University Of Rochester

UNIVERSITY OF ROCHESTER ''NATIONAL INERTIAL CONFINEMENT FUSION PROGRAM'' *NEW AWARD

NATIONAL INERTIAL CONFINEMENT FUSION PROGRAM

THIS PROPOSAL PRESENTS THE PLANNED PROGRAM AT THE UNIVERSITY OF ROCHESTER’S LABORATORY FOR LASER ENERGETICS (LLE) FOR THE NEXT FIVE-YEAR PERIOD (FY24–FY28) AND SUMMARIZES LLE’S ACCOMPLISHMENTS DURING THE CURRENT PERIOD (FY19–FY23). LLE’S RESEARCH ACTIVITIES FOCUS ON SUPPORTING THE MISSIONS OF THE NATIONAL NUCLEAR SECURITY ADMINISTRATION (NNSA) IN INERTIAL CONFINEMENT FUSION (ICF), HIGH-ENERGY-DENSITY (HED) PHYSICS, AND LASER AND OPTICAL SCIENCE AND TECHNOLOGY. LLE OPERATES THE OMEGA LASER FACILITY (INCLUDING THE 60-BEAM OMEGA AND THE FOUR-BEAM OMEGA EP LASER SYSTEMS) AS NNSA’S PRINCIPAL HED USER FACILITY. TOGETHER WITH THE UNIVERSITY OF ROCHESTER’S NEW HED PHYSICS CURRICULUM, LLE PROVIDES A UNIQUE, MISSION-ORIENTED EDUCATIONAL EXPERIENCE THAT PREPARES STUDENTS FOR A CAREER WITHIN THE NATIONAL SECURITY COMPLEX. BY ENHANCING THIS PIPELINE, LLE HAS SIGNIFICANTLY EXPANDED THE NUMBER OF GRADUATES ENTERING THE NNSA WORKFORCE, WHICH IS HELPING TO FILL THE NEEDS OF THE STOCKPILE STEWARDSHIP PROGRAM.

NA-123.1 NATIONAL INTERTIAL CONFINEMENT FUSION PROGRAM

NEW AWARD. FOLLOW-ON TO DE-FC 03-85DP40200 SCOEP=RESEARCH ININERTIAL CONFINEMENT FUSION;O PERATION & MGMT OF THE NATIONAL LASER USER'S FACILITY; UPGR

NA-123.1 NATIONAL INTERTIAL CONFINEMENT FUSION PROGRAM

UNIVERSITY OF ROCHESTER-NCORP RESEARCH BASE

THE UNIVERSITY OF ROCHESTER'S CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTE

COMPARATIVE GENOMES OF LONGEVITY

ENVIRONMENTAL AGENTS AS MODULATORS OF DISEASE PROCESSES

THE UNIVERSITY OF ROCHESTER'S CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTE

NEUROCIRCUITRY OF OCD: EFFECTS OF MODULATION

THE REGIONAL CENTERS OF EXCELLENCE IN SUBSTANCE USE DISORDER EDUCATION PROGRAM

UNITS FOR HIV/AIDS CLINICAL TRIALS NETWORKS

THEORETICAL AND EXPERIMENTAL STUDIES OF ELEMENTARY PARTICLES AND FIELDS

CTSA COORDINATING CENTER FOR LEADING INNOVATION AND COLLABORATION (CLIC)

RESEARCH INFRASTRUCTURE: MIDSCALE RI-1 (M1:DP): OMEGA-EP-PUMPED OPTICAL PARAMETRIC AMPLIFIER LINE (EP-OPAL) FACILITY DESIGN -THIS AWARD SUPPORTS THE DESIGN OF A NEW, WORLD-LEADING, HIGH POWER LASER USER FACILITY AT THE UNIVERSITY OF ROCHESTER. THIS DESIGN PROJECT FOR THE FACILITY TO BE CALLED EP-OPAL ENVISIONS TWO NEW POWERFUL LASERS TO BE LOCATED AT THE UNIVERSITY'S LABORATORY FOR LASER ENERGETICS (UR/LLE). EP-OPAL WILL EMPLOY A TECHNIQUE DEVELOPED AT UR/LLE FOR THE GENERATION OF VERY POWERFUL, ULTRASHORT LASER PULSES THAT WAS RECOGNIZED BY THE 2018 NOBEL PRIZE IN PHYSICS. EP-OPAL AIMS TO PUSH BEYOND THE CURRENT STATE OF THE ART IN PEAK LASER POWER TO ACHIEVE AND STUDY EXTREME PHYSICAL CONDITIONS, SUCH AS ULTRAHIGH ELECTROMAGNETIC FIELDS, TEMPERATURES, AND PRESSURES THAT REPRESENT THE FRONTIER OF SCIENCE IN STUDYING MATTER IN THE UNIVERSE. ONCE COMPLETED, EP-OPAL WILL BE THE HIGHEST-POWER LASER SYSTEM IN THE WORLD. THE TWO LASER BEAMS COMBINED WILL DELIVER APPROXIMATELY THE SAME TOTAL POWER AS INCIDENT ON THE EARTH?S SURFACE FROM THE SUN, BUT FOCUSED INTO AN AREA SMALLER THAN THE CROSS-SECTION OF A HUMAN HAIR. THE DESIGN EFFORT WILL ENGAGE THE U.S. INDUSTRY TO DEVELOP CRITICAL LASER OPTICS AND WILL INCLUDE HANDS-ON TRAINING OF A NEW GENERATION OF LASER FACILITY DESIGNERS AND BUILDERS. THE EP-OPAL FACILITY DESIGN AWARD SUPPORTS DESIGN OF TWO 25-PETAWATT LASERS USING OPTICAL PARAMETRIC CHIRPED-PULSE AMPLIFICATION, AS WELL AS ASSOCIATED EXPERIMENTAL AND DIAGNOSTICS SYSTEMS. THE DESIGN WILL BE GUIDED BY THE MOST PRESSING SCIENTIFIC QUESTIONS THAT CAN BE ANSWERED USING SUCH A LASER SYSTEM IN FOUR AREAS OF FRONTIER RESEARCH: PARTICLE ACCELERATION AND ADVANCED LIGHT SOURCES, HIGH-FIELD PHYSICS AND QUANTUM ELECTRODYNAMICS, LABORATORY ASTROPHYSICS AND PLANETARY PHYSICS, AND LASER-DRIVEN NUCLEAR PHYSICS. SPECIFICALLY, THE MAIN AIMS OF THE PROJECT ARE: (1) DESIGN THE EP-OPAL FACILITY, INCLUDING LASERS, EXPERIMENTAL SYSTEMS AND DIAGNOSTICS, TO ADDRESS A WIDE ARRAY OF COMPELLING SCIENCE; (2) DESIGN AND PROTOTYPE HIGH-ENERGY LASER AMPLIFIERS WITH SHOT-CYCLE TIMES OF A FEW MINUTES; (3) DESIGN AND PROTOTYPE LARGE-OPTICS PRODUCTION AND CHARACTERIZATION SYSTEMS. THE EP-OPAL FACILITY IS ENVISIONED TO SERVE AS A LEARNING ENVIRONMENT AND A HUB FOR DIVERSE SCIENTIFIC NETWORKS, OFFERING OPPORTUNITIES FOR FUNDAMENTAL RESEARCH AND INNOVATION AS WELL AS MEDICAL, INDUSTRIAL AND NATIONAL SECURITY APPLICATIONS. THE EP-OPAL FACILITY DESIGN EFFORT WILL ENGAGE COLLABORATORS AT THE UNIVERSITY OF BUFFALO, THE UNIVERSITY OF CALIFORNIA - IRVINE, THE UNIVERSITY OF NOTRE DAME, THE OHIO STATE UNIVERSITY, THE UNIVERSITY OF MARYLAND - COLLEGE PARK, THE UNIVERSITY OF MICHIGAN - ANN ARBOR, AND AN INDUSTRIAL PARTNER PLYMOUTH GRATING LABORATORY. 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.

UNIVERSITY OF ROCHESTER VACCINE AND TREATMENT EVALUATION UNIT (VTEU)

SSC DETECTOR RESEARCH & DEVELOPMENT

HEERF CARES ACT INSTITUTIONAL SHARE APPLICATION

CENTER FOR MATTER AT ATOMIC PRESSURES

UNIVERSIITY OF ROCHESTER CENTER FOR MEDICAL COUNTERMEASURES AGAINST RADIATION

TRAINING IN ENVIRONMENTAL TOXICOLOGY

PRE- AND POSTNATAL EXPOSURE PERIODS FOR CHILD HEALTH: COMMON RISKS AND SHARED MECHANISMS

UNIVERSITY OF ROCHESTER DEVELOPMENTAL CENTER FOR AIDS RESEARCH

NEUROPROTECTION STUDIES IN PD: A COORDINATING CENTER

THE UNIVERSITY OF ROCHESTER'S CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTE

FOR-DMD:DOUBLE-BLIND RANDOMIZED TRIAL TO OPTIMIZE STEROID REGIMEN IN DUCHENNE MD

EMERGENY GRANT FUNDS FOR STUDENTS DUE TO CAMPUS DISRUPTIONS BASED ON COVID-19

TRANSFORM: TRANSLATIONAL RESEARCH THAT ADAPTS NEW SCIENCE FOR MALTREATMENT PREVENTION

MUSCULAR DYSTROPHY COOPERATIVE RESEARCH CENTER

UNIVERSITY OF ROCHESTER CANCER CENTER CCOP RESEARCH BASE

TRANSLATING MOLECULAR SIGNAL PATHWAYS TO ORTHOPAEDIC TRAUMA CARE

NEURAL BASIS OF CAUSAL INFERENCE: REPRESENTATIONS, CIRCUITS, AND DYNAMICS

CORE GRANT FOR VISION RESEARCH

SPORE IN LYMPHOMA

VASCULAR RELATIONS OF BLOOD CELLS AND PROTEINS

CENTER OF RESEARCH TRANSLATION ON THE OSTEOIMMUNOLOGY OF BONE INFECTION

MEDICAL SCIENTIST TRAINING PROGRAM GRANT

NEUROCIRCUITRY UNDERLYING DBS EFFECTS IN OCD: A WINDOW INTO MECHANISMS OF ACTION

FUSION SCIENCE CENTER FOR EXTREME STATES OF MATTER AND FAST IGNITION PHYSICS

HOW SLEEP CLEARS YOUR BRAIN: SLOW WAVES, GLYMPHATIC WASTE REMOVAL, AND SYNAPTIC DOWN-SELECTION

NOVEL ADJUNCTIVE THERAPIES FOR NEUROAIDS

IP21-002, ENHANCED SURVEILLANCE NETWORK FOR ENTERIC AND RESPIRATORY VIRUSES IN CHILDREN: ASSESSING DISEASE BURDEN, NATURAL HISTORY, AND VACCINE EFFECTIVENESS

A HUB FOR BROADBAND LASER-PLASMA SCIENCE FOCUSED ON INERTIAL FUSION ENERGY DRIVING THE SCIENCE AND TECHNOLOGY OF A MULTIPLE BEAM HIGH-BANDWIDTH LASER FOR IFE

AN EXPERIMENTAL/COMPUTATIONAL APPROACH FOR UNDERSTANDING SALIVARY FLUID SECRETION

COORDINATION AND STATISTICS FOR COQ10 IN HD 2CARE

UNITS FOR HIV/AIDS CLINICAL TRIALS NETWORKS

BIOREPOSITORY FOR INVESTIGATION OF DISEASES OF THE LUNG (BRINDL) - PHASE II

NEURAL CIRCUIT CONTROL OF FLUID AND SOLUTE CLEARANCE DURING SLEEP - PROGRAM ABSTRACT: THIS PROPOSAL AIMS TO IDENTIFY THE NEURAL CIRCUIT MECHANISMS THAT CONTROL PERIARTERIAL CEREBROSPINAL FLUID (CSF) PUMPING AND GLYMPHATIC CLEARANCE OF FLUID AND SOLUTES. WE HAVE DEVELOPED A COLLABORATION TO QUANTIFY CSF TRANSPORT DYNAMICS IN BOTH HUMANS AND MICE ACROSS SEVERAL SCALES, SPANNING MOLECULAR TRANSPORT, NEURONAL AND GLIAL ACTIVITY, VASCULAR AND BRAIN-WIDE FLUID DYNAMICS. WE PROPOSE THAT COORDINATED NEURAL ACTIVITY DURING SLEEP DRIVES GLOBAL AND LOCAL CHANGES IN BLOOD VOLUME, WHICH IN TURN ARE THE PRIMARY DRIVERS OF CSF TRANSPORT. OUR MODEL ESTABLISHES A NOVEL CONCEPTUAL FRAMEWORK, NAMELY THAT NEURONAL CIRCUITS CONTROL CLEARANCE VIA THEIR EFFECTS ON ASTROCYTES AND THE VASCULATURE, OPENING AN ARRAY OF TESTABLE HYPOTHESES ACROSS SPATIAL SCALES AND SPECIES. PROJECT 1 WILL BUILD QUANTITATIVE FLUID-DYNAMICAL MODELS TO ESTABLISH HOW ARTERIAL DILATION, MEDIATED BY NEURAL ACTIVITY, DRIVES PERIARTERIAL CSF PUMPING AND GLYMPHATIC EFFLUX ACROSS LENGTH SCALES. MODELS FOR BOTH MICE AND HUMANS, INFORMED BY EXPERIMENTS IN PROJECTS 2-4, WILL DRIVE HYPOTHESES TO BE TESTED IN THOSE PROJECTS. PROJECT 2 WILL DISSECT HOW NEURAL ACTIVITY TRANSMITS CA2+/CAMP SIGNALING TO THE NEUROVASCULAR UNIT, THEREBY ALTERING THE PHYSICAL DIMENSIONS AND FUNCTIONAL PROPERTIES OF THE PERIVASCULAR SPACES. VIRAL TAGGING COMBINED WITH OPTOGENETIC STIMULATION OF INDIVIDUAL CELL POPULATIONS WILL REVEAL NEURAL EFFECTS ON CSF FLOW, MEASURED BY PARTICLE TRACKING. THE PROJECT WILL ALSO PROVIDE THE FIRST SYSTEMATIC ANALYSIS LINKING PERIARTERIAL CSF INFLOW WITH GLYMPHATIC SOLUTE CLEARANCE. PROJECT 3 WILL DISSECT THE LOCAL NEURAL AND GLOBAL NEUROMODULATORY DRIVERS OF VASODYNAMICS DURING NREM SLEEP USING OPTOGENETIC AND CHEMOGENETIC MANIPULATIONS. ADDITIONALLY, LOCAL AND GLOBAL ARTERIAL DYNAMICS DURING SLEEP WILL BE IMAGED, PROVIDING KEY INFORMATION ON THE VASCULAR PUMPING OF CSF MOVEMENT. PROJECT 4 WILL USE NOVEL MRI-BASED TECHNIQUES TO ESTABLISH HOW NEURAL ACTIVITY AND LARGE-SCALE FLUID FLOW ARE LINKED IN THE HUMAN BRAIN. BY DRIVING LOCAL NEURAL ACTIVITY WITH SENSORY STIMULATION, AND IMAGING SPONTANEOUS NEUROVASCULAR AND CSF DYNAMICS ACROSS AROUSAL STATES, IT WILL TEST HOW SPECIFIC SPATIOTEMPORAL PATTERNS OF NEURAL ACTIVITY AFFECT HEMODYNAMICS AND CSF FLOW IN WAKEFULNESS AND NREM SLEEP. THE PROJECTS WILL BE SUPPORTED BY CORES FOCUSED ON VIRAL TOOLS, DATA SCIENCE, AND ADMINISTRATION, ALL OVERSEEN BY INTERNAL AND EXTERNAL ADVISORY COMMITTEES. TOGETHER, THE PROJECTS WILL PROVIDE A QUANTITATIVE, CIRCUIT-BASED UNDERSTANDING OF THE NEURAL MECHANISMS GOVERNING BRAIN FLUID FLOW AND SOLUTE CLEARANCE DURING SLEEP.

MORRIS K. UDALL CENTER AT THE UNIVERSITY OF ROCHESTER (UR-UDALL CENTER)

NEW; SISGR: MODULAR NANOSCALE AND BIOMIMETIC ASSEMBLIES FOR PHOTOCATALYTIC HYDROGEN GENERATION; PI: KARA BREN

DATA COORDINATION CENTER FOR STEADY-PD3

AGE-17 FOLLOW-UP OF HOME VISITING INTERVENTION

FUNCTIONAL IMAGING OF GANGLION CELLS IN THE LIVING MAMMALIAN EYE

CENTER FOR BIOPHYSICAL ASSESSMENT AND RISK MANAGEMENT

CONTINUITY OF LIMBIC CIRCUIT THROUGH THE BASAL GANGLIA

CA2+I AND SECRETORY DYNAMICS IN PAROTID ACINAR CELLS

FUSION SCIENCE CENTER FOR EXTREME STATES OF MATTER AND FAST IGNITION PHYSICS

THE HUMAN LUNG BIOMOLECULAR MULTI-SCALE ATLAS PROGRAM (HUBMAP-LUNG) - PROJECT SUMMARY/ABSTRACT OVERALL RESEARCH PLAN THE HUMAN LUNG BIOMOLECULAR MULTI-SCALE ATLAS PROGRAM (HUBMAP-LUNG) THE HUMAN BIOMOLECULAR ATLAS PROGRAM (HUBMAP) IS ENTERING THE PRODUCTION PHASE, WITH AN EMPHASIS ON PROGRESSIVE, HIGH SENSITIVITY AND SPECIFICITY ASSAYS, PRIORITIZING SPATIAL BIOMOLECULAR ANALYSIS. OUR TISSUE MAPPING CENTER (TMC) PROPOSAL WILL FOCUS ON ONE ORGAN SYSTEM, COMPRISED OF TWO LUNGS AND RELATED RESPIRATORY TRACT (TRACHEA TO ALVEOLI) THAT FOR SIMPLICITY WE REFER TO AS THE “LUNG”. OUR TMC WILL GENERATE, STANDARDIZE, AND VALIDATE EXTENSIVE DATA FROM HIGH CONTENT, HIGH-THROUGHPUT IMAGING AND `OMICS TECHNOLOGY TO PRODUCE SYSTEMATIC HUMAN LUNG TISSUE MAPS AT HIGH RESOLUTION. WE WILL TAKE A LONG VIEW OF AN ATLAS, AS A COLLECTION OF 2D AND 3D MAPS CONTAINING IMAGES, TABULAR DATA, FACTS ABOUT MULTIPLE LOCATIONS AT VARYING RESOLUTION, AND INDEXES OF NAMED OBJECTS KEYED TO COORDINATES OF A LOCATIONAL GRID ANALOGOUS TO LATITUDE AND LONGITUDE, TO CARTOGRAPHICALLY PRESENT THE WHOLE RANGE OF SALIENT FEATURES OF THE HUMAN LUNG. TO ACCOMPLISH THIS TASK, OUR CENTER BRINGS TOGETHER INVESTIGATORS FROM FIVE INSTITUTIONS, THE UNIVERSITY OF ROCHESTER (URMC), UNIVERSITY OF CALIFORNIA AT SAN DIEGO (UCSD), PACIFIC NORTHWEST NATIONAL LABORATORY (PNNL), UNIVERSITY OF WASHINGTON (UW), AND UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL (UNC), EACH WITH COMPLEMENTARY LUNG-FOCUSED ACADEMIC INTERESTS, KNOWLEDGE, AND INTER- CONSORTIA NETWORK CONNECTIONS AND WITH INTERNATIONALLY RECOGNIZED EXPERTISE IN LUNG AND STATE-OF-THE-ART BIOMOLECULAR TECHNOLOGIES. OUR LUNG DATA PROVIDED TO THE HUBMAP DATA PORTAL IN PHASE I HAS BEEN FOCUSED TO SINGLE NUCLEUS RNA-SEQUENCING, CHROMATIN AVAILABILITY AND BEGINNING SPATIAL TRANSCRIPTOMICS. IN ADDITION TO FURTHER INCREASING REPRESENTATION OF HUMAN DIVERSITY IN THESE DATA TYPES, THE NEXT PHASE OF OUR TMC TURNS PRIMARY EFFORT TOWARD DETERMINING SPATIAL ORGANIZATION OF CELLS AND MATRICES DEFINED BY NOT ONLY GENE EXPRESSION BUT ALSO PROTEINS, PROTEIN MODIFICATIONS, LIPIDS AND SELECT METABOLITES CRITICAL TO SPECIFIC CELL FUNCTION WITHIN ANATOMICAL AND FUNCTIONAL NICHES. WITH THE RECOGNIZED VALUE OF GLOBAL INVESTIGATIVE EFFORTS WITHIN AND OUTSIDE THE CONSORTIUM, THE SPECIFIC AIMS OF THE TMC OVERALL COMPONENT CONCENTRATE ON COMMUNICATION AND COLLABORATION WITHIN THE TMC, BETWEEN ALL HUBMAP COMPONENTS AND SYNERGISTICALLY AMONG NATIONAL AND INTERNATIONAL RESEARCHERS AND CONSORTIA.

AUDITORY PROCESSING OF COMPLEX SOUNDS

FACTORS MODIFYING THE TOXICITY OF METHYLMERCURY IN A FISH-EATING POPULATION

TRNA PROCESSING

16/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT UNIVERSITY OF ROCHESTER

UNIVERSITY OF ROCHESTER INTELLECTUAL AND DEVELOPMENTAL DISABILITIES RESEARCH CENTER

AUDITORY AND INTEGRATIVE PROCESSES IN PREFRONTAL CORTEX

OVERALL: THE UNIVERSITY OF ROCHESTER RESOURCE-BASED CENTER FOR MUSCULOSKELETAL BIOLOGY AND MEDICINE

FUNCTION OF FIXATIONAL INSTABILITY DURING NATURAL VIEWING

A MULTIFACETED PROMPTING INTERVENTION FOR URBAN CHILDREN WITH ASTHMA

INTERDISCIPLINARY LEADERSHIP EDUCATION NEURODEVELOPMENTAL AND REL

ESTABLISHMENT OF THE WNY SPATIAL BIOLOGY RESOURCE CENTER - PROJECT SUMMARY THE UNIVERSITY OF ROCHESTER MEDICAL CENTER (URMC) IS COMMITTED TO ADVANCING RESEARCH EXCELLENCE BY PROVIDING STATE-OF-THE-ART FACILITIES AND CUTTING-EDGE TECHNOLOGIES FOR BIOMEDICAL AND BIOLOGICAL RESEARCH. SPATIAL ‘OMICS IS TRANSFORMATIVE NEW TECHNOLOGY THAT SEEKS TO HARNESS THE POWER OF ‘OMICS (EG. GENOMICS, PROTEOMICS, METABOLOMICS, LIPIDOMICS) TO PROVIDE A DEEP MOLECULAR PROFILE OF INDIVIDUAL CELLS IN A WAY THAT MAINTAINS THE SPATIAL RELATIONSHIPS THAT EXIST BETWEEN CELLS AND THEIR SURROUNDINGS IN INTACT TISSUES. THE URMC PROPOSES THE ESTABLISHMENT OF THE WESTERN NEW YORK SPATIAL BIOLOGY RESEARCH CENTER (SBRC). THIS PIONEERING INITIATIVE WILL INTEGRATE TISSUE PROCESSING, HISTOLOGY, GENOMICS, AND BIOINFORMATICS/DATA ANALYTICS INTO A UNIFIED ORGANIZATIONAL ENTITY, CLOSELY INTEGRATED WITH TISSUE AND BIOBANKING EFFORTS. THE 5,700 SQUARE FEET OF WET- AND DRY-LAB SPACE IS CENTRALLY LOCATED TO RESEARCHERS WHERE THE SBRC WILL SERVE AS A COMPREHENSIVE HUB FOR SPATIAL OMICS RESEARCH, ENABLING VALIDATION AND DISCOVERY AT AN UNPRECEDENTED SCALE. BY CENTRALIZING URS EXPERTISE IN HISTOLOGY, GENOMICS, AND BIOINFORMATICS AND POSITIONING THE SBRC NEAR THE WILMOT BIOBANK, WE WILL FOSTER INNOVATIVE COLLABORATIONS, ENHANCE ACCESSIBILITY, AND STREAMLINE RESEARCH TO ACCELERATE SCIENTIFIC DISCOVERY. WE WILL DEVELOP DATA ANALYTICS EXCELLENCE BY ESTABLISHING A MODERNIZED DATA ANALYTICS COLLABORATIVE SPACE, EQUIPPED WITH ADVANCED IT INFRASTRUCTURE, TO ENABLE THE ANALYSIS OF LARGE-SCALE SPATIAL ‘OMICS DATASETS AND TO DEVELOP NOVEL ANALYTICAL TECHNIQUES INTEGRATING MULTILEVEL ‘OMICS DATA. ADDITIONALLY, THE CREATION OF THIS NEW COLLABORATIVE DRY-LAB SPACE WILL CATALYZE INTERDISCIPLINARY PARTNERSHIPS AND THE DEVELOPMENT OF NOVEL RESEARCH METHODOLOGIES. THROUGH DYNAMIC COLLABORATIONS WITH OUR REGIONAL AND NATIONAL PARTNERS, THE SBRC WILL SERVE AS A CENTRAL HUB FOR TRANSFORMATIVE CROSS-DISCIPLINARY SCIENCE. OUR COMMITMENT TO TRAINING THE NEXT GENERATION OF RESEARCHERS WILL ENSURE THAT SCIENTISTS ARE EQUIPPED WITH CUTTING-EDGE SKILLS IN SPATIAL OMICS, EMPOWERING THEM TO TACKLE URGENT SCIENTIFIC CHALLENGES AND DISCOVER LIFE-CHANGING CURES. THE SBRC IS STRATEGICALLY POSITIONED TO ELEVATE TRANSLATIONAL RESEARCH IN KEY AREAS SUCH AS MUSCULOSKELETAL DISEASES, CANCER BIOLOGY, AUTOIMMUNITY, AND NEUROSCIENCE. BY PROVIDING RESEARCHERS WITH ACCESS TO CUTTING-EDGE METHODOLOGIES, SBRC WILL EMPOWER NEW SCIENTIFIC BREAKTHROUGHS. MOREOVER, IT ALIGNS WITH THE UNIVERSITY OF ROCHESTER'S EDUCATIONAL MISSION BY OFFERING ADVANCED TRAINING IN BIOINFORMATICS AND DATA ANALYSIS, THEREBY BROADENING THE ADOPTION OF SPATIAL OMICS ACROSS DIVERSE RESEARCH DOMAINS. THIS INITIATIVE REPRESENTS A TRANSFORMATIVE STEP FORWARD IN PROMOTING RESEARCH EXCELLENCE AT THE UNIVERSITY OF ROCHESTER AND BEYOND. BY FOSTERING CRITICAL ADVANCEMENTS IN HEALTH-RELATED RESEARCH AND SERVING AS A REGIONAL RESOURCE FOR TRANSLATIONAL DISCOVERY AND EDUCATION, SBRC WILL SOLIDIFY URMC'S POSITION AS A LEADER IN BIOMEDICAL INNOVATION.

SENATOR PAUL D. WELLSTONE MUSCULAR DYSTROPHY SPECIALIZED RESEARCH CENTER

COMPARATIVE EFFECTIVENESS OF EIBI AND ADAPTIVE ABA FOR CHILDREN WITH AUTISM

DATA COORDINATION AND BIOSTATISTICS CENTER FOR THE NORDIC NETWORK

ROCHESTER NETWORK LEAD ACADEMIC PARTICIPATING SITE

QUANTUM IMAGING: NEW METHODS AND APPLICATIONS

A XENOPUS LAEVIS RESEARCH RESOURCE FOR IMMUNOBIOLOGY

MOLECULAR RECOGNITION DURING PRE-MRNA SPLICING

EARLY LIFE AIR POLLUTION EXPOSURES AS A RISK FACTOR FOR NEURODEVELOPMENTAL DISORDERS - ABSTRACT NUMEROUS STUDIES NOW REPORT ASSOCIATIONS BETWEEN AIR POLLUTION (AP) EXPOSURE AND NEURODEVELOPMENTAL DISORDERS (NDDS), INCLUDING AUTISM SPECTRUM DISORDER, SCHIZOPHRENIA, AND ATTENTION DEFICIT DISORDER, ALL OF WHICH SHARE NUMEROUS FEATURES. MY STUDIES OF EARLY POSTNATAL (HUMAN 3RD TRIMESTER BRAIN EQUIVALENT) INHALATION EXPOSURES TO CONCENTRATED AMBIENT ULTRAFINE (UFP, CONSIDERED THE MOST REACTIVE COMPONENT OF AP) PARTICLES (CAPS) IN MICE PRODUCED NUMEROUS NEUROPATHOLOGICAL AND BEHAVIORAL FEATURES OF THESE NDDS AND OF THEIR SHARED HYPOTHESIZED MECHANISMS, INCLUDING MALE BIAS, PROVIDING BIOLOGICAL PLAUSIBILITY FOR THE EPIDEMIOLOGICAL STUDIES. ADDITIONALLY, CAPS EXPOSURES MARKEDLY ELEVATED BRAIN LEVELS OF METALS AND TRACE ELEMENTS, INCLUDING REDOX METALS (FE, CU) AS WELL AS S, CA, AND AL, FINDINGS INDICATIVE OF BRAIN METAL DYSHOMEOSTASIS. THIS PROPOSAL SEEKS TO TEST THE OVERARCHING HYPOTHESIS THAT AP-INDUCED BRAIN METAL DYSHOMEOSTASIS CONTRIBUTES TO MALE- BIASED NDD PHENOTYPES VIA PRODUCTION OF NEUROINFLAMMATION AND OXIDATIVE STRESS TESTED IN A SERIES OF QUESTIONS DESIGNED TO ACCELERATE THE UNDERSTANDING OF MECHANISMS, AND TRANSLATIONAL RELEVANCE OF SUCH EFFECTS IN 5 KEY INTEGRATED QUESTIONS EMANATING FROM THESE NOVEL, DRAMATIC AND UNEXPECTED FINDINGS: 1) ARE TOXIC TRACE ELEMENT CONTAMINANTS OF UFPS A SOURCE OF CAPS-INDUCED NDD PHENOTYPIC FEATURES, SPECIFICALLY ELEVATED BRAIN FE AND S (INHALED FE NANOPARTICLES AND/OR SO2) BOTH OF WHICH ARE KNOWN NEUROTOXICANTS VIA FERROPTOTIC AND OXIDATIVE STRESS MECHANISMS? 2) WHAT ACCOUNTS FOR MALE BIAS IN UFP-INDUCED NEUROTOXICITY? DOES IT REFLECT AN EARLIER COLONIZATION OF MALE BRAIN BY ACTIVATED MICROGLIA AND THEIR INTERACTIONS WITH FE UPTAKE? 3) WHAT ARE THE PORTALS OF ENTRY OF UFPS INTO BRAIN? WE UTILIZE THE PRECOCIAL AFRICAN SPINY MOUSE WITH ITS EXTENDED GESTATIONAL PERIOD RELATIVE TO THE ALTRICIAL C57 MOUSE IN WHICH 3RD TRIMESTER OCCURS POSTNATALLY AND CAN INCLUDE NASAL AND OLFACTORY UPTAKE TO DETERMINE WHETHER THE AFRICAN SPINY MOUSE MIGHT SERVE AS A MORE RELEVANT HUMAN MODEL. 4) HOW DOES NANOPARTICLE PROCESSING IN BRAIN SUBSEQUENTLY INFLUENCE/MODULATE TOXICITY AND DOES IT GENERATE TOXIC OR PROTECTIVE MECHANISMS E.G., ALTERATIONS IN THE FERRITIN CAGE? 5) DOES POST-MORTEM BRAIN TISSUE FROM HUMANS THAT HAD BEEN DIAGNOSED WITH NDDS (NEUROBIOBANK) CONTAIN EXOGENOUS METAL NANOPARTICLES AS WE SEE, E.G., WITH FE LOCATED WITHIN DAMAGED MYELIN IN CORPUS CALLOSUM AFTER CAPS? THESE INTEGRATED EFFORTS WILL BEGIN TO ELABORATE MECHANISMS OF AP-INDUCED NDDS AND ASSOCIATED SEX DIFFERENCES, TO DEFINE THE MOST RELEVANT MOUSE MODEL, AND TO DETERMINE THE NEED TO REGULATE AIR METAL LEVELS FOR PUBLIC HEALTH PROTECTION.

MORE THAN A MOVEMENT DISORDER: APPLYING PALLIATIVE CARE TO PARKINSON'S DISEASE

PRE- AND POSTNATAL EXPOSURE PERIODS FOR CHILD HEALTH: COMMON RISKS AND SHARED MECHANISMS

COMPLEX LEARNING AND SKILL TRANSFER WITH VIDEO GAMES (TOPIC#9)

MITOCHONDRIA AND NO? IN CARDIAC ISCHEMIC PRECONDITIONING

NONSENCE-MEDIATED MRNA DECAY: PIONEER ROUND OF TRANSLATION

ACCELERATE CLINICAL TRIALS IN CMT (ACTCMT) STUDY

METHYL MERCURY EFFECTS ON ADOLESCENT DEVELOPMENT

SENSORY INTEGRATION FOR HEADING PERCEPTION

CAPACITY BUILDING ASSISTANCE (CBA) FOR HIGH IMPACT HIV PREVENTION PROGRAM INTEGRATION

STUDIES OF THE FATE OF THE OSTEOCLAST

MONITORING AND MITIGATION OF NEUROLOGICAL INJURIES TO OPTIMIZE RESILIENCE AFTER REPETITIVE HEAD IMPACTS (MONITOR RHI)

CREATINE SAFETY AND EFFICACY IN HD: COORDINATION AND STATISTICAL CENTER

BIOREPOSITORY FOR INVESTIGATION OF NEONATAL DISEASES OF LUNG-NORMAL (BRINDL-NL)

HIGH ENERGY DENSITY QUANTUM MATTER

INTERPARENTAL CONFLICT AND PARENTING

SUPPRESSION AND EXACERBATION OF B AND T CELL RESPONSES *

NEW; TITLE: RESOLVING THE ISSUE. THE DYNAMICS OF MAGNETIZED ASTROPHYSICAL JETS THROUGH PULSED POWER HEDP LABORATORY STUDIES; PI - ADAM FRANK

AIM-FOR-RA - RHEUMATOID ARTHRITIS (RA) AFFECTS APPROXIMATELY 1% OF THE POPULATION AND IS CHARACTERIZED BY INFLAMMATION AND JOINT DAMAGE, OFTEN LEADING TO CONSIDERABLE DISABILITY AND PAIN IN BOTH EARLY AND ESTABLISHED STAGES. KEY AREAS OF UNMET NEED IN THE FIELD INCLUDE THE: 1) HIGHLY HETEROGENEOUS AND UNPREDICTABLE DISEASE COURSE, 2) RARITY OF LASTING REMISSIONS, 3) FAILURE OF CURRENTLY AVAILABLE TREATMENTS TO ACHIEVE LOW DISEASE ACTIVITY AND/OR LIMIT PROGRESSIVE JOINT DAMAGE IN MANY PATIENTS, AND 4) LACK OF ROBUST BIOMARKERS NECESSARY TO PERSONALIZE APPROPRIATE TREATMENT STRATEGIES. WE PROPOSE THAT CELLULAR AND MOLECULAR VARIATION IN SYNOVIAL TISSUE UNDERLIES THIS HETEROGENEITY AND THAT UNDERSTANDING THE BASIS FOR THIS WILL IMPROVE THE PREDICTION OF DISEASE COURSE AND PROVIDE A RATIONALE FOR THE TIMELY SELECTION OF PRECISION TREATMENT STRATEGIES WITH HIGHER RATES OF SUSTAINED RA CONTROL. THROUGH SUSTAINED COLLABORATIVE GLOBAL TEAM-SCIENCE, THE AIM-FOR-RA TEAM HAS ALREADY DEVELOPED STATE-OF- THE-ART PROTOCOLS THAT DECONSTRUCTED RA SYNOVIAL BIOPSY TISSUES - AN INNOVATION THAT PROFOUNDLY ADVANCED KNOWLEDGE IN CELLS AND PATHWAYS INVOLVED IN RA PATHOGENESIS, IDENTIFIED NOVEL TREATMENT TARGETS, IDENTIFIED DISEASE BIOMARKERS, AND OPENED NEW OPPORTUNITIES IN DISEASE PREVENTION. HOWEVER, IT REMAINS UNCLEAR HOW MOLECULAR INTERACTIONS IN THE SYNOVIUM RELATE TO THE EVOLUTION OF DEFINED CLINICAL OUTCOMES, FROM THE AT-RISK PRECLINICAL PERIOD TO ARTHRITIS ONSET, AND THEN THROUGH TO SYNOVITIS OUTCOME. THEREFORE, AIM-FOR-RA DISEASE TEAM (DT) AIMS TO RELATE DISEASE-RELEVANT SYNOVIAL CELLULAR PATHWAYS AND DYNAMIC CROSSTALK TO ENVIRONMENTAL EXPOSURES, DISEASE OUTCOMES AND TREATMENT RESPONSE, THEREBY RECONSTRUCTING THE DISEASE PATHOGENESIS TRAJECTORY. IN A DMARD-NAÏVE RA CROSS- SECTIONAL SYNOVIAL BIOPSY-BASED STUDY OF 50 RA PATIENTS ACROSS 9 SITES USING HARMONIZED PROTOCOLS AND INTEGRATED TECHNOLOGIES, AIM 1 WILL DELIVER HIGH-QUALITY MULTIMODAL CLINICAL PHENOTYPE AND HISTOLOGY DATA, ALONG WITH SYNOVIAL TISSUE AND OTHER BIOSAMPLES, TO EVALUATE HOW SYNOVIAL CELLULAR AND MOLECULAR PATHWAYS RELATE TO DISEASE ONSET. WITH LONGITUDINAL FOLLOW-UP AND REPEAT BIOPSY OF THESE INDIVIDUALS AFTER METHOTREXATE MONOTHERAPY, AIM 2 WILL ADDRESS WHETHER SYNOVIAL SIGNATURES AND MULTI-MODAL DATA PREDICT FIRST-LINE METHOTREXATE RESPONSE, OR FAILURE IN PATIENTS WITH EARLY PREVIOUSLY UNTREATED DISEASE. FINALLY, IN AIM 3, IN PATIENTS WITH METHOTREXATE INADEQUATE RESPONSE WE WILL ADDRESS WHETHER DISTINCT SYNOVIAL CELLULAR OR MOLECULAR FEATURES PREDICT A POSITIVE RESPONSE TO BIOLOGIC THERAPIES DIRECTLY TARGETING THESE FEATURES. THE OUTCOMES OF THIS PROGRAM WILL HAVE POTENTIAL FOR RAPID TRANSLATIONAL APPLICATION TO IMPROVE TREATMENT OUTCOMES AT ALL RA DISEASE STAGES. COLLECTIVELY, THE COLLABORATIVE, GLOBAL AIM-FOR-RA TEAM THAT HAS MADE SEMINAL OBSERVATIONS REGARDING RA DISEASE PATHOGENESIS IS IDEALLY SUITED TO INFORM THE KEY QUESTIONS AND MEET MAJOR UNMET NEEDS IN THE FIELD.

NEURAL BASIS OF DEPTH PERCEPTION

MEDIATORS OF CANCER CELL HOMEOSTASIS: INTERVENTION TARGETS COMMON TO DIVERSE TYPES OF CANCER

LATE SODIUM CURRENT BLOCKADE IN HIGH-RISK ICD PATIENTS - CCC - LEAD APPLICATION

ELLIPSS: ELUCIDATING THE LANDSCAPE OF IMMUNOENDOTYPES IN PSORIATIC SKIN AND SYNOVIUM - ABSTRACT PSORIATIC SPECTRUM DISEASES (PSD) AFFECT OVER 8 MILLION INDIVIDUALS IN THE U.S. LIVING WITH PSORIASIS (PSO) OR PSORIATIC ARTHRITIS (PSA) AND ENCOMPASS HETEROGENEOUS PHENOTYPES OF DISEASE, RANGING FROM PLAQUE, GUTTATE, PALMOPLANTAR, INVERSE, PUSTULAR, AND ERYTHRODERMIC FORMS OF PSORIASIS, TO SYNOVIAL, ENTHESIAL, AND AXIAL FORMS OF PSA. HERE, WE ASSEMBLED A WORLD CLASS MULTIDISCIPLINARY TEAM OF SCIENTISTS IN PSD COHORT ASSEMBLY, CLINICAL PHENOTYPING, BIOSAMPLE ACQUISITION, PATHOLOGY, STATISTICS, AND BIOINFORMATICS, FOR THE ACCELERATING MEDICINES PARTNERSHIP AUTOIMMUNE AND IMMUNE-MEDIATED DISEASES (AMP AIM) PSD DISEASE TEAMS (DTS). THE MAJOR SCIENTIFIC GOALS OF THE PSD DT ARE TO UNDERSTAND THE CELLULAR AND MOLECULAR COMPOSITION OF DISTINCT PSD ENDOTYPES AND HOW THEY LINK WITH PHENOTYPES, TO IDENTIFY HOW KEY PATHOGENIC OR REGULATORY CELLS SPATIALLY INTERACT WITH EACH OTHER AND WITH ENVIRONMENTAL CUES (I.E., MICROBIOME), AND TO DEFINE AT A SINGLE-CELL LEVEL HOW THE TRANSITION TO PSA UNFOLDS IN THE SETTING OF PSO. TO ACCOMPLISH THE GOALS OF THE PSD AMP, WE PROPOSE THE CREATION OF THE ELLIPSS (ELUCIDATING THE LANDSCAPE OF IMMUNOENDOTYPES IN PSORIATIC SKIN AND SYNOVIUM) DISEASE TEAM (DT). THE AIMS OF THE ELLIPSS TEAM ARE TO 1) TO ENROLL DIVERSE PSD COHORTS AND PERFORM CLINICAL PHENOTYPING, DATA CAPTURE, AND TISSUE COLLECTION. 2) TO IMPLEMENT AN EFFECTIVE MANAGEMENT PLAN FOR THE ELLIPSS MULTIDISCIPLINARY TEAM. 3) TO OPTIMIZE INTERFACE OF ELLIPSS TEAM WITH AMP-AIM NETWORK. LASTLY, A ROBUST OPPORTUNITIES FUND (OF) MANAGEMENT PROGRAM IS PROPOSED UNDER THE DIRECTION AND LEADERSHIP OF DR. JAMES T. ELDER AT UNIVERSITY OF MICHIGAN. THE ELLIPSS PSD DT WILL EFFICIENTLY INTEGRATE WITH THE AMP AIM NETWORK, FACILITATE COLLECTION OF PSD BIOSAMPLES, AND HELP PROVIDE AN UNPRECEDENTED VIEW OF CELL TYPES AND STATES, ALONG WITH SPATIAL AND TISSUE INTERACTIONS (SKIN, JOINT, BLOOD, MICROBIOME) TO DECONSTRUCT/RECONSTRUCT THE PSORIATIC DISEASE SPECTRUM.

CELL DEATH PATHWAYS IN GLAUCOMATOUS NEURODEGENERATION

EXECUTIVE FUNCTION IN CHILDREN WITH HYPERTENSION

ACCELERATING PHOTORECEPTOR REPLACEMENT THERAPY WITH IN-VIVO CELLULAR IMAGING OF RETINAL FUNCTION - ABSTRACT TO RESTORE HIGH QUALITY, USABLE VISION IN PATIENTS, IT IS IMPORTANT TO DEVELOP REGENERATIVE THERAPIES IN MODELS THAT SHARE KEY FEATURES OF THE HUMAN VISUAL SYSTEM, PARTICULARLY A FOVEA, THE RETINAL AREA SPECIALIZED FOR HIGH ACUITY VISION. PRE-CLINICAL TESTING HAS BEEN CHALLENGING DUE TO BOTH THE ABSENCE OF MODELS OF FOVEAL VISION LOSS AND THE DIFFICULTY OF DEMONSTRATING RESTORED FUNCTION. UNDER PREVIOUS AGI FUNDING, THE ADVANCED RETINAL IMAGING ALLIANCE AT THE UNIVERSITY OF ROCHESTER HAS RECENTLY OVERCOME THESE CHALLENGES TO CREATE A PRE-CLINICAL TESTING PLATFORM LEVERAGING ADAPTIVE OPTICS TECHNOLOGY TO: 1.) CREATE LOCALIZED REGIONS OF PHOTORECEPTOR ABLATION IN THE FOVEA THAT ARE AXIALLY CONFINED, AND 2.) OPTICALLY READ OUT RESTORED RETINAL GANGLION CELL FUNCTION BY PERFORMING CELLULAR SCALE CALCIUM IMAGING IN THE LIVING EYE. THIS SYSTEM WAS DEVELOPED TO MEET THE NEEDS OF PHOTORECEPTOR REPLACEMENT THERAPY, WHICH REQUIRES PHOTORECEPTOR LOSS WITH PRESERVED HOST RETINAL CIRCUITRY. FURTHERMORE, A HIGH-RESOLUTION IN VIVO IMAGING APPROACH IS WELL SUITED FOR PRE-CLINICAL EVALUATION OF REGENERATIVE THERAPIES WHERE THE TIMESCALES OF RESTORED CONNECTIVITY ARE UNKNOWN AND FUNCTIONAL INTEGRATION OCCURS ON THE CELLULAR SCALE. IN THIS PROPOSAL, WE WILL USE OUR PLATFORM TO GENERATE PRE-CLINICAL DATA THAT WILL INFORM FUTURE CLINICAL TRIALS OF PHOTORECEPTOR REPLACEMENT THERAPY IN PATIENTS. FUNCTIONAL INTEGRATION OF TRANSPLANTED PHOTORECEPTORS WITH THE HOST RETINA REQUIRES BOTH HIGH-DENSITY DELIVERY OF HIGH-QUALITY DONOR PHOTORECEPTORS AND A HOST RETINA WITH THE CAPACITY FOR SYNAPTOGENESIS. WE HAVE ASSEMBLED A CONSORTIUM THAT CAN EXPLORE AND OPTIMIZE BOTH SIDES OF THIS INTERACTION. IN CONTINUED COLLABORATION WITH A TEAM AT THE UNIVERSITY OF WISCONSIN LED BY DAVID GAMM, A CLINICIAN AND EXPERT IN PHOTORECEPTOR REPLACEMENT THERAPY, WE WILL EVALUATE SURVIVAL AND FUNCTIONAL INTEGRATION OF TRANSPLANTED PHOTORECEPTOR PRECURSORS DELIVERED TO THE SUB-RETINAL SPACE AS AGGREGATES OR FOLLOWING INCORPORATION INTO CUSTOM BIODEGRADABLE SCAFFOLDS. IN COLLABORATION WITH A TEAM AT UNIVERSITY OF CALIFORNIA, BERKELEY LED BY TERESA PUTHUSSERY, AN EXPERT IN RETINAL REMODELLING IN RETINAL DEGENERATION MODELS AND RETINAL HISTOLOGY, WE WILL EXAMINE THE IMPACT OF THE LOSS OF PHOTORECEPTOR SIGNALLING ON INNER RETINA. WE WILL EXPLORE WHETHER DEAFFERENTED CONE BIPOLAR CELLS CAN REMODEL AND FUNCTIONALLY INTEGRATE WITH DONOR PHOTORECEPTORS AND WHETHER RETINAL HYPERACTIVITY DEVELOPS IN THE FOVEA AS IT DOES IN RODENT. TO MAKE MEANINGFUL PROGRESS TOWARD RESTORING VISION IN PATIENTS WHO HAVE LIVED WITH VISION LOSS FOR MANY YEARS, WE WILL EXAMINE HOW THESE PHENOMENA DEVELOP IN THE FOVEA OVER TIME AND WHETHER THE REGENERATIVE POTENTIAL OF THE HOST CAN BE IMPROVED BY THERAPEUTIC INTERVENTIONS SUCH AS RETINOIC ACID BLOCKERS. THESE STUDIES WILL ALLOW US TO FULLY CHARACTERIZE OUR NOVEL PHOTORECEPTOR ABLATION MODEL AND DEPLOY IT WITH PHOTORECEPTOR REPLACEMENT THERAPIES TO ADVANCE THE FIELD TOWARD CLINICAL TRIALS.

CORNEAL WOUND HEALING: OCULAR OPTICS AFTER LASER SURGERY

CDC INJURY CONTROL RESEARCH CENTER FOR PREVENTING SUICIDE (CDC ICRC S)

BIOMARKERS OF ATOPY BEGINNING EARLY (BABE) - PROJECT SUMMARY/ABSTRACT – OVERALL ATOPIC DERMATITIS (AD) OFTEN PRECEDES SENSITIZATION TO FOOD ALLERGENS AND THE DEVELOPMENT OF CLINICAL FOOD ALLERGY (FA) DUE TO COMPROMISED SKIN BARRIER FUNCTION ALLOWING ALLERGEN SENSITIZATION THROUGH SKIN. A LARGE BODY OF DATA FROM EUROPE AND NORTH AMERICA SUGGEST THAT LIVING ON FARMS IS ASSOCIATED WITH A DECREASED RISK OF ASTHMA AND ATOPIC DISEASES. ASTHMA HAS BEEN A FOCUS OF FARMING LIFESTYLE STUDIES; HOWEVER, LITTLE IS KNOWN ABOUT THE PROTECTIVE MECHANISMS OF FARMING LIFESTYLE ON DEVELOPMENT OF AD AND FA WHICH OFTEN PRECEDE RESPIRATORY ALLERGIES AND ASTHMA. THE FARM LIFESTYLE PROTECTION AGAINST ALLERGIC DISEASES COMPRISES LIKELY THREE PREREQUISITES: 1) INNATE IMMUNE TRAINING AND A MODIFIED IMMUNE RESPONSE UPON RE-EXPOSURE, 2) GENERATION OF SUPPRESSIVE REGULATORY T CELLS, AND 3) PRESERVED BARRIER FUNCTION. HERE, WE PROPOSE TO ASSESS THESE PRECONDITIONS IN AN EXTENDED LONGITUDINAL BIRTH COHORT STUDY AMONG THE OLD ORDER MENNONITES (OOM), A POPULATION PRACTICING TRADITIONAL, SINGLE-FAMILY FARMING WITH A LOWER RATE OF ASTHMA AND ALLERGIC DISEASES, INCLUDING ATOPIC DERMATITIS AND FOOD ALLERGIES IN EARLY CHILDHOOD. BIOMARKERS OF ATOPY BEGINNING EARLY (BABE) WILL TEST THE OVERALL HYPOTHESIS THAT PERTURBED SKIN BARRIER FUNCTION, IMMUNE MILLIEU AND MICROBIOME DRIVE THE DEVELOPMENT OF ATOPIC DERMATITIS, TH2 INFLAMMATION, ALLERGIC SENSITIZATION AND FA, WHEREAS A HEALTHY GUT MICROBIOME MODULATES THE PROTECTIVE METABOLITE POOL SUCH AS SHORT CHAIN FATTY ACIDS AND TRYPTOPHAN METABOLITES AND PROTECTIVE TREG IMMUNE DEVELOPMENT. PROJECT 1 UTILIZES DEEP METAGENOMIC SEQUENCING TO ASSESS INFANT GUT MICROBIOME COMPOSITION AND CORRESPONDING METABOLOME TO SHOW THAT OOM INFANT GUT MICROBIOME IS DISTINCT FROM URBAN INFANTS. PROJECT 2 ASSESSES MARKERS OF ALLERGIC SENSITIZATION AND PROTECTIVE IMMUNE DEVELOPMENT UTILIZING MULTIPARAMETER SPECTRAL FLOW, UNBIASED CLUSTERING ANALYSIS AND TRANSCRIPTOMIC STUDIES TO DEMONSTRATE THAT URBAN INFANTS HAVE A HIGHER NUMBER OF HYPERINFLAMMATORY MONOCYTES AND TH2-SKEWED T CELL SUBSETS DETECTED IN EARLY INFANCY, WHEREAS OOM HAVE GUT-HOMING MEMORY TREGS. PROJECT 3 WILL CHARACTERIZE SKIN BARRIER FUNCTION, MICROBIOME AND IMMUNE CELL TRANSCRIPTOME. OUR LONGITUDINAL BIRTH COHORT ZOOM1, FUNDED BY A U01 GRANT, IS NOW 2-5 YEARS OLD AND IS A SHARED FOUNDATION FOR THE THREE PROJECTS (78 OOM AND 79 URBAN). WE WILL ADD ANOTHER 120 INFANTS AS A ZOOM2 COHORT (80 URBAN AND 40 OOM). WE WILL ALSO REPLICATE KEY T CELL BIOMARKERS IN LARGER INFANT COHORTS (START EATING EARLY DIET ”SEED” AND MICROBIOME AND ALLERGIC ASTHMA PRECISION PREVENTION “MAAP2”). THE INFRASTRUCTURE TO RECRUIT, COLLECT AND SHARE SAMPLES AND DATA IS PROVIDED BY THE COHORT ADMIN & BIOREPOSITORY AND DATA MANAGEMENT & BIOINFORMATICS CORES. THE ADMIN CORE WILL PROVIDE OVERALL FINANCIAL AND ADMINISTRATIVE INFRASTRUCTURE. THESE STUDIES AIM TO IDENTIFY BIOMARKERS, MECHANISMS, AND PROTECTIVE STRATEGIES AGAINST ATOPIC AND FOOD ALLERGY.

MOLECULAR MECHANISM OF AGE-RELATED DECLINE OF NONHOMOLOGOUS DNA END JOINING

TRAINING PROGRAM IN ORAL SCIENCE

TRP CHANNELS AS FUNDAMENTAL SENSORS OF THE CEREBRAL MICROCIRCULATION - PROJECT SUMMARY OPTIMAL FLOW OF BLOOD WITHIN THE BRAIN IS ENSURED BY TWO PROCESSES: (1) AUTOREGULATION, A COLLECTION OF INTRINSIC MECHANISMS THAT CONTINUOUSLY ADJUST THE MICROCIRCULATION TO MAINTAIN A CONSTANT FLOW OF BLOOD IN THE FACE OF CHANGES IN PERFUSION PRESSURE, AND (2) NEUROVASCULAR COUPLING, AN ENSEMBLE OF CEREBRAL VASCULATURE PHYSIOLOGICAL PROCESSES THAT TIGHTLY MATCH LOCAL BLOOD FLOW TO THE NEEDS OF METABOLICALLY ACTIVE REGIONS OF THE BRAIN. THESE DISTINCTIVE RESPONSES ARE NECESSARY FOR BRAIN HEALTH AND FUNCTION BUT REMAIN INCOMPLETELY UNDERSTOOD. FURTHER, LOSS OF MICROVASCULAR CONTROL IS ASSOCIATED WITH COMMON AGE-RELATED CEREBROVASCULAR PATHOLOGIES, INCLUDING STROKE, CEREBRAL SMALL VESSEL DISEASES (CSVDS), AND VASCULAR COGNITIVE IMPAIRMENT AND DEMENTIA (VCID). THE OVERARCHING GOAL OF THIS PROPOSAL IS TO ADDRESS THIS CRITICAL KNOWLEDGE GAP BY PROVIDING A BETTER UNDERSTAND OF HOW THE BRAIN’S EVER-CHANGING MILIEU OF PHYSICAL, ENVIRONMENTAL, ENDOCRINE, PARACRINE, METABOLIC, AND NEUROCHEMICAL STIMULI ARE SENSED BY THE CEREBRAL MICROVASCULATURE AT THE CELLULAR LEVEL, AND HOW THESE SIGNALS ARE PROCESSED TO ENSURE HOMEOSTASIS AND ADAPTABILITY. THE PRIMARY MECHANISTIC FOCUS OF OUR RESEARCH IS ION CHANNELS OF THE TRANSIENT RECEPTOR POTENTIAL (TRP) FAMILY—POLYMODAL SENSORS OF MANY TYPES OF PHYSICAL AND CHEMICAL STIMULI PRESENT IN ALL CELLS. OVER THE PAST 10 YEARS, OUR RESEARCH TEAM HAS DISCOVERED THAT TRPM4 (TRP MELASTATIN 4) AND TRPML1 (TRP MUCOLIPIN 1) CHANNELS IN CEREBRAL VASCULAR SMOOTH MUSCLE CELLS ARE IMPORTANT FOR THE DEVELOPMENT OF MYOGENIC TONE, A FUNDAMENTAL AUTOREGULATORY MECHANISM, AND HAS DEMONSTRATED CRITICAL SENSORY ROLES FOR TRPA1 (TRP ANKYRIN 1) AND TRPV3 (TRP VANILLOID 3) CHANNELS ON THE ENDOTHELIUM OF CEREBRAL ARTERIES AND ARTERIOLES. CONTINUING WITH THIS THEME AND USING ADVANCED BIOMEDICAL IMAGING APPROACHES AND NEXT-GENERATION GENETIC MOUSE MODELS, WE WILL WEAVE TOGETHER THE CENTRAL CONCEPTS ESTABLISHED BY OUR INDEPENDENT PROJECTS TO DEVELOP A COMPREHENSIVE OVERVIEW OF TRP CHANNELS AS CELLULAR SENSORS IN THE CEREBRAL MICROVASCULATURE. EXAMPLES OF PROPOSED STUDIES INCLUDE INVESTIGATIONS THAT WILL DEFINE THE NANOSCALE ARCHITECTURE OF TRP CHANNEL SIGNALING NETWORKS IN HEALTH AND DISEASE USING SUPERRESOLUTION MICROSCOPY, ELUCIDATE HOW TRPML1 CHANNELS ARE ENDOGENOUSLY REGULATED IN SMOOTH MUSCLE CELLS TO PREVENT VASCULAR HYPERCONTRACTILITY DURING MYOGENIC VASOCONSTRICTION, AND TEST THE HYPOTHESIS THAT TRPA1 CHANNELS ON BRAIN CAPILLARY ENDOTHELIAL CELLS ACT AS DETECTORS OF REACTIVE OXYGEN SPECIES TO PROMOTE NEUROVASCULAR COUPLING. WE WILL LAYER BASIC SCIENCE INVESTIGATIONS INTENDED TO ELUCIDATE FUNDAMENTAL REGULATORY MECHANISMS WITH RESEARCH DESIGNED TO UNDERSTAND HOW PROCESSES CONTROLLED BY TRP CHANNELS GO WRONG AND CONTRIBUTE TO THE TRANSFORMATION OF HEALTHY SMALL VESSELS IN THE BRAIN TO A DISEASE STATE DURING AGING. TO FURTHER THIS GOAL, WE ARE DEVELOPING AND CHARACTERIZING NEW GENETIC MODELS OF AGE-RELATED CSVDS AND VCID IN COLLABORATION WITH INVESTIGATORS AT UCSF, AND PROPOSE TO USE THIS UNIQUE RESOURCE TO EXPLORE THEMES THAT INCLUDE THE INVOLVEMENT OF TRPM4, TRPML1, AND TRPA1 CHANNELS IN CEREBRAL VASCULAR DYSFUNCTION DURING AGE-RELATED CSVDS AND VCID.

MECHANISMS OF ACTION OF NON-CODING RNA MOLECULES

ENHANCED SURVEILLANCE FOR NEWLY PREVENTABLE DISEASES (ARI AND AGE SURVEILLANCE) ROCHESTER, NY

RETINAL MECHANISMS AND VISUAL RESOLUTION

EFFECT OF NEONATAL HYPEROXIA ON ALVEOLAR DEVELOPMENT AND INFECTION

POVIDONE IODINE EFFICACY STUDY (PIES) - SEVERE EARLY CHILDHOOD CARIES (S-ECC) IS DIFFICULT TO TREAT EFFECTIVELY AND HAS AN ALARMING AND DISTRESSING TENDENCY TO RECUR FOLLOWING TREATMENT. S-ECC IS A PARTICULARLY ACUTE FORM OF EARLY CHILDHOOD CARIES (ECC) THAT IS CHARACTERIZED BY AN OVERWHELMING CARIES-PROMOTING MICROBIAL CHALLENGE, INCLUDING MUTANS STREPTOCOCCI (MS) AND LACTOBACILLI (LB). THE STANDARD OF CARE FOR ECC/S-ECC REVOLVES AROUND TREATMENT IN A SURGICAL OPERATING SUITE UNDER GENERAL ANESTHESIA, FOLLOWED BY APPLICATION OF 5% TOPICAL FLUORIDE VARNISH, FAMILY COUNSELING REGARDING FEEDING BEHAVIORS AND ORAL HYGIENE INSTRUCTION. CLINICAL STUDIES DEMONSTRATE APPROXIMATELY 40% OF CHILDREN TREATED FOR S-ECC WILL DEVELOP NEW CARIES LESIONS WITHIN 12 MONTHS AFTER DENTAL SURGERY. REDUCING CARIOGENIC ORAL MICROBIOTA WITH A TOPICAL ANTI-MICROBIAL AGENT IS A POTENTIAL APPROACH TO REDUCTION OF RECURRENT DISEASE IN YOUNG CHILDREN WITH S-ECC. RECENT STUDIES HAVE SHOWN THAT 10% POVIDONE IODINE (POLYVINYLPYRROLIDONE-IODINE, 10% PVPI) APPEARS PROMISING IN PREVENTING DENTAL CARIES IN YOUNG CHILDREN. A META- ANALYSIS OF ANTIMICROBIAL INTERVENTIONS AND THE ORAL MICROBIOTA ASSOCIATED WITH ECC HIGHLIGHT THE PAUCITY OF HIGH- QUALITY RANDOMIZED CONTROLLED TRIALS ON THE EFFICACY OF ANTIMICROBIAL AGENTS, INCLUDING PVPI. THE DATA FROM THE NATIONAL HEALTH AND NUTRITIONAL EXAMINATION SURVEY (NHANES 2011-2014) INDICATES THAT THE PREVALENCE OF ECC IN US PRESCHOOL CHILDREN IS 24% AND RANGES BETWEEN 11% AND 72%. THE CLINICAL, SOCIAL AND PUBLIC HEALTH IMPACT OF ECC/S-ECC IS UNDERSCORED BY ITS ASSOCIATION WITH INCREASED RISK OF NEW CARIES LESIONS IN THE PRIMARY DENTITION, A HIGHER RISK OF CARIES ONSET IN THE PERMANENT DENTITION, HOSPITALIZATIONS, EMERGENCY ROOM VISITS, HIGH TREATMENT COSTS, LOST SCHOOL DAYS, DIMINISHED ABILITY TO LEARN AND A PROFOUND IMPACT ON A CHILD’S QUALITY OF LIFE. THE PRIMARY OBJECTIVE OF THIS UG3/UH3 APPLICATION IS TO ASSESS THE EFFICACY OF 10% PVPI IN CHILDREN WITH S-ECC TO PREVENT, IN PART OR IN WHOLE, NEW CAVITATED CARIES LESIONS THAT REQUIRE SURGICAL INTERVENTION AFTER ORAL REHABILITATION. THE SPECIFIC AIMS ARE: 1 (UG3): TO FINALIZE THE STUDY PROTOCOL, DEVELOP THE MANUAL OF PROCEDURES (MOP), FINALIZE QUALITY MANAGEMENT AND DATA MANAGEMENT PLANS, FINALIZE STUDY CASE REPORT FORMS (CRFS) AND SET-UP DATA MANAGEMENT SYSTEM; 2 (UH3): TO CONDUCT A SINGLE CENTER RANDOMIZED, DOUBLE-BLIND, PLACEBO- CONTROLLED PHASE II TRIAL (RCT) TO EVALUATE THE EFFICACY OF TOPICAL 10% PVPI TO PREVENT NEW CAVITATED CARIES LESIONS WHEN APPLIED TO THE TEETH OF CHILDREN WITH S-ECC FOLLOWING ORAL REHABILITATION; 3 (UH3): TO MEASURE SEVERITY AND INCIDENCE OF NEW DENTAL CARIES IN CHILDREN WITH S-ECC FOLLOWING ORAL REHABILITATION WHO ARE RECEIVING QUARTERLY TOPICAL 10% PVPI; 4 (UH3): TO ASSESS THE EFFECT OF TOPICAL 10% PVPI ON DIVERSITY AND COMPOSITION OF ORAL MICROBIOTA, INCLUDING CARIOGENIC MS, LB AND CANDIDA SPECIES TO BETTER UNDERSTAND THE MECHANISM OF ACTION OF 10% PVPI ON THE ORAL MICROBIOME. THE PRIMARY OUTCOME WILL BE TIME FROM RANDOMIZATION UNTIL CAVITATED CARIOUS LESION (ICDAS CODE 3) IS FIRST DETECTED POST-SURGERY. CARIES INCREMENT WILL BE MEASURED WITH THE INTERNATIONAL CARIES DETECTION AND ASSESSMENT SYSTEM (ICDAS). THE APPROVED FDA IND FOR THIS TRIAL IS #108961.

"(MURI 04) RELATIONSHIP BETWEEN PHYSICOCHEMICAL CHARACTERISTICS AND TOXICOLOGICAL PROPERTIES OF NANOMATERIALS"

DEVELOPING AND TESTING MODELS OF THE AUDITORY SYSTEM WITH & WITHOUT HEARING LOSS

MULTIDISCIPLINARY TRAINING IN PULMONARY RESEARCH

ROCHESTER PREVENTION RESEARCH CENTER

SCHOOL-BASED ASTHMA THERAPY: STAGE 2 EFFECTIVENESS STUDY REVISED

HUMAN IMMUNOLOGY CENTER AT THE UNIVERSITY OF ROCHESTER

EVOLUTION OF CIS-REGULATORY SEQUENCES

ADAPTIVE OPTICS INSTRUMENTATION FOR ADVANCED OPHTHALMIC IMAGING

REGULATION OF EPIGENOME STABILITY BY SIRT6 DURING AGING. SUPPLEMENT: DOES CENTENARIAN VARIANT OF SIRT6 OR BOWHEAD WHALE SIRT6 CONFER PROTECTION FROM ALZHEIMER'S DISEASE?

THE ROLE OF ASTROCYTES IN ISCHEMIC STROKE

PHASE 3 TRIAL OF INOSINE FOR PARKINSON'S DISEASE - DCC

PTH EFFECTS OF CRANIOFACIAL ALLOGRAFTS

B CELLS AND DRAINING LYMPH NODE FUNCTION IN ARTHRITIC FLAIR

THIS GRANT WILL SUPPORT THE PARTICULATE MATTER CENTER AT THE UNIVERSITY OF ROCHESTER, WHICH WILL CONDUCT AN INTEGRATED RESEARCH PROGRAM ON THE SOURC

INSTITUTIONAL CAREER DEVELOPMENT CORE

CANCER CONTROL RESEARCH TRAINING CURRICULUM (R25T)

ROCHESTER PREVENTION RESEARCH CENTER

REGULATION OF NORMAL AND DEFECTIVE HUMAN GENES

EXPERIMENTAL THERAPEUTICS IN NEUROLOGICAL DISEASE

NERVOUS SYSTEM CHANNELOPATHIES: PATHOGENESIS & TREATMENT

ROCHESTER PARTNERSHIP TO ADVANCE RESEARCH AND ACADEMIC CAREERS IN DEAF SCHOLARS

INTERDISCIPLINARY LEADERSHIP EDUCATION NEURODEVELOPMENTAL AND REL

SELECTIVE P450 OXIDATION CATALYSTS FOR SYNTHESIS OF BIOACTIVE MOLECULES

COMMUNITY PARTNERSHIP FOR BREASTFEEDING PROMOTION AND SUPPORT: CREATING SYSTEM CH

PRE- AND POSTDOCTORAL TRAINING PROGRAM IN IMMUNOLOGY

EFFECTIVENESS TRIAL OF WINGMAN-CONNECT IMPLEMENTED ACROSS CAREER PHASES - ABSTRACT MILITARY SUICIDE RATES INCREASED 61% FROM 2008 – 2019 AND RATES HAVE INCREASED FASTER IN THE U.S. AIR FORCE (USAF) COMPARED TO OTHER BRANCHES. CURRENTLY, THE PREDOMINANT MILITARY SUICIDE PREVENTION APPROACH IS TO TRY TO REMEDIATE SUICIDE RISK AFTER SUICIDAL INDIVIDUALS ARE IDENTIFIED. NO RCT-VALIDATED UNIVERSAL PROGRAMS SHOWN TO REDUCE VULNERABILITY TO SUICIDE ARE IN WIDE USE. TO FILL THIS GAP, THE WINGMAN-CONNECT PROGRAM IS A GROUP-BASED INTERVENTION THAT STRENGTHENS PROTECTIVE RELATIONSHIP NETWORKS AND SKILLS FOR MANAGING CAREER AND PERSONAL CHALLENGES, TO REDUCE VULNERABILITY TO SUICIDE ACROSS THE BROAD USAF POPULATION. THIS PROPOSED HYBRID EFFECTIVENESS-IMPLEMENTATION TRIAL TESTS THE EFFECTIVENESS OF THE WINGMAN-CONNECT PROGRAM ON INDIVIDUAL SUICIDE RISK AND ON BASE-LEVEL SUICIDE ATTEMPTS. WE WILL EXAMINE THEORY-DRIVEN MEDIATORS AND MODERATORS AND IMPLEMENTATION OF THE PROGRAM AS DELIVERED BY US AIR FORCE (NOT RESEARCH) PERSONNEL UNDER REAL WORLD CONDITIONS ACROSS 2 SEQUENTIAL EARLY CAREER PHASES. THIS EFFECTIVENESS STUDY IS THE CRITICAL NEXT STAGE IN THE TRANSLATIONAL PIPELINE TOWARD LARGE-SCALE ROLL-OUT TO PREVENT SUICIDE DEATHS. TO RIGOROUSLY TEST EFFECTIVENESS, WE CO-DEVELOPED WITH USAF PARTNERS A 2-STAGE RANDOMIZED DESIGN. (1) THE FIRST STAGE OF RANDOMIZATION WILL BE AT INITIAL TECHNICAL TRAINING, IN WHICH 396 CLASSES OF USAF PERSONNEL WILL BE RANDOMIZED TO WINGMAN-CONNECT OR TO AN ACTIVE CONTROL (N=2,970 AIRMEN) AND FOLLOWED FOR ONE YEAR. THESE CLASSES SEND A HIGH PROPORTION OF GRADUATES TO 8 OPERATIONAL BASES. (2) THE SECOND STAGE OF RANDOMIZATION WILL OCCUR AMONG THESE 8 OPERATIONAL BASES, WHICH WILL BE RANDOMIZED IN PAIRS TO START IMPLEMENTING WC AT 4- MONTH INTERVALS (STEPPED WEDGE DESIGN). ONCE WC HAS BEEN INITIATED AT EACH BASE, ALL ENTERING FIRST-TERM AIRMEN WILL RECEIVE WC, WITH ~17,400 TOTAL AIRMEN TRAINED ACROSS ALL BASES. THIS 2-STAGE DESIGN WILL YIELD ROBUST, MULTI-LEVEL EFFECTIVENESS FINDINGS. AIM 1: TEST EFFECTIVENESS OF WC ON REDUCING (A) SELF-REPORTED SUICIDE RISK AND (B) BASE-LEVEL RATES OF SUICIDE ATTEMPTS. WE WILL EVALUATE (A) INDIVIDUAL LEVEL OUTCOMES OF SUICIDE RISK, DEPRESSION, AND OCCUPATIONAL PROBLEMS UP TO 1 YR; AND (B) BASE-LEVEL ADMINISTRATIVE RECORDS OF SUICIDE ATTEMPTS. AIM 2: EVALUATE THEORY-PROPOSED NETWORK HEALTH MEDIATORS AND MODERATORS. WC IS EXPECTED TO INCREASE AIRMEN'S POSITIVE SOCIAL BONDS, GROUP COHESION, MORALE, AND HEALTHY COPING NORMS IN THEIR SOCIAL NETWORKS; THOSE CHANGES WILL CONTRIBUTE TO REDUCED SUICIDE RISK, DEPRESSION AND OCCUPATIONAL PROBLEMS. AIM 3: EXAMINE IMPLEMENTATION DETERMINANTS AND MECHANISMS, AND REFINE IMPLEMENTATION PACKAGE. KEY IMPLEMENTATION OUTCOMES WILL BE USAF IMPLEMENTERS' FIDELITY DELIVERING WC (N=24-30) AND ENGAGEMENT IN TRAINING/TECHNICAL SUPPORT. IMPLEMENTER FIDELITY AND ENGAGEMENT IS EXPECTED TO BE PREDICTED BY BASE IMPLEMENTATION CLIMATE AND WC EMBEDDEDNESS INTO BASE COMMUNICATIONS AND SUPPORT ACTIVITIES.

(MQC) MULTI-SCALE PROBES OF CORRELATION AND CAUSATION IN SILICON

A TRANSLATIONAL CENTER FOR BARRIER MPS - ABSTRACT (OVERALL) THE UNIVERSITY OF ROCHESTER (UR) AND DUKE UNIVERSITY WILL ESTABLISH A TRANSLATIONAL CENTER FOR BARRIER MPS (TRACE-BMPS) TO CREATE DRUG DEVELOPMENT TOOLS (DDTS) FOCUSED ON THE ROLE OF BARRIER FUNCTIONS IN DISEASE, INJURY, AND INFECTION. THE OVERALL GOAL OF THE CENTER IS TO SUBMIT FULL QUALIFICATION PACKAGES TO THE FDA FOR FIVE DDTS RELEVANT TO THE TREATMENT OF: 1) CENTRAL NERVOUS SYSTEM (CNS) DISORDERS, 2) FIBROSIS, 3) MUSCULOSKELETAL AUTOIMMUNE DISEASE, 4) SEPSIS, AND 5) OSTEOMYELITIS. FOR EACH DDT WE HAVE ASSEMBLED AN EXPERIENCED AND MULTIDISCIPLINARY TEAM TO ESTABLISH REPRODUCIBILITY OF BIOMARKER ASSESSMENTS FOR CLINICALLY IMPORTANT CONTEXTS OF USE (COU). EACH DDT WILL BE BASED ON AN EXISTING, VALIDATED MPS MODEL AND LEVERAGE THE MODULAR ΜSIM MPS PLATFORM WHICH PROVIDES DESIGN FLEXIBILITY ALONG WITH TRANSLATIONALLY RELEVANT PERMEABILITY AND IMAGING AT THE INTERFACE BETWEEN TISSUE COMPARTMENTS. THE TRACE-BMPS WILL COMPRISE: 1) A QUALIFICATION PROGRAM (QP), 2) A RESOURCE CORE (RC), AND 3) AN ADMINISTRATIVE CORE (AC). THESE UNITS WILL WORK TOGETHER TO ACHIEVE THE CENTER’S FIVE-YEAR MISSION WHILE ESTABLISHING SUSTAINABILITY THROUGH COMMERCIALIZATION, COLLABORATION, AND RESOURCE SHARING. THE QP WILL DEVELOP DDTS AND STANDARD OPERATING PROCEDURES (SOPS) AND ACHIEVE ANSWER-IN-SAMPLE-OUT FUNCTIONALITY THROUGH LIVE CELL IMAGING AND INTEGRATED SENSOR TECHNOLOGIES. REPRODUCIBILITY FOR EACH DDT WILL BE ESTABLISHED IN AT LEAST TWO LABORATORIES. QUALIFICATION PLANS AND PACKAGES WILL BE SUBMITTED TO THE FDA IN A COLLABORATION BETWEEN REGULATORY SCIENTISTS AT UR AND DUKE. WORKING WITH MANUFACTURERS, THE RC WILL QUALIFY EVERY DDT COMPONENT BEFORE DISTRIBUTION TO DEVELOPMENT TEAMS. THE RC WILL ALSO ADVANCE DDTS TO ARRAYED FORMATS THAT ARE COMPATIBLE WITH AUTOMATED PLATE READERS AND LIQUID HANDLERS. THE AC WILL INCLUDE AN EXECUTIVE COMMITTEE THAT WILL DIRECT THE CENTER WITH INPUT FROM STAKEHOLDERS, INCLUDING PHARMACEUTICAL COMPANIES WHO WILL DEFINE END USER NEEDS. THE AC WILL ALSO MANAGE FORMAL REPORTING AND OTHER INTERACTIONS WITH THE NIH, FDA, AND THE NCATS CENTER HUB. THE DYSREGULATED TRANSPORT OF CELLS AND MOLECULES BETWEEN TISSUES IS THE UNDERLYING CAUSE OF MANY DISEASES AND IS APPLICABLE TO THE DEVELOPMENT OF DRUG PROGRAMS. ADDITIONALLY, THE DELIVERY OF DRUGS TO AFFECTED TISSUES DEPENDS ON THE ABILITY TO CROSS THESE BARRIERS. DESPITE THE FUNDAMENTAL SIGNIFICANCE OF TISSUE BARRIERS IN MEDICINE, MOST MICROPHYSIOLOGICAL SYSTEMS (MPS) DO NOT PROVIDE RELIABLE ACCESS TO QUANTITATIVE ASSESSMENTS CELLULAR AND MOLECULAR EXCHANGES AT TISSUE BARRIERS. BY FOCUSING ON DDTS SPECIALLY DESIGNED TO PROVIDE THESE METRICS, THE TRACE-BMPS ADDRESSES AN UNMET NEED IN DRUG DEVELOPMENT. THIS FOCUS, ALONG WITH THE UNIQUE TECHNOLOGIES THAT ENABLE IT, WILL ALSO MAKE THE TRACE-BMPS A UNIQUE AND VALUABLE CONTRIBUTOR TO THE FORTHCOMING TRACE-MPS NETWORK.

CORTICAL SUBSTRATES OF WORKING MEMORY FOR VISUAL MOTION

SUPPORTING RNASTRUCTURE: SOFTWARE FOR RNA ANALYSIS

GERIATRICS WORKFORCE ENHANCEMENT PROGRAM

CORE HISTONE TALL INTERACTIONS AND FUNCTION IN CHROMATIN

NEUROPHYSIOLOGICAL ASPECTS OF VISION-BASED SPEED OF PROCESSING COGNITIVE TRAINING IN OLDER ADULTS WITH MILD COGNITIVE IMPAIRMENT

DEVELOPING A P01 TO ADDRESS COGNITIVE IMPAIRMENT AND TREATMENT TOLERABILITY IN PATIENTS WITH ADVANCED CANCER - ABSTRACT THIS APPLICATION ENTITLED “DEVELOPING A P01 TO ADDRESS COGNITIVE IMPAIRMENT AND TREATMENT TOLERABILITY IN PATIENTS WITH ADVANCED CANCER” IS BEING SUBMITTED IN RESPONSE TO “ADMINISTRATIVE SUPPLEMENTS TO ADVANCE DEVELOPMENT OF TRANSDISCIPLINARY AND LARGE-SCALE POPULATION SCIENCE AND CANCER CONTROL RESEARCH PROJECTS. THIS APPLICATION IS LED BY 3 INTERNATIONALLY RENOWNED EXPERTS (DRS. JANELSINS, MOHILE, MUSTIAN) IN THE FIELDS OF CANCER-RELATED COGNITIVE IMPAIRMENT (CRCI), TOLERABILITY, GERIATRIC ONCOLOGY, AND EXERCISE ONCOLOGY, WITH OVER 75 COLLABORATIVE PUBLICATIONS. THE GOAL OF THIS SUPPLEMENT IS TO PROVIDE THE RESOURCES FOR PLANNING A SUCCESSFUL LARGE-SCALE, SYNERGISTIC PROGRAM PROJECT APPLICATION. PEOPLE LIVING WITH ADVANCED CANCER ARE UNIQUE AND DIFFERENT FROM PATIENTS TREATED FOR EARLY-STAGE DISEASE, AS THEY OFTEN HAVE COMPLEX MEDICAL TRAJECTORIES AND TREATMENT PLANS, LEADING TO ONGOING SUPPORTIVE CARE NEEDS DUE TO INCURABLE DISEASE. CRCI IS ONE OF THE MOST PREVALENT AND BURDENSOME COMPLICATIONS, AFFECTING MANY PATIENTS WITH ADVANCED CANCER. OUR ULTIMATE GOAL IS TO SUBMIT A P01 APPLICATION THAT ADDRESSES AND INTERVENES ON CRCI TO IMPROVE TREATMENT TOLERABILITY. SPECIFICALLY, OUR TEAM PLANS TO DEVELOP P01 PROJECTS TO BETTER UNDERSTAND THE EXPERIENCE OF CRCI IN PATIENTS WITH ADVANCED CANCER. OUR TEAM WILL ALSO DEVELOP P01 PROJECTS TO TEST NOVEL EXERCISE AND DIET INTERVENTIONS TO IMPROVE CRCI AND TREATMENT TOLERABILITY. THIS RESEARCH ALIGNS WITH NCI AND DIVISION OF CANCER CONTROL AND POPULATION SCIENCE (DCCPS) PRIORITIES. OUR PROPOSED RESEARCH SPECIFICALLY ADDRESSES NCI’S NOTICE OF SPECIAL INTEREST: SURVIVORSHIP RESEARCH FOR PEOPLE LIVING WITH ADVANCED AND METASTATIC CANCERS (NOT-CA-25-024) AND PAR-23-059. THIS RESEARCH ALSO ALIGNS WITH THE PRIORITIES OF WILMOT CANCER INSTITUTE, NCI’S NEWEST DESIGNATED CANCER CENTER (P30CA272302). THE MPIS HAVE IDENTIFIED POTENTIAL PROJECT PIS; THIS TEAM HAS BEEN MEETING FOR THE PAST TWO YEARS TO UNDERSTAND OUR MULTI-DISCIPLINARY EXPERTISE, BRAINSTORM, AND CONDUCT INITIAL LITERATURE REVIEWS AND PILOT STUDIES. THIS SUPPLEMENT IS PERFECTLY TIMED TO REFINE OUR P01 RESEARCH PROJECTS, SYNERGY, AND METHODS. OUR SUPPLEMENT OBJECTIVES INCLUDE: 1) IDENTIFY AND FINALIZE KEY RESEARCH TEAM MEMBERS, CORES, AND INFRASTRUCTURE, 2) CONDUCT PRELIMINARY RESEARCH TO FINALIZE AN INTEGRATED BIOLOGICAL MODEL RELATED TO CRCI AND INTERVENTIONS, AND 3) FINALIZE AN OVERARCHING THEORETICAL FRAMEWORK, SYNERGY, AND RESEARCH PROJECTS. KEY DELIVERABLES INCLUDE FINALIZED: 1) PROJECT PIS/MPIS, 2) EAB MEMBERS, 3) CORES, 4) INFRASTRUCTURE PARTNERSHIPS, 5) BIOLOGICAL SIGNATURES AND INTEGRATED MODEL, 6) OVERALL THEORETICAL FRAMEWORK, 7) SYNERGY MAP, 8) 3-4 RESEARCH PROJECTS, 9) NCI PRE-SUBMISSION MEETING, AND 10) NEW PRELIMINARY DATA PUBLICATIONS. WE ARE CONFIDENT THAT WE WILL MEET THESE DELIVERABLES AND SUBMIT OUR APPLICATION IN SEPTEMBER, 2026.

ATTENTION-DRIVEN ENHANCEMENT OF VISUAL TRAINING IN CORTICAL BLINDNESS

COMPONENTS OF EFFECTIVE SUICIDE PREVENTION IN THE USAF

TELEMEDICINE ENHANCED ASTHMA MANAGEMENT - UNITING PROVIDERS FOR TEENS (TEAM-UP FOR TEENS)

TRAINING GRANT IN VISION SCIENCE

ULTRASOUND IMAGING OF BREAST BY USE OF A HEMISPHERIC ARRAY AND INVERSE SCATTERING

NON-INVASIVE, LIVING HISTOLOGY OF CAPILLARY STRUCTURE AND SINGLE CELL BLOOD FLOW IN MOUSE MODEL OF DIABETIC RETINOPATHY

LIPID DROPLETS AS PROTEIN SEQUESTRATION SITES

POST-DOCTORAL TRAINING IN SUICIDE PREVENTION RESEARCH

T CELL MIGRATION AND CARDIOVASCULAR TOXICITY IN IMMUNOTHERAPY

SIRT6 AND VASCULAR ENDOTHELIAL HOMEOSTASIS

THE NEURAL MECHANISMS OF HYPERTENSION

EFFECTS OF TCDD ON T LYMPHOCYTE DIFFERENTIATION

THE FUNCTIONAL ROLE OF CORTICOGENICULATE FEEDBACK IN VISION

ROCHESTER PREVENTION RESEARCH CENTER

THE ROLE OF THE ORGAN OF CORTI FOR COCHLEAR POWER TRANSMISSION

NRSA TRAINING CORE

SIGNAL TRANSDUCTION MECHANISMS THAT MEDIATE NORMAL AND PATHOLOGIC ANGIOGENESIS

RESEARCH TRAINING IN PREVENTIVE CARDIOLOGY

ASSESSING TELE-HEALTH OUTCOMES IN MULTIYEAR EXTENSIONS OF PARKINSON'S DISEASE TRIALS-2 (AT-HOME PD-2) - THE COVID-19 PANDEMIC HAS DISRUPTED CLINICAL RESEARCH AND HIGHLIGHTED THE VALUE OF PATIENT CENTERED RESEARCH METHODS THAT ENABLE PARTICIPATION FROM THE HOME AND COLLECTION OF DATA DIRECTLY FROM PARTICIPANTS. SUCH DECENTRALIZED RESEARCH STUDIES THAT HARNESS VIDEO VISITS, DIGITAL TOOLS AND PARTICIPANT REPORTING, CAN REACH A LARGE, GEOGRAPHICALLY DISPERSED POPULATION OF PARTICIPANTS, INCREASE THE FREQUENCY AND SCOPE OF EVALUATION, AND REDUCE THE BURDEN OF PARTICIPATION. PARKINSON’S DISEASE, A CLINICALLY HETEROGENEOUS NEURODEGENERATIVE DISORDER THAT CAUSES PROGRESSIVE DISABILITY, IS WELL SUITED TO SUCH A MODEL. TRADITIONAL ASSESSMENTS ARE TYPICALLY SUBJECTIVE, INSENSITIVE TO CHANGE, AND LIMITED TO EPISODIC ADMINISTRATION AND THEREFORE FAIL TO CAPTURE THE COMPLEXITY OF PARKINSON’S DISEASE. AT-HOME PD, THE LARGEST ON-GOING DECENTRALIZED LONGITUDINAL OBSERVATIONAL PARKINSON’S DISEASE STUDY WITH DIGITAL TOOLS, IS REMOTELY CHARACTERIZING ~225 PARTICIPANTS WITH PARKINSON’S DISEASE FROM TWO NINDS-FUNDED, PHASE 3 CLINICAL TRIALS, STEADY-PD III AND SURE-PD3. THESE STUDIES YIELDED COHORTS WITH COMPREHENSIVE CLINICAL PHENOTYPING, WHOLE GENOME SEQUENCING, AND SERIAL PLASMA COLLECTION. AT-HOME PD PARTICIPANTS ARE BEING CHARACTERIZED THROUGH VIDEO VISITS, SMARTPHONE-BASED ASSESSMENTS, AND AN ONLINE SURVEY PLATFORM. THE COHORT IS NOW APPROACHING MID-STAGE PARKINSON’S DISEASE, PRESENTING AN OPPORTUNITY TO ADVANCE OUR UNDERSTANDING OF THIS UNDER-STUDIED POPULATION, IMPROVE THE PREDICTION OF CLINICALLY RELEVANT DISEASE MILESTONES LIKE FALLS AND COGNITIVE IMPAIRMENT, QUANTIFY PHYSICAL ACTIVITY, AND IDENTIFY SENSITIVE REMOTE DISEASE MEASURES. THIS PROJECT WILL EXTEND THE FOLLOW-UP OF THIS COHORT BY 3 YEARS AND EXPAND DIGITAL PHENOTYPING OF PARTICIPANTS, USING SMARTPHONE-BASED ASSESSMENTS AND TWO WRIST-WORN SENSORS. THE AIMS OF THIS PROJECT ARE TO 1) EVALUATE THE EXTENT TO WHICH DIGITAL TOOLS AND REMOTE PARTICIPANT REPORTING CAN IMPROVE THE PREDICTION OF CLINICALLY RELEVANT DISEASE MILESTONES COMPARED WITH TRADITIONAL MEASURES, 2) QUANTIFY LONGITUDINAL CHANGE IN PHYSICAL ACTIVITY, STEPS TAKEN, AND GAIT IN MID-STAGE PARKINSON’S DISEASE IN THE REAL-WORLD, AND 3) EXPLORE THE RELATIONSHIP BETWEEN PHYSICAL ACTIVITY AND CLINICAL OUTCOMES IN MID-STAGE PARKINSON’S DISEASE. WE WILL GENERATE A DATASET WITH APPROXIMATELY 10 CONTINUOUS YEARS OF DATA ON PD PROGRESSION THAT BEGINS PRIOR TO USE OF DOPAMINERGIC MEDICATIONS AND PROGRESSES TO MIDSTAGE PARKINSON’S DISEASE AND BEYOND. THIS RICH DATASET WILL ACCELERATE THERAPEUTIC DEVELOPMENT BY FILLING KNOWLEDGE GAPS IN THE MID-STAGE PARKINSON’S DISEASE POPULATION, HELPING TO OPTIMIZE MODELS FOR CONDUCTING PATIENT-CENTERED REMOTE RESEARCH, EVALUATING NEW METHODS FOR PREDICTING DISEASE OUTCOMES, AND EVALUATING REMOTE OUTCOME MEASURES.

ACCELERATING VISION RESTORATION WITH IN-VIVO CELLULAR IMAGING OF RETINAL FUNCTION

PIRE: DUST STIMULATED DRAWN-DOWN OF ATMOSPHERIC CO2 AS A TRIGGER FOR NORTHERN HEMISPHERE GLACIATION

RAMAN SPECTROSCOPIC PLATFORM FOR TRANSCUTANEOUS MONITORING OF BONE QUALITY

CHIP-SCALE INTEGRATED COMB-BASED HYPERSPECTRAL TENSOR CORE

VASCULAR INFLAMMATION AND ATHEROSCLEROSIS

THE EVOLUTIONARY AND FUNCTIONAL GENOMICS OF SATELLITE DNA

OXIDATIVE STRESS AND VASCULAR SMOTH MUSCLE CELL GROWTH

FOLDING RNA: FROM AIDS TO THE HUMAN GENOME

MUCOSAL IMMUNITY TO TOXOPLASMA GONDII

NEUTROPHIL-ENDOTHELIAL INTERACTIONS AND BARRIER FUNCTION IN SEPSIS

UNDERSTAND BIOLOGICAL FACTORS UNDERLYING EARLY CHILDHOOD CARIES DISPARITY FROM THE ORAL MICROBIOME IN EARLY INFANCY - SUMMARY EARLY CHILDHOOD CARIES (ECC) IS THE MOST COMMON CHRONIC CHILDHOOD DISEASE. ALTHOUGH LARGELY PREVENTABLE, ECC AFFECTS ONE THIRD OF SOCIOECONOMICALLY DISADVANTAGED AND RACIAL/ETHNIC MINORITY PRESCHOOL CHILDREN IN THE US. EFFECTIVELY REDUCING ECC DISPARITY REQUIRES A BETTER UNDERSTANDING OF ITS BIOLOGICAL FACTORS FROM BIRTH TO EARLY CHILDHOOD INCLUDING IDENTIFYING DIFFERENTIAL EXPOSURE TO RISK FACTORS BY RACE AND SOCIOECONOMIC STATUS. WHILE ECC IS AN INFECTIOUS DISEASE INITIATED BY THE ORAL MICROBIOTA (BACTERIA AND FUNGI), THE INTERPLAY BETWEEN HOST, ENVIRONMENT, AND ORAL MICROBIOTA AFFECTS THE ONSET AND SEVERITY OF ECC. HOWEVER, TO DATE, FEW STUDIES HAVE EXAMINED THE EARLY-LIFE LONGITUDINAL DEVELOPMENT OF ORAL MICROBIOTA IN UNDERSERVED CHILDREN, AND NONE HAVE UTILIZED COMPREHENSIVE METHODS TO EXAMINE MULTIPLATFORM (HOST AND ENVIRONMENTAL) FACTORS THAT CONTRIBUTE TO THE ESTABLISHMENT OF CARIOGENIC MICROFLORA AND ONSET OF ECC AMONG THE UNDERSERVED CHILDREN. ORAL MICROBIOME IN EARLY INFANCY (OMEI) STUDY WILL ADDRESS THIS URGENT NEED TO UNDERSTAND BIOLOGICAL FACTORS RELATED TO ECC AMONG UNDERSERVED RACIAL/ETHNIC MINORITY GROUPS. THE OMEI LEVERAGES A RECENTLY ARCHIVED BIRTH COHORT THAT COMPROMISES 160 LOW-INCOME MINORITY INFANTS (PRIMARILY BLACK/AFRICAN AMERICAN) AND A COMPREHENSIVE COLLECTION OF MEDICAL/ORAL HEALTH RECORDS AND ~1760 SALIVARY/SUPRAGINGIVAL SAMPLES (OBTAINED VIA NIDCR KL2TR001999 AND K23DE027412, PI: XIAO). THE OMEI BUILDS UPON OUR PREVIOUS WORK THAT 1) REVEALED RACIAL BACKGROUND IS ASSOCIATED WITH EARLY-LIFE ORAL MICROBIOME DEVELOPMENT IN THE CONTEXT OF ECC; 2) DEMONSTRATED ORAL BACTERIAL-FUNGAL CROSS-KINGDOM INTERACTIONS AND THEIR ASSOCIATIONS WITH ECC; 3) IDENTIFIED HUMAN GENES RELATED TO HOST-S. MUTANS-DENTAL CARIES INTERACTIONS; AND 4) DEVELOPED MACHINE-LEARNING PREDICTION MODELS FOR ECC. IN AIM 1, WE WILL USE METAGENOMIC ANALYSIS TO DEFINE THE CRITICAL ASSEMBLY AND FUNCTIONAL DEVELOPMENT OF THE ORAL MICROBIOME (BACTERIA AND FUNGI) IN EARLY INFANCY (BIRTH TO TWO YEARS) AMONG ALL INFANTS AND THEIR RESPECTIVE RACIAL GROUPS. IN AIM 2, WE WILL USE COMPUTATIONAL MODELING TO IDENTIFY DETERMINANTS (MATERNAL, GENETIC, AND IMMUNE FACTORS) OF INFANTS’ ORAL MICROBIOME DEVELOPMENT. IN AIM 3, WE WILL USE HIGH- DIMENSIONAL STATISTICAL MACHINE LEARNING APPROACHES TO INTEGRATE MULTI-PLATFORM (MATERNAL, MICROBIAL, GENETIC, IMMUNE, AND ENVIRONMENTAL) DATA TO IDENTIFY BIOLOGICAL FACTORS UNDERLYING ECC ETIOPATHOGENESIS AND DEVELOP ECC PREDICTION MODELS. THE OMEI WILL BE THE FIRST STUDY THAT EXAMINES THE EARLY-LIFE BIOLOGICAL FACTORS UNDERLYING ECC DISPARITY FROM AN INFANTS’ ORAL MICROBIOME PERSPECTIVE. RISK FACTORS REVEALED FROM OMEI COULD BE USED AS TARGETS FOR ECC EARLY PREDICTION AND PREVENTION SPECIFICALLY SUITABLE FOR UNDERSERVED CHILDREN. AN INTEGRATED HEALTH DISPARITIES RESEARCH TEAM WITH INVESTIGATORS FROM MULTIPLE DISCIPLINES (MICROBIOME, PERINATAL ORAL HEALTH, METAGENOMIC SEQUENCING, HIGH-DIMENSIONAL BIOSTATISTICS, GENETICS, AND HEALTH DISPARITIES), TOGETHER WITH AN OUTSTANDING INTERNAL-EXTERNAL ADVISORY COMMITTEE, WILL ENSURE THE SUCCESS OF THE PROPOSED OMEI PROJECT.

DELINEATING THE ROLE OF TIMP3 IN MACULAR DEGENERATION

OXIDATIVE STRESS IN ORAL STREPTOCOCCI

PARA-VASCULAR BASIS OF SMALL VESSEL DISEASE

SENSORY ORGAN FORMATION IN THE INNER EAR

OPTIMIZING FUNCTIONAL OUTCOMES OF OLDER SURVIVORS AFTER CHEMOTHERAPY

PEER-LED SUICIDE PREVENTION: PROMOTING HEALTHY FAMILY ROLE TRANSITIONS FOR MILITARY PERSONNEL

STRENGTHENING EFFECTIVENESS, IMPLEMENTATION DISCOVERY IN A SUICIDE PREVENTION RCT

THE PREVALENCE AND MECHANISM OF SELECTIVITY IN BASAL AUTOPHAGY

STRONG MEMORIAL HOSPITAL CCBHC EXPANSION - STRONG MEMORIAL HOSPITAL CCBHC EXPANSION THIS PROJECT EXPANDS THE STRONG MEMORIAL HOSPITAL CERTIFIED COMMUNITY BEHAVIORAL HEALTH CLINIC'S ABILITY TO PROVIDE THE FULL RANGE OF 24/7 BEHAVIORAL HEALTH PHONE CRISIS SERVICES PROVIDED BY MASTER'S PREPARED CRISIS CLINICIANS AND PROVIDE ACCESSIBILITY TO DIRECT CLINICAL SUBSTANCE USE DISORDER TREATMENT IN COMMUNITY BASED PRIMARY CARE SETTINGS THROUGHOUT THE REGION. THE FOCUS OF THIS PROJECT IS TO PROVIDE IMMEDIATELY AVAILABLE CRISIS SUPPORT FOR PERSONS WHO ARE MOST MOTIVATED TO SEEK HELP WHEN IN ACTIVE CRISIS. THROUGH 24/7 PHONE ACCESS TO MASTER'S PREPARED CLINICIANS TRAINED IN EVIDENCE-BASED SCREENING AND ASSESSMENT TOOLS INCLUDING MOTIVATIONAL INTERVIEWING FOR MENTAL HEALTH AND SUBSTANCE USE DISORDERS AND ABILITY TO CONNECT DIRECTLY TO THE APPROPRIATE LEVEL OF FOLLOW-UP BASED ON A CLINICAL ASSESSMENT, INCLUDING DISPATCH OF A MOBILE CLINICAL TEAM, OR APPOINTMENTS. IN COMMUNITY BASED PRIMARY CARE SETTINGS AS WELL AS OTHER HEALTH SYSTEM BASED SETTINGS THE PROJECT WILL ENGAGE AN ADDITIONAL 200 PATIENTS A YEAR FOR EACH OF TWO YEARS INTO TREATMENT WHO HAVE NEVER BEEN OR NOT BEEN IN TREATMENT IN PAST 12 MONTHS. THE PROJECT PROPOSES TO USE THE CCBHC EXPANSION GRANT TO FUND POSITIONS THAT ARE NOT REIMBURSABLE SUCH AS THE CRISIS CALL CENTER STAFF, BUT WHO COULD BE SUPPORTED THROUGH INCREASE IN CLINIC ENROLLMENT AND RECEIVING FULL RANGE OF CCBHC REQUIRED SERVICES UNDER THE PPS REIMBURSEMENT MODEL. IT ALSO PROPOSES TO USE THE FUNDS TO SUPPORT THE INFRASTRUCTURE REQUIRED TO DEVELOP THIS EXPANSION TO TRULY MEET PATIENTS, NOT READILY AMENABLE TO 'STANDARD TREATMENT MODELS', WHERE THEY ARE TO FACILITATE TIMELY ASSESSMENT, INTERVENTION, ENGAGEMENT IN TREATMENT TO BUILD RESILIENCE AND ABILITY TO RECOVER THEIR FULL POTENTIAL. THE INTEGRATION OF MENTAL HEALTH, SUBSTANCE USE DISORDER AND PHYSICAL HEALTH SCREENING, MONITORING AND INTERVENTION IS AT THE CORE OF OUR STRONG MEMORIAL HOSPITAL CCBHC AND THIS EXPANSION PROPOSAL BRINGS THIS RANGE OUTSIDE OF THE 'BRICKS AND MORTAR' OF THE PHYSICAL CLINIC INTO THE COMMUNITY AND REGION WE SERVE. THE PROJECT IS DESIGNED TO BE A COMPREHENSIVE, CENTRALIZED, DEPLOYABLE RESOURCE TO SUPPORT THE TREATMENT OF CO-OCCURRING SUBSTANCE USE AND MENTAL HEALTH DISORDERS IN THE HEALTH SYSTEM THROUGHOUT THE FINGER LAKES AND SOUTHERN TIER REGIONS OF NEW YORK STATE WHERE BEHAVIORAL HEALTH SERVICES ARE LIMITED. THE CCBHC EXPANSION PROJECT WILL DELIVER CARE THROUGH THE FOLLOWING SERVICE DELIVERY MODELS: 1) CENTRALIZED TRIAGE AND TELEMEDICINE FROM THE CURRENT CCBHC SITE LOCATION, 2) A MOBILE CLINIC MODEL DISPATCHING CLINICIANS DIRECTLY TO PATIENTS TO DELIVER CARE (E.G. AT THEIR PCP, IN THE HOSPITAL, AT A COMMUNITY AGENCY OR CENTER, ETC.) AND 3) A 24-HOUR CRISIS HOTLINE. THE CLINICAL TEAMS OF THE CCBHC EXPANSION PROJECT WILL USE TELEMEDICINE TO DELIVER CARE WHEN APPROPRIATE. THE 24/7 CRISIS HOTLINE WOULD BE AVAILABLE TO CCBHC PATIENTS AND RESPOND TO AND/OR TRIAGE ANY SUBSTANCE USE AND/OR MENTAL HEALTH CRISIS.

ACTÍVATEXTO: ADVANCING SMOKING CESSATION AND PHYSICAL ACTIVITY AMONG LATINOS - PROJECT SUMMARY OVERCOMING THE BURDEN OF TOBACCO USE AMONG LATINOS DEMANDS INNOVATIVE, EFFECTIVE, ACCESSIBLE, CULTURALLY APPROPRIATE, AND COMMUNITY-ENGAGED SOLUTIONS. OVER THE PAST EIGHT YEARS, IN PARTNERSHIP WITH THE LATINOS CONTRA EL TABACO (SPANISH FOR: LATINOS AGAINST TOBACCO) COMMUNITY ADVISORY BOARD (CAB), OUR TEAM HAS DEVELOPED DECÍDETEXTO, THE FIRST CULTURALLY-ACCOMMODATED SMOKING CESSATION TEXT MESSAGING INTERVENTION FOR LATINOS (AVAILABLE IN ENGLISH AND SPANISH). OUR RECENTLY COMPLETED RANDOMIZED CONTROLLED TRIAL (RCT; N=457) DEMONSTRATED THAT LATINOS RECEIVING THE DECÍDETEXTO INTERVENTION WERE SIGNIFICANTLY MORE LIKELY THAN THOSE RECEIVING STANDARD OF CARE (SMOKING CESSATION PRINTED MATERIALS) TO BE SMOKING ABSTINENT AT MONTH 6 (34.1% VS 20.6%; P<0.001). DESPITE THE PROVEN EFFICACY OF DECÍDETEXTO AMONG LATINOS, WE DID NOT ADDRESS THE FACT THAT 75% OF PARTICIPANTS DID NOT MEET THE RECOMMENDED LEVELS OF PHYSICAL ACTIVITY [AT LEAST 150 MINUTES OF MODERATE TO VIGOROUS PHYSICAL ACTIVITY (MVPA) PER WEEK]. MOREOVER, WE DID NOT LEVERAGE THE POTENTIAL ROLE OF PHYSICAL ACTIVITY IN ENHANCING CESSATION RATES DESPITE EVIDENCE SUGGESTING THAT MVPA MAY ENHANCE CESSATION RATES. THUS, WE DEVELOPED ACTÍVATEXTO, AN INNOVATIVE MOBILE INTERVENTION THAT INCORPORATES PHYSICAL ACTIVITY INTO THE DECÍDETEXTO INTERVENTION. SPECIFICALLY, ACTÍVATEXTO INTEGRATES FOUR COMPONENTS: 1) A TEXT MESSAGING PROGRAM THAT PROMOTES BOTH SMOKING CESSATION AND PHYSICAL ACTIVITY, 2) WEARABLE DEVICES TO MONITOR PHYSICAL ACTIVITY, 3) SMOKING CESSATION PHARMACOTHERAPY (I.E., NICOTINE REPLACEMENT THERAPIES), AND 4) AN ONLINE DASHBOARD WHERE THE RESEARCH TEAM MANAGES PARTICIPANTS’ INCOMING AND OUTGOING DATA FROM BOTH THE TEXT MESSAGING PROGRAM AND WEARABLE DEVICES. PILOT TESTED AMONG LATINOS WHO SMOKE AND DO NOT MEET THE RECOMMENDED LEVELS OF PHYSICAL ACTIVITY (N=20), ACTÍVATEXTO GENERATED HIGH SATISFACTION, INCREASED MINUTES OF MVPA PER WEEK, AND RESULTED IN NOTEWORTHY CESSATION RATES (70% OF PARTICIPANTS WERE SMOKING ABSTINENT AT MONTH 3). OUR MULTIDISCIPLINARY TEAM IS UNIQUELY POISED TO CONDUCT THE FIRST COMPREHENSIVE RESEARCH EFFORT TO STUDY THE SYNERGISM OF SMOKING CESSATION AND PHYSICAL ACTIVITY IN A MOBILE INTERVENTION AMONG LATINOS. WE WILL USE A HYBRID TYPE I EFFECTIVENESS- IMPLEMENTATION RESEARCH DESIGN TO ASSESS THE EFFICACY OF ACTÍVATEXTO AND THE BARRIERS AND FACILITATORS OF ITS IMPLEMENTATION. SPECIFIC AIMS ARE: AIM 1. ASSESS THE EFFICACY OF ACTÍVATEXTO, A MOBILE INTERVENTION THAT PROMOTES BOTH SMOKING CESSATION AND PHYSICAL ACTIVITY, COMPARED TO A MOBILE INTERVENTION THAT SOLELY PROMOTES SMOKING CESSATION, ON SMOKING ABSTINENCE AT MONTH 6 AMONG LATINOS. AIM 2. ASSESS PHYSICAL ACTIVITY, SELF-EFFICACY, AND PERCEIVED STRESS AS MEDIATORS OF THE PRESUMED TREATMENT EFFECT ON COTININE-VERIFIED 7-DAY POINT PREVALENCE ABSTINENCE AT MONTH 6 AMONG LATINOS. AIM 3. EXAMINE THE BARRIERS AND FACILITATORS TO IMPLEMENT ACTÍVATEXTO AMONG LATINOS.

APPLICATIONS OF SLOW LIGHT IN OPTICAL FIBERS

ROCHESTER BRIDGES TO THE DOCTORATE FOR DEAF AND HARD OF HEARING STUDENTS

COORDINATION AND STATISTICS FOR COQ10 IN PD IN PHASE 3

CONTRIBUTION OF INCREASED VDR AND CAR TO HYPERCALCIURIA IN THE GHS RAT

TRANSCRIPTIONAL PROFILING TO DISCRIMINATE BACTERIAL AND NON-BACTERIAL RESPIRATORY ILLNESSES

CAPACITY BUILDING ASSISTANCE (CBA) FOR HEALTH DEPARTMENTS PROGRAM

CLINICAL AND BASIC SCIENCE STUDIES IN LONG QT SYNDROME TYPE 3

ESTIMATES OF INFLUENZA VACCINE EFFECTIVENESS

DEVELOPMENT AND EVALUATION OF AN EVIDENCE-BASED MOBILE HEALTH CAREGIVER INTERVENTION FOR FASD

BRAIN SIGNATURE OF SARS-COV-2 INFECTION AND ITS IMPACT ON LONG-TERM COGNITIVE FUNCTIONING IN OLDER ADULTS - SEVERAL REPORTS HAVE HIGHLIGHTED THE PRESENCE OF COGNITIVE AND PSYCHIATRIC MANIFESTATION ASSOCIATED WITH SEVERE ACUTE RESPIRATORY SYNDROME-CORONAVIRUS 2 (SARS-COV-2) INFECTION. AUTOPSY AND CSF STUDIES SUGGEST THAT COVID-19 ASSOCIATED INJURY OF THE CENTRAL NERVOUS SYSTEM DERIVES FROM A COMBINATION OF COAGULOPATHY, ENDOTHELIAL INJURY WITH SUBSEQUENT ALTERATION OF THE BLOOD BRAIN BARRIER, INFECTION AND ACTIVATION OF MICROGLIA AND MACROPHAGES FOLLOWED BY RELEASE OF CYTOKINES. THE NEUROCOGNITIVE SYMPTOMS MAY PERSIST IN THE SUBACUTE PHASE OF THE RECOVERY WHILE IT REMAINS TO BE DETERMINED WHAT THE LONG-TERM EFFECTS WILL BE. THE DOCUMENTED INVOLVEMENT OF THE BRAIN MICROCIRCULATION BY SARS-COV-2 INFECTION, IS LIKELY TO CONTRIBUTE TO CEREBRAL SMALL VESSEL DISEASE (CSVD). CSVD PATHOGENESIS IS NOT FULLY UNDERSTOOD AND IS LIKELY MULTIFACTORIAL. AMONG THE FACTORS THAT MAY LINK COVID-19 TO CSVD ARE DIRECT INJURY TO ENDOTHELIAL CELLS, PLATELETS AND LEUKOCYTE ACTIVATION. THESE PROCESSES CAN THEN LEAD TO AN ALTERED BLOOD BRAIN BARRIER (BBB) WITH INCREASED CROSSING OF ACTIVATED MONOCYTES INTO THE BRAIN PARENCHYMA. CSVD IS CLINICALLY QUITE RELEVANT SINCE IT IS A LEADING CAUSE OF COGNITIVE IMPAIRMENT AND DEMENTIA. THERE ARE SEVERAL UNKNOWNS THAT JUSTIFY THE IMPLEMENTATION OF THIS PROPOSAL. WE DO NOT KNOW WHETHER THERE IS AN INCREASED BURDEN OF CSVD IN THOSE OLDER ADULTS WHO HAVE BEEN INFECTED BY SARS-COV-2 AND WHETHER THERE WILL BE AN ACCELERATED PROGRESSION OF CSVD IN THIS POPULATION. IT IS ALSO UNCLEAR WHETHER THE INITIAL ENDOTHELIAL DYSFUNCTION INDUCED BY THE INFECTION MAY PERSIST IN A MILDER FORM THAT IS SUFFICIENT TO MAINTAIN A CHRONICALLY ALTERED CEREBRAL MICROCIRCULATION. IF THIS OCCURS, IT WILL CONTRIBUTE TO SEVERAL NEURODEGENERATIVE DISORDERS INCLUDING VASCULAR DEMENTIA AND ALZHEIMER DISEASE. IN THIS PROPOSAL, WE WILL FOCUS ON OLDER INDIVIDUALS AGED BETWEEN =65 AND 80, WHO WERE INFECTED WITH SARS- COV-2 AT LEAST SIX MONTHS PRIOR TO STUDY ENROLMENT, WHO WERE HOSPITALIZED BUT NOT ADMITTED TO A CRITICAL CARE UNIT AND DID NOT HAVE A SIGNIFICANT NEUROLOGICAL HISTORY PRIOR TO SARS-COV-2 INFECTION. WE WILL MATCH BY AGE AND SEX, 150 COVID-19 PATIENTS WITH 150 CONTROLS WHO WILL BE FOLLOWED FOR TWO YEARS. CSVD WILL BE ASSESSED VIA STATE- OF THE-ART MAGNETIC RESONANCE MULTIMODALITY IMAGING. WE WILL ADDRESS THE SPECIFIC AIMS LISTED BELOW. AIM 1: TO ASSESS THE SEVERITY AND PROGRESSION OF CSVD IN INDIVIDUALS PREVIOUSLY INFECTED BY SARS-COV-2 COMPARED TO AGE AND SEX MATCHED CONTROLS. SUB-AIM 1: TO ASSESS THE IMPACT OF SARS-COV-2 ON BRAIN MICROSTRUCTURE INTEGRITY. AIM 2: TO ASSESS IN INDIVIDUALS PREVIOUSLY INFECTED BY SARS-COV-2, COMPARED TO CONTROLS, CHANGES IN CEREBROVASCULAR FUNCTION AND ITS ASSOCIATION TO PERIPHERAL MAKERS OF ENDOTHELIAL FUNCTION AND ALTERED BLOOD BRAIN BARRIER. AIM 3: TO ASSESS CHANGES IN COGNITIVE PERFORMANCE AND ITS RELATION TO IMAGING METRICS IN INDIVIDUALS PREVIOUSLY INFECTED BY SARS-COV-2 COMPARED TO CONTROLS.

MITOCHONDRIAL ROS MICRODOMAINS AND NEURONAL ISCHEMIA