Georgia State University Research Foundation Inc

THE SCIENCE OF DECISION MAKING: CONNECTING PEOPLE AND POLICY

THERAPEUTICS TARGETING FILOVIRAL INTERFERON-ANTAGONIST AND REPLICATION FUNCTIONS

CROSS-INSTITUTIONAL COLLABORATION AND REIMAGINING TOWARD EQUITY, ACCESS, AND TEACHER EFFECTIVENESS: EXPANDING AND SUSTAINING PROJECT CREATE

FY 2009 TEACHER QUALITY PARTNERSHIPS GRANTS

NATIONAL CENTER FOR SPECIAL RESEARCH (NCSER)

NEW COE CA "DOD CENTER OF EXCELLENCE IN ADVANCED COMPUTING AND SOFTWARE (COE-ACS)"

EDUCATION RESEARCH AND DEVELOPMENT CENTERS

STRENGTHENING THE UNIVERSITY-DISTRICT-COMMUNITY PARTNERSHIP: COMPASSION, REFLECTION AND EQUITY FOR ATLANTA TEACHER EFFECTIVENESS (CREATE)

CENTER FOR BEHAVIORAL NEUROSCIENCE

MULTIVARIATE METHODS FOR IDENTIFYING MULTI-TASK/MULTIMODAL BRAIN IMAGING BIOMARKE

MECHANISMS OF EVASION OF THE INNATE AND ADAPTIVE IMMUNE RESPONSES TO FILOVIRUSES

FIRST IN THE WORLD - VALIDATION

STARVE AND KILL: ENGINEERED ANTIGENS TARGETING NUTRIENT ACQUISITION PATHWAYS ESSENTIAL FOR GONOCOCCAL INFECTION AND DISEASE

NURTURES

CREATE (COLLABORATION AND REFLECTION TO ENHANCE ATLANTA TEACHER EFFECTIVENESS)

CENTER OF EXCELLENCE: ENVIRONMENTAL HEALTH DISPARITIES CORE

IMPLEMENTATION GRANT: COMMUNITY-SOIL-AIR-WATER (CSAW): A MODEL COMMUNITY-BASED LEARNING ECOSYSTEM TO TRANSFORM GEOSCIENCES -THE COMMUNITY-SOIL-AIR-WATER (CSAW) LEARNING ECOSYSTEM WILL INTEGRATE JUSTICE, EQUITY, DIVERSITY, AND INCLUSION INTO THE PRACTICES OF COLLABORATING WITH COMMUNITIES IN GEOSCIENCES RESEARCH. TO EXPAND CAPACITY AND ACCOUNTABILITY IN SOCIO-ENVIRONMENTAL RESEARCH COLLABORATIONS BETWEEN GEOSCIENTISTS AND COMMUNITY PARTNERS, CSAW WILL BRING TOGETHER THREE ACADEMIC PARTNERS (GEORGIA STATE UNIVERSITY, A PREDOMINANTLY BLACK INSTITUTION, SPELMAN COLLEGE, A HISTORICALLY BLACK COLLEGE, AND EMORY UNIVERSITY) WITH TWO COMMUNITY ORGANIZATIONS: THE WEST ATLANTA WATERSHED ALLIANCE AND ECO-ACTION. THIS PROJECT WILL ADDRESS THE QUESTION: HOW CAN GEOSCIENTISTS LEARN FROM, CONTRIBUTE TO, AND FIND SOLUTIONS WITH COMMUNITIES FACING FUNDAMENTAL PROBLEMS RELATED TO EARTH SYSTEMS? CSAW WILL EXAMINE HOW A LEARNING ECOSYSTEM MODEL CENTERED IN COMMUNITY-ENGAGED, PLACE-BASED RESEARCH CAN INCREASE: (1) RECRUITMENT, RETENTION, AND TRAINING OF DIVERSE GEOSCIENTISTS; AND (2) CAPACITY FOR AND ACCOUNTABILITY WITHIN COLLABORATION BETWEEN GEOSCIENTISTS AND COMMUNITIES ADDRESSING SOCIO-ENVIRONMENTAL PROBLEMS. COHORTS OF FACULTY AND COMMUNITY ORGANIZERS ALONG WITH 12 POST-BACCALAUREATE (POSTBAC) SCHOLARS AND 15 MASTER?S STUDENTS WILL BE TRAINED IN BUILDING OUTREACH AND RESEARCH PROJECTS WITH COMMUNITY PARTNERS USING A FRAMEWORK OF SHARED VALUES OF EQUITY, TRANSPARENCY, AND ACCOUNTABILITY. THESE PROJECTS WILL ADDRESS CRITICAL NEEDS IN PLACE-BASED EARTH SYSTEMS RESEARCH INCLUDING SOIL LEAD AND OTHER HEAVY METAL CONTAMINATION AND RADON EXPOSURE; AIR POLLUTION, CLIMATE CHANGE, AND HEAT MAPPING; AND WATER POLLUTION, URBAN FLOODING, AND GREEN STORMWATER INFRASTRUCTURE. THE OVERALL GOALS AND OBJECTIVES OF THE PROJECT ARE TO BUILD A BRIDGE: 1) BUILD AND FORMALIZE THE CSAW LEARNING ECOSYSTEM WITH ALL COHORT MEMBERS TO SOLVE SOCIO-ENVIRONMENTAL CHALLENGES; 2) RECRUIT DIVERSE COHORTS OF POSTBACS AND MASTER?S STUDENTS AND TRAIN THEM IN PROFESSIONAL DEVELOPMENT, COMMUNITY ENGAGEMENT, AND NETWORKING, WITH A FOCUS ON CENTERING JUSTICE, EQUITY, AND INCLUSION; 3) IMPLEMENT TRAINING, PROGRAMMING, AND PEDAGOGY PROTOCOLS TO RECRUIT, MENTOR, AND SUPPORT DIVERSE STUDENTS, COMMUNITY COLLABORATORS, AND FACULTY IN THE GEOSCIENCES; 4) DEVELOP AN ASSET-BASED MODEL OF COLLABORATION WITH COMMUNITY-DRIVEN RESEARCH TO INCLUDE FORMAL TRAINING, ACCOUNTABILITY, AND ASSESSMENT FOR ENGAGEMENT PRACTICES AND OUTCOMES; AND 5) GROW A NETWORK, MATERIALS, AND PROTOTYPE TO EXPAND THE CSAW LEARNING ECOSYSTEM MODEL TO OTHER COMMUNITIES, UNIVERSITIES, AND INSTITUTIONS. CSAW PARTNERSHIPS WILL ADVANCE A BROAD RANGE OF SCHOLARSHIP ON SOCIO-ENVIRONMENTAL PROBLEMS AND THEIR SOLUTIONS, AND ON BEST PRACTICES FOR GEOSCIENTISTS IN COMMUNITY ENGAGEMENT, ACCOUNTABILITY, AND CO-PRODUCTION. CSAW WILL PROVIDE A WELL-EVALUATED AND SUCCESSFUL MODEL TO ADOPT IN TRANSFORMATIVE GEOSCIENCES WORK ACROSS DISCIPLINES. THROUGH BROADENING PARTICIPATION OF UNDERREPRESENTED GROUPS AND BUILDING AND ENHANCING PARTNERSHIPS WITH COMMUNITY ADVOCACY GROUPS, THE CSAW LEARNING ECOSYSTEM WILL PROVIDE A PROTOTYPE TO PROMOTE GEOSCIENCE TRANSFORMATIONS AT OTHER INSTITUTIONS AND ACROSS DISCIPLINES. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.

COINSTAC: DECENTRALIZED, SCALABLE ANALYSIS OF LOOSELY COUPLED DATA

AMPK AS A REDOX SENSOR AND MODULATOR

INNOVATIONS IN DEVELOPING RESIDENT EDUCATORS AND MENTORS

MINING THE GENOMEWIDE SCAN: GENETIC PROFILES OF STRUCTURAL LOSS IN SCHIZOPHRENIA

NOVEL INFLUENZA A NANOVACCINES FOR BROAD CROSS PROTECTION

NEISSERIA GONORRHOEAE METAL TRANSPORTERS THAT SUBVERT NUTRITIONAL IMMUNITY

INTERROGATING STRESS-RELIEVING NEURAL CIRCUITS TO ALLEVIATE CARDIOVASCULAR DISEASE

IDENTIFICATION AND PRE-CLINICAL EVALUATION OF MEASLES VIRUS INHIBITORS

LEADERSHIP EDUCATION IN NEURODEVELOPMENTAL AND RELATED DISORDERS TRAINING PROGRAM

PATHOPHYSIOLOGY OF TLR5KO COLITIS

CREST CENTER FOR DYNAMIC MULTISCALE AND MULTIMODAL BRAIN MAPPING OVER THE LIFESPAN [D-MAP]

DEVELOPMENT OF A BROAD-SPECTRUM INHIBITOR AGAINST SEASONAL AND HIGHLY-PATHOGENIC INFLUENZA VIRUSES

AMP-ACTIVATED KINASE IN DIABETIC COMPLICATIONS

DECONSTRUCTING INFLAMMATION AND ALTERED MICROBIOTA IN METABOLIC SYNDROME

EXPLORING THE MILLIARCSECOND FRONTIER: OPEN ACCESS TO THE RENEWED CHARA ARRAY

NEURONS EXPRESSING ANGIOTENSIN TYPE 2 RECEPTORS IN THE NTS AS AN ACCESS POINT FOR CARDIOVASCULAR CONTROL.

ADVANCING INNOVATIVE PARTNERSHIPS AND PATHWAYS TO ADDRESS MENTAL HEALTH WORKFORCE SHORTAGES IN GEORGIA SCHOOLS

LEADERSHIP EDUCATION IN NEURODEVELOPMENTAL AND RELATED DISORDERS TRAINING PROGRAM

NOVEL NONLINEAR OPTICAL PROCESSES IN ACTIVE, RANDOM AND NANOSTRUCTURED SYSTEMS

TEACHER QUALITY ENHANCEMENT GRANTS FOR STATE AND PARTNERSHIPS - PARTNERSHIP GRANTS

NEUROCOGNITIVE BASES OF TREATMENT RESISTANCE IN DEVELOPMENTAL DYSLEXIA

REACTIVE NITROGEN AND ACCELERATED ATHEROSCLEROSIS IN TYPE I DIABETES

INFLUENZA VACCINES INDUCING BROADLY CROSS PROTECTIVE IMMUNITY

ADDRESSING SOCIAL DETERMINANTS OF HEALTH IN THE MOST DIVERSE SQUARE MILE IN AMERICA

STRUCTURE-BASED DESIGN OF CORONAVIRUS SUBUNIT VACCINES

RATIONAL DESIGN AND EVALUATION OF NOVEL MRNA VACCINES AGAINST MERS-COV

BIOBEHAVIORAL FOUNDATIONS AND DEVELOPMENT OF COGNITIVE COMPETENCE

ENABLING MILLIARCSECOND ASTROPHYSICS: OPEN ACCESS FOR THE CHARA ARRAY

NOVEL NANOBODIES TO PREVENT AND TREAT SARS-COV-2 AND OTHER PATHOGENIC HUMAN CORONAVIRUSES

MULTIVALENT NANOCLUSTER UNIVERSAL INFLUENZA VACCINE GIVEN BY MICRONEEDLE PATCH

ENHANCING SAFETY AND WELL-BEING OF CHILDREN OF ADULT DRUG COURT PARTICIPANTS

COMMUNICATING ABOUT NICOTINE AND DIFFERENTIAL RISKS OF TOBACCO PRODUCTS

VLP VACCINE TECHNOLOGY

DATA DRIVEN DYNAMIC ACTIVITY/CONNECTIVITY METHODS FOR EARLY DETECTION OF ALZHEIMER?S - PROJECT SUMMARY/ABSTRACT THE DEVELOPMENT OF BIOMARKERS FOR IDENTIFYING PRECLINICAL OR PRODROMAL ALZHEIMER’S DISORDER ARE OF GREAT IN- TEREST. WHILE SOME INITIAL RESULTS BASED ON RESTING FMRI HAVE BEEN PRESENTED, ACCURACY, ROBUSTNESS, AND RELIA- BILITY ARE STILL RELATIVELY LOW. ONE HIGHLY PROMISING DIRECTION IS THE DEVELOPMENT OF DYNAMIC FUNCTIONAL ACTIVITY AND FUNCTIONAL CONNECTIVITY APPROACHES. THESE APPROACHES HAVE BEEN SHOWN TO BE ESPECIALLY PROMISING MOST LIKELY DUE TO THE HIGHLY DYNAMIC NATURE OF THE BRAIN AND THE UNCONSTRAINED NATURE OF RESTING FMRI. CURRENTLY, THERE ARE NO METHODS THAT CAN PROVIDE A FULL CHARACTERIZATION OF TEMPORAL, SPATIAL, AND SPATIO-TEMPORAL DYNAMICS NOR CAN MOST EXISTING APPROACHES CHARACTERIZE HETEROGENOUS SUBGROUPS OR COMPLEX MULTISCALE RELATIONSHIPS. WE WILL DEVELOP NEW METHODS THAT CAN EFFECTIVELY CAPTURE DYNAMIC CONNECTIVITY AND PROVIDE SUMMARY METRICS WITH A FOCUS ON INDIVIDUALIZED PREDICTION OF ALZHEIMER’S DISEASE WELL PRIOR TO THE ONSET OF THE ILLNESS. WE PROPOSE A NOVEL FAMILY OF MODELS THAT BUILDS ON THE WELL-STRUCTURED FRAMEWORK OF JOINT BLIND SOURCE SEPARATION TO CAPTURE A MORE COMPLETE CHARACTERIZATION OF (POTENTIALLY NONLINEAR) SPATIO-TEMPORAL DYNAMICS. OUR MODELS WILL ALSO PRO- DUCE A RICH SET OF METRICS TO CHARACTERIZE THE AVAILABLE DYNAMICS AND ENABLE IN DEPTH COMPARISON WITH CURRENTLY AVAILABLE MODELS. WE SHOW EVIDENCE THAT SUCH MEASURES ARE LIKELY TO BE CONSIDERABLY MORE SENSITIVE AND MORE ACCURATE IN CLASSIFYING INDIVIDUALS. WE WILL EXTENSIVELY VALIDATE OUR APPROACHES IN A VARIETY OF WAYS INCLUDING SIMULATIONS, CONCURRENT EEG/FMRI DATA, AND EVALUATION ON A LARGE NORMATIVE DATA SET. WE WILL APPLY THE DEVEL- OPED METHODS TO SEVERAL LARGE DATASETS INCLUDING A LARGE LONGITUDINAL SAMPLE OF INDIVIDUALS WHO HAVE BEEN SCANNED AT EMORY UNIVERSITY WITH RESTING FMRI WHO ALSO HAVE CSF AMYLOID AND TAU PET MEASURES. WE WILL USE THE DEVELOPED MARKERS TO PREDICT COGNITIVE DECLINE, AMYLOID, AND TAU LEVELS IN THESE DATA AND INCLUDE BOTH A DISCOVERY DATA SET AS WELL AS AN INDEPENDENT REPLICATION DATA SET. SUCCESSFUL COMPLETION OF OUR AIMS WILL BE AN IMPORTANT FIRST STEP TOWARDS PROVIDING AN OPPORTUNITY TO DEVELOP AND EVALUATE INTERVENTIONS EARLY ENOUGH TO HAVE A POSITIVE IMPACT ON LONG-TERM PROGNOSIS. WE WILL PROVIDE OPEN SOURCE TOOLS AND RELEASE DATA THROUGHOUT THE DURATION OF THE PROJECT VIA GITHUB, A WEB PORTAL AND THE NITRC REPOSITORY, HENCE ENABLING OTHER INVESTIGATORS TO COMPARE THEIR OWN METHODS WITH OUR OWN AS WELL AS TO APPLY THEM TO A LARGE VARIETY OF BRAIN DISORDERS. OUR TOOLS ALSO HAVE WIDE APPLICATION TO THE STUDY OF THE HEALTHY BRAIN AS WELL AS MANY OTHER DISEASES. 37

RESEARCH IN HEAVY ION NUCLEAR REACTIONS

MALE/FEMALE DIFFERENCES IN PSYCHOSIS AND MOOD DISORDERS:DYNAMIC IMAGING-GENOMIC MODELS FOR CHARACTERIZING AND PREDICTING PSYCHOSIS AND MOOD D

GRADUATE PSYCHOLOGY EDUCATION PROGRAMS

POLYMERASE INHIBITORS OF RESPIRATORY SYNCYTIAL VIRUS

MEANINGFUL ENGAGEMENT AND QUALITY OF LIFE AMONG ASSISTED LIVING RESIDENTS WITH DEMENTIA

ASSESSING THE INTENDED AND UNINTENDED CONSEQUENCES OF E-CIGARETTE TV ADVERTISING

CONTROLLING VSMC PROLIFERATION AND MIGRATION

EXAMINING CARBON MONOXIDE TO TREAT INFLAMMATORY CONDITIONS USING EXPERIMENTAL COLITIS MODELS

HIGH ANGULAR RESOLUTION COMMUNITY SCIENCE AT THE CHARA ARRAY -THE CENTER FOR HIGH ANGULAR RESOLUTION ASTRONOMY (CHARA) ARRAY IS THE NATION?S PREMIER FACILITY FOR LONG BASELINE OPTICAL INTERFEROMETRY. WITH THE NUMBER AND SIZE OF ITS TELESCOPES, THE LENGTH OF ITS BASELINES, AND THE RANGE OF WAVELENGTHS COVERED BY ITS BEAM COMBINERS, THE CHARA ARRAY IS A UNIQUELY POWERFUL FACILITY FOR MILLIARCSECOND IMAGING. WITH ADAPTIVE OPTICS AND FOUR NEW BEAM COMBINERS, THE ARRAY IS REACHING DEEPER THAN EVER. SINCE 2004 CHARA RESULTS HAVE APPEARED IN SOME 245 PAPERS IN THE REFEREED LITERATURE. THIS INCLUDES OBSERVATIONS OBTAINED DURING THE HIGH-DEMAND OPEN ACCESS PROGRAM SUPPORTED BY NSF FOR SOME YEARS, AND OPERATED IN COLLABORATION WITH NSF?S NATIONAL OPTICAL-INFRARED RESEARCH LABORATORY. THIS AWARD EXTENDS THAT PROGRAM FOR ANOTHER THREE YEARS, AND INCLUDES A NEW SNAPSHOT IMAGING MODE. THE TEAM ALSO PLANS TO OFFER USER SUPPORT, COMMUNITY WORKSHOPS, AND AN ACCESSIBLE DATA ARCHIVE. CHARA WILL FOSTER COLLABORATIONS WITH AMATEUR ASTRONOMERS THROUGH THE AMERICAN ASSOCIATION OF VARIABLE STAR OBSERVERS. CHARA TRAINS GRADUATE STUDENTS TO BUILD AND USE PRECISION TECHNOLOGY. THE CHARA ARRAY ACHIEVES SUB-MILLIARCSECOND RESOLUTION AT VISIBLE AND NEAR-INFRARED WAVELENGTHS, AND CAN BE USED TO RESOLVE THE RADII OF STARS ALL ALONG THE MAIN SEQUENCE AND AT DIFFERENT STAGES AS STARS EVOLVE OFF THE MAIN SEQUENCE. THE ARRAY REVEALS THE IMPACT OF LIMB- AND GRAVITY-DARKENING, THE SPATIAL DISTRIBUTION AND SIZE OF STAR-SPOTS AND ACTIVITY IN CONVECTION ZONES, AND PROVIDES PHYSICAL PROPERTIES OF EXOPLANET HOST STARS. THE CHARA ARRAY RESOLVES BINARY STARS, MAPS ORBITS, AND PROBES INTERACTING SYSTEMS. EXTRAGALACTIC OBSERVATIONS PROBE THE STRUCTURE OF ACTIVE GALACTIC NUCLEI CORES TO SHOW HOW SUPERMASSIVE BLACK HOLES IMPACT ACCRETION AND TRIGGER OUTFLOWS. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.- SUBAWARDS ARE NOT PLANNED FOR THIS AWARD.

WRITING IN ADULT SECONDARY EDUCATION CLASSES (W-ASE)

(SURI) SPACE DOMAIN AWARENESS IN A PHOTON-STARVED ENVIRONMENT (SDAPSE)

FLEXIBLE MULTIVARIATE MODELS FOR LINKING MULTI-SCALE CONNECTOME AND GENOME DATA IN ALZHEIMER'S DISEASE AND RELATED DISORDERS

PHOTOPERIODIC CONTROL OF OBESITY

DEVELOPING INHIBITORS OF SEASONAL AND PANDEMIC INFLUENZA VIRUSES - SUMMARY INFLUENZA VIRUSES ARE A LEADING CAUSE OF HUMAN DISEASE DUE TO RESPIRATORY VIRAL INFECTION WORLDWIDE. IT IS THE OVERARCHING OBJECTIVE OF THIS PROJECT TO ADVANCE PRODRUG CONJUGATES OF 4’-FLUOROURIDINE (4’-FLU), A NOVEL PYRIMIDINE ANALOG WITH CONFIRMED BROAD ORAL EFFICACY AGAINST INFLUENZA VIRUSES, AND AT LEAST ONE NON-NUCLEOSIDE INHIBITOR OF THE INFLUENZA VIRUS POLYMERASE COMPLEX, TO THE STAGE OF FORMAL PRECLINICAL DEVELOPMENT AND ASSEMBLY OF AN INVESTIGATIONAL NEW DRUG-ENABLING PACKAGE. THE PROJECT DESIGN IS DRIVEN BY OUR UNDERLYING HYPOTHESIS THAT EFFECTIVE NEXT-GENERATION THERAPEUTICS FOR THE TREATMENT OF INFLUENZA MUST BE ORALLY AVAILABLE, DISPLAY A BROAD INDICATION SPECTRUM AGAINST INFLUENZA VIRUS ISOLATES OF HUMAN, AVIAN, AND SWINE LINEAGES, AND IDEALLY COVER BOTH INFLUENZA A (IAV) AND B (IBV) VIRUSES. THESE PRODUCT PROFILE DEMANDS ARE DERIVED FROM THE CLINICAL BURDEN IMPOSED BY THE DIVERSE SPECTRUM OF SEASONAL INFLUENZA VIRUSES, THE PANDEMIC POTENTIAL ARISING FROM SPILLOVER OF ZOONOTIC AVIAN VIRUSES INTO THE HUMAN POPULATION, AND CURRENT FDA RECOMMENDATIONS THAT RECOGNIZE OUTPATIENT ADULTS SUFFERING FROM SEASONAL INFLUENZA AS THE PRIMARY PATIENT POPULATION FOR INITIAL CLINICAL TESTING. THESE DEVELOPMENTAL OBJECTIVES ARE BEST MET WITH DIRECT ACTING THERAPEUTICS, SINCE HOST-TARGETED ANTIVIRAL THERAPIES, ALTHOUGH OFTEN TANTALIZINGLY BROAD IN INDICATION RANGE, ARE PRONE TO UNACCEPTABLE SIDE EFFECTS THAT ARE INCOMPATIBLE WITH THE PRIMARY PATIENT GROUP PURSUED. IN PREVIOUS WORK UNDERPINNING THIS PROGRAM, WE HAVE DEMONSTRATED BROAD-SPECTRUM ANTIVIRAL ACTIVITY OF 4’-FLU IN CULTURED CELLS AND ANIMAL INFECTION MODELS AGAINST A CLINICALLY SIGNIFICANT PANEL OF RNA VIRUSES. AGAINST THE INFLUENZA VIRUS INDICATION, 4’-FLU HAS CONFIRMED ORAL EFFICACY AGAINST SEASONAL, PANDEMIC, AND HIGHLY PATHOGENIC AVIAN INFLUENZA VIRUSES IN RODENT AND NON-RODENT MODELS. THE COMPOUND TRIGGERS IMMEDIATE CHAIN TERMINATION OF THE INFLUENZA VIRUS RNA-DEPENDENT RNA POLYMERASE (RDRP) COMPLEX AND CARRIES A HIGH BARRIER TO VIRAL RESISTANCE. IN PREPARATION OF CLINICAL DEVELOPMENT, WE HAVE GENERATED PRODRUG CONJUGATES OF 4’-FLU TO OPTIMIZE DELIVERY ACROSS THE GASTROINTESTINAL EPITHELIUM. TO BROADEN OUR INFLUENZA VIRUS RDRP INHIBITOR PORTFOLIO, WE HAVE IDENTIFIED A SET OF NON-NUCLEOSIDE RDRP INHIBITORS IN A LARGE-SCALE HIGH-THROUGHPUT SCREENING CAMPAIGN THAT WILL BE ADVANCED SIMULTANEOUSLY AS COMPANION DRUGS OR FOR COMBINATION THERAPY IN A MULTI- PRONGED APPROACH. TO SELECT A CLINICAL CANDIDATE FOR FORMAL DEVELOPMENT, 4’-FLU PRODRUG CONJUGATES WILL BE SUBJECTED TO DE-RISKING EFFICACY AND TOLERABILITY TESTING IN RELEVANT RODENT AND NON-RODENT ANIMAL MODELS AND DOSING PARADIGMS EXPLORED THROUGH INTERFACING OF DYNAMIC PK PROFILES WITH PERFORMANCE IN HUMAN AIRWAY EPITHELIUM ORGANOIDS (AIM 1). NON-NUCLEOSIDE RDRP INHIBITOR LEAD CANDIDATE SCAFFOLDS WILL BE SYNTHETICALLY DEVELOPED, MECHANISTICALLY CHARACTERIZED, AND SUBJECTED TO PROOF-OF-CONCEPT EFFICACY TESTING (AIM 2). EMERGING NON-NUCLEOSIDE LEADS WILL BE QUERIED FOR COMBINATION THERAPY WITH THE 4’-FLU CLINICAL CANDIDATE AND THE EFFECT OF MONO- AND COMBINATION THERAPY ON SUPPRESSING INFLUENZA VIRUS TRANSMISSION DETERMINED IN FERRETS (AIM 3).

1) TO SUPPORT FOR A PROGRAM AS DESCRIBED IN "DUAL MASTER'S PROGRAM IN APPLIED ECONOMMICS FOR INDONESIANS";2) TO OBLIGATE FUNDS $805 267;3) TO PR

PERSONALIZED INTEGRATED ALCOHOL AND SEXUAL ASSAULT PREVENTION AMONG COLLEGE STUDENTS - PROJECT ABSTRACT THE OVERARCHING GOAL OF THIS R01 IS TO TEST THE EFFICACY OF A BEHAVIORAL INTERVENTION FOR HEAVY EPISODIC DRINKING (HED) AND SEXUAL ASSAULT AMONG COLLEGE STUDENTS. SEXUAL AND GENDER MINORITY (SGM) STUDENTS EXPERIENCE SEXUAL ASSAULT AND ENGAGE IN HED AT EVEN HIGHER RATES THAN THEIR CISGENDER, HETEROSEXUAL PEERS. THEREFORE, TAILORED AND PERSONALIZED INTERVENTIONS ARE NEEDED FOR HED AND SEXUAL ASSAULT TO ADDRESS THE UNIQUE NEEDS OF COLLEGE STUDENTS BASED ON GENDER IDENTITY AND SEXUAL ORIENTATION. THE ALCOHOL AND SEXUAL ASSAULT PREVENTION (ASAP) PROGRAM WAS DEVELOPED BY THE RESEARCH TEAM WITH AN NIAAA-FUNDED PLANNING GRANT (R34) AND IS THE ONLY INTERVENTION THAT TARGETS BOTH HED AND SEXUAL ASSAULT (VICTIMIZATION RISK REDUCTION, PERPETRATION PREVENTION, AND BYSTANDER INTERVENTION TRAINING) IN AN INTEGRATED MANNER. ASAP PROVIDES TAILORED CONTENT ON ALCOHOL USE AND SEXUAL ASSAULT BASED ON GENDER IDENTITY AND SEXUAL ORIENTATION USING A SOCIAL NORMS AND PERSONALIZED FEEDBACK APPROACH. USABILITY TESTING AND FINDINGS FROM A RANDOMIZED CONTROLLED PILOT FEASIBILITY TRIAL SUGGEST USABILITY, FEASIBILITY, AND PRELIMINARY EFFICACY AND WARRANT RIGOROUS RANDOMIZED CONTROLLED TRIAL TESTING. ASAP IS DELIVERED IN A BRIEF, WEB-BASED FORMAT, AND ALTHOUGH SHORT-TERM OUTCOMES ARE PROMISING, MORE EFFORT IS NEEDED TO ENSURE LONG-TERM EFFICACY. THEREFORE, THE CURRENT STUDY INCLUDES AN ASSESSMENT OF ASAP AS WELL AS AN INNOVATIVE ASSESSMENT OF A 6-MONTH BOOSTER (ASAP+BOOSTER) SESSION TO DETERMINE THE MOST EFFECTIVE WAY TO DISSEMINATE ASAP TO COLLEGES NATIONWIDE IF FOUND TO BE EFFECTIVE. THE CURRENT STUDY INCLUDES THE FOLLOWING AIMS: 1A) TO TEST THE EFFICACY OF ASAP AND ASAP+BOOSTER AMONG COLLEGE STUDENTS IN REDUCING HED AND SEXUAL ASSAULT BOTH SHORT- AND LONG-TERM AMONG THREE RISK GROUPS (1. CISGENDER HETEROSEXUAL MEN; 2. CISGENDER HETEROSEXUAL WOMEN; 3. SGM); 1B) TEST THE RELATIVE EFFICACY OF A BOOSTER SESSION ON LONG-TERM ALCOHOL USE AND SA OUTCOMES; AND 2) INVESTIGATE THE MECHANISMS THROUGH WHICH ASAP CONDITIONS IMPACT ALCOHOL USE AND SA. OUTCOMES WILL BE ASSESSED AT 3-, 6-, 9-, AND 12-MONTHS POST- INTERVENTION. BY ACCOMPLISHING THESE AIMS, WE WILL ASSESS THE EFFICACY OF ASAP, A PROMISING INTERVENTION DEVELOPED BY THE RESEARCH TEAM. ASAP HAS THE POTENTIAL TO REDUCE ALCOHOL USE AMONG YOUNG ADULTS AS WELL AS REDUCE COLLEGE SA AND INCLUDES A FOCUS ON SGM POPULATIONS, ADDRESSING NIAAA AND PUBLIC HEALTH PRIORITIES.

SEX DIFFERENCES IN THE SOCIAL BRAIN

LIBERATE

PROMOTING PROSOCIAL BYSTANDER BEHAVIOR IN INTOXICATED MEN: EVALUATION OF REALCONSENT2.0

NEUROBIOLOGY OF SOCIAL BEHAVIOR

PAWS: EFFICACY

HEALTHY START INITIATIVE - PROJECT TITLE: GEORGIA STRONG FAMILIES PROGRAM (GSFP) ADDRESS: 55 PARK PLACE ATLANTA, GEORGIA 30303 PROJECT DIRECTOR NAME: TWANNA NELSON CONTACT PHONE NUMBER: 4044130301 EMAIL ADDRESS: TNELSON45@GSU.EDU WEBSITE ADDRESS: HTTPS://GHPC.GSU.EDU/ GRANT FUNDS REQUESTED: $1,100,000 ANNUALLY POPULATION SERVED: THE GSFP TARGET POPULATION IS BLACK WOMEN OF CHILDBEARING AGE (14-51) RESIDING IN THE PROJECT AREA. THIS POPULATION HAS BEEN DETERMINED TO HAVE THE HIGHEST INFANT AND MATERNAL MORTALITY RATES THEREBY NEEDING THE SUPPORT OF HEALTHY START. CHALLENGE (NEEDS ADDRESSED) THE HEALTHY START FUNDING WILL PROVIDE GEORGIA WITH AN OPPORTUNITY TO FURTHER STRENGTHEN THE SYSTEM OF CARE FOR FAMILIES AND EXPAND SERVICES. GEORGIA CONTINUES TO NEED LAYERED EARLY INTERVENTION AND PREVENTION SERVICES TO ADDRESS ADVERSE HEALTH OUTCOMES. GEORGIA IS SEEN AT THE TOP OF MANY LISTS, INCLUDING FORBES’ 2023 WORST STATES FOR HEALTHCARE LIST, WHICH COMPILES TWENTY-FOUR METRICS SPANNING FOUR KEY CATEGORIES: HEALTH ACCESS, HEALTHCARE OUTCOMES, HEALTHCARE COST, AND QUALITY OF HOSPITAL CARE. MORE SPECIFICALLY THE 3-YEAR IMR (2019-2021) FOR THE TARGET POPULATION IN THE EIGHT COUNTIES IS 12.5 (COMPARED TO 5.9 FOR WHITE WOMEN IN THE SAME REGION), THE 3-YEAR PRETERM BIRTH RATE IS 17.8 (COMPARED TO 12.2 FOR WHITE WOMEN), AND THE 3-YEAR LOW BIRTHWEIGHT RATE IS 17.8 (COMPARED TO 12.2 FOR WHITE WOMEN). THIS EIGHT-COUNTY REGION IS SERVED BY TWO HOSPITALS WITH OBSTETRIC CARE, TWO RURAL HEALTH CLINICS, AND HAS AN OB-GYN PROVIDER RATE OF 7.7, WITH HALF OF THE COUNTIES NOT HAVING ANY OB-GYN PROVIDERS WITHIN THE COUNTY. METHODOLOGY (PROPOSED SERVICES): THE GOAL OF THE GSFP IS TO IMPROVE CHILD AND FAMILY OUTCOMES BY IMPLEMENTING STRATEGIES WITHIN A COMMUNITY-BASED PUBLIC HEALTH MATERNAL AND EARLY CHILDHOOD SYSTEM. GSFP IS DESIGNED TO 1) IMPROVE COORDINATION OF SERVICES FOR CHILDREN AND FAMILIES AT THE STATE AND LOCAL LEVELS; AND 2) PROVIDE COMPREHENSIVE SERVICES TO IMPROVE OUTCOMES FOR CHILDREN AND FAMILIES WHO RESIDE IN CRISP, CLAY, DOOLY, MUSCOGEE, STEWART, SUMTER, TALBOT, AND TAYLOR COUNTIES. THE PROJECT AREA IS COMPRISED OF MOSTLY RURAL COUNTIES. FUNDING SUPPORTS THE IMPLEMENTATION OF GSFP WHICH TARGETS THE NEEDS OF EXPECTANT PARENTS, CHILDREN AGED FROM BIRTH TO 18 MONTHS, AND THEIR FAMILIES. THE SYSTEM FUNCTIONS INCLUDE IDENTIFICATION, REFERRAL, SCREENING, PARENT EDUCATION, AND LINKAGE TO APPROPRIATE COMMUNITY SERVICES. THIS REQUIRES STRONG COLLABORATIONS BETWEEN COMMUNITY AGENCIES SERVING CHILDREN AND FAMILIES, WHICH THE GSFP HAS HISTORICALLY BEEN SUCCESSFUL THROUGH ITS ESTABLISHED COMMUNITY CONSORTIUM. ONE MAJOR SERVICE STRATEGY FOR THIS SYSTEM IS THE USE OF THE PARTNERS FOR HEALTHY BABIES HOME-VISITING MODEL. THE GSFP WILL PROVIDE BOTH VIRTUAL AND IN-PERSON VISITS TO ENSURE FAMILIES ARE SUPPORTED BEFORE, DURING, AND AFTER PREGNANCY. THE GSFP WILL ALSO PROVIDE ENHANCED SERVICES TO THE TARGET POPULATION THROUGH A NURSE PRACTITIONER (NP) AND PROVISIONS FOR DOULAS SERVICES. THE NP WILL PROVIDE HOME VISITS, AND EDUCATION TO FAMILIES AND STAFF ON WARNING SIGNS ALONG WITH AN EMPHASIS ON ENCOURAGING POSTPARTUM FOLLOW-UP AND CARE. MOTHERS ENROLLED WILL HAVE ACCESS TO DOULA SERVICES DURING PREGNANCY, FOR SUPPORT DURING CHILDBIRTH AND UP TO 3 MONTHS POSTPARTUM. GSFP WILL BE INTENTIONAL ABOUT INCORPORATING MENTAL/BEHAVIORAL HEALTH AS A KEY STRATEGY TO IMPROVING BOTH PHYSICAL AND MENTAL WELL-BEING. THE GSFP WILL ADDRESS MENTAL AND BEHAVIORAL HEALTH CHALLENGES IN THE FATHER, MOTHER, AND INFANTS TO ENSURE A HIGHER QUALITY OF LIFE. IMPLEMENTATION ALSO INCLUDES THE DEVELOPMENT OF A COHESIVE PLAN TO PROMOTE PROGRAM QUALITY AND EFFECTIVENESS, AS WELL AS A COORDINATED DATA SYSTEM TO GUIDE DECISION-MAKING AND ASSIST COUNTIES IN MONITORING PROGRESS TOWARD DESIRED RESULTS AND CONTINUOUS QUALITY IMPROVEMENT.

INFANT-TODDLER COURT PROGRAM - CENTER OF EXCELLENCE FOR CHILDREN’S BEHAVIORAL HEALTH GEORGIA HEALTH POLICY CENTER GEORGIA STATE UNIVERSITY 55 PARK PLACE, ATLANTA, GA 30303 (404) 413-0314 HTTPS://GACOEONLINE.GSU.EDU/ PROJECT DIRECTOR: ANN MUKHERJEE, MPP EMAIL ADDRESS: AHEDGES@GSU.EDU THE CENTER OF EXCELLENCE FOR CHILDREN’S BEHAVIORAL HEALTH (COE OR CENTER) IS SEEKING HRSA FUNDING OPPORTUNITY HRSA-22-073, INFANT-TODDLER COURT PROGRAM – STATE AWARD. THE CENTER IS SEEKING $625,000 PER YEAR FOR A 5-YEAR PROJECT PERIOD. THE CENTER PROPOSES A 5-YEAR PROJECT BEGINNING WITH A YEARLONG PLANNING PHASE TO DEVELOP AN INFANT-TODDLER COURT (ITC) LEADERSHIP TEAM AND STATEWIDE ACTION PLAN THAT WILL GUIDE 4 YEARS OF ITC IMPLEMENTATION. DURING IMPLEMENTATION, THE COE WILL INITIATE 3 ITC TEAMS IN LOCAL JURISDICTIONS THROUGH A REQUEST FOR APPLICATIONS (RFA) PROCESS AND PROVIDE STATEWIDE LEADERSHIP AND COORDINATION TO INCREASE CAPACITY FOR AND KNOWLEDGE OF THE ITC APPROACH ACROSS THE STATE. THE GOAL OF GEORGIA’S INFANT-TODDLER COURT (ITC) PROGRAM IS TO IMPROVE STATEWIDE SYSTEMS AND POLICIES TO SUPPORT YOUNG CHILDREN (AGES 0-3) AND THEIR FAMILIES WHO ARE INVOLVED, OR AT RISK OF INVOLVEMENT, WITH THE CHILD WELFARE SYSTEM, AND BUILD CAPACITY TO PREVENT CHILD MALTREATMENT MORE BROADLY. THE STATE WILL ACHIEVE THIS GOAL BY EXPANDING EVIDENCE-BASED INFANT-TODDLER COURT TEAMS AND IMPROVING EARLY DEVELOPMENTAL HEALTH AND WELL-BEING OF INFANTS, TODDLERS, AND THEIR FAMILIES BY COMPLETING THE FOLLOWING OBJECTIVES: ESTABLISH LEADERSHIP CAPACITY IN GEORGIA TO INFORM ITC IMPLEMENTATION THROUGH THE CREATION AND TRAINING OF A STATE-LEVEL ITC LEADERSHIP TEAM. THE LEADERSHIP TEAM WILL INCLUDE STATE-LEVEL PARTNERS, LOCAL LEADERS, AND FAMILIES WITH LIVED EXPERIENCE. DEVELOP A STATE ACTION PLAN TO GUIDE ITC IMPLEMENTATION IN THE STATE THROUGH A SYSTEMATIC PROCESS LED BY THE STATE-LEVEL ITC LEADERSHIP TEAM AND INVOLVING THE ITC NATIONAL RESOURCE CENTER, RELEVANT STAKEHOLDERS, AND FAMILIES WITH LIVED EXPERIEN CE. INCREASE CAPACITY THROUGH TRAINING OF STATE AND LOCAL PARTNERS IN THE ITC APPROACH AND TOPICS RELATED TO THE DEVELOPMENTAL HEALTH, MENTAL HEALTH, AND WELL-BEING OF VERY YOUNG CHILDREN. ESTABLISH LOCAL CAPACITY FOR ITC IMPLEMENTATION BY ESTABLISHING THREE LOCAL ITC SITES THROUGH A REQUEST FOR APPLICATIONS PROCESS INFORMED BY THE STATE ACTION PLAN, ITC LEADERSHIP TEAM, AND FAMILIES WITH LIVED EXPERIENCE. IMPROVE YOUTH AND FAMILY OUTCOMES DURING AND AFTER CHILD WELFARE AND/OR COURT INVOLVEMENT DEMONSTRATED THROUGH COLLECTION AND EVALUATION OF PROGRAM OUTCOMES DATA AT THE THREE LOCAL ITC SITES. ESTABLISH SUSTAINABILITY AND SCALING PLANS UTILIZING EVALUATION DATA AND LEARNINGS FROM IMPLEMENTATION TO INFORM SUSTAINABILITY AND FUTURE SCALING OF THE MODEL ACROSS GEORGIA. THE COE IS POSITIONED TO LEAD THIS WORK GIVEN ITS CURRENT LEADERSHIP IN STATEWIDE INITIATIVES BUILDING INFANT AND EARLY CHILDHOOD SYSTEMS OF CARE AND DEVELOPING SYSTEMS OF CARE FOR CHILDREN WITH BEHAVIORAL HEALTH NEEDS. THE CENTER HAS ESTABLISHED MULTI-SECTOR AND CROSS-AGENCY PARTNERSHIPS THROUGHOUT THE STATE, INCLUDING CONNECTIONS AND ENGAGEMENT WITH FAMILIES WHO HAVE LIVED EXPERIENCE NAVIGATING SERVICES FOR THEIR YOUNG CHILDREN ACROSS MULTIPLE STATE AGENCIES. THE COE AND ITS PARTNERS RECOGNIZE THE INCREDIBLE IMPORTANCE OF THE PRENATAL TO 3 PERIOD OF LIFE. THIS FOUNDATION OF COMMON UNDERSTANDING THAT YOUNG CHILDREN HAVE UNIQUE DEVELOPMENTAL NEEDS IS A STRENGTH OF THE STATE PARTNERS AND WILL HELP THE LEADERSHIP TEAM TRANSITION QUICKLY FROM KICK-OFF TO PLANNING AND IMPLEMENTATION.

ESTABLISHING SMOKE-FREE HOMES WITH FAMILIES INVOLVED IN CHILD PROTECTIVE SERVICES: AN EFFECTIVENESS-IMPLEMENTATION TRIAL OF AN INTEGRATED PROGRAM - PROJECT ABSTRACT CHILD EXPOSURE TO SECONDHAND SMOKE (SHS) IS LINKED TO MULTIPLE FORMS OF CANCER THROUGHOUT THE LIFESPAN. YOUNG CHILDREN LIVING IN LOW-SOCIOECONOMIC STATUS HOUSEHOLDS ARE AT INCREASED RISK FOR SHS EXPOSURE. FAMILIES INVOLVED WITH THE CHILD PROTECTION SYSTEM AS THE RESULT OF SUBSTANTIATED CHILD MALTREATMENT ARE AN ESPECIALLY HIGH-RISK GROUP FOR SHS, AS THESE FAMILIES ARE OFTEN LIVING IN POVERTY AND REPORT HIGH DAILY SMOKING RATES. IMPORTANTLY, CHILD MALTREATMENT VICTIMIZATION ALSO INCREASES RISK OF CANCER AND PREMATURE DEATH FROM CANCER, INDEPENDENT OF PARENT SMOKING BEHAVIOR. IDENTIFYING WAYS TO BROADLY DISSEMINATE EFFECTIVE SHS PREVENTION PROGRAMS TO THESE HIGH-RISK FAMILIES IS AN IMPORTANT STRATEGY FOR REDUCING CANCER DISPARITIES. WE PROPOSE AN EFFECTIVENESS-IMPLEMENTATION HYBRID TRIAL TYPE 1 TO EXAMINE THE IMPACT OF INTEGRATING TWO EVIDENCE-BASED PROGRAMS, SOME THINGS ARE BETTER OUTSIDE (SHS PREVENTION PROGRAM) AND SAFECARE® (CHILD MALTREATMENT PREVENTION PROGRAM), ON ESTABLISHING A SMOKE-FREE HOME AND ON IMPLEMENTATION PROCESS OUTCOMES. AIM 1 FOCUSES ON THE REFINEMENT OF THE STANDARDIZED INTEGRATION (SYSTEMATIC BRAIDING) OF THE TWO PROGRAMS INTO “SMOKE-FREE SAFECARE (SFSC).” AIMS 2 AND 3 FOCUS ON THE HYBRID TRIAL. FIFTY CERTIFIED SAFECARE PROVIDERS WILL BE RECRUITED AND RANDOMLY ASSIGNED TO DELIVER EITHER SFSC OR STANDARD SAFECARE. PROVIDERS WILL EACH SERVE TEN RESEARCH FAMILIES (N = 500) WHO MEET THE INCLUSION CRITERIA (MOTHER OR ANOTHER PERSON RESIDING IN THE HOME SMOKES AT HOME). THE PRIMARY OUTCOME, SMOKE-FREE HOME STATUS, WILL BE MEASURED VIA SELF-REPORT AT 4-TIMEPOINTS (BASELINE, 8-WEEKS, 20-WEEKS, AND 1-YEAR), AND VALIDATED VIA AIR NICOTINE MONITOR AT 8 WEEKS AND 1-YEAR (AIM 2). PROCESS MEASURES WILL BE COLLECTED TO EXAMINE HOW THE BRAIDED INTERVENTION IMPACTS PROVIDER FIDELITY, DELIVERY TIME AND COSTS, AND OTHER PROCESS MEASURES (AIM 3). IF EFFECTIVE, SFSC CAN BE EFFICIENTLY DISSEMINATED FOR WIDESPREAD ADOPTION BY THE NATIONAL SAFECARE TRAINING AND RESEARCH CENTER TO THE OVER 100 ACCREDITED SAFECARE AGENCIES ACROSS THE UNITED STATES AND WORLDWIDE THAT SERVE PARENTS INVOLVED WITH CHILD PROTECTION SERVICES, REDUCING CANCER RISK AND DISPARITIES FOR A HIGH-RISK POPULATION.

ORTHOGONAL UBIQUITIN TRANSFER TO PROFILE E3 SUBSTRATE SPECIFICITY

CYBERCORPS SCHOLARSHIP FOR SERVICE: CYBERSECURITY WORKFORCE PREPARATION IN THE AGE OF ARTIFICIAL INTELLIGENCE -THIS PROJECT AIMS TO ADDRESS THE GROWING NEED FOR A HIGHLY-SKILLED NATIONAL CYBERSECURITY WORKFORCE CAPABLE OF RESPONDING TO RAPIDLY EVOLVING CHALLENGES IN THE AGE OF ARTIFICIAL INTELLIGENCE (AI). WITH FUNDING FROM THE NSF CYBERCORPS(R) SCHOLARSHIP FOR SERVICE (SFS) PROGRAM, GEORGIA STATE UNIVERSITY (GSU) WILL PRODUCE GRADUATES CAPABLE OF ASSUMING A VARIETY OF CYBERSECURITY ROLES IN THE U.S. GOVERNMENT. MOREOVER, THE PROJECT WILL INCREASE THE DIVERSITY OF THE FEDERAL CYBERSECURITY WORKFORCE, LEVERAGING GSU'S POSITION AS A MINORITY-SERVING INSTITUTION (MSI). THE SFS PROJECT WILL EMPHASIZE RECRUITING AND GRADUATING HIGHLY QUALIFIED CANDIDATES FROM GROUPS THAT HAVE REMAINED UNDERREPRESENTED IN THE CYBERSECURITY FIELD, INCLUDING THOSE WITH MILITARY-AFFILIATIONS, FIRST-GENERATION COLLEGE ATTENDEES, AND LOW-INCOME STUDENTS. THIS PROJECT'S UNIQUE AND INNOVATIVE FOCUS WILL IMPACT THE NATION'S COMPETITIVENESS AND THE U.S. GOVERNMENT BY PRODUCING HIGHLY SKILLED CYBERSECURITY PROFESSIONALS WHO CAN DEVELOP AND DEPLOY TRUSTWORTHY CYBERSYSTEMS TO ADDRESS GRAND CHALLENGES FACING SOCIETY. GSU HAS ESTABLISHED A STRONG CURRICULUM IN CYBERSECURITY AND PRIVACY THAT BALANCES TECHNICAL RIGOR AND HANDS-ON EXPERIENCES, OFFERING STUDENTS THE OPPORTUNITY TO STUDY VARIOUS TOPICS IN CYBERSECURITY AND PRIVACY. THE PROJECT FOCUSES ON TRAINING AND PREPARING A WORKFORCE WITH INTEGRATED CYBERSECURITY, PRIVACY, AI, AND MACHINE LEARNING COMPETENCIES TO APPLY AI EXPERTISE TO CYBERSECURITY AND BUILD ROBUST AND TRUSTWORTHY AI SYSTEMS. STUDENTS WILL BE PREPARED WITH THE KNOWLEDGE AND PRACTICAL SKILLS TO APPLY AI EXPERTISE AND UNDERSTAND AI'S SAFETY, SECURITY, PRIVACY, RELIABILITY, FAIRNESS, AND ETHICAL IMPLICATIONS. OVER A FIVE-YEAR PERIOD THE PROJECT WILL PROVIDE SCHOLARSHIPS TO 25 STUDENTS STUDYING ISSUES AT THE INTERSECTION OF CYBERSECURITY AND AI. THE SFS STUDENTS WILL PARTICIPATE IN AN INTENSIVE ACADEMIC PROGRAM IN CYBERSECURITY, PRIVACY, AND TRUSTWORTHY AI, INCLUDING COURSEWORK AND RESEARCH IN CUTTING-EDGE AREAS TO SHARPEN THE STUDENTS' ABILITY FOR CREATIVE THINKING, MAKING THEM BETTER CYBERSECURITY PROFESSIONALS. IN ADDITION TO COMPLETING RIGOROUS, REQUIRED COURSEWORK, THE SFS SCHOLARS WILL ENGAGE IN EXPERIENTIAL LEARNING THROUGH OPPORTUNITIES FOR INDIVIDUAL AND GROUP RESEARCH PROJECTS AND OTHER EXTRACURRICULAR ACTIVITIES, WHICH WILL PROVIDED DEEPLY TECHNICAL AS WELL AS INTERDISCIPLINARY LEARNING EXPERIENCES AND LEADERSHIP DEVELOPMENT TAILORED TO EACH STUDENT'S PREPARATION AND ASPIRATION. THIS PROJECT IS SUPPORTED BY THE CYBERCORPS(R) SCHOLARSHIP FOR SERVICE (SFS) PROGRAM, WHICH FUNDS PROPOSALS ESTABLISHING OR CONTINUING SCHOLARSHIP PROGRAMS IN CYBERSECURITY AND ALIGNS WITH THE U.S. NATIONAL CYBER STRATEGY TO DEVELOP A SUPERIOR CYBERSECURITY WORKFORCE. FOLLOWING GRADUATION, SCHOLARSHIP RECIPIENTS ARE REQUIRED TO WORK IN CYBERSECURITY FOR A FEDERAL, STATE, LOCAL, OR TRIBAL GOVERNMENT ORGANIZATION FOR THE SAME DURATION AS THEIR SCHOLARSHIP SUPPORT. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.

SEX DIFFERENCES IN STRESS INOCULATION OF ADDICTION-LIKE PHENOTYPES

ASSESSING THE EFFECTIVENESS OF THE SECOND CHANCE ACT GRANT PROGRAM THROUGH A PHASED EVALUATION APPROACH USING AN IMPLEMENTATION SCIENCE MIXED METHODS APPROACH

DATA-DRIVEN SOLUTIONS FOR TEMPORAL, SPATIAL, AND SPATIOTEMPORAL DYNAMIC FUNCTIONAL CONNECTIVITY - PROJECT SUMMARY/ABSTRACT EXISTING APPROACHES TO ESTIMATE AND CHARACTERIZE WHOLE BRAIN TIME-VARYING CONNECTIVITY FROM FMRI DATA HAVE SHOWN CONSIDERABLE PROMISE, WITH EXPONENTIAL GROWTH IN RESEARCH IN THIS FIELD. WE AND OTHERS HAVE DEVELOPED A POWERFUL SET OF TOOLS THAT ARE NOW IN WIDE USE IN THE COMMUNITY. HOWEVER, THE IMPACT OF MENTAL ILLNESS ON BRAIN CONNECTIVITY IS COMPLEX, AND AS WE SHOW, LIMITATIONS IN EXISTING METHODS OFTEN RESULT IN MISSING IMPORTANT FEATURES ASSOCIATED WITH BRAIN DISORDERS (E.G. TRANSIENT FRACTIONATION OF THE SPATIAL STRUCTURE OF BRAIN NETWORKS). SOME OF THESE IMPORTANT LIMITATIONS INCLUDE 1) THE MOST WIDELY-USED APPROACHES OFTEN REQUIRE A NUMBER OF PRIOR AND LIMITING ASSUMPTIONS THAT ARE NOT WELL STUDIED, 2) METHODS OFTEN ASSUME LINEAR RELATIONSHIPS EITHER WITHIN OR BETWEEN NETWORKS OVER TIME, AND 3) METHODS ASSUME SPATIALLY FIXED NODES AND IGNORE THE POSSIBILITY OF SPATIALLY FLUID EVOLUTION OF NETWORKS OVER TIME. WE PROPOSE A NOVEL FAMILY OF MODELS THAT BUILDS ON THE WELL-STRUCTURED FRAMEWORK OF JOINT BLIND SOURCE SEPARATION TO CAPTURE A MORE COMPLETE CHARACTERIZATION OF (POTENTIALLY NONLINEAR) SPATIO-TEMPORAL DYNAMICS WHILE PROVIDING A WAY TO RELAX OTHER LIMITING ASSUMPTIONS. OUR MODELS WILL ALSO PRODUCE A RICH SET OF METRICS TO CHARACTERIZE THE AVAILABLE DYNAMICS AND ENABLE IN DEPTH COMPARISON WITH CURRENTLY AVAIL- ABLE MODELS INCLUDING THOSE THAT ARE MODEL BASED. WE WILL EXTENSIVELY VALIDATE OUR APPROACHES IN A VARIETY OF WAYS INCLUDING SIMULATIONS AND EVALUATION OF RIGOR AND ROBUSTNESS IN LARGE NORMATIVE DATA SETS. FINALLY, WE WILL APPLY THE DEVELOPED TOOLS TO STUDY THE IMPORTANT AREA OF DYNAMIC PROPERTIES IN MENTAL ILLNESSES INCLUDING SCHIZ- OPHRENIA, BIPOLAR DISORDER, AND THE AUTISM SPECTRUM. THERE IS CONSIDERABLE EVIDENCE OF DISRUPTION OF DYNAMICS IN ALL THREE DISORDERS, AND AS WE SHOW THE USE OF STATIC (OR EVEN EXITING DYNAMIC) APPROACHES CAN MISS IMPORTANT INFORMATION ABOUT BRAIN RELATED DIFFERENCES ASSOCIATED WITH EACH. WE WILL PROVIDE OPEN SOURCE TOOLS AND RELEASE DATA THROUGHOUT THE DURATION OF THE PROJECT VIA A WEB PORTAL AND THE NITRC REPOSITORY, HENCE ENABLING OTHER INVESTIGATORS TO USE OUR APPROACHES AND COMPARE THEIR OWN METHODS WITH OUR OWN. OUR TOOLS HAVE WIDE APPLI- CATION TO THE STUDY OF THE HEALTHY BRAIN AS WELL AS MANY OTHER DISEASES SUCH AS ALZHEIMER'S DISEASE AND ATTENTION DEFICIT HYPERACTIVITY DISORDER. 38

CRCNS: CYTOSKELETAL MECHANISMS OF DENDRITE ARBOR SHAPE DEVELOPMENT

MINDFULNESS-BASED SMOKING CESSATION ENHANCED WITH MOBILE TECHNOLOGY FOR LOW-INCOME SMOKERS

COMBINATIONAL REGULATION OF INFLAMMATION IN OTITIS MEDIA

INTESTINAL MICROBIOTA-MEDIATED ROTAVIRUS VACCINE FAILURE - PROJECT SUMMARY INFECTION OF GUT EPITHELIA BY ATTENUATED ROTAVIRUS (RV) VACCINES SERVES TO PROTECT MILLIONS OF LIVES ANNUALLY. IT IS INCREASINGLY APPRECIATED THAT GUT MICROBIOTA, WHICH SHAPE THE MILIEU IN WHICH ROTAVIRUSES ENCOUNTER THE EPITHELIUM IS A PIVOTAL DETERMINANT OF ROTAVIRUS VACCINE EFFICACY. INDEED, RV VACCINES HAVE PROVEN TO BE MUCH LESS EFFECTIVE IN DEVELOPING COUNTRIES WHICH ARE KNOWN TO HAVE STARK DIFFERENCES IN GUT MICROBIOTA COMPOSITION. OUR PUBLISHED WORK DEMONSTRATES THAT MICROBIOTA CAN BOTH DIRECTLY IMPACT RV AND, MOREOVER, IMPACT GUT EPITHELIA TO PREVENT AGAINST ITS ENTRY AND REPLICATION. FURTHERMORE, OUR UNPUBLISHED WORK COMPELLINGLY ARGUES FOR A CENTRAL ROLE FOR GUT MICROBIOTA COMPOSITION IN RV VACCINE INEFFICACY. SPECIFICALLY, WE FIND THAT TRANSPLANT OF MICROBIOTA FROM NON-RV VACCINE RESPONDING CHILDREN CONFERS A MICROBIOTA-DEPENDENT NON-RESPONDER PHENOTYPE. IN ADDITION, CULTURING INFANT FECAL SAMPLES IN BIOREACTOR CONTINUOUS CULTURE SYSTEMS YIELDS SUPERNATANTS THAT DIFFERENTIALLY INHIBIT RV VACCINE REPLICATION IN VITRO. HENCE, THE CENTRAL GOALS OF THIS PROPOSAL ARE TO IDENTIFY AND ISOLATE MICROBIOTA CONSTITUENTS THAT DRIVE RV VACCINE INEFFICACY IN HUMANS AND DETERMINE MECHANISMS BY WHICH THEY ACT. FINDINGS FROM THIS WORK WILL ADVANCE OUR FUNDAMENTAL KNOWLEDGE ON BACTERIAL-VIRAL INTERACTIONS IN THE GUT, MECHANISTICALLY ENLIGHTEN HOW MICROBIOTA CAN IMPACT REPLICATION AND RESPONSE TO LIVE, ATTENUATED ORAL VACCINES AND POTENTIALLY AID IN THE DEVELOPMENT OF NOVEL STRATEGIES TO REDUCE THE BURDEN OF ENTERIC VIRAL INFECTIONS.

RATIONAL DESIGN OF TRANSFERRIN BINDING PROTEIN-BASED VACCINES TO COMBAT GONORRHEA

SMOKERS' DECISION-MAKING ABOUT TOBACCO USE: THE INTERPLAY OF AFFECTIVE AND COGNITIVE FACTORS WITH PRODUCT CHARACTERISTICS

THE DEVELOPMENT OF JOINT ATTENTION AFTER INFANCY

ALTERED CNS INTERCELLULAR SIGNALING MECHANISMS IN CARDIOVASCULAR DISEASE

DEVELOPING STEM PROFESSIONALS AS EDUCATORS AND TEACHER LEADERS

THE NATIONAL CENTER ON CHILD TRAFFICKING: INNOVATION AND DISSEMINATION OF EVIDENCE-BASED TRAUMA TREATMENT AND SERVICES FOR CHILDREN AND FAMILIES IMPACTED BY TRAFFICKING - .“THE NATIONAL CENTER ON CHILD TRAFFICKING: INNOVATION AND DISSEMINATION OF EVIDENCE-BASED TRAUMA TREATMENT AND SERVICES FOR CHILDREN AND FAMILIES IMPACTED BY TRAFFICKING” WILL ESTABLISH A NATIONAL NETWORK OF EXPERTS IN TRAUMA, TRAFFICKING, AND IMPLEMENTATION SCIENCE TO DEVELOP, ADAPT, DELIVER, AND DISSEMINATE PRODUCTS, RESOURCES, AND INTERVENTIONS TO IMPROVE OUTCOMES FOR YOUTH AND FAMILIES WHO HAVE EXPERIENCED COMMERCIAL SEXUAL EXPLOITATION AND TRAFFICKING (CSET). YOUTH WHO HAVE EXPERIENCED CSET HAVE VERY HIGH RATES OF TRAUMA EXPOSURE, INCLUDING EARLY TRAUMA (E.G. SEXUAL ABUSE, TRAUMATIC LOSS/ SEPARATION, FAMILY VIOLENCE) AS WELL AS TRAUMA WHILE BEING TRAFFICKED (E.G. PHYSICAL/SEXUAL VIOLENCE BY TRAFFICKERS/ PURCHASERS). THE CUMULATIVE IMPACT OF THESE TRAUMATIC EXPERIENCES LEADS TO HIGH RATES OF POST-TRAUMATIC STRESS, DEPRESSION, ANXIETY, SUBSTANCE USE, AND SELF-INJURY. CSET OCCURS TO YOUTH OF ALL AGES, GENDERS, AND RACES/ETHNICITIES; HOWEVER, YOUTH OF COLOR AND LGBTQ YOUTH ARE SIGNIFICANTLY OVER-REPRESENTED AND MALES ARE UNDERIDENTIFIED. THE NATIONAL CENTER ON CHILD TRAFFICKING (NCCT) WILL INCREASE AND IMPROVE ACCESS TO TRAUMA-FOCUSED EVIDENCE-BASED MENTAL TREATMENTS AND TRAUMA-INFORMED INTERVENTIONS GUIDED BY PRINCIPLES OF TRAUMA-INFORMED CARE TAILORED AND ADAPTED TO MEET THE NEEDS OF YOUTH WHO HAVE EXPERIENCED CSET, AS WELL AS INCREASE AND IMPROVE TRAUMA AND TRAFFICKING AWARENESS AND COLLABORATIVE MULTI-DISCIPLINARY CROSS-SECTOR RESPONSE. THE NCCT WILL (1) DEVELOP AND DISSEMINATE NATIONAL PRACTICE STANDARDS AND CONSENSUS GUIDELINES FOR MH TREATMENT CROSSCUTTING EBPS TO 1000 MENTAL HEALTH PROFESSIONALS AND WEBINAR TRAINING TO 4000 PROFESSIONALS, (2) DELIVER AND EVALUATE TRAINING OF TF-CBT FOR CSET TO 250 THERAPISTS IN 5 SAMHSA/HHS REGIONS, DEVELOP RESOURCES FOR THERAPISTS AND TRAINERS TO ENHANCE DISSEMINATION AND SERVICE DELIVERY, DISSEMINATE TO 1000 PROVIDERS, (3) DEVELOP AND DISSEMINATE STANDARDS, GUIDELINES, AND TRAINING ADDRESSING CO-OCCURRING TRAUMA AND SUBSTANCE USE PROBLEMS TO 1000 MENTAL HEALTH AND SUBSTANCE ABUSE PROFESSIONALS, WEBINAR TRAINING TO 1600 PROFESSIONALS, INTEGRATE THE GUIDELINES INTO AN EXISTING EVIDENCE-BASED TRAUMA AND SUBSTANCE USE TREATMENT, RISK REDUCTION THROUGH FAMILY THERAPY, AND TRAIN 50 THERAPISTS IN THE ADAPTED MODEL, (4) ADAPT AND DISSEMINATE TRAINING IN TRAUMA-INFORMED PARENTING, THE RESOURCE PARENT CURRICULUM, ADAPTED FOR YOUTH WHO HAVE EXPERIENCED CSET TO 100 RPC FACILITATORS, (5) ADAPT AND DISSEMINATE TRAINING IN TRAUMA-INFORMED RESIDENTIAL CARE, THINK TRAUMA. TO 50 THINK TRAUMA TRAINERS, AND TRAIN STAFF AT TARGETED CSET CONGREGATE CARE/RESIDENTIAL TREATMENT PLACEMENTS, (6) DEVELOP AND DISSEMINATE RESOURCES FOR MDT AND CSET SPECIALIST PROFESSIONALS, INCLUDING PRACTICE GUIDELINES AND TRAINING CURRICULA (FORECAST) INCORPORATING CSET RESPONSE TO 650 PROFESSIONALS, WEBINAR TRAINING TO 400 PROFESSIONALS, (7) DEVELOP SECONDARY TRAUMATIC STRESS/COMPASSION FATIGUE AWARENESS MATERIALS AND STRATEGIES AND DELIVER TRAINING IN THE PRACTICES TO 1000 PROFESSIONALS SERVING YOUTH WHO HAVE EXPERIENCED CSET. OVER 11,000 PEOPLE WILL BE IMPACTED BY THE PROJECT THROUGH RESOURCES DEVELOPED AND DISSEMINATED AND TRAININGS PROVIDED (1490 Y2, 2565 Y3, 2630 Y4, 5250 Y5).

COMPARATIVE IMMUNOLOGY OF FILOVIRUS RESERVOIR ROUSETTUS AEGYPTIACUS

NOVEL NONLINEAR OPTICAL PROCESSES IN ACTIVE, RANDOM AND NANOSTRUCTURED SYSTEMS

IMPROVING OUTCOMES OF GEORGIA'S CHILDREN AND FAMILIES AFFECTED BY SUBSTANCE ABUSE: STRENGTHENING THE PARTNERSHIP BETWEEN THE DEPARTMENT OF FAMILY AND CHILDREN SERVICES AND FAMILY TREATMENT COURTS

SNRK IN ISCHEMIC VASCULAR DISEASES

GEOSPATIAL FACTORS & IMPACTS: MEASUREMENT AND USE

SPECIAL EDUCATION RESEARCH GRANTS

CRCNS: MOLECULAR AND COMPUTATIONAL DISSECTION OF COLD NOCICEPTION

FUNCTIONAL ANALYSIS OF FLAVIVIRUS GENETIC RESISTANCE.

ASSESSMENT OF APPROACH-AVOIDANCE MOTIVATION IN NEUROPSYCHIATRIC DISORDERS - ABSTRACT PAR-18-30 “DEVELOPMENT AND OPTIMIZATION OF TASKS AND MEASURES FOR FUNCTIONAL DOMAINS OF BEHAVIOR” ENCOURAGES RESEARCH PROJECTS THAT WILL DEVELOP AND OPTIMIZE NEW OR EXISTING TASKS AND MEASURES FOR THE RESEARCH DOMAIN CRITERIA (RDOC). THIS CALL STEMS FROM WORKGROUPS OF THE NATIONAL ADVISORY MENTAL HEALTH COUNCIL THAT IDENTIFIED SIGNIFICANT GAPS IN THE RDOC MEASUREMENT TOOLKIT. IN THE NEGATIVE VALENCE SYSTEMS (NVS) DOMAIN, ONE PRIORITY AREA IS THE NEED FOR BEHAVIORAL PARADIGMS FOR IDENTIFYING AREAS OF OVERLAP AND DISTINCTION BETWEEN NVS, WHICH MOTIVATE DEFENSIVE AVOIDANCE BEHAVIORS, AND POSITIVE VALENCE SYSTEMS (PVS), WHICH MOTIVATE REWARD-APPROACH BEHAVIORS. WE CONTEND THAT APPROACH-AVOIDANCE (AP-AV) PARADIGMS OFFER A PROMISING SOLUTION. AP-AV TASKS ARE ESSENTIALLY BEHAVIORAL APPROACH TESTS THAT ENABLE ASSESSMENT OF OVERT BEHAVIORAL RESPONSES TO ACUTE THREATS. THE AIMS OF THIS PROPOSAL ARE TO DEMONSTRATE THE (1) PSYCHOMETRIC ADEQUACY (TEST-RETEST RELIABILITY) AND (2) DIAGNOSTIC/PREDICTIVE VALIDITY OF A USER-FRIENDLY INSTRUCTED AP-AV-TASK WE’VE DEVELOPED FOR ASSESSING PSYCHOSOCIAL DYSFUNCTION ASSOCIATED WITH ANXIETY, DEPRESSION, PSYCHOSIS, AND OTHER CONDITIONS. OUR AIMS BUILD UPON EXTENSIVE PRELIMINARY RESEARCH IN OUR LAB DEVOTED TO OPTIMIZING TASK PARAMETERS, MEASURES AND ADMINISTRATION. THIS WORK HAS THE POTENTIAL TO YIELD AN EASY-TO-USE AND WIDELY DISSEMINABLE AP-AV TASK FOR IDENTIFYING AREAS OF OVERLAP AND DISTINCTION BETWEEN NVS AND PVS, AS WELL AS A GENERAL AP-AV METHODOLOGY THAT IS ADAPTABLE FOR ASSESSING OVERT BEHAVIORAL RESPONSES TO ACUTE THREATS. TO ACHIEVE THESE AIMS, WE WILL RECRUIT THREE MATCHED GROUPS OF ADULTS (HEALTHY, ELEVATED SOCIAL ANXIETY, AND ELEVATED SOCIAL ANHEDONIA). INCLUSION OF GROUPS WITH ANXIETY AND ANHEDONIA ARE NECESSARY TO ASSESS DIAGNOSTIC AND PREDICTIVE VALIDITY. PARTICIPANTS WILL COMPLETE STANDARDIZED CLINICAL ASSESSMENTS AND COMPLETE THE INSTRUCTED AP-AV TASK MULTIPLE TIMES DURING TWO NEUROIMAGING SESSIONS, SEPARATED BY 10-14 DAYS. BETWEEN IMAGING SESSIONS, ECOLOGICAL MOMENTARY ASSESSMENTS (EMA) WILL CAPTURE MOOD, MOTIVATIONAL LEVEL, FREQUENCY OF REAL-LIFE APPROACH/AVOIDANCE, AND EMOTIONAL REGULATION STRATEGY USE. THIS RESEARCH IS THEORETICALLY SIGNIFICANT BECAUSE IT HIGHLIGHTS THE RELEVANCE OF THEORIES OF AP-AV MOTIVATION FOR RESEARCH DEVOTED TO IDENTIFYING AREAS OF OVERLAP AND DISTINCTION BETWEEN NVS AND PVS. THIS RESEARCH IS METHODOLOGICALLY INNOVATIVE BECAUSE IT WILL PRODUCE A USER-FRIENDLY AP-AV TASK WITH STRONG PSYCHOMETRIC PROPERTIES FOR USE IN BEHAVIORAL (STAND-ALONE) OR NEUROIMAGING RESEARCH. OUTCOME DATA WILL ALSO PROVIDE THE NECESSARY EMPIRICAL FOUNDATION FOR FUTURE INVESTIGATIONS INTO THE SUITABILITY OF AP-AV TASKS FOR USE WITH INDIVIDUALS WHO VARY WIDELY IN AGE, ABILITY, AND/OR SEVERITY OF DISORDER.

DEVELOPMENT OF INNOVATIVE THERAPEUTICS FOR OTITIS MEDIA

EVALUATION AND OPTIMIZATION OF A JUST-IN-TIME MESSAGING INTERVENTION TO REDUCE ALCOHOL-FACILITATED INTIMATE PARTNER VIOLENCE PERPETRATION AMONG AT-RISK YOUNG ADULT MEN AND WOMEN - PROJECT SUMMARY YOUNG ADULT MEN AND WOMEN PERPETRATE INTIMATE PARTNER VIOLENCE (IPV) AT HIGH RATES. A SUMMARY OF OVER 30 YEARS OF RESEARCH CONCLUDES THAT ALCOHOL IS A CAUSAL FACTOR OF IPV, PARTICULARLY ACUTE ALCOHOL INTOXICATION, HIGHLIGHTING THE CRITICAL NEED FOR INTERVENTIONS DELIVERED PROXIMALLY TO DRINKING EPISODES – A PERIOD OF INCREASED RISK FOR IPV. YET DESPITE THE HIGH SOCIETAL AND PERSONAL COSTS ASSOCIATED WITH HEAVY DRINKING AND IPV AND THE HIGH PREVALENCE OF ALCOHOL FACILITATED IPV, EMPIRICALLY SUPPORTED INTERVENTIONS ARE LACKING, PARTICULARLY THOSE THAT ARE LOW RESOURCE AND EASILY SCALABLE FOR WIDE DISSEMINATION. IT IS INCREASINGLY FEASIBLE TO DELIVER JUST-IN- TIME (JIT) INTERVENTIONS VIA MOBILE TECHNOLOGY, PARTICULARLY THOSE THAT ADAPT OVER TIME TO AN INDIVIDUAL'S CHANGING NEEDS TO PROVIDE APPROPRIATE INTERVENTION STRATEGIES BASED ON REAL TIME, REAL WORLD CONTEXT – JUST-IN- TIME ADAPTIVE INTERVENTIONS (JITAIS). JITAIS HAVE BEEN EVALUATED FOR A RANGE OF BEHAVIORAL HEALTH ISSUES INCLUDING ALCOHOL USE; HOWEVER, NO EMPIRICALLY SUPPORTED JITAIS FOR ALCOHOL-FACILITATED IPV PERPETRATION EXIST. TO DEVELOP JITAIS, JIT INTERVENTIONS ARE OPTIMIZED THROUGH INNOVATIVE MICRO-RANDOMIZED TRIALS (MRTS) IN WHICH INDIVIDUALS ARE MICRO-RANDOMIZED TO RECEIVE DIFFERENT INTERVENTION STRATEGIES AT CRITICAL TIME POINTS TO DETERMINE WHEN A MESSAGE IS BEST DELIVERED, WHICH TYPE OF MESSAGE IS MOST IMPACTFUL FOR WHOM, AND UNDER WHAT CONDITIONS. THUS, THE PRESENT APPLICATION WILL COMBINE A TRADITIONAL RCT TO EVALUATE THE EFFICACY OF DELIVERING JIT MESSAGES TO REDUCE ALCOHOL FACILITATED IPV PERPETRATION WITH A MRT TO OPTIMIZE THE SELECTION AND ADAPTATION OF MESSAGES FOR A FUTURE JITAI. THE PROPOSED INTERVENTION FOCUSES ON THEORETICALLY AND EMPIRICALLY SUPPORTED TARGETS FOR IPV PERPETRATION CONSISTENT WITH THE I3 MODEL – THE PREVAILING UNIFYING THEORY OF IPV PERPETRATION – INCLUDING DISTRESS TOLERANCE SKILLS, EMOTION REGULATION SKILLS, AND ALCOHOL REDUCTION STRATEGIES. AN RCT BY THE PI (K08AA021745) SUPPORTS THESE INTERVENTION TARGETS FOR REDUCING ALCOHOL USE AND IPV PERPETRATION AMONG WOMEN WITH SEXUAL ASSAULT HISTORIES, AND A RECENT PILOT STUDY SUPPORTS THE FEASIBILITY AND ACCEPTABILITY OF DELIVERING THESE JIT MESSAGES USING A MRT DESIGN TO AT-RISK MEN AND WOMEN WITH GOOD EFFECTS OF THE INTERVENTION ON KEY ALCOHOL AND IPV OUTCOMES. AS SUCH, WE PROPOSE TO EVALUATE THE EFFICACY OF THIS JIT MESSAGING INTERVENTION IN 400 HEAVY DRINKING YOUNG ADULTS WITH RECENT IPV PERPETRATION. PARTICIPANTS WILL BE RANDOMIZED TO THE JIT MESSAGING INTERVENTION OR AN ASSESSMENT ONLY CONTROL (RCT DESIGN). ALL PARTICIPANTS WILL COMPLETE A BASELINE SURVEY, 30-DAYS OF TWICE DAILY MONITORING, AND 1-, 3-, AND 6-MONTH FOLLOW- UP SURVEYS. WITHIN THE INTERVENTION ARM (MRT DESIGN), INDIVIDUALS WILL BE MICRO-RANDOMIZED AFTER EACH MORNING AND EVENING REPORT DURING THE 30 DAYS OF MONITORING TO (1) RECEIVE A JIT MESSAGE OR NOT, AND (2) IF YES, TO ONE OF THREE MESSAGE TYPES (DISTRESS TOLERANCE SKILL, ER SKILL, ALCOHOL REDUCTION STRATEGY). THIS INNOVATIVE DESIGN WILL OPTIMIZE THE SELECTION AND ADAPTATION OF JIT MESSAGES FOR A FUTURE JITAI TO REDUCE ALCOHOL FACILITATED IPV.

IMPROVING THE HEALTH OF PEOPLE WITH INTELLECTUAL/DEVELOPMENTAL DISABILITIES AND MOBILITY LIMITATIONS IN GEORGIA - NEARLY 28% OF ADULTS LIVING IN GEORGIA HAVE SOME TYPE OF DISABILITY. GEORGIANS WITH INTELLECTUAL ANDDEVELOPMENTAL DISABILITIES (IDD) AND THOSE WITH MOBILITY LIMITATIONS (ML) EXPERIENCE PROFOUND HEALTHDISPARITIES COMPARED TO ADULTS WITHOUT DISABILITIES. THEY ARE MORE LIKELY TO REPORT HAVING POOR OR FAIR HEALTH,EXPERIENCE A DISPROPORTIONATE BURDEN OF PREVENTABLE CHRONIC CONDITIONS, AND REPORT SIGNIFICANTLY MOREMENTALLY UNHEALTHY DAYS COMPARED TO ADULTS WITHOUT DISABILITIES. THESE DISPARITIES ARE INFLUENCED BY ANUMBER OF POLICY, SYSTEM, AND ENVIRONMENTAL FACTORS, INCLUDING LACK OF ACCESS TO ADEQUATELY TRAINEDHEALTHCARE PROVIDERS AND FINANCIAL BARRIERS TO RECEIVING CARE. DESPITE INCREASING EFFORTS TO ADDRESS DISABILITYHEALTH DISPARITIES AT THE NATIONAL LEVEL, COORDINATED AND CONTEXT-SPECIFIC EFFORTS TO REDUCE HEALTHINEQUITIES FOR PEOPLE WITH DISABILITIES LIVING IN GEORGIA HAVE NOT BEEN REALIZED.IN THIS APPLICATION, THE CENTER FOR LEADERSHIP IN DISABILITY AT GEORGIA STATE UNIVERSITY DESCRIBES ACOMPREHENSIVE PLAN TO REDUCE HEALTH DISPARITIES AMONG ADULTS WITH IDD AND ADULTS WITH ML INGEORGIA. THROUGH A COOPERATIVE AGREEMENT WITH THE CENTERS FOR DISEASE CONTROL AND PREVENTION, NATIONALCENTER ON BIRTH DEFECTS AND DEVELOPMENTAL DISABILITIES, WE PROPOSE TO:1) ESTABLISH, EXPAND, AND ENHANCE PARTNERSHIPS WITH STATEWIDE AND NATIONAL PARTNERS;2) CONDUCT NEEDS ASSESSMENTS TO IDENTIFY GAPS IN ACCESSIBLE PREVENTIVE HEALTH CARE AND HEALTHPROMOTION SERVICES AVAILABLE TO ADULTS WITH IDD AND ADULTS WITH ML;3) ADMINISTER AND EVALUATE A TRAINING FOR HEALTHCARE PROVIDERS ON ACCESSIBLE HEALTH CARE;4) IMPLEMENT AND EVALUATE A DEMONSTRATION PROJECT TO LINK ADULTS WITH IDD TO ACCESSIBLE PREVENTIVEHEALTH CARE AND HEALTH PROMOTION PROGRAMS IN THEIR COMMUNITIES;5) IMPLEMENT AND EVALUATE EVIDENCE-BASED HEALTH PROMOTION INTERVENTIONS AND POLICY, SYSTEMS, ANDENVIRONMENTAL CHANGES; AND6) DISSEMINATE KEY FINDINGS AND LESSONS LEARNED.SEVERAL OF THE STRATEGIES DESCRIBED ABOVE WILL B E DESIGNED IN PARTNERSHIP WITH OTHER STATE DISABILITY ANDHEALTH PROGRAMS AND IMPLEMENTED WITH A NUMBER OF GEORGIA COLLABORATORS. WE WILL SCALE THESE STRATEGIESAND ACTIVITIES STATEWIDE USING A PHASED IMPLEMENTATION APPROACH TO FACILITATE CONTINUOUS PROGRAMQUALITY IMPROVEMENT AND SUPPORT PROGRAM SUSTAINABILITY.EXPECTED OUTCOMES TO BE ACHIEVED DURING THE PERIOD OF PERFORMANCE INCLUDE STRENGTHENEDENGAGEMENT WITH STATE AND NATIONAL PARTNERS; INCREASED KNOWLEDGE OF DISPARITIES AND NEEDS AT THESTATEWIDE AND HEALTH DISTRICT LEVELS; INCREASED COMPETENCY AMONG HEALTHCARE PROVIDERS TO SERVE ADULTS WITHIDD AND ADULTS WITH ML; INCREASED KNOWLEDGE AMONG ADULTS WITH IDD ABOUT PREVENTIVE HEALTHCARE ANDHEALTH BEHAVIORS, AND BARRIERS TO RECEIVING HEALTH CARE AND ENGAGING IN HEALTH BEHAVIORS; INCREASEDENGAGEMENT IN HEALTH PROMOTION PROGRAMS AMONG ADULTS WITH IDD AND ADULTS WITH ML; INCREASED POLICY,SYSTEM, AND ENVIRONMENTAL CHANGES IMPLEMENTED AT THE STATE AND HEALTH DISTRICT LEVELS; AND INCREASEDKNOWLEDGE AMONG HEALTH PROFESSIONALS AND POLICYMAKERS ABOUT WAYS TO IMPROVE DISABILITY HEALTH EQUITY.BEYOND THE PERIOD OF PERFORMANCE, IMPLEMENTING AND EVALUATING OUR PROPOSED PLAN WILL RESULT IN ANINCREASED NUMBER OF PROVIDERS THAT CAN OFFER ACCESSIBLE PREVENTIVE HEALTH CARE, AND FEWER UNMETPREVENTIVE HEALTH CARE NEEDS, IMPROVED HEALTH BEHAVIORS, AND REDUCED PREVALENCE OF CHRONIC CONDITIONSAND RISK FACTORS AMONG ADULTS WITH IDD AND ADULTS WITH ML IN OUR STATE. THE PROPOSED PROJECT WILL CONTRIBUTETOWARD ADVANCING HEALTH EQUITY FOR PEOPLE WITH DISABILITIES IN GEORGIA AND THROUGHOUT THE NATION.

A DECENTRALIZED MACRO AND MICRO GENE-BY-ENVIRONMENT INTERACTION ANALYSIS OF SUBSTANCE USE BEHAVIOR AND ITS BRAIN BIOMARKERS

UNIVERSITY CENTERS FOR EXCELLENCE IN DEVELOPMENTAL DISABILITIES

PROXIMAL EFFECTS OF ALCOHOL ON SAME-SEX INTIMATE PARTNER VIOLENCE

EARLY-STAGE PRECLINICAL VALIDATION OF CARBON MONOXIDE PRODRUGS FOR ACUTE KIDNEY INJURY - IN RESPONSE TO PAR-19-294 (EARLY-STAGE PRECLINICAL VALIDATION OF THERAPEUTIC LEADS FOR DISEASES OF INTEREST TO THE NIDDK), WE PROPOSE TO CONDUCT PRECLINICAL VALIDATION OF CARBON MONOXIDE (CO) AS A THERAPEUTIC AGENT FOR TREATING ACUTE KIDNEY INJURY (AKI), WHICH AFFLICTS A LARGE NUMBER OF PATIENTS WITH SERIOUS AND SOMETIMES FATAL CONSEQUENCES. CURRENTLY, THERE ARE NO TREATMENT OPTIONS AVAILABLE OTHER THAN MAINTENANCE THERAPY. THEREFORE, DEVELOPING DISEASE MODIFYING TREATMENT FOR AKI WILL ADDRESS AN IMPORTANT, UNMET MEDICAL NEED. THE PROPOSED WORK OF DEVELOPING CO-BASED THERAPEUTICS IS BASED ON CO’S ENDOGENOUS SIGNALING ROLES, THE AVAILABILITY OF A LARGE AMOUNT OF LITERATURE EVIDENCE TO SHOW CO’S CYTO- AND ORGAN-PROTECTIVE EFFECTS, OUR UNIQUE CHEMISTRY WORK TO PACK “CO IN A PILL” THROUGH INNOVATIVE PRODRUG DESIGN FOR EASY DELIVERY THROUGH PHARMACEUTICALLY ACCEPTABLE FORMS, AND OUR OWN EXTENSIVE PRELIMINARY RESULTS IN DEMONSTRATING THE ORGAN-PROTECTIVE EFFECTS OF SUCH CO PRODRUGS IN ANIMAL MODELS OF KIDNEY ISCHEMIA REPERFUSION INJURY AND RHABDOMYOLYSIS INJURIES, LIVER INJURY, SYSTEMIC INFLAMMATION, AND GI INFLAMMATION SUCH AS THE COLON AND STOMACH, AMONG OTHERS. IN THIS APPLICATION, WE PROPOSE TO EXAMINE SOME KEY PRECLINICAL VALIDATION ISSUES AND AIM TO PRODUCE ONE OR MORE LEAD COMPOUNDS READY FOR IND-ENABLING WORK BY THE END OF THE GRANT PERIOD. A VERY IMPORTANT ASPECT IS OUR PLAN TO USE MULTIPLE ANIMAL MODELS INCLUDING THE EXAMINATION IN LARGE ANIMALS SUCH AS PIG TO CONDUCT THE PHARMACOLOGICAL ASSESSMENT, WHICH SHOULD GIVE ENHANCED CHANCE OF SUCCESS WHEN TRANSLATING INTO HUMAN. SPECIFICALLY, WE PROPOSE TO PURSUE THE FOLLOWING SPECIFIC AIMS (1) DESIGN, SYNTHESIS, AND ASSESSMENT OF CO PRODRUGS, (2) THERAPEUTIC VALIDATION OF CO PRODRUG EFFICACY IN MOUSE MODELS OF AKI, AND (3) THERAPEUTIC VALIDATION OF CO PRODRUGS IN PIG MODELS OF AKI. THE PROPOSED WORK WILL BRIDGE THE GAP BETWEEN OUR LONG-TERM GOAL OF DEVELOPING CO-BASED THERAPEUTICS AND THE NEED FOR PRECLINICAL ASSESSMENTS. UPON COMPLETION OF THE PROJECT, WE WILL HAVE DEVELOPED AND FULLY VALIDATED THE EFFICACY OF A SERIES OF INNOVATIVE CO PRODRUGS THAT CAN EITHER DELIVER CO SYSTEMICALLY OR SELECTIVELY TARGET THE KIDNEY AND ALLOW FOR RENAL ENRICHMENT. FURTHER, WE WILL ALSO HAVE DEVELOPED A PIPELINE FOR BACKUP CANDIDATES. COLLECTIVELY, THE PROPOSED WORK WILL BE A MAJOR STEP IN DEVELOPING CO-BASED THERAPEUTICS AGAINST AKI AND OTHER FORMS OF ORGAN INJURY.

ROLE OF CD98 IN INTESTINAL PERMEABILITY

COLLABORATIVE RESEARCH: CHEMISTRY COALITIONS, WORKSHOPS AND COMMUNITIES OF SCHOLARS

DESIGNING MAGNETIC RESONANCE PROTEIN-BASED CONTRAST AGENTS WITH HIGH RELAXIVITY

HDAC1 AS A NUTRIENT SENSOR IN THE DEVELOPMENT AND PROGRESSION OF NAFLD - NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) IS A GROWING METABOLIC DISORDER THAT IS CLOSELY ASSOCIATED WITH OBESITY AND INSULIN RESISTANCE/TYPE 2 DIABETES. NAFLD BEGINS WITH A SIMPLE HEPATIC STEATOSIS, WHICH IN SOME INDIVIDUALS MAY PROGRESS TO NONALCOHOLIC STEATOHEPATITIS (NASH), AN ADVANCED ABNORMITY THAT MAY FURTHER LEAD TO FIBROSIS, CIRRHOSIS, LIVER FAILURE OR CANCER. WHEREAS ENHANCED DE NOVO LIPOGENESIS AND FATTY ACID INFLUX INITIATE THE HEPATIC STEATOSIS, HEPATIC INFLAMMATION TRIGGERS THE TRANSITION FROM HEPATIC STEATOSIS TO NASH AND IS AN IMPORTANT DRIVING FORCE OF THE PATHOLOGICAL PROGRESSION TOWARDS FIBROGENESIS. HOWEVER, THE EXACT MECHANISMS UNDERLYING THE DEVELOPMENT AND PROGRESSION OF NAFLD REMAIN POORLY UNDERSTOOD. WHILE NUMEROUS STUDIES HAVE BEEN DEVOTED TO THE EVALUATION OF GENETIC FACTORS INVOLVED IN OBESITY AND ITS ASSOCIATED COMPLICATIONS SUCH AS NAFLD, MUCH IS UNKNOWN ABOUT EPIGENETIC CHANGES IN THIS PROCESS. EPIGENETIC REGULATION, INCLUDING HISTONE ACETYLATION, IS A MOLECULAR LINK BETWEEN ENVIRONMENTAL FACTORS (E.G., DIETS) AND COMPLEX DISEASES (E.G., NAFLD). HISTONE DEACETYLASE 1 (HDAC1) ACTS TO REMOVE ACETYL GROUPS FROM LYSINE RESIDUES IN HISTONES, THEREBY INHIBITING GENE EXPRESSION. OUR PRELIMINARY DATA SUGGESTED THAT LIVER-SPECIFIC DELETION OF HDAC1 DECREASED HEPATIC LIPID ACCUMULATION, INFLAMMATION AND FIBROSIS IN MICE. THEREFORE, WE HYPOTHESIZE THAT HDAC1 PLAYS A CENTRAL ROLE IN THE DEVELOPMENT OF NAFLD. AIM 1 WILL DETERMINE THE ROLE OF HDAC1 IN PROMOTING HEPATIC STEATOSIS. WE HAVE GENERATED GENETIC MODELS WITH LIVER SPECIFIC DELETION OR OVEREXPRESSION OF HDAC1. WE WILL DETERMINE: 1) WHETHER AND HOW LIVER-SPECIFIC DELETION OF HDAC1 PREVENTS, WHEREAS SPECIFIC OVEREXPRESSION OF HDAC1 PROMOTES HEPATIC STEATOSIS IN MICE; 2) WHETHER DOWN-REGULATION OF THE TRANSCRIPTIONAL REPRESSOR KLF3 MEDIATES THE EFFECT OF HDAC1 IN PROMOTING HEPATIC LIPID STORAGE VIA REGULATION OF PPAR. AIM 2 WILL DETERMINE THE ROLE OF HDAC1 IN PROMOTING HEPATIC INFLAMMATION IN THE DEVELOPMENT OF NASH. HEPATIC INFLAMMATION TRIGGERS THE TRANSITION FROM HEPATIC STEATOSIS TO NASH. WE WILL DETERMINE: 1) WHETHER LIVER-SPECIFIC DELETION OF HDAC1 PREVENTS, WHEREAS SPECIFIC OVEREXPRESSION OF HDAC1 PROMOTES NASH IN MICE; 2) WHETHER DOWN-REGULATION OF THE TRANSCRIPTIONAL REPRESSOR KLF3 MEDIATES THE EFFECT OF HDAC1 IN PROMOTING HEPATIC CHEMOTAXIS AND INFLAMMATION VIA REGULATION OF C-JUN. AIM 3 WILL DETERMINE THE MECHANISM UNDERLYING REGULATION OF HDAC1 BY EXCESS NUTRIENTS. O-GLCNACYLATION HAS EMERGED AS A KEY NUTRIENT SENSOR THAT REGULATES CELLULAR METABOLIC PATHWAYS IN RESPONSE TO OVER-NUTRITIONAL CUES. WE WILL DETERMINE WHETHER HDAC1 O-GLCNACYLATION BY EXCESS NUTRIENTS SUCH AS GLUCOSE AND SATURATED FATTY ACIDS, LEVELS OF WHICH ARE COMMONLY ELEVATED IN OBESITY, INCREASES HDAC1 PROTEIN STABILITY BY PREVENTING UBIQUITINATION AND PROTEASOMAL DEGRADATION, LEADING TO ENHANCED HDAC1 PROTEIN CONTENT AND ACTIVITY. THIS PROJECT WILL DEFINE THE ROLE OF HDAC1 AS A NUTRIENT SENSOR THAT REGULATES HEPATIC LIPID METABOLISM AND INFLAMMATION IN THE DEVELOPMENT AND PROGRESSION OF NFALD. OUR STUDIES COULD GUIDE THE DEVELOPMENT OF THE EPIGENETIC REGULATION AS NEW THERAPEUTIC TARGETS IN THE TREATMENT OF NAFLD.

NOVEL THERAPEUTICS AGAINST RESPIRATORY SYNCYTIAL VIRUS INFECTION

UNIVERSITY CENTERS FOR EXCELLENCE IN DEVELOPMENTAL DISABILITIES

SEX-DEPENDENT REGULATION OF SOCIAL REWARD BY OXYTOCIN IN THE MESOLIMBIC REWARD CIRCUITRY - PROJECT SUMMARY THE REWARDING PROPERTIES OF SOCIAL INTERACTIONS ARE CRITICAL TO THE EXPRESSION OF ADAPTIVE SOCIAL BEHAVIOR AND TO THE DEVELOPMENT AND MAINTENANCE OF SOCIAL RELATIONSHIPS. LITTLE IS KNOWN, HOWEVER, ABOUT THE FACTORS THAT DETERMINE THE REWARD VALUE OF SOCIAL INTERACTIONS OR ABOUT THE BASIC NEURAL MECHANISMS THAT UNDERLIE SOCIAL REWARD, PARTICULARLY IN FEMALES. WE DO KNOW THAT THE MESOLIMBIC DOPAMINE SYSTEM (MDS) IS CENTRAL TO THE NEURAL CIRCUITRY CONTROLLING THE REWARDING PROPERTIES OF MANY OTHER STIMULI SUCH AS DRUGS OF ABUSE. A PRIMARY COMPONENT OF THE MDS IS DOPAMINE (DA)-CONTAINING NEURONS IN THE VENTRAL TEGMENTAL AREA (VTA) THAT PROJECT TO THE NUCLEUS ACCUMBENS (NAC) AS WELL AS TO OTHER SITES SUCH AS THE MEDIAL PREFRONTAL CORTEX. CRITICAL INPUTS TO THE MDS INCLUDE OXYTOCIN (OT)-CONTAINING PROJECTIONS FROM THE HYPOTHALAMUS. WE AND OTHERS HAVE DEMONSTRATED THAT, IN MALE RODENTS, ACTIVATION OF OT RECEPTORS IN THE CAUDAL VTA AND IN THE NAC IS ESSENTIAL FOR THE REWARDING PROPERTIES OF SOCIAL INTERACTION. REMARKABLY, DESPITE THE CONSIDERABLE EVIDENCE FOR SEX DIFFERENCES IN OT REGULATION OF SOCIAL BEHAVIORS, THE ROLE OF OT IN REGULATING SOCIAL REWARD IN FEMALES HAS NOT BEEN INVESTIGATED. THIS PROJECT WILL PROVIDE SUBSTANTIAL NEW INFORMATION ON THE FACTORS THAT DETERMINE THE REWARD VALUE OF SOCIAL INTERACTIONS AND ON THE NEURAL MECHANISMS THAT MEDIATE SOCIAL REWARD BY TESTING THIS SERIES OF INTEGRATED HYPOTHESES IN MALE AND FEMALE SYRIAN HAMSTERS. BASED ON PUBLISHED AND PRELIMINARY DATA FROM OUR LAB AND OTHERS, WE HAVE HYPOTHESIZED THAT: 1) THERE IS AN INVERTED U RELATIONSHIP BETWEEN THE “DOSE” OF SOCIAL INTERACTIONS AND SOCIAL REWARD, 2) THIS DOSE-RESPONSE RELATIONSHIP IS INITIATED AT LOWER DOSES IN FEMALES THAN IN MALES, AND 3) THIS SEX DIFFERENCE IS MEDIATED BY DIFFERENTIAL OT-INDUCED DA RELEASE IN THE MDS. THIS PROJECT HAS SUBSTANTIAL POTENTIAL FOR TRANSLATION TO CLINICALLY-RELATED PROBLEMS BY PROVIDING: 1) NEW INFORMATION ON HOW SOCIAL STIMULI CAN TRANSITION FROM BEING REWARDING TO BEING LESS REWARDING OR EVEN AVERSIVE, 2) POTENTIAL MECHANISMS FOR UNDERSTANDING WELL-KNOWN SEX DIFFERENCES IN THE INCIDENCE OF NEUROPSYCHIATRIC AND NEURODEVELOPMENTAL DISORDERS FOR WHICH DYSFUNCTIONAL SOCIAL RELATIONSHIPS ARE AN IMPORTANT SYMPTOM, AND 3) THE POTENTIAL FOR DEVELOPMENT OF GENDER- SPECIFIC TREATMENTS FOR THESE DISORDERS.

UNIFIED MULTIVARIATE DATA-DRIVEN SOLUTIONS FOR STATIC AND DYNAMIC BRAIN CONNECTIVITY

DEVELOPMENT OF A NOVEL STRATEGY TO PRODUCE ANTIBACTERIAL GLYCOCONJUGATE VACCINES

CENTER FOR LEADERSHIP IN DISABILITY AT GEORGIA STATE UNIVERSITY

ADVANCING UNDERSTANDING OF RACISM-RELATED HEALTH DISPARITIES BEGINNING BEFORE BIRTH: A MULTISITE STUDY WITH BLACK AND LATINA PREGNANT WOMEN - DESCRIPTIVE TITLE: ADVANCING UNDERSTANDING OF RACISM-RELATED HEALTH DISPARITIES BEFORE BIRTH PROJECT SUMMARY/ABSTRACT RACIAL AND ETHNIC INJUSTICE ARE PREVALENT AND DEVASTATING CAUSES OF STRESS AND SUBSEQUENT HEALTH DISPARITIES. BLACK AND LATINA WOMEN EXPERIENCE A HIGHER BURDEN OF PREGNANCY COMPLICATIONS, MATERNAL MORTALITY, AND PRETERM BIRTH COMPARED TO WHITE WOMEN. THESE DISPARITIES IN BIRTH OUTCOMES ARE EXACERBATED BY SYSTEMS OF CARE THAT NEGLECT OR INVALIDATE THE EXPERIENCES OF PREGNANT WOMEN OF COLOR, CONTRIBUTING TO HIGH-RISK DELIVERIES, UNNECESSARY OBSTETRIC INTERVENTIONS, AND DEATH OF WOMEN AND INFANTS. YET, NO STUDIES HAVE EXAMINED WHETHER EXPERIENCES OF RACISM PRENATALLY AFFECT FETAL HEALTH AND DEVELOPMENT THROUGH A PROCESS OF “BIOLOGICAL EMBEDDING” OF RACISM MEASURED DAILY DURING PREGNANCY. THIS STUDY WILL ADDRESS THREE MAJOR GAPS IN THE LITERATURE TO DATE. FIRST, EXPERIENCES OF RACISM AND DISCRIMINATION ARE OFTEN MEASURED GLOBALLY, MISSING THE CUMULATIVE NATURE OF STRESS EXPOSURE ON FETAL PHYSIOLOGICAL DEVELOPMENT. SECOND, IT IS UNCLEAR WHETHER SPECIFIC PARTNER BEHAVIORS (E.G., VALIDATION OF RACISM-RELATED EXPERIENCES) AND/OR CULTURALLY-GROUNDED COPING STRATEGIES GROUNDED IN THE RADICAL HEALING FRAMEWORK (E.G., RACIAL/ETHNIC IDENTITY, ACTIVISM) CAN BUFFER EFFECTS OF RACISM ON MATERNAL PHYSIOLOGY, FETAL PHYSIOLOGY, AND BIRTH OUTCOMES. THIRD, GIVEN THE NOVELTY OF THIS RESEARCH PROGRAM, IT IS IMPORTANT TO INTEGRATE QUALITATIVE METHODS THAT CENTER THE EXPERIENCES OF BLACK AND LATINA WOMEN DURING THIS TRANSFORMATIVE AND VULNERABLE LIFE STAGE. THE OBJECTIVE OF THIS PROPOSAL IS TO ADVANCE UNDERSTANDING OF RACISM-RELATED HEALTH DISPARITIES IN PREGNANT WOMEN AND INFANTS BY (1) ENROLLING BLACK AND LATINA WOMEN DURING THE 2ND AND 3RD TRIMESTER OF PREGNANCY AND ASSESSING DAILY RACISM EXPERIENCES THROUGH DAILY DIARY ASSESSMENTS (14 CONSECUTIVE DAYS TRIMESTER); (2) MEASURING MATERNAL AND FETAL PSYCHOPHYSIOLOGY DURING THE THIRD TRIMESTER (E.G., HEART RATE, HEART RATE VARIABILITY); (3) ASSESSING NEWBORN NEURODEVELOPMENT WITHIN 48 HOURS OF BIRTH; AND (4) EXPLORING CULTURALLY-GROUNDED BUFFERS AND QUALITATIVE EXPERIENCES OF RACISM ON WOMEN AND INFANTS. WE WILL ENROLL 400 PREGNANT WOMEN FROM THE ATLANTA, GA AND SALT LAKE CITY, UT METRO AREAS (N=200/SITE), USING ESTABLISHED PROTOCOLS FOR RECRUITING AND RETAINING WOMEN DURING THIS DEVELOPMENTAL STAGE. PARTICIPATING WOMEN WILL COMPLETE QUESTIONNAIRES AND A 2-WEEK DAILY DIARY OF STRESSORS RELATED TO RACISM IN THE 2ND AND 3RD TRIMESTER. IN THE 3RD TRIMESTER, WOMEN WILL COMPLETE THESE MEASURES, A QUALITATIVE INTERVIEW, AND TWO WEEKS OF IN-HOME MATERNAL AND FETAL PHYSIOLOGICAL MEASURES, WHICH INCLUDES AN INNOVATIVE MEASURE OF FETAL HEART RATE (HR) AND HR VARIABILITY (HRV). WOMEN WILL ALSO COMPLETE A STRUCTURED INTERACTION TASK WITH THEIR ROMANTIC PARTNER OR CLOSEST SUPPORT PERSON; INVOLVING DISCUSSIONS OF HOW EACH COPE WITH RACISM-RELATED STRESSORS. WITHIN 48 HOURS OF BIRTH, INFANTS WILL COMPLETE THE NICU NETWORK NEUROBEHAVIORAL SCALE (NNNS) TO ASSESS HOW PRENATAL EXPOSURE TO RACISM MAY AFFECT NEWBORN BIRTH OUTCOMES. THIS SHORT-TERM LONGITUDINAL STUDY LAYS THE FOUNDATION FOR FURTHER FOLLOW-UP OF INFANTS AND WOMEN INTO EARLY CHILDHOOD AND A PROGRAMMATIC LINE OF RESEARCH DEVOTED TO UNDERSTANDING AND INTERVENING WITH MARGINALIZED MOTHERS AND CHILDREN TO REDUCE THE EFFECTS OF RACISM ON FAMILY HEALTH AND WELLBEING.

INVERSE NEUROVASCULAR COUPLING IN THE HYPOTHALAMUS AND ITS ROLE IN POSITIVE FEEDBACK REGULATION OF VASOPRESSIN NEURONS IN HEALTH AND DISEASE - NEUROVASCULAR COUPLING (NVC) LINKS INCREASES IN NEURONAL ACTIVITY WITH A RAPID AND SPATIALLY RESTRICTED INCREASE IN LOCAL BLOOD FLOW. KNOWLEDGE ON THE CELLULAR MECHANISMS DRIVING NVC HAS BEEN FOCUSED ON TRANSIENT EXTEROCEPTIVE SENSORY STIMULATION AND LIMITED TO SUPERFICIAL DORSAL BRAIN AREAS (CORTEX). THUS, LESS IS UNDERSTOOD ON NVC DYNAMICS OF DEEPER BRAIN REGIONS, WHICH CAN BE ACTIVATED BY SLOW, SUSTAINED, AND WIDESPREAD STIMULI (E.G., PHYSIOLOGICAL DISTURBANCES OF BODILY HOMEOSTASIS). DERANGEMENT IN HOMEOSTATIC PROCESSES IS A KEY DRIVER OF PATHOLOGICAL MECHANISMS IN PREVALENT DISEASES SUCH AS NEUROHUMORAL ACTIVATION IN HEART FAILURE (HF). TO ADDRESS THIS CRITICAL GAP IN OUR KNOWLEDGE, WE DEVELOPED A NOVEL EXPERIMENTAL APPROACH THAT ENABLES INTEROCEPTIVE-INDUCED NVC DURING A CHALLENGE TO BODILY HOMEOSTASIS. OUR PRELIMINARY DATA SHOW THAT CONTRARY TO THE CANONICAL NVC RESPONSE, A SYSTEMIC AND PHYSIOLOGICAL HOMEOSTATIC CHALLENGE (ACUTE SALT-LOADING) PROGRESSIVELY INCREASED VASOPRESSIN (VP) NEURONAL FIRING, EVOKED ACTIVITY-DEPENDENT VASOCONSTRICTION AND DECREASED LOCAL BLOOD FLOW IN THE HYPOTHALAMIC SUPRAOPTIC NUCLEUS (SON). THE SALT-INDUCED INVERSE NVC (INVC) RESPONSE WAS SLOW, SUSTAINED AND WIDESPREAD, AND MEDIATED BY THE DENDRITIC RELEASE OF VP WITHIN THE SON. INVC RESULTED IN LOCAL TISSUE HYPOXIA, WHICH EVOKED FURTHER EXCITATION OF VP NEURONS. BASED ON THESE OBSERVATIONS, WE HYPOTHESIZE THAT INVC IS A PHYSIOLOGICAL PROCESS THAT CONTRIBUTES TO POSITIVE FEEDBACK MODULATION OF THE VP NEURONAL POPULATION SO THAT THE PHYSIOLOGICAL DISTURBANCE CAN BE EFFICIENTLY CORRECTED. STILL, THE PRECISE SIGNALING MECHANISMS AND CELLULAR TARGETS MEDIATING THIS NOVEL PHYSIOLOGICAL MODALITY OF NVC, AND MORE IMPORTANTLY, WHETHER AN ABERRANT INVC RESPONSE CONTRIBUTES TO EXACERBATED VP NEURONAL ACTIVITY CHARACTERISTIC OF PREVALENT CARDIOMETABOLIC DISEASES, SUCH AS HF, REMAINS UNKNOWN. USING A MULTIDISCIPLINARY APPROACH, IN AIM 1 WE WILL ELUCIDATE THE PRECISE SIGNALING MECHANISMS AND CELLULAR TARGETS MEDIATING ACTIVITY- DEPENDENT INVC IN THE SON (NEURON-TO-VESSEL SIGNALING). IN AIM 2, WE WILL DETERMINE THE MECHANISMS AND TARGETS BY WHICH THE INVC EVOKES THE POSITIVE FEEDBACK MODULATION OF VP NEURONAL FIRING ACTIVITY (VASCULO-TO- NEURON SIGNALING). FINALLY, IN AIM3, WE WILL ELUCIDATE MECHANISMS CONTRIBUTING TO EXACERBATED INVC-MEDIATED POSITIVE FEEDBACK REGULATION OF VP NEURONS IN A DISEASE STATE (HF). BOTH IN VIVO AND EX VIVO NOVEL APPROACHES (2-PHOTON IMAGING, PATCH-CLAMP ELECTROPHYSIOLOGY, AND EX VIVO CANNULATION OF SON ARTERIOLES) WILL BE USED IN NOVEL TRANSGENIC RAT MODELS THAT ENABLE VISUALIZATION (EGFP) AND MANIPULATION (OPTO- AND CHEMOGENETICALLY) OF VP NEURONS IN THE SON. THE ACTIVATION OF ACID-SENSING ION CHANNELS (ASIC) AND MODULATION OF ASTROCYTE GLUTAMATE TRANSPORTERS WILL BE INVESTIGATED AS KEY MOLECULAR TARGETS. WE EXPECT RESULTS FROM THIS WORK TO CONTRIBUTE TO A BETTER UNDERSTANDING OF FUNDAMENTAL MECHANISMS UNDERLYING NVC RESPONSES IN DIFFERENT BRAIN REGIONS AND UNDER DIFFERENT ACTIVITY-DEPENDENT MODALITIES. MOREOVER, WE ANTICIPATE OUR STUDIES TO UNVEIL NOVEL PATHOLOGICAL MECHANISMS AND THERAPEUTIC TARGETS FOR THE TREATMENT OF HIGHLY PREVALENT CARDIOMETABOLIC DISEASES. 1

SEASONAL AND UNIVERSAL VACCINATION IN AGED POPULATIONS WITH PRE-EXISTING IMMUNITY - PROJECT SUMMARY CURRENT INFLUENZA (FLU) VACCINATION BASED ON HYPERVARIABLE HEMAGGLUTININ (HA) PROTEIN FAILS TO PROVIDE EFFECTIVE CROSS PROTECTION. THE EFFICACY OF VACCINATION IS LOW IN THE AGED POPULATIONS EVEN WITH PRE-EXISTING IMMUNITY. THE IMPACTS OF PRE-EXISTING IMMUNITY ON THE IMMUNOGENICITY AND EFFICACY OF UNIVERSAL AND SEASONAL VACCINATION LARGELY REMAIN NOT WELL UNDERSTOOD IN THE AGED POPULATIONS. DEVELOPMENT OF NEW FLU VACCINES AND VACCINATION STRATEGIES IMPROVING CROSS PROTECTIVE EFFICACY IN YOUNG NAÏVE AND AGED HOSTS WITH PRE-EXISTING IMMUNITY IS OF HIGH PRIORITY. MONO CONSERVED ANTIGENIC TARGETS INDUCING CROSS PROTECTION TESTED IN NAÏVE ANIMAL MODELS INCLUDE THE FLU A VIRUS M2 EXTRACELLULAR DOMAIN (M2E), HA-STALK DOMAINS, AND NEURAMINIDASE (NA) WERE REPORTED BUT INSUFFICIENT FOR TRANSLATION TO HUMANS. THE MULTI-TARGET UNIVERSAL VACCINES IN NAÏVE AND AGED HOSTS WITH PRE-EXISTING IMMUNITY REMAIN TO BE DEVELOPED. WE DEVELOPED HETEROLOGOUS TANDEM REPEAT OF M2E (5XM2E) PRESENTED ON IMMUNOGENIC VIRUS-LIKE PARTICLES (5XM2E VLP). VACCINATION WITH 5XM2E VLP WAS EFFECTIVE IN BROADENING CROSS PROTECTION BUT SUBOPTIMAL. A FURTHER IMPROVED UNIVERSAL VACCINE SHOULD BE DEVELOPED. OUR PRELIMINARY STUDIES FOUND SYNERGISTIC EFFECTS ON IMPROVING CROSS PROTECTION BY BOTH M2E AND NA IMMUNITY. THEREFORE, AS A NEW UNIVERSAL VACCINE CANDIDATE, WE DEVELOPED A MULTI NA + 5XM2E VLP VACCINE CONTAINING MULTI-SUBTYPE NA AND 5XM2E ON THE SAME VLP PARTICLE. IN ADDITION, WE NEWLY DESIGNED GENETICALLY LINKED NOVEL RECOMBINANT M2E-STALK UNIVERSAL PROTEIN VACCINES EFFECTIVELY INDUCING BOTH M2E AND HA-STALK IMMUNITY AND CONFERRING BROAD CROSS- GROUP PROTECTION. ADJUVANTED UNIVERSAL VACCINATION WILL OVERCOME THE AGING-RELATED IMMUNE SENESCENCE BY ACTIVATING T AND B IMMUNE CELLS IN NAÏVE HOSTS OR AGED POPULATIONS UNDER PRE-EXISTING IMMUNITY. IN THIS PROJECT, WE WILL TEST THE HYPOTHESIS THAT NEW UNIVERSAL VACCINATION INDUCING MULTI IMMUNITY (M2E, STALK, NA) WILL ENHANCE THE BREADTH AND EFFICACY OF CROSS PROTECTION IN ADULT AND AGED POPULATIONS WITH OR WITHOUT PRE-EXISTING IMMUNITY. UNDER AIM 1, WE WILL DETERMINE THE EFFICACY OF MULTI-TARGET UNIVERSAL VACCINES IN YOUNG ADULT MICE AND FERRETS UNDER NAÏVE AND PRE-EXISTING IMMUNE CONDITIONS. IN AIM 2 STUDIES, WE WILL DETERMINE THE DURABILITY OF CROSS PROTECTIVE IMMUNITY BY MULTI TARGETING NEW UNIVERSAL VACCINES AND TEST A VACCINATION STRATEGY ENHANCING CROSS PROTECTION IN AGED MOUSE AND FERRET ANIMAL MODELS. IN THE AIM 3, WE WILL INVESTIGATE CROSS PROTECTIVE IMMUNE MECHANISMS OF MULTI TARGETING UNIVERSAL VACCINATION IN YOUNG AND AGED MOUSE MODELS. THE OUTCOMES IN THIS PROJECT WILL BE HIGHLY SIGNIFICANT IN THE ASPECT OF TRANSLATIONAL SCIENCE AND RELEVANCE TO IMPROVE THE CROSS PROTECTIVE EFFICACY OF FLU VACCINATION.

GEORGIA STATE PHYSICAL ACTIVITY AND NUTRITION PROGRAM (G-SPAN) - THOUGH SIGNIFICANT INVESTMENTS AND PROGRESS HAVE BEEN MADE IN NUTRITION AND PHYSICAL ACTIVITY, HEALTH DISPARITIES PERSIST IN OBESITY PREVALENCE, CHRONIC DISEASE PREVALENCE, PHYSICAL FITNESS, FOOD AND NUTRITION SECURITY, BREASTFEEDING PREVALENCE, AND EARLY CARE AND EDUCATION ACROSS GEORGIA. THIS PROPOSAL DETAILS A PLAN TO EXPAND EXISTING INITIATIVES AND ESTABLISH NEW POLICY, SYSTEMS AND ENVIRONMENTAL (PSE) STRATEGIES AND ACTIVITIES IN THE STATE OF GEORGIA THAT WILL IMPROVE THE CAPACITY OF STATE, REGIONAL, AND LOCAL AGENCIES TO ADDRESS THESE DISPARITIES EFFECTIVELY. THE PLAN STRATEGIES FOCUS ON NUTRITION, PHYSICAL ACTIVITY, BREASTFEEDING, AND EARLY CARE EDUCATION OBESITY PREVENTION/FARM TO EARLY CARE. SPECIFICALLY, THIS PROPOSAL SEEKS TO ADDRESS INEQUITIES IN EACH OF THESE AREAS WITHIN PRIORITY POPULATIONS IN SELECT GEOGRAPHIC REGIONS OF GEORGIA. BY BRINGING TOGETHER VARIOUS STATE AND LOCAL PARTNERS, INCLUDING THE VOICE OF COMMUNITIES IMPACTED BY THESE DISPARITIES, THIS PROPOSAL WILL STRENGTHEN EXISTING PARTNERSHIPS AND EXPAND THEIR CAPACITY TO ACHIEVE IMPROVED HEALTH OUTCOMES. WITH EXTENSIVE EXPERIENCE IN SUPPORTING STATE LEVEL PSE CHANGE, PROGRAM DEVELOPMENT AND COLLECTIVE IMPACT EVALUATION, THE GEORGIA HEALTH POLICY CENTER (GHPC) LOCATED AT 55 PARK PLACE NE, 8TH FLOOR, ATLANTA, GA 30303, WILL ACT AS THE BACKBONE ORGANIZATION FOR THIS COOPERATIVE AGREEMENT. IN CLOSE PARTNERSHIP WITH STATE AND LOCAL AGENCIES, SUCH AS THE GEORGIA DEPARTMENTS OF PUBLIC HEALTH (GDPH) AND EARLY CARE AND LEARNING (DECAL), WHOLESOME WAVE GEORGIA, GA CHAPTER-AMERICAN ACADEMY OF PEDIATRICS/GA BREASTFEEDING COALITION, HEALTHMPOWERS, AND CHILDREN’S HEALTHCARE OF ATLANTA/STRONG4LIFE, WE SEEK TO IMPROVE OUTCOMES IN EACH OF THE 4 STRATEGY AREAS. EXAMPLES OF THESE OUTCOMES INCLUDE: NUTRITION OUTCOMES - INCREASED NUMBER OF YOUTH/CHILD-SERVING AND COMMUNITY-BASED OUT OF SCHOOL TIME SETTINGS THAT ADOPT NUTRITION GUIDELINES TO SUPPORT INCREASED ACCESS TO HEALTHIER FOODS - INCREASED UPTAKE AND EXPANSION OF GEORGIA FRESH FOR LESS VOUCHER REDEMPTION - INCREASED NUMBER OF HEALTH SYSTEMS AND HEALTH CLINICS THAT ADOPT PRODUCE PRESCRIPTION PROGRAMS PHYSICAL ACTIVITY OUTCOMES - INCREASED POLICIES, PLANS, OR COMMUNITY DESIGN CHANGES THAT INCREASE ACCESS TO PA - BUILT ENVIRONMENT INTERVENTION APPROACHES ADOPTED THAT CONNECT ACTIVITY-FRIENDLY ROUTES TO EVERYDAY DESTINATIONS TO INCREASE PA - INDIVIDUALS AND COMMUNITIES ENROLLED IN ACTIVE PEOPLE, HEALTHY NATIONSM INITIATIVE BREASTFEEDING OUTCOMES - INCREASED ACCESS TO PROGRAMS THAT PROVIDE CONTINUITY OF CARE FOR BF FAMILIES - REGIONAL BF COALITIONS AND CADRE OF BF CHAMPIONS ESTABLISHED WHO COALESCE AROUND A COMMON AGENDA, STATE PLAN CREATION, AND COLLABORATE ON INTEGRATED AND REINFORCING ACTIVITIES ACROSS REGIONS - REPLICATE EXISTING PATHWAY 2 ACADEMIC PROGRAM FOR PRE-SERVICE HUMAN LACTATION PROFESSIONALS AT 1 HBCU AND 1 UNIVERSITY TO PREPARE IBCLCS EARLY CARE EDUCATION OUTCOMES - INCREASED STATE LEVEL ECE POLICIES AND ACTIVITIES THAT IMPROVE NUTRITION, PA, BR AND FARM TO ECE INCLUDING ESTABLISHED QRIS STANDARDS AND MEASURES FOR EACH STRATEGIES - GEORGIA FTECE PROVIDER NETWORK ESTABLISHED AS A HUB FOR CHILD CARE PROVIDERS TO ACCESS FTECE RELATED RESOURCES, TRAINING OPPORTUNITIES, AND TA SUPPORT - IMPROVED KNOWLEDGE AND ADOPTION OF FTECE STRATEGIES IN ECE SITES IN TARGET GEOGRAPHIC REGIONS & COMPLETION OF GFTECE STRATEGIC PLAN OBJECTIVES STATEWIDE BEYOND THE 4 STRATEGY AREAS OUTLINED, THIS PROPOSAL WILL ALSO SEEK TO IMPROVE THE CAPACITY AND ABILITY OF PARTNERS IN TARGET REGIONS OF GA IMPLICATED BY HEALTH INEQUITIES TO ADOPT PSE CHANGE THROUGH REGIONAL CAPACITY BUILDING GRANTS. A COLLECTIVE IMPACT EVALUATION FRAMEWORK WILL BE EMPLOYED TO UNDERSTAND CONTEXTS AND MECHANISMS THAT SUPPORT REGIONAL PSE AND BEHAVIOR CHANGE. QUALITY IMPROVEMENT WILL BE FACILITATED VIA A COMMUNITY-LED MONITORING LEARNING AND ADAPTATION (CLM) FRAMEWORK TO SUPPORT MODIFICATIONS TO PSE STRATEGIES AND ACTION PLANS TO ACHIEVE IDENTIFIED OUTCOMES.

ENGLISH LANGUAGE ACQUISITION: NATIONAL PROFESSIONAL DEVELOPMENT PROGRAM

MECHANISMS OF ALCOHOL-FACILITATED INTIMATE PARTNER VIOLENCE

EQUIPPING SCHOOLS, COMMUNITIES, AND UNIVERSITIES FOR EXCELLENCE IN LANGUAGE ACQUISITION (ESCUELA)

ATOMIC LEVEL COMPOSITIONAL COMPLEXITY FOR ELECTROCATALYSIS (ATOMIC-C2E)

ROLE OF VCP IN CORONARY ISCHEMIC INJURY

HETEROCYCLE BINDING AND BIOLOGY IN THE DNA MINOR GROOVE

MRI: DEVELOPMENT OF A FIBER-LINKED MOBILE TELESCOPE FACILITY FOR THE CHARA ARRAY

A NEW MOLECULAR LEXICON FOR SEQUENCE-SPECIFIC DNA RECOGNITION

TRANSITION AND POSTSECONDARY PROGRAMS FOR STUDENTS WITH INTELLECTUAL DISABILITIES (TPSID)

AUTOPHAGY AND VSMC MIGRATION

NOVEL VACCINE TO ENHANCE BREADTH OF INFLUENZA IMMUNITY BY SKIN VACCINATION

BIOSYNTHESIS OF POLYSACCHARIDES

FUNDC1 AND DIABETIC CARDIOMYOPATHY

SOLAR ENERGY CONVERSION IN PHOTOSYSTEM I STUDIED USING TIME-RESOLVED VISIBLE AND INFRARED DIFFERENCE SPECTROSCOPY

SPECIAL EDUCATION - RESEARCH AND INNOVATION TO IMPROVE SERVICES AND RESULTS FOR CHILDREN WITH DISABILITIES - IMPROVING READING OUTCOMES FOR CHILDREN

CROSSTALK BETWEEN SENSORY GHRELIN SIGNALING AND ADIPOSE TISSUE SYMPATHETIC OUTFLOW REGULATES METABOLIC HOMEOSTASIS

NOVEL REGULATION OF MUCOSAL INNATE DEFENSE BY AMPK IN OTITIS MEDIA - MUCIN, A MAJOR PROTEIN COMPONENT IN MUCUS, PLAYS A CRITICAL ROLE IN MUCOSAL INNATE DEFENSE BY PROVIDING A PHYSICAL BARRIER AND TRAPPING PATHOGENS FOR MUCOCILIARY CLEARANCE. IF UNCONTROLLED, EXCESSIVE MUCIN PRODUCTION OVERWHELMS MUCOCILIARY CLEARANCE AND CAUSES CONDUCTIVE HEARING LOSS IN OTITIS MEDIA (OM) AND MUCUS OBSTRUCTION IN LUNG INFECTIONS. THEREFORE, MUCIN PRODUCTION MUST BE TIGHTLY REGULATED. HOWEVER, THE MOLECULAR MECHANISMS UNDERLYING THE TIGHT REGULATION OF MUCIN REMAIN LARGELY UNKNOWN. OTITIS MEDIA (OM) IS THE MOST COMMON CHILDHOOD BACTERIAL INFECTION AND THE LEADING CAUSE OF CONDUCTIVE HEARING LOSS. IT REMAINS A MAJOR HEALTH PROBLEM AND A SUBSTANTIAL SOCIOECONOMIC BURDEN. S. PNEUMONIAE, SP, REPRESENTS A MAJOR GRAM-POSITIVE BACTERIAL PATHOGEN FOR OM. CURRENTLY AVAILABLE SP VACCINES HAVE A LIMITED IMPACT ON OM. MOREOVER, INAPPROPRIATE ANTIBIOTIC USE INCREASED ANTIBIOTIC-RESISTANCE. THERE IS AN URGENT NEED FOR DEVELOPING INNOVATIVE NON-ANTIBIOTIC THERAPEUTIC AGENT FOR SUPPRESSING MUCUS OVERPRODUCTION. OUR LONG-TERM GOAL IS TO ELUCIDATE THE MOLECULAR MECHANISMS UNDERLYING OM PATHOGENESIS AND IDENTIFY NOVEL THERAPEUTIC TARGETS. IN CONTRAST TO THE RELATIVELY WELL-KNOWN TOLL-LIKE RECEPTOR (TLR)-DEPENDENT MECHANISMS BY WHICH SP AND PNEUMOLYSIN (PLY – A KEY VIRULENCE FACTOR PRODUCED BY VIRTUALLY ALL CLINICAL SP ISOLATES) INDUCE HOST MUCOSAL IMMUNE RESPONSE, THE TLR-INDEPENDENT MECHANISMS INCLUDING THE KEY REGULATORS REMAIN LARGELY UNCLEAR. ADENOSINE 5’-MONOPHOSPHATE-ACTIVATED PROTEIN KINASE A1 (AMPKA1) HAS EMERGED AS A MASTER REGULATOR OF HOST ENERGY HOMEOSTASIS. ITS ROLE IN INFECTIOUS DISEASES, IN PARTICULAR IN THE HOST MUCOSAL INNATE DEFENSE RESPONSE, E.G. MUCUS PRODUCTION, REMAINS LARGELY UNCLEAR. OUR ENCOURAGING PRELIMINARY DATA SUGGEST THAT SP AND PLY MAY UP-REGULATE MUCIN MUC5AC AND MUC5B VIA ACTIVATION OF AMPKA1 IN A TLR2/4-INDEPENDENT MANNER IN THE MIDDLE EAR AND AIRWAY EPITHELIAL CELLS IN VITRO AND IN THE MOUSE MODELS OF BOTH ACUTE AND CHRONIC OM. INTERESTINGLY, SP AND PLY MAY ACTIVATE AMPKA1 BY INDUCING NOVEL NON-TRADITIONAL (PROTEIN DEGRADATION- INDEPENDENT) UBIQUITINATION OF AMPKA1 LIKELY VIA DOWNREGULATING A KEY DEUBIQUITINASE CYLD. TOGETHER, THESE EXCITING PRELIMINARY DATA HAVE THUS PROVIDED A SOLID FOUNDATION FOR US TO HYPOTHESIZE THAT [1] AMPKA1 ACTS AS A KEY REGULATOR FOR SP-INDUCED UP-REGULATION OF MUC5AC AND MUC5B VIA TLR-INDEPENDENT SIGNALING; [2] ACTIVATION OF AMPKA1 BY INTERPLAY BETWEEN POLYUBIQUITINATION AND PHOSPHORYLATION PLAYS A CRITICAL ROLE IN SP- INDUCED UP-REGULATION OF MUC5AC AND MUC5B (HYPOTHESIS). TO TEST OUR HYPOTHESIS, WE WILL PURSUE TWO SPECIFIC AIMS TO DETERMINE (AIM 1) THE ROLE OF AMPKA1 IN OM PATHOGENESIS IN BOTH AOM AND COM; AND (AIM 2) HOW SP ACTIVATES AMPKA1. THESE STUDIES WILL SIGNIFICANTLY ADVANCE OUR UNDERSTANDING OF THE KEY REGULATORS INCLUDING AMPK IN TLR-INDEPENDENT HOST MUCOSAL INNATE DEFENSE IN BACTERIAL INFECTIONS AND LEAD TO THE IDENTIFICATION OF NOVEL THERAPEUTIC TARGETS FOR CONTROLLING MUCUS OVERPRODUCTION. OUR AMPK SIGNALING STUDIES MAY ALSO HELP UNDERSTAND MOLECULAR MECHANISMS OF OTHER AMPK-RELATED DISEASES (SIGNIFICANCE AND IMPACT).

EFFECTIVENESS EVALUATION OF `STEP UP STEP IN? (SUSI): A CAMPAIGN TO PROMOTE SOCIAL NORMS AGAINST SEXUAL VIOLENCE

IDENTIFYING BARRIERS TO OPTIMIZING DATA SHARING AND ACCELERATE DISCOVERY IN ALZHEIMER?S DISEASE AND RELATED DEMENTIA RESEARCH - IT IS A PIVOTAL TIME FOR ALZHEIMER’S DISEASE AND RELATED DEMENTIAS (ADRD) RESEARCH TO HARNESS DATA SHARING AND ACCELERATE THERAPEUTIC DISCOVERY. DATA SHARING IS IMPORTANT TO ADVANCE RESEARCH BECAUSE IT SUPPORTS LARGE DATA SETS THAT ARE MORE REPRESENTATIVE OF THE POPULATION, INCREASING THE ABILITY TO DETECT GENERALIZABLE CONTRIBUTORS TO DISEASE. SHARING DATA INCREASES EFFICIENCY BY ALLOWING INVESTIGATORS TO BUILD UPON EACH OTHER’S WORK AND PREVENTS REDUNDANT DATA GENERATION. FOR OF THESE REASONS, THE NATIONAL INSTITUTES OF HEALTH HAS COMMITTED TO PROMOTING DATA SHARING TO ACCELERATE RESEARCH IN THE BIOSCIENCES SINCE 1997. NEVERTHELESS, OUR PRELIMINARY DATA INDICATE THAT IN ADRD INDIVIDUAL, INSTITUTIONAL, AND SYSTEM-LEVEL BARRIERS ARE IMPEDING OPTIMAL DATA SHARING. FURTHERMORE, THE POLICIES OF INSTITUTIONS, PUBLISHERS, AND FUNDERS MAY BE INCOMPATIBLE WITH ONE ANOTHER, PREVENTING OR DISCOURAGING INVESTIGATORS FROM SHARING DATA. EFFORTS TO EXPONENTIALLY EXPAND ADRD RESEARCH ACHIEVEMENT THROUGH DATA REPOSITORIES AND RESEARCH CONSORTIA WILL FAIL TO MEET THERAPEUTIC DISCOVERY GOALS IF INVESTIGATORS CANNOT OR WILL NOT SHARE DATA. TO ADDRESS THIS RISK AND IDENTIFY EFFECTIVE INTERVENTIONS TO IMPROVE THE PREVALENCE AND QUALITY OF DATA SHARING, CURRENT GAPS IN KNOWLEDGE REGARDING ADRD INVESTIGATORS’ SHARING PRACTICES, PERCEPTIONS OF POLICIES, AND NAVIGATION OF BARRIERS MUST BE CLOSED. WE PROPOSE TO FURTHER EXPLORE THESE PROVOCATIVE PRELIMINARY FINDINGS, COLLECTING GENERALIZABLE DATA TO BETTER UNDERSTAND ADRD INVESTIGATORS’ PRACTICES AND PERCEPTIONS OF DATA SHARING RESPONSIBILITIES. SUCH DATA WOULD SUPPORT DEVELOPMENT OF INTERVENTIONS THAT MITIGATE BARRIERS CONSIDERING UNIQUE CHALLENGES ASSOCIATED WITH CONDUCTING ADRD RESEARCH AND THE DISTINCTIVE SUBCULTURE OF THE FIELD. OUR GOAL IS TO PROVIDE ADRD INVESTIGATORS WITH TOOLS THAT PROMOTE DATA SHARING AND FACILITATE ADHERENCE TO DATA SHARING POLICIES, INCLUDING THE NIH DATA MANAGEMENT AND SHARING POLICY (EFFECTIVE 2023). WE WILL CONDUCT SURVEYS WITH ADRD INVESTIGATORS TO BETTER UNDERSTAND THE PREVALENCE OF DATA SHARING AND WITHHOLDING PRACTICES AND GAIN CLARITY ABOUT BARRIERS TO DATA SHARING. FOLLOWING SURVEYS, WE WILL CONDUCT IN-DEPTH INTERVIEWS WITH A SUBSET OF SUBJECTS TO COLLECT AND ANALYZE THEIR NARRATIVE DESCRIPTIONS OF BARRIERS TO DATA SHARING AND HOW THEY NAVIGATE SUCH BARRIERS. THIS WILL PROVIDE RICH UNDERSTANDING OF INVESTIGATORS’ UNIQUE EXPERIENCES. FINALLY, WE WILL COMPARE INVESTIGATORS’ REPORTED EXPERIENCES WITH VARIOUS POLICIES THAT GUIDE ADRD SCIENTIFIC PRACTICES. THIS WILL INCLUDE POLICIES FROM JOURNALS, ACADEMIC/RESEARCH CENTERS, REPOSITORIES, CONSORTIA, AND OTHERS. WE WILL MAKE RECOMMENDATIONS OF INTERVENTIONS WHICH MIGHT MITIGATE BARRIERS TO DATA SHARING. THIS STUDY IS CRITICAL TO PROMOTING OPTIMAL DATA SHARING BEHAVIORS THAT ARE NEEDED TO ADVANCE THERAPEUTIC RESEARCH IN ADRD.

FACILE SYNTHESIS OF O-GLYCANS AND O-GLYCOPEPTIDES

MECHANISM OF PARAMYXOVIRUS REPLICATION

NEW; QUANTUM NANOPLASMONICS THEORY; PI- STOCKMAN, MARK I.

NOVEL ANTHRAQUINONES INDUCE APOPTOSIS BY DISRUPTION MDM2/MDM4 INTERACTIONS

SEXUALLY DIMORPHIC VASOPRESSIN CIRCUITS IN THE CONTROL OF SOCIAL INTEREST - PROJECT SUMMARY DISORDERS OF SOCIAL BEHAVIOR ARE INCREASINGLY PREVALENT AND POSE A SUBSTANTIAL BURDEN TO SOCIETY. THESE DISORDERS OFTEN SHOW SEX DIFFERENCES IN PREVALENCE, EXPRESSION, AND SEVERITY. ONE EXPLANATION FOR THESE DIFFERENCES REFLECTS DYSFUNCTION IN THE SEXUALLY DIFFERENTIATED SOCIAL BRAIN. A PARTICULARLY RELEVANT NEUROPEPTIDE SYSTEM IN THIS RESPECT IS THE ARGININE VASOPRESSIN (AVP) INNERVATION OF THE BRAIN, WHICH SHOWS MARKED SEX DIFFERENCES ACROSS MANY SPECIES, INCLUDING HUMANS, AND HAS BEEN IMPLICATED IN AGGRESSIVE AS WELL AS AFFILIATIVE BEHAVIOR. INDEED, THE MAIN RECEPTOR FOR AVP IN THE BRAIN, V1AR, HAS BEEN LINKED TO SOCIAL BEHAVIOR, INCLUDING THAT OF HUMANS. DESPITE THE SIGNIFICANCE OF THIS SYSTEM, FEW STUDIES HAVE DIRECTLY ASSESSED HOW, WHEN, AND WHERE AVP AND V1AR SYSTEMS INTERACT TO INFLUENCE SOCIAL INTEREST IN ADULTS. HERE WE FOCUS ON THE INTERACTION BETWEEN THE SEXUALLY DIMORPHIC AVP CELLS OF THE BED NUCLEUS OF THE STRIA TERMINALIS (BNST) AND ITS MAJOR TARGET, THE LATERAL SEPTUM (LS), AN AREA WITH THE HIGHEST EXPRESSION OF V1AR IN VERTEBRATE BRAINS. IN THE FIRST AIM, WE WILL TEST THE NECESSITY OF LS V1AR CELLS FOR SOCIAL INTEREST BY OPTOGENETIC INHIBITION OF THESE CELLS OR BY GENETICALLY KNOCKING OUT V1AR IN LS. IN ADDITION, WE WILL COMBINE OPTOGENETIC STIMULATION OF BNST AVP CELLS AND V1AR KNOCKDOWN IN LS IN VIVO AND EX VIVO TO TEST WHETHER AVP FROM THE BNST SPECIFICALLY ACTS ON LS V1AR CELLS TO ALTER BEHAVIOR AND CELLULAR PHYSIOLOGY. THE SECOND AIM WILL TEST WHETHER V1ARS IN THE LS ARE SUFFICIENT FOR DRIVING SOCIAL INTEREST BY OPTOGENETIC EXCITATION OF THESE CELLS. THE THIRD AIM WILL TEST WHETHER V1AR CELLS IN THE LS ENCODE SOCIAL INTEREST IN A SEXUALLY DIMORPHIC MANNER, AND WHETHER THIS ENCODING IS ALTERED BY BNST AVP CELL ACTIVITY (VIA CHEMOGENETIC INHIBITION). THIS PROJECT WILL SIGNIFICANTLY ENHANCE OUR MECHANISTIC UNDERSTANDING OF HOW THE BRAIN CONTROLS SOCIAL BEHAVIOR DIFFERENTLY IN MALES AND FEMALES AND MAY GIVE INSIGHT AS TO WHY MANY BEHAVIORAL DISORDERS SHOW STRIKING SEX DIFFERENCES IN MORBIDITY. ALTHOUGH RECENTLY MAJOR ADVANCES HAVE BEEN MADE IN UNDERSTANDING THE NEURAL BASIS OF SOCIAL BEHAVIOR, HOW SUCH BEHAVIOR IS CONTROLLED DIFFERENTLY IN MALES AND FEMALES IS, BY AND LARGE, UNKNOWN. THIS GRANT WILL ADDRESS THESE ISSUES.

STUDY OF ARENAVIRUS ASSEMBLY - THE DEVASTATING IMPACT ON PUBLIC HEALTH, GLOBAL ECONOMY AND SOCIAL STABILITY INCURRED BY THE COVID-19 PANDEMIC IN THE LAST TWO YEARS HAS HIGHLIGHTED THE IMPORTANCE OF BASIC RESEARCH INTO ZOONOTIC PATHOGENS. THIS APPLICATION DESCRIBES STRUCTURAL AND FUNCTIONAL STUDIES INTO THE RODENT-BORNE HUMAN PATHOGEN LYMPHOCYTIC CHORIOMENINGITIS VIRUS (LCMV), A MEMBER OF THE ARENAVIRIDAE FAMILY IN THE BUNYAVIRALES ORDER. LIKE OTHER MEMBERS OF THE SAME FAMILY, LCMV HAS A NEGATIVE SENSE, BI-SEGMENTED GENOME CONSISTING OF A LARGE (L) AND A SMALL (S) SEGMENT. THE L SEGMENT ENCODES THE RNA-DEPENDENT RNA POLYMERASE (L RDRP) PROTEIN AND THE MULTI-FUNCTIONAL MATRIX PROTEIN (Z). THE S SEGMENT ENCODES THE VIRAL NUCLEOPROTEIN (NP) AND THE GLYCOPROTEIN (GP) PRECURSOR OF THE GLYCOPROTEIN COMPLEX (GPC) THAT IS LATER CLEAVED INTO A STABLE SIGNAL PEPTIDE (SSP), GP1, AND GP2. IN THE VIRION, NUCLEOCAPSIDS OF NP COATED L AND S SEGMENTS ASSOCIATED WITH THE L PROTEIN ARE COPACKAGED THROUGH INTERACTIONS WITH MEMBRANE-ASSOCIATED Z PROTEINS, WHICH ALSO INTERACT WITH GPS EMBEDDED IN THE MEMBRANE ENVELOPE. ALTHOUGH STRUCTURES OF INDIVIDUAL PROTEINS FROM AVS HAVE BEEN SOLVED BY X-RAY CRYSTALLOGRAPHY OR CRYO ELECTRON MICROSCOPY (CRYOEM), THE ARCHITECTURAL ORGANIZATION OF THESE PROTEINS IN THE VIRION AND THE ASSEMBLY MECHANISM OF NP AND RNA INTO THE NUCLEOCAPSID ARE POORLY UNDERSTOOD. WE HYPOTHESIZE THAT NP INTERACTS WITH GENOMIC RNA SEGMENTS AND L RDRP TO FORM A NUCLEOCAPSID, WHICH IS RECRUITED TO GP-DECORATED MEMBRANE PATCHES THROUGH Z FOR BUDDING OF VIRIONS. THE PROPOSED STRUCTURAL AND FUNCTIONAL STUDIES AIM TO TEST THIS HYPOTHESIS OF LCMV VIRION AND NUCLEOCAPSID ASSEMBLY WITH TECHNIQUES JUST ESTABLISHED BY OUR TEAM IN THE COLLABORATIVE STUDIES OF VESICULAR STOMATITIS VIRUS (VSV), ANOTHER NEGATIVE SENSE RNA VIRUS. SPECIFICALLY, CRYO ELECTRON TOMOGRAPHY (CRYOET) WILL BE USED TO RECONSTRUCT THE FIRST 3D MODEL OF THE LCMV VIRION AT MOLECULAR RESOLUTION AND ATOMIC MODELS OF INDIVIDUAL PROTEINS WILL BE FITTED INTO THE VIRION TOMOGRAM TO ESTABLISH THE ARCHITECTURAL FRAMEWORK OF THE VIRION AND TO UNVEIL MOLECULAR INTERACTIONS AMONG GP, Z, NP AND L PROTEINS (AIM 1). NEAR-ATOMIC RESOLUTION WITH NOVEL SUB-PARTICLE RECONSTRUCTION METHOD WILL BE USED TO IMAGE FULLY ASSEMBLED NUCLEOCAPSIDS CONSISTING OF NP PROTEIN AND GENOMIC RNA SEGMENT TO DEFINE THE PROTEIN-RNA INTERACTIONS AT ATOMIC DETAILS. THE NUCLEOCAPSID STRUCTURE WILL BE USED TO GUIDE SUB-PARTICLE RECONSTRUCTION WORKFLOW AND BE COMPLEMENTED BY IN SITU STRUCTURES OF NUCLEOCAPSIDS FROM VIRIONS (AIM 2). IN BOTH AIMS, STRUCTURE-GUIDED FUNCTIONAL STUDIES WILL BE PERFORMED TO TEST HYPOTHESES OF ASSEMBLY MECHANISMS OF LCMV NUCLEOCAPSID AND VIRION. STRUCTURE-FUNCTION RELATIONSHIP RELEVANT TO VIRAL RNA SYNTHESIS WILL ALSO BE EXPLORED. OVERALL, THE ANTICIPATED RESULTS WILL PROVIDE NEW INSIGHTS INTO THE MECHANISM OF VIRION ASSEMBLY AND VIRAL RNA SYNTHESIS, NOT ONLY FOR LCMV BUT ALSO FOR ARENAVIRUSES IN GENERAL. THE PROPOSED STUDIES HARNESS CUTTING-EDGE TECHNOLOGIES IN STRUCTURAL BIOLOGY AND WILL GENERATE NEW KNOWLEDGE OF VIRAL STRUCTURES CURRENTLY UNAVAILABLE TO ANY OF ARENAVIRUSES. AS SUCH, THE INNOVATIVE STUDIES SHALL MAKE UNIQUE CONTRIBUTIONS BY ACCELERATING DISCOVERIES OF ANTIVIRAL AGENTS AND VACCINES TO CONTROL FUTURE AV OUTBREAKS.

FLAGELLIN-INDUCED GUT EPITHELIAL CHEMOKINE SECRETION

HEMISPHERIC SPECIALIZATION AND COMMUNICATION

PEPTIDERGIC CONTROL OF APPETITIVE INGESTIVE BEHAVIORS

CELL DEATH AND NEURAL SEX DIFFERENCES

GEORGIA STATE UNIVERSITY EXPANDING QUALITY SBMH SERVICES FOR UNDERSERVED POPULATIONS WITH INCLUSIVE PRACTICES (GSU-EQUIP)

BASIS OF READING DEFICITS IN AFRICAN-AMERICAN CHILDREN

INHIBITION OF RESISTANT VARIANTS OF HIV PROTEASE

UP-REGULATION OF MUCIN GENE TRANSCRIPTION-OTITIS MEDIA

CONVOYS OF CARE: DEVELOPING COLLABORATIVE CARE PARTNERSHIPS IN ASSISTED LIVING

NEGATIVE REGULATION OF INNATE IMMUNITY IN INFLUENZA VIRUS INFECTION - INFLUENZA VIRUS IS A MAJOR PATHOGEN CAUSING SEASONAL EPIDEMICS OF DISEASE IN THE WORLD. AIRWAY EPITHELIUM ACTS AS THE FIRST LINE OF HOST ANTIVIRAL DEFENSE. INFLUENZA VIRUS-INDUCED INNATE IMMUNITY PLAYS A CRITICAL ROLE IN VIRAL CLEARANCE. HOWEVER, IF UNCONTROLLED, DYSREGULATED INNATE IMMUNE RESPONSES CONTRIBUTE SIGNIFICANTLY TO THE MORBIDITY AND MORTALITY. THEREFORE, INFLUENZA VIRUS-INDUCED INNATE IMMUNE RESPONSES MUST BE TIGHTLY REGULATED. THE MOLECULAR MECHANISMS UNDERLYING THE TIGHT REGULATION OF INFLUENZA VIRUS-INDUCED INNATE IMMUNITY REMAIN LARGELY UNKNOWN. CURRENTLY AVAILABLE INFLUENZA VACCINES AND ANTIVIRAL DRUGS HAVE A LIMITED IMPACT ON INFLUENZA VIRUS INFECTION DUE TO THE MISMATCHES BETWEEN THE VACCINE STRAINS AND THE CIRCULATING STRAINS AS WELL AS NEWLY EMERGING MUTANT VIRUSES AND DRUG-RESISTANT VIRUS STRAINS. THERE IS AN URGENT NEED FOR DEVELOPING INNOVATIVE THERAPEUTIC STRATEGIES FOR IMPROVING INNATE IMMUNITY. OUR LONG-TERM GOAL IS TO ELUCIDATE THE MOLECULAR MECHANISMS UNDERLYING THE TIGHT REGULATION OF HOST INNATE IMMUNE RESPONSES IN INFLUENZA VIRUS INFECTION AND IDENTIFY NOVEL THERAPEUTIC TARGETS. IN CONTRAST TO THE RELATIVELY WELL-STUDIED POSITIVE REGULATORS SUCH AS RIG-I LIKE RECEPTOR (RLR) IN REGULATING ANTIVIRAL RESPONSE, THE MOLECULAR MECHANISMS, IN PARTICULAR THE NEGATIVE REGULATORS, INVOLVED IN THE TIGHT REGULATION OF HOST ANTIVIRAL INNATE IMMUNE RESPONSES STILL REMAIN LARGELY UNKNOWN. PIRIN, A KEY SIGNALING REGULATORY PROTEIN, HAS BEEN SHOWN TO BE INVOLVED IN CANCER AND FIBROSIS. ITS ROLE IN INFECTIOUS DISEASES, IN PARTICULAR IN REGULATING HOST INNATE IMMUNE RESPONSES REMAINS UNCLEAR. OUR ENCOURAGING PRELIMINARY DATA SUGGEST THAT PIRIN MAY NEGATIVELY REGULATE INFLUENZA VIRUS-INDUCED INNATE IMMUNITY IN ADENOSINE DEAMINASES ACTING ON RNA 1 (ADAR1)- AND PHOSPHOGLYCERATE KINASE 1 (PGK1)-DEPENDENT MANNERS IN AIRWAY EPITHELIAL CELLS IN VITRO AND IN THE MOUSE MODELS OF INFLUENZA VIRUS INFECTION. MOREOVER, PIRIN IS HIGHLY EXPRESSED IN LUNG, ESPECIALLY IN AIRWAY EPITHELIUM, AND PIRIN DEPLETION IMPROVES ANTI-VIRAL INNATE IMMUNE RESPONSES, VIRAL CLEARANCE AND HOST SURVIVAL. TOGETHER, THESE EXCITING PRELIMINARY DATA HAVE THUS LAID A SOLID FOUNDATION FOR US TO HYPOTHESIZE THAT [1] PIRIN ACTS AS A KEY NEGATIVE REGULATOR FOR INFLUENZA VIRUS-INDUCED INNATE IMMUNITY IN AIRWAY EPITHELIUM; [2] PIRIN INHIBITS INFLUENZA VIRUS-INDUCED INNATE IMMUNITY VIA (1) INTERACTING WITH ADAR1, AND PIRIN- ADAR1 SIGNALING AXIS INHIBITS RIG-I-DEPENDENT ANTI-VIRAL INNATE IMMUNE RESPONSE VIA NEGATIVELY CROSS-TALKING WITH RAS-RELATED NUCLEAR PROTEIN (RAN), A POSITIVE REGULATOR OF ANTI-VIRAL RESPONSE AND (2) INHIBITING PGK1, A POSITIVE REGULATOR, IN INFLUENZA VIRUS INFECTION (HYPOTHESIS). TO TEST OUR HYPOTHESIS, WE WILL PURSUE THREE SPECIFIC AIMS TO DETERMINE (AIM 1) THE ROLE OF PIRIN IN AIRWAY EPITHELIUM IN INFLUENZA VIRUS INFECTION AND ITS THERAPEUTIC POTENTIAL; (AIM 2 & 3) THE MOLECULAR MECHANISMS UNDERLYING NEGATIVE REGULATION OF ANTIVIRAL INNATE IMMUNITY BY PIRIN VIA ADAR1-DEPENDENT NEGATIVE CROSS-TALK WITH RAN (AIM 2) AND INHIBITING PGK1 (AIM 3). THESE STUDIES MAY NOT ONLY SIGNIFICANTLY ADVANCE OUR UNDERSTANDING OF THE NEGATIVE REGULATION OF INNATE IMMUNITY BUT MAY ALSO LEAD TO THE IDENTIFICATION OF NOVEL THERAPEUTIC TARGETS FOR TREATING INFLUENZA VIRUS INFECTIONS.

LIVER KINASE B1 IN ANGIOGENESIS

REGISTRY AND EDUCATION FOR HEMOGLOBINOPATHIES AND HEMOVIGILANCE/TRANSFUSION THERAPY

NEUTROPHIL-EPITHELIAL INTERACTION MEDIATED BY ADENOSINE

FUNCTIONAL ROLE OF P68 TYROSINE PHOSPHORYLATION IN CANCER METASTASIS

SEX DIFFERENCES IN THE NEURAL CONTROL OF SOCIAL BEHAVIOR

ADVANCED COMPUTATIONAL MODELING OF MOLECULAR MACHINES IN GENE REGULATION AND DNA REPAIR - PROJECT SUMMARY/ABSTRACT GENOMIC DNA IS THE INFORMATION REPOSITORY OF THE CELL, ENCODING THE MYRIAD OF PROTEINS REQUIRED TO SUSTAIN LIFE. TO HARNESS THIS INFORMATION, CELLS DEPEND ON RNA POLYMERASES - DYNAMIC BIOMOLECULAR MACHINES THAT FIRST TRANSCRIBE THE GENETIC CODE INTO RNA. TRANSCRIPTION IS A COMPLEX AND HIGHLY REGULATED PROCESS THAT GOVERNS CELL GROWTH, DIFFERENTIATION, DEVELOPMENT AND ALL RESPONSES TO ENVIRONMENTAL CHANGE. IMPORTANTLY, THE BIOCHEMICAL PATHWAYS THAT ORCHESTRATE THE EXPRESSION AND REPAIR OF GENES ARE INTRICATELY INTERTWINED. AS A CONSEQUENCE, MANY HUMAN DISEASES TRACE THEIR ORIGINS TO DEFICIENCIES IN GENE REGULATION OR DNA REPAIR. UNDERSTANDING THE MOLECULAR-LEVEL MECHANISMS THAT UNDERLIE GENE EXPRESSION AND TRANSCRIPTION-COUPLED DNA REPAIR (TCR) IS A GRAND CHALLENGE IN BIOMEDICAL SCIENCE. PROGRESS TOWARD THIS GOAL HAS BEEN HINDERED BY THE SIZE, COMPLEXITY AND DYNAMIC NATURE OF THE ASSEMBLIES THAT ACCOMPLISH TRANSCRIPTION AND TCR. IN INITIAL STUDIES WITH OUR EXPERIMENTAL COLLABORATORS WE COMBINED COMPUTATIONAL MODELING WITH CRYO-ELECTRON MICROSCOPY DATA TO DETERMINE STRUCTURES OF TRANSCRIPTION PREINITIATION COMPLEXES (PICS) FROM ALL THREE CLASSES OF RNA POLYMERASES (POL I, POL II AND POL III). THE STRUCTURES CAPTURED THE PICS IN MULTIPLE FUNCTIONAL STATES COVERING THE PATH FROM PROMOTER RECOGNITION TO THE FORMATION OF A PROFICIENT ELONGATION COMPLEX. THESE RESULTS OFFER AN UNPRECEDENTED OPPORTUNITY FOR INTEGRATIVE MODELING TO CONNECT THE EXPERIMENTALLY OBSERVED STATES, DELINEATE DNA REMODELING DURING THE EARLY STAGES OF TRANSCRIPTION AND UNCOVER THE CRITICAL MECHANISMS OF TRANSCRIPTION REGULATION. SPECIFICALLY, WE WILL LEVERAGE COMPUTATIONAL AND STRUCTURAL SYSTEMS BIOLOGY APPROACHES TO 1) DETERMINE HOW THE POL I, II AND III TRANSCRIPTION MACHINERIES RECOGNIZE AND OPEN PROMOTER DNA; 2) EXAMINE HOW THE TRANSCRIPTION FACTOR TFIID ASSOCIATES WITH PROMOTER DNA AND SERVES AS A PLATFORM FOR ASSEMBLING THE PIC; AND 3) UNCOVER THE KEY FUNCTIONS OF TWO RECOGNIZED TCR MASTER COORDINATORS, TRANSCRIPTION FACTOR IIH (TFIIH) AND COCKAYNE SYNDROME B PROTEIN (CSB). OUR WORK WILL BENEFIT FROM SYNERGISTIC COLLABORATIVE INTERACTIONS WITH WORLD-CLASS EXPERIMENTAL GROUPS TO INFORM, VALIDATE, AND EXTEND OUR MODELS. PARALLEL ADVANCES IN COMPUTATION AND CRYO-EM WILL YIELD KEY INSIGHTS INTO THE STRUCTURE, DYNAMICS AND FUNCTION OF GENE REGULATORY COMPLEXES WHILE MAKING DIRECT CONNECTION TO GENETIC DISEASE PHENOTYPES. SUCCESS OF THE PROJECT WILL THUS HAVE MAJOR IMPACTS - BOTH IN UNDERSTANDING THE ETIOLOGY OF CANCERS AND INHERITED GENETIC DISORDERS AND IN OFFERING A STRUCTURAL FRAMEWORK TO DEVISE EFFECTIVE TREATMENTS.

REGULATING NEUTROPHIL RESPONSE DURING CHRONIC INFLAMMATION THROUGH SIRPA ALTERATI

RFA-DP-24-004, PRC CORE: PROMOTING SOCIAL CONNECTEDNESS IN THE MOST DIVERSE SQUARE MILE IN AMERICA

SCC-IRG TRACK 1: SMART AND SAFE PRESCRIBED BURNING FOR RANGELAND AND WILDLAND URBAN INTERFACE COMMUNITIES -PRESCRIBED FIRES HAVE LONG BEEN USED BY RANCHERS AND FARMERS IN THE GREAT PLAINS AS A LAND MANAGEMENT TOOL. THEY HELP FARMING AND GRAZING BY REPLENISHING THE SOIL, INCREASING FORAGE PRODUCTION, AND PROTECTING PRAIRIES FROM INVASIVE OVERGROWTH. THEY ARE ALSO USED BY RURAL AND WILDLAND URBAN INTERFACE (WUI) COMMUNITIES TO REMOVE BUILT-UP FUELS FOR REDUCING RISKS OF WILDFIRES. DESPITE THE MANY BENEFITS OF PRESCRIBED FIRES, THERE ARE SAFETY AND ENVIRONMENTAL CONCERNS FOR PRESCRIBED BURN EVENTS. ON THE SAFETY ASPECT, AN ESCAPED FIRE OR A FIRE REIGNITED FROM SMOLDERING FUELS CAN BECOME UNCONTROLLED AND RESULT IN SEVERE PROPERTY DAMAGES AND INJURIES TO PEOPLE. ON THE ENVIRONMENTAL ASPECT, SMOKE FROM PRESCRIBED FIRES CAUSES AIR POLLUTION FOR LOCAL COMMUNITIES AND COMMUNITIES DOWNWIND. TO MANAGE AND MINIMIZE THESE CONCERNS, OPTIMAL PLANNING AND EXECUTION OF PRESCRIBED FIRES ARE CRUCIAL. THE OBJECTIVE OF THIS PROJECT IS TO DEVELOP A COMMUNITY SENSING, PLANNING, AND LEARNING INFRASTRUCTURE TO SUPPORT SMART AND SAFE PRESCRIBED BURNING FOR COMMUNITIES THAT USE PRESCRIBED FIRES FOR RANGELAND AND WILDFIRE RISK MANAGEMENT. THE DEVELOPED INFRASTRUCTURE WILL BE INTEGRATED INTO A CLOUD-BASED PLATFORM TO SUPPORT LANDOWNERS TO OPTIMALLY PLAN AND OPERATE PRESCRIBED BURNS, COLLECT AND SHARE DATA ABOUT BURNING, AND TRAIN FIRE OPERATORS TO LEARN THE MOST EFFECTIVE WAYS OF BURNING. THE PROJECT WILL ALSO PROMOTE TECHNOLOGY AWARENESS FOR BUILDING SMART COMMUNITIES IN RURAL AREAS, BY INCREASING PARTNERSHIPS AMONG ACADEMIA, RURAL COMMUNITIES, AND LOCAL GOVERNMENTS. THE INTEGRATED RESEARCH OF THIS PROJECT INCLUDES: 1) TECHNICAL RESEARCH ON MULTI-SCALE SENSING AND DATA FUSION, DATA-DRIVEN BURN CONDITION MODELING, GRASSLAND FUEL MAPPING & HOTSPOT DETECTION, AND FIRE BEHAVIOR MODELING AND SIMULATION; 2) SOCIAL SCIENCE RESEARCH THAT ADDRESSES THE KNOWLEDGE GAP ON HOW COMMUNITIES ENGAGE WITH AND COORDINATE BURN PRACTICES THROUGH THE USE OF TECHNOLOGY; AND 3) COMMUNITY ENGAGEMENT THAT DEVELOPS TOOLS, DATA REPOSITORIES, AND ACTIVITIES TO SUPPORT COMMUNITIES? SMART AND SAFE PRESCRIBED BURNING. THE MULTISCALE SENSING AND DATA FUSION INTEGRATE DATA FROM HETEROGENEOUS SOURCES INCLUDING SATELLITE REMOTE SENSING, UNMANNED AIRCRAFT SYSTEMS, AND CROWDSOURCED REPORTS. WE WILL WORK WITH TWO COMMUNITIES IN KANSAS TO EVALUATE AND DEMONSTRATE THE DEVELOPED RESEARCH: 1) THE GYP HILLS COMMUNITY REPRESENTS A RANGELAND COMMUNITY WHERE AN AVERAGE PRESCRIBED FIRE COVERS OVER HUNDREDS OF ACRES FOR GRASSLANDS PRIMARILY USED FOR GRAZING; 2) THE EASTERN KANSAS COMMUNITY REPRESENTS A SUBURBAN WUI COMMUNITY WHERE PRESCRIBED FIRES ARE EMPLOYED AT A SMALLER SCALE. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.

DEVELOPMENT OF ANTI-ANGIOGENESIS THERAPY TARGETING INTEGRIN

SUPPRESSION OF AUTOPHAGY-DEPENDENT CLEARANCE MITOCHONDRIA IN TYPE 2 DIABETES

DISSEMINATING SAFECARE TO PREVENT CHILD MALTREATMENT AND NEGATIVE HEALTH OUTCOMES

REGENERATIVE REHABILITATIVE PRINCIPLES IN MODULATING WEIGHT BEARING AND JOINT KINEMATICS TO DELAY POST-TRAUMATIC KNEE OSTEOARTHRITIS - PROJECT S U MMARY KNEE INJURIES, E.G., MENISCUS TEARS, INCREASE THE RISK OF DEVELOPING POST-TRAUMATIC OSTEOARTHRITIS (PTOA) BY AT LEAST 10 FOLD. PTOA LEADS TO DISABILITY WITH A SUBSTANTIAL HEALTHCARE COST OF $3 BILLION PER YEAR IN THE US. ALTHOUGH REHABILITATION IS REQUIRED AFTER INJURY, CURRENT PROTOCOLS ONLY ADDRESS THE RETURN TO PRE-INJURY ACTIVITIES. CRITICAL KNOWLEDGE GAPS EXIST REGARDING HOW TO OPTIMIZE EARLY REHABILITATION EFFORTS TO PRESERVE LONG-TERM KNEE CARTILAGE HEALTH. USING A WELL-ESTABLISHED RAT PTOA MODEL, WE PROPOSE TO CHARACTERIZE RESPONSES OF KNEE CARTILAGE TO THE MANIPULATION OF THREE ELEMENTS COMMONLY IMPLEMENTED DURING POST-INJURY REHABILITATION: 1) DURATIONS OF INITIAL NON-WEIGHT BEARING, 2) MODIFICATIONS OF PHYSICAL ACTIVITY LEVEL, AND 3) DEVIATIONS IN LOWER-LIMB JOINT KINEMATICS. THE USE OF A PRE-CLINICAL RAT MODEL PROVIDES THE EXPERIMENTAL CONTROL OVER DISEASE TIMELINE TO FACILITATE A MECHANISTIC STUDY TO UNDERSTAND PTOA. OUR OVERALL HYPOTHESIS IS THAT POST-INJURY INTERVENTIONS THAT EMPHASIZE MAINTAINING PRE-INJURY KNEE LOADING PROFILE (E.G. MINIMIZING WEIGHT-BEARING RESTRICTION, REGAINING PHYSICAL ACTIVITY LEVEL, OR REDUCING DEVIATIONS IN JOINT KINEMATICS) WILL DELAY PTOA. WE WILL SYSTEMATICALLY TEST THIS HYPOTHESIS USING INNOVATIVE EXPERIMENTAL APPROACHES AND TECHNOLOGIES TO ADDRESS THE KNOWLEDGE GAPS IN THE PTOA REHABILITATION LITERATURE AS DESCRIBED IN THE FOLLOWING AIMS. (AIM 1) NON-WEIGHT BEARING DURATIONS IN RATS AFTER THE MEDIAL MENISCAL TRANSECTION (MMT) SURGERY PERFORMED ON THE LEFT HIND LIMB WILL BE VARIED USING HIND-LIMB SUSPENSION. THE COMPARISONS OF CARTILAGE HEALTH AMONG VARYING EXPOSURES OF SUSPENSION DETERMINES THE CAUSAL EFFECT OF INITIAL NON-WEIGHT BEARING ON PTOA PROGRESSION. THE USE OF HIND- LIMB SUSPENSION INSTEAD OF LIMB IMMOBILIZATION REDUCES HARMFUL CONSEQUENCES OF JOINT CONTRACTURE AND IS MORE IN LINE WITH CURRENT PRACTICE OF PRESCRIBING INITIAL NON-WEIGHT BEARING AFTER KNEE INJURIES. (AIM 2) POST-INJURY PHYSICAL ACTIVITY LEVELS WILL BE MODIFIED BY VARYING THE AMOUNT OF DAILY TREADMILL RUNNING. RATS’ PRE-INJURY ACTIVITY LEVELS WILL FIRST BE ESTABLISHED TO ALLOW STANDARDIZED QUANTIFICATION OF POST-INJURY ACTIVITY MODIFICATION (% OF PRE-MMT). THE CAUSAL EFFECT OF POST-INJURY ACTIVITY LEVEL ON PTOA PROGRESSION CAN THEN BE DETERMINED. (AIM 3) 3D HIND-LIMB JOINT KINEMATICS WILL BE ASSESSED USING BIPLANAR X-RAY MOTION ANALYSIS AT MULTIPLE TIME POINTS BEFORE AND AFTER MMT TO DETERMINE WHETHER EARLY POST-INJURY JOINT KINEMATIC DEVIATIONS ARE PREDICTIVE OF THE ULTIMATE SEVERITY OF PTOA. USING X-RAY VIDEOS TO DIRECTLY QUANTIFY 3D BONE MOVEMENTS CAN OVERCOME THE SIGNIFICANT ERRORS ASSOCIATED WITH THE USE OF SKIN MARKERS. FOR ALL THREE AIMS, WE WILL INCORPORATE OUR CONTRAST ENHANCED MICROCT ANALYSIS WITH CONVENTIONAL HISTOPATHOLOGY TO PROVIDE COMPLEMENTARY EVALUATIONS OF THE 3D MICROSTRUCTURE/COMPOSITIONS OF KNEE CARTILAGE. FINDINGS FROM THIS INNOVATIVE WORK WILL PROVIDE INSIGHT INTO THE POTENTIAL CAUSAL EFFECTS OF POST-INJURY REHABILITATIVE MODIFICATIONS IN LIMB WEIGHT BEARING AND JOINT KINEMATICS ON PTOA PROGRESSION. SUCH NEW KNOWLEDGE IS FUNDAMENTAL TO ADVANCING OUR UNDERSTANDING OF THE PATHOGENESIS OF PTOA AND DEVELOPING TRANSLATIONAL RESEARCH TO REDUCE PTOA BY OPTIMIZING POST-INJURY REHABILITATION.

ELUCIDATING VASCULAR NEUROPILIN 1 (NRP1) FUNCTIONS IN RESPONSE TO NOVEL INTERACTIONS WITH INSULIN SUBSTRATES - PROJECT SUMMARY/ABSTRACT OBESITY IS EMERGING A MAJOR PUBLIC HEALTH CHALLENGE IN THE UNITED STATES, AND AROUND THE WORLD. IT CORRELATES WITH SEVERAL COMORBIDITIES INCLUDING, CARDIOVASCULAR DISEASES AND METABOLIC SYNDROMES. ADDITIONALLY, EPIDEMIOLOGICAL DATA SUGGEST STRONG LINKS BETWEEN OBESITY AND CANCER; HOWEVER, MECHANISTIC CONNECTIONS BETWEEN OBESITY AND THESE PATHOLOGICAL CONDITIONS REMAIN INCOMPLETE. SPECIFICALLY, INSULIN RESISTANCE IS CHARACTERIZED BY ATTENUATED WHOLE-BODY SENSITIVITY TO INSULIN AND MAY RESULT IN ELEVATED LEVELS OF CIRCULATING FREE FATTY ACIDS (FFAS). ESSENTIAL METABOLIC FUNCTIONS AND SIGNALING PATHWAYS UNDER THIS CONDITION BECOMES DYSREGULATED, AND ALTER FINELY-TUNED REGULATION OF GLUCOSE, LIPID AND OVERALL ENERGY HEMOSTASIS. THEREFORE, OBESITY IS CENTRAL TO PREVENTABLE PATHOLOGICAL CONDITIONS DUE TO DIRECT INSTIGATION OF METABOLIC PERTURBATIONS AND ASSOCIATED INFLAMMATORY RESPONSES. IMPORTANTLY, ELUCIDATING NOVEL METABOLIC, AS WELL AS ANGIOGENIC REGULATORS MAY PROVIDE UNIQUE INSIGHT OF DISEASE CONDITIONS, SUCH AS CARDIOVASCULAR DISEASES AND CANCER THAT DEPEND ON THESE PROCESSES. STUDIES ON METABOLISM AND CELLULAR ENERGETICS HAVE INCLUDED SKELETAL MUSCLES, ADIPOSE AND HEPATIC CELLS GIVEN PROMINENT ROLES THESE TISSUES PLAY WITH RESPECT TO LIPID UTILIZATION AND STORAGE. HOWEVER, THE RESPONSE OR CONTRIBUTIONS OF VASCULAR TARGETS WITH RESPECT TO METABOLIC SYNDROMES, INCLUDING OBESITY- INSTIGATED PERTURBATIONS REMAIN UNCLEAR. AT THE NEXUS OF PROPOSED `VASCULAR RESPONSE TARGET' IS TRANSMEMBRANE, NEUROPILIN-1 (NRP1) RECEPTOR. WE HYPOTHESIZE THAT OBESITY AND CONCOMITANT INCREASE OF CIRCULATING FFAS PROMOTE THE EXPRESSION AND INTERACTION OF NRP1 WITH INSULIN SUBSTRATES, WHICH VASCULAR NRP1 FUNCTIONS.

MICROBIOME AND IMMUNOSENESCENCE OF T CELLS REPERTOIRE

AUTOREACTIVE CD4 T CELLS IN HEALTHY MICE

MECHANISMS OF LIPOPHAGY, THE SELECTIVE AUTOPHAGY OF LIPID DROPLETS

BEHAVIORAL HEALTH WORKFORCE EDUCATION AND TRAINING PROGRAM

ANTIGENIC SPECIFICITIES OF INTESTINAL CD4+FOXP3+ T CELLS

INTERROGATING DISTINCT ANGIOTENSIN TYPE-1 AND TYPE-2 RECEPTOR CONTAINING BRAIN CIRCUITS TO UNDERSTAND AND ALLEVIATE HYPERTENSION

ENGLISH LANGUAGE ACQUISITION: NATIONAL PROFESSIONAL DEVELOPMENT PROGRAM

CYTOMEGALOVIRUS RETINITIS PATHOGENESIS: MECHANISMS OF RETINAL TISSUE DESTRUCTION

LESSONS FROM THE PANDEMIC: THE EFFECTS OF REMOTE INSTRUCTIONAL DELIVERY AND RECOVERY STRATEGIES ON STUDENT OUTCOMES

VTA MC3R NEURONS IN THE CONTROL OF FEEDING AND BODY WEIGHT

PRE-CLINICAL VALIDATION OF A NOVEL PROTEIN DRUG CANDIDATE FOR ASH AND NASH TREATMENT - SUMMARY ALCOHOLIC STEATOHEPATITIS (ASH) AND NONALCOHOLIC STEATOHEPATITIS (NASH) AFFECTS A LARGE POPULATION IN US AND WORLDWIDE. CURRENTLY, MAJOR UNMET MEDICAL NEEDS INCLUDE LACK OF METHOD OR AGENT TO SPECIFICALLY DEPLETE ACTIVATED HSC AND CAPILLARIZED LSEC AS WELL AS NONINVASIVE METHODOLOGY AND REAGENTS TO VISUALIZE COLLAGEN BUILD-UP, HSC ACTIVATION, AND LSEC CAPILLARIZATION IN FIBROTIC LIVER. WE HAVE DEVELOPED A PROTEIN DRUG CANDIDATE (REFERRED TO AS “PROAGIO”) THAT TARGETS INTEGRIN AVSS3 AT A NOVEL SITE TO INDUCE APOPTOSIS OF INTEGRIN AVSS3 EXPRESSING CELLS BY A NOVEL MECHANISM. PROAGIO SPECIFICALLY INDUCES APOPTOSIS OF INTEGRIN V3 EXPRESSING CELLS WITH A HIGH EFFICACY BY RECRUITING & ACTIVATING CASPASE 8 AT CYTOPLASMIC DOMAIN OF. WE DEMONSTRATED IN OUR PRELIMINARY STUDIES THAT TREATMENT OF MICE THAT CARRIES LIVER FIBROSIS/CIRRHOSIS INDUCED BY TAA/ALCOHOL CCL4 AND THE HIGH-FAT DIET INDUCE NASH MICE WITH PROAGIO REVERSED LIVER FIBROSIS/CIRRHOSIS. IN ADDITION, WE HAVE DEVELOPED NOVEL PROTEIN MRI CONTRAST AGENTS (PROCAS) THAT ALLOW US TO ASSESS COLLAGEN CONTENTS AND INTEGRIN AVSS3 POSITIVE HSCS & LSECS IN FIBROTIC LIVER. MR IMAGING OF FIBROTIC MICE DEMONSTRATED SUPERIOR PROPERTIES OF OUR DEVELOPED CONTRAST AGENTS FOR COLLAGEN AND INTEGRIN V3 POSITIVE CELL ASSESSMENT. PRELIMINARY TOXICITY ANALYSES WITH HEALTHY MICE INDICATE THAT PROAGIO AND OUR DEVELOPED MRI CONTRAST AGENTS ARE NOT TOXIC TO MICE AT VERY HIGH DOSE. THE GOAL OF THIS PROJECT IS TO VIGOROUSLY PRE-CLINICAL VALIDATION OF PROAGIO AS A DRUG CANDIDATE FOR ASH/NASH PATIENT TREATMENT. WE WILL ACHIEVE OUR OBJECTIVE BY THREE SPECIFIC AIMS. AIM 1 IS TO EXAMINE THE EFFECTIVENESS OF PROAGIO IN REVERSAL OF LIVER FIBROSIS USING HIGH-FAT DIET PLUS MULTIPLE BINGE ALCOHOL AND CHRONIC ALCOHOL BINGE INDUCED ASH MODELS. INVESTIGATION OF THE EFFECTS OF PROAGIO IN ASH MOUSE MODELS WILL FURTHER PRE-CLINICAL VALIDATION OF PROAGIO AS AN ASH/NASH TREATMENT DRUG. AIM 2 IS TO MONITOR AND VALIDATE THE EFFECTS OF PROAGIO ON COLLAGEN AND HSC IN FIBROTIC LIVER BY MR IMAGING USING OUR DEVELOPED MRI CONTRAST AGENTS. OUR MR IMAGING AIDED VALIDATION WILL NOT ONLY VALIDATE THE EFFECTIVENESS OF PROAGIO AS AN ASH/NASH TREATMENT AGENT, BUT ALSO VALIDATE THE TARGET AND MECHANISM OF DRUG ACTION. AIM 3 IS PRE-CLINICAL VALIDATIONS OF PROAGIO AS AN ASH/NASH TREATMENT DRUG CANDIDATE VIA TOXICOLOGY (TOX) AND PHARMACOKINETIC (PK) ANALYSES. OUR STUDY WILL OPEN A NEW AVENUE FOR ASH/NASH TREATMENT AND DIAGNOSIS/PROGNOSIS BY PROTEIN DESIGN. SUCCESS IN OUR STUDIES WILL NOT ONLY DEVELOP A NEW PROTEIN DRUG FOR LIVER FIBROSIS/CIRRHOSIS TREATMENT BUT ALSO TEST HIGHLY EFFECTIVE MRI CONTRAST AGENTS THAT ALLOW US TO ACCURATELY AND NON-INVASIVELY MONITOR FIBROSIS PROGRESSION AND REGRESSION FOR ASSESSMENT OF TREATMENT EFFECTS. SUCH DEVELOPMENT IS EXPECTED TO FILL IN THE MAJOR MEDICAL GAPS AND TO FACILITATE TO DEVISE TREATMENT STRATEGY TO REVERSE FIBROSIS AND FOLLOW HIGH RISK PATIENTS.

SELECTIVE NITROGEN ATOM TRANSFER FOR APPLICATIONS IN BIOMEDICAL SCIENCES

CHEMOKINE SIGNALING IN EPC ANGIOGENESIS: A ROLE OF LYSINE METHYLATION

PROJECT SOCIAL CODE: LEVERAGING ROBOTICS AND STEM ENVIRONMENTS TO TEACH SOCIAL SKILLS AT THE ELEMENTARY LEVEL

MACROPHAGE AMPK, INFLAMMATION, AND ATHEROSCLEROSIS

ACQUIRING LANGUAGE WITH A COCHLEAR IMPLANT: THE ROLE OF SEQUENTIAL LEARNING

PREVENTION OF HIGH FAT DIET-INDUCED VASCULAR INJURY

TRANSITION TO TEACHING PROGRAM -- LOCAL

EDUCATIONAL OPPORTUNITY CENTERS PROGRAM

IMPACT OF ADVANCED AGE ON OPIATE ANALGESIA

FECAL EXOSOMES AS A SOURCE OF MIRNA BIOMARKERS FOR DIAGNOSING THE DEGREE OF COLITIS AND AS A DRUG DELIVERY SYSTEM TO REDUCE COLITIS

SSS REGULAR

GRADUATE PSYCHOLOGY EDUCATION PROGRAMS

MKP1, VSMC, AND VASCULAR REMODELING

CRYO-ELECTRON AND BIOCHEMICAL ANALYSIS OF NATIVE PARAMYXOVIRUS FUSION COMPLEXES

COMMUNICATING FOR HEALTH EQUITY IN DIGITAL ENVIRONMENTS - ABSTRACT SMOKING IS INCREASINGLY CONCENTRATED IN SOCIOECONOMICALLY DISADVANTAGED POPULATIONS THAT MIGHT NOT HAVE BEEN REACHED BY THE POLICIES AND COMMUNICATION CAMPAIGNS TO THE SAME DEGREE AS THE MORE PROSPEROUS GROUPS. IN THE RAPIDLY CHANGING MEDIA LANDSCAPE, NEW APPROACHES TO DEVELOPING AND TESTING MESSAGES ARE NEEDED. THIS PROJECT WILL USE AN INNOVATIVE COMBINATION OF QUALITATIVE, EYE TRACKING, AND QUANTITATIVE (DISCRETE CHOICE EXPERIMENT, RANDOMIZED CLINICAL TRIAL) STUDIES TO DEVELOP AND EVALUATE TOBACCO EDUCATION MESSAGE STRATEGIES DELIVERED ON DIGITAL CHANNELS THAT COMMUNICATE COMPLEX SCIENTIFIC CONCEPTS TO THE PUBLIC, PARTICULARLY THE PRIORITY POPULATIONS. THESE STRATEGIES WILL BE DEVELOPED IN THE CONTEXT OF THE FDA-PROPOSED BAN ON MENTHOL IN CIGARETTES AND FLAVORS IN CIGAR PRODUCTS (“FLAVOR BAN”). FLAVOR BAN HAS THE POTENTIAL TO SAVE HUNDREDS OF THOUSAND OF LIVES, BUT CAN BE UNDERMINED BY MISINFORMATION AND MISPERCEPTIONS. LITTLE RESEARCH HAS SYSTEMATICALLY DOCUMENTED THE MISPERCEPTIONS OR DEVELOPED MESSAGES TO CORRECT THEM. OUR PROJECT PROPOSES TO ADDRESS THIS IMPORTANT GAP BY DEVELOPING AND TESTING STRATEGIES TO REACH PRIORITY POPULATIONS WITH MESSAGES ON DIGITAL CHANNELS. THIS PROJECT WILL PROVIDE THAT RESEARCH BY PURSUING THESE SPECIFIC AIMS: (1) IDENTIFY EFFECTIVE MESSAGE ATTRIBUTES FOR DIGITAL CHANNELS USING A CO-CREATION APPROACH; (2) QUANTIFY THE RELATIVE IMPORTANCE OF DIFFERENT ATTRIBUTES OF DIGITAL MESSAGES USING A COMBINATION OF A DISCRETE CHOICE EXPERIMENT AND AN EYE- TRACKING STUDY; AND (3) TEST THE IMPACT OF MESSAGES ON BEHAVIORAL OUTCOMES IN A CONTEXT OF DIGITAL SOCIAL MEDIA IN A RANDOMIZED CLINICAL TRIAL WITH A NATIONALLY REPRESENTATIVE SAMPLE OF FLAVORED COMBUSTED TOBACCO PRODUCT USERS. THE RESULTS WILL HELP ELIMINATE TOBACCO-RELATED DISPARITIES AND INCREASE THE EFFECTIVENESS OF TOBACCO EDUCATIONAL MESSAGES AMONG THE POPULATION FOR WHOM ANTI-TOBACCO MESSAGES HAVE NOT BEEN OPTIMALLY EFFECTIVE.

IMPACT OF HEMODYNAMICS ON EFFEROCYTOSIS IN ENDOTHELIAL CELLS - PROJECT SUMMARY/ABSTRACT FLOWING BLOOD GENERATES A FRICTIONAL FORCE CALLED SHEAR STRESS THAT PLAYS AN IMPORTANT ROLE IN ENDOTHELIAL DYSFUNCTION AND ATHEROSCLEROSIS. BRANCHES AND BENDS OF ARTERIES ARE EXPOSED TO LOW AND DISTURBED FLOW (D-FLOW), A MECHANICAL ENVIRONMENT THAT PROMOTES VASCULAR DYSFUNCTION AND ATHEROSCLEROSIS. CONVERSELY, PHYSIOLOGICALLY HIGH SHEAR STRESS GENERATED FROM STEADY LAMINAR FLOW (S-FLOW) IS PROTECTIVE. HELICAL FLOW (H-FLOW) ASSOCIATED WITH ADVANCED SHEAR STRESS EXISTS NOT ONLY IN THE ASCENDING AORTA BUT ALSO IN OTHER PARTS SUCH AS THE RIGHT CORONARY ARTERY, DESCENDING AORTA, COMMON ILIAC ARTERY, AND COMMON FEMORAL ARTERY. H-FLOW MAY HAVE SEVERAL POSITIVE PHYSIOLOGICAL ROLES, SUCH AS SUPPRESSING/ELIMINATING AREAS OF FLOW STAGNATION, PREVENTING THE ACCUMULATION OF ATHEROGENIC LIPIDS ON THE LUMINAL SURFACES OF ARTERIES, AND ENHANCING OXYGEN TRANSPORT FROM THE BLOOD TO THE ARTERIAL WALL. ENDOTHELIAL CELLS (ECS) ARE CRITICAL SENSORS OF THE SHEAR STRESS THAT CONTRIBUTES TO ATHEROSCLEROSIS. EFFEROCYTOSIS IS A PROCESS BY WHICH APOPTOTIC TISSUE IS RECOGNIZED FOR ENGULFMENT BY PHAGOCYTIC CELLS, SUCH AS PROFESSIONAL PHAGOCYTES (E.G., MACROPHAGES AND IMMATURE DENDRITIC CELLS) AND NON-PROFESSIONAL PHAGOCYTES (E.G., ECS, EPITHELIAL CELLS, FIBROBLASTS, AND SOME STROMAL CELLS). DEFECTIVE EFFEROCYTOSIS IN MACROPHAGES PROMOTES ADVANCED ATHEROSCLEROSIS. HOWEVER, THE MECHANISMS BY WHICH SHEAR STRESS ENVIRONMENTS REGULATE EC EFFEROCYTOSIS AND ITS IMPLICATIONS IN ATHEROSCLEROSIS REMAIN LARGELY UNKNOWN. THE CENTRAL HYPOTHESIS TO BE TESTED IN THIS PROJECT IS THAT BLOOD FLOW PATTERNS REGULATE EC EFFEROCYTOSIS AND SUBSEQUENT ENDOTHELIAL DYSFUNCTION AND CONTRIBUTE TO THE DEVELOPMENT OF ATHEROSCLEROSIS. OUR LONG-TERM GOAL IS TO DISSECT THE RELATIONSHIP BETWEEN BLOOD FLOW PATTERNS AND EC EFFEROCYTOSIS AND ITS ROLE IN THE DEVELOPMENT OF ATHEROSCLEROSIS. OUR SPECIFIC AIMS ARE AIM 1- DEFINE THE ROLE OF BLOOD FLOW PATTERNS IN EC EFFEROCYTOSIS AND ENDOTHELIAL DYSFUNCTION, AIM 2- DETERMINE THE ROLE OF MERTK IN ENDOTHELIAL MECHANOTRANSDUCTION, AND AIM 3- EVALUATE THE CONTRIBUTION OF EC EFFEROCYTOSIS IN ATHEROSCLEROSIS. DEFINING THE MECHANISMS OF EFFEROCYTOSIS REGULATION WILL BE NECESSARY TO TARGET ENDOTHELIAL MECHANOTRANSDUCTION AND SUBSEQUENT ENDOTHELIAL DYSFUNCTION. THE PROPOSED RESEARCH IS INNOVATIVE IN THE SENSE THAT WE WILL CONNECT BLOOD FLOW PATTERNS, EC EFFEROCYTOSIS, AND ENDOTHELIAL MECHANOTRANSDUCTION. WE WILL ALSO EVALUATE THE NOVEL MECHANISM OF EC EFFEROCYTOSIS AND ITS CONTRIBUTION TO ATHEROSCLEROSIS.

INTEGRATIVE MODELING OF BIOMOLECULAR MACHINERY IN NUCLEOTIDE EXCISION REPAIR - PROJECT SUMMARY/ABSTRACT NUCLEOTIDE EXCISION REPAIR (NER) IS AN ESSENTIAL GENOME MAINTENANCE PATHWAY THAT DETECTS AND REMOVES HARMFUL DNA LESIONS RESULTING FROM EXPOSURE TO ENVIRONMENTAL CARCINOGENS, TOXINS, ALKYLATING AGENTS, REACTIVE OXYGEN SPECIES AND ULTRAVIOLET RADIATION. NER STANDS OUT AMONG ALL DNA REPAIR PATHWAYS FOR ITS ABILITY TO REMOVE THE WIDEST ARRAY OF STRUCTURALLY UNRELATED LESIONS. THE NEED TO PROCESS A WIDE VARIETY OF DAMAGED SITES HAS GIVEN RISE TO A REMARKABLY COMPLEX MOLECULAR MACHINERY. DEFECTS IN THIS MACHINERY PROVIDE A PARADIGM FOR THE DIVERSE CLINICAL CONSEQUENCES OF DNA DAMAGE AND ARE ASSOCIATED WITH SEVERE HUMAN DISEASES – 1) ULTRAVIOLET RADIATION- SENSITIVE SYNDROME; 2) XERODERMA PIGMENTOSUM, CHARACTERIZED WITH EXTREME CANCER PREDISPOSITION; 3) CEREBRO- OCULO-FACIO-SKELETAL SYNDROME; 4) TRICHOTHIODYSTROPHY; AND 5) COCKAYNE SYNDROME, ASSOCIATED WITH PREMATURE AGEING AND ACCELERATED NEURODEGENERATION. FURTHERMORE, NER IS INTRICATELY INTERTWINED WITH OTHER VITAL PATHWAYS THAT ORCHESTRATE THE EXPRESSION AND REPAIR OF GENES. THUS, UNDERSTANDING THE MOLECULAR MECHANISMS OF NER IS A GRAND CHALLENGE IN BIOMEDICAL SCIENCE. PROGRESS TOWARD THIS GOAL HAS BEEN HINDERED BY THE SIZE, COMPLEXITY AND DYNAMIC NATURE OF THE ASSEMBLIES THAT ACCOMPLISH NER. TO OVERCOME THIS CRITICAL BARRIER TO PROGRESS, WE WILL EMPLOY INTEGRATIVE MODELING METHODS, COMBINING STATE-OF-THE-ART COMPUTATION WITH EXPERIMENTAL DATA FROM CRYO-ELECTRON MICROSCOPY (CRYO-EM), SITE-DIRECTED MUTAGENESIS, CROSSLINKING MASS SPECTROMETRY (XL-MS), HYDROGEN DEUTERIUM EXCHANGE (HDX) MASS SPECTROMETRY AND SMALL ANGLE X-RAY SCATTERING (SAXS) TO ELUCIDATE THE ASSEMBLY, FUNCTION AND REGULATION OF KEY NER COMPLEXES. SPECIFICALLY, OUR FOCUS IS ON TRANSCRIPTION FACTOR IIH (TFIIH) AS THE CENTERPIECE OF THE NER MACHINERY. IN AIM1, WE WILL ELUCIDATE THE FUNCTIONAL DYNAMICS OF TFIIH AND DISCOVER KEY ALLOSTERIC RESIDUE NETWORKS ENABLING THE FUNCTION OF THIS RECOGNIZED NER MASTER COORDINATOR. WE WILL ALSO DECIPHER THE EFFECTS OF TFIIH DISEASE MUTATIONS, PROVIDING A NOVEL PARADIGM FOR THE DIVERSE CLINICAL MANIFESTATIONS OF NER IMPAIRMENT. IN AIM2, WE WILL UNRAVEL THE MECHANISMS OF TFIIH-ASSOCIATED LESION SCANNING AND DNA DAMAGE VERIFICATION. IN AIM3, WE WILL SYNTHESIZE DIVERSE STRUCTURAL DATA TO CREATE AN INTEGRATIVE MODEL OF THE MOST CRUCIAL INTERMEDIATE IN NER – THE PRE-INCISION COMPLEX. HYBRID MODELS WILL DEFINE THE STRUCTURAL ELEMENTS ALLOWING TFIIH TO SERVE AS A MOBILE PLATFORM FOR THE ASSEMBLY AND REMODELING OF THE NER MACHINERY. OUR WORK WILL BENEFIT FROM SYNERGISTIC COLLABORATIVE INTERACTIONS WITH WORLD-CLASS EXPERIMENTAL GROUPS TO INFORM, VALIDATE, AND EXTEND OUR MODELS. PARALLEL COMPUTATIONAL AND EXPERIMENTAL ADVANCES WILL YIELD KEY INSIGHTS INTO THE STRUCTURE, DYNAMICS AND FUNCTION OF NER COMPLEXES WHILE MAKING DIRECT CONNECTION TO GENETIC DISEASE PHENOTYPES. SUCCESS OF THE PROJECT WILL THUS HAVE MAJOR IMPACTS - BOTH IN UNDERSTANDING DISEASE ETIOLOGY AND IN OFFERING A STRUCTURAL FRAMEWORK TO DEVISE EFFECTIVE TREATMENTS.

MECHANISMS UNDERLYING OPPOSING NEURONAL RESPONSES TO BRIEF VS. PROLONGED DOPAMINE

CTE TEACHER LABOR MARKETS, ATTRIBUTES, AND STUDENT OUTCOMES

EPIGENETIC REGULATION OF BROWN FAT THERMOGENESIS BY THE HISTONE DEMETHYLASE KDM6A