Yale University

INSULIN RESISTANCE INTERVENTION AFTER STROKE TRIAL

CLINICAL AND TRANSLATIONAL SCIENCE AWARD

DATA COORDINATION CENTER FOR THE RMN

YALE UNIVERSITY CLINICAL AND TRANSLATIONAL SCIENCE AWARD PROGRAM

GRADUATE RESEARCH FELLOWSHIP PROGRAM

EXPERMENTAL STUDIES

MEDICAL SCIENTIST TRAINING PROGRAM

PSYCHOTHERAPY DEVELOPMENT RESEARCH CENTER

GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP)

YALE TOBACCO CENTER OF REGULATORY SCIENCE

PERUVIAN/BRAZILIAN AMAZON CENTER OF EXCELLENCE IN MALARIA

TAS::89 0222::TAS; NEW; RELATIVISTIC HEAVY ION PHYSICS; PI - JOHN HARRIS

REGULATION OF LIVER BY NUCLEAR CA2+ SIGNALING

MOLECULAR MECHANISMS OF ARTERIGENESIS

CONSUMER ASSESSMENT OF HEALTHCARE PROVIDERS AND SYSTEMS

RESEARCH IN ELEMENTARY PARTICLES AND INTERACTIONS

PREDOCTORAL PROGRAM IN CELLULAR AND MOLECULAR BIOLOGY

GEORGE M O'BRIEN KIDNEY CENTER AT YALE

TOWARDS FAULT-TOLERANCE IN A HARDWARE-EFFICIENT MODULAR ARCHITECTURE

GRANT

PROGRAM IN MACROMOLECULAR STRUCTURE, MOTION, CONTROL

MATERIALS LIMITS ON COHERENCE IN CHARGE QUBITS

YALE CENTER FOR MENDELIAN GENOMICS

MOLECULAR BASIS OF VIRAL AND CELLULAR TRANSFORMATION

ERROR-CORRECTED QUANTUM REGISTERS FOR A MODULAR SUPERCONDUCTING QUANTUM COMPUTER

CELLULAR AND MOLECULAR STUDIES OF RENAL TRANSPORT

YALE TRANSDISCIPLINARY COLLABORATIVE CENTER FOR HEALTH DISPARITIES RESEARCH (YALE-TCC)

CENTER FOR INNOVATIVE STRUCTURES AND PHENOMENA

BRINGING RESEARCH TO IMPACT FOR DEVELOPMENT, GLOBAL ENGAGEMENT, AND UTILIZATION (BRIDGE-U) UNDER EXISTING SCIENCE, TECHNOLOGY, INNOVATION, AND PARTNERSHIP ANNUAL PROGRAM STATEMENT APS NO.: 7200AA18APS00003

TAS::89 0227::TAS RECOVERY ACT HIGH ENERGY PHYSICS RESEARCH, TASKS A, B, C, D, F, G, K AND J

STUDIES ON TRANSFER RNA

ADDRESSING RISK THROUGH COMMUNITY TREATMENT FOR INFECTIOUS DISEASE AND OPIOID USE DISORDER NOW (ACTION) AMONG JUSTICE-INVOLVED POPULATIONS

THIS PROJECT IS AIMED AT DEVELOPING A LOW COST NOVEL DEVICE FOR BREAST MRI. MRI IS A PROVEN MODALITY FOR IMAGING CANCERS OF THE BREAST AND THE PRIMARY FACTOR LIMITING ITS WIDESPREAD USE IS ACCESS WHICH IS LIMITED DUE TO THE HIGH COST OF MRI MACHINES AND DIFFICULT SITING DUE TO THEIR LARGE SIZE. IMPROVED ACCESS TO BREAST MRI COULD MAKE ANNUAL SCREENING AVAILABLE FOR THE MAJORITY OF WOMEN AND IN TURN THIS WOULD SAVE MANY LIVES. EARLY DETECTION OF CANCER IS A KEY TO IMPROVED OUTCOMES. INCLUDING BREAST MRIS AS PART OF AN ANNUAL EXAM FOR ALL WOMEN WOULD HAVE A MAJOR POSITIVE OUTCOME ON WOMENS HEALTH. THERE ARE NO SUBRECIPIENTS.

MECHANISMS OF SOCIAL ENGAGEMENT IN AUTISM SPECTRUM DISORDERS

1/8-PREDICTORS AND MECHANISMS OF CONVERSION TO PSYCHOSIS

YALE HEAD AND NECK CANCER SPORE: OVERCOMING TREATMENT RESISTANCE IN HEAD AND NECK CANCER

POLYCYSTIC KIDNEY DISEASE: A DISORDER OF GLOMERULOTUBULAR SYNCHRONIZATION

TARGETING BREAST CANCER BRAIN METASTASES WITH AN ANTI-DNA AUTOANTIBODY

RISK STRATIFICATION IN OLDER PERSONS WITH ACUTE MYOCARDIAL INFARCTION: SILVER-AMI

CELLULAR, MOLECULAR, AND FUNCTIONAL IMAGING APPROACHES TO UNDERSTANDING EARLY NEURODEVELOPMENT IN AUTISM

YALE CENTER FOR MENDELIAN DISORDERS

SYSTEMS ANALYSIS OF PHENOTYPIC SWITCH IN CONTROL OF CANCER INVASION

THIS PROPOSED PROJECT FOCUSES ON ESTIMATING HOW KEY FACTORS CONTRIBUTING TO EMISSIONS, AIR QUALITY AND HEALTH AFFECT REGIONAL AND LOCAL DIFFERENCES I

NEUROEXPLORER: ULTRA-HIGH PERFORMANCE HUMAN BRAIN PET IMAGER FOR HIGHLY-RESOLVED IN VIVO IMAGING OF NEUROCHEMISTRY

TRANSCRIPTIONAL ATLAS OF HUMAN BRAIN DEVELOPMENT

MECHANISMS OF BILE SECRETION AND CHOLESTASIS

WEST CAMPUS B3(WB3)VIVARIUM

STRUCTURE AND FUNCTION OF ARP 2/3 COMPLEX

MOLECULAR AND CELLULAR BASIS OF COGNITIVE AGING IN PREFRONTAL CORTICAL NETWORKS

LINKS BETWEEN PRODUCTION AND PERCEPTION IN SPEECH

FATTY ACID AMIDE HYDROLASE (FAAH) INHIBITOR TREATMENT OF CANNABIS USE DISORDER (CUD)

A SYSTEMS APPROACH TO THE DEVELOPMENT AND FUNCTION OF C4 PHOTOSYNTHESIS

SILENT ALLOSTERIC MODULATION OF MGLUR5 FOR SAFE AND EFFECTIVE THERAPY OF ALZHEIMER'S DISEASE

STRATEGIES TO OVERCOME IMMUNE RESISTANCE IN HEAD AND NECK CANCERS

OXOMANGANESE CATALYSTS FOR SOLAR FUEL PRODUCTION

YALE ALZHEIMER DISEASE RESEARCH CENTER

PREDOCTORAL TRAINING PROGRAM IN GENETICS

YOUNG WOMEN WITH ACUTE MYOCARDIAL INFARCTION

FYN INHIBITION BY AZD0530 FOR ALZHEIMERS DISEASE

NEURONEX: THE FABRIC OF THE PRIMATE NEOCORTEX AND THE ORIGIN OF MENTAL REPRESENTATIONS. FROM TRANSCRIPTOMICS TO SINGLE NEURONS AND NEURONAL NETWORKS.

PREDICTIVE PERSONALIZED PUBLIC HEALTH (P3H): A NOVEL PARADIGM TO TREAT INFECTIOUS DISEASE

ORIGIN OF CORTICAL SPECIES-SPECIFIC DISTINCTIONS

FUNCTIONAL GENOMICS OF HUMAN BRAIN DEVELOPMENT

ALCOHOL AND MULTISUBSTANCE USE IN THE VETERANS AGING COHORT STUDY

MODERNIZATION OF THE YALE PET CORE - POSITRON EMISSION TOMOGRAPHY (PET) IS A POWERFUL IMAGING MODALITY THAT ENABLES VISUALIZATION AND QUANTIFICATION OF BIOLOGICAL FUNCTIONS USING RADIOPHARMACEUTICALS. HOWEVER, DUE TO THE SHORT HALF-LIVES OF PET ISOTOPES (E.G., 20 MINUTES FOR C-11, 2 HOURS FOR F-18), THE ENTIRE PROCESS FROM CYCLOTRON TO RADIOPHARMACEUTICAL SYNTHESIS TO QUALITY CONTROL TO INJECTION, AND IMAGING MUST BE STREAMLINED TO ENSURE EFFICIENCY AND RADIOCHEMICAL YIELD. THE RADIOPHARMACY FACILITIES AT THE YALE SCHOOL OF MEDICINE (YSM) ARE HOUSED WITHIN THE YALE PET CORE WHICH OPERATES AS A REVENUE-NEUTRAL INTER-SERVICE PROVIDER OFFERING FULL PET STUDY SERVICES EXCLUSIVELY FOR RESEARCH. THE PET CORE SERVES INVESTIGATORS IN PSYCHIATRY, NEUROLOGY, CARDIOLOGY, ENDOCRINOLOGY, AND BASIC NEUROSCIENCE. INVESTIGATORS ARE PART OF A LARGE NIH-FUNDED COMMUNITY AT YALE AND THROUGHOUT NEW ENGLAND, AS WELL AS SEVERAL INSTITUTIONS NATIONALLY THROUGH CLINICAL TRIALS RECRUITING SUBJECTS IN THE YALE PET CORE. SINCE ITS INCEPTION IN 2006, THE PET CORE HAS GROWN RAPIDLY, PERFORMING PET IMAGING RESEARCH STUDIES IN HUMANS AND A VARIETY OF ANIMAL SPECIES. OVER 1,100 SCANS ARE PROJECTED FOR 2025. DESPITE A SIGNIFICANT INCREASE IN THE NUMBER OF SCANNERS AND EFFICIENCY IN THE PET CORE, RADIOCHEMISTRY PRODUCTION CAPABILITIES HAVE NOT GROWN ACCORDINGLY. CURRENTLY, THERE ARE 7 PET SCANNERS AVAILABLE FOR ROUTINE USE, WITH MORE EXPECTED TO BE INSTALLED SHORTLY, WHILE THE RADIOPHARMACY FACILITIES WERE ORIGINALLY DESIGNED TO SUPPORT RADIOTRACER PRODUCTION FOR 3 PET SCANNERS. TO OPERATE AVAILABLE PET SCANNERS AT FULL CAPACITY, THE PET CORE WILL REQUIRE A SUBSTANTIAL INCREASE TO THE EXISTING RADIOCHEMISTRY INFRASTRUCTURE. THIS WOULD SIGNIFICANTLY REDUCE THE WAITING TIME (4-6 WEEKS) TO PERFORM A PET SCAN. FURTHERMORE, A UNIQUE OPPORTUNITY EXISTS TO EXPAND AND UPDATE THE PET CORE FACILITIES TO BRING THE RADIOPHARMACY MANUFACTURING TO 21 CFR PART 212 CURRENT GOOD MANUFACTURING PRACTICE (CGMP) FOR PET DRUG PRODUCTION. SINCE THE RADIOCHEMISTRY AND RADIOPHARMACY FACILITIES HAVE NOT UNDERGONE A MAJOR REDESIGN SINCE 2006, A SIGNIFICANT UPGRADE IS NECESSARY. THIS WILL ENABLE THE PRODUCTION OF APPROVED COMPOUNDS IN THE AREAS OF ONCOLOGY, NEURODEGENERATION AND CARDIAC IMAGING, WHILE ENABLING SHIPPING RADIOPHARMACEUTICALS FOR HUMAN USE OUTSIDE THE YALE CAMPUS. MOST IMPORTANTLY, THE EXPANSION AND UPGRADES TO THE RADIOCHEMISTRY FACILITIES WILL ENHANCE THE INVESTIGATORS’ ABILITY TO EFFICIENTLY WORK ON THE DISCOVERY AND DEVELOPMENT OF NOVEL RADIOCHEMISTRY COMPOUNDS FOCUSED ON THE DETECTION, UNDERSTANDING, AND TREATMENT OF DISEASE AND STREAMLINE TRANSLATION TO RADIOPHARMACEUTICAL PRODUCTION. THE PET CORE MULTI-PHASE RENOVATION AND EXPANSION PROJECT WILL OCCUR WITHIN THE MAGNETIC RESONANCE RESEARCH CENTER BUILDING (MRC). THE REQUESTED C06 FUNDS WILL BE USED IN THREE PHASES TO: I) BUILD A NEW RADIOCHEMISTRY/RADIOPHARMACY/QC LAB CGMP SUITE, II) UPGRADE THE EXISTING RADIOCHEMISTRY LAB TO CGMP, AND III) CONVERT THE QC LAB TO A RESEARCH HOT CHEMISTRY LAB. THIS SCOPE WILL ACCELERATE DISCOVERY AND DEVELOPMENT OF NOVEL RADIOCHEMISTRY COMPOUNDS, ENABLE SHIPPING OF PET RADIOTRACERS TO OUTSIDE ENTITIES, REDUCE WAITING TIME FOR PET IMAGING AND MAXIMIZE YALE’S UNIQUE PET RESOURCES’ REACH AND ACCESSIBILITY.

TM INTERACTIONS IN MEMBRANE PROTEIN FOLDING AND FUNCTION

TRANSFORM-HF CCC

OOCYTE DEVELOPMENT IN DROSOPHILA

ALCOHOL ASSOCIATED OUTCOMES AMONG HIV+/- AGING VETERANS

TAS::89 0222::TAS - NUCLEAR PHYSICS-EXPERIMENTAL RESEARCH

THIS AWARD IS ISSUED FOR A PROGRAM TO SUPPORT BUILDING EFFECTIVE, RESILIENT, AND TRUSTED POLICE ORGANIZATIONS IN MEXICO.

SYNDECAN FUNCTION IN ENDOTHELIAL CELLS

GENETICS OF OPIOID DEPENDENCE

GAINING EARLY AWARENESS AND READINESS FOR UNDERGRADUATE PROGRAMS (GEAR UP PARTNERSHIP)

MENTAL HEALTH NEW ENGLAND TECHNOLOGY TRANSFER CENTER (MH-NETT)

THE IDENTIFICATION AND CHARACTERIZATION OF GENETIC VARIANTS UNDERLYING CARDIOVASCULAR DISEASES

PATHOGENESIS OF YOUTH ONSET PRE DIABETES AND TYPE 2 DIABETES.

EVOLUTIONARY GENETICS OF TSETSE AND ITS SYMBIONTS

THIS COOPERATIVE AGREEMENT SHALL BE PERFORMED IN ACCORDANCE WITH STATEMENT OF WORK, ENTITLED 'IDEAL: AN INTELLIGENT DESIGN ENVIRONMENT FOR ASYNCHRONO

EMBED: PRAGMATIC TRIAL OF USER-CENTERED CLINICAL DECISION SUPPORT TO IMPLEMENT EMERGENCY DEPARTMENT-INITIATED BUPRENORPHINE FOR OPIOID USE DISORDER

RF CONTROL AND MEASUREMENT OF SUPERCONDUCTING QUBITS

GEAR-UP

BII: PREDICTING THE GLOBAL HOST-VIRUS NETWORK FROM MOLECULAR FOUNDATIONS -THE VIRAL EMERGENCE RESEARCH INITIATIVE BIOLOGY INTEGRATION INSTITUTE (VERENA BII) WILL INTEGRATE DATA AND BIOLOGICAL THEORY ACROSS THE FIELDS OF MICROBIOLOGY, IMMUNOLOGY, ECOLOGY, EVOLUTION, AND GLOBAL CHANGE BIOLOGY, WORKING TOWARDS A UNIFIED UNDERSTANDING THAT IMPROVES OUR ABILITY TO PREDICT VIRAL EMERGENCE. THE COVID-19 PANDEMIC HIGHLIGHTS A PRESSING NEED TO UNDERSTAND THE ECOLOGY AND EVOLUTION OF EMERGING VIRUSES. THESE GLOBAL DYNAMICS ARE DETERMINED FIRST AND FOREMOST BY THE GENETIC CODE OF BOTH VIRUSES AND THEIR HOSTS, AND BY MICROSCOPIC INTERACTIONS BETWEEN THE TWO AT THE LEVEL OF PROTEINS AND CELLS. HOWEVER, BIOLOGISTS FREQUENTLY STRUGGLE TO CONNECT THEORY ACROSS THESE SCALES. AT THE HEART OF THIS RESEARCH EFFORT IS AN OPEN CLEARINGHOUSE OF BIG DATA, CREATING NEW OPPORTUNITIES TO APPLY ARTIFICIAL INTELLIGENCE TO REAL-WORLD PROBLEMS. TO FOSTER A CORE SET OF DATA FLUENCY AND INTERDISCIPLINARY RESEARCH SKILLS, THE LIGHTHOUSE LEARNING COMMUNITY WILL TRAIN PARTICIPANTS AT EVERY CAREER STAGE IN THE BOUNDARY-SPANNING SCIENCE OF THE HOST-VIRUS NETWORK, INCLUDING MORE THAN 100 EARLY CAREER SCIENTISTS. UNDERGRADUATES WILL BE INTRODUCED TO BOTH BIOLOGY AND DATA SCIENCE THROUGH A COURSE-BASED UNDERGRADUATE RESEARCH EXPERIENCE IN ?THE FUNDAMENTALS OF DISEASE SURVEILLANCE,? WHILE GRADUATE STUDENTS AND POSTDOCTORAL FELLOWS WILL EXPLORE THESE METHODS DEEPER THROUGH A BIOLOGY INTEGRATION WORKSHOP SERIES, INCLUDING A NEW SUMMER IN THE CAPITOL PROGRAM IN WASHINGTON, D.C. THIS COHORT OF EMERGING SCHOLARS WILL USE OPEN SOURCE MATERIALS, K-12 OUTREACH, AND DIGITAL MEDIA TO HARNESS PUBLIC INTEREST IN EMERGING DISEASES LIKE COVID-19, RAISING AWARENESS ABOUT KEY ISSUES WHILE SHARING THE IMPORTANCE OF BASIC BIOLOGICAL RESEARCH TO SAVE LIVES AND PROTECT ECOSYSTEMS. TO IDENTIFY THE MECHANISTIC AND MOLECULAR RULES OF LIFE THAT GOVERN HOST-VIRUS DYNAMICS AT PLANETARY SCALES, THE VERENA BII WILL LEVERAGE A UNIQUE MIX OF DATA SYNTHESIS, COMPUTATIONAL INNOVATION, FIELD SAMPLING, AND LABORATORY EXPERIMENTS TO IDENTIFY THE MOLECULAR UNDERPINNINGS OF HOST-VIRUS INTERACTIONS. AN UNPRECEDENTED COMPARATIVE STUDY OF THE CHIROPTERAN WITHIN-HOST ENVIRONMENT WILL GENERATE AND TEST HYPOTHESES ABOUT THE IMMUNOLOGICAL ADAPTATIONS THAT ALLOW BATS TO TOLERATE DEADLY VIRUSES. IN PARALLEL, MODEL-GUIDED EXPERIMENTS WILL MEASURE THE FEATURES OF THE INVERTEBRATE IMMUNE SYSTEM THAT PLAY THE GREATEST ROLE IN MOSQUITOES? COMPETENCE AS ARBOVIRAL VECTORS. TOGETHER, THESE MODEL SYSTEMS WILL ILLUMINATE THE HARD-CODED BASIS OF HOST-VIRUS COMPATIBILITY, SUPPORTING NEW MACHINE LEARNING METHODS TO PREDICT ECOLOGICAL AND EVOLUTIONARY NETWORKS AND ANTICIPATE GLOBAL RISKS OF VIRAL EMERGENCE IN A CHANGING CLIMATE. MORE BROADLY, THE VERENA BII WILL EXPAND AN EXISTING ROLE AS A HUB OF OPEN DATA, SOFTWARE, AND CYBERINFRASTRUCTURE FOR HOST-VIRUS INTERACTIONS, EXPERIMENTAL VIROLOGY, AND WILDLIFE DISEASE SURVEILLANCE. 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.

MOLECULAR GENETIC ANALYSIS OF SALMONELLA CELL INVASION

PARAMEDIC REFERRALS FOR INCREASED INDEPENDENCE AND DECREASED DISABILITY IN THE ELDERLY (PRIDE)

DNA REPAIR IN CANCER BIOLOGY AND THERAPY

INVESTIGATION OF NEUTRINO PROPERTIES AND FUNDAMENTAL SYMMETRIES AT YALE

CHRONIC DTH AND IFN-GAMMA IN HUMAN GRAFT ARTERIOSCLEROSIS

NEURAL MECHANISMS OF ITCH

FOOD CUES, STRESS, MOTIVATION FOR HIGHLY PALATABLE FOODS AND WEIGHT GAIN

HIGH-RESOLUTION QUANTUM CONTROL OF CHEMICAL REACTIONS

SENSELAB: INTEGRATION OF MULTIDISCIPLINARY SENSORY DATA

INJURY AND RECOVERY IN DEVELOPING BRAIN

MOBILE HEALTH FOR IMPLEMENTATION OF HOME-BASED TB CONTACT INVESTIGATION IN UGANDA

ENDOTHELIAL-TO-MESENCHYMA TRANSITION AND ATHEROSCLEROSIS

IN VIVO PATHWAY DISCOVERY IN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE

BIPOLAR & SCHIZOPHRENIA CONSORTIUM FOR PARSING INTERMEDIATE PHENOTYPES

TRANSCRIPTIONAL AND EPIGENETIC SIGNATURES OF HUMAN BRAIN DEVELOPMENT AND AUTISM

FLUCTUATIONS IN IONIC CURRENT THROUGH MEMBRANE CHANNELS

PREDOCTORAL PROGRAM IN BIOPHYSICS

1/2 CELL TYPE AND REGION-SPECIFIC REGULATORY NETWORKS IN HUMAN BRAIN DEVELOPMENT AND DISORDERS

YALE SCOR ON GENDER-SENSITIVE TREATMENT FOR TOBACCO DEPENDENCE

TREATMENT OF OBESITY AND BINGE EATING: BEHAVIORAL WEIGHT LOSS VERSUS STEPPED CARE

NATURALLY-ACQUIRED AND VACCINE-MEDIATED IMMUNITY TO LEPTOSPIROSIS

CHINESE HERBAL MEDICINE AS A NOVEL PARADIGM FOR CANCER CHEMOTHERAPY

SIGNALING MECHANISMS AND FUNCTIONS RELATED TO PATHO-PHYSIOLOGY OF VASCULAR, LUNG AND BLOOD SYSTEMS

WORMGUIDES: A RESOURCE FOR GLOBAL UNDERSTANDING IN DYNAMIC EMBRYONIC SYSTEMS

ALLOIMMUNITY TO PROGENITOR CELL-DERIVED HUMAN VASCULAR CELLS

INTEGRATED RF AND B-MODE DEFORMATION ANALYSIS FOR 4D STRESS ECHOCARDIOGRAPHY

EXPANDING MEDICATION ASSISTED THERAPIES IN UKRAINE

A RANDOMIZED CONTROLLED TRIAL TO REDUCE PNEUMONIA IN NURSING HOME RESIDENTS

GENETIC AND CELLULAR MECHANISMS OF NAFLD AND HEPATIC INSULIN RESISTANCE

IMPACTS OF INDIVIDUAL AND SOCIAL BEHAVIOR ON INFLUENZA DYNAMICS AND CONTROL

ACME: ADVANCED COLD MOLECULE ELECTRON ELECTRIC DIPOLE MOMENT SEARCH

YALE RHEUMATIC DISEASE RESEARCH CORE CENTER

ARTERIOGENESIS AND ARTERIAL BRANCHING

MOLECULAR MECHANISMS OF CELLULAR MOTILITY

GENE TARGETS FOR IVH

CORTICAL DYNAMICS AND NEURAL/BEHAVIORAL PERFORMANCE

CORE CENTER FOR QUANTITATIVE NEUROSCIENCE WITH MAGNETIC RESONANCE (QNMR)

CELL TRANSFORMATION BY BOVINE PAPILLOMAVIRUS

(MURI) HIGH COHERENCE QUANTUM PHONONIC CIRCUITS

MECHANISM AND INHIBITION OF HIV REVERSE TRANSCRIPTASE

8/8-PREDICTORS AND MECHANISMS OF CONVERSION TO PSYCHOSIS

COMPUTER-AIDED DESIGN OF ANTI-HIV DRUGS

SOMATIC MOSAICISM IN THE BRAIN OF TOURETTE SYNDROME

GRADUATE RESEARCH FELLOWSHIP PROGRAM

REGULATION OF EXOCYTOSIS STUDIES WITH FLIPPED SNARES

RNA METABOLISM IN TRYPANOSOMES

DEFINING THE ROLE OF MUTATIONAL BURDEN IN SUSTAINING NORMAL HOMEOSTASIS DURING AGING

GENOMIC ANALYSIS OF TISSUE AND CELLULAR HETEROGENEITY IN IPF

NOVEL INSIGHTS INTO THE MOLECULAR AND CELLULAR MECHANISM REGULATING LIPID METABOLISM AND ATHEROSCLEROSIS

PROTECTING PRIVACY AND FACILITATING SHARED ACCESS OF CLINICAL AND GENETIC DATA OF SPECIAL POPULATIONS

CENTER FOR CARDIOVASCULAR OUTCOMES RESEARCH AT YALE UNIVERSITY

POWERING THE BRAIN: THE CELL BIOLOGY OF NEUROENERGETICS

FUNCTIONAL RELEVANCE OF CFTR TRAFFICKING IN VIVO TO INTESTINAL DISEASE

NEUROGENETIC PROCESSES IN THE FETAL BRAIN

IDENTIFYING ENHANCERS WITH HUMAN-SPECIFIC DEVELOPMENTAL FUNCTIONS

FUNCTIONAL CIRCUITRY OF VISUAL ADAPTATION

STRUCTURAL CORRELATES OF PRESTIN ACTIVITY.

THE IMPACT OF HIV INFECTION ON IMMUNOLOGIC, TRANSCRIPTOMIC, AND METABOLOMIC SIGNATURES OF MEDICATION-ASSISTED THERAPY FOR OPIOID ADDICTION

ION PUMP PARTNERS: REGULATORS OF SORTING AND FUNCTION

DEVELOPMENT AND ORGANIZATION OF THE HUMAN FRONTAL CORTEX

EASTERN CARIBBEAN HEALTH OUTCOMES RESEARCH NETWORK (ECHORN

INTRACRANIAL MULTIMODAL PHYSIOLOGICAL MONITORING IN ACUTE BRAIN INJURY - PROJECT SUMMARY PRESENT DAY MULTIMODAL MONITORING FOR TRAUMATIC BRAIN INJURY (TBI) IS LIMITED IN ITS IMPLEMENTATION AS IT NECESSITATES MULTIPLE INVASIVE PROBES TO MEASURE INTRACRANIAL PRESSURE (ICP), INTRACRANIAL EEG (ICEEG), INTRACRANIAL TEMPERATURE (ICT), AND BRAIN TISSUE OXYGEN (PBTO2), THE MAJORITY OF WHICH REQUIRE THEIR OWN INSTRUMENTATION AND MONITORS. WHILE THERE IS INCREASING EVIDENCE TO SUPPORT MULTIMODAL MONITORING IN TBI AND OTHER ACUTE BRAIN INJURIES, THE PRESENT CUMBERSOME SYSTEMS MAKE IT NEARLY IMPOSSIBLE TO USE OUTSIDE OF MAJOR LEVEL 1 TRAUMA CENTERS. THE CHALLENGES INCLUDE THE NEED FOR EXPERTISE WITH BOTH PROBE PLACEMENT AND DATA INTERPRETATION AS WELL AS THE INTEGRATION OF MULTIPLE ELECTRONIC UNITS FROM DIFFERENT VENDORS WITH DIVERSE SOFTWARE SYSTEMS, EACH REQUIRING TRAINING, IT AND BIOMEDICAL ENGINEERING SUPPORT. COUPLED WITH THIS IS AN INCREASED RISK OF BLEEDING AND INFECTION FROM THE MULTIPLE ENTRY POINTS INTO BRAIN PARENCHYMA. OUR OBJECTIVE IS TO DEVELOP A SINGLE SOURCE BRAIN MONITORING SOLUTION FOR THE MANAGEMENT OF SEVERE TBI. WE WILL INTEGRATE THE MODALITIES INDICATED FOR SEVERE TBI (ICP, ICEEG, ICT, PBTO2) IN A BRAIN IMPLANTABLE DEVICE CALLED THE NEUROPROBE WITH A TARGET DIAMETER WHICH IS EQUIVALENT TO, OR SMALLER THAN, INDIVIDUAL CURRENT PROBES. WE WILL DEVELOP A SINGLE INTERFACE DEVICE CALLED THE NEUROLINK TO ACQUIRE THE MULTI-MODAL INTRACRANIAL DATA FROM THE NEUROPROBE AS WELL AS SCALP EEG AND PATIENT PHYSIOLOGICAL DATA INCLUDING SYSTEMIC BLOOD PRESSURE (SBP), HEART RATE (HR), MEAN ARTERIAL PRESSURE (MAP) AND BLOOD OXYGEN (SPO2) AND TRANSMIT THESE SENSOR SIGNALS TO MONITORS AS A TIME- LOCKED SINGLE DIGITAL DATA STREAM. WE WILL DEVELOP A DISPLAY UNIT CALLED THE NEUROMONITOR TO ANALYZE AND DISPLAY THE ACQUIRED MULTIMODAL DATA IN A SYNCHRONIZED REAL-TIME MANNER. WE CALL THE COMPOSITE SOLUTION CREATED BY THE NEUROPROBE, NEUROLINK, AND NEUROMONITOR DEVICES THE NEUROPROBE SOLUTION. THE TECHNOLOGICAL DEVELOPMENT OF THE NEUROPROBE SOLUTION DRAMATICALLY EXPANDS THE CAPABILITIES OF THE EXISTING ICEEG DEPTH ELECTRODES DEVELOPED AT YALE UNIVERSITY AND MULTIMODAL PROBES CURRENTLY ON THE MARKET. THE KEY INNOVATIONS OF THE NEUROPROBE SOLUTION ARE: 1. INTEGRATION OF MULTIPLE PHYSIOLOGIC SENSORS ON A SINGLE INTRACRANIAL PROBE (NEUROPROBE). 2. SIMPLIFICATION OF NEUROPROBE TO ALLOW PLACEMENT AT BEDSIDE IN A CIVILIAN OR MILITARY FACILITY. 3. DEVELOPMENT OF A MULTIMODAL INTERFACE DEVICE (NEUROLINK) TO STORE AND RELAY TIME-LOCKED DIGITAL DATA ACQUIRED FROM THE NEUROPROBE AND EXTRACRANIAL SENSORS TO THE NEUROMONITOR AND OTHER CLINICAL MONITORS. 4. DEVELOPMENT OF AN IPAD SIZED MONITOR (NEUROMONITOR) TO ANALYZE AND DISPLAY MULTIMODAL DATA. 5. TIME-LOCKED MULTI-STREAM DATA TRANSFER WHICH ALLOWS FOR REAL-TIME AND POST-HOC DATA REVIEW AND ANALYSIS. THIS INNOVATIVE SOLUTION ALLOWS ACQUISITION AND INTEGRATION OF DATA FROM MULTIPLE PHYSIOLOGICAL PARAMETERS THROUGH A STANDARD SMALL TABLET CREATING A SIMPLE SINGLE END-TO-END SOLUTION FROM SENSORS TO MULTIMODAL DATA ANALYSIS AND DISPLAY IN AN OTHERWISE FRAGMENTED AND COMPLEX DOMAIN.

STUDIES OF TRANSFER RNA

EXPLOITING RIBOSWITCH SENSORS TO REVEAL ANTIBIOTICS UPTAKE AND RETENTION IN GRAM NEGATIVE BACTERIA

CENTER FOR POLYCYSTIC KIDNEY DISEASE RESEARCH AT YALE

HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR YOUNG ADULTS WITH SICKLE CELL DISEASE - CLINICAL COORDINATING CENTER

YALE TRAINING PROGRAM IN HEALTH SERVICES RESEARCH

PET IMAGING OF SV2A AND OTHER BIOMARKERS IN ALZHEIMER'S DISEASE

EVALUATION OF THE DOMESTIC VIOLENCE HOMICIDE PREVENTION INITIATIVE

NEW MECHANISMS OF HETEROTAXY AND CONGENITAL HEART DISEASE: NUCLEOPORINS AT CILIA

METHODS IN NEPHROLOGIC RESEARCH

PREDOCTORAL TRAINING AT THE INTERFACE CHEMISTRY AND BIOLOGY

ACTIN MYOSIN INTERACTIONS IN CELL MOTILITY

COMPARATIVE ANALYSIS OF C3 AND C4 LEAF DEVELOPMENT IN RICE, SORGHUM AND MAIZE

CONSORTIUM TO IMPROVE OUTCOMES IN HIV/AIDS, ALCOHOL, AGING & MULTI-SUBSTANCE USE

MOLECULAR GENETICS OF PARVOVIRAL DNA REPLICATION

G PROTEIN SIGNALING IN THE C. ELEGANS NERVOUS SYSTEM

TYPHOID TOXIN AND SALMONELLA TYPHI PATHOGENESIS

COORDINATED MEDICAL TREATMENT OF OPIOID USE DISORDER AND INFECTIOUS DISEASE

CENTER FOR ENDOMETRIAL BIOLOGY AND ENDOMETRIOSIS

EPIDEMIOLOGY OF DISABILITY AND RECOVERY IN OLDER PERSONS

REGULATION OF AUTOPHAGOSOME MEMBRANE DYNAMICS BY THE ATGB FAMILY OF PROTEINS

GENETIC ANALYSIS OF LEGIONELLA PHAGOSOME TRAFFICKING

MECHANISM OF MEMBRANE FUSION BY SNARE PROTEINS

FOSTERING MOTHERS' EMOTIONALLY-RESPONSIVE PARENTING

IMMUNE CONTROL OF TUBERCULOSIS BY IFN-GAMMA-INDUCIBLE LRG-47

EXPANDS CLIMATE-SMART VEGETABLE, CORN, SOYBEAN, BARLEY, RYE, PEANUT, CHICKEN, AND BEEF MARKETS IN IL, MO, AND GA AND SUPPORTS FARMERS IMPLEMENTING AND MONITORING CLIMATE-SMART PRACTICES.

ROLES OF SLC26A6 IN RENAL NACI TRANSPORT AND PREVENTION OF OXALATE UROLITHIASIS

FUNCTION OF TOLL-LIKE RECEPTORS THROUGHOUT GESTATION

REGULATION OF GLUTAMATE RECEPTORS BY CALCIUM-DEPENDENT PROTEIN KINASE

UNDERSTANDING EVOKED AND RESTING-STATE FMRI THROUGH MULTI SCALE IMAGING

OPTIMIZING REVASCULARIZATION BY EC TRANSPLANTATION

BIOIMAGING AND INTERVENTION IN LOCALIZATION-RELATED EPILEPSY

INTEGRATED STEPPED CARE FOR UNHEALTHY ALCOHOL USE IN HIV

ROLE OF MTOR AND SYNAPTOGENESIS IN THE ACTIONS OF RAPID-ACTING ANTIDEPRESSANTS

(MURI 08) NANOCATALYSTS FOR PROPULSION APPLICATIONS

NSMDS: IMPROVING MATERIAL SAFETY THROUGH THE MINIMIZATION OF OXIDATIVE STRESS POTENTIAL: A MECHANISTIC UNDERSTANDING OF ROS GENERATION IN IN VITRO A

DEVELOPMENT OF NOVEL IMMUNOTHERAPIES FOR BREAST CANCER

UNDERSTANDING HEMOTOPOIETIC NEOPLASIAS USING HUMANIZED MICE

NIAMS: CORT

INTERDISCIPLINARY RESEARCH ON STRESS, SELF-CONTROL & ADDICTION

CARBON DIOXIDE REMOVAL AND HIGH-PERFORMANCE COMPUTING: PLANETARY BOUNDARIES OF EARTH SHOTS

A NOVEL APPROACH FOR CELL-TYPE CLASSIFICATION AND CONNECTIVITY IN THE HUMAN BRAIN

MICROBIAL PROGRAMMING OF T-CELL MIGRATION FROM GUT TO BRAIN - PROJECT SUMMARY THE GUT-BRAIN AXIS IS EMERGING AS A CENTRAL MEDIATOR OF HEALTH AND DISEASE. MULTIPLE STUDIES HAVE ASSOCIATED GUT MICROBIOTA COMPOSITION WITH NEUROINFLAMMATORY AND NEURODEGENERATIVE DISEASES, AND SEVERAL RECENT STUDIES SUGGEST TRAFFICKING OF IMMUNE CELLS FROM THE GUT TO THE BRAIN. HOWEVER, MECHANISTIC UNDERSTANDING OF HOW GUT- EDUCATED T-CELLS GET TO THE BRAIN AND WHY THIS AXIS EXISTS AT ALL ARE UNCLEAR. WE RECENTLY DISCOVERED THAT CD4 T- CELLS ARE PRESENT IN MOUSE AND HUMAN BRAIN AND ANATOMICALLY LOCALIZE TO THE SUBFORNICAL ORGAN IN THE BRAIN AT STEADY STATE. IN HUMANS AND MICE, WE PERFORMED DEEP TRANSCRIPTIONAL AND FUNCTIONAL PROFILING OF CNS CD4 T- CELLS AND FOUND THAT THEY ARE TH1-LIKE. USING MOUSE MODELS, WE FOUND THAT CNS CD4-T-CELL-DERIVED IFN IS REQUIRED FOR CNS HOMEOSTASIS BY SIGNALING TO ASTROCYTES. WE FOUND THAT CNS T-CELLS ARE DERIVED FROM BOTH THE GUT AND ALSO, SURPRISINGLY, THE WHITE ADIPOSE TISSUE, AND CAN BE PHENOTYPICALLY SHAPED BY THE STATES OF BOTH THE GUT MICROBIOTA COMPOSITION AND THE STATE OF THE FAT. TRANSCRIPTIONAL AND FUNCTIONAL PROFILING ACROSS BRAIN, WHITE FAT, AND GUT IN MOUSE AND HUMANS IDENTIFIED POTENTIAL MECHANISMS OF HOW CD4 T-CELLS GET FROM THE GUT TO THE BRAIN. IN THIS PROPOSAL, WE WILL IDENTIFY THE MECHANISMS BY WHICH GUT MICROBIOTA AND THE WHITE FAT CONTROL THE CD4 T-CELL COMPARTMENT.

ANGIOGENSIS AND ISCHEMIA

MOLECULAR DIVERSITY AMONG HIPPOCAMPAL AND ENTORHINAL CELLS IN AGING AND ALZHEIMER'S DISEASE - ABSTRACT ALZHEIMER’S DISEASE (AD) IS THE LEADING CAUSE OF DEMENTIA (60-80%), AFFECTING TENS OF MILLIONS OF PEOPLE GLOBALLY AND, DUE TO LONGER LIFESPANS AND AGING POPULATIONS, PERHAPS HUNDREDS OF MILLIONS MORE BY 2050. AD PATHOLOGY IS FIRST OBSERVED IN ALLOCORTICAL AND LIMBIC AREAS WITHIN THE CEREBRUM, IN PARTICULAR MEDIAL TEMPORAL CORTICAL REGIONS CRITICAL FOR LEARNING AND MEMORY INCLUDING THE HIPPOCAMPAL FORMATION AND ENTORHINAL CORTEX (HIP-EC). WITHIN THESE AREAS, PATHOLOGY EXHIBITS SUBREGIONAL AND CELL TYPE SPECIFICITY, WITH LAYER 2 OF ENTORHINAL CORTEX AND THE HIPPOCAMPAL CA1 FIELD (SOMMER’S SECTOR) EXHIBITING PATHOLOGICAL HALLMARKS BEFORE DENTATE GYRUS GRANULE CELLS AND OTHER MAJOR HIPPOCAMPAL NEURONAL SUBTYPES. UNDERSTANDING THE MOLECULAR BASIS OF THIS SELECTIVE VULNERABILITY (AND CONVERSELY THE RESILIENCE OF OTHER CELL TYPES) WILL PROVIDE NEW INSIGHTS INTO THE ETIOLOGY OF AD, BUT TO DATE ONLY LIMITED EFFORTS HAVE BEEN MADE TO UNDERSTAND THE MOLECULAR SIGNATURES DIFFERENTIATING NEURONAL AND NON-NEURONAL CELLS IN HIP-EC. WE THEREFORE PROPOSE TO CONDUCT SINGLE NUCLEAR RNA SEQUENCING (SNRNA-SEQ) AND SINGLE NUCLEAR ASSAY FOR TRANSPOSASE ACCESSIBLE CHROMATIN (SNATAC- SEQ) IN 5 REGIONS OF HIP-EC OF AD BRAINS, YOUNG/MID ADULT AND AGED NEUROTYPICAL “CONTROL” HUMAN BRAINS, AND YOUNG ADULT AND AGED RHESUS MACAQUE BRAINS. THIS WILL ALLOW US TO DEVELOP A HIGH RESOLUTION CELL CENSUS OF HIP-EC WHICH WILL IN TURN ALLOW US TO IDENTIFY ENRICHED GENES, GENE EXPRESSION PATTERNS, GENE REGULATORY NETWORKS, AND BIOLOGICAL PROCESSES POTENTIALLY MEDIATING CELL TYPE SPECIFIC DIFFERENCES IN THE AD AND AGED HIP-EC.

TOWARD COMPREHENSIVE MODELS OF NATURALISTIC COOPERATION AND COMPETITION IN PRIMATES - PROJECT SUMMARY THE FLEXIBLE ABILITY TO WORK TOGETHER FOR MUTUAL BENEFITS WHILE COMPETING AGAINST OTHERS FOR LIMITED RESOURCES IS A HALLMARK OF ADVANCED SOCIAL COGNITION. COOPERATIVE AND COMPETITIVE INTERACTIONS ARE HIGHLY DYNAMIC AND COMPLEX. HOWEVER, STUDYING THE PRECISE BEHAVIORAL MECHANISMS OF THESE INTERACTIONS HAS BEEN CHALLENGING. THIS IS PARTLY DUE TO THE FACT THAT THE STANDARD ANIMAL MODELS IN LAB STUDIES DO NOT RELIABLY COOPERATE. MOREOVER, TYPICAL STUDIES DO NOT INCLUDE MULTIDIMENSIONAL BEHAVIORAL MEASUREMENTS THAT ARE ESSENTIAL TO UNDERSTAND SUCH COMPLEX INTERACTIONS. THEREFORE, THERE IS A NEED TO INVESTIGATE COMPLEX SOCIAL INTERACTIONS IN A SPECIES WHOSE SOCIAL STRUCTURE STRONGLY DEPENDS ON BOTH COOPERATION AND COMPETITION, WHILE TRACKING MULTIPLE ACTION-BASED AND INTERNAL STATE-RELATED VARIABLES TO OBTAIN A COMPREHENSIVE UNDERSTANDING OF SOCIAL BEHAVIOR. THE MARMOSET IS AN EXCELLENT SPECIES FOR STUDYING COMPLEX SOCIAL INTERACTIONS GROUNDED IN CONTEXT-DEPENDENT COOPERATIVE AND COMPETITIVE TENDENCIES WITHIN THEIR NATURAL ETHOLOGY. THE FIRST MAJOR GOAL OF THIS PROPOSAL IS TO SIMULTANEOUSLY AND CONTINUOUSLY COLLECT MULTIDIMENSIONAL BIOBEHAVIORAL MEASUREMENTS, BOTH ACTION-BASED AND INTERNAL STATE-BASED, DURING NATURALISTIC COOPERATIVE AND COMPETITIVE INTERACTIONS BETWEEN FREELY MOVING MARMOSETS. WE AIM TO UNDERSTAND THE FUNCTIONAL AND DIRECTIONALLY CAUSAL DEPENDENCIES OF THESE BIOBEHAVIORAL VARIABLES IN COOPERATIVE AND COMPETITIVE BEHAVIORS. THE SECOND MAJOR GOAL IS TO BUILD COMPREHENSIVE AND EMPIRICALLY TESTABLE GENERATIVE MODELS OF PRIMATE SOCIAL INTERACTION AND TO VALIDATE OUR UNDERSTANDING ITERATIVELY BETWEEN THE MODELS AND THE EXPERIMENTS. WE WILL USE MULTIPLE MODELING APPROACHES TO EXPLOIT THEIR STRENGTHS: MULTI-AGENT REINFORCEMENT LEARNING WITH RECURRENT NEURAL NETWORKS WILL BE USED TO LEARN COMPLEX PATTERNS FOR PREDICTION, AND THE STRUCTURE AND INPUTS TO THESE MODELS WILL BE INFORMED BY DYNAMIC BAYESIAN NETWORKS TO INCREASE THE INTERPRETABILITY OF THE MODELS. WE WILL USE AN EMBODIED AGENT-BASED FRAMEWORK, WITH THE RECURRENT NEURAL NETWORKS DRIVING MUSCULOSKELETAL MODELS OF MARMOSETS, TO BETTER MODEL COOPERATIVE AND COMPETITIVE INTERACTIONS OF NONHUMAN PRIMATES. WITH THE COMPREHENSIVE BIOBEHAVIORAL DATA AND THE MUSCULOSKELETAL MODEL, WE WILL BUILD GENERALIZABLE MODELS OF PRIMATE SOCIAL INTERACTION VIA A MULTI-LEVEL CONSTRAINTS-BASED FRAMEWORK. FINALLY, WE WILL VALIDATE THE GENERATIVE MODELS OF PRIMATE SOCIAL INTERACTION BY INDUCING MULTIPLE TYPES OF IN SILICO ENVIRONMENTAL AND TASK MANIPULATIONS THAT ARE DESIGNED TO PREDICTABLY ALTER SOCIAL STRATEGIES AND CARRYING OUT THOSE EXPERIMENTS IN VIVO THAT SIGNIFICANTLY ALTER THE RESULTING SOCIAL STRATEGY. OVERALL, WE AIM TO PROVIDE THE MOST COMPREHENSIVE UNDERSTANDING OF PRIMATE SOCIAL INTERACTIONS TO DATE, ALONG WITH NOVEL GENERATIVE MODELS OF SUCH BEHAVIOR.

MOLECULAR GENETIC PATHOGENESIS OF INTRACRANIAL ANEURYSMS

MODELS OF SBIRT FOR OPIOID DEPENDENT PATIENTS IN THE EMERGENCY DEPARTMENT

AMPK-ACTIVATOR METFORMIN TO PROMOTE PODOCYTE SURVIVAL IN FSGS: A PILOT TRIAL

EXERCISE IN GENETIC CARDIOVASCULAR CONDITIONS

MRSEC: MATERIALS RESEARCH SCIENCE AND ENGINEERING CENTER FOR RESEARCH ON INTERFACE STRUCTURES AND PHENOMENA

TARGETING OF SOMATIC HYPERMUTATION IN THE GENOME

ACME: ADVANCED COLD MOLECULE ELECTRON ELECTRIC DIPOLE MOMENT SEARCH

CFTR MODULATES INNATE IMMUNE RESPONSE IN THE BILIARY EPITHELIUM. ROLE IN THE PATH

MULTISCALE IMAGING OF SPONTANEOUS ACTIVITY IN CORTEX: MECHANISMS, DEVELOPMENT AND FUNCTION

ESTABLISHING A BLUEPRINT FOR NUCLEAR PORE COMPLEX ASSEMBLY