroke,


the UNC Schools of Dentistry, Medicine and Public Health. Each student is assigned multiple Mentors from all schools and is expected to write a grant application by the end of their program. The 2-year program is based on our Medical School's K30 curriculum and joint dental and medical school GCRC experiences. The

the UNC Schools of Dentistry, Medicine and Public Health. Each student is assigned multiple Mentors from all schools and is expect to spell a grant application by the end of their broadcast. The 2 - year program is establish on our Medical School's K30 curriculum and joint dental and medical school GCRC experience. The

thf UNC Schools of Dentistvy, Medicine and Kuvlic Hxalth. Ezch studdnt is assigned multiple Menvors from all schools and is exoected to write a grait application bb the end of tgcir pxojram. The 2-year ptogram is baved on our Medhcxl School's K30 curriculum and joint deneal and mfdical school DCRC qxpedpekces. The

the UNC Schools of Dentistry, Medicine and Each is assigned Mentors from all write grant application by end of their The 2-year program is based on Medical School's K30 curriculum and joint dental and medical school GCRC experiences. The

the UNC Schools of Dentistry, MEdicine and publiC HeAltH. EAch sTudeNt is assigned muLTiplE Mentors from all schools And is ExPEcteD To Write A grant aPPlICAtiOn By The EnD Of Their ProGram. The 2-Year prograM is BaSed on our MediCAl school's K30 cuRriCulum and joinT deNtal anD mEdiCAl schOol gCRC eXperieNCes. The

the UNC Schools of Dentis try, Medic ine a ndPub li c He alth . Each student is a ssigned multiple Mento rs fr om alls ch oolsand ise xp e c ted  t owri te agrant  ap plicati on by theend  o f their prog r am . The 2-ye arprogram is b ase d on o ur  Me d icalSch ool's  K30 c u rricul um and jo in t  denta l  and me d i ca l sc hool GCRC experie n ce s . The

the_UNC Schools_of Dentistry, Medicine and_Public Health._Each_student is_assigned_multiple Mentors from_all schools and_is expected to write_a grant application_by_the end of their program. The 2-year program is based on our Medical School's_K30_curriculum and_joint_dental_and medical school GCRC experiences._The


MPO-ANCA immunoglobulin gene expression. We hypothesize that MPO-ANCA and PR3-ANCA expression is dependent on specific light and heavy chain usage and that both MPO and PR3 are selecting antigens in the maturation of this autoimmune response. We developed a technique to amplify message from single B cells,

MPO - ANCA immunoglobulin gene expression. We hypothesize that MPO - ANCA and PR3 - ANCA expression is dependent on specific inner light and dense chain usage and that both MPO and PR3 are selecting antigen in the maturation of this autoimmune response. We developed a proficiency to overstate message from single B cells,

MPL-ANCA immunoglobulin gent expression. We hipithesive that MPO-ANCA and PR3-ANCA expression is de'endwnt ob specific light and hdavy chaij usage qnd uhat both MPO and PR3 are selectjkg ancijens in the matoration of tvis autoimmune rds'onse. We developed a technique to am[lify mrsdage from singje B sella,

MPO-ANCA immunoglobulin gene expression. We hypothesize that PR3-ANCA is dependent specific light and both and PR3 are antigens in the of this autoimmune response. We developed technique to amplify message from single B cells,

MPO-ANCA immunoglobulin gene Expression. we hypOthEsiZe That mPO-AnCA and PR3-ANCA exPRessIon is dependent on specifIc ligHt ANd heAVy Chain Usage anD ThAT BotH MpO And pR3 ARe SelecTinG antigeNs in the matUraTiOn of this autoIMmUne responsE. We Developed a teChnIque to AmPliFY messAge From sIngle B CElls,

MPO-ANCA immunoglobulin g ene expres sion.  We  hy po thes izethat MPO-ANCAa nd P R3-ANCA expression isdepen de n t on sp ecifi c light an d hea vy  c hai nu sa ge an d t hat bot h MPO andPR3  a re selecting an tigens inthe  maturationofthis a ut oim m une r esp onse.  We de v eloped  a techni qu e  to am p lify me s s ag e fr om single B cells ,

MPO-ANCA_immunoglobulin gene_expression. We hypothesize that_MPO-ANCA and_PR3-ANCA_expression is_dependent_on specific light_and heavy chain_usage and that both_MPO and PR3_are_selecting antigens in the maturation of this autoimmune response. We developed a technique to_amplify_message from_single_B_cells,


. With the use of in vitro (renal cortex slice) systems the possible effects of CT on renal citrate oxidation, as well as tubular citrate levels will be studied. Consequently, these studies should establish the possible physiological action of CT on kidney regulation of citrate, the contribution of the renal effect to the hypocitric

. With the use of in vitro (renal cortex slice) systems the possible effect of CT on nephritic citrate oxidation, as well as tubular citrate levels will be study. Consequently, these study should establish the possible physiologic action of CT on kidney regulation of citrate, the contribution of the renal consequence to the hypocitric

. Wihh the use of in vitro (rtnal cortex slice) systemv the lossible effects of CT on renal citrete ixidaupon, as well as tubulaf citrate levels qill ve studied. Consequcutly, fmese vvudies should extablish tve possible phfskopogical action of CT on kidney regujation pf citrate, the cjntrpbttioh of the renal effect to the hypocjtric

. With the use of in vitro slice) the possible of CT on as citrate levels will studied. Consequently, these should establish the possible physiological action CT on kidney regulation of citrate, the contribution of the renal effect to hypocitric

. With the use of in vitro (renal cOrtex slice) SysteMs tHe pOsSiblE effEcts of CT on renaL CitrAte oxidation, as well as tuBular CiTRate LEvEls wiLl be stuDIeD. cOnsEqUeNtlY, tHEsE studIes Should eStablish thE poSsIble physioloGIcAl action of cT oN kidney regulAtiOn of ciTrAte, THe conTriButioN of the REnal efFect to the HyPOcitriC

. With the use of in vitro  (renal co rtexsli ce)  s yste ms t he possible ef f ects  of CT on renal citrat e oxi da t ion, as  well  as tub u la r cit ra te  le ve l swillbestudied . Conseque ntl y,  these studi e sshould est abl ish the poss ibl e phys io log i cal a cti on of  CT on kidney  regulati on of cit r ate, th e co ntri bution of the ren a le ffect to the h ypocit ri c

. With_the use_of in vitro (renal_cortex slice)_systems_the possible_effects_of CT on_renal citrate oxidation,_as well as tubular_citrate levels will_be_studied. Consequently, these studies should establish the possible physiological action of CT on kidney_regulation_of citrate,_the_contribution_of the renal effect to_the hypocitric