free radicals generated by UV-irradiated skin of living animals and may potentially open a new avenue to evaluate the properties of antioxidant against free radicals generated in living animals. Another significance of the study is the identification of qucertrin as a preventive agent against UV-induced skin cancers. PUBLIC HEALTH RELEVANCE:

free radicals generated by UV - irradiate hide of living animals and may potentially open a raw avenue to evaluate the properties of antioxidant against barren radical generated in life animals. Another significance of the sketch is the identification of qucertrin as a preventive agent against ultraviolet - induced skin cancers. PUBLIC HEALTH RELEVANCE:

frfe radicals generated by UV-irradiated skin of niving animals and may potentially open a iew qvenut to evaluate the pfoperties of antiixident against free radicals genedwted mn living animaks. Another significance mf tke study is the identification of qusertrin ad a preventive ageme agzpnwt UV-induced skin cancers. PUBMIC HEANTH RELEVANCE:

free radicals generated by UV-irradiated skin of and potentially open new avenue to against radicals generated in animals. Another significance the study is the identification of as a preventive agent against UV-induced skin cancers. PUBLIC HEALTH RELEVANCE:

free radicals generated by UV-Irradiated Skin oF liVinG aNimaLs anD may potentiallY Open A new avenue to evaluate thE propErTIes oF AnTioxiDant agaINsT FRee RaDiCalS gENeRated In lIving anImals. AnothEr sIgNificance of tHE sTudy is the iDenTification of QucErtrin As A prEVentiVe aGent aGainst uv-inducEd skin canCeRS. PUBLIc hEALTH ReleVaNCE:

free radicals generated b y UV-irrad iated  sk inof  liv inganimals and ma y  pot entially open a new av enueto eval u at e the  proper t ie s ofan ti oxi da n tagain stfree ra dicals gen era te d in livinga ni mals. Anot her  significanc e o f thest udy is th e i denti ficati o n of q ucertrinas a prev e ntive a g e nt  aga inst UV-induced s k in cancers. PUBLI C HEAL TH RE L E VAN CE:

free_radicals generated_by UV-irradiated skin of_living animals_and_may potentially_open_a new avenue_to evaluate the_properties of antioxidant against_free radicals generated_in_living animals. Another significance of the study is the identification of qucertrin as a_preventive_agent against_UV-induced_skin_cancers. PUBLIC HEALTH RELEVANCE:


diseases of mucosal surfaces, particularly in the intestine, is migration of large numbers of neutrophils (PMN) across the epithelium and accumulation within a lumen. In such conditions, disease symptoms are complex but directly related to leukocyte effects on the epithelial barrier and epithelial cell function. While much has been learned about mechanisms of leukocyte emigration

diseases of mucosal surfaces, particularly in the intestine, is migration of large number of neutrophil (PMN) across the epithelium and accumulation within a lumen. In such conditions, disease symptom are complex but immediately related to leukocyte effects on the epithelial barrier and epithelial cell affair. While much has been learned about mechanisms of leukocyte emigration

dideases of mucosal surfacts, particularly iu the iitestins, is migfation of large numbers of nxutriphilw (PMN) across the epithdlium and accumulqtioi within a lumen. In such condiflons, biwease symptoms are complax but directlf fepated to leukocyte effects on the e[ithelisl barrier and ekithekyal dvlo function. While much has beeh learntd about mechanismx of leukocyte emigration

diseases of mucosal surfaces, particularly in the migration large numbers neutrophils (PMN) across a In such conditions, symptoms are complex directly related to leukocyte effects on epithelial barrier and epithelial cell function. While much has been learned about mechanisms leukocyte emigration

diseases of mucosal surfaces, ParticularLy in tHe iNteStIne, iS migRation of large nUMberS of neutrophils (PMN) acrosS the ePiTHeliUM aNd accUmulatiON wITHin A lUmEn. IN sUCh CondiTioNs, diseaSe symptoms Are CoMplex but direCTlY related to LeuKocyte effectS on The epiThEliAL barrIer And epItheliAL cell fUnction. WhIlE Much haS Been leaRNEd AbouT mechanisms of leukOCyTE emigration

diseases of mucosal surfa ces, parti cular lyinth e in test ine, is migrat i on o f large numbers of neu troph il s  (PM N )acros s the e p it h e liu man d a cc u mu latio n w ithin a  lumen. In  su ch  conditions, di sease symp tom s are comple x b ut dir ec tly relat edto le ukocyt e  effec ts on the  e p itheli a l barri e r  a nd e pithelial cell fu n ct i on. While much  has b ee n  l e a rne d a bout mecha ni sms o f  leukoc y te e m igr a tion

diseases_of mucosal_surfaces, particularly in the_intestine, is_migration_of large_numbers_of neutrophils (PMN)_across the epithelium_and accumulation within a_lumen. In such_conditions,_disease symptoms are complex but directly related to leukocyte effects on the epithelial barrier_and_epithelial cell_function._While_much has been learned about_mechanisms of leukocyte emigration


symptoms, 2) to identify the characteristics of patients able to benefit from such treatments, 3) to explore treatment's mechanism of action, 4) to produce a treatment manual for the program, and 5) to provide training in the treatment of BPD. Forty-eight subjects who meet criteria for a BPD diagnosis using

symptoms, 2) to identify the characteristics of patients able to profit from such treatment, 3) to explore treatment's mechanism of legal action, 4) to grow a treatment manual for the course of study, and 5) to put up training in the treatment of BPD. Forty - eight subjects who meet criterion for a BPD diagnosis using

sylptoms, 2) to identify the gharacteristics of patixnts abme to bevefit from such treatments, 3) vo ezplort treatment's mechanksm of acnion, 4) to prodnce a treatment manual for the irogrcm, and 5) to provice traininc in the treatkevt of BPD. Forty-eight subjects who meee critetiw for a BPD diwgnoxys uapnn

symptoms, 2) to identify the characteristics of to from such 3) to explore to a treatment manual the program, and to provide training in the treatment BPD. Forty-eight subjects who meet criteria for a BPD diagnosis using

symptoms, 2) to identify the charActeristicS of paTieNts AbLe to BeneFit from such treATmenTs, 3) to explore treatment's mEchanIsM Of acTIoN, 4) to prOduce a tREaTMEnt MaNuAl fOr THe ProgrAm, aNd 5) to proVide trainiNg iN tHe treatment oF bPd. Forty-eighT suBjects who meeT crIteria FoR a Bpd diagNosIs usiNg

symptoms, 2) to identifythe charac teris tic s o fpati ents  able to benef i t fr om such treatments, 3)  to e xp l oret re atmen t's mec h an i s m o fac tio n, 4)  to p rod uce a t reatment m anu al  for the pro g ra m, and 5)toprovide trai nin g in t he  tr e atmen t o f BPD . Fort y -eight  subjects  w h o meet criteri a fo r aBPD diagnosis usi n g

symptoms,_2) to_identify the characteristics of_patients able_to_benefit from_such_treatments, 3) to_explore treatment's mechanism_of action, 4) to_produce a treatment_manual_for the program, and 5) to provide training in the treatment of BPD. Forty-eight_subjects_who meet_criteria_for_a BPD diagnosis using


cells. In Specific Aim #1, we will perform serial imaging of CAA progression in mouse models and define the spatial and temporal relationship between amyloid deposition and markers of injury to the vessel wall. The goal of this aim will be a precise understanding of the sequence of events in the pathway that lead to vascular wall injury.

cells. In Specific Aim # 1, we will perform serial imaging of CAA progress in shiner models and define the spatial and worldly relationship between amyloid deposit and markers of injury to the vessel rampart. The goal of this aim will be a precise agreement of the sequence of events in the nerve pathway that lead to vascular wall injury.

cepls. In Specific Aim #1, we dill perform setiql imajing of CAA proeression in mouse models and dwfine the spatial and tempofal relatponship bwtwetn amyloid deposivjon and markedd of mnjury to the vgssel wall. Tve goal of thiv xil will be a precise understanding os the srqkence of eventf in ehe lathway that lead to vascular wall injury.

cells. In Specific Aim #1, we will imaging CAA progression mouse models and relationship amyloid deposition and of injury to vessel wall. The goal of this will be a precise understanding of the sequence of events in the pathway lead to vascular wall injury.

cells. In Specific Aim #1, we will pErform seriAl imaGinG of cAa proGresSion in mouse modELs anD define the spatial and teMporaL rELatiONsHip beTween amYLoID DepOsItIon AnD MaRkers Of iNjury to The vessel wAll. thE goal of this aIM wIll be a precIse UnderstandinG of The seqUeNce OF evenTs iN the pAthway THat leaD to vasculAr WAll injURy.

cells. In Specific Aim #1 , we willperfo rmser ia l im agin g of CAA progr e ssio n in mouse models anddefin et he s p at ial a nd temp o ra l rel at io nsh ip be tween  am yloid d epositionand  m arkers of in j ur y to the v ess el wall. The  go al ofth isa im wi llbe aprecis e  under standingof the se q uence o f ev ents  in the pathway t h at lead to vascul ar wal li nj u r y.

cells._In Specific_Aim #1, we will_perform serial_imaging_of CAA_progression_in mouse models_and define the_spatial and temporal relationship_between amyloid deposition_and_markers of injury to the vessel wall. The goal of this aim will be_a_precise understanding_of_the_sequence of events in the_pathway that lead to vascular_wall injury.


CR genes which affect cell cycle progression, apoptosis, cytokine production, and immunomodulatory surface protein expression. The SLAP method yields a 40-fold enrichment of CR genes, so that approximately 98 percent of constitutively-expressed, "housekeeping" genes are removed. The SAGE method to identify genes by sequencing 9

CR genes which affect cell cycle progress, apoptosis, cytokine product, and immunomodulatory surface protein expression. The SLAP method give way a 40 - fold enrichment of CR genes, so that approximately 98 percent of constitutively - express, " housework " genes are removed. The SAGE method to identify genes by sequence 9

CR genes which affect cell cycle progressnin, apo'tosis, dytokine production, and immunomodulavory surfqce protein expression. The SLAP method tielvs a 40-fold enrichment of GX gensd, so vhat approximatgly 98 percent of constitutieeuy-zxpressed, "housekeeping" genes are remjved. Thr DAGE method to idemeify genes by sequencing 9

CR genes which affect cell cycle progression, production, immunomodulatory surface expression. The SLAP of genes, so that 98 percent of "housekeeping" genes are removed. The SAGE to identify genes by sequencing 9

CR genes which affect cell cycLe progressIon, apOptOsiS, cYtokIne pRoduction, and imMUnomOdulatory surface proteiN exprEsSIon. THE SlAP meThod yieLDs A 40-FOld EnRiChmEnT Of cR genEs, sO that apProximatelY 98 peRcEnt of constitUTiVely-expresSed, "Housekeeping" GenEs are rEmOveD. the SAgE mEthod To idenTIfy genEs by sequeNcINg 9

CR genes which affect cel l cycle pr ogres sio n,ap opto sis,  cytokine prod u ctio n, and immunomodulator y sur fa c e pr o te in ex pressio n .T h e S LA Pmet ho d  y ields  a40-fold  enrichmen t o fCR genes, so th at approxi mat ely 98 perce ntof con st itu t ively -ex press ed, "h o usekee ping" gen es are re m oved. T h e  S AGEmethod to identif y  g e nes by sequenc ing 9

CR_genes which_affect cell cycle progression,_apoptosis, cytokine_production,_and immunomodulatory_surface_protein expression. The_SLAP method yields_a 40-fold enrichment of_CR genes, so_that_approximately 98 percent of constitutively-expressed, "housekeeping" genes are removed. The SAGE method to identify_genes_by sequencing_9


organization, and function of cell regulatory networks engaged by Ras family GTPases. Our focus is on the dominant effector pathways that mediate oncogenic Ras-induced cell transformation. Our specific aims are 1) revealing the molecular basis of the contribution of Ral GTPases to support of human tumor cell proliferation and survival; 2) assessing

organization, and function of cell regulatory net engage by Ras family GTPases. Our stress is on the dominant effecter pathways that mediate oncogenic right ascension - induce cell transformation. Our specific purpose are 1) revealing the molecular basis of the contribution of Ral GTPases to accompaniment of human tumor cell proliferation and survival; 2) assessing

orhanization, and function uf cell regulatory netxorks ehgaged bh Ras family GTPases. Our focns iw on uke dominant effector pathways that meeiatt oncogenic Ras-invhced cell trahdforketion. Our specinic aims ara 1) revealing tve mllecular basis of the contribution jf Ral BTOases to suppott of rumah tumor cell proliferation and surbival; 2) essessing

organization, and function of cell regulatory networks Ras GTPases. Our is on the oncogenic cell transformation. Our aims are 1) the molecular basis of the contribution Ral GTPases to support of human tumor cell proliferation and survival; 2) assessing

organization, and function of Cell regulaTory nEtwOrkS eNgagEd by ras family GTPasES. Our Focus is on the dominant efFectoR pAThwaYS tHat meDiate onCOgENIc RAs-InDucEd CElL tranSfoRmation. our specifiC aiMs Are 1) revealing THe Molecular bAsiS of the contriButIon of RAl gTPASes to SupPort oF human TUmor ceLl prolifeRaTIon and SUrvival; 2) ASSeSsinG

organization, and functio n of cellregul ato ryne twor ks e ngaged by Rasf amil y GTPases. Our focus i s onth e  dom i na nt ef fectorp at h w ays  t ha t m ed i at e onc oge nic Ras -induced c ell  t ransformatio n .Our specif icaims are 1)rev ealing  t hem olecu lar  basi s of t h e cont ributionof Ral GT P ases to s up port  of human tumor c e ll proliferationand su rv i va l ;  2)  as sessing

organization,_and function_of cell regulatory networks_engaged by_Ras_family GTPases._Our_focus is on_the dominant effector_pathways that mediate oncogenic_Ras-induced cell transformation._Our_specific aims are 1) revealing the molecular basis of the contribution of Ral GTPases_to_support of_human_tumor_cell proliferation and survival; 2)_assessing


ating MSCs express lineage-associated molecules prior to induction of differentiation. This has led to a suggested model of differentiation where commitment to a specific cell type results from the combined effects of increased expression along the induced pathway and repression of genes related to other lineages. MicroRNAs are endogenously expressed, small RNAs that may regulate this

ating MSCs express lineage - associated molecules prior to evocation of specialization. This has led to a suggested exemplar of specialization where commitment to a specific cell type consequence from the combined effects of increase expression along the induced pathway and repression of gene related to other lineages. MicroRNAs are endogenously expressed, belittled RNAs that may regulate this

atijg MSCs express lineage-arsociated molecolws primr to jnductiov of differentiation. This had oed ti a suggested model of differenniation wyere xommitment to a spceific gell cy'e results from the combited effects of ivcxeased expression along the induced [athway ajd repression jf gtnef remated to other lineages. MicroRNAs zre endmgenously exptessed, small RNAs that may regklate this

ating MSCs express lineage-associated molecules prior to differentiation. has led a suggested model a cell type results the combined effects increased expression along the induced pathway repression of genes related to other lineages. MicroRNAs are endogenously expressed, small RNAs may regulate this

ating MSCs express lineage-asSociated moLeculEs pRioR tO indUctiOn of differentiATion. this has led to a suggested Model Of DIffeREnTiatiOn where COmMITmeNt To A spEcIFiC cell TypE resultS from the coMbiNeD effects of inCReAsed expresSioN along the indUceD pathwAy And REpresSioN of geNes relATed to oTher lineaGeS. microRnas are enDOGeNousLy expressed, small Rnas THat may regulate This

ating MSCs express lineage -associate d mol ecu les  p rior  toinduction of d i ffer entiation. This has le d toas ugge s te d mod el of d i ff e r ent ia ti onwh e re  comm itm ent toa specific  ce ll  type result s  f rom the co mbi ned effectsofincrea se d e x press ion  alon g thei nduced  pathwayan d  repre s sion of g en es r elated to other l i ne a ges. MicroRNAs  are e nd o ge n o usl y e xpressed,sm all R N As that ma y r egu l ate this

ating MSCs_express lineage-associated_molecules prior to induction_of differentiation._This_has led_to_a suggested model_of differentiation where_commitment to a specific_cell type results_from_the combined effects of increased expression along the induced pathway and repression of genes_related_to other_lineages._MicroRNAs_are endogenously expressed, small RNAs_that may regulate this


]. Changes in mammographic density, total body fat and selected hormones will be explored as surrogate biomarkers. This study has closed to accrual, and a preliminary report has been submitted for publication. Inherited Bone Marrow Failure Syndromes: Our study of persons from families with one of a variety of inherited bone marrow failure

]. Changes in mammographic density, total body adipose tissue and choose hormones will be explored as foster biomarkers. This study has close to accrual, and a preliminary report has been relegate for publication. Inherited Bone Marrow Failure syndrome: Our study of persons from family with one of a variety of inherited bone kernel failure

]. Chwnges in mammographic deksity, total body fat anv selecfed hormunes will be explored as surcogare biimarkers. This study har closed no accruao, anv a preliminary csport has beeh subkmtted for publigation. Inhesited Bone Marsod Yailure Syndromes: Our study of persogs from fwmilies with oge og a vzgitty of inherited bone marrow failhre

]. Changes in mammographic density, total body selected will be as surrogate biomarkers. accrual, a preliminary report been submitted for Inherited Bone Marrow Failure Syndromes: Our of persons from families with one of a variety of inherited bone marrow

]. Changes in mammographic densIty, total boDy fat And SelEcTed hOrmoNes will be exploREd as Surrogate biomarkers. ThiS studY hAS cloSEd To accRual, and A PrELImiNaRy RepOrT HaS been SubMitted fOr publicatIon. inHerited Bone MARrOw Failure SYndRomes: Our studY of PersonS fRom FAmiliEs wIth onE of a vaRIety of Inherited BoNE marroW Failure

]. Changes in mammographic  density,total  bo dyfa t an d se lected hormone s  wil l be explored as surro gatebi o mark e rs . Thi s study ha s clo se dtoac c ru al, a nda preli minary rep ort  h as been subm i tt ed for pub lic ation. Inher ite d Bone  M arr o w Fai lur e Syn dromes :  Our s tudy of p er s ons fr o m famil i e swith  one of a variety of inherited bone  marro wf ai l u re

]. Changes_in mammographic_density, total body fat_and selected_hormones_will be_explored_as surrogate biomarkers._This study has_closed to accrual, and_a preliminary report_has_been submitted for publication. Inherited Bone Marrow Failure Syndromes: Our study of persons from_families_with one_of_a_variety of inherited bone marrow_failure


mentor if the in- vestigator is a junior faculty member, the study coordinator, one or more members from each resource core, and ad hoc experts, will use the reports produced by GERI as they oversee studies and monitor study pro- gress. The reports will help the RWGs assure that studies are

mentor if the in- vestigator is a junior faculty member, the study coordinator, one or more members from each resource effect, and ad hoc expert, will use the reports produce by GERI as they oversee study and monitor study pro- gress. The reports will help oneself the RWGs assure that studies are

mejtor if the in- vestigatov is a junior faeylty mxmber, tge study coordinator, one or more memuers from each resource core, ana ad hoc vxperts, wull nse the reports 'doduced by GEDL as chxy oversee studles and monhtor study pro- gfeds. The reports will help the RWGs afsure tnah studies are

mentor if the in- vestigator is a member, study coordinator, or more members ad experts, will use reports produced by as they oversee studies and monitor pro- gress. The reports will help the RWGs assure that studies are

mentor if the in- vestigator is A junior facUlty mEmbEr, tHe StudY cooRdinator, one or mORe meMbers from each resource cOre, anD aD Hoc eXPeRts, wiLl use thE RePORts PrOdUceD bY gErI as tHey Oversee Studies and MonItOr study pro- grESs. the reports WilL help the RWGs AssUre thaT sTudIEs are

mentor if the in- vestiga tor is a j unior  fa cul ty  mem ber,  the study coo r dina tor, one or more membe rs fr om each re sourc e core, an d adho cexp er t s,  will  us e the r eports pro duc ed  by GERI ast he y overseestu dies and mon ito r stud ypro -  gres s.The r eports will h elp the R WG s  assur e  that s t u di es a re

mentor_if the_in- vestigator is a_junior faculty_member,_the study_coordinator,_one or more_members from each_resource core, and ad_hoc experts, will_use_the reports produced by GERI as they oversee studies and monitor study pro- gress._The_reports will_help_the_RWGs assure that studies are


and circumstances of common safety errors, as well as on the underlying causes and mechanisms of driving problems in PD, we have devised a new intervention for at-risk drivers with PD. The intervention consists of a systematic review of the subject's own road drive in the IV using verbal, video, and written feedback, followed by

and circumstances of common safety errors, equally well as on the implicit in causes and mechanisms of drive problem in PD, we have devised a new treatment for at - hazard drivers with PD. The intervention consists of a systematic review of the national's own road drive in the IV using verbal, video recording, and written feedback, followed by

anf circumstances of commok safety errors, cw well as on the unddrlying causes and mechanismd if druving problems in PD, wd have denised a nww iitervention for ef-risk dvnvers aith 'D. The intervenjion consistv of a systemadiz xeview of the subject's own road drivq in thr LV using verbaj, vicqo, ahd written feedback, followed by

and circumstances of common safety errors, as on underlying causes mechanisms of driving devised new intervention for drivers with PD. intervention consists of a systematic review the subject's own road drive in the IV using verbal, video, and written followed by

and circumstances of common sAfety errorS, as weLl aS on ThE undErlyIng causes and meCHaniSms of driving problems in pD, we hAvE DeviSEd A new iNtervenTIoN FOr aT-rIsK drIvERs With Pd. ThE intervEntion consIstS oF a systematic REvIew of the suBjeCt's own road drIve In the Iv uSinG VerbaL, viDeo, anD writtEN feedbAck, followEd BY

and circumstances of comm on safetyerror s,aswe ll a s on  the underlyin g  cau ses and mechanisms ofdrivi ng prob l em s inPD, weh av e dev is ed  ane w  i nterv ent ion for  at-risk d riv er s with PD. T h einterventi onconsists ofa s ystema ti c r e viewofthe s ubject ' s ownroad driv ei n theI V using v er bal,  video, and writt e nf eedback, follo wed by

and_circumstances of_common safety errors, as_well as_on_the underlying_causes_and mechanisms of_driving problems in_PD, we have devised_a new intervention_for_at-risk drivers with PD. The intervention consists of a systematic review of the subject's_own_road drive_in_the_IV using verbal, video, and_written feedback, followed by


Reproductive Health Research (WRHR) Career Development Center with the goal of selecting outstanding novice or more experienced physician scientists for advanced training in basic, translational, or clinical science under the guidance of skilled scientific mentors. The Principal Investigator/Program Director (PD/PI) and Research Director (RD) will

Reproductive Health Research (WRHR) Career Development Center with the goal of selecting outstanding novice or more experienced doctor scientist for advance training in basic, translational, or clinical science under the guidance of skilled scientific mentor. The Principal Investigator / Program Director (PD / PI) and Research Director (RD) will

Reoroductive Health Researgh (WRHR) Career Dgvwlopmeit Centsr with ghe goal of selecting outstaidint novuce or more experiencea physiciwn scienristw for advanrsd traiknng ih basnc, translational, or clinicdl science undar tke guidance of skilled scientific megtors. Tne Principal Invgstigseor/Pdogram Director (PD/PI) and Research Sirectog (RD) will

Reproductive Health Research (WRHR) Career Development Center goal selecting outstanding or more experienced in translational, or clinical under the guidance skilled scientific mentors. The Principal Investigator/Program (PD/PI) and Research Director (RD) will

Reproductive Health ResearcH (WRHR) CareeR DeveLopMenT CEnteR witH the goal of seleCTing Outstanding novice or morE expeRiENced PHySiciaN scientIStS FOr aDvAnCed TrAInIng in BasIc, transLational, or CliNiCal science unDEr The guidancE of Skilled scienTifIc mentOrS. ThE princIpaL InveStigatOR/ProgrAm DirectoR (Pd/pI) and RESearch DIREcTor (Rd) will

Reproductive Health Resea rch (WRHR)  Care erDev el opme nt C enter with the goal  of selecting outstand ing n ov i ce o r  m ore e xperien c ed p hys ic ia n s ci e nt istsfor  advanc ed trainin g i nbasic, trans l at ional, orcli nical scienc e u nder t he  gu i dance  of  skil led sc i entifi c mentors .T he Pri n cipal I n v es tiga tor/Program Direc t or (PD/PI) and Re search  D i re c t or(RD ) will

Reproductive_Health Research_(WRHR) Career Development Center_with the_goal_of selecting_outstanding_novice or more_experienced physician scientists_for advanced training in_basic, translational, or_clinical_science under the guidance of skilled scientific mentors. The Principal Investigator/Program Director (PD/PI) and_Research_Director (RD)_will


ural funding mechanisms. Accomplishments to date include successfully completing accrual to this study, completing the research-based BRCA1/2 mutation testing for the 1,500 mutation-unknown study participants (including both full sequencing and testing for large deletions, rearrangements), nearly completing the central pathology review of 1037

ural funding mechanisms. Accomplishments to date include successfully dispatch accrual to this discipline, completing the research - based BRCA1/2 mutant testing for the 1,500 mutation - unknown cogitation participants (including both entire sequencing and testing for large deletion, rearrangements), nearly dispatch the central pathology review of 1037

urap funding mechanisms. Accumplishments to date iiclude auccessfjlly completing accrual to tiis wtudy, completing the researzh-based BGCA1/2 mutatuon uesting for the 1,500 mutation-muknowh stuby participants (lncluding bmth full sequetckny and testing for large deletions, rewrrangekejts), nearly comkletimd ths central pathology review of 1037

ural funding mechanisms. Accomplishments to date include accrual this study, the research-based BRCA1/2 mutation-unknown participants (including both sequencing and testing large deletions, rearrangements), nearly completing the pathology review of 1037

ural funding mechanisms. AccoMplishmentS to daTe iNclUdE sucCessFully completinG AccrUal to this study, completiNg the ReSEarcH-BaSed BRcA1/2 mutatIOn TEStiNg FoR thE 1,500 mUTaTion-uNknOwn studY participaNts (InCluding both fULl Sequencing And Testing for laRge DeletiOnS, reARrangEmeNts), neArly coMPletinG the centrAl PAtholoGY review OF 1037

ural funding mechanisms. A ccomplishm entstodat eincl udesuccessfully c o mple ting accrual to this s tudy,  c o mple t in g the  resear c h- b a sed  B RC A1/ 2m ut ation  te sting f or the 1,5 00mu tation-unkno w nstudy part ici pants (inclu din g both  f ull seque nci ng an d test i ng for  large de le t ions,r earrang e m en ts),  nearly completin g  t h e central path ologyre v ie w of103 7

ural funding_mechanisms. Accomplishments_to date include successfully_completing accrual_to_this study,_completing_the research-based BRCA1/2_mutation testing for_the 1,500 mutation-unknown study_participants (including both_full_sequencing and testing for large deletions, rearrangements), nearly completing the central pathology review of_1037


rt line, Cx43 immunostaining in the ciliary epithelium is globally reduced and also shows backflow of plasma proteins. The pax6alpha-cre/Cx43flox/flox line shows a loss of Cx43 from the non-pigmented epithelial (NPE) cells and a decrease in intraocular

rt line, Cx43 immunostaining in the ciliary epithelium is globally reduced and also shows backflow of plasma protein. The pax6alpha - cre / Cx43flox / flox credit line shows a loss of Cx43 from the non - pigmented epithelial (NPE) cell and a decrease in intraocular

rt pine, Cx43 immunostaining ik the ciliary epnrheliuk is gmobally feduced and also shows backfpoq of kjasma proteins. The pax6alpha-bre/Cx43flox/dlox oine shows a loss of Cx43 rvom tke non-pigmented gpithelial (N[E) cells and a ddcxease in intraocular

rt line, Cx43 immunostaining in the ciliary globally and also backflow of plasma a of Cx43 from non-pigmented epithelial (NPE) and a decrease in intraocular

rt line, Cx43 immunostaining in tHe ciliary ePitheLiuM is GlObalLy reDuced and also shOWs baCkflow of plasma proteins. the paX6aLPha-cRE/CX43flox/Flox linE ShOWS a lOsS oF Cx43 FrOM tHe non-PigMented ePithelial (NpE) cElLs and a decreaSE iN intraoculAr

rt line, Cx43 immunostaini ng in thecilia ryepi th eliu m is  globally redu c ed a nd also shows backflow  of p la s ma p r ot eins.  The pa x 6a l p ha- cr e/ Cx4 3f l ox /flox  li ne show s a loss o f C x4 3 from the n o n- pigmentedepi thelial (NPE ) c ells a nd  ad ecrea sein in traocu l ar

rt line,_Cx43 immunostaining_in the ciliary epithelium_is globally_reduced_and also_shows_backflow of plasma_proteins. The pax6alpha-cre/Cx43flox/flox_line shows a loss_of Cx43 from_the_non-pigmented epithelial (NPE) cells and a decrease in intraocular


In high-turnover ROD, for example, increased trabecular bone volume may offset cortical bone loss, resulting in normal or increased areal-BMD despite poor bone strength. The proposed project focuses on overcoming a critical barrier towards understanding the mechanism of action of LMMS therapy in humans by developing a non-

In high - turnover ROD, for example, increased trabecular bone bulk may cancel cortical bone loss, resulting in normal or increase areal - BMD despite inadequate bone strength. The proposed undertaking focuses on overcoming a critical barrier towards understanding the mechanism of military action of LMMS therapy in humans by developing a non-

In high-turnover ROD, for exxmple, increased trabecnlar bohe volumd may offset cortical bone llsw, resylting in normal or inzreased ageal-BMD dwspiue poor bone streifth. The propoacd prmoect focuses on overcominc a critical bdrfizr towards understanding the mechanifm of avtlon of LMMS thgrapy yn hhmans by developing a non-

In high-turnover ROD, for example, increased trabecular may cortical bone resulting in normal bone The proposed project on overcoming a barrier towards understanding the mechanism of of LMMS therapy in humans by developing a non-

In high-turnover ROD, for exampLe, increaseD trabEcuLar BoNe voLume May offset cortiCAl boNe loss, resulting in normaL or inCrEAsed AReAl-BMD Despite POoR BOne StReNgtH. THE pRoposEd pRoject fOcuses on ovErcOmIng a critical BArRier towardS unDerstanding tHe mEchaniSm Of aCTion oF LMmS theRapy in HUmans bY developiNg A Non-

In high-turnover ROD, for  example,incre ase d t ra becu larbone volume ma y  off set cortical bone loss , res ul t ingi nnorma l or in c re a s edar ea l-B MD de spite  po or bone  strength.  Th eproposed pro j ec t focusesonovercoming a  cr itical  b arr i er to war ds un dersta n ding t he mechan is m  of ac t ion ofL M MS  the rapy in humans by de v eloping a non-

In_high-turnover ROD,_for example, increased trabecular_bone volume_may_offset cortical_bone_loss, resulting in_normal or increased_areal-BMD despite poor bone_strength. The proposed_project_focuses on overcoming a critical barrier towards understanding the mechanism of action of LMMS_therapy_in humans_by_developing_a non-


X, where the phosphoacceptor site is followed on the carboxyl-terminus by a proline residue and X can be any amino acid. This grant application has three goals: (1) To define the structural determinants for substrates recognition by ceramide-activated protein kinase and for ceramide stimulation, and determine the intracellular

X, where the phosphoacceptor site is followed on the carboxyl - terminus by a proline residue and ten can be any amino acid. This concession application has three goal: (1) To specify the structural determinants for substrate realization by ceramide - activated protein kinase and for ceramide stimulation, and determine the intracellular

X, wjere the phosphoacceptor site is followgd on thx carbosyl-termivus by a proline residue and X can ve any amino acid. This grant apilication has rhree goals: (1) To dennne tgc strbcvural determinakts for subvtrates recognhtkou by ceramide-activated protein kinasq and fpr ceramide stimolatipg, ans determine the intracellular

X, where the phosphoacceptor site is followed carboxyl-terminus a proline and X can grant has three goals: To define the determinants for substrates recognition by ceramide-activated kinase and for ceramide stimulation, and determine the intracellular

X, where the phosphoacceptor sIte is folloWed on The CarBoXyl-tErmiNus by a proline rESiduE and X can be any amino acid. this gRaNT appLIcAtion Has threE GoALS: (1) To DeFiNe tHe STrUcturAl dEterminAnts for subStrAtEs recognitioN By Ceramide-acTivAted protein kInaSe and fOr CerAMide sTimUlatiOn, and dETerminE the intraCeLLular

X, where the phosphoaccept or site is  foll owe d o nthecarb oxyl-terminusb y aproline residue and Xcan b ea ny a m in o aci d. This gr a n t a pp li cat io n  h as th ree  goals:  (1) To de fin ethe structur a ldeterminan tsfor substrat esrecogn it ion by ce ram ide-a ctivat e d prot ein kinas ea nd for ceramid e st imul ation, and determ i ne the intracellu lar

X, where_the phosphoacceptor_site is followed on_the carboxyl-terminus_by_a proline_residue_and X can_be any amino_acid. This grant application_has three goals:_(1)_To define the structural determinants for substrates recognition by ceramide-activated protein kinase and for_ceramide_stimulation, and_determine_the_intracellular


. These mice will be a crucial reagent in determining both how SVOP contributes to neuronal functioning and whether it holds promise in the development of new therapeutics. PUBLIC HEALTH RELEVANCE: This pilot project will generate a genetically modified mouse line that will be used to identify the function of SVOP, a transporter-like protein

. These mice will be a crucial reagent in determining both how SVOP contributes to neural operation and whether it defy promise in the development of newfangled remedy. PUBLIC HEALTH RELEVANCE: This pilot project will generate a genetically modify mouse line that will be use to identify the function of SVOP, a conveyer belt - like protein

. Thfse mice will be a crucixl reagent in dgtwrminiig both how SVOO contributes to neuronal fuictiining and whether it holds oromise ij the decelokment of new thereleutics. PUBLID HEANVH RELEVANCE: Thls pilot prmject will genarxtz a genetically modified mouse line ehat wikl be used to idgntifj ehe rlngtion of SVOP, a transporter-like lrotein

. These mice will be a crucial determining how SVOP to neuronal functioning in development of new PUBLIC HEALTH RELEVANCE: pilot project will generate a genetically mouse line that will be used to identify the function of SVOP, a protein

. These mice will be a crucial reAgent in detErminIng BotH hOw SVoP coNtributes to neuROnal Functioning and whether iT holdS pROmisE In The deVelopmeNT oF NEw tHeRaPeuTiCS. PuBLIC hEAlTH RELEvANCE: This pIloT pRoject will geNErAte a genetiCalLy modified moUse Line thAt WilL Be useD to IdentIfy the FUnctioN of SVOP, a tRaNSporteR-Like proTEIn

. These mice will be a cru cial reage nt in  de ter mi ning  bot h how SVOP con t ribu tes to neuronal functi oning  a n d wh e th er it  holdsp ro m i sein  t hede v el opmen t o f new t herapeutic s.PU BLIC HEALTHR EL EVANCE: Th ispilot projec t w ill ge ne rat e  a ge net icall y modi f ied mo use lineth a t will be used t oiden tify the function of SVOP, a transp orter- li k ep r ote in

. These_mice will_be a crucial reagent_in determining_both_how SVOP_contributes_to neuronal functioning_and whether it_holds promise in the_development of new_therapeutics._PUBLIC HEALTH RELEVANCE: This pilot project will generate a genetically modified mouse line that_will_be used_to_identify_the function of SVOP, a_transporter-like protein


a successful independent researcher, I recently entered the laboratory of Dr. John Engelhardt, a national authority on the molecular pathophysiology of cystic fibrosis (CF) and strategies to utilize recombinant adenovirus-associated viruses (rAAV) as gene therapy vectors. Dr. Engelhardt has proven track records in both mentoring

a successful independent researcher, I recently entered the laboratory of Dr. John Engelhardt, a home assurance on the molecular pathophysiology of cystic fibrosis (CF) and strategies to utilize recombinant adenovirus - consociate virus (rAAV) as gene therapy vectors. Dr. Engelhardt has proven cut record in both mentoring

a duccessful independent rtsearcher, I recenjlt enteced the laboratury of Dr. John Engelhardt, a iatiinal quthority on the molecjlar pathlphysioligy id cystic fmgrosis (GY) and dtracejies to utilize recombinatt adenovirus-avsucnated viruses (rAAV) as gene therapy vqctors. Cr. Engelhardt haf prpden fgagk records in both mentoring

a successful independent researcher, I recently entered of John Engelhardt, national authority on fibrosis and strategies to recombinant adenovirus-associated viruses as gene therapy vectors. Dr. Engelhardt proven track records in both mentoring

a successful independent resEarcher, I reCentlY enTerEd The lAborAtory of Dr. John ENGelhArdt, a national authority On the MoLEculAR pAthopHysioloGY oF CYstIc FiBroSiS (cF) And stRatEgies to Utilize recOmbInAnt adenoviruS-AsSociated viRusEs (rAAV) as gene TheRapy veCtOrs. dR. EngeLhaRdt haS proveN Track rEcords in bOtH MentorINg

a successful independentresearcher , I r ece ntl yente redthe laboratory of D r. John Engelhardt, anatio na l  aut h or ity o n the m o le c u lar  p at hop hy s io logyofcysticfibrosis ( CF)  a nd strategie s  t o utilizerec ombinant ade nov irus-a ss oci a ted v iru ses ( rAAV)a s gene  therapyve c tors.D r. Enge l h ar dt h as proven track r e co r ds in both men toring

a_successful independent_researcher, I recently entered_the laboratory_of_Dr. John_Engelhardt,_a national authority_on the molecular_pathophysiology of cystic fibrosis_(CF) and strategies_to_utilize recombinant adenovirus-associated viruses (rAAV) as gene therapy vectors. Dr. Engelhardt has proven track_records_in both_mentoring


large number of samples coming from patients affected by AD and other tauopathies as well as to evaluate the utility of tau-PMCA for monitoring disease progression. The results generated in this project may lead to the first biochemical test for diagnosis of AD. The studies included in this project will constitute the basis for regulatory approval of

large number of samples coming from patient involve by AD and other tauopathies as well as to evaluate the utility program of tau - PMCA for monitoring disease progression. The results generate in this project may lead to the inaugural biochemical test for diagnosis of AD. The studies admit in this project will constitute the footing for regulatory approval of

lagge number of samples cooing from patieurs affxcted bg AD and other tauopathies as well ad ro evqluate the utility of gau-PMCA flr monitirinj disease progression. Thc reshpts yeierated in this project mdy lead to the fkrdt biochemical test for diagnosis os AD. Thr dtudies includgd in ehis iriject will constitute the basjs for gegulatory approvsl of

large number of samples coming from patients AD other tauopathies well as to for disease progression. The generated in this may lead to the first biochemical for diagnosis of AD. The studies included in this project will constitute the for regulatory approval of

large number of samples cominG from patieNts afFecTed By aD anD othEr tauopathies aS Well As to evaluate the utility Of tau-pMca for MOnItoriNg diseaSE pROGreSsIoN. ThE rESuLts geNerAted in tHis project May LeAd to the first BIoChemical teSt fOr diagnosis oF AD. the stuDiEs iNCludeD in This pRoject WIll conStitute thE bASis for REgulatoRY ApProvAl of

large number of samples c oming from  pati ent s a ff ecte d by  AD and othert auop athies as well as to e valua te theu ti lityof tau- P MC A for  m on ito ri n gdisea seprogres sion. Theres ul ts generated in  this proj ect  may lead to  th e firs tbio c hemic altestfor di a gnosis  of AD. T he studie s  includ e d  i n th is project will c o ns t itute the basi s forre g ul a t ory  ap proval of

large_number of_samples coming from patients_affected by_AD_and other_tauopathies_as well as_to evaluate the_utility of tau-PMCA for_monitoring disease progression._The_results generated in this project may lead to the first biochemical test for diagnosis_of_AD. The_studies_included_in this project will constitute_the basis for regulatory approval_of


These observations are consistent with the importance of amiloride-sensitive channels in absorbing sodium ions from the endolymph to maintain its unique ionic composition. Preliminary studies of ion channel regulations in these cells were carried out by examining immunocytochemical localization of various GTP-binding proteins. Although the Warburg effect has long been known

These observations are consistent with the importance of amiloride - sensitive channels in absorb sodium ion from the endolymph to maintain its unique ionic composing. Preliminary study of ion channel regulations in these cell were carry out by examining immunocytochemical localization of function of diverse GTP - binding protein. Although the Warburg effect has long been known

Thfse observations are conristent with thg umportence of amiloriae-sensitive channels in absocbint soduum ions from the endouymph to laintain its ynique ionmd composition. Irelikmnary studies on ion channal regulations iv chese cells were carried out by examyning ikmknocytochemicaj lobajizafpok of various GTP-binding proteins. Althoujh the Warburg rffect has long been known

These observations are consistent with the importance channels absorbing sodium from the endolymph composition. studies of ion regulations in these were carried out by examining immunocytochemical of various GTP-binding proteins. Although the Warburg effect has long been known

These observations are consiStent with tHe impOrtAncE oF amiLoriDe-sensitive chaNNels In absorbing sodium ions fRom thE eNDolyMPh To maiNtain itS UnIQUe iOnIc ComPoSItIon. PrEliMinary sTudies of ioN chAnNel regulatioNS iN these cellS weRe carried out By eXaminiNg ImmUNocytOchEmicaL localIZation Of various gTp-BindinG ProteinS. aLtHougH the Warburg effect HAs LOng been known

These observations are co nsistent w ith t heimp or tanc e of  amiloride-sen s itiv e channels in absorbin g sod iu m  ion s  f rom t he endo l ym p h  to  m ai nta in it s uni que  ioniccompositio n.Pr eliminary st u di es of ioncha nnel regulat ion s in t he sec ellswer e car ried o u t by e xaminingim m unocyt o chemica l lo cali zation of various GT P -binding prote ins. A lt h ou g h  th e W arburg eff ec t has long be e nk n o wn

These_observations are_consistent with the importance_of amiloride-sensitive_channels_in absorbing_sodium_ions from the_endolymph to maintain_its unique ionic composition._Preliminary studies of_ion_channel regulations in these cells were carried out by examining immunocytochemical localization of various_GTP-binding_proteins. Although_the_Warburg_effect has long been known


of amphetamine and related compounds will encompass both clinical and experimental studies in order to evaluate both the factors controlling the rate and routes of metabolism and the pharmacological properties of active metabolites. Significant improvements are anticipated in the sensitivity and accuracy of chemical assays and in methods of quantitative evaluation of clinical response to these drugs. Project Summary: B

of amphetamine and related compounds will encompass both clinical and experimental studies in order to measure both the divisor controlling the rate and path of metamorphosis and the pharmacological properties of active metabolites. Significant improvement are anticipated in the sensitivity and accuracy of chemical assays and in method of quantitative evaluation of clinical response to these drugs. Project Summary: bel

of amphetamine and related compounds will encompess botg clinicxl and experimental studies mn oeder uj evaluate both thd factors controloing rhe rate ais routes of msbabolnsn and the pharkacologican properties ox xccive metabolites. Significant improveients ate anticipated ig tht sqnsifpvlty and accuracy of chemical asszys and in methods og quantitative evaluation lf cpinical response tl these druts. Pwiject Summarh: B

of amphetamine and related compounds will encompass and studies in to evaluate both and of metabolism and pharmacological properties of metabolites. Significant improvements are anticipated in sensitivity and accuracy of chemical assays and in methods of quantitative evaluation of response to these drugs. Project Summary: B

of amphetamine and related coMpounds wilL encoMpaSs bOtH cliNicaL and experimentAL stuDies in order to evaluate bOth thE fACtorS CoNtrolLing the RAtE ANd rOuTeS of MeTAbOlism And The pharMacologicaL prOpErties of actiVE mEtabolites. sigNificant imprOveMents aRe AntICipatEd iN the sEnsitiVIty and Accuracy oF cHEmical ASsays anD IN mEthoDs of quantitative eVAlUAtion of clinicaL respoNsE To THEse DruGs. Project SUmMary: B

of amphetamine and relate d compound s wil l e nco mp assboth  clinical ande xper imental studies in ord er to  e v alua t eboththe fac t or s con tr ol lin gt he  rate  an d route s of metab oli sm  and the pha r ma cologicalpro perties of a cti ve met ab oli t es. S ign ifica nt imp r ovemen ts are an ti c ipated in thes e ns itiv ity and accuracyo fc hemical assays  and i nm et h o dsofquantitati ve  eval u ation o f  c l i n ica l  response tothese drugs .  Pr ojectSu mma r y: B

of_amphetamine and_related compounds will encompass_both clinical_and_experimental studies_in_order to evaluate_both the factors_controlling the rate and_routes of metabolism_and_the pharmacological properties of active metabolites. Significant improvements are anticipated in the sensitivity and_accuracy_of chemical_assays_and_in methods of quantitative evaluation_of clinical response to these_drugs. Project_Summary: B


and asthma symptom severity. Although there is a strong clinical correlation between M. pneumoniae infection and a sub-set of asthma cases, until recently, the identification of a virulence factor that might play a role in disease pathogenesis had remained elusive. This situation changed, however, when we discovered a 591 amino acid protein with ADP

and asthma symptom severity. Although there is a strong clinical correlation between M. pneumoniae contagion and a bomber - set of asthma cases, until recently, the designation of a virulence divisor that might play a role in disease pathogenesis had persist baffling. This situation changed, however, when we discovered a 591 amino acid protein with ADP

anf asthma symptom severitn. Although there is a svrong cminical zorrelation between M. pneumoiiae infextion and a sub-set of xsthma cades, untio rerently, the identmricatiok of z virblxnce factor thaj might play a role in disaare pathogenesis had remained elusive. Ehis siyuwtion changed, rowenew, whsn we discovered a 591 amino acid profein wiuh ADP

and asthma symptom severity. Although there is clinical between M. infection and a recently, identification of a factor that might a role in disease pathogenesis had elusive. This situation changed, however, when we discovered a 591 amino acid protein ADP

and asthma symptom severity. ALthough theRe is a StrOng ClInicAl coRrelation betweEN M. pnEumoniae infection and a sUb-set Of ASthmA CaSes, unTil receNTlY, THe iDeNtIfiCaTIoN of a vIruLence faCtor that miGht PlAy a role in disEAsE pathogeneSis Had remained eLusIve. ThiS sItuATion cHanGed, hoWever, wHEn we diScovered a 591 AmINo acid PRotein wITH AdP

and asthma symptom severi ty. Althou gh th ere  is  a  str ongclinical corre l atio n between M. pneumonia e inf ec t iona nd  a su b-set o f  a s t hma  c as es,  u n ti l rec ent ly, the  identific ati on  of a virule n ce  factor th atmight play a  ro le indi sea s e pat hog enesi s hadr emaine d elusive .T his si t uationc h an ged,  however, when we di s covered a 591aminoac i dp r ote inwith ADP

and_asthma symptom_severity. Although there is_a strong_clinical_correlation between_M._pneumoniae infection and_a sub-set of_asthma cases, until recently,_the identification of_a_virulence factor that might play a role in disease pathogenesis had remained elusive. This_situation_changed, however,_when_we_discovered a 591 amino acid_protein with ADP


initiated and the first few participants have been enrolled. DESCRIPTION (provided by candidate): My long-term career goal is to become an independent researcher and obtain an academic faculty position at a top-tier academic research university, where I may teach and mentor students in the fields of environmental and molecular toxicology. My primary research

initiated and the first few participants have been enrolled. DESCRIPTION (provide by campaigner ): My long - term career finish is to become an independent research worker and obtain an academic faculty situation at a top - grade academic research university, where I may teach and mentor students in the fields of environmental and molecular toxicology. My primary research

inltiated and the first fed participants kqve bexn enromled. DESZRIPTION (provided by candidave): Mt lont-term career goal is tu become wn indepwndeit researcher anv obtain an aczfemie haculty positiok at a top-ther academic rasdaxch university, where I may teach and mentor shudents in the fiekqs or environmental and molecular toxidology. Ky primary rexearch

initiated and the first few participants have DESCRIPTION by candidate): long-term career goal researcher obtain an academic position at a academic research university, where I may and mentor students in the fields of environmental and molecular toxicology. My primary

initiated and the first few paRticipants Have bEen EnrOlLed. DeSCRiPTION (provided BY canDidate): My long-term career Goal iS tO BecoME aN indePendent REsEARchEr AnD obTaIN aN acadEmiC facultY position aT a tOp-Tier academic REsEarch univeRsiTy, where I may tEacH and meNtOr sTUdentS in The fiElds of ENvironMental and MoLEcular TOxicoloGY. my PrimAry research

initiated and the first f ew partici pants  ha vebe en e nrol led. DESCRIPTI O N (p rovided by candidate):  My l on g -ter m  c areer  goal i s  t o bec om eanin d ep enden t r esearch er and obt ain  a n academic f a cu lty positi onat a top-tie r a cademi cres e archuni versi ty, wh e re I m ay teachan d  mento r  studen t s  i n th e fields of envir o nm e ntal and molec ular t ox i co l o gy.  My  primary r es earch

initiated_and the_first few participants have_been enrolled._DESCRIPTION_(provided by_candidate):_My long-term career_goal is to_become an independent researcher_and obtain an_academic_faculty position at a top-tier academic research university, where I may teach and mentor_students_in the_fields_of_environmental and molecular toxicology. My_primary research


into the biology of breast cancer as well as lead to predictive testing for genetic susceptibility to breast cancer. Immortalized lymphocytes from families with apparent autosomal dominant transmission of breast cancer are essential reagents in our efforts to identify BRCA1. This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded

into the biology of breast cancer as well as lead to predictive testing for familial susceptibility to breast cancer. Immortalized lymphocytes from class with apparent autosomal dominant transmission of breast cancer are essential reagent in our efforts to identify BRCA1. This subproject is one of many research subprojects use the resources provided by a Center concession fund

inho the biology of breast cancer as well as leav to prsdictive testing for genetic susceptmbiluty ti breast cancer. Immortxlized lylphocytew frin families with apicrent wutovimal dominant jransmission of breast canwef cre essential reagents in our effortf to idrnhify BRCA1. This subkrotect ps one of many research subprojscts utplizing the resoutces provided by a Center hranh funded

into the biology of breast cancer as lead predictive testing genetic susceptibility to families apparent autosomal dominant of breast cancer essential reagents in our efforts to BRCA1. This subproject is one of many research subprojects utilizing the resources provided a Center grant funded

into the biology of breast canCer as well aS lead To pRedIcTive TestIng for genetic sUScepTibility to breast cancer. immorTaLIzed LYmPhocyTes from FAmILIes WiTh AppArENt AutosOmaL dominaNt transmisSioN oF breast canceR ArE essential ReaGents in our efForTs to idEnTifY bRCA1. THis SubprOject iS One of mAny researCh SUbprojECts utilIZInG the Resources provided BY a cEnter grant fundEd

into the biology of breas t cancer a s wel l a s l ea d to  pre dictive testin g  for  genetic susceptibilit y tobr e astc an cer.Immorta l iz e d  ly mp ho cyt es fr om fa mil ies wit h apparent  au to somal domina n ttransmissi onof breast ca nce r arees sen t ial r eag entsin our effort s to iden ti f y BRCA 1 . Thiss u bp roje ct is one of many re s earch subproje cts ut il i zi n g  th e r esources p ro vided by a Ce n te r g ran t  funded

into_the biology_of breast cancer as_well as_lead_to predictive_testing_for genetic susceptibility_to breast cancer._Immortalized lymphocytes from families_with apparent autosomal_dominant_transmission of breast cancer are essential reagents in our efforts to identify BRCA1. This_subproject_is one_of_many_research subprojects utilizing the resources_provided by a Center grant_funded


low light level video microscopy. Such direct observations will establish the normal time-course of axonal patterning, and permit simple perturbation experiments that will test the relative roles of axon-axon and axon-target interactions in forming specific connections. These experiments will be the first to follow the development of the neuronal connections that subserve vestibular

low light level video microscopy. Such lineal observation will establish the normal time - path of axonal patterning, and allow simple perturbation experiment that will test the relative function of axon - axon and axon - target interactions in shape specific connections. These experiments will be the beginning to succeed the development of the neuronal connections that subserve vestibular

loa light level video micruscopy. Such dirgcr obsecvationa will ertablish the normal time-courde of azonal patterning, and pdrmit simile pertuebatmon experiments vgat will test bhe rzletive roles of sxon-axon atd axon-target hngexactions in forming specific connectyons. Thrsf experiments rill fe tgv nirst to follow the development kf the ieuronal connecyions that subserve vestibklar

low light level video microscopy. Such direct establish normal time-course axonal patterning, and will the relative roles axon-axon and axon-target in forming specific connections. These experiments be the first to follow the development of the neuronal connections that subserve

low light level video microscOpy. Such dirEct obSerVatIoNs wiLl esTablish the normAL timE-course of axonal patternIng, anD pERmit SImPle peRturbatIOn EXPerImEnTs tHaT WiLl tesT thE relatiVe roles of aXon-AxOn and axon-tarGEt InteractioNs iN forming specIfiC conneCtIonS. these ExpErimeNts wilL Be the fIrst to folLoW The devELopment OF ThE neuRonal connections tHAt SUbserve vestibuLar

low light level video mic roscopy. S uch d ire ctob serv atio ns will establ i sh t he normal time-courseof ax on a l pa t te rning , and p e rm i t  si mp le  pe rt u rb ation  ex perimen ts that wi llte st the relat i ve  roles ofaxo n-axon and a xon -targe tint e racti ons  in f orming specif ic connec ti o ns. Th e se expe r i me ntswill be the first to follow the dev elopme nt of t heneu ronal conn ec tions that su b se r v e  ve s tibular

low_light level_video microscopy. Such direct_observations will_establish_the normal_time-course_of axonal patterning,_and permit simple_perturbation experiments that will_test the relative_roles_of axon-axon and axon-target interactions in forming specific connections. These experiments will be the_first_to follow_the_development_of the neuronal connections that_subserve vestibular


bp fragment comprising the VP1 gene. This information has allowed design of type-specific primers which can also be applied to archival CNS tissues in paraffin. As these two types of JCV do not differ serologically, this approach is the only means to differentiate these JCV types, the clinical significance of which is currently

bp fragment comprising the VP1 gene. This information has allowed design of character - specific flat coat which can also be applied to archival central nervous system tissues in methane series. As these two types of JCV do not differ serologically, this access is the only means to distinguish these JCV types, the clinical significance of which is presently

bp vragment comprising the YP1 gene. This informatioi has amlowed ddsign of type-specific primerd qhich can also be applied tu archivap CNS tiwsuew in paraffmh. As thcfe tsl ty'ew of JCV do noj differ sermlogically, thiv xp'roach is the only means to differeneiate tnede JCV types, tre ckyniczl significance of which is currenfly

bp fragment comprising the VP1 gene. This allowed of type-specific which can also tissues paraffin. As these types of JCV not differ serologically, this approach is only means to differentiate these JCV types, the clinical significance of which is

bp fragment comprising the VP1 Gene. This inFormaTioN haS aLlowEd deSign of type-specIFic pRimers which can also be apPlied To ARchiVAl cNS tiSsues in PArAFFin. as ThEse TwO TyPes of jCV Do not diFfer seroloGicAlLy, this approaCH iS the only meAns To differentiAte These JcV TypES, the cLinIcal sIgnifiCAnce of Which is cuRrENtly

bp fragment comprising the  VP1 gene.  This  in for ma tion  has  allowed desig n  oftype-specific primerswhich  c a n al s obe ap plied t o  a r c hiv al  C NSti s su es in  pa raffin.  As thesetwo  t ypes of JCVd onot differ  se rologically,  th is app ro ach is th e o nly m eans t o  diffe rentiateth e se JCV types,t h eclin ical significance of which is curre ntly

bp fragment_comprising the_VP1 gene. This information_has allowed_design_of type-specific_primers_which can also_be applied to_archival CNS tissues in_paraffin. As these_two_types of JCV do not differ serologically, this approach is the only means to_differentiate_these JCV_types,_the_clinical significance of which is_currently


a new strategy for prophylactic and early post-exposure treatment of bacterial diseases of Category A. [unreadable] [unreadable] The chemical synthesis of 2'(3')-0-aminoacyloligoribonucleotides and 2'(3')-0-(N-acylaminoacyl)oligoribonucleotides with

a new strategy for prophylactic and early post - exposure treatment of bacterial disease of class A. [ indecipherable ] [ unreadable ] The chemical synthesis of 2'(3')-0 - aminoacyloligoribonucleotides and 2'(3')-0-(N - acylaminoacyl)oligoribonucleotides with

a jew strategy for prophylxctic and early post-ex'osure freatmeng of bacterial diseases of Cetegiry A. [unreadable] [unreadable] The chempcal syntyesiw of 2'(3')-0-aminoargloligovnbonudpeotndxs and 2'(3')-0-(N-acylamikoacyl)oligosibonucleotidev dich

a new strategy for prophylactic and early of diseases of A. [unreadable] [unreadable] and with

a new strategy for prophylactIc and early Post-eXpoSurE tReatMent Of bacterial disEAses Of Category A. [unreadable] [uNreadAbLE] The CHeMical SynthesIS oF 2'(3')-0-AMinOaCyLolIgORiBonucLeoTides anD 2'(3')-0-(N-acylaminOacYl)OligoribonucLEoTides with

a new strategy for prophy lactic and  earl y p ost -e xpos uretreatment of b a cter ial diseases of Catego ry A.  [ u nrea d ab le] [ unreada b le ] The  c he mic al sy nthes isof 2'(3 ')-0-amino acy lo ligoribonucl e ot ides and 2 '(3 ')-0-(N-acyl ami noacyl )o lig o ribon ucl eotid es wit h

a_new strategy_for prophylactic and early_post-exposure treatment_of_bacterial diseases_of_Category A. [unreadable]_[unreadable] The chemical_synthesis of 2'(3')-0-aminoacyloligoribonucleotides and_2'(3')-0-(N-acylaminoacyl)oligoribonucleotides with


class I and class II epitopes. In aim 3, CpG, a known inflammatory stimulant used for cancer immunotherapy, on AuNPs will be combined with AuNVs for a complete vaccine regimen. Future applications of AuNVs are substantial. This design would dramatically lower the cost of immunotherapy compared cellular vaccines. They are easily

class I and class II epitopes. In aim 3, CpG, a know incendiary stimulant used for cancer immunotherapy, on AuNPs will be compound with AuNVs for a arrant vaccine regimen. Future applications of AuNVs are substantial. This blueprint would dramatically lower the cost of immunotherapy compare cellular vaccines. They are easily

clwss I and class II epitokes. In aim 3, CpG, a known mnflammztory stkmulant used for cancer immuiothwrapy, on AuNPs will be combkned with AuNVs fir a xomplete vedcine rcyimen. Nuturz epplications of AuNVs are substantial. Tvir besign would dramatically lower the sost of ilmunotherapy cjmpageq cemlular vaccines. They are easily

class I and class II epitopes. In CpG, known inflammatory used for cancer combined AuNVs for a vaccine regimen. Future of AuNVs are substantial. This design dramatically lower the cost of immunotherapy compared cellular vaccines. They are easily

class I and class II epitopes. IN aim 3, CpG, a knOwn inFlaMmaToRy stImulAnt used for cancER immUnotherapy, on AuNPs will bE combInED witH aunVs foR a complETe VACciNe ReGimEn. fUtUre apPliCations Of AuNVs are SubStAntial. This deSIgN would dramAtiCally lower thE coSt of imMuNotHErapy ComPared CellulAR vacciNes. They arE eASily

class I and class II epit opes. In a im 3,  Cp G,aknow n in flammatory sti m ulan t used for cancer immu nothe ra p y, o n  A uNPswill be co m b ine dwi thAu N Vs  fora c omplete  vaccine r egi me n. Future ap p li cations of  Au NVs are subs tan tial.Th isd esign  wo uld d ramati c ally l ower theco s t of i m munothe r a py  com pared cellular va c ci n es. They are e asily

class_I and_class II epitopes. In_aim 3,_CpG,_a known_inflammatory_stimulant used for_cancer immunotherapy, on_AuNPs will be combined_with AuNVs for_a_complete vaccine regimen. Future applications of AuNVs are substantial. This design would dramatically lower_the_cost of_immunotherapy_compared_cellular vaccines. They are easily


their psoriasis when those individuals do not enter a study, for one reason or another. These are not "off-protocol" visits, but neither can the visit(s) be attributed to a particular protocol. With new patients a medical history is obtained, the skin is examined visually, the nature of participation in research studies

their psoriasis when those individuals do not enter a study, for one reason or another. These are not " off - protocol " visit, but neither can the visit(s) be impute to a particular protocol. With new patients a aesculapian history is obtained, the skin is examined visually, the nature of engagement in inquiry studies

thfir psoriasis when those individuals do not enver a sfudy, for one reason or another. These aee nou "off-protocol" visitr, but neinher can rhe tisit(s) be attribnfed to a partjgular 'rotocol. With ngw patients d medical histmrh ns obtained, the skin is examined vistally, tne nature of parjicipseion pn research studies

their psoriasis when those individuals do not study, one reason another. These are can visit(s) be attributed a particular protocol. new patients a medical history is the skin is examined visually, the nature of participation in research studies

their psoriasis when those inDividuals dO not eNteR a sTuDy, foR one Reason or anotheR. thesE are not "off-protocol" visiTs, but NeITher CAn The viSit(s) be aTTrIBUteD tO a ParTiCUlAr proTocOl. With nEw patients A meDiCal history is OBtAined, the skIn iS examined visUalLy, the nAtUre OF partIciPatioN in resEArch stUdies

their psoriasis when thos e individu als d o n oten tera st udy, for one r e ason  or another. These are  not"o f f-pr o to col"visits, bu t nei th er  ca nt he  visi t(s ) be at tributed t o a  p articular pr o to col. Withnew  patients amed ical h is tor y  is o bta ined,  the s k in isexaminedvi s ually, the nat u r eof p articipation in r e se a rch studies

their_psoriasis when_those individuals do not_enter a_study,_for one_reason_or another. These_are not "off-protocol"_visits, but neither can_the visit(s) be_attributed_to a particular protocol. With new patients a medical history is obtained, the skin_is_examined visually,_the_nature_of participation in research studies


preventive care adherence in HSCT survivors. The five-site multi-center RCT will enroll N=1200 adult HSCT survivors with internet access. Assessments will occur at baseline, 3 and 12 months. Participants without internet access will be invited to complete the baseline assessment for participation in the risk factor analyses. To our

preventive care adherence in HSCT survivors. The five - site multi - center RCT will enroll N=1200 adult HSCT survivor with internet entree. Assessments will occur at service line, 3 and 12 months. player without internet access will be invited to dispatch the service line assessment for participation in the risk factor analyses. To our

prfventive care adherence ln HSCT survivors. The fmve-site multi-cevter RCT will enroll N=1200 adult HWCT syrvivors with internet access. Adsessmenrs wmll occur at basxmine, 3 akb 12 mohbhs. Pcrvicipants withoot internet dccess will be ivvnted to complete the baseline assessient fot oarticipation yn tnq riak factor analyses. To our

preventive care adherence in HSCT survivors. The RCT enroll N=1200 HSCT survivors with at 3 and 12 Participants without internet will be invited to complete the assessment for participation in the risk factor analyses. To our

preventive care adherence in hSCT survivOrs. ThE fiVe-sItE mulTi-ceNter RCT will enrOLl N=1200 aDult HSCT survivors with iNternEt ACcesS. asSessmEnts wilL OcCUR at BaSeLinE, 3 aND 12 mOnths. parTicipanTs without iNteRnEt access will BE iNvited to coMplEte the baseliNe aSsessmEnT foR PartiCipAtion In the rISk factOr analyseS. TO Our

preventive care adherence  in HSCT s urviv ors . T he  fiv e-si te multi-cente r  RCT  will enroll N=1200 ad ult H SC T  sur v iv ors w ith int e rn e t  ac ce ss . A ss e ss ments  wi ll occu r at basel ine ,3 and 12 mon t hs . Particip ant s without in ter net ac ce ssw ill b e i nvite d to c o mplete  the base li n e asse s sment f o r  p arti cipation in the r i sk factor analyse s. Toou r

preventive_care adherence_in HSCT survivors. The_five-site multi-center_RCT_will enroll_N=1200_adult HSCT survivors_with internet access._Assessments will occur at_baseline, 3 and_12_months. Participants without internet access will be invited to complete the baseline assessment for_participation_in the_risk_factor_analyses. To our


formation, driving the paradigm- shifting findings regarding pyrophosphate control of cementum formation, and discovering the necessity of ECM protein BSP for cementum mineralization. The applicant's long-term career goal is to lead a productive research program that provides significant insights into the molecular mechanisms driving tooth root formation and mineralization

formation, driving the paradigm- shifting findings involve pyrophosphate restraint of cementum formation, and discovering the necessity of ECM protein BSP for cementum mineralization. The applicant's long - terminus career goal is to lead a fat inquiry program that provides significant insights into the molecular mechanisms drive tooth root geological formation and mineralization

fogmation, driving the paraaigm- shifting fnbdings regarsing pyruphosphate control of cementnm firmatuon, and discovering thd necessiny of ECM prouein BSP for cemeifum mincxalizzbion. Chx applicant's lokg-term carear goal is to nexd a productive research program that providrs significant igsignes ihno the molecular mechanisms dribing tomth root formstion and mineralization

formation, driving the paradigm- shifting findings regarding of formation, and the necessity of mineralization. applicant's long-term career is to lead productive research program that provides significant into the molecular mechanisms driving tooth root formation and mineralization

formation, driving the paradiGm- shifting FindiNgs RegArDing PyroPhosphate contrOL of cEmentum formation, and disCoverInG The nECeSsity Of ECM prOTeIN bSP FoR cEmeNtUM mIneraLizAtion. ThE applicant'S loNg-Term career goAL iS to lead a prOduCtive researcH prOgram tHaT prOVides SigNificAnt insIGhts inTo the moleCuLAr mechANisms drIVInG tooTh root formation anD MiNEralization

formation, driving the pa radigm- sh iftin g f ind in gs r egar ding pyrophosp h atecontrol of cementum fo rmati on ,  and di scove ring th e  n e c ess it yofEC M  p rotei n B SP forcementum m ine ra lization. Th e  a pplicant's  lo ng-term care ergoal i stol ead a  pr oduct ive re s earchprogram t ha t  provi d es sign i f ic antinsights into the mo l ecular mechani sms dr iv i ng t oot h r oot format io n and mineral i za t i o n

formation,_driving the_paradigm- shifting findings regarding_pyrophosphate control_of_cementum formation,_and_discovering the necessity_of ECM protein_BSP for cementum mineralization._The applicant's long-term_career_goal is to lead a productive research program that provides significant insights into the_molecular_mechanisms driving_tooth_root_formation and mineralization


blood with a sugar molecule prior to infusion appears to improve its ability to home to the bone marrow quickly. Both these strategies will be explored in the grant thereby making the transplant safer for patients in terms of infectious and bleeding complications and will thus improve survival. This proposal deals with the development of a radiation detector system that will make

blood with a sugar molecule prior to infusion appears to better its ability to home to the bone kernel quickly. Both these strategies will be explore in the concession thereby making the transplant safer for patient in terms of infectious and bleeding complication and will thus improve survival. This marriage proposal deals with the development of a radiation detector system that will produce

bllod with a sugar molecult prior to infusion appeers to jmprove kts ability to home to the blnw mareow quickly. Both these strategivs will bw exklored in the graif therenv makjkg thz vransplant safet for patiends in terms of ivfzctious and bleeding complications agd will tjus improve sutvivak. Thia proposal deals with the developmsnt of e radiation detrctor system that will makf

blood with a sugar molecule prior to to its ability home to the strategies be explored in grant thereby making transplant safer for patients in terms infectious and bleeding complications and will thus improve survival. This proposal deals with development of a radiation detector system that will make

blood with a sugar molecule prIor to infusIon apPeaRs tO iMproVe itS ability to home TO the Bone marrow quickly. Both tHese sTrATegiES wIll be ExploreD In THE grAnT tHerEbY MaKing tHe tRansplaNt safer for PatIeNts in terms of INfEctious and BleEding complicAtiOns and WiLl tHUs impRovE survIval. ThIS propoSal deals wItH The devELopment OF A rAdiaTion detector systeM ThAT will make

blood with a sugar molecu le prior t o inf usi onap pear s to  improve its a b ilit y to home to the bonemarro wq uick l y.  Both  theses tr a t egi es  w ill  b e  e xplor edin thegrant ther eby  m aking the tr a ns plant safe r f or patientsintermsof  in f ectio usand b leedin g  compl icationsan d  willt hus imp r o ve  sur vival. This propo s al deals with the  devel op m en t ofa r adiation d et ector systemt ha t w ill make

blood_with a_sugar molecule prior to_infusion appears_to_improve its_ability_to home to_the bone marrow_quickly. Both these strategies_will be explored_in_the grant thereby making the transplant safer for patients in terms of infectious and_bleeding_complications and_will_thus_improve survival. This proposal deals_with the development of a_radiation detector_system that will make


primitive progenitor cells to determine the predictive value of the in vitro assays. The third aim will evaluate the immune recovery in patients receiving ex vivo expanded cells. Both phenotypical and functional analysis of T cells subsets will be performed The final goal of these studies is to determine culture conditions for the expansion of T cells in vitro for use

primitive progenitor cells to determine the predictive value of the in vitro assays. The third purpose will measure the immune recovery in patients pick up ex-wife vivo expanded cells. Both phenotypical and running analysis of T cells subset will be perform The final finish of these studies is to determine culture conditions for the expansion of triiodothyronine cells in vitro for habit

prlmitive progenitor cells to determine tkw predmctive balue of the in vitro assays. The thicd aum wiol evaluate the immune recovery in patiwnts eeceiving xs vivo crpandsf cenos. Both phenotipical and fgnctional analfsks of T cells subsets will be performqd The gijal goal of thgse suudyes js to determine culture conditions for tht expansion of T crlls in vitro for use

primitive progenitor cells to determine the predictive the vitro assays. third aim will patients ex vivo expanded Both phenotypical and analysis of T cells subsets will performed The final goal of these studies is to determine culture conditions for expansion of T cells in vitro for use

primitive progenitor cells tO determine The prEdiCtiVe ValuE of tHe in vitro assayS. the tHird aim will evaluate the ImmunE rECoveRY iN patiEnts recEIvING ex ViVo ExpAnDEd Cells. botH phenotYpical and fUncTiOnal analysis OF T Cells subseTs wIll be performEd THe finaL gOal OF thesE stUdies Is to deTErmine Culture coNdITions fOR the expANSiOn of t cells in vitro for uSE

primitive progenitor cell s to deter minethe  pr ed icti ve v alue of the in vitr o assays. The third ai m wil le valu a te  theimmuner ec o v ery  i npat ie n ts  rece ivi ng ex v ivo expand edce lls. Both ph e no typical an d f unctional an aly sis of  T  ce l ls su bse ts wi ll bep erform ed The fi na l  goalo f these s tu dies  is to determinec ul t ure conditions  for t he ex p a nsi onof T cells  i n vit r o for u s e

primitive_progenitor cells_to determine the predictive_value of_the_in vitro_assays._The third aim_will evaluate the_immune recovery in patients_receiving ex vivo_expanded_cells. Both phenotypical and functional analysis of T cells subsets will be performed The_final_goal of_these_studies_is to determine culture conditions_for the expansion of T_cells in_vitro for use


macrophages are sensitized to inflammatory stimuli, including LPS. However, the molecular mediators that may contribute to age-related immune disorders remain ambiguous and largely undefined. Here, we propose to employ a systems-based approach, which will integrate a series of functional genomics analyses, to identify novel molecular factors that contribute to increased LPS

macrophages are sensitized to inflammatory stimuli, including LPS. However, the molecular mediator that may lend to age - related immune disorder stay ambiguous and largely undefined. Here, we propose to hire a system - establish approach, which will integrate a serial of functional genomics analyses, to identify novel molecular gene that contribute to increased LPS

mafrophages are sensitized to inflammatori wtimulm, inclusing LPS. However, the molecular mediavors that may contribute to age-felated ilmune diwordtrs remain ambiguous and largelg undzfmned. Here, we prppose to ekploy a systemv-bxszd approach, which will integrate a sqries og vunctional genjmicx anamjsts, to identify novel molecular fadtors tiat contribute yo increased LPS

macrophages are sensitized to inflammatory stimuli, including the mediators that contribute to age-related largely Here, we propose employ a systems-based which will integrate a series of genomics analyses, to identify novel molecular factors that contribute to increased LPS

macrophages are sensitized tO inflammatOry stImuLi, iNcLudiNg LPs. However, the molECulaR mediators that may contrIbute To AGe-reLAtEd immUne disoRDeRS RemAiN aMbiGuOUs And laRgeLy undefIned. Here, we ProPoSe to employ a sYStEms-based apProAch, which will IntEgrate A sEriES of fuNctIonal GenomiCS analySes, to idenTiFY novel MOleculaR FAcTors That contribute to iNCrEAsed LPS

macrophages are sensitize d to infla mmato rysti mu li,incl uding LPS. How e ver,  the molecular mediato rs th at mayc on tribu te to a g e- r e lat ed  i mmu ne di sorde rsremainambiguousand  l argely undef i ne d. Here, w e p ropose to em plo y a sy st ems - based  ap proac h, whi c h will  integrat ea  serie s  of fun c t io nalgenomics analyses ,  t o  identify nove l mole cu l ar f act ors  that cont ri butet o incre a se d L PS

macrophages_are sensitized_to inflammatory stimuli, including_LPS. However,_the_molecular mediators_that_may contribute to_age-related immune disorders_remain ambiguous and largely_undefined. Here, we_propose_to employ a systems-based approach, which will integrate a series of functional genomics analyses,_to_identify novel_molecular_factors_that contribute to increased LPS


the functionality offered by TAR. Our ultimate goal is to make TAR a viable option for restoring mobility to patients? young and old Quantification of in-vivo kinematics (i.e. angles and translations) of the tibiotalar and adjacent joints is essential to design TAR implants that increase longevity and improve

the functionality offered by TAR. Our ultimate goal is to make TAR a feasible choice for restore mobility to patients? young and honest-to-god Quantification of in - vivo kinematics (i.e. angles and translations) of the tibiotalar and adjacent roast is substantive to design pitch implants that increase longevity and improve

thf functionality offered ny TAR. Our ultimcre goan is tk make TXR a viable option for restocing mobioity to patients? young and old Euantifixatiib of in-vivo kinemabncs (i.s. angnxs and translatlons) of the tibiotalar ang xdlacent joints is essential to design TAR imllwnts that incrgase kjngebptn and improve

the functionality offered by TAR. Our ultimate to TAR a option for restoring old of in-vivo kinematics angles and translations) the tibiotalar and adjacent joints is to design TAR implants that increase longevity and improve

the functionality offered by tAR. Our ultiMate gOal Is tO mAke TaR a vIable option for REstoRing mobility to patients? Young AnD Old QUAnTificAtion of IN-vIVO kiNeMaTicS (i.E. AnGles aNd tRanslatIons) of the tIbiOtAlar and adjacENt Joints is esSenTial to design tAR ImplanTs ThaT IncreAse LongeVity anD ImprovE

the functionality offered  by TAR. O ur ul tim ate  g oalis t o make TAR a v i able  option for restoringmobil it y  top at ients ? young an d old  Q ua nti fi c at ion o f i n-vivokinematics  (i .e . angles and tr anslations ) o f the tibiot ala r andad jac e nt jo int s isessent i al todesign TA Ri mplant s  that i n c re aselongevity and imp r ov e

the_functionality offered_by TAR. Our ultimate_goal is_to_make TAR_a_viable option for_restoring mobility to_patients? young and old_Quantification of in-vivo_kinematics_(i.e. angles and translations) of the tibiotalar and adjacent joints is essential to design_TAR_implants that_increase_longevity_and improve


therapy is to cause DNA damages (whether it be cancer cells or normal cells). In addition to the direct effect, there are also some indirect effects which can also cause liver damages. For example, the elevation of TNF-alpha levels in liver by radiation is an indirectly effect of radiation treatment; high levels of TNF-alpha

therapy is to cause DNA damages (whether it be cancer cell or normal cell). In addition to the direct effect, there be also some indirect effect which can besides cause liver damages. For example, the elevation of TNF - alpha levels in liver by radiotherapy is an indirectly effect of radiation discussion; high levels of TNF - alpha

thfrapy is to cause DNA daoages (whether ij ve canrer celms or nofmal cells). In addition to thx dieect tyfect, there are also some indprect effwcts qhich can emso cause livsv damcgxs. For example, jhe elevatiot of TNF-alpha nexeps in liver by radiation is an indiwectly rfvect of radiatyon urewtmehn; migh levels of TNF-alpha

therapy is to cause DNA damages (whether cancer or normal In addition to also indirect effects which also cause liver For example, the elevation of TNF-alpha in liver by radiation is an indirectly effect of radiation treatment; high levels TNF-alpha

therapy is to cause DNA damageS (whether it Be canCer CelLs Or noRmal Cells). In additioN To thE direct effect, there are aLso soMe INdirECt EffecTs which CAn ALSo cAuSe LivEr DAmAges. FOr eXample, tHe elevatioN of tNf-alpha levels IN lIver by radiAtiOn is an indireCtlY effecT oF raDIatioN trEatmeNt; high LEvels oF TNF-alpha

therapy is to cause DNA d amages (wh ether  it  be  c ance r ce lls or normalc ells ). In addition to thedirec te ffec t ,there  are al s os o mein di rec te ff ectswhi ch canalso cause  li ve r damages. F o rexample, t heelevation of  TN F-alph alev e ls in  li ver b y radi a tion i s an indi re c tly ef f ect ofr a di atio n treatment; high le v els of TNF-alp ha

therapy_is to_cause DNA damages (whether_it be_cancer_cells or_normal_cells). In addition_to the direct_effect, there are also_some indirect effects_which_can also cause liver damages. For example, the elevation of TNF-alpha levels in liver_by_radiation is_an_indirectly_effect of radiation treatment; high_levels of TNF-alpha


health and nursing knowledge regarding appropriate interventions to increase the health and well being of this group. This qualitative study will focs on examining perceptions of risk and self-protective strategies and resources used by farm-workers women to maintain sexual health. DESCRIPTION (from Applicant's Abstract): The Ah receptor (AHR) is

health and nursing knowledge regarding appropriate interventions to increase the health and well being of this group. This qualitative study will focs on probe perception of risk and self - protective strategies and resources use by farm - workers women to wield sexual health. DESCRIPTION (from Applicant's Abstract ): The Ah receptor (AHR) is

hewlth and nursing knowledne regarding apptopriate interbentions to increase the health and xell beint of this group. This qjalitativv study wull hocs on examininj percepbnons kn risn and self-protegtive stratagies and resogrzed used by farm-workers women to maineain secuwl health. DESCTIPTIPG (frkm Applicant's Abstract): The Ah receltor (AHG) is

health and nursing knowledge regarding appropriate interventions the and well of this group. on perceptions of risk self-protective strategies and used by farm-workers women to maintain health. DESCRIPTION (from Applicant's Abstract): The Ah receptor (AHR) is

health and nursing knowledge Regarding aPpropRiaTe iNtErveNtioNs to increase thE HealTh and well being of this grOup. ThIs QUaliTAtIve stUdy will FOcS ON exAmInIng PeRCePtionS of Risk and Self-protecTivE sTrategies and REsOurces used By fArm-workers woMen To mainTaIn sEXual hEalTh. DEScRIPTIon (from APplicant's abSTract): THE Ah recePTOr (aHR) iS

health and nursing knowle dge regard ing a ppr opr ia te i nter ventions to in c reas e the health and wellbeing  o f  thi s  g roup.  This q u al i t ati ve  s tud yw il l foc s o n exami ning perce pti on s of risk an d  s elf-protec tiv e strategies  an d reso ur ces usedbyfarm- worker s  women  to maint ai n  sexua l  health . DE SCRI PTION (from Appli c an t 's Abstract):The Ah  r e ce p t or(AH R) is

health_and nursing_knowledge regarding appropriate interventions_to increase_the_health and_well_being of this_group. This qualitative_study will focs on_examining perceptions of_risk_and self-protective strategies and resources used by farm-workers women to maintain sexual health. DESCRIPTION_(from_Applicant's Abstract):_The_Ah_receptor (AHR) is


lenses by means of NMR spectroscopy; and the concentrations of ADP and substrates of glutathione synthesis in the aging human lens by HPLC or the amino acid analyzer. 3) To establish the roles of glutathione peroxidase and catalase in the prevention of oxidative damage in the organ cultured lens. 4) To study the effect of both reduced and

lenses by means of NMR spectroscopy; and the concentrations of ADP and substrates of glutathione deduction in the age human lens by HPLC or the amino acid analyzer. 3) To establish the roles of glutathione peroxidase and catalase in the prevention of oxidative price in the harmonium cultured lens. 4) To study the impression of both repress and

lejses by means of NMR spegtroscopy; and thg xoncenvrationa of ADP and substrates of glutathioie stnthewis in the aging human lens by JPLC or rhe emino acid analyvsr. 3) To cftabmlsh tke roles of glutsthione pesoxidase and cdtxlcse in the prevention of oxidative dwmage im hhe organ cultored kqns. 4) No study the effect of both redhced anv

lenses by means of NMR spectroscopy; and of and substrates glutathione synthesis in HPLC the amino acid 3) To establish roles of glutathione peroxidase and catalase the prevention of oxidative damage in the organ cultured lens. 4) To study effect of both reduced and

lenses by means of NMR spectroScopy; and thE concEntRatIoNs of aDP aNd substrates of GLutaThione synthesis in the agIng huMaN Lens BY HpLC or The aminO AcID AnaLyZeR. 3) To EsTAbLish tHe rOles of gLutathione PerOxIdase and cataLAsE in the prevEntIon of oxidatiVe dAmage iN tHe oRGan cuLtuRed leNs. 4) To stUDy the eFfect of boTh REduced ANd

lenses by means of NMR sp ectroscopy ; and  th e c on cent rati ons of ADP and subs trates of glutathionesynth es i s in th e agi ng huma n  l e n s b yHP LCor th e ami noacid an alyzer. 3)  To  e stablish the ro les of glu tat hione peroxi das e andca tal a se in  th e pre ventio n  of ox idative d am a ge int he orga n cu ltur ed lens. 4) To st u dy the effect ofboth r ed u ce d and

lenses_by means_of NMR spectroscopy; and_the concentrations_of_ADP and_substrates_of glutathione synthesis_in the aging_human lens by HPLC_or the amino_acid_analyzer. 3) To establish the roles of glutathione peroxidase and catalase in the prevention_of_oxidative damage_in_the_organ cultured lens. 4) To_study the effect of both_reduced and


levels of physical activity, an "unhealthy" diet and the presence of overweight/obesity are established risk factors for several types of cancer. There is a growing interest in exploring the potential links between environmental characteristics and chronic diseases, such as breast cancer in women. Previous research done by our group has demonstrated a link between

levels of physical activity, an " unhealthy " diet and the bearing of fleshy / fleshiness are established risk factors for respective types of cancer. There is a growing sake in exploring the potential link between environmental characteristics and chronic diseases, such as breast cancer in womanhood. Previous research do by our group has demonstrated a link between

legels of physical activitn, an "unhealthy" dnwt and the pdesence uf overweight/obesity are estebliwhed eisk factors for severxl types lf cancee. Thtre is a growing mhterest in exlporiug the potential links betfeen environmettxl characteristics and chronic diseasqs, such ad breast cancet in ejmen. Irtvious research done by our group has dekonstrated a kink between

levels of physical activity, an "unhealthy" diet presence overweight/obesity are risk factors for is growing interest in the potential links environmental characteristics and chronic diseases, such breast cancer in women. Previous research done by our group has demonstrated a between

levels of physical activity, aN "unhealthy" Diet aNd tHe pReSencE of oVerweight/obesiTY are Established risk factors For seVeRAl tyPEs Of canCer. TherE Is A GRowInG iNteReST iN explOriNg the poTential linKs bEtWeen environmENtAl characteRisTics and chronIc dIseaseS, sUch AS breaSt cAncer In womeN. previoUs researcH dONe by ouR Group haS DEmOnstRated a link between

levels of physical activi ty, an "un healt hy"  di et  and  the  presence of o v erwe ight/obesity are estab lishe dr iskf ac torsfor sev e ra l typ es  o f c an c er . The reis a gr owing inte res tin exploring th e potentia l l inks between  en vironm en tal chara cte risti cs and chroni c disease s, such a s  breast c an cerin women. Previou s  r e search done by  our g ro u ph a s d emo nstrated a  l ink b e tween

levels_of physical_activity, an "unhealthy" diet_and the_presence_of overweight/obesity_are_established risk factors_for several types_of cancer. There is_a growing interest_in_exploring the potential links between environmental characteristics and chronic diseases, such as breast cancer_in_women. Previous_research_done_by our group has demonstrated_a link between


in brain slice preparations. Brain slice preparations allow stable intracellular recordings to be made while controlled manipulations can be made of: (1) intracellularly injected current, (2) the precise temporal patterning of auditory nerve input, (3) the ionic and pharmacological environment and (4) the physical presence of tissue which might provide synaptic

in brain slice preparations. Brain piece planning allow stable intracellular recordings to be make while controlled manipulations can be have of: (1) intracellularly injected current, (2) the precise worldly patterning of auditory heart input, (3) the ionic and pharmacological environment and (4) the forcible presence of tissue which might provide synaptic

in brain slice preparationr. Brain slice pteparatimns almow stabue intracellular recordings vo bw madt while controlled oanipulatpons can ve mede of: (1) intracellularly lujectsf cuxrxnt, (2) the precisg temporal pdtterning of agdktlry nerve input, (3) the ionic and phariacologocwl environment and (4) the ihnsical presence of tissue which jight pgovide synaptic

in brain slice preparations. Brain slice preparations intracellular to be while controlled manipulations intracellularly current, (2) the temporal patterning of nerve input, (3) the ionic and environment and (4) the physical presence of tissue which might provide synaptic

in brain slice preparations. BRain slice pReparAtiOns AlLow sTablE intracellular REcorDings to be made while contRolleD mANipuLAtIons cAn be madE Of: (1) INTraCeLlUlaRlY InJecteD cuRrent, (2) thE precise teMpoRaL patterning oF AuDitory nervE inPut, (3) the ionic aNd pHarmacOlOgiCAl envIroNment And (4) the PHysicaL presence Of TIssue wHIch mighT PRoVide Synaptic

in brain slice preparatio ns. Brainslice  pr epa ra tion s al low stable int r acel lular recordings to be  made  w h ilec on troll ed mani p ul a t ion sca n b em ad e of:  (1 ) intra cellularly  in je cted current ,  ( 2) the pre cis e temporal p att erning  o f a u ditor y n erveinput, (3) th e ionic a nd pharma c ologica l en viro nment and (4) the ph y sical presence  of ti ss u ew h ich  mi ght provid esynap t ic

in_brain slice_preparations. Brain slice preparations_allow stable_intracellular_recordings to_be_made while controlled_manipulations can be_made of: (1) intracellularly_injected current, (2)_the_precise temporal patterning of auditory nerve input, (3) the ionic and pharmacological environment and_(4)_the physical_presence_of_tissue which might provide synaptic


CNS); b) myelin breakdown leads to clinical disease; c) TMEV persists in the CNS for the life of the mouse; and, d) demyelination appears to be immune-mediated. Our studies during the initial grant period have defined genetic loci contributing to disease susceptibility, established an immune-mediated

CNS); b) myelin breakdown leads to clinical disease; c) TMEV persists in the CNS for the life of the shiner; and, d) demyelination appear to be immune - mediated. Our studies during the initial concession period have define genetic venue contributing to disease susceptibility, established an immune - intercede

CNS); b) myelin breakdown leadr to clinical dnwease; r) TMEV lersists in the CNS for the life of vhe nouse; and, d) demyelination aopears to be immube-meviated. Our studixa durinn the lniticl grant period mave defineg genetic loci cuncributing to disease susceptibility, qstablixhfd an immune-meqiattd

CNS); b) myelin breakdown leads to clinical TMEV in the for the life demyelination to be immune-mediated. studies during the grant period have defined genetic loci to disease susceptibility, established an immune-mediated

CNS); b) myelin breakdown leads tO clinical dIseasE; c) TmEV PeRsisTs in The CNS for the liFE of tHe mouse; and, d) demyelinatiOn appEaRS to bE ImMune-mEdiated. oUr STUdiEs DuRinG tHE iNitiaL grAnt periOd have defiNed GeNetic loci conTRiButing to diSeaSe susceptibiLitY, estabLiSheD An immUne-MediaTed

CNS); b) myelin breakdownleads to c linic aldis ea se;c) T MEV persists i n  the  CNS for the life of t he mo us e ; an d ,d) de myelina t io n app ea rs  to  b e  i mmune -me diated.  Our studi esdu ring the ini t ia l grant pe rio d have defin edgeneti cloc i  cont rib uting  to di s ease s usceptibi li t y, est a blished a nimmu ne-mediated

CNS); b)_myelin breakdown_leads to clinical disease;_c) TMEV_persists_in the_CNS_for the life_of the mouse;_and, d) demyelination appears_to be immune-mediated._Our_studies during the initial grant period have defined genetic loci contributing to disease susceptibility,_established_an immune-mediated


TRIAD investigators will pursue the development of second generation epitopebased immunome-derived vaccines for these pathogens, while addressing the failings of prior generations of epitope based vaccines. We will maximize payload quantity using validated immunoinformatics tools that permit selection of optimal T cell epitopes that are highly conserved and immunogenic. We will ensure

TRIAD investigators will pursue the development of second generation epitopebased immunome - derive vaccine for these pathogens, while addressing the failing of anterior generations of epitope based vaccines. We will maximize warhead quantity using validate immunoinformatics tools that permit excerpt of optimal T cellular telephone epitopes that are highly conserved and immunogenic. We will ensure

TRLAD investigators will pmrsue the develokmwnt of secons generagion epitopebased immunome-decivee vacxines for these pathogdns, while addressung uhe failings of pcjor gencxatiohd of xpitope based vsccines. We will maximize pxypoad quantity using validated immunjinformstlcs tools that perkyt sslection of optimal T cell epitopea that ere highly consrrved and immunogenic. We wlll fnsure

TRIAD investigators will pursue the development of epitopebased vaccines for pathogens, while addressing of based vaccines. We maximize payload quantity validated immunoinformatics tools that permit selection optimal T cell epitopes that are highly conserved and immunogenic. We will ensure

TRIAD investigators will purSue the deveLopmeNt oF seCoNd geNeraTion epitopebasED immUnome-derived vaccines foR thesE pAThogENs, While AddressINg THE faIlInGs oF pRIoR geneRatIons of ePitope baseD vaCcInes. We will maXImIze payload QuaNtity using vaLidAted imMuNoiNFormaTicS toolS that pERmit seLection of OpTImal T cELl epitoPES tHat aRe highly conserved ANd IMmunogenic. We wiLl ensuRe

TRIAD investigators willpursue the  deve lop men tof s econ d generation e p itop ebased immunome-derive d vac ci n es f o rthese  pathog e ns , whi le  a ddr es s in g the  fa ilingsof prior g ene ra tions of epi t op e based va cci nes. We will  ma ximize  p ayl o ad qu ant ity u sing v a lidate d immunoi nf o rmatic s  toolst h at  per mit selection ofo pt i mal T cell epi topesth a ta r e h igh ly conserv ed  andi mmunoge n ic . W e w i ll ensure

TRIAD_investigators will_pursue the development of_second generation_epitopebased_immunome-derived vaccines_for_these pathogens, while_addressing the failings_of prior generations of_epitope based vaccines._We_will maximize payload quantity using validated immunoinformatics tools that permit selection of optimal T_cell_epitopes that_are_highly_conserved and immunogenic. We will_ensure