West Virginia University Research Corporation

WEST VIRGINIA IDEA-CTR

TAS::89 0213::TAS U.S. - CHINA CLEAN ENERGY RSEARCH CENTER ADVANCED COAL TECHNOLOGY COLLABORATION

WEST VIRGINIA STROKE COBRE

TUMOR MICROENVIRONMENT (TME) COBRE

MARCELLUS SHALE ENERGY AND ENVIRONMENT LABORATORY (MSEEL)

CONSTRUCTION OF NEW ANIMAL FACILITY ANNEX FOR WEST VIRGINIA UNIVERSITY

COMMUNITY PROJECT FUNDING/CONGRESSIONALLY DIRECTED SPENDING - CONSTRUCTION - WEST VIRGINIA UNIVERSITY SCHOOL OF DENTISTRY IS THE ONLY DENTAL SCHOOL IN WEST VIRGINIA. THE SCHOOL OPENED IN 1957 AND GRADUATED THE FIRST CLASS OF DENTISTS IN 1961. EXCEPT FOR SEVERAL SMALL-SCALE CLINIC UPGRADES, THE SCHOOL APPEARS MUCH AS IT DID IN 1957. ORAL HEALTH IS OUR PRIORITY AND OUR MISSION. OUR VISION IS TO BE THE DENTAL SCHOOL OF CHOICE FOR STUDENTS, FACULTY, STAFF AND PATIENTS. DEFINED BY INNOVATION IN EDUCATION, PATIENT CARE, RESEARCH, AND SERVICE, THE SCHOOL OF DENTISTRY FOSTERS THE DEVELOPMENT OF HIGHLY SKILLED GRADUATES COMMITTED TO CLINICAL EXCELLENCE. THE GRADUATES FROM SCHOOL OF DENTISTRY PROGRAMS PROVIDE ORAL HEALTH CARE IN RURAL COMMUNITIES ACROSS WEST VIRGINIA. APPROXIMATELY 83% OF THE DENTISTS PRACTICING WITHIN THE STATE ARE GRADUATES OF THE SCHOOL OF DENTISTRY. AS A LAND-GRANT UNIVERSITY, WE ARE COMMITTED TO ELIMINATING ORAL HEALTH DISPARITIES ACROSS WEST VIRGINIA. THE WVU SCHOOL OF DENTISTRY IS AT THE VERY CENTER OF IMPROVING AND ADVANCING ORAL HEALTH, AND ACCESS TO CARE TO BUILD A HEALTHIER WEST VIRGINIA. THE WV ORAL HEALTH COALITION HAS ESTABLISHED A STRONG PARTNERSHIP WITH THE SCHOOL OF DENTISTRY TO CREATE INNOVATIVE AND VIABLE SOLUTIONS TO ADDRESS ORAL HEALTH INEQUITIES AND GAPS IN ACCESS TO CARE ACROSS WEST VIRGINIA. THE NEXT, TRANSFORMATIONAL PHASE IN THE HISTORY OF WVU SCHOOL OF DENTISTRY WILL BE THE EXPANSION AND RENOVATION OF EXISTING DENTAL CLINIC SPACE AND CONSOLIDATING ALL PROGRAMS ON THE HEALTH SCIENCES CENTER CAMPUS. THE RENOVATIONS AND UPGRADES WILL TRANSFORM DENTAL EDUCATION AND PRACTICE TO MEET THE ORAL HEALTH NEEDS OF WEST VIRGINIA FAMILIES, PROVIDE EXCELLENCE IN TRAINING FOR NEW GENERATIONS OF DENTAL PROFESSIONALS, ENABLE THE SCHOOL TO COMPETE FOR AND RETAIN WELL-QUALIFIED FACULTY AND STUDENTS, AND PROPEL DENTAL RESEARCH TO FURTHER SUPPORT PATIENT CARE, EDUCATION AND OUTREACH PROGRAMMING. THE SCHOOL OF DENTISTRY OFFERS A 4-YEAR PREDOCTORAL (DDS) PROGRAM AND 4-YEAR BS IN DENTAL HYGIENE. THE SCH OOL ALSO OFFERS SEVEN ADVANCED EDUCATION AND POSTDOCTORAL RESIDENCY PROGRAMS. THESE INCLUDE ORAL AND MAXILLOFACIAL SURGERY, ORTHODONTICS, ENDODONTICS, PERIODONTICS, PROSTHODONTICS, PEDIATRIC DENTISTRY AND A GENERAL PRACTICE RESIDENCY. THE COMPREHENSIVE RENOVATION OF THE ACADEMIC AND CLINICAL FACILITY WILL PROVIDE STATE-OF-THE-ART EQUIPMENT AND TECHNOLOGIES FOR PATIENT TREATMENT, STUDENT EDUCATION, OUTREACH, AND RESEARCH. THE GOAL IS TO CONSOLIDATE AND COMPLEMENT THE SCHOOL’S COMPREHENSIVE PROGRAMMING BY RETURNING POSTDOCTORAL TRAINING AND CLINIC SPACE FROM SUNCREST TOWNE CENTRE TO THE MAIN SCHOOL OF DENTISTRY CAMPUS WITHIN HEALTH SCIENCES CENTER. ADDITIONAL SPACE HAS BEEN ALLOCATED IN THE HEALTH SCIENCES CENTER TO ALLOW FOR THIS PLANNED EXPANSION. CENTRAL TO RENOVATION PLANNING WAS THE DEVELOPMENT OF TWO INDEPENDENT PHASES OF THE RENOVATION. EACH PHASE IS DISTINCT AND SEPARATE AND STANDS INDEPENDENTLY ON ITS OWN WITH RESPECT TO BUILD, FINANCING AND OCCUPANCY FOR CLINICAL CARE. OPERATIONS AT SUNCREST TOWNE CENTRE INCLUDE THE INNOVATION CENTER, DENTAL GROUP PRACTICE, AND RESIDENCY PROGRAMS IN ORTHODONTICS, PERIODONTICS AND PROSTHODONTICS. PHASE ONE INCLUDES RENOVATION OF THE EXISTING SPACE IN THE DENTAL SCHOOL AND HEALTH SCIENCES CENTER TO HOUSE THE ORTHODONTIC AND PEDIATRIC DENTISTRY DEPARTMENTS, THE INNOVATION CENTER AND DENTAL GROUP PRACTICE. THE PROJECTED COST OF PHASE ONE IS $12,785,000. A FOLLOW-ON RENOVATION INITIATIVE WILL INCLUDE CONSTRUCTION AND CONSOLIDATION OF THE SPECIALTY CLINICS AND ADVANCED EDUCATION PROGRAMS. ENHANCED AND MODERNIZED FACILITIES AND EQUIPMENT WILL BE AN INCENTIVE FOR THE RECRUITMENT OF THE BEST AND BRIGHTEST FACULTY, STUDENTS, AND STAFF. THIS WILL ALLOW OUR GRADUATES TO BE WELL PREPARED TO ENTER THE WORK FORCE CONFIDENT IN THEIR SKILLS AND ABILITIES TO PROVIDE EXCELLENCE PATIENTS DESERVE AND EXPECT. WE ARE COMMITTED TO IMPROVING THE ORAL HEALTH OF WEST VIRGINIA FAMILIES ENTRUSTED TO OUR CARE.

ODEP DISABILITY GRANTS

VISUAL SCIENCES CENTER OF BIOMEDICAL RESEARCH EXCELLENCE - PROJECT SUMMARY/ABSTRACT THE OVERARCHING GOAL OF THE VISUAL SCIENCES COBRE (VS-COBRE) IS TO OPTIMIZE INFRASTRUCTURE AND MENTORING TO SUPPORT A SUSTAINABLE, MULTIDISCIPLINARY, AND COLLABORATIVE RESEARCH ENVIRONMENT AT WVU AROUND VISUAL SCIENCES. THE ESTABLISHMENT OF THE VS-COBRE WILL STRENGTHEN THE SCIENTIFIC COMMUNITY FOCUSED ON UNDERSTANDING PROCESSES THAT ARE ESSENTIAL TO VISUAL HEALTH WITH THE LONG-TERM GOAL OF CONTRIBUTING TO NOVEL APPROACHES FOR PREVENTION AND TREATMENT OF BLINDING DISEASES THAT DISPROPORTIONATELY AFFECT APPALACHIA'S POPULATION. WEST VIRGINIA HAS THE 2ND HIGHEST RATE OF VISUAL DISABILITY IN THE NATION, AND THE INCIDENCE IS PROJECTED TO DOUBLE BY 2050. WE WILL ACHIEVE OUR GOALS BY COMPLETING THE FOLLOWING AIMS: AIM1, SUPPORT PROJECT LEADERS (PLS) TO ACHIEVE INDEPENDENT EXTRAMURAL FUNDING; AIM 2, PROMOTE THE FUNDAMENTAL UNDERSTANDING OF THE VISUAL SYSTEM THROUGH OPTIMIZING RELEVANT TECHNICAL INFRASTRUCTURE; AIM 3, PROMOTE A COMPREHENSIVE, MULTIDISCIPLINARY APPROACH TO IMPACTFUL VISUAL SCIENCES RESEARCH; AND AIM 4: IMPLEMENT A RIGOROUS STRATEGY TO EVALUATE THE EFFECTIVENESS OF THE VS-COBRE TOWARDS PROMOTING A ROBUST CENTER OF EXCELLENCE IN VISUAL SCIENCES. WITH OUR EXISTING STRENGTHS AND RESEARCH INFRASTRUCTURE NETWORK, COUPLED WITH THE INITIATIVES PROPOSED IN THIS VS-COBRE, INCLUDING MENTORING OF OUR FOUR-PROMISING JUNIOR PLS, WE ARE WELL-POSITIONED TO ACHIEVE OUR GOAL. THE CREATION OF A CENTER OF EXCELLENCE PROVIDES A VENUE FOR INTEGRATING EFFORTS ACROSS THE CAMPUS, INCLUDING ACTIVITIES SUPPORTED BY NIGMS INCLUDING THE WV CTSI AND OTHER COBRES, THE CLINICAL ENTERPRISE IN THE DEPARTMENT OF OPHTHALMOLOGY AND VISUAL SCIENCES, AND INVESTIGATIONS LED BY BASIC BIOLOGISTS IN THE DEPARTMENTS OF BIOCHEMISTRY, NEUROSCIENCE, BIOLOGY, AND THE PROGRAM IN BIOMEDICAL ENGINEERING. THE VS-COBRE WILL COALESCE VISION SCIENTISTS AROUND A COMMON THEME, ENHANCE THE INTELLECTUAL ENVIRONMENT, AND CULTIVATE CROSS COLLABORATIONS. WHEN THE INVESTIGATORS PROPOSED FOR SUPPORT BY THIS GRANT ACHIEVE INDEPENDENCE BY OBTAINING AN R01-EQUIVALENT AWARD, WE WILL LEVERAGE THE VS-COBRE TO RECRUIT ADDITIONAL JUNIOR SCIENTISTS WHOSE WORK PERTAINS TO VISUAL SCIENCES. THE CORE FACILITIES AND RESEARCH INFRASTRUCTURE SUPPORTED BY THE COBRE WILL ALSO ALLOW OUR INVESTIGATORS TO PRODUCE RESEARCH RESULTS THAT WILL TRANSLATE TO PATIENTS, MOVING US TOWARD OUR ULTIMATE GOAL OF REDUCING THE BURDEN OF VISUAL IMPAIRMENT AND ITS COMORBIDITIES IN THE APPALACHIAN REGION, THROUGHOUT THE NATION, AND WORLDWIDE.

THE IDEA STATE CONSORTIUM FOR A CLINICAL RESEARCH RESOURCE CENTER: INCREASING CLINICAL TRIALS IN IDEA STATES THROUGH COMMUNICATION OF OPPORTUNITIES, EFFECTIVE MARKETING, AND WORKFORCEDEVELOPMENT - THERE ARE CURRENTLY NEARLY 8,000 CLINICAL TRIALS AND OBSERVATIONAL COHORT STUDIES FUNDED BY THE NATIONAL INSTITUTES OF HEALTH IN THE UNITED STATES, YET LESS THAN 10% OF THESE STUDIES ARE CONDUCTED IN INSTITUTIONAL DEVELOPMENT AWARD (IDEA) STATES THAT SERVE UNDERREPRESENTED MINORITY AND RURAL POPULATIONS. NOT SURPRISINGLY, ONLY APPROXIMATELY 7% OF EXPENDITURES FOR CLINICAL TRIALS AND OBSERVATIONAL STUDIES GO TO THE 23 IDEA STATES AND PUERTO RICO. BARRIERS THAT LIMIT EXPANSION OF CLINICAL TRIAL AND COHORT STUDIES IN IDEA STATES INCLUDE LACK OF EFFECTIVE COMMUNICATION TO TRIAL SPONSORS OF THE EXPERTISE AND CAPABILITY THAT IDEA INSTITUTIONS POSSESS TO EFFECTIVELY CONDUCT CLINICAL STUDIES, EFFECTIVE COMMUNICATION TO IDEA INVESTIGATORS REGARDING CLINICAL TRIALS OPPORTUNITIES, AND LACK OF CLINICAL TRIAL COORDINATORS. THE OVERALL GOAL OF THIS PROJECT IS TO INCREASE NUMBERS OF CLINICAL TRIALS AND OBSERVATIONAL COHORT STUDIES IN IDEA STATES, THEREBY INCREASING TRIAL AVAILABILITY AND PARTICIPATION OF MINORITY AND RURAL POPULATIONS HISTORICALLY UNDERREPRESENTED IN CLINICAL TRIALS. WE WILL ACHIEVE THIS GOAL BY ESTABLISHING THE IDEA STATE CONSORTIUM FOR CLINICAL RESEARCH RESOURCE CENTER (ISCORE-RC) COMPRISED OF THE CLINICAL TRIALS SERVICE CENTER AND THE CLINICAL RESEARCH COORDINATOR (CRC) DEVELOPMENT PROGRAM TO ADDRESS THE IDENTIFIED BARRIERS THROUGH ACCOMPLISHMENT OF THE FOLLOWING SPECIFIC AIMS. AIM 1 - EFFECTIVELY COMMUNICATE AND MARKET TO CLINICAL TRIAL SPONSORS THE EXPERTISE, QUALITY, AND CAPACITY OF IDEA STATE INSTITUTIONS TO CONDUCT CLINICAL TRIALS. WE WILL ACCOMPLISH THIS AIM THROUGH SEVERAL TACTICS TO INCLUDE LEVERAGING THE TRINETX PLATFORM THAT CONNECTS CLINICAL TRIAL SPONSORS WITH INSTITUTIONS SERVING RELEVANT PATIENT POPULATIONS TO IDENTIFY SITES WITH POTENTIALLY ELIGIBLE PARTICIPANTS FOR SPECIFIC CLINICAL TRIALS, CREATING A REPOSITORY CONTAINING SITE-SPECIFIC PROFILES SHOWCASING STRENGTHS OF INDIVIDUAL IDEA STATE TRIAL GROUPS, ESTABLISHING AN ISCORE-RC WEBSITE THAT PROVIDES A PUBLIC RESOURCE TO DEMONSTRATE BENEFITS OF PARTNERING WITH IDEA ORGANIZATIONS TO INCREASE CLINICAL TRIAL PARTICIPANT REPRESENTATION FROM UNDERSERVED POPULATIONS, AND FACILITATING NETWORKING OF SPONSORS WITH INVESTIGATORS. AIM 2 - COMMUNICATE TO IDEA STATE INVESTIGATORS CLINICAL TRIAL OPPORTUNITIES. TO ACCOMPLISH THIS GOAL, WE WILL DEVELOP SITE SPECIFIC SEARCH CRITERIA IN CLINICALTRIALS.GOV THAT WILL ALLOW THE ISCORE-RC CLINICAL TRIALS SERVICE CORE TO MONITOR RELEVANT CLINICAL TRIALS OF INTEREST CURRENTLY IN THE PARTICIPANT RECRUITMENT PHASE. AIM 3 - TRAIN A CADRE OF SKILLED CLINICAL RESEARCH COORDINATORS. ENTRY INTO THIS PROGRAM WILL BE OPEN TO EXPERIENCED CLINICAL PERSONNEL AS WELL AS TO NON-CLINICAL INDIVIDUALS. BOTH PART-TIME AND FULL-TIME EFFORT OF TRAINEES WILL BE ACCOMMODATED. THE PROGRAM WILL INCLUDE AN ONLINE DIDACTIC PORTION, JOURNAL CLUB, AND SEMINAR SERIES AS WELL AS A PROMINENT EXPERIENTIAL COMPONENT TO BE CONDUCTED AT PARTICIPATING SITES. UPON COMPLETION OF THE CORE CONTENT, PARTICIPANTS WILL RECEIVE A CRC BASIC TRAINING CERTIFICATE AND WILL BE ELIGIBLE FOR FURTHER TRAINING TOWARDS AN ADVANCED TRAINING CERTIFICATE AND MEMBERSHIP IN THE ISCORE-RC CRC ACADEMY, A NETWORKING AND PROFESSIONAL DEVELOPMENT PLATFORM THAT INCLUDES CURRENT RESEARCH COORDINATORS AT PARTICIPATING SITES AS WELL AS TRAINEES.

MECHANISMS OF COGNITIVE DECLINE DURING AGING

THE RESEARCH TEAM WILL DESIGN AND BUILD A HYBRID MICROWAVE-ASSISTED HEATING PROCESS (HMAP) FOR THE CALCINATION AND SINTERING OF SOLID-OXIDE ELECTROLYSIS CELL (SOEC) MATERIALS AND CELLS. THE PROJECT WILL SPAN FROM THE LAB DEMONSTRATION OF SMALL SAMPLES TO COMMERCIAL SIZE (=100 CM2). THE FINAL DELIVERABLE OF THE PROJECT WILL RESULT IN A HARDWARE SET (TWO HYBRID MICROWAVE-ASSISTED KILNS) CAPABLE OF DEMONSTRATING LOW-RISK SCALABILITY TO HIGH-VOLUME MANUFACTURING (HVM). THE FIRST KILN WILL ASSIST IN THE RAPID CALCINATION OF ELECTRODE AND ELECTROLYTE POWDERS USED TO FABRICATE SOECS. THE SECOND KILN WILL PERMIT THE ACCELERATED AND LOW-POWER SINTERING OF ALL LAYERS OF AN SOEC TO PRODUCE FULLY FUNCTIONAL SOECS.

HEALTHY START: ELIMINATING DISPARITIES IN PERINATAL HEALTH

ANALYSIS OF GEOTHERMAL DEEP DIRECT-USE COMBINED WITH RESERVOIR THERMAL ENERGY STORAGE ON THE WEST VIRGINIA UNIVERSITY CAMPUS-MORGANTOWN, WV

HEALTH CARE AND OTHER FACILITIES

CENTER FOR KINETIC EXPERIMENT, THEORY, AND INTEGRATED COMPUTATION (KINETIC) PHYSICS

HEALTHY START: ELIMINATING DISPARITIES IN PERINATAL HEALTH

COBRE FOR SIGNAL TRANSDUCTION AND CANCER

2026 JOB ACCOMMODATION NETWORK JAN

TAS::89 0331::TAS RECOVERY ACT - TRANSPORTATION ELECTRIFICATION AWARD TO WEST VIRGINIA UNIVERSITY

EASEMENT REVIEW UNDER THE FARM AND RANCH LANDS PROTECTION PROGRAM (FRPP)

PIRE: AN INTERNATIONAL PULSAR TIMING ARRAY FOR GRAVITATIONAL WAVE DETECTION

LEADERSHIP IN THE AREA OF DISABILITIES (LEND)

THE NANOGRAV PHYSICS FRONTIERS CENTER -THIS AWARD TO THE NORTH AMERICAN NANOHERTZ OBSERVATORY FOR GRAVITATIONAL WAVES (NANOGRAV) SUPPORTS THEIR GOAL OF CHARACTERIZING THE LOW-FREQUENCY GRAVITATIONAL-WAVE (GW) UNIVERSE THROUGH RADIO TIMING OBSERVATIONS OF PRECISE CELESTIAL CLOCKS CALLED MILLISECOND PULSARS. NANOGRAV HAS ALREADY DISCOVERED THE TELLTALE SPATIAL CORRELATIONS AMONG PULSE ARRIVAL TIMES EXPECTED FROM A STOCHASTIC BACKGROUND OF GWS. THIS BACKGROUND IS LIKELY TO HAVE A SIGNIFICANT CONTRIBUTION FROM THE SUPERMASSIVE BLACK HOLE BINARIES FORMED WHEN GALAXIES MERGE. FUTURE NANOGRAV MEASUREMENTS OF THE PROPERTIES OF THE STOCHASTIC BACKGROUND WILL PLACE UNIQUE CONSTRAINTS ON THE GROWTH AND EVOLUTION OF GALAXIES THROUGH COSMIC TIME. THERE MAY ALSO BE BACKGROUND CONTRIBUTIONS FROM MORE EXOTIC SOURCES SUCH AS COSMIC STRINGS, PHASE TRANSITIONS IN THE EARLY UNIVERSE, AND RELIC GWS FROM INFLATION; DETECTING ANY OF THESE WOULD BE TRANSFORMATIVE AND COULD DRAMATICALLY CHANGE OUR UNDERSTANDING OF THE UNIVERSE. THIS AWARD WILL ENABLE NANOGRAV TO CONSTRUCT A MORE SENSITIVE DATA SET THAT WILL ALLOW CONSTRAINTS ON THE ORIGIN OF THIS STOCHASTIC BACKGROUND, AND SEARCHES FOR INDIVIDUAL SUPERMASSIVE BLACK HOLE BINARIES, WHOSE DETECTION WILL HERALD A NEW ERA OF MULTI-MESSENGER NANOHERTZ GW ASTROPHYSICS. THIS WORK REQUIRES THE SYNERGY OF EXPERTS IN GRAVITATIONAL PHYSICS, DATA ANALYSIS, AND ASTROPHYSICS COMING TOGETHER IN A COLLABORATIVE ENVIRONMENT. IN ADDITION TO MONITORING A KNOWN LIST OF MILLISECOND PULSARS, NANOGRAV ROUTINELY DISCOVERS NEW MSPS TO ADD TO THEIR STUDY. NANOGRAV OBSERVATIONS ALSO ENABLE HIGH-IMPACT SYNERGISTIC SCIENCE, INCLUDING CONSTRAINING THE DENSE MATTER EQUATION OF STATE, MAKING DYNAMICAL TESTS OF GENERAL RELATIVITY, FURTHER UNDERSTANDING THE IONIZED INTERSTELLAR MEDIUM, AND DISCOVERING EXOTIC NEUTRON STAR SYSTEMS AND RADIO TRANSIENTS. NANOGRAV REACHES LARGE NUMBERS OF THE GENERAL PUBLIC THROUGH EXHIBITS AND TALKS, AS WELL AS A GROWING SOCIAL MEDIA PRESENCE. AN ASSOCIATED STUDENT RESEARCH PROGRAM, NANOGRAV STARS, REACHES MORE THAN 100 UNDERGRADUATE STUDENTS EVERY YEAR, AND THE PULSAR SCIENCE COLLABORATORY INVOLVES HUNDREDS OF MIDDLE AND HIGH SCHOOL STUDENTS AND THEIR TEACHERS. THIS AWARD IS SUPPORTED BY THE PHYSICS SECTION AND THE ASTRONOMICAL SCIENCES SECTION WITHIN THE MATHEMATICAL AND PHYSICAL SCIENCES DIRECTORATE. 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 PLANNED FOR THIS AWARD.

DE-FE0031819 WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION DEVELOPMENT OF CORROSION- AND EROSION-RESISTANT COATINGS FOR ADVANCED ULTRA-SUPERCRITICAL MATERIALS

FEASIBILITY OF DEEP BRAIN STIMULATION AS A NOVEL TREATMENT FOR REFRACTORY OPIOID USE DISORDER - ABSTRACT: AS THE NATIONAL TOLL FROM THE OPIOID EPIDEMIC CONTINUES TO WORSEN, WEST VIRGINIA LEADS THE NATION IN OVERDOSE DEATHS, WITH 52 DEATHS PER 100,000 POPULATION, AND THE ECONOMIC IMPACT OF THE OPIOID EPIDEMIC ON WEST VIRGINIA IS ESTIMATED AT AROUND $1 BILLION. THE IMPACT OF THE OPIOID EPIDEMIC IS NOT LIMITED TO WEST VIRGINIA; NATIONALLY, MORE THAN 63,000 OVERDOSE DEATHS OCCURRED IN 2016. UNFORTUNATELY, DESPITE THE GROWING NECESSITY OF TREATMENT FOR OPIOID USE DISORDER (OUD), MOST PATIENTS DO NOT RESPOND TO THE CURRENT STANDARD OF CARE. THE SUCCESS RATE OF PATIENTS INITIALLY STABILIZED ON THE GOLD STANDARD OF TREATMENT, MEDICATION ASSISTED THERAPY (MAT) IN CONJUNCTION WITH PSYCHOSOCIAL INTERVENTIONS, IS CURRENTLY LESS THAN 50%. THOSE WHO FAIL THE GOLD STANDARD HAVE A HIGH RISK OF OVERDOSE OR OTHER COMPLICATIONS. DUE TO THE GROWING NUMBER OF OUD PATIENTS AND THE LIMITATIONS OF CURRENT TREATMENT, IT IS CLEAR THAT NEW TREATMENT OPTIONS ARE NEEDED TO CONFRONT THIS PROBLEM. DEEP BRAIN STIMULATION (DBS) HAS BEEN USED FOR MANY YEARS TO SUCCESSFULLY TREAT MOVEMENT DISORDERS SUCH AS PARKINSONS, AND HAS SHOWN PROMISE IN INVESTIGATIONS FOR OTHER MENTAL DISORDERS. WE HYPOTHESIZE THAT IMPLANTING THE DBS DEVICE IN THE NUCLEUS ACCUMBENS REGION OF THE BRAIN WILL MODULATE THE REWARD AND BEHAVIOR SELF- REGULATION NETWORKS, WHICH WILL DECREASE OPIOID CRAVINGS. THIS PROPOSAL AIMS TO TEST SAFETY, FEASIBILITY, AND TOLERABILITY IN AN INITIAL COHORT OF 4 PARTICIPANTS DURING THE UG3 PHASE. THIS WILL ALLOW FOR AN EVALUATION OF SAFETY AND TOLERABILITY OF DBS IN PARTICIPANTS WITH TREATMENT-REFRACTORY OUD AND A HISTORY OF LIFE-THREATENING COMPLICATIONS SECONDARY TO OPIOID USE. IF THE UG3 PHASE IS SUCCESSFUL FOLLOWING INTENSIVE MONITORING OF THE 4 PARTICIPANTS, THE UH3 PHASE WILL CONSIST OF A RANDOMIZED, CONTROLLED PROOF-OF-CONCEPT STUDY WITH 16 PARTICIPANTS. THESE PARTICIPANTS AGAIN WILL HAVE TREATMENT-REFRACTORY OUD AND A HISTORY OF LIFE-THREATENING COMPLICATIONS SECONDARY TO OPIOID USE. DURING THE UH3 PHASE, THE MECHANISM OF DBS IMPACT ON OUD WILL BE INVESTIGATED THROUGH BOTH NEUROIMAGING AND MEASUREMENT OF EXECUTIVE FUNCTION.

AS PART OF A COOPERATIVE PARTNERSHIP WITH NASA GODDARD SPACE FLIGHT CENTER (GSFC) WEST VIRGINIA UNI

STORAGE TANK EMISSIONS ASSESSMENTS IN THE MARCELLUS (STEAM) TO ACQUIRE NEW KNOWLEDGE WITH SCIENCE (TANKS) THE OVERALL OBJECTIVE IS TO ACQUIRE NEW, SCIENCE-BASED KNOWLEDGE TO IMPROVE THE OVERALL UNDERSTANDING OF METHANE AND OTHER EMISSIONS FROM STORAGE TANKS AT UPSTREAM AND MIDSTREAM OIL AND NATURAL GAS SITES IN PORTIONS OF THE APPALACHIAN BASIN, WHICH ARE KNOWN TO CONTRIBUTE TO METHANE AND VOLATILE ORGANIC COMPOUND (VOC) EMISSIONS THAT IMPACT LOCAL AND GLOBAL AIR QUALITY.

WEST VIRGINIA UNIVERSITY INJURY CONTROL RESEARCH CENTER

MODEL STATE-SUPPORTED AREA HEALTH EDUCATION CENTERS

MODEL STATE-SUPPORTED AREA HEALTH EDUCATION CENTERS

BIPARTISAN INFRASTRUCTURE LAW (BIL) - SEPARATION OF RARE EARTH OXIDES AND REDUCTION TO METAL PRODUCTS THE OVERALL OBJECTIVE OF THIS PROJECT IS TO DESIGN, DEVELOP, AND DEPLOY INNOVATIVE PROCESS TECHNOLOGIES TO PRODUCE SALABLE RARE EARTH METALS AND CRITICAL MINERALS (CM) FROM ACID MINE DRAINAGE (AMD) FEEDSTOCKS AT A REDUCED COST TO REDUCE OUR NATION’S VULNERABILITY FROM INTERNATIONAL COMPETITORS.

THIS PROJECT FOCUSES ON INTEGRATING HIGH-TEMPERATURE SOLID OXIDE ELECTROLYSIS (HTSE) WITH SOLAR CONCENTRATOR-TES TO GENERATE HYDROGEN FOR FURTHER USE IN SYNGAS AND OTHER FUEL PRODUCTION. THE PROPOSED WORK WILL DESIGN AND VALIDATE AN INNOVATIVE SYSTEM PROTOTYPE FOR PRODUCING GREEN HYDROGEN USING THE ADDITION OF SOLAR HEAT SUPPLY IN HOT STEAM GENERATION FOR HIGH-TEMPERATURE ELECTROLYSIS. THE TARGET LEVEL OF PERFORMANCE IS “TIER 2. DEVELOP, DESIGN, DE-RISK”. THE PROJECT WILL START FROM A TYPICAL TECHNOLOGY READINESS LEVEL (TRL) 3, WITH THE FOLLOWING OBJECTIVES.

DESCRIPTION:THIS COOOPERATIVE AGREEMENT WILL PROVIDE FUNDING UNDER THE INFRASTRUCTURE INVESTMENT AND JOBS ACT (IIJA) (ALSO KNOWN AS THE BIPARTISAN INFRASTRUCTURE LAW (BIL)) TO WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION TO CONDUCT ELIGIBLE TECHNICAL ASSISTANCE-RELATED ACTIVITIES AS AUTHORIZED BY CERCLA 104(K)(7) AND PROVIDE TECHNICAL ASSISTANCE ON BROWNFIELDS-RELATED ISSUES TO COMMUNITIES IN EPA REGION 3. WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION WILL ASSIST THESE COMMUNITIES TO ADDRESS THE CHALLENGE OF ASSESSING, CLEANING UP, AND PREPARING BROWNFIELD SITES FOR REDEVELOPMENT. THIS ACTION PROVIDES PARTIAL FEDERAL FUNDING IN THE AMOUNT OF $3,300,000. FEDERAL FUNDS IN THE AMOUNT OF $1,700,000 ARE CONTINGENT UPON AVAILABILITY OF ADDITIONAL FUNDING. ACTIVITIES:WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION WILL HELP STAKEHOLDERS UNDERSTAND COMPLEX BROWNFIELDS-RELATED ISSUES BY PROVIDING SPECIALIZED KNOWLEDGE AND GUIDING COMMUNITIES THROUGH THE ASSESSMENT, CLEANUP AND REVITALIZATION PROCESS. THIS COOPERATIVE AGREEMENT PROVIDES TECHNICAL ASSISTANCE IN SIX SUBJECT AREAS: (1) COMMUNITY INVOLVEMENT, (2) HEALTH IMPACTS OF BROWNFIELD SITES, (3) SCIENCE AND TECHNOLOGY RELATING TO BROWNFIELDS ASSESSMENT, REMEDIATION, AND SITE PREPARATION, (4) INTEGRATED APPROACHES TO BROWNFIELDS ASSESSMENT CLEANUP AND REDEVELOPMENT, (5) BROWNFIELDS FINANCE, AND (6) STATE, TERRITORIAL TRIBAL, AND LOCAL GOVERNMENT BROWNFIELDS PROGRAMS.SUBRECIPIENT:SUBAWARDEES WILL HELP STAKEHOLDERS UNDERSTAND COMPLEX BROWNFIELDS-RELATED ISSUES BY PROVIDING SPECIALIZED KNOWLEDGE AND GUIDING COMMUNITIES THROUGH THE ASSESSMENT, CLEANUP AND REVITALIZATION PROCESS. THIS COOPERATIVE AGREEMENT PROVIDES TECHNICAL ASSISTANCE IN THE SIX SUBJECT AREAS: (1) COMMUNITY INVOLVEMENT, (2) HEALTH IMPACTS OF BROWNFIELD SITES, (3) SCIENCE AND TECHNOLOGY RELATING TO BROWNFIELDS ASSESSMENT, REMEDIATION, AND SITE PREPARATION, (4) INTEGRATED APPROACHES TO BROWNFIELDS ASSESSMENT CLEANUP AND REDEVELOPMENT, (5) BROWNFIELDS FINANCE, (6) STATE, TERRITORIAL TRIBAL, AND LOCAL GOVERNMENT BROWNFIELDS PROGRAMS. THE RECIPIENT INTENDS TO ISSUE SUBAWARD AGREEMENTS TO ITS PARTNERS IN COMPLIANCE WITH APPENDIX A OF EPA'S SUBAWARD POLICY.OUTCOMES:EXPECTED OUTCOMES INCLUDE COMMUNITIES, ESPECIALLY SMALL, RURAL, TRIBAL, AND DISADVANTAGED COMMUNITIES, INCREASING THEIR KNOWLEDGE OF BROWNFIELD-RELATED ISSUES AND CAPACITY TO ADVANCE BROWNFIELD SITES TOWARD CLEANUP AND REUSE. THE INTENDED BENEFICIARIES INCLUDE A BROAD RANGE OF STAKEHOLDERS (E.G., TRIBAL, STATE, LOCAL AND OTHER NON-GOVERNMENTAL ENTITIES), ESPECIALLY SMALL, RURAL AND UNDERSERVED COMMUNITIES FACING BROWNFIELDS CHALLENGES.

DE-FE0031834 WITH WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION TITLED ''DEVELOPMENT AND TESTING OF AN INTEGRATED ACID MINE DRAINAGE (AMD) TREATMENT AND RARE EARTH/CRITICAL MINERAL PLANT''.

EXPANDS MARKETS FOR CLIMATE-SMART BEEF IN VA AND WV AND SUPPORTS FARMER IMPLEMENTATION AND MONITORING OF CLIMATE-SMART PRACTICES. GRAZING REGENERATIVELY FOR APPALACHIAN SUSTAINABLE SOLUTIONS (GRASS)

COBRE IN SENSORY NEUROSCIENCE

COBRE FOR SIGNAL TRANSDUCTION AND CANCER PHASE III

HEALTH CARE AND OTHER FACILITIES

2025 JOB ACCOMMODATION NETWORK JAN

LEADERSHIP IN THE AREA OF DISABILITIES (LEND)

BIL-THE OVERALL OBJECTIVE OF THIS PROJECT IS TO DEVELOP SCALABLE, 5×5 CM2 PLANAR, LARGE-FORMAT, PROTON-CONDUCTING SOLID OXIDE ELECTROLYTE CELLS (P-SOECS) TO ACHIEVE HYDROGEN GENERATION AT ELECTROLYZING CURRENT DENSITY OF 1 A/CM2 @ 1.3 V/CELL AT =550OC LOW-TEMPERATURE OPERATION, =85% HIGH FARADAIC EFFICIENCY, AND =5 MV/KHR DEGRADATION FOR 1000 H.

RYAN WHITE PART C OUTPATIENT EIS PROGRAM

REMOTE MICROVASCULAR DYSFUNCTION AFTER PARTICULATE MATTER EXPOSURE

I/UCRC PHASE II: CENTER FOR IDENTIFICATION TECHNOLOGY RESEARCH

WV PREVENTION RESEARCH CENTER

THE MISSION OF THE WVSGC IS TO DEVELOP A STATEWIDE INFRASTRUCTURE THAT WILL ENHANCE THE STATE S COMPETITIVENESS IN AEROSPACE-RELATED RESEARCH EDUCATION AND INDUSTRIAL ACTIVITIES.

WEST VIRGINIA PREVENTION RESEARCH CENTER

DEVELOPMENT OF MRNA-PLATFORM VACCINES - PROJECT SUMMARY PERTUSSIS IS A RESPIRATORY DISEASE CAUSED BY THE OBLIGATE HUMAN PATHOGEN BORDETELLA PERTUSSIS. TWO GENERATIONS OF PERTUSSIS VACCINES HAVE BEEN DEVELOPED AND LICENSED: WHOLE CELL PERTUSSIS (DTP) AND ACELLULAR PERTUSSIS (DTAP/TDAP). PERTUSSIS WAS THOUGHT TO BE A DISEASE OF THE PAST BUT HAS RECENTLY RE-EMERGED. THE NUMBER OF CASES OF PERTUSSIS IN 2012 WAS 48-FOLD OVER THE LOWEST YEAR ON RECORD (1976), WHICH WAS ALSO A 50-YEAR HIGH. WHILE THE INCREASE OF PERTUSSIS HAS MULTIPLE POTENTIAL REASONS, EPIDEMIOLOGICAL STUDIES CLEARLY SUGGEST THAT THE DURATION OF IMMUNITY OF BOTH DTAP AND TDAP WANES QUICKLY EACH YEAR AFTER A BOOSTER, AND REGRESSES TO NON- PROTECTIVE LEVELS IN HUMANS. EACH DOSE OF WHOLE CELL VACCINE CONTAINS HUNDREDS OF ANTIGENS, OF WHICH NUMEROUS ARE IMMUNODOMINANT. WHOLE CELL VACCINES ALSO INDUCE T HELPER 1 AND 17 (TH1/TH17) CELLULAR IMMUNE RESPONSES. ON THE OTHER HAND, ACELLULAR VACCINES FOCUS TH2-MEDIATED HUMORAL RESPONSES EXCLUSIVELY TO PERTUSSIS TOXIN, FILAMENTOUS HEMAGGLUTININ, PERTACTIN, AND FIMBRIAE. WE AIM TO DEVELOP A VACCINE THAT WOULD INDUCE TH1 RESPONSES AND INCLUDE A GREATER NUMBER OF ANTIGENS THAN ACELLULAR VACCINES. MRNA VACCINES PROVIDE A PLATFORM THAT CAN BE EASILY MODIFIED FOR THE TARGETED ANTIGEN/PATHOGEN AND THEY INDUCE TH1 RESPONSES. MRNA VACCINES ENCODE THE ANTIGEN, WHICH ONCE EXPRESSED, RESULTS IN IMMUNITY MEDIATED BY TFH RESPONSES. WE USED AN MRNA PLATFORM TO SCREEN ANTIGENS OF B. PERTUSSIS AND IDENTIFIED A PROTECTIVE MULTIVALENT FORMULATION (MRNA-DTP10; 8 PERTUSSIS ANTIGENS WITH DIPHTHERIA AND TETANUS ANTIGENS) IN A MURINE CHALLENGE MODEL. IN THIS PROJECT, WE WILL FURTHER EXTEND OUR STUDIES AND INVESTIGATE THE CORRELATES OF PROTECTION OF THE MRNA-PERTUSSIS VACCINE IN THE MURINE MODEL WITH LONGEVITY STUDIES AND EXAMINE DTAP PRIME / MRNA-BOOST EFFECTS (SA1). NEXT, WE WILL UTILIZE THE COUGHING RAT MODEL OF PERTUSSIS WITH WHOLE BODY PLETHYSMOGRAPHY TO COMPARE MRNA, WHOLE CELL, AND ACELLULAR IMMUNITY FOR PROTECTION AGAINST COUGH (SA2). WE WILL STUDY THE MRNA PERTUSSIS VACCINE IN IMMUNOGENICITY AND CHALLENGE EXPERIMENTS USING THE BABOON MODEL OF PERTUSSIS (SA3). LASTLY, WE WILL AIM TO DEVELOP A SUITE OF ASSAYS TO PHENOTYPE ANTIBODIES PRODUCED BY MRNA PERTUSSIS VACCINES AND BRIDGE EACH OF THE PERTUSSIS MODELS, WHICH WILL FACILITATE CLINICAL DEVELOPMENT. THROUGH THESE STUDIES, WE AIM TO CHARACTERIZE THE MRNA-PERTUSSIS IMMUNITY AND DEVELOP A CLEARER UNDERSTANDING OF HOW THIS VACCINE PLATFORM CAN BE USED TO OVERCOME “COMPLEX OR DIFFICULT” PATHOGENS THAT EMPLOY NUMEROUS VIRULENCE FACTORS. WE EXPECT THE DATA ACQUIRED IN EACH AIM WILL RESULT IN A DEEPER UNDERSTANDING OF PERTUSSIS IMMUNITY AS WELL AS ILLUMINATE THE MRNA PLATFORM FOR BACTERIAL VACCINES.

FY09 CONGRESSIONALLY SELECTED FUNDS

RII TRACK 2 FEC: MULTI-SCALE INTEGRATIVE APPROACH TO DIGITAL HEALTH: COLLABORATIVE RESEARCH AND EDUCATION IN SMART HEALTH IN WEST VIRGINIA AND ARKANSAS

PROPOSAL FOR FY 2010 CONGRESSIONAL APPROPRIATIONS ACT

CHANGES IN COENZYME A LEVELS ARE A KEY MECHANISM REGULATING METABOLIC PATHWAYS

WEST VIRGINIA EARLY CHILDHOOD OBESITY PREVENTION PROJECT

WVU PROGRAM FOR RETAINING INSTITUTIONAL DIVERSITY AND EQUITY

WEST VIRGINIA PREVENTION RESEARCH CENTER

DEVELOPMENT OF CONTINUOUS SOLVENT EXTRACTION PROCESSES FOR COAL-DERIVED CARBON PRODUCTS

APPALACHIAN TRAINING PROGRAM IN OCCUPATIONAL HEALTH AND SAFETY

WVU INJURY CONTROL RESEARCH CENTER

GOALS&OBJECTIVES THE OVERARCHING GOAL OF THE NASA WEST VIRGINIA SPACE GRANT CONSORTIUM (WVSGC) IS TO EXTEND THE BENEFITS OF NASA'S RESEARCH AND EDUCA

WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION. CLEAN CITIES FY 09 PETROLEUM REDUCTION TECHNOLOGIES PROJECTS FOR TRANSPORTATION SECTOR. DE-PS26-09NT

DEVELOPMENT OF ANTI-LPS THERAPEUTIC ANTIBODIES FOR THE TREATMENT OF PSEUDOMONAS AERUGINOSA INFECTIONS - SUMMARY THE GOAL OF THIS PROPOSAL IS TO DEVELOP THERAPEUTIC ANTIBODIES FOR THE TREATMENT OF MULTIDRUG RESISTANT (MDR) P. AERUGINOSA INFECTIONS, WITH AN EMPHASIS ON SEPSIS. WITH THE RISE IN ANTIMICROBIAL RESISTANCE AROUND THE WORLD WE ARE RUNNING OUT OF THERAPEUTIC OPTIONS AGAINST MDR P. AERUGINOSA. OUR LABORATORY HAS IDENTIFIED A POTENTIAL SOLUTION TO ADDRESS THIS PROBLEM: A THERAPEUTIC ANTIBODY COCKTAIL THAT TARGETS THE LIPOPOLYSACCHARIDE OF P. AERUGINOSA. ONE OF THE ANTIBODIES PRESENT IN THE COCKTAIL (WVU-VDC-S3D4, OR S3D4 FOR SHORT) COMPLETELY PROTECTS MICE AGAINST LETHAL SEPSIS, PREVENTING BACTERIAL DISSEMINATION AND CYTOKINE STORM. THIS ANTIBODY IS ALSO MORE POTENT THAN VACCINATION WITH A P. AERUGINOSA WHOLE CELL VACCINE OR PASSIVE IMMUNIZATION WITH SERUM FROM WHOLE CELL VACCINATED MICE. MOST INTERESTINGLY, S3D4 IS ALSO CAPABLE OF DIRECTLY KILLING P. AERUGINOSA IN VITRO IN THE ABSENCE OF COMPLEMENT OR IMMUNE CELLS. IN THIS PROPOSAL, WE WILL CHARACTERIZE THE MECHANISM OF ACTION OF S3D4, FORMULATE IT IN AN LPS MULTIVALENT ANTIBODY COCKTAIL, AND EVALUATE EFFICACY AGAINST MDR P. AERUGINOSA. TO DO THIS, WE WILL EVALUATE HOST AND BACTERIAL FACTORS INVOLVED IN S3D4 FUNCTION (AIMS 1 AND 2). WE WILL THEN COMBINE IT AS COCKTAIL WITH THREE ADDITIONAL ANTIBODIES THAT TARGET THE 6 LPS SEROGROUPS THAT CAUSE 87% OF P. AERUGINOSA BLOODSTREAM INFECTION. EFFICACY IN VITRO AND IN VIVO WILL BE EVALUATED WITH MDR CLINICAL ISOLATES (AIM 3). WE WILL ALSO EVALUATE EFFICACY AGAINST P. AERUGINOSA BIOFILMS. WE HYPOTHESIZE THAT A MULTIVALENT ANTI-LPS COCKTAIL OF ANTIBODIES, ALONE OR IN COMBINATION WITH STANDARD OF CARE ANTIBIOTICS, WILL BE EFFICACIOUS FOR THE PREVENTION AND TREATMENT OF MDR P. AERUGINOSA SEPSIS. BY THE COMPLETION OF THESE STUDIES, WE ANTICIPATE TO ELUCIDATE THE MECHANISM OF ACTION OF A NOVEL CLASS OF ANTIBODIES THAT CAN DIRECTLY KILL P. AERUGINOSA IN VITRO, WHICH WILL HELP WITH THE PRODUCTION OF ADDITIONAL ANTIBODIES WITH SIMILAR FUNCTIONS AGAINST OTHER MDR ORGANISMS. WE WILL ALSO PRODUCE PROOF OF CONCEPT DATA TO SUPPORT THE GENERATION ANTIBODY THERAPY AGAINST P. AERUGINOSA INFECTIONS. ALTOGETHER, THIS PROJECT WILL GENERATE IMPORTANT KNOWLEDGE TO IMPROVE THE LIVES OF PATIENTS AFFECTED BY THIS MDR BACTERIUM.

IN VIVO MONITORING OF TUMOR MICROENVIRONMENT REGULATION BY MACROPHAGES

IMPACT OF PARTICLE AND OZONE INHALATION CO-EXPOSURE ON ALVEOLAR EPITHELIAL REGENERATION

WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION

WEST VIRGINIA SPACE GRANT CONSORTIUM

PROFILING CHEMICAL TUMOR MICROENVIRONMENT: APPLICATION FOR DIAGNOSTICS & THERAPY

RECOVERY OF RARE EARTH ELEMENTS FROM COAL MINE DRAINAGE

ESTABLISHED IN 1991 THE NASA WEST VIRGINIA SPACE GRANT CONSORTIUM (WVSGC) IS COMPRISED OF SEVEN UNIVERSITIES AND FOUR COLLEGES PLUS EIGHT BUSINESS A

PHOTORECEPTOR NEURON SPECIFIC ALTERNATIVE SPLICING OF MESSENGER RNA

IMPORTANCE OF SMALL GTPASES IN PHOTORECEPTOR FUNCTION

THE ROLE OF HEF1 PROTEIN IN DIVISION AND INVASION OF METASTATIC BREAST CANCER

RYAN WHITE PART C OUTPATIENT EIS PROGRAM

COBRE TRANSITIONAL CENTER IN NEUROSCIENCE

PREDOCTORAL TRAINING IN STROKE AND ITS CO-MORBIDITIES

DIRECT UTILIZATION OF COAL SYNGAS IN HIGH TEMPERATURE FUEL CELLS

NRT-HDR: BRIDGES IN DIGITAL HEALTH

THE ROLE OF TISSUE NONSPECIFIC ALKALINE PHOSPHATASE IN BRAIN ENDOTHELIAL CELL HOMEOSTASIS - PROJECT SUMMARY THE OBJECTIVE OF THIS APPLICATION IS TO DETERMINE HOW TISSUE NONSPECIFIC ALKALINE PHOSPHATASE (TNAP) ENZYMATIC ACTIVITY MAINTAINS CEREBROVASCULAR FUNCTION WITHIN THE NEUROVASCULAR UNIT (NVU). BRAIN MICROVASCULAR ENDOTHELIAL CELLS (BMECS) COMPRISE THE CEREBRAL MICROVASCULATURE AND SERVE AS THE STRUCTURAL FOUNDATION OF THE BLOOD-BRAIN BARRIER (BBB) AND. INCREASED PERMEABILITY AND DIMINISHED INTEGRITY OF BMECS ARE TWO COMMON MECHANISMS THROUGH WHICH CEREBROVASCULAR FUNCTION IS COMPROMISED IN HUMAN DISEASE. TNAP IS A HIGHLY ENRICHED ENZYME IN CEREBRAL MICROVESSELS WHOSE FUNCTION IN BRAIN BMECS IS POORLY UNDERSTOOD. OUR PRELIMINARY DATA DEMONSTRATE THAT TNAP ACTIVITY STIMULATES A NOVEL SIGNALING MECHANISM WHICH PROTECTS AGAINST THE LOSS OF CEREBRAL MICROVASCULAR INTEGRITY AND PERMEABILITY. THESE INTRIGUING FINDINGS LED US TO PROPOSE THE CENTRAL HYPOTHESIS THAT TNAP MAINTAINS NVU HOMEOSTASIS DURING CEREBRAL ISCHEMIA BY PRESERVING BBB INTEGRITY. WE WILL UTILIZE MICE WITH A VE-CADHERIN-CRE DRIVEN CONDITIONAL DELETION OF TNAP IN ENDOTHELIAL CELLS (VECKO) AND ITS WILD TYPE LITTERMATES TO INTERROGATE THE ROLE OF TNAP IN BMECS. WE WILL COMPARE RESPONSES IN YOUNG (4-5 MONTHS) AND AGED (18-20 MONTHS) MICE TO ASSESS THE AGE-DEPENDENT EFFECTS OF BRAIN ENDOTHELIAL TNAP ON INDICES OF BRAIN ENDOTHELIAL BARRIER PERMEABILITY COMBINED WITH VASCULAR NETWORK ANALYSIS AND FUNCTIONAL BEHAVIORAL OUTCOMES. AIM 1 WILL ELUCIDATE THE CONTRIBUTION OF BRAIN ENDOTHELIAL CELL TNAP TO NVU DYSFUNCTION IN ISCHEMIC STROKE IN YOUNG MICE. WE WILL EMPLOY THE TRANSIENT MIDDLE ARTERY OCCLUSION MODEL TO ASSESS QUANTITATIVE DIFFERENCES IN CEREBROVASCULAR OUTCOMES AND BEHAVIORAL INDICES. AIM 2 WILL DETERMINE THE IMPACT OF BRAIN ENDOTHELIAL CELL TNAP ON AGE-DEPENDENT IMPAIRMENT OF THE NVU. THIS AIM WILL ASSESS THE IMPACT TNAP ON BMEC FUNCTION IN AGING AND THE PUTATIVE AGE-DEPENDENT INTERACTIONS IN ISCHEMIC STROKE. AIM 3 WILL DETERMINE HOW THE TNAP-RHO ASSOCIATED KINASE (ROCK) PATHWAY REGULATES THE BARRIER FUNCTION AND WHETHER PHARMACOLOGICAL INHIBITION OF THE ROCK PATHWAY PROTECTS AGAINST THE LOSS OF BARRIER INTEGRITY AND FUNCTIONAL DEFICITS ASSOCIATED ISCHEMIC STROKE IN BOTH YOUNG AND AGED MICE. TAKEN TOGETHER, THE STUDIES IN THIS PROPOSAL WILL DELINEATE A NOVEL MECHANISM THROUGH WHICH BRAIN ENDOTHELIAL CELL TNAP ENZYME ACTIVITY PRESERVES NVU FUNCTION IN ISCHEMIC STROKE AND IMPROVES FUNCTIONAL RECOVERY POST-STROKE. THE OVERALL RESULTS WILL CONTRIBUTE TO OUR LIMITED UNDERSTANDING OF THE BASIC BIOLOGY OF TNAP’S ROLE AT THE BBB AND ITS CONTRIBUTION TO NVU HOMEOSTASIS IN HUMAN HEALTH AND DISEASE.

THE PROJECT WILL PROVIDE TRAINING AND HANDS-ON TECHNICAL ASSISTANCE TO HELP SMALL OR VERY SMALL PUBLIC DRINKING WATER SYSTEMS PROTECT THEIR SOURCES

RAMP: TRAINING IN THE ONE HEALTH FRAMEWORK: STUDIES IN ANIMALS AND ENVIRONMENTS THAT AFFECT HUMAN HEALTH IN WEST VIRGINIA (ONE HEALTH WV) -THIS PROJECT WILL ESTABLISH ONE HEALTH WEST VIRGINIA, A NETWORK CONNECTING RESEARCH MENTORS IN THE ONE HEALTH AREA WITH POSTBACCALAUREATE MENTEES FROM RESEARCH-DISADVANTAGED BACKGROUNDS. RESEARCH SPANS THREE CORE ONE HEALTH THEMES: WATER USE AND QUALITY, ENVIRONMENTAL CONTAMINATION, AND BIOLOGICAL CORRELATES OF DISEASE. WEST VIRGINIA IS ONE OF THE MOST AT-RISK STATES FOR INFECTIOUS DISEASE, RANKS AT OR NEAR THE BOTTOM IN MOST US CHRONIC DISEASE CATEGORIES, AND CURRENTLY RANKS 50TH NATIONALLY IN POPULATION GROWTH, WITH CONSISTENT POPULATION LOSS DRIVEN BY INDIVIDUALS UNDER THE AGE OF FIFTY. THIS PROJECT WILL ADDRESS THE URGENT SOCIETAL NEED FOR RECRUITMENT AND RETENTION OF EDUCATED YOUNGER INDIVIDUALS IN THE REGION BY PROVIDING TRAINING, MOTIVATIONAL OPPORTUNITIES, AND PATHWAYS TO A WIDE RANGE OF CAREER PATHWAYS OR GRADUATE STUDY IN STEM FIELDS. IT WILL INCREASE THE POOL OF SKILLED INDIVIDUALS BY BRIDGING THE GAP BETWEEN AN UNDERGRADUATE DEGREE AND SUCCESSFUL STEM CAREER FOR STUDENTS WITH LITTLE OR NO PREVIOUS RESEARCH EXPERIENCE. THROUGH INTENTIONAL RECRUITMENT AND CULTURALLY-AWARE TRAINING OF MENTORS FROM DIVERSE BACKGROUNDS, THIS PROJECT WILL BROADEN PARTICIPATION IN STEM FIELDS. THE TRAINING NETWORK WILL PROVIDE RIGOROUS MENTEE TRAINING IN SCIENTIFIC RESEARCH AREAS AROUND THE ONE HEALTH THEME. IT WILL ALSO ESTABLISH A PIPELINE FOR MENTEES TO TRANSITION SUCCESSFULLY INTO ACADEMIC, CORPORATE, NON-GOVERNMENTAL ORGANIZATION (NGO), AND GOVERNMENTAL EMPLOYMENT. THE NETWORK WILL INCORPORATE RESEARCH GROUPS FROM WEST VIRGINIA UNIVERSITY, WEST VIRGINIA STATE UNIVERSITY, AND MARSHALL UNIVERSITY. A TOTAL OF 30 MENTEES WILL WORK WITH FACULTY MENTORS IN FULL-TIME, 12-MONTH POSITIONS TO EXPLORE ISSUES IN THE ONE HEALTH THEME. DURING THE COURSE OF THIS PROGRAM, MENTEES WILL ACQUIRE TRAINING WITH CUTTING EDGE SCIENTIFIC EQUIPMENT, ETHICAL AND SAFE RESEARCH CONDUCT, EFFECTIVE EXPERIMENTAL DESIGN, AND SCIENTIFIC WRITING AND COMMUNICATION. THEY WILL ACQUIRE SKILLS IN LABORATORY, FIELD, AND DATA ANALYSIS TECHNIQUES THAT ARE IMMEDIATELY APPLICABLE IN THE CURRENT STEM WORKPLACE (ACADEMIC OR OTHERWISE). MENTEE PROJECTS STUDYING ENVIRONMENTAL POLLUTANTS AND CONTAMINANTS WILL INFORM EFFECTIVE WIDESPREAD MITIGATION EFFORTS, AND RESEARCH ON INSECT AND WILDLIFE HEALTH WILL PROVIDE ESSENTIAL INSIGHTS TO GLOBAL DISEASE PREVENTION, SURVEILLANCE, AND CONTROL. 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.

CITER CODESIGN INITIATIVE

DE-FE0031866, NEW AWARD TO WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION, ''MICROWAVE CATALYSIS FOR PROCESS INTENSIFIED MODULAR PRODUCTION OF CARBON NANOMATERIALS FROM NATURAL GAS''

MOUNTAINEER MATHEMATICS MASTER TEACHERS: SUPPORTING TEACHER LEADERSHIP AND NETWORKED IMPROVEMENT OF MATHEMATICS EDUCATION IN WEST VIRGINIA

IGERT: REN@WVU - RESEARCH AND EDUCATION IN NANOTOXICOLOGY AT WEST VIRGINIA UNIVERSITY

IMPACT OF SEX DIFFERENCES ON MOLECULAR DETERMINANTS OF AD RISK AND RESPONSIVENESS TO TREATMENT - ABSTRACT: THERE ARE SIGNIFICANT DIFFERENCES BETWEEN MEN AND WOMEN IN THE INCIDENCE AND SEVERITY OF LATE- ONSET ALZHEIMER’S DISEASE (LOAD). AFTER MENOPAUSE, WOMEN ARE MORE LIKELY TO DEVELOP LOAD, AND SYMPTOMS OF THE DISEASE INCLUDING COGNITIVE IMPAIRMENT ARE MORE SEVERE. THESE SYMPTOMS ARE EXACERBATED BY HIGH CHOLESTEROL WHICH, AT MIDLIFE, IS A MAJOR RISK FACTOR FOR LOAD. THERE IS A SUBSTANTIAL GAP IN OUR KNOWLEDGE OF HOW ESTROGEN AND CHOLESTEROL INTERACT. WE PROPOSE TO EXAMINE THE ROLE OF ESTROGEN AND CHOLESTEROL IN LOAD SEX DIFFERENCES BY STUDYING MALE AND FEMALE CHOLESTEROL-FED RABBITS – AN UNCONVENTIONAL BUT PROMISING MODEL OF LOAD. THESE RABBITS SHOW SIGNIFICANT SEX DIFFERENCES IN AD-LIKE PATHOLOGY, ESTROGEN RECEPTOR TRANSCRIPTIONAL ACTIVITY AND PROTEIN EXPRESSION, AND DIFFERENCES IN COGNITION. CHOLESTEROL-FED FEMALE RABBITS DEVELOP BETA AMYLOID (ASS) DEPOSITS MORE SLOWLY THAN CHOLESTEROL-FED MALES AND ELIMINATING PERIPHERAL ESTROGEN BY OVARIECTOMY MORE THAN DOUBLES ASS LEVELS, SUGGESTING A PROTECTIVE ROLE FOR ESTROGEN. WE HAVE EVIDENCE THAT A CHOLESTEROL DIET ALTERS ESTROGEN RECEPTORS, SIGNIFICANTLY INCREASES SERUM AND HIPPOCAMPAL LEVELS OF THE CHOLESTEROL METABOLITE, 27-HYDROXYCHOLESTEROL (27-OHC), AND FEMALE CHOLESTEROL-FED RABBITS REMEMBER HIPPOCAMPALLY-DEPENDENT LEARNING BETTER THAN CHOLESTEROL-FED MALES. 27-OHC IS A WELL-DOCUMENTED ENDOGENOUS SELECTIVE ESTROGEN RECEPTOR MODULATOR THAT MAY PLAY A ROLE IN LEARNING AND MEMORY BECAUSE PATIENTS WITH MILD COGNITIVE IMPAIRMENT (MCI) AND AD SHOW ELEVATED 27-OHC LEVELS AND WE HAVE EVIDENCE THAT CHOLESTEROL-FED RABBITS HAVE ELEVATED 27-OHC AND MEMORY DEFICITS. WE ALSO HAVE DATA SHOWING THERE ARE SEX DIFFERENCES IN THE TRANSCRIPTIONAL ACTIVITY OF ESTROGEN RECEPTORS AND EXPRESSION OF PROTEINS IN THE PRESYNAPTIC ACTIVE ZONE AND POSTSYNAPTIC DENSITY THAT ARE HIGHER IN FEMALE CHOLESTEROL-FED RABBITS THAN IN MALES. OUR RESEARCH FOCUS ON CHOLESTEROL-INDUCED INCREASES IN 27-OHC HAS DIRECT CLINICAL RELEVANCE BECAUSE MIDLIFE HYPERCHOLESTEROLEMIA IS A SIGNIFICANT RISK FACTOR FOR LOAD AND, AS NOTED, 27-OHC IS ELEVATED IN MCI AND LOAD. IN THREE SPECIFIC AIMS, WE WILL MANIPULATE ESTROGEN (AIM 1), 27-OHC (AIM 2), AND ESTROGEN RECEPTORS (AIM 3) IN CHOLESTEROL-FED RABBITS TO TEST THE HYPOTHESIS THAT SEX DIFFERENCES IN AD-LIKE COGNITIVE IMPAIRMENT AND PATHOLOGY ARE A FUNCTION OF ESTROGEN AND CAN BE RESCUED WITH ESTROGEN RECEPTOR MODULATION. USING BEHAVIORAL, ELECTROPHYSIOLOGICAL, HISTOCHEMICAL, AND MOLECULAR BIOLOGICAL TECHNIQUES, WE WILL DETERMINE THE MECHANISMS BY WHICH ESTROGEN RECEPTOR MODULATION AFFECTS MEMORY, NEURAL FUNCTION, MARKERS OF CHOLESTEROL AND ASS PROCESSING, AND ASS AND TAU LEVELS IN INTACT AND CASTRATED MALE AND IN INTACT AND OVARIECTOMIZED FEMALE CHOLESTEROL-FED RABBITS. OUR EXPERTISE IN AND TRACK RECORD OF BEHAVIORAL, HISTOCHEMICAL, ELECTROPHYSIOLOGICAL, AND MOLECULAR BIOLOGICAL RESEARCH IN CHOLESTEROL-FED RABBITS MAKES US A PARTICULARLY WELL-SUITED TEAM TO CONDUCT THESE EXPERIMENTS, FURTHER VALIDATE THIS NON-TRANSGENIC MODEL OF LOAD, AND POSITIONS US TO HELP UNDERSTAND THE IMPACT OF SEX DIFFERENCES ON THE MOLECULAR DETERMINANTS OF LOAD RISK AND RESPONSIVENESS TO TREATMENT.

AN ANIMAL MODEL FOR DEVELOPING TREATMENTS OF PTSD CORE FEATURES

RURAL HEALTH RESEARCH GRANT PROGRAM COOPERATIVE AGREEMENT

DEVELOPMENT OF MUCOSAL VACCINES TO PROTECT AGAINST PERTUSSIS

PHARMACY NALOXONE DISTRIBUTION: ASSESSING A NEW TOOL TO REDUCE OVERDOSE MORTALITY

WEST VIRGINIA PEDIATRIC CLINICAL TRIALS NETWORK-2

MECHANISMS OF CORONARY FLOW REGULATION BY ADENOSINE

UNIVERSITY CENTERS FOR EXCELLENCE IN DEVELOPMENTAL DISABILITIES EDUCATION, RESEARCH, AND SERVICES (UCEDD)

COBRE TRANSITIONAL CENTER IN NEUROSCIENCE

CONTINUATION OF RESEARCH, COMMERCIALIZATION, AND WORKFORCE DEVELOPMENT IN THE POLYMER/ELECTRONICS RECYCLING INDUSTRY

ROLE OF AIPL1 IN INHERITED RETINAL DEGENERATIVE DISEASE

UNMANNED SYSTEM ALGORITHM DEVELOPMENT

ADVANCED COMMUNICATIONS FOR WIRELESS SENSOR NETWORKS

CENTER FOR EXCELLENCE IN DISABILITIES (CED)

MECHANISMS REGULATING PROTEASOMAL SUBSTRATE DEGRADATION

HEALTH CARE AND OTHER FACILITIES

IN-SITU MVA OF CO2 SEQUESTRATION USING SMART FIELD TECHNOLOGY

SYNAPSE-SPECIFIC EFFECTS OF SYNAPTICALLY RELEASED ZINC: IMPLICATIONS FOR AUDITORY PROCESSING

I/UCRC CGI: COLLABORATIVE RESEARCH - I/UCRC FOR IDENTIFICATION TECHNOLOGY RESEARCH

FOSTERING AN ADMIN PARTNERSHIP AND TRAVEL SUPPORT BTW WV UNIV AND THE NORTHEASTERN AREA ASSOCIATION OF STATE FORESTERS

A PET/CT SCANNER FOR GUIDING TREATMENT OF HEAD AND NECK CANCER

WEST VIRGINIA MANUFACTURING EXTENSION PARTNERSHIP SOLUTIONS FOR WEST VIRGINIA MANUFACTURERS

VACCINE DEVELOPMENT AGAINST BACTERIAL PATHOGENS BASED ON IRON ACQUISITION PROTEINS

INTENSIFIED DYNAMIC NON-EQUILIBRIUM REACTIONS BY PULSED MICROWAVE HEATING FOR EFFICIENT CHEMICAL PROCESSING

AWARD NUMBER: DE-EE0009654 RECIPIENT: WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION NEW AWARD TITLED, FAST SIMULATION OF REAL DRIVING EMISSIONS FROM HEAVY-DUTY DIESEL VEHICLE INTEGRATED WITH ADVANCED AFTERTREATMENT SYSTEM

PURPOSE:THE PURPOSE OF THIS GRANT IS TO PROVIDE THE FUNDS NECESSARY FOR THE WEST VIRGINIA UNIVERSITY (WVU) TO PURCHASE A FOCUSED ION-BEAM SCANNING ELECTRON MICROSCOPE (FIB-SEM). THIS INSTRUMENT WILL BE HOUSED IN THE ELECTRON MICROSCOPY FACILITIES (EMF) OF THE WVU SHARED RESEARCH FACILITIES AND WILL BE AVAILABLE TO A WIDE USER BASE OF UNIVERSITY RESEARCHERS.ACTIVITIES TO BE PERFORMED:THE DIRECTOR OF THE SHARED RESEARCH FACILITY WILL LEAD A TEAM OF FACULTY THAT WILL EVALUATE COMMERCIALLY AVAILABLE FIB-SEM INSTRUMENTS AND CHOOSE THE ONE THAT IS BEST SUITED TO THE UNIVERSITY NEEDS. THE INSTRUMENT WILL BE INSTALLED IN A FACILITY OUTFITTED WITH THE NECESSARY ANCILLARY EQUIPMENT AND APPROPRIATE ENVIRONMENTAL CONDITIONS. THE MANAGER OF THE EMF WILL PROVIDE TRAINING FOR ALL USERS AND BE RESPONSIBLE FOR ROUTINE MAINTENANCE OF THE MICROSCOPE AND USE OF SERVICE CONTRACTS WHEN APPROPRIATE. A WIDE VARIETY OF USERS THROUGHOUT THE UNIVERSITY IN AREAS SUCH AS NEUROSCIENCE ENGINEERING, BIOCHEMICAL SCIENCES, AND ADVANCED MATERIALS SCIENCE WILL USE THE MICROSCOPE FOR 3-D NANOSCALE IMAGING AND PATTERNING, CROSS-SECTIONING OF TECHNOLOGICAL MATERIALS TO REVEAL BURIED LAYERS AND THE PREPARATION OF SPECIMENS FOR TRANSMISSION ELECTRON MICROSCOPY.EXPECTED OUTCOMES:A FIB-SEM IS AN IMPORTANT PIECE OF INSTRUMENTATION FOR A SHARED USE ELECTRON MICROSCOPY FACILITY SUCH AS THE ONE AT WVU. IT ENABLES SOPHISTICATED NANOSCALE 3-D RECONSTRUCTIONS OF ADVANCED MATERIALS FROM ELECTRON MICROCOPY IMAGES, THE ABILITY TO SHAPE AND MODIFY MATERIALS ON REMARKABLY SMALL LENGTH SCALES AND IT IS ESSENTIAL FOR THE PREPARATION OF MATERIALS FOR FURTHER ANALYSIS BY TRANSMISSION ELECTRON MICROSCOPY. WVU RESEARCHERS WILL USE THIS TOOL TO STUDY A WIDE ARRAY OF NANOSCALE PHENOMENA INCLUDING; THE IN VIVO DEGRADATION MECHANISMS AFFECTING IMPLANTABLE NEURO-PROSTHETICS AND ELECTRODES UTILIZED FOR NERVE STIMULATION; THE INTERNAL CELLULAR STRUCTURE IN MOUSE ROD NEURON CELLS THAT SERVE AS MODELS FOR STUDIES OF EYE DISEASES; THE PATTERNING OF NOVEL MICROFLUIDIC DEVICES; THE DEGRADATION MECHANISMS OF CATHODES FOR SOLID OXIDE FUEL CELLS; AND THE SURFACE STRUCTURE OF SUPERCONDUCTING MATERIALS FOR USE IN ADVANCED DETECTORS FOR NASA.UNITED STATES DEPARTMENT OF COMMERCENATIONAL INSTITUTE OF STANDARDS AND TECHNOLOGYMATERIAL MEASUREMENT LABORATORY100 BUREAU DRIVE, MS 8300GAITHERSBURG, MARYLAND 20899INTENDED BENEFICIARIES:THE IMAGES AND SPECIMENS GENERATED USING THE FIB-SEM INSTRUMENTATION WILL GREATLY BENEFIT THE USER BASE OF WVU UNIVERSITY RESEARCHERS. THEIR WORK WILL ULTIMATELY LEAD TO SIGNIFICANT SOCIETAL BENEFIT IN AREAS INCLUDING NEUROLOGICAL MEDICINE, OUR UNDERSTANDING OF EYE DISEASE, FUEL CELLS FOR THE HYDROGEN ECONOMY AND THE EXPLORATION OF SPACE. THE AVAILABILITY OF THIS INSTRUMENT WILL ALSO BE GREATLY BENEFICIAL FOR THE TRAINING OF STUDENTS TO PREPARE THEM FOR PARTICIPATION IN ADVANCED MANUFACTURING FIELDS.SUBRECIPIENT ACTIVITIES:THE RECIPIENT DOES NOT INTEND TO SUBAWARD FUNDS.

RISK AND RESILIENCE PATHWAYS LINKING COMMUNITY ADVERSITY, DECISION MAKING, AND ALCOHOL MISUSE: A PROSPECTIVE STUDY OF APPALACHIAN ADOLESCENTS

RESEARCH TRAINING PROGRAM IN BEHAVIORAL AND BIOMEDICAL SCIENCES

INNOVATIVE PRE- EMPLOYMENT TRANSITION SERVICES (PRE-ETS) TRAINING PROGRAM FOR VR COUNSELORS

ROLE OF CYP P450S IN THE REGULATION OF VASCULAR TONE THROUGH ADENOSINE RECEPTORS

ROLE OF NKB IN THE CONTROL OF GNRH SECRETION BY OVARIAN STEROIDS

WEST VIRGINIA UNIVERSITY UCEDD FY23-27

SEDENTARY BEHAVIOR AND CARDIOVASCULAR HEALTH IN YOUNG WOMEN - ABSTRACT WOMEN HAVE MORE RAPID CARDIOVASCULAR DISEASE (CVD) RISK DEVELOPMENT COMPARED TO MEN DURING YOUNG ADULTHOOD; YET, LITTLE RESEARCH HAS STUDIED FACTORS THAT COULD CURTAIL CVD RISK DEVELOPMENT DURING THIS CRITICAL PERIOD FOR YOUNG WOMEN. THE NULLIPAROUS PREGNANCY OUTCOMES STUDY MONITORING MOTHERS-TO-BE HEART HEALTH STUDY (NUMOM2B HHS) IS A UNIQUE, MULTI-CENTER, LONGITUDINAL COHORT, ORIGINATING DURING THE FIRST PREGNANCY, THAT IS NOW STUDYING ASSOCIATIONS BETWEEN ADVERSE PREGNANCY OUTCOMES (APO) AND MODIFIABLE CVD RISK IN WOMEN. THIS ANCILLARY APPLICATION TO NUMOM2B HHS AIMS TO TEST OUR HYPOTHESES THAT SEDENTARY BEHAVIOR (SED) IS A KEY, MODIFIABLE RISK FACTOR FOR CVD RISK DEVELOPMENT IN YOUNG WOMEN, INCLUDING THOSE WITH APO. SED IS LOW-INTENSITY BEHAVIOR IN A SEATED, RECLINING, OR LYING POSTURE AND HAS RECENTLY BEEN IDENTIFIED AS A CVD RISK FACTOR THAT IS DISTINCT FROM INSUFFICIENT MODERATE-TO-VIGOROUS INTENSITY ACTIVITY (MVPA). ACUTE PROLONGED SITTING RESULTS IN MARKED, ADVERSE RESPONSES SUCH AS INCREASED BLOOD PRESSURE (BP), GLUCOSE, AND LIPIDS. YET, MAJOR RESEARCH GAPS PRECLUDE THE DEVELOPMENT AND TESTING OF SPECIFIC SED-REDUCTION INTERVENTIONS, ESPECIALLY FOR YOUNG WOMEN. MOST STUDIES MEASURE SED POORLY (E.G., BY SELF-REPORT) AND DO NOT STATISTICALLY CONSIDER THAT SED IS PART OF AN ALL-DAY ACTIVITY PATTERN (OR COMPOSITION). FURTHER, MECHANISMS OF HOW SED LEADS TO CVD ARE UNCLEAR, FURTHER LIMITING INTERVENTION DEVELOPMENT. LAST, ALMOST NO STUDIES FOCUS ON YOUNG WOMEN. OUR PRELIMINARY DATA SUGGEST THAT SED IS STRONGLY ASSOCIATED WITH APOS AND REDUCED CARDIOVASCULAR HEALTH (E.G., BP) IN YOUNG WOMEN POST-PREGNANCY. FURTHER, OUR LABORATORY HAS RECENTLY DEMONSTRATED NOVEL ASSOCIATIONS BETWEEN SED AND MECHANISTIC CVD MEASURES, INCLUDING GREATER ARTERIAL STIFFNESS (HIGHER PULSE WAVE VELOCITY [PWV]) AND WORSE AUTONOMIC FUNCTION (LOWER HEART RATE VARIABILITY [HRV]). COLLECTIVELY, SED IS A NOVEL, UNDERSTUDIED RISK FACTOR FOR REDUCED CARDIOVASCULAR HEALTH THAT OUR DATA SUGGEST IS HIGHLY RELEVANT FOR YOUNG WOMEN. WE HAVE A UNIQUE, EFFICIENT, AND TIME-SENSITIVE OPPORTUNITY TO ADDRESS THESE GAPS BY ADDING GOLD STANDARD SED ASSESSMENT VIA ACTIVPAL THIGH-MOUNTED ACCELEROMETER TO THE UPCOMING HHS2 EXAM. IN THIS CONTEMPORARY AND DIVERSE FEMALE COHORT (N=4,050, AGE=36±6 YEARS), WE AIM TO QUANTIFY CROSS-SECTIONAL AND LONGITUDINAL ASSOCIATIONS OF SED WITH THE CLINICAL COMPONENTS OF IDEA CARDIOVASCULAR HEALTH (BP, BMI, TOTAL CHOLESTEROL, FASTING GLUCOSE) BY USING STATE-OF-THE-ART STATISTICAL METHODS THAT CONSIDER THE COMPOSITIONAL NATURE OF SED AND 24-HR ACTIVITY AND CAN CORRECT EXISTING, LONGITUDINAL SELF-REPORTED SED VIA REGRESSION CALIBRATION. ALSO, WE ADD HRV AND PWV IN PITTSBURGH AND INDIANA (N=950) TO EFFICIENTLY STUDY ASSOCIATIONS BETWEEN SED AND SUBCLINICAL, MECHANISTIC CVD OUTCOMES IN YOUNG WOMEN. AIM 3 WILL STUDY INTERRELATIONSHIPS OF SED, APO HISTORY, AND IDEAL CARDIOVASCULAR HEALTH TO IDENTIFY NOVEL RISK REDUCTIONS STRATEGIES IN THIS HIGH-RISK GROUP WITH LIMITED TREATMENT OPTIONS. THIS RESEARCH WILL PROVIDE CRITICAL DATA TO RIGOROUSLY LINK SED, CVD RISK, AND CONTRIBUTING MECHANISMS AND WILL INFORM AGE- AND SEX-SPECIFIC SED INTERVENTIONS TO TEST IN YOUNG WOMEN, INCLUDING THOSE WITH APO.

PRIMARY CARE TRAINING AND ENHANCEMENT - LANGUAGE AND DISABILITY ACCESS - THE LONG-TERM GOAL OF THIS APPLICATION IS TO IMPROVE THE HEALTH OUTCOMES OF INDIVIDUALS LIVING IN THE RURAL, APPALACHIAN REGION OF WEST VIRGINIA (WV). WEST VIRGINIANS EXPERIENCE NUMEROUS PHYSICAL AND MENTAL HEALTH CONDITIONS ACROSS THEIR LIFETIME. MORE INDIVIDUALS IN THIS RURAL, APPALACHIAN REGION ARE LIKELY TO EXPERIENCE CHRONIC HEALTH CONDITIONS THAN OTHERS WITHIN THE NATION. THIS INCREASED RISK IS ASSOCIATED WITH LONG-STANDING SOCIAL DETERMINANT FACTORS SUCH AS AN AGING POPULATION, A LIMITED ECONOMY, AND MEDICALLY UNDERSERVED ENVIRONMENTS. WHILE THIS REGION OF THE UNITED STATES HAS HISTORICALLY BEEN CHARACTERIZED BY A HOMOGENOUS AND STATIC DWELLER GROUP, AN INCREASE IN THE MIGRANT POPULATION HAS BEEN RECORDED WITHIN THE LAST DECADE. MIGRANTS AND OTHER RESIDENTS WHO SPEAK ENGLISH AS A SECOND LANGUAGE HAVE IDENTIFIED SIGNIFICANT CHALLENGES FOR RURAL PRIMARY CARE AND THE LARGER HEALTHCARE SYSTEM THROUGHOUT THE STATE. THIS, COUPLED WITH THE EXISTING HEALTH LITERACY NEEDS AND A RISING PROPORTION OF INDIVIDUALS WITH ACUTE AND/OR CHRONIC DISABILITIES, SERVES AS THE IMPETUS FOR THIS DUAL-FOCUSED APPLICATION OF LANGUAGE ASSISTANCE AND DISABILITY-BASED TRAINING INITIATIVES. OUR OBJECTIVES ADDRESS OPPORTUNITIES TO INCREASE THE NUMBER OF MEDICAL STUDENTS AND RESIDENTS, PARTICULARLY THOSE WHO PLAN TO PRACTICE WITHIN THE RURAL AND PRIMARY CARE SETTINGS, WHO ARE TRAINED TO PROVIDE CULTURALLY AND LINGUISTICALLY APPROPRIATE CARE TO ALL INDIVIDUALS, INCLUDING THOSE WITH PHYSICAL, INTELLECTUAL, AND/OR DEVELOPMENTAL DISABILITIES. THE RUGGED WV LANDSCAPE HAS PRODUCED CONSISTENT CHALLENGES FOR PROVIDING HEALTHCARE. TELEMEDICINE AND OTHER CREATIVE SERVICE COORDINATION PROGRAMS HAVE BEEN CREATED IN RESPONSE TO THESE CHALLENGES. RECRUITMENT EFFORTS TO INCENTIVIZE A RETURNING HEALTHCARE WORKFORCE HAVE ALSO BEEN IMPLEMENTED WITH INCREASING SUCCESS. THE UNDERGRADUATE AND GRADUATE MEDICAL EDUCATION TEAMS AT THE LAND-GRANT UNIVERSITY IN WV HAVE BUILT A SUPPORTIVE INFR ASTRUCTURE WITH A COLLABORATIVE MENTALITY THAT HAS ALREADY IDENTIFIED INITIAL NEEDS PERTINENT TO THOSE WHO SPEAK ENGLISH AS A SECOND LANGUAGE, HAVE LIMITED HEALTH LITERACY PROFICIENCY, AND/OR HAVE DISABILITIES. THIS APPLICATION BUILDS UPON A STRONG COLLABORATION BETWEEN THE WEST VIRGINIA UNIVERSITY SCHOOL OF MEDICINE (WVU SOM), THE WVU CENTER FOR EXCELLENCE IN DISABILITIES (WVU CED), AND THE WVU EBERLY SCHOOL OF ARTS AND SCIENCES, REPRESENTED BY THE DEPARTMENT OF WORLD LANGUAGES, THE CENTER FOR HUMANITIES, AND THE ENGLISH AS A SECOND LANGUAGE (ESL) PROGRAM. THIS COLLABORATION HAS PRODUCED EVIDENCE-BASED INITIATIVES FOR UNDERGRADUATE AND GRADUATE HEALTH SCIENCE STUDENTS THAT ARE IMPLEMENTED IN A VARIETY OF SETTINGS THROUGHOUT THE CURRICULAR PATHWAY FOR EACH DISCIPLINE INCLUDING MEDICINE, NURSING, PHARMACY, SOCIAL WORK, AND PUBLIC HEALTH. THIS COLLABORATIVE INFRASTRUCTURE HAS ALSO IMPLEMENTED EARLY TRAINING PROGRAMMING FOR MEDICAL STUDENT AND RESIDENTS TO TEST THEM FOR FEASIBILITY AND IMPACT. THIS PROPOSAL WILL COORDINATE THE EXISTING INITIATIVES, EXPAND THEM ACROSS THE CURRICULUM, AND IDENTIFY NEW OPPORTUNITIES FOR LEARNING FOR STUDENTS DURING THEIR FOUR YEARS OF MEDICAL SCHOOL AND RESIDENCY. PROPOSED ACTIVITIES ARE, AND WILL CONTINUE TO BE, CO-DESIGNED AND IMPLEMENTED BY PATIENTS REPRESENTING THE TWO GROUPS IN THIS APPLICATION: PATIENTS WHO SPEAK ENGLISH AS A SECOND LANGUAGE AND/OR THOSE WITH PHYSICAL, INTELLECTUAL, AND/OR DEVELOPMENTAL DISABILITIES. ACTIVITIES WILL BE AVAILABLE TO STUDENTS AT THREE CAMPUSES LOCATED IN KEY LOCATIONS ACROSS WV: MORGANTOWN, MARTINSBURG, AND CHARLESTON, WV. LASTLY, THE PROPOSED BUDGET INCLUDES PERSONNEL, INFRASTRUCTURE, AND OTHER RESOURCES REQUIRED TO SUCCESSFULLY DEVELOP, IMPLEMENT, AND STRENGTHEN THE PROPOSED DUAL-TRACK, TRAINING OPPORTUNITIES. THESE COLLECTIVE CHALLENGES AND EFFORTS TO RESOLVE GAPS IN TRAINING AND SERVICES IN WV SERVE AS THE IMPETUS FOR THIS APPLICATION.

DEVELOPMENT OF DIRECT CARBON FUEL CELL (DCFD) FOR DOD APPLICATION

PRIMARY CARE TRAINING AND ENHANCEMENT-COMMUNITY PREVENTION AND MATERNAL HEALTH

UNDERSTANDING IL-27 AS A NEGATIVE REGULATOR OF PROTECTIVE IMMUNITY DURING NEONATAL SEPSIS - PROJECT SUMMARY MICROBIAL INFECTIONS ARE A MAJOR CAUSE OF INFANT MORTALITY WORLDWIDE. FOR PARTICULARLY VULNERABLE POPULATIONS SUCH AS PRE-TERM AND LOW BIRTHWEIGHT BABIES, THE RISK OF INVASIVE INFECTIONS FURTHER ESCALATES. THE NEONATAL PERIOD IS DEFINED BY A DISTINCT, OFTEN DESCRIBED AS IMMATURE, IMMUNE SYSTEM. MANY FEATURES OF A PROTECTIVE HOST RESPONSE TO INFECTION ARE DEFICIENT AS COMPARED WITH OLDER CHILDREN AND ADULTS. OUR LABORATORY HAS IDENTIFIED THAT EXPRESSION OF THE IMMUNE SUPPRESSIVE CYTOKINE INTERLEUKIN (IL)-27 IS ELEVATED IN HUMAN AND MURINE NEONATES. OTHER RECENT STUDIES HAVE SHOWN IL-27 TO BE A BIOMARKER FOR EARLY ONSET NEONATAL SEPSIS. THIS SUGGESTS THAT ELEVATED IL-27 MAY REPRESENT A RISK FACTOR AND WHEN FURTHER INCREASED DURING BACTERIAL CHALLENGE, COMPROMISE THE HOST IMMUNE RESPONSE. THE OVERALL PREMISE OF THE CURRENT PROPOSAL IS THAT IL-27 IS A HOST MOLECULE THAT REPRESENTS A TARGET FOR IMMUNE INTERVENTION TO IMPROVE THE HOST RESPONSE AND REDUCE SUSCEPTIBILITY TO BACTERIAL INFECTION EARLY IN LIFE. WE PRESENT STRONG EVIDENCE IN A MOUSE MODEL THAT THE ABSENCE OF IL-27 SIGNALING TRANSLATES TO INCREASED SURVIVAL, IMPROVED WEIGHT GAIN, AND ENHANCED CLEARANCE OF BACTERIA DURING NEONATAL SEPSIS. TO ADVANCE OUR KNOWLEDGE OF HOW IL-27 REGULATES THE IMMUNE RESPONSE DURING NEONATAL SEPSIS, WE NEED TO IDENTIFY THE COMPLETE REPERTOIRE OF CELL TYPES RESPONSIBLE FOR IL-27 PRODUCTION, UNDERSTAND HOW THESE POPULATION MAY CHANGE OVER THE COURSE OF INFECTION, AND FURTHER DEFINE THEIR FUNCTIONALITY. WE WILL ADDRESS THIS GAP IN UNDERSTANDING USING AN IL-27 REPORTER MOUSE THAT EXPRESSES A FLUORESCENT PROTEIN UNDER CONTROL OF THE IL-27P28 PROMOTER. USING WHOLE-ANIMAL IMAGING OF THE REPORTER MOUSE COUPLED WITH LUMINESCENT BACTERIA, THIS WILL ALLOW US TO IDENTIFY IL-27 PRODUCERS, SORT THEM FOR FURTHER FUNCTIONAL ANALYSIS, AND CORRELATE THEIR PRESENCE IN INFECTED TISSUES WITH THE BACTERIAL BURDEN. WE ALSO SEEK TO UNDERSTAND CELLULAR SIGNALING PATHWAYS REQUIRED FOR IL-27-MEDIATED SUPPRESSIVE ACTIVITY AND COMPROMISED CONTROL OF THE BACTERIAL BURDEN. WE HYPOTHESIZE THAT SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION (STAT)-3 SIGNALS DOWNSTREAM OF IL-27 RECEPTOR BINDING TO INTERFERE WITH LYSOSOMAL TRAFFICKING AND ACIDIFICATION. THE NET RESULT IS COMPROMISED BACTERIAL CLEARANCE. LASTLY, A PRIMARY OBJECTIVE IS TO INVESTIGATE THE OUTCOMES OF ANTAGONIZING IL- 27 DURING NEONATAL SEPSIS WITH THE AIM OF ESTABLISHING AN IMMUNOTHERAPEUTIC APPROACH FOR AN INFECTIOUS DISEASE FOR WHICH WE CAN CURRENTLY ONLY OFFER ANTIBIOTICS AND SUPPORTIVE CARE. ANTIBIOTIC RESISTANCE CONFOUNDS OUR RELIANCE ON THIS APPROACH. ADMINISTRATION OF A NEUTRALIZING ANTIBODY CONJUGATED TO A FLUORESCENT TAG WILL ALLOW FOR VISUALIZATION OF TISSUE PENETRATION IN REAL TIME AND DIRECTLY CORRELATE THE PRESENCE OF THE ANTAGONIST WITH CONTROL OF BACTERIAL GROWTH. AT THE COMPLETION OF THIS PROJECT, WE EXPECT TO HAVE PERFORMED PRECLINICAL VALIDATION OF A PROMISING IMMUNOTHERAPEUTIC APPROACH TO IMPROVE IMMUNOLOGICAL RESPONSES AND SUSCEPTIBILITY TO INFECTION DISEASE IN NEWBORNS, AS WELL AS PROVIDED AN ENHANCED UNDERSTANDING OF HOW IL-27 REGULATES HOST IMMUNITY AND INTERACTIONS WITH BACTERIAL PATHOGENS DURING NEONATAL SEPSIS.

OSCILLATING LINEAR ENGINE AND ALTERNATOR

CHOLESTEROL AND COPPER AFFECT LEARNING AND MEMORY

RURAL INTEGRATION MODELS FOR PARENTS AND CHILDREN TO THRIVE: A TWO-GENERATIONAL APPROACH TO STRENGT

ADVERSE CONSEQUENCES OF LIGHT AT NIGHT FOR CEREBRAL ISCHEMIA

APPALACHIAN TRAINING PROGRAM IN OCCUPATIONAL HEALTH AND*

PET-EPRI

PROTEASOME FUNCTION IN ALZHEIMER'S DISEASE

MECHANISMS OF DIABETIC CARDIOMYOPATHY: MITOCHONDRIA SUBPOPULATIONS BROUGHT TO FOC

OPERATING CENTER RENEWAL PROPOSAL FOR THE CENTER FOR IDENTIFICATION TECHNOLOGY RESEARCH (CITER): AN I/UCRC IN BIOMETRICS

EXPLORING BOUNDARY STATES IN DIRAC MATERIALS: GRAPHENE AND TOPOLOGICAL INSULATORS

INFLATION REDUCTION ACT (IRA) – RESEARCH, DEVELOPMENT AND DEPLOYMENT OF THE METHANE MITIGATION SYSTEM THE OBJECTIVE OF THE PROPOSED WORK IS THE CONTINUED RESEARCH, DEVELOPMENT AND DEPLOYMENT PROTOTYPE METHANE MITIGATION SYSTEMS (MMS) AT ACTIVE NATURAL GAS COMPRESSION SITES. SUCCESSFUL DEPLOYMENT WILL SERVE AS CASE STUDIES TO BOLSTER COMMERCIALIZATION EFFORTS AND HIGHLIGHT TO INDUSTRY THE IMMEDIATE EMISSIONS REDUCTIONS BENEFITS AND WILL OCCUR ON MEDIUM AND LARGE DISPLACEMENT ENGINES (3500 AND 3600 SERIES).

DISCOVERY AND DEVELOPMENT OF SMALL MOLECULE AND ANTIBODY THERAPEUTICS USING ARTIFICIAL INTELLIGENCE AND MACHINE LEARNING.

TAS::89 0213::TAS #DE-FE0002994, NEW AWARD WITH WEST VIRIGNIA UNIVERSITY ENTITLED "WVU HYDROGEN FUEL DISPENSING STATION"

THE DEVELOPMENT OF AN ADVANCED INFRARED HYDROGEN FUEL FLEXIBLE BOILER FOR FOOD AND BEVERAGE INDUSTRY

NOVEL INTERNEURONS MEDIATING FEEDFORWARD THALAMOCORTICAL INHIBITION

GLAUCOMA MANAGEMENT IN THE AFRICAN-DERIVED DEVELOPING WORLD USING TRABECULOPLASTY

DIETARY MANIPULATIONS IN RABBITS INDUCE THE CELLULAR, NEUROPATHOLOGICAL, AND COGNITIVE HALLMARKS OF LATE-ONSET ALZHEIMER'S DISEASE - ABSTRACT: DESPITE THE SIGNIFICANT CONTRIBUTIONS OF TRANSGENIC MOUSE MODELS TO OUR UNDERSTANDING OF ALZHEIMER’S DISEASE, NIA HAS CONCLUDED THAT THESE MODELS MAY BE “OF POOR PREDICTIVE VALUE IN HUMAN CLINICAL TRIALS” [RFA- AG-21-003]. AS A RESULT, THERE IS A NEED FOR NEW, INNOVATIVE, NON-RODENT, MAMMALIAN MODELS THAT BETTER RECAPITULATE THE CELLULAR, NEUROPATHOLOGICAL, AND COGNITIVE HALLMARKS OF LATE-ONSET ALZHEIMER’S DISEASE (LOAD). THESE SHOULD INCLUDE MODELS IN WHICH RISK FACTORS FOR LOAD CAN BE SYSTEMATICALLY INDUCED, AND IN WHICH COGNITIVE DEFICITS THAT ARE THE EARLIEST HALLMARKS OF LOAD CAN BE ASSESSED. THERE IS CONVINCING EPIDEMIOLOGICAL EVIDENCE THAT DIET AND LIFESTYLE ARE IMPORTANT DETERMINANTS OF COGNITIVE FUNCTION, BUT IT IS UNCLEAR HOW FACTORS SUCH AS HIGH CHOLESTEROL, OBESITY, AND DIABETES INCREASE THE LIKELIHOOD OF COGNITIVE DEFICITS. THE PURPOSE OF THE CURRENT PROPOSAL IS TO DEVELOP, CHARACTERIZE, AND VALIDATE UNCONVENTIONAL, MAMMALIAN MODELS THAT RECAPITULATE THE CELLULAR, NEUROPATHOLOGICAL, AND COGNITIVE HALLMARKS OF LOAD. THE STRATEGY IS TO FEED MALE AND FEMALE RABBITS A LONG-TERM, LOW-DOSE CHOLESTEROL DIET IN AIM 1, A HIGH-FAT DIET IN AIM 2, AND A DIET HIGH IN BOTH SUGAR AND FAT IN AIM 3 TO RECREATE LOAD-LIKE PATHOLOGY AND STUDY THE EFFECTS OF HYPERCHOLESTEROLEMIA, OBESITY, AND HYPERGLYCEMIA ON LEARNING AND MEMORY USING A RANGE OF INCREASINGLY COMPLEX TASKS – WELL-UNDERSTOOD PARADIGMS THAT ARE ALTERED IN LOAD PATIENTS AND WE HAVE SHOWN TO BE AFFECTED BY DIETARY MANIPULATIONS IN RABBITS. WE WILL ALSO ASSESS THE CELLULAR AND NEUROPATHOLOGICAL EFFECTS OF HYPERCHOLESTEROLEMIA, OBESITY, AND HYPERGLYCEMIA INCLUDING THEIR IMPACT ON THE NEUROBIOLOGY OF LEARNING AND MEMORY. COMPELLING PRELIMINARY DATA PROVIDE EVIDENCE THAT A SHORT-TERM, HIGH-DOSE CHOLESTEROL DIET, A HIGH-FAT DIET, AND CHEMICALLY-INDUCED DIABETES HAVE DELETERIOUS EFFECTS ON A RANGE OF LEARNING AND MEMORY TASKS. PRELIMINARY ELECTROPHYSIOLOGICAL EVIDENCE SHOWS THAT FEEDING A DIET HIGH IN CHOLESTEROL OR HIGH IN FAT CAN IMPAIR A WELL-KNOWN FORM OF SYNAPTIC PLASTICITY THOUGHT TO UNDERLIE LEARNING AND MEMORY – LONG-TERM POTENTIATION. PUBLISHED AND PRELIMINARY PATHOPHYSIOLOGICAL DATA SHOW SIGNIFICANT DIET- INDUCED CHANGES IN CELLULAR AND NEUROPATHOLOGICAL MARKERS OF LOAD. TAKEN TOGETHER, THESE DATA PROVIDE PROOF OF CONCEPT, BUT THE LEVELS OF HYPERCHOLESTEROLEMIA AND HYPERGLYCEMIA WERE HIGH AND, ALTHOUGH THEY RECAPITULATED LOAD-LIKE PATHOLOGIES INCLUDING BETA AMYLOID ACCUMULATION, THEY ALSO PRODUCED OFF-TARGET PATHOLOGY. IT IS THEREFORE IMPORTANT TO ESTABLISH, CHARACTERIZE, AND VALIDATE THE COGNITIVE AND PATHOPHYSIOLOGICAL EFFECTS OF MILDER, MORE LONG-TERM DIETARY MANIPULATIONS THAT INDUCE THE TYPES AND LEVELS OF HYPERCHOLESTEROLEMIA, OBESITY, AND HYPERGLYCEMIA THAT ARE MORE CLINICALLY RELEVANT. OUR EXPERTISE IN AND TRACK RECORD OF INDUCING SIGNIFICANT BEHAVIORAL, ELECTROPHYSIOLOGICAL, AND PATHOPHYSIOLOGICAL CHANGES BY MANIPULATING DIETS IN ADULT RABBITS MAKES US WELL-SUITED TO DEVELOP, CHARACTERIZE, AND VALIDATE THESE UNCONVENTIONAL MODELS OF LOAD – MODELS THAT MAY REPRESENT IMPROVED TRANSLATIONAL POTENTIAL BY BETTER REPLICATING THE CELLULAR, NEUROPATHOLOGICAL, AND COGNITIVE FEATURES OF LOAD THAN CURRENT RODENT MODELS.

ROLE OF PROTEIN IMPORT IN THE DEVELOPMENT OF THE DIABETIC HEART - PROJECT SUMMARY CARDIOVASCULAR COMPLICATIONS ACCOUNT FOR THE MAJORITY OF DEATHS IN DIABETIC PATIENTS. MITOCHONDRIAL DYSFUNCTION IS CENTRAL TO THE DISEASE AND IT PRECIPITATES CONTRACTILE IMPAIRMENT, LEADING TO DEATH. HOWEVER, THE PRECISE MECHANISMS THAT CAUSE MITOCHONDRIAL DYSFUNCTION IN THE DIABETIC HEART REMAIN UNCLEAR. USING TYPE 2 DIABETIC HUMAN (PATIENT) AND MOUSE (DB/DB) MODELS, WE OBSERVED PRONOUNCED DISRUPTION TO MITOCHONDRIAL STRUCTURE AND FUNCTION, WHICH WERE ASSOCIATED WITH THE LOSS OF MITOCHONDRIAL PROTEINS. THE VAST MAJORITY OF MITOCHONDRIAL PROTEINS ARE NUCLEAR GENOME-ENCODED AND REQUIRE IMPORT INTO THE MITOCHONDRION. IMPORT OCCURS THROUGH A COORDINATED SET OF MACHINERY CONTAINING AN ACTIVE MOTOR, DRIVEN BY MITOCHONDRIAL HEAT SHOCK PROTEIN 70 (MTHSP70). WE OBSERVED DECREASED MTHSP70 CONTENT IN CARDIAC MITOCHONDRIA FROM TYPE 2 DIABETIC PATIENTS AND DB/DB MICE, AND A DECREASE IN MITOCHONDRIAL PROTEIN IMPORT. FOLLOWING IMPORT, MITOCHONDRIAL PROTEINS ARE REFOLDED INTO NATIVE STRUCTURES TO BECOME FUNCTIONAL. MTHSP70 ALSO PARTICIPATES IN THE REFOLDING PROCESS, AND WORKS SYNERGISTICALLY WITH LON PEPTIDASE 1, MITOCHONDRIAL (LONP1), AN AAA+ PROTEASE OF THE MITOCHONDRIAL MATRIX. WE HAVE ALSO OBSERVED A DECREASE IN LONP1 IN THE TYPE 2 DIABETIC HEART. WHEN MITOCHONDRIAL PROTEIN IMPORT IS NOT FUNCTIONING PROPERLY, AGGREGATED NUCLEAR GENOME-ENCODED PROTEINS ACCUMULATE ON THE EXTERIOR OF THE MITOCHONDRION LEADING TO A PHENOMENON TERMED MITOCHONDRIAL PRECURSOR OVER-ACCUMULATION STRESS. CURRENTLY, IT IS UNCLEAR WHAT FACTORS CONTRIBUTE TO A DECREASE IN PROTEIN IMPORT EFFICIENCY AND REFOLDING OR WHETHER MANIPULATION OF THESE PROCESSES CAN RESTORE MITOCHONDRIAL PROTEOMIC MAKE-UP, MITOCHONDRIAL FUNCTION AND CARDIAC CONTRACTILE PERFORMANCE IN THE DIABETIC HEART. OUR PROPOSED STUDIES ADDRESS THIS CRITICAL GAP IN KNOWLEDGE. THE INFORMATION WILL ENHANCE OUR UNDERSTANDING OF THESE PROCESSES AND AID IN THE DEVELOPMENT OF THERAPEUTIC STRATEGIES THAT TARGET SPECIFIC IMPORT CONSTITUENTS THAT CONTRIBUTE TO LOSS OF MITOCHONDRIAL PROTEINS. THE CENTRAL HYPOTHESIS TO BE TESTED IS THAT DECREASED PROTEIN IMPORT AND REFOLDING IN THE TYPE 2 DIABETIC HEART CAUSES LOSS OF MITOCHONDRIAL PROTEINS AND MITOCHONDRIAL PRECURSOR OVER-ACCUMULATION STRESS LEADING TO MITOCHONDRIAL DYSFUNCTION AND CONTRACTILE IMPAIRMENT. THE OBJECTIVES OF THIS APPLICATION ARE TO (1) IDENTIFY SUBMITOCHONDRIAL LOCATIONS WHERE PROTEIN IMPORT IS COMPROMISED IN TYPE 2 DIABETIC MITOCHONDRIA AND THE IMPACT ON IMPORT MACHINERY; (2) EVALUATE THE IMPACT OF TYPE 2 DIABETES MELLITUS ON MITOCHONDRIAL PROTEIN REFOLDING AND THE SYNERGISTIC INFLUENCE OF MTHSP70 AND LONP1; AND (3) DETERMINE THE EXTENT OF MITOCHONDRIAL AND PROTEOMIC STRESS THAT OCCURS IN THE TYPE 2 DIABETIC HEART, DUE TO FAILED MITOCHONDRIAL PROTEIN IMPORT CONTRIBUTING TO MITOCHONDRIAL PRECURSOR OVER-ACCUMULATION STRESS. COMPLETION OF THESE STUDIES IS EXPECTED TO PROVIDE FUNDAMENTAL MOLECULAR INSIGHT INTO THE MECHANISMS CONTRIBUTING TO THE LOSS OF NUCLEAR GENOME-ENCODED MITOCHONDRIAL PROTEINS IN THE TYPE 2 DIABETIC HEART AND THE CELLULAR CONSEQUENCES LEADING TO MITOCHONDRIAL AND CARDIAC DYSFUNCTION.

PSYCHOSOCIAL STRESS-INDUCED VASCULAR CONTRIBUTIONS TO COGNITIVE IMPAIRMENT AND ALZHEIMER'S DISEASE: THE ROLE OF XANTHINE OXIDASE - ABSTRACT: VASCULAR CONTRIBUTIONS TO COGNITIVE IMPAIRMENT AND DEMENTIA (VCID) IS THE SECOND LEADING CAUSE OF DEMENTIA BEHIND ALZHEIMER'S DISEASE (AD), AND IS A FREQUENT CO-MORBIDITY WITH AD. FURTHERMORE, THE DELETERIOUS EFFECT OF VASCULAR PATHOLOGIES COMBINED WITH AD PATHOLOGY LEADS TO INCREASED LIKELIHOOD OF DEMENTIA. DESPITE THE IMPORTANCE OF VCID, LITTLE IS KNOWN ABOUT ITS MOLECULAR MECHANISMS UNDERLYING VASCULAR AND COGNITIVE DYSFUNCTION. THIS HAS LED THE NIH TO PRIORITIZE STUDIES EXAMINING VASCULAR CONTRIBUTIONS TO DEMENTIA, AND ITS INTERPLAY WITH AD. CHRONIC PSYCHOSOCIAL STRESS IS A RISK FACTOR OF VCID. OUR PRELIMINARY DATA SHOWING THAT CHRONIC STRESS LEADS TO CONSIDERABLE CEREBROVASCULAR AND NEUROINFLAMMATORY CHANGES THAT HAVE SIMILAR FUNDAMENTAL CHANGES EVIDENT IN THE PROGRESSION OF AD HAS LED US TO FOCUS ON THIS PROCESS. ENDOTHELIAL DYSFUNCTION IS A CRITICAL DETERMINANT OF VASCULAR DISEASE AND PREDICTOR OF CLINICAL EVENTS. XANTHINE OXIDOREDUCTASE (XOR) IS A MAJOR SOURCE OF OXIDATIVE PRODUCTS (HYDROGEN PEROXIDE AND SUPEROXIDE) AND URIC ACID. THE LIVER IS THE SITE OF GREATEST XOR ACTIVITY AND THE MAIN SOURCE OF CIRCULATING XOR ACTIVITY. AS SUCH, XOR CAN NEGATIVELY AFFECT THE VASCULATURE. OUR PRELIMINARY DATA SUGGEST THAT CHRONIC STRESS INCREASES XOR ACTIVITY RESULTING IN CEREBROVASCULAR DYSFUNCTION AND INCREASED INFLAMMATION LEADING TO COGNITIVE IMPAIRMENT. OUR CENTRAL HYPOTHESIS IS THAT CHRONIC STRESS ELEVATES HEPATIC XOR, WHICH IS RELEASED INTO THE CIRCULATION DIRECTLY CAUSING CEREBROVASCULAR DYSFUNCTION AND THE ACTIVATION OF INFLAMMATION VIA A TLR4 PATHWAY RESULTING IN COGNITIVE DECLINE WHICH ACCELERATES DEMENTIA/AD PATHOLOGY. AIM 1 USES A LIVER (HEPATOCYTE)-AND ENDOTHELIAL-SPECIFIC XOR CONDITIONAL KO (HXDH-/-) MOUSE AND A LIVER-SPECIFIC XOR OVEREXPRESSION TOOL TO MANIPULATE THE XOR PATHWAY DURING 8 WEEKS OF CHRONIC STRESS AND TO EXAMINE THE PATHOLOGY OF VCID. IN AIM 2, WE WILL USE THE GLOBAL-AND- ENDOTHELIAL-SPECIFIC TLR4-/- MOUSE, ALONG WITH PHYSIOLOGICAL APPROACHES TO MANIPULATE THE TLR4/NF-B PATHWAY, AGAIN IN THE CONTEXT OF CHRONIC STRESS AND DETERMINE VCID PATHOLOGY. IN AIM 3, WE WILL USE THE INCREASE IN XOR ACTIVITY WITH CHRONIC STRESS AND SWITCH ITS BAD OXIDATIVE PRODUCTS TO NITRIC OXIDE BY SUPPLEMENTING WITH NITRITE AND DETERMINE ITS ACTIONS ON THE PATHOLOGY OF VCID. COMPLEMENTARY EXPERIMENTS WILL ALSO EXAMINE THE INTERACTION OF VCID AND AD, BY MANIPULATING THE XOR PATHWAY (USING FEBUXOSTAT) AND DETERMINING IF WE CAN DELAY THE PATHOLOGICAL PROGRESSION OF AD (3XTG-AD MICE). PILOT DATA SUPPORT THIS HYPOTHESIS. THUS, THE OVERALL GOAL OF THESE STUDIES IS TO DETERMINE THE ETIOLOGY OF THE STRESS-RELATED XOR AND PRO-INFLAMMATORY CHANGES IN MEDIATING VCID, AND ITS PROGRESSION TO AD PATHOLOGY. THE STUDIES WILL FILL GAPS IDENTIFIED BY THE NIH REGARDING THE NEED FOR UNDERSTANDING OF VASCULAR CONTRIBUTIONS TO COGNITIVE IMPAIRMENT AND DEMENTIA.

GERIATRIC EDUCATION CENTERS

UCEDD - CENTER FOR EXCELLENCE IN DISABILITIES

STROMAL CELL FUNCTION FOLLOWING CHEMOTHERAPY

RESEARCH TRAINING PROGRAM IN THE BEHAVIORAL AND BIOMEDICAL SCIENCES

ACCELNET-IMPLEMENTATION: THE INTERNATIONAL PULSAR TIMING ARRAY

PEPTIDE-VACCINE DEVELOPMENT AGAINST LYME DISEASE

DE-FE0032054 TITLED MID-APPALACHIAN CARBON ORE, RARE EARTH AND CRITICAL MINERALS INITIATIVE. NEW AWARD TO THE WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION

EPSCOR GRADUATE FELLOWSHIP PROGRAM (EGFP): TRAINING THE NEXT GENERATION OF SCIENTIFIC AND WORKFORCE LEADERS TO ENHANCE INTERDISCIPLINARY RESEARCH -THE NATIONAL SCIENCE FOUNDATION (NSF) EPSCOR GRADUATE FELLOWSHIP PROGRAM (EGFP) SUPPORTS EGFP DESIGNATED INSTITUTIONS AND PROGRAMS IN EPSCOR JURISDICTIONS BY PROVIDING FUNDING FOR GRADUATE FELLOWSHIPS FOR NEW OR CONTINUING EGFP-ELIGIBLE APPLICANTS. EGFP AWARDS PROVIDE FUNDING FOR A TOTAL OF THREE YEARS OF STIPEND AND AN ASSOCIATED COST-OF-EDUCATION (COE) ALLOWANCE FOR EACH NSF EPSCOR GRADUATE FELLOW. THIS AWARD TO WEST VIRGINIA UNIVERSITY (WVU) PROVIDES SUPPORT FOR THIRTEEN FELLOWS FOR A THREE-YEAR PERIOD. FELLOWS WILL FOCUS ON INTERDISCIPLINARY STUDIES REQUIRED TO ENHANCE WV?S ECONOMIC DEVELOPMENT IN SUPPORT OF EVOLVING ENERGY OPTIONS. GRADUATE STUDENTS WILL WORK WITH MENTORS FROM ACROSS NINE DEPARTMENTS ON RESEARCH THAT INCLUDES TOPICS SUCH AS THE BIOECONOMY, ECOSYSTEM RESILIENCE, ENVIRONMENTAL CHEMISTRY, PHOTOPHYSICS WITHIN PHOTOCATALYTIC MATERIALS, AND TECHNO-ECONOMIC ANALYSIS. BY BUILDING A COHORT OF STUDENTS THAT WILL ENHANCE INTERDISCIPLINARY RESEARCH, THE PROGRAM WILL SEEK TO TRANSFORM THE GRADUATE EDUCATION ENVIRONMENT OF WVU AND ENHANCE WVU?S LEADERSHIP IN FUTURE ECONOMIC TRANSITIONS. THIS AWARD SUPPORTS FELLOWS CONDUCTING RESEARCH ON SPECIFIC TOPICS OR AREAS THAT ALIGN WITH INTERESTS IDENTIFIED BY THE DIRECTORATE FOR BIOLOGICAL SCIENCES (BIO), DIRECTORATE FOR ENGINEERING (ENG), DIRECTORATE FOR GEOSCIENCES (GEO), DIRECTORATE FOR MATHEMATICAL AND PHYSICAL SCIENCES (MPS), AND DIRECTORATE FOR SOCIAL, BEHAVIORAL, AND ECONOMIC SCIENCES (SBE) AT THE NATIONAL SCIENCE FOUNDATION. 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.

EFRI NEWLAW: MAGNETIC FIELD FREE MAGNETO-OPTICS AND CHIRAL PLASMONICS WITH DIRAC MATERIALS

AFFECTIVE CONSEQUENCES OF CHEMOTHERAPY

SIMULATING CARDIAC SURGERY FOR CHILDREN WITH SEVERE CONGENITAL HEART DISEASE

QUSEC-TAQS: ENTANGLEMENT- ENHANCED MULTIPHOTON FLUORESCENCE IMAGING OF IN VIVO NEURAL FUNCTION -THIS PROJECT IS JOINTLY FUNDED BY THE QUANTUM SENSING CHALLENGES (QUSEC) PROGRAM, AND THE ESTABLISHED PROGRAM TO STIMULATE COMPETITIVE RESEARCH (EPSCOR). TWO-PHOTON IMAGING USES INTENSE LASER PULSES TO EXCITE FLUORESCENT PROTEINS WITHIN LIVING TISSUES AND IS WIDESPREAD IN THE BIOLOGICAL SCIENCES FOR FUNCTIONAL IMAGING OF TIME-VARYING PROCESSES. THE TWO-PHOTON ABSORPTION PROCESS HAS INCREASED SPATIAL RESOLUTION COMPARED TO ONE-PHOTON ABSORPTION BUT IS LESS EFFICIENT AND THUS REQUIRES HIGH LIGHT INTENSITY TO INCREASE THE LIKELIHOOD THAT TWO PHOTONS WILL ARRIVE AT A FLUOROPHORE SIMULTANEOUSLY. THIS RESEARCH PROJECT WILL PRODUCE EXCITATION LIGHT SOURCES WITH QUANTUM ENTANGLEMENT BETWEEN PHOTONS, WHICH WILL INCREASE THE LIKELIHOOD OF TWO PHOTONS ARRIVING SIMULTANEOUSLY, THUS MAKING TWO-PHOTON ABSORPTION AND IMAGING MORE EFFICIENT. IMPROVED EFFICIENCY WILL ENABLE LOWER LASER INTENSITIES, REDUCING DAMAGE TO TISSUE, ENABLING LONGER AND MORE FREQUENT MEASUREMENTS. SIMILAR ENTANGLEMENT EFFECTS WILL ALSO IMPROVE THE EFFICIENCY OF THREE-PHOTON ABSORPTION, WHICH OPERATES AT A WAVELENGTH THAT PENETRATES MORE DEEPLY INTO TISSUE. EXISTING TWO-PHOTON IMAGING FACILITIES AT WEST VIRGINIA UNIVERSITY WILL BE UPGRADED WITH QUANTUM-ENTANGLED LIGHT SOURCES. POSTDOCTORAL, GRADUATE AND UNDERGRADUATE RESEARCHERS WILL BE TRAINED IN AN INTERDISCIPLINARY LABORATORY SETTING COMBINING PHYSICS, BIOLOGY, AND NEUROSCIENCE. TEACHING MODULES WILL BE DEVISED TO RAISE QUANTUM AWARENESS IN A QUANTUM SUMMER SCHOOL FOR UNDERGRADUATES. FLUORESCENCE IMAGING USING 2-PHOTON EXCITATION REPRESENTS THE STATE-OF-THE-ART FOR FUNCTIONAL IMAGING OF NEURONS WITHIN THE NERVOUS SYSTEM. NEURAL DYNAMICS CAN BE CAPTURED BY RECORDING FLUORESCENCE IMAGES AS A FUNCTION OF TIME. YET THERE REMAIN LIMITATIONS TO 2-PHOTON FLUORESCENCE IMAGING STEMMING FROM THE INEFFICIENCY OF THE EXCITATION PROCESS, WHICH RELIES ON SIMULTANEOUS ABSORPTION OF TWO INDEPENDENT PHOTONS FROM A LASER PULSE. SIMULTANEOUS ABSORPTION IS UNLIKELY WITH CLASSICAL PHOTON DISTRIBUTIONS; THUS 2-PHOTON EXCITATION REQUIRES INTENSE EXCITATION THAT CAN DAMAGE TISSUE AND REDUCES THE EXPERIMENTAL DURATION IN LIVE ANIMALS. THIS PROJECT LEVERAGES QUANTUM CORRELATIONS BETWEEN TIME-ENERGY-ENTANGLED PHOTONS TO ENHANCE THE EFFICIENCY OF MULTI-PHOTON IMAGING IN THE BRAINS OF LIVING ANIMALS (FRUIT FLIES AND MICE). MULTI-PHOTON IMAGING WILL REPORT NEURON ACTIVITY THROUGH THE EXCITATION OF THE GCAMP FAMILY OF FLUORESCENT CALCIUM INDICATORS. IMPROVED EFFICIENCY WILL ENABLE IMAGING DEEPER INTO THE TISSUE, BETTER IMAGING EARLIER IN DEVELOPMENT, AND IMAGING OF OTHERWISE WEAKLY EXPRESSED FLUOROPHORES, ALL WHILE REDUCING DAMAGE DUE TO PHOTOTOXICITY. THIS WILL ALLOW LONGER MEASUREMENT TIMES AND REQUIRE FEWER LIVE ANIMALS TO BE PREPARED, INCREASING THE EFFICIENCY OF TIME AND MONEY ALLOTTED TO RESEARCH. EXTENSION TO 3-PHOTON ABSORPTION WITH EVEN LONGER WAVELENGTHS WILL ALLOW PENETRATION THROUGH MORE OPAQUE MATERIALS SUCH AS INSECT CUTICLE OR RODENT SKULL. 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.

EFRI BRAID: UNSUPERVISED CONTINUAL LEARNING WITH HIERARCHICAL TIMESCALES AND PLASTICITY MECHANISMS -HUMANS AND ANIMALS CAN EASILY ADAPT TO THEIR ENVIRONMENT WITH LIMITED INFORMATION. THEY SENSE THE WORLD AROUND THEM AND CONTINUOUSLY ADAPT THEIR BEHAVIOR TO THE CURRENT SITUATION BY CHANGING THE ?CONFIGURATION? OF THEIR NERVOUS SYSTEM, A PHENOMENON CALLED PLASTICITY. THOUGH THIS ABILITY SEEMS NATURAL TO HUMANS, IT IS VERY DIFFICULT TO ACHIEVE IN SOFTWARE OR HARDWARE SYSTEMS. IN ADDITION, CURRENT CONTINUOUS LEARNING METHODS ARE TRAINED UNDER UNREALISTIC CONDITIONS AND REQUIRE SUPERVISION. THIS PROJECT AIMS TO UNDERSTAND HOW TO ENDOW AUTONOMOUS AGENTS, SUCH AS ROBOTS, WITH THE ADAPTABILITY AND RESILIENCY OF BIOLOGY. BIOLOGICAL PLASTICITY IN WEAKLY ELECTRIC FISH WILL GUIDE ENGINEERING OF NEW MACHINE LEARNING ALGORITHMS. THESE ALGORITHMS WILL ENABLE AUTONOMOUS AGENTS TO CONTINUOUSLY SENSE AND ADAPT TO THEIR ENVIRONMENT WITHOUT INTERRUPTING OPERATIONS FOR MANUAL TRAINING. THIS INTERDISCIPLINARY PROJECT IS INTEGRATED WITH A RANGE OF OUTREACH ACTIVITIES INVOLVING LOCAL HIGH SCHOOLS AND UNDERGRADUATE STUDENTS. WORKSHOPS AND DEMONSTRATIONS ON BIOLOGY-INSPIRED MACHINE LEARNING WILL BE ORGANIZED, AIMED AT SPURRING INTEREST OF RURAL STUDENTS IN CODING AND ROBOTICS. A GRAND CHALLENGE IN ARTIFICIAL INTELLIGENCE (AI) IS HOW TO ACHIEVE UNSUPERVISED CONTINUAL LEARNING IN THE OPEN WORLD. CURRENT METHODS USED IN AI AND MACHINE LEARNING OPERATE WITH SINGLE-MODALITY DATA, COLLECTED AND CONSUMED IN CONTROLLED CONDITIONS, TYPICALLY IN A SUPERVISED MANNER. HOWEVER, BIOLOGICAL SYSTEMS ACHIEVE LIFELONG LEARNING BY PROCESSING STREAMS OF MULTISENSORY DATA THAT CONTINUOUSLY SHAPE THEIR NEURAL NETWORKS (PLASTICITY) WHILE RETAINING PREVIOUS KNOWLEDGE (STABILITY). THIS DYNAMIC ADAPTATION OPERATES UNSUPERVISED, ON A RANGE OF TIMESCALES AND RULES. THE PROJECT WILL STUDY THOSE PRINCIPLES OBSERVED IN THE CEREBELLAR FEEDBACK PATHWAYS OF ELECTRIC FISH, WHICH ARE RESPONSIBLE FOR DRIVING PLASTICITY, ENABLING ADAPTATION OF ITS FUNCTION AT DIFFERENT TIMESCALES AND LEARNING AND FORGETTING AT MULTIPLE SPEEDS. THIS WILL ENABLE THE TRANSLATIONAL DEVELOPMENT OF NOVEL PARADIGMS IN CONTINUAL LEARNING THAT WILL SUPPORT NEW LEVELS OF RESILIENCY AND LIFELONG LEARNING IN REAL-TIME AUTONOMOUS SYSTEMS IN THE OPEN WORLD. TO ACHIEVE THIS GOAL THE PROJECT WILL OVERCOME SOME KEY TECHNICAL HURDLES, E.G., IN ENABLING 1) DATA EFFICIENCY IN PROCESSING INPUTS CONTINUOUSLY AS TIME-VARIANT, POTENTIALLY CORRELATED, DATA STREAMS IN A FULLY UNSUPERVISED MANNER; 2) FLEXIBILITY TO LEARN AND FORGET AT DIFFERENT SPEEDS; 3) GENERATION OF SUITABLE INTERNAL REPRESENTATIONS FROM MULTIPLE MODALITIES TO IMPROVE AUTONOMOUS RESILIENCE. THIS PROJECT IS JOINTLY FUNDED BY THE EMERGING FRONTIERS IN RESEARCH AND INNOVATION BRAIN-INSPIRED DYNAMICS FOR ENGINEERING ENERGY-EFFICIENT CIRCUITS AND ARTIFICIAL INTELLIGENCE PROGRAM (BRAID) AND THE ESTABLISHED PROGRAM TO STIMULATE COMPETITIVE RESEARCH (EPSCOR). 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.

EDI SPECIAL PROJECTS

MITOCHONDRIAL PYRUVATE TRANSPORT IN RETINAL HEALTH AND DISEASE - PROJECT SUMMARY/ABSTRACT THE RETINA IS THE MOST METABOLICALLY ACTIVE NEURONAL TISSUE IN THE HUMAN BODY. THE DEFECT IN THE ENERGY METABOLISM OF PHOTORECEPTOR NEURONS AND THEIR SUPPORTING CELLS INCLUDING GLIA AND RETINAL PIGMENT EPITHELIUM (RPE), EMERGES AS AN IMPORTANT UNDERLYING CAUSE FOR RETINAL DEGENERATIVE DISEASES SUCH AS INHERITED RETINAL DEGENERATION AND AGING-RELATED MACULAR DEGENERATION (AMD). PREVIOUS STUDIES AND DATA FROM OUR LAB SUPPORT THAT PHOTORECEPTORS, GLIAL CELLS, AND RPE ARE BIOCHEMICALLY ADAPTED TO FORM A METABOLIC ECOSYSTEM: 1) RPE TRANSPORTS GLUCOSE FROM CHOROID BLOOD SUPPLY TO PHOTORECEPTORS; 2) PHOTORECEPTORS METABOLIZE MOST OF THE GLUCOSE INTO LACTATE; 3) LACTATE INHIBITS GLYCOLYSIS IN RPE TO FACILITATE GLUCOSE TRANSPORT; 4) LACTATE STIMULATE MÜLLER GLIA TO SYNTHESIZE GLUTAMINE FOR PHOTORECEPTORS. THE LONG TERM GOAL OF THIS PROJECT IS TO DEFINE THE METABOLIC INTERACTIONS BETWEEN PHOTORECEPTORS AND MÜLLER GLIA AND BETWEEN RPE AND OUTER RETINA IN VIVO AND IDENTIFY THEIR ROLES IN RETINAL FUNCTION AND DEGENERATION. MITOCHONDRIAL PYRUVATE CARRIER (MPC) CONTROLS THE ENTRY OF PYRUVATE FROM GLYCOLYSIS INTO MITOCHONDRIA FOR OXIDATIVE METABOLISM. WE RECENTLY FOUND THAT THE DELETION OF MPC IN THE RETINA DEPLETES GLUTAMINE AND GLUTAMATE, INHIBITS GLUTAMINE UTILIZATION AND ENHANCING KETONE BODY OXIDATION, RESULTING IN A PROGRESSIVE DECLINE OF VISUAL FUNCTION AND RETINAL DEGENERATION. OUR PRELIMINARY DATA SHOWED THAT THE DELETION OF MPC IN PHOTORECEPTORS CAUSES MUCH MILDER PHENOTYPE THAN WHOLE RETINA KNOCKOUT, SUPPORTING THE METABOLIC INTERACTION THAT LACTATE IS UTILIZED BY OTHER CELLS. THE OBJECTIVE OF THIS PROPOSAL IS TO INVESTIGATE THE ROLES OF MITOCHONDRIAL PYRUVATE TRANSPORT IN PHOTORECEPTOR, MÜLLER CELLS AND RPE IN METABOLIC INTERACTIONS, VISUAL FUNCTION, AND RETINAL SURVIVAL. WE PLAN TO CONDITIONALLY KNOCKOUT MPC IN PHOTORECEPTORS, GLIA OR RPE SEPARATELY AND RIGOROUSLY TEST OUR HYPOTHESIS USING ADVANCED TRACER METHODOLOGY, MASS SPECTROMETRY, IN VIVO INFUSION WITH 13C TRACERS, HIGH-RESOLUTION IMAGING OF METABOLITES, VISUAL FUNCTION TESTS, OPTICAL COHERENCE TOMOGRAPHY, AND TRANSMISSION ELECTRON MICROSCOPY. THE OUTCOME OF THIS RESEARCH WILL ESTABLISH A CONCEPTUAL FRAMEWORK FOR RETINAL METABOLISM THAT DESCRIBES HOW GLUCOSE IS TRANSPORTED AND UTILIZED IN DIFFERENT RETINAL CELLS AND DESCRIBES HOW DISRUPTION OF METABOLISM IN ONE KIND OF RETINAL CELLS IMPACTS THE METABOLISM, FUNCTION, AND VIABILITY OF OTHER RETINAL CELLS. THIS NEW KNOWLEDGE WILL PROVIDE THE BASIS FOR UNDERSTANDING THE MECHANISMS OF RETINAL DEGENERATIVE DISEASES AND LAY THE FOUNDATION FOR DEVELOPING NEW TREATMENTS. 1

DE-FE0031768 WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION PROJECT TITLE ''BOILER HEALTH MONITORING USING A HYBRID FIRST PRINCIPLES-ARTIFICIAL INTELLIGENCE MODEL''

WEST VIRGINIA INNOVATIVE CARDIOVASCULAR WELLNESS INITIATIVE - INDIVIDUALS WITH CARDIOVASCULAR DISEASE (CVD) FACE CONSIDERABLE CHALLENGES IN THEIR HEALTH AND WELL-BEING, AND DESPITE SIGNIFICANT IMPROVEMENTS IN CVD PREVENTION AND MANAGEMENT STRATEGIES, DISPARITIES LINKED TO POORLY ADAPTED POLICIES AND PRACTICES, AND RACIAL INEQUITY, HAVE LEFT DISADVANTAGED POPULATIONS BEHIND. THE WEST VIRGINIA UNIVERSITY OFFICE OF HEALTH SERVICES RESEARCH (OHSR) PROPOSES THE WEST VIRGINIA INNOVATIVE CARDIOVASCULAR WELLNESS INITIATIVE TO ADDRESS THE SUBSTANTIAL BURDEN OF CVD IN WEST VIRGINIA (WV), THE STATE WITH THE GREATEST CVD BURDEN IN THE UNITED STATES. THIS INITIATIVE WILL FOCUS ON TWO QUALIFYING CENSUS TRACTS (54039000900 AND 54039000700) LOCATED IN CHARLESTON, WV, WITH ADULTS AGED 18 AND OLDER WITH A HYPERTENSION CRUDE PREVALENCE RATE OF 53% OR HIGHER. BOTH TRACTS ARE MORE URBAN THAN RURAL COMPARED TO THE REST OF THE STATE, AND BOTH ARE HOME TO SUBSTANTIALLY HIGHER PROPORTIONS OF RACIAL MINORITIES, SPECIFICALLY BLACK OR AFRICAN AMERICAN. FURTHER, THESE REGIONS HAVE SUBSTANTIAL AGING AND IMPOVERISHED POPULATIONS, INCLUDING THOSE WITH LOW EDUCATIONAL ATTAINMENT AND HOUSEHOLD INCOME. THE PURPOSE OF THE WEST VIRGINIA CARDIOVASCULAR WELLNESS INITIATIVE IS TO CREATE, IMPLEMENT, AND DISSEMINATE A SYSTEM OF CARE TO ADDRESS CVD RISK FACTORS INCLUDING HYPERTENSION AND HIGH CHOLESTEROL, IMPROVE CLINICAL AND COMMUNITY LINKAGES, AND INCREASE USE OF SOCIAL SUPPORT SERVICES IN DISPARATE POPULATIONS. THE SHORT-TERM AND INTERMEDIATE OUTCOMES OF THIS INITIATIVE FOCUS ON IMPROVING THE HEALTH AND WELL-BEING OF THE APPROVED POPULATIONS VIA IMPROVED BLOOD PRESSURE CONTROL, REDUCED HEALTH DISPARITIES, AND INCREASED UTILIZATION OF SOCIAL SUPPORT SERVICES IN PARTNER HEALTH CARE AND COMMUNITY SETTINGS. THIS INITIATIVE IS A COORDINATED EFFORT ACROSS PARTNERS AND ORGANIZATIONS THAT DO AND THOSE THAT DO NOT RECEIVE FUNDING FROM THE CENTERS FOR DISEASE CONTROL AND PREVENTION (CDC). OHSR AND CABIN CREEK HEALTH SYSTEMS WILL COLLABORATE TO IMPLEMENT A ND DISSEMINATE THE SYSTEM OF CARE DEVELOPED TO ADDRESS CVD RISK TO OTHER HEALTH SYSTEMS USING A LEARNING COLLABORATIVE. THE LEARNING COLLABORATIVE WILL CONSIST OF ORGANIZATIONS WITH MISSIONS, VISIONS, AND VALUES COMPLEMENTARY TO THE INTENT AND GOALS OF THIS INITIATIVE. WV SHARES THE CDC’S VISION OF REDUCED DISPARITIES IN CARDIOVASCULAR HEALTH AND IMPROVED CARDIOVASCULAR HEALTH FOR ALL.

DIRECT UTILIZATION OF COAL SYNGAS IN HIGH TEMPERATURE FUEL CELLS: DEBRADATION MECHANISMS AND ...

TRANSPORTABLE EMISSIONS TESTING LABORATORY FOR ALTERNATIVE VEHICLES EMISSIONS TESTING

BIOSYNTHESIS AND TRAFFICKING OF PHOSPHODIESTERASE IN THE RETINAL PHOTORECEPTORS

LONG TERM ENVIRONMENTAL AND ECONOMIC IMPACTS OF COAL LIQUEFACTION IN CHINA

BLANCHETTE ROCKERFELLER NEUROSCIENCE INSTITUTE TO SUPPORT MOLECULAR STUDIES OF DISEASES IN MEMORY

NANOHYBRID COMPOSITES MINIMIZE ANTIBIOTIC RESISTANT INFECTIONS - PROJECT SUMMARY/ABSTRACT: OPEN FRACTURES ARE FREQUENTLY (MORE THAN 150,000 CASES IN THE U.S. EVERY YEAR) SEEN AND HAVE HIGH (~10%) INFECTION RATES. OPEN FRACTURE-ASSOCIATED INFECTIONS ARE CLINICALLY DEVASTATING, AND HAVE LED TO REDUCED LIMB FUNCTION, SECONDARY OPERATIONS, DELAYED UNION/NONUNION, AND DEATH. INFECTION HAS LED TO SIGNIFICANTLY HIGH COSTS IN HEALTHCARE, RESULTING IN APPROXIMATELY $500 MILLION OF ADDITIONAL COSTS IN MANAGING OPEN FRACTURES EACH YEAR IN THE U.S. FURTHER COMPLICATING THE PROBLEM, ALARMINGLY HIGH PERCENTAGES (E.G., 32.2% FOR TIBIAL FRACTURES) OF OPEN FRACTURE INFECTIONS ARE ASSOCIATED WITH ANTIBIOTIC RESISTANT BACTERIA, WHICH HAVE LED TO A TWO-FOLD INCREASE IN MORBIDITY AND MORTALITY, AND HAVE MADE THE DRUG CHOICES FOR INFECTION MANAGEMENT INCREASINGLY LIMITED. THE LONG-TERM GOAL OF THIS APPLICATION IS TO DEVELOP TRANSLATIONAL STRATEGIES TO PREVENT OR TREAT BONE INFECTIONS IN CLINICAL SETTINGS. THE OBJECTIVE OF THIS PROJECT IS TO DEVELOP SAFE ANTIMICROBIAL NANOHYBRID METHODS TO REDUCE ANTIBIOTIC RESISTANT INFECTIONS IN OPEN FRACTURES. THE CENTRAL HYPOTHESIS IS THAT NANOHYBRIDING TWO UNIQUE ANTIMICROBIAL MATERIALS WITH DIFFERENT DIMENSIONS AT THE NANOMETER SCALE WILL SYNERGISTICALLY ENHANCE ANTIMICROBIAL PROPERTIES AND SIGNIFICANTLY REDUCE HOST TOXICITY. THERE ARE THREE SPECIFIC AIMS: (I) TO TEST THE HYPOTHESIS THAT INNOVATIVE SILVER NANOPARTICLE-CARBON NANOTUBE (AGNP-CNT) NANOHYBRIDS PRESENT HIGH ANTIMICROBIAL PROPERTIES AGAINST VARIOUS BACTERIA SEEN IN OPEN FRACTURES AND LOW TOXICITY TOWARD CELLS IMPORTANT TO BONE. (II) TO TEST THE HYPOTHESIS THAT AGNP-CNT NANOHYBRIDS PRESENT HIGH ANTIMICROBIAL PROPERTIES AND LOW HOST TOXICITY IN PREVENTING ANTIBIOTIC RESISTANT INFECTIONS IN AN ANIMAL MODEL. (III) TO TEST THE HYPOTHESIS THAT BIOENGINEERING AGNP-CNT NANOHYBRIDS ON IMPLANT SURFACES ENHANCES PRECLINICAL OUTCOMES. SPECIFICALLY, THE IN VITRO ANTIMICROBIAL PROPERTIES OF AGNP-CNT NANOHYBRIDS WILL BE TESTED AGAINST A VARIETY OF BACTERIA AND THEIR CYTOTOXICITY PROPERTIES TOWARD MULTIPLE HUMAN CELLS WILL BE DETERMINED. THE NANOHYBRIDS WILL BE TESTED IN AN OPEN FEMUR FRACTURE RAT MODEL TO ASSESS THEIR EFFECTS ON INFECTION, HEALING, AND HOST TOXICITY. MOREOVER, THE NANOHYBRIDS WILL BE BIOENGINEERED ON ORTHOPAEDIC IMPLANTS AND THEIR COATINGS WILL BE TESTED BOTH IN VITRO AND IN VIVO; DELIVERING ANTIMICROBIALS AT THE IMPLANT SURFACE IS EXPECTED TO ACHIEVE HIGH ANTIMICROBIAL LEVELS AT THE RIGHT PLACE TO MINIMIZE SYSTEMIC TOXICITY. THIS PROJECT WILL CONTRIBUTE NEW KNOWLEDGE ON HOW HYBRIDING TWO MATERIALS WITH DIFFERENT DIMENSIONS AT THE NANOMETER SCALE MAY SYNERGISTICALLY INCREASE ANTIMICROBIAL PROPERTIES AND REDUCE HOST TOXICITY. THE EXPECTED OUTCOME IS A BIOLOGICALLY SAFE, NANOTECHNOLOGY-BASED STRATEGY THAT WILL DRIVE AND BROADEN THE SAFE USE OF SILVER AND CARBON NANOTUBES FOR LOCAL BIOMEDICAL APPLICATIONS (E.G., OPEN FRACTURE FIXATION). THE NANOHYBRIDS MAY BE ENGINEERED ON VARIOUS MEDICAL PRODUCTS – RANGING FROM BONE GRAFTS, DENTAL IMPLANTS, AND CATHETERS, TO BANDAGES AND NEEDLES – TO REDUCE INFECTIONS WHILE IMPROVING RECOVERY.

ROLE OF THE MITOCHONDRIAL LONP1 IN MYOCARDIAL ISCHEMIA AND REPERFUSION INJURY PROTECTION - PROJECT SUMMARY ISCHEMIA-REPERFUSION (IR) INJURY IS A SIGNIFICANT CHALLENGE IN TREATING MYOCARDIAL INFARCTION (MI), THE LEADING CAUSE OF DEATH IN THE UNITED STATES. MITOCHONDRIAL REACTIVE OXYGEN SPECIES (MTROS) GENERATED BY ELECTRON TRANSPORT CHAIN (ETC) COMPLEX-I ARE THE PRINCIPAL MEDIATORS OF IR INJURY. EXCESS MTROS GENERATED DURING EARLY IR TRIGGERS VICIOUS CYCLES OF FREE RADICAL PRODUCTION PROMOTING CARDIOMYOCYTE DEATH. THEREFORE, UNDERSTANDING THE EARLY MOLECULAR EVENTS OF REPERFUSION WILL PROVIDE NEW TARGETS FOR DEVELOPING NOVEL INTERVENTIONS FOR LIMITING CARDIAC INJURY. OUR PUBLISHED FINDINGS SHOW THAT LONP1- A MAJOR MITOCHONDRIAL STRESS RESPONSE PROTEASE MITIGATES OXIDATIVE STRESS-INDUCED DAMAGE DURING EARLY IR; THEREFORE, LONP1 COULD BE A PROMISING TARGET FOR ATTENUATING REPERFUSION INJURY. OUR LONG-TERM GOAL IS TO LEVERAGE THE MITOCHONDRIAL PROTEIN QUALITY CONTROL MECHANISMS OF LONP1 AS A PIVOTAL POINT TO DEVELOP THERAPEUTIC STRATEGIES FOR MITIGATING IR INJURY AND POST MI- HEART FAILURE. OUR PUBLISHED FINDINGS SHOW THAT INCREASED LONP1 EXPRESSION IN THE HEART INDUCED BY ISCHEMIC PRECONDITIONING (IPC) OR TRANSGENIC OVEREXPRESSION (LONTG) REDUCED IR INJURY AND FAVORS CARDIOPROTECTION. WHEREAS, LONP1 DOWNREGULATION (LONP1+/-) ABROGATED IPC-MEDIATED CARDIOPROTECTION. IMPORTANTLY, LONTG HEARTS SHOWED REDUCED LEVELS OF COMPLEX-I SUBUNITS (BUT NOT COMPLEX II-V SUBUNIT) AND OXIDATIVE DAMAGE DURING EARLY IR (WITHIN 30 MIN REPERFUSION) COMPARED TO NTG CONTROLS. CONVERSELY, OUR ADDITIONAL FINDINGS SHOW THAT LONP1 DOWNREGULATION IN CARDIOMYOCYTES UPREGULATED COMPLEX-I ACTIVITY, INCREASED SUPEROXIDE LEVELS, AND SHOWED EARLY REPERFUSION-INDUCED CELL DEATH ACTIVATION. IN ADDITION, WE HAVE IDENTIFIED A SMALL MOLECULE ACTIVATOR OF LONP1 THAT SIGNIFICANTLY REDUCED HYPOXIA-REOXYGENATION (H/R) INDUCED MYOCYTE DEATH IN A DOSE-DEPENDENT MANNER IN VITRO. WITH ADDITIONAL DATA ON IR-INDUCED ACETYLATION OF COMPLEX-I MATRIX SUBUNITS AND LONP1 DEPENDENT COMPLEX-I REMODELING DURING IR, WE HYPOTHESIZE THAT LONP1 MITIGATES MYOCARDIAL INJURY BY SUPPRESSING EXCESS MTROS GENERATION THROUGH TIGHT REGULATION OF COMPLEX-I DURING EARLY IR. WE WILL TEST OUR HYPOTHESIS BY THE FOLLOWING SPECIFIC AIMS: AIM 1 WILL DELINEATE THE MECHANISM(S) BY WHICH LONP1 MODULATES COMPLEX-I LEVELS, ACTIVITY AND REDUCES OXIDATIVE STRESS DURING IR. AIM 2 WILL TEST THAT LONP1 REMODELS COMPLEX-I AND ITS ASSOCIATED SUPERCOMPLEXES BY DEGRADING IR-INDUCED POST-TRANSLATIONALLY MODIFIED (PTM) COMPLEX-I MATRIX SUBUNITS, THEREBY REDUCE MTROS DURING EARLY IR. AIM 3 WILL DETERMINE THE THERAPEUTIC POTENTIAL OF LONP1 ACTIVATORS IN TREATING MYOCARDIAL IR INJURY IN VIVO. BY DETERMINING THE MOLECULAR MECHANISMS OF LONP1-MEDIATED CARDIOPROTECTION AND THE THERAPEUTIC POTENTIAL OF LONP1 ACTIVATORS, WE WILL DEFINE THE ROLE OF LONP1 IN CARDIOPROTECTION AND DEVELOP NOVEL THERAPEUTIC TOOLS AND STRATEGIES TO MITIGATE IR INJURY.

PROTEIN-PROTEIN COVALENT BONDING AND TREPONEMA MOTILITY

PROLINE METABOLISM IN RETINAL HEALTH - PROJECT SUMMARY/ABSTRACT AGE-RELATED MACULAR DEGENERATION (AMD) IS THE LEADING CAUSE OF BLINDNESS IN THE ELDERLY. A COMMON FEATURE IN AMD IS THE EARLY DAMAGE OF RETINAL PIGMENT EPITHELIUM (RPE), A MONOLAYER OF CELLS BETWEEN PHOTORECEPTORS AND CHOROID. RPE CONTROLS NUTRIENT TRANSPORT FROM CHOROID BLOOD SUPPLY TO THE OUTER RETINA AND MULTIPLE LINES OF EVIDENCE SHOW THAT THE ALTERED METABOLISM IN RPE IS THE UNDERLYING MECHANISM FOR AMD. THE LONG-TERM GOAL OF THIS PROJECT IS TO IDENTIFY KEY METABOLIC FEATURES OF RPE AND THE ROLES THAT THEY PLAY IN AMD. WE RECENTLY FOUND THAT BESIDES GLUCOSE, RPE PREFERENTIALLY USES PROLINE, AN AMINO ACID, TO FUEL ITS METABOLISM. MUTATIONS OF ENZYMES IN PROLINE METABOLISM IN HUMANS COULD CAUSE CHORIORETINAL ATROPHY OR RETINAL DEGENERATION. THE OBSERVATION THAT A PROLINE TRANSPORTER IS HIGHLY ENRICHED IN RPE BUT NOT IN PHOTORECEPTORS, FURTHER SUPPORTING OUR FINDING. THE PROLINE TRANSPORTER IS A NOVEL RISK GENE LINKED TO AMD. IN OUR PRELIMINARY DATA, WE SHOW THAT KNOCKOUT OF THE PROLINE TRANSPORTER BLOCKS PROINE UTILIZATION AND IMPAIRS VISUAL FUNCTION. THE OBJECTIVE OF THIS PROPOSAL IS TO STUDY PROLINE METABOLISM IN RPE AND ITS ROLE IN RETINAL DEGENERATION. WE PLAN TO RIGOROUSLY INVESTIGATE THE ROLE OF PROLINE IN HEALTHY AND DISEASED RPE USING ADVANCED TRACER METHODOLOGY, MASS SPECTROMETRY, IN VIVO INFUSION, LIVE IMAGING, AND PROLINE TRANSPORTER KNOCKOUT MOUSE MODELS. THE OUTCOME OF THIS RESEARCH WILL BE TO ESTABLISH A CONCEPTUAL FRAMEWORK FOR RPE METABOLISM THAT DESCRIBES HOW RPE USES NUTRIENTS TO MAINTAIN METABOLIC HOMEOSTASIS WITH THE OUTER RETINA. THIS NEW KNOWLEDGE WILL PROVIDE THE BASIS FOR UNDERSTANDING THE MECHANISMS OF AMD AND LAY THE FOUNDATION FOR DEVELOPING NEW TREATMENTS.

RURAL COMMUNITIES OPIOID RESPONSE-IMPLEMENTATION

DISEASE MECHANISMS OF CONE OPSIN MUTANTS AND TREATMENT STRATEGIES

WVU IDENTIFICATION TECHNOLOGY RESEARCH AND TRANSITION CENTER (CITER - TRAC)

TRAVEL PROGRAM SUPPORT FOR THE NORTHEAST AND MIDWEST STATE FORESTERS ALLIANCE

MECHANISMS BEHIND RETINAL PHOTORECEPTOR CELLS OUTER SEGMENT BIOGENESIS

DEVELOPING RESEARCH CAPACITY FOR AIDS MALIGNANCY IN KENYA

FORAGE-BASED PARASITE CONTROL IN SHEEP AND GOATS IN THE NORTHEAST U.S.

SUSCEPTIBILITY AND RESILIENCE TO ADVERSE CHILDHOOD EXPERIENCES: A ROLE FOR PERINEURONAL NETS

DEVELOPMENT OF A PEM-PET-CT BREAST IMAGING AND BIOPSY DEVICE

ASSESSING FUGITIVE METHANE EMISSIONS IMPACT USING NATURAL GAS ENGINES IN UNCONVENTIONAL RESOURCE DEVELOPMENT

NASA STRATEGIC GOAL 4: ENHANCE CAPABILITIES AND OPERATIONS TO CATALYZE CURRENT AND FUTURE MISSION SUCCESS. NASA INVESTMENTS IN STEM ENGAGEMENT ARE FOCUSED ON BUILDING A FUTURE STEM WORKFORCE THROUGH PROGRAM ELEMENTS DESIGNED TO BOLSTER CAPACITY AND TO ATTRACT ENGAGE AND ENABLE STUDENTS TO MOVE TOWARD STEM CAREERS THROUGH NASA-UNIQUE OPPORTUNITIES.

RYAN WHITE TITLE IV WOMEN, INFANTS, CHILDREN, YOUTH AND AFFECTED FAMILY MEMBERS AIDS HEALTHCARE

THE WEST VIRGINIA PEDIATRIC CLINICAL TRIALS NETWORK

MRI: DEVELOPMENT OF A CHIME OUTRIGGER TELESCOPE

APPALACHIAN GERONTOLOGY EXPERIENCES - ADVANCING DIVERSITY IN AGING RESEARCH

WVU ENVIRONMENTAL CENTER

INTEGRATIVE SYSTEMS APPROACH TO IDENTIFY LOCAL ONCOGENIC MODULATION OF THE IL12 AXIS

TARGETING SHP2 AS A PRECISION MEDICINE FOR THE TREATMENT OF HER2-POSITIVE BREAST CANCER

DEVELOPMENT OF VSSI-PROBE TECHNOLOGY FOR IN SITU PROBING BIOLOGICAL SYSTEMS USING MASS SPECTROMETRY

ROLE OF BK CHANNELS IN K+-DRIVEN COLONIC WATER SECRETION IN HEALTH AND DISEASE

DISES: ENHANCING ECOLOGICAL AND COMMUNITY RESILIENCY THROUGH SUSTAINABLE FORESTRY AND FOREST-BASED CLIMATE SOLUTIONS -INTEREST IN FOREST-BASED CLIMATE SOLUTIONS (FBCS) HAS RAPIDLY INCREASED IN RECENT YEARS, DUE TO THE RISING DESIRE OF CORPORATIONS TO ASSIST IN MITIGATING CLIMATE CHANGE, VARIOUS FINANCIAL INCENTIVES, AND GOVERNMENTAL REGULATIONS. FORESTS IN THE EASTERN US ARE A PARTICULARLY PROMISING AREA FOR FBCS PROJECTS DUE TO THEIR LARGE CARBON STORAGE CAPACITY AND LOW RISK OF ADVERSE CLIMATE CHANGE IMPACTS. HOWEVER, THERE ARE MASSIVE UNCERTAINTIES REGARDING THESE PROJECTS, PARTICULARLY: 1) THEIR EFFICACY IN REMOVING AND STORING CARBON LONG-TERM, AND 2) THE POTENTIAL OF THESE PROJECTS TO BENEFIT AND REVITALIZE THE RURAL COMMUNITIES IN WHICH THEY ARE BASED. ANSWERING THESE QUESTIONS IN THE EASTERN US IS COMPLICATED BY THE INTRICACIES OF THE FOREST CARBON CYCLE, THE MOSAIC OF LAND MANAGEMENT AND OWNERSHIP IN THE REGION, AND UNKNOWNS REGARDING THE DEGREE TO WHICH FBCS INVESTMENT FLOWS TO, AND IS RETAINED BY, LOCAL COMMUNITIES. THIS RESEARCH SEEKS TO DEEPEN OUR UNDERSTANDING OF FBCS EFFICACY AND EQUITY FROM ECOLOGICAL, ECONOMIC, AND POLITICAL PERSPECTIVES. THIS PROJECT INCLUDES THREE APPROACHES. FIRST, A NETWORK OF LONG-TERM FOREST MANAGEMENT PLOTS IS SAMPLED TO QUANTIFY HOW COMMON MANAGEMENT PRACTICES IMPACT FOREST CARBON STORAGE, CLIMATE RESILIENCE, AND VARIOUS CO-BENEFITS SUCH AS WATER/NUTRIENT RETENTION AND BIODIVERSITY. SECOND, SMALL LANDOWNERS ARE SURVEYED, AND ECONOMIC MODELS ARE EMPLOYED TO UNDERSTAND THE BARRIERS THAT THESE POPULATIONS FACE WHEN ENROLLING IN CARBON MARKETS. THIRD, THROUGH ETHNOGRAPHIC ANALYSIS, TAXATION DATA, AND STAKEHOLDER INTERVIEWS, THIS RESEARCH INVESTIGATES HOW FBCS PROGRAMS DISTRIBUTE BENEFITS AND COSTS TO THE RURAL COMMUNITIES IN WHICH THEY ARE BASED. INTEGRATING THESE APPROACHES ALLOWS FOR A TEST OF THE HYPOTHESIS THAT INCREASING EFFICACY AND EQUITY OF FBCS PROJECTS ALSO INCREASES RURAL RESILIENCY TO DECARBONIZATION AND CLIMATE CHANGE. SPECIFICALLY, THIS IS ACHIEVED BY: (1) DEMONSTRATING HOW FOREST ECOSYSTEM AND COMMUNITY RESILIENCY ARE LINKED, (2) PROVIDING INTEGRATED POLICY SOLUTIONS THAT ENHANCE THE EQUITY AND EFFICACY OF FBCS IN TANDEM, AND (3) IDENTIFYING HOW THESE FINDINGS CAN BE APPLIED TO OTHER FORESTED COMMUNITIES THAT ARE TRANSITIONING FROM A RESOURCE EXTRACTION ECONOMY. 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 PLANNED FOR THIS AWARD.

DEVELOPMENT OF A COMBINED MRI-PET SYSTEM FOR CONTEMPORANEOUS FUNCTIONAL IMAGING

CELL AND MOLECULAR BIOLOGY TRAINING PROGRAM AT WEST VIRGINIA UNIVERSITY

INDUCTION OF NEOPLASTIC TRANSFORMATION AND CANCER STEM CELLS BY CARBON NANOTUBES

DECELLULARIZED MATRIX AND CARTILAGE REGENERATION

TARGETING CD44-MEDIATED CALCIUM SIGNALING FOR THE TREATMENT OF RELAPSED MYELOMA

AGE INFLUENCES NEUROPOIETIC SIGNALING AT THE NEUROVASCULAR UNIT FOLLOWING STROKE

NEUROENDOCRINE CONTROL OF SEASONALITY

SYSTEMATIC ASSESSMENT OF MULTI-WALLED CARBON NANOTUBES IN PULMONARY DISEASE

WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION LABORATORY CONTROL NUMBER 1562-1515 PROJECT TITLE ''RENEWABLE ENERGY TO FUELS THROUGH PLASMA CATALYTIC SYNTHESIS OF AMMONIA''

ELKHORN CREEK/TUG FORK WATERSHED PROJECT

ROLE OF C-JUN N-TERMINAL KINASE SIGNALING IN CORTICAL INTERNEURON MIGRATION

TARGETING MUSCLE FATIGABILITY DURING CACHEXIA - PROJECT SUMMARY/ABSTRACT CLINICALLY, NEARLY ALL BREAST CANCER PATIENTS AT THE TIME OF DIAGNOSIS AND PRIOR TO TREATMENT HAVE SOME DEGREE OF MUSCLE DYSFUNCTION RESULTING IN FATIGUE THAT RANGES FROM MILD TO DEBILITATING AND MAY WORSEN DURING AND AFTER CHEMOTHERAPY, RADIATION, AND/OR SURGERY. ADVERSE SYSTEMIC EFFECTS OF TUMOR GROWTH CAN OFTEN RESULT IN TREATMENT CESSATION AND GREATER MORTALITY IN LATE STAGES OF DISEASE. THE LONG-TERM GOAL OF MY WORK IS TO IDENTIFY POTENTIAL THERAPEUTIC TARGETS FOR FATIGUE AND A MECHANISM LINKING BC WITH SYSTEMIC MUSCLE FATIGUE. THE SPECIFIC GOAL OF THIS PROPOSAL IS TO UTILIZE OUR MURINE MODEL TO CHARACTERIZE THE MOLECULAR ADAPTATIONS IN MUSCLE AND IDENTIFY TARGETS TO ATTENUATE FATIGUE IN PATIENTS WITH BREAST CANCER. THE CENTRAL RESEARCH HYPOTHESIS IS THAT REGULATION OF MITOCHONDRIAL BIOENERGETICS VIA A PPAR-AGONIST WILL ATTENUATE BREAST TUMOR-ASSOCIATED MUSCLE FATIGUE. THREE SPECIFIC AIMS HAVE BEEN PROPOSED TO TEST THIS HYPOTHESIS, USING MURINE MODELS OF BREAST CANCER AND NOVEL IN VITRO MODELS OF PPAR-ACTIVITY. IN SPECIFIC AIM 1, WE WILL TEST THE WORKING HYPOTHESIS THAT BREAST TUMOR GROWTH IMPAIRS MITOCHONDRIAL BIOENERGETICS RESULTING IN ATP DEFICIENCY AND SUBSEQUENT MUSCLE FATIGUE THROUGH ABERRANT FUNCTION OF MITOCHONDRIAL ELECTRON TRANSPORT CHAIN (ETC) COMPLEX V. IN SPECIFIC AIM 2, WE WILL TEST THE WORKING HYPOTHESIS THAT BREAST TUMOR-DERIVED MIR-27A-3P INTERACTS WITH REGULATORY COMPONENTS OF PPAR WITHIN SKELETAL MUSCLE TO DECREASE ITS FUNCTION AS A TRANSCRIPTION FACTOR, THEREBY SPECIFICALLY INDUCING ALTERATIONS IN MITOCHONDRIAL FUNCTION. IN SPECIFIC AIM 3, WILL TEST THE WORKING HYPOTHESIS THAT PIOGLITAZONE WILL ATTENUATE BREAST TUMOR-ASSOCIATED FATIGUE BY UPREGULATING PPAR TRANSCRIPTIONAL ACTIVITY IN SKELETAL MUSCLE, THEREBY RESCUING MITOCHONDRIAL BIOENERGETICS AND ATP PRODUCTION. BC-PDOX MICE AND CONTROLS TREATED WITH AND WITHOUT PIOGLITAZONE WILL BE EVALUATED FOR MUSCLE FATIGUE, MITOCHONDRIAL BIOENERGETICS AND ATP CONTENT. THIS PROJECT IS CONCEPTUALLY INNOVATIVE IN ITS USE OF A PRECLINICAL MOUSE MODEL THAT PHENOTYPICALLY AND TRANSCRIPTIONALLY MIMICS BC-ASSOCIATED MUSCLE FATIGUE IN THE ABSENCE OF CACHEXIA. OUR APPROACH IS BOTH UNIQUE AND PRACTICAL IN THAT IT SEEKS TO LAY THE FOUNDATION FOR REPURPOSING AN EXISTING FDA-APPROVED PPAR-AGONIST FOR TREATMENT OF FATIGUE IN PATIENTS WITH BC, DIRECTLY ADDRESSING A KEY KNOWLEDGE GAP IN THIS FIELD. THE OUTCOMES OF THIS PROJECT WILL IMPACT THE TREATMENT OF CANCER- RELATED FATIGUE, WITH THE POTENTIAL TO OFFER EARLY-STAGE BC-PATIENTS A TREATMENT STRATEGY TARGETING THIS DEBILITATING SYMPTOM BEFORE THE ONSET OF CACHEXIA. THE AIMS AND OBJECTIVES OF THIS PROJECT REFLECT THE GOALS OF THE NCI, AS DESCRIBED IN THEIR MISSION STATEMENT, BY SPECIFICALLY CONDUCTING RESEARCH THAT WILL ADVANCE SCIENTIFIC KNOWLEDGE AND BE APPLICABLE TO A LARGE POPULATION OF PATIENTS AS WELL AS HELPING IMPROVE PATIENTS’ QUALITY OF LIFE DURING AND FOLLOWING COMPLETION OF CANCER-ASSOCIATED THERAPY.

THE ROLE OF EPIGENETICS AND MIRNAS IN IPF