University Of Massachusetts

THE CENTER FOR ADVANCING POINT OF CARE IN HEART, LUNG, BLOOD AND SLEEP DISEASES

EDUCATION STABILIZATION FUND - PHASE 2

COOPERATIVE AGREEMENTS TO SUPPORT INNOVATIVE EXCHANGE INFORMATION TECHNOLOGY SYSTEMS

CARES ACT HIGHER EDUCATION EMERGENCY RELIEF FUND

EDUCATION STABILIZATION FUND - PHASE 2

UNIVERSITY OF MASSACHUSETTS CENTER FOR CLINICAL AND TRANSLATIONAL SCIENCE

NATIONAL CENTER ON PROGRAM MANAGEMENT AND FISCAL OPERATIONS

TAS::89 0227::TAS RECOVERY; RECOVERY ACT - POLYMER-BASED MATERIALS FOR HARVESTING SOLAR ENERGY -- EFRC; PI - THOMAS RUSSELL

NATIONAL HEAD START CENTER ON PROGRAM MANAGEMENT AND FISCAL OPERATIONS

CARES ACT HIGHER EDUCATION EMERGENCY RELIEF FUND

UNIVERSITY OF MASSACHUSETTS LOWELL - INSTITUTIONAL FUNDING FROM THE HIGHER EDUCATION EMERGENCY RELIEF FUND

TRANSFORMING CLINICAL PRACTICES INITIATIVE - PTN

WORKER HEALTH AND SAFETY TRAINING COOPERATIVE AGREEMENT

UMASS BOSTON-DF/HCC U54 PARTNERSHIP (2 OF 2)

UNIVERSITY OF MASSACHUSETTS LOWELL EMERGENCY FINANCIAL AID GRANTS UNDER CARES ACT

COOPERATIVE AGREEMENT FOR RESEARCH AND DEVELOPMENT - SLIMMER3

CELLULAR IMMUNITY TO CATEGORY A-C VIRUSES IN HUMANS

ANALYSIS OF THE GENETIC POTENTIAL & GENE EXPRESSION OF MICROBIAL COMMUNITIES INVOLVED IN THE IN SITU BIOREMEDIATION OF URANIUM

CENTER FOR COLLABORATIVE ADAPTIVE SENSING OF THE ATMOSPHERE (CASA)

MASSACHUSETTS AI AND TECHNOLOGY CENTER FOR CONNECTED CARE IN AGING AND ALZHEIMER'S DISEASE (MAITC) - PROJECT SUMMARY: OVERALL MORE THAN 90% OF OLDER AMERICANS WOULD PREFER TO STAY IN THEIR HOMES AS LONG AS POSSIBLE AS THEY AGE. HOWEVER, THE PREVALENCE OF CHRONIC ILLNESS INCLUDING ALZHEIMER'S DISEASE (AD) AND ALZHEIMER'S DISEASE RELATED DEMENTIAS (ADRD) CAN MAKE THE GOAL OF SUCCESSFUL AGING AT HOME OUT OF REACH WITHOUT SUBSTANTIAL SUPPORT. AT- HOME HEALTH CARE TECHNOLOGIES HOLD SIGNIFICANT PROMISE TO PROVIDE MANY NEEDED FORMS OF SUPPORT, BUT HAVE NOT BEEN SPECIFICALLY DEVELOPED FOR OLDER ADULTS, AD/ADRD PATIENTS, CAREGIVERS, AND THEIR CLINICIANS. MANY EXISTING HEALTH MONITORING TECHNOLOGIES ARE BURDENSOME TO USE FOR OLDER ADULTS, ARE NOT SUFFICIENTLY ACCURATE, HAVE SPECIFIC ALGORITHMIC BIASES, AND LACK ADEQUATE USABILITY, AND THE RESULTING DELUGE OF DATA OFTEN FAILS TO PROVIDE INFORMATION THAT CAN USEFULLY INFORM CAREGIVERS AND SUPPORT CLINICAL DECISIONS. FURTHER, MANY CURRENT TREATMENT AND INTERVENTION REGIMES ARE LIMITED IN TERMS OF THEIR ABILITY TO BE REMOTELY DELIVERED, MANAGED AND ADAPTED TO PATIENT NEEDS AND CAREGIVER ABILITIES OVER TIME. THE MASSACHUSETTS AI AND TECHNOLOGY CENTER FOR CONNECTED CARE IN AGING AND ALZHEIMER'S DISEASE (MAITC) IS A MULTIDISCIPLINARY CENTER SPANNING FIVE SITES – THE UNIVERSITY OF MASSACHUSETTS AMHERST, BRIGHAM AND WOMEN’S HOSPITAL, MASSACHUSETTS GENERAL HOSPITAL, BRANDEIS UNIVERSITY AND NORTHEASTERN UNIVERSITY – THAT AIMS TO FOSTER INTERDISCIPLINARY RESEARCH ON THE DEVELOPMENT, VALIDATION AND TRANSLATION OF EMERGING AI- ENHANCED TECHNOLOGIES TO ENHANCE CONNECTIONS BETWEEN OLDER ADULTS, CAREGIVERS, AND CLINICIANS IN ORDER TO MORE EFFECTIVELY SUPPORT HEALTHY AGING AS WELL AS THE CARE OF PATIENTS WITH AD/ADRD AT HOME. TO ACHIEVE THIS OBJECTIVE, MAITC WILL PURSUE THE FIVE AIMS. THE FIRST IS TO APPLY A RIGOROUS PROCESS WHICH INVOLVES ELICITING STAKEHOLDER NEEDS TO DRIVE THE FOCI OF PILOT STUDIES AND IDENTIFYING PROMISING TECHNOLOGIES SUITABLE FOR INCORPORATION INTO PILOT RESEARCH PROJECTS. THE SECOND IS TO FORM AND SUPPORT A MULTIDISCIPLINARY COMMUNITY OF ENGINEERS, COMPUTER SCIENTISTS, BEHAVIORAL SCIENTISTS, MEDICAL RESEARCHERS, NURSES AND CLINICIANS WORKING TO ADVANCE THE GOALS OF THE MAITC. THE THIRD IS TO PROVIDE ACCESS TO STATE-OF-ART VALIDATION FACILITIES, DIVERSE COHORTS ACROSS RURAL AND URBAN AREAS, AND TRANSLATION AND COMMERCIALIZATION SERVICES TO ENABLE RAPID, ROBUST AND MULTI-FACETED VALIDATION AND TRANSLATION OF AI-ENHANCED TECHNOLOGIES. THE FOURTH IS TO ADMINISTER A PILOT PROJECT GRANTING PROCESS AND ENSURE THAT THE PILOT PROJECTS ARE RESPONSIVE TO STAKEHOLDER NEEDS, USE EMERGING AI AND RELATED TECHNOLOGIES THAT HAVE SIGNIFICANT POTENTIAL TO IMPROVE INTERACTIONS BETWEEN OLDER ADULTS, LAY CAREGIVERS, AND CLINICIANS. THE FIFTH IS TO PROVIDE TRAINING TO DEVELOPERS, CLINICIANS, AND OTHER STAKEHOLDERS AND TO DISSEMINATE FINDINGS TO DIVERSE RESEARCH, DEVELOPMENT AND PRACTICE COMMUNITIES TO ACCELERATE FURTHER DEVELOPMENT OF PROMISING TECHNOLOGIES AND PROMOTE THE ADOPTION OF VALIDATED TECHNOLOGIES BEYOND THE MAITC. THROUGH THESE COORDINATED EFFORTS, WE HOPE TO IMPROVE THE LIVES OF OLDER ADULTS AND THEIR CAREGIVERS.

NATIONAL NETWORK OF LIBRARIES OF MEDICINE NEW ENGLAND (REGION 8) AND PUBLIC HEALTH COORDINATION OFFICE

MASSACHUSETTS MEDICAID INFRASTRUCTURE AND COMPREHENSIVE EMPLOYMENT OPPORTUNITIES

NSEC: CENTER FOR HIERARCHICAL MANUFACTURING

HIGHER EDUCATION EMERGENCY RELIEF FUND-IHE/INSTITUTION

NONHUMAN PRIMATE REAGENT RESOURCE

CENTER FOR THE PROMOTION OF HEALTH IN THE NEW ENGLAND WORKPLACE

BIOMARKERS FOR THERAPY OF FSHD (U54)

OPTIMIZATION OF HIV VACCINES FOR THE INDUCTION OF CROSS-REACTIVE ANTIBODIES

HIGHER EDUCATION EMERGENCY RELIEF FUND

CENTER FOR BRAIDING INDIGENOUS KNOWLEDGES AND SCIENCE (CBIKS) -THE NATURAL AND BUILT ENVIRONMENTS OF OUR MODERN WORLD INTERACT IN COMPLEX WAYS THAT AFFECT OUR GLOBAL COMMUNITY. UNDERSTANDING THESE INTERACTIONS AND THEIR EFFECTS ON SOCIETY REQUIRES COLLABORATION, COORDINATION, AND SHARING OF KNOWLEDGE AND DATA AMONG RESEARCHERS, COMMUNITIES, AND ORGANIZATIONS. THE CENTER FOR BRAIDING INDIGENOUS KNOWLEDGES AND SCIENCE (CBIKS) ADVANCES KNOWLEDGE ABOUT ENVIRONMENTAL VARIABILITY AND ITS EFFECTS ON FOOD AND CULTURAL SYSTEMS AT LOCAL AND GLOBAL SCALES THROUGH A FOCUS ON COMBINING INDIGENOUS KNOWLEDGE (IK) WITH WESTERN SCIENCE (WS) IN EFFECTIVE, ETHICAL, AND NOVEL WAYS. BASED ON A COMPARATIVE ANALYSIS OF OVER 30 PLACE-BASED PROJECTS TO BE CARRIED OUT BY CBIKS AND NEARLY 60 PARTNERING INSTITUTIONS AND INDIGENOUS COMMUNITIES, CBIKS DEVELOPS A SET OF GENERALIZABLE FINDINGS, TOOLS, TRAININGS, PROTOCOLS, AND BEST PRACTICES FOR INTEGRATING IK AND WS. THROUGH ITS RESEARCH ACTIVITIES, THE CBIKS TEAM ASPIRES TO FUNDAMENTALLY TRANSFORM HOW CHALLENGES RELATED TO ENVIRONMENTAL VARIABILITY, FOOD SYSTEMS, AND CULTURAL HERITAGE CONSERVATION ARE APPROACHED. CBIKS BROADENS THE PARTICIPATION OF GROUPS UNDERREPRESENTED IN SCIENCE, PRINCIPALLY THROUGH THE REALIZATION OF A COHORT OF INDIGENOUS SCIENTISTS WHO WILL LEAD FUTURE EFFORTS IN INTEGRATED WS AND IK RESEARCH IN THE AREAS OF ARCHAEOLOGY, GEOSCIENCES, NATURAL, AND ENVIRONMENTAL SCIENCES. THE CBIKS TEAM MENTORS AND PROVIDES RESEARCH OPPORTUNITIES FOR NUMEROUS POSTDOCTORAL RESEARCHERS, GRADUATE STUDENT RESEARCH ASSISTANTS, UNDERGRADUATE STUDENT RESEARCHERS, AND INDIGENOUS COMMUNITY MEMBER AND YOUTH RESEARCH ASSISTANTS, ACROSS MULTIPLE RESEARCH HUBS AND WORKING GROUPS. INSTITUTIONAL ENGAGEMENT INCLUDES TWO TRIBAL COLLEGES, FOUR AMERICAN INDIAN AND ALASKA NATIVE-SERVING INSTITUTIONS, TWO HISPANIC SERVING INSTITUTIONS, TWO ASIAN AMERICAN AND NATIVE AMERICAN PACIFIC ISLANDER SERVING INSTITUTIONS, A NATIVE HAWAIIAN SERVING INSTITUTION, A NATIVE AMERICAN SERVING NON-TRIBAL INSTITUTION, AND NUMEROUS OTHER PUBLIC AND PRIVATE RESEARCH INSTITUTIONS. DATA AND FINDINGS FROM CBIKS ARE WIDELY DISSEMINATED THROUGH A PUBLICLY ACCESSIBLE REPOSITORY AS WELL AS FORMAL AND INFORMAL LEARNING ACTIVITIES FOR K-12 STUDENTS AND TEACHERS, SCIENTISTS, AND COMMUNITIES. CBIKS IS ORGANIZED BASED ON INDIGENOUS MODELS OF CONSENSUS DECISION-MAKING AND INTERGENERATIONAL LEARNING AND RESPONSIBILITY AND HAS THREE MAIN AIMS: 1) TO DEVELOP A COMMON PUBLICLY ACCESSIBLE REPOSITORY FOR THE STORAGE, ORGANIZATION, AND SHARING OF METHODS, ETHICS, AND GUIDELINES FOR EFFECTIVE INTEGRATION OF IK AND WS SYSTEMS; 2) TO IMPLEMENT METHODOLOGIES THROUGH A SERIES OF PLACE-BASED STUDIES IN PARTNERSHIP WITH 57 INDIGENOUS COMMUNITIES AT 8 REGIONAL HUBS, EACH CONSTITUTING A DIFFERENT NATURAL ENVIRONMENT; AND 3) TO AGGREGATE AND DISTILL DATA FROM THE PLACE-BASED STUDIES THROUGH WORKING GROUPS WITH THE OBJECTIVES OF ADVANCING KNOWLEDGE ON ENVIRONMENTAL VARIABILITY, FOOD SYSTEMS, AND CULTURAL RESOURCES AND REFINING METHODOLOGIES AND ETHICAL GUIDELINES FOR INTEGRATED IK AND WS RESEARCH. EIGHT REGIONAL RESEARCH HUBS INCLUDE PARTNERS FROM MULTIPLE INSTITUTIONS ACROSS THE SOCIAL SCIENCES, GEOSCIENCES, AND ENVIRONMENTAL SCIENCES, AND EACH WORKS IN PARTNERSHIP WITH DIVERSE INDIGENOUS COMMUNITIES. SEVEN WORKING GROUPS SERVE ALL RESEARCH HUBS, FOCUSING ON A RANGE OF CROSS-CUTTING THEMES RELATED TO RESEARCH DEVELOPMENT AND DESIGN, DATA SHARING, AND SCIENCE EDUCATION, TRAINING, AND DISSEMINATION. THROUGH THIS CONVERGENT AND COLLABORATIVE MODEL, CBIKS CAN ADVANCE NOT ONLY WHAT WE KNOW ABOUT INTERACTIONS BETWEEN THE NATURAL WORLD AND HUMAN SOCIETIES, BUT ALSO HOW WE INVESTIGATE AND ADDRESS RELATED SOCIETAL CHALLENGES. 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.

CENTER FOR 3D STRUCTURE AND PHYSICS OF THE GENOME

MATERIALS RESEARCH SCIENCE AND ENGINEERING CENTER ON POLYMERS

NSEC: CENTER FOR HIERARCHICAL MANUFACTURING

SSI/SSDI DEMONSTRATIONS

STRUCTURAL ANNOTATION OF THE HUMAN GENOME

MODELS AND GENE THERAPIES FOR AAT DEFICIENCY - PROJECT SUMMARY (OVERALL) ALPHA-1 ANTITRYPSIN DEFICIENCY (AATD) IS CAUSED BY MUTATIONS IN THE SERPINA1 GENE. THE E342K (PI*Z) MUTANT ALLELE IS VERY COMMON AMONG THOSE OF EUROPEAN ANCESTRY, AND E342K HOMOZYGOTES ENCODE A PROTEIN WITH IMPAIRED SECRETION, RESULTING IN DEFICIENT AAT SERUM LEVELS. SINCE AAT NORMALLY PROTECTS ELASTIN IN THE LUNG FROM DEGRADATION, LOSS OF EFFECTIVE AAT TRIGGERS LUNG INFLAMMATION, AIRWAYS OBSTRUCTION AND EMPHYSEMA, WHICH IS THE PRIMARY LIFE-LIMITING MANIFESTATION OF AATD. THE PROJECTS WITHIN THIS PROPOSAL SEEK TO PURSUE NUMEROUS PARALLEL STRATEGIES TO DEVELOP A GENE THERAPY FOR AATD. MOST OF THESE STRATEGIES REVOLVE AROUND THE USE OF RECOMBINANT ADENO-ASSOCIATED VIRUS (RAAV)-BASED VECTORS, A PLATFORM TECHNOLOGY THAT HAS BEEN VERY SUCCESSFUL FOR OTHER GENETIC DISEASES. IN PROJECT 1, OPTIMIZED RAAV VECTORS WILL BE STUDIED IN GENETICALLY DEFINED ANIMAL MODELS (INCLUDING MICE AND FERRETS) IN COMPARISON WITH TRANSGENIC RECONSTITUTION STUDIES USING A REGULATED CONDITIONAL TRANSGENIC SYSTEM TO COMPARE TWO RELEVANT POTENTIAL TARGET REPLACEMENT LEVELS (11ΜM AND 25ΜM) AND CLINICALLY RELEVANT ENDPOINTS WILL BE STUDIED. IN PROJECT 2, NOVEL CRISPR VARIANTS WILL BE USED FOR GENE EDITING, BASE EDITING AND PRIME EDITING STRATEGIES TO TREAT AATD. IN PROJECT 3, WE WILL SCREEN NATURALLY OCCURRING AAV CAPSID LIBRARIES OBTAINED FROM REMOTE POPULATIONS IN WESTERN CHINA TO IDENTIFY CAPSIDS WITH ENHANCED EFFICACY AND SAFETY FOR AATD GENE THERAPY. FINALLY, IN PROJECT 4, WE WILL USE NOVEL TREG AND CAR-TREG STRATEGIES TO SELECTIVELY MODULATE ANTI-VECTOR IMMUNE RESPONSES. THERE WILL ALSO BE TWO CORES. CORE A WILL PROVIDE EACH PROJECT WITH IMPORTANT VECTOR IMMUNOLOGY ASSAYS, WHICH CAN IDENTIFY LIMITATIONS DUE TO HOST IMMUNE RESPONSES TO AAV CAPSIDS, THE AAT TRANSGENE OR TO CAS9-DERIVED PROTEINS. CORE B WILL PROVIDE ANIMAL MODELS AND PHYSIOLOGIC MEASUREMENTS IN THE ANIMAL MODELS FOR TESTING OF OPTIMIZED RAAV VECTORS, GENE EDITING TOOLS AND IMMUNE MODULATION APPROACHES. PROGRAM INVESTIGATORS HAVE A TRACK RECORD OF INTERACTIONS AND COLLABORATIONS THAT WE ANTICIPATE WILL CONTINUE IN FUTURE YEARS.

AIDS EDUCATION TRAINING CENTERS

EVOLUTION & MAINTENANCE OF MEMORY CD8 T CELLS

RESEARCH AND DEVELOPMENT EFFORT CONDUCTED IN ACCORDANCE WITH THE RECIPIENT'S PROPOSAL ENTITLED 'SOLDIER LIGHTWEIGHT INTEGRATED MULTIFUNCTIONAL MATERI

INNATE AND ADAPTIVE IMMUNITY IN EXPERIMENTAL AND HUMAN GONOCCOCAL INFECTION

THE CENTER FOR ACCELERATING PRACTICES TO END SUICIDE THROUGH TECHNOLOGY TRANSLATION (CAPES) - CAPES OVERALL: PROJECT SUMMARY/ABSTRACT SIGNIFICANCE: RECENTLY, WE HAVE SEEN MASSIVE GROWTH IN AVAILABILITY OF EMPIRICALLY SUPPORTED TECHNOLOGIES ENABLING SUICIDE RISK IDENTIFICATION, MONITORING, AND PREVENTION IN HEALTHCARE SETTINGS. HOWEVER, OUR KNOWLEDGE OF EFFECTIVE, EFFICIENT STRATEGIES TO TRANSLATE THESE TECHNOLOGIES INTO CLINICAL PRACTICE IS WEAK. AS A RESULT, THESE TECHNOLOGIES ARE NOT BEING OPTIMALLY DEPLOYED TO PREVENT SUICIDES. THE CENTER FOR ACCELERATING PRACTICES TO END SUICIDE THROUGH TECHNOLOGY TRANSLATION ( CAPES ) WILL BRIDGE THIS RESEARCH-TO-PRACTICE GAP. INVESTIGATORS: CAPES TRANSDISCIPLINARY FACULTY, ADVISORS, AND CONSULTANTS HAVE EXTENSIVE EXPERTISE IN THE DISCIPLINES REQUIRED TO SUCCESSFULLY SUPPORT THE CAPES MISSION AND ITS INDIVIDUAL PROJECTS, PRODUCING SYNERGISTIC INSIGHTS AND DISCOVERY. COMBINED, THE TEAM HAS OVER 1,000 HIGH-IMPACT PUBLICATIONS IN FIELDS RELEVANT TO OR DIRECTLY STUDYING THE INTERSECTION OF SUICIDE PREVENTION, IMPLEMENTATION SCIENCE, DIGITAL HEALTH TECHNOLOGY DEVELOPMENT AND TRANSLATION TO PRACTICE, HEALTH DISPARITIES, STUDY DESIGN AND ANALYSIS, AND HEALTHCARE SYSTEMS- BASED CHANGE. THIS SCIENTIFIC DEPTH WILL BE ACCOMPANIED BY LONGITUDINAL ENGAGEMENT OF DIVERSE STAKEHOLDERS. INNOVATION: CAPES WILL BE THE FIRST NIMH CENTER FOCUSED ON ACCELERATING EVIDENCE-BASED SUICIDE CARE BY LEVERAGING TECHNOLOGY SOLUTIONS ACROSS MULTIPLE HEALTHCARE SETTINGS. FURTHER, IT WILL LEVERAGE INNOVATIONS IN IMPLEMENTATION SCIENCE, PERSON-CENTERED DESIGN, HYBRID CLINICAL TRIAL DESIGN, TECHNOLOGY-RELATED ECONOMICS EVALUATIONS, BUSINESS DEVELOPMENT, AND ETHICS TO MAXIMIZE SCIENTIFIC AND PUBLIC HEALTH IMPACT. APPROACH: THE CAPES ADMINISTRATIVE CORE WILL COLLABORATE WITH THE METHODS CORE TO MAXIMIZE THE CENTER’S IMPACT BY CREATING SYNERGY; PRIORITIZING EVIDENCE-BASED, SCALABLE TECHNOLOGIES FOR STUDY; CREATING RELEVANCE ACROSS MULTIPLE SETTINGS AND DIVERSE PATIENT POPULATIONS; LEVERAGING THE ZERO SUICIDE FRAMEWORK TO ALIGN WITH PRIORITIES OF THE NATIONAL ACTION ALLIANCE FOR SUICIDE PREVENTION AND NIMH; AND FOSTERING BUSINESS DEVELOPMENT AND TECHNOLOGY TRANSFER TO HELP ENSURE SUCCESSFUL PUBLIC DISSEMINATION, ADOPTION, AND SUSTAINABILITY. ENVIRONMENT: UMASS AND WORCESTER POLYTECHNIC INSTITUTE HAVE AN ESTABLISHED HISTORY OF SUCCESSFULLY CARRYING OUT COLLABORATIVE STUDIES AND ARE PERFECTLY SITUATED TO SUPPORT THIS CENTER. THEIR NETWORKED CAPABILITIES, COMBINED WITH OTHER ACADEMIC, HEALTH SYSTEM, BUSINESS, AND COMMUNITY PARTNERS, PROVIDE LAYERED, COMPLEMENTARY RESOURCE ACCESS FOR CLINICAL CARE IMPROVEMENT, TECHNOLOGY DEVELOPMENT, TECHNOLOGY TRANSFER FROM RESEARCH SETTINGS TO CLINICAL USE, AND WIDESPREAD DISSEMINATION OF CAPES RESOURCES. IMPACT: LED BY ACCOMPLISHED INVESTIGATORS WITH ACCESS TO POWERFUL RESOURCES, CAPES WILL BE IDEALLY SITUATED TO ANSWER THE CRITICAL RESEARCH QUESTIONS POSED IN THIS PROPOSAL AND REACH MANY DIVERSE SETTINGS AND PATIENT POPULATIONS. CAPES INNOVATIVE EMBRACE OF EVIDENCE-BASED SUICIDE CARE TECHNOLOGIES, COMBINED WITH A STRONG FOCUS ON ZERO SUICIDE ALIGNMENT, IMPLEMENTATION SCIENCE ADVANCES, TECHNOLOGY TRANSFER, AND MULTI-CHANNEL DISSEMINATION, POSITION IT FOR TRANSFORMATIONAL IMPACT ON SUICIDE PREVENTION IN HEALTHCARE SETTINGS.

SUPPORTING TREATMENT ACCESS AND RECOVERY FOR CO-OCCURRING OPIOID USE AND MENTAL HEALTH DISORDERS (STAR-COD) - PROJECT SUMMARY / ABSTRACT OPIOID USE HAS DRAMATICALLY INCREASED IN THE UNITED STATES SINCE 2000, AND DISPROPORTIONALLY AFFECTS INDIVIDUALS WITH CO-OCCURRING MENTAL HEALTH DISORDERS (COD). INDIVIDUALS WITH COD ARE VULNERABLE TO SUBSTANCE USE RELAPSES, MENTAL HEALTH SYMPTOM EXACERBATIONS, OPIOID OVERDOSES, SUICIDE, HOMELESSNESS, AND CRIMINAL JUSTICE INVOLVEMENT. ALTHOUGH MEDICATION FOR OPIOID USE DISORDER (MOUD) IS THE GOLD STANDARD OF CARE, ENGAGEMENT RATES ARE AS LOW AS 18% WHICH NEGATIVELY IMPACT OUTCOMES. IN ADDITION, THERE IS MIXED EVIDENCE REGARDING THE INCREMENTAL THERAPEUTIC BENEFIT OF ADDING SINGLE BEHAVIORAL INTERVENTIONS TO IMPROVE MOUD OUTCOMES, DESPITE BEING RECOMMENDED IN CLINICAL PRACTICE GUIDELINES. FURTHERMORE, WHILE MULTI-COMPONENT INTERVENTIONS EXIST, LITTLE IS KNOWN ABOUT THEIR INCREMENTAL THERAPEUTIC EFFECT ON OUTCOMES IN CONJUNCTION WITH MOUD AND STANDARD MEDICAL MANAGEMENT FOR THOSE WITH A COD. MAINTAINING INDEPENDENCE AND SOBRIETY THROUGH SYSTEMS INTEGRATION, OUTREACH AND NETWORKING (MISSION) IS ONE SUCH MULTI-COMPONENT, CROSS-DISCIPLINARY, TEAM-BASED TREATMENT APPROACH, COMBINING 3 EVIDENCE-BASED PRACTICES ALONG WITH MOUD: 1) DUAL RECOVERY THERAPY (DRT), WHICH IS INTEGRATED GROUP THERAPY FOR COD; 2) PEER SUPPORT (PS), OFFERING SUPPORT FOR PEOPLE IN RECOVERY BY PEOPLE IN RECOVERY; AND 3) CRITICAL TIME INTERVENTION (CTI), A TIME-LIMITED FORM OF ASSERTIVE COMMUNITY TREATMENT. ALTHOUGH THE EFFECTIVENESS OF MISSION IS WELL ESTABLISHED, GIVEN THE DIFFICULTY WITH IMPLEMENTATION UPTAKE IN LARGE SYSTEMS DUE TO ITS COMPLEXITY AND THE NEED TO IMPROVE OUTCOMES FOR THOSE WITH A COD WHO RECEIVE MOUD, A CRITICAL NEXT STEP IS TO UNDERSTAND THE INCREMENTAL THERAPEUTIC BENEFIT OF MISSION + MOUD, AND IDENTIFY HIGHEST VALUE MISSION COMPONENTS THAT DRIVE THE LARGEST CLINICAL IMPROVEMENT AND OFFER THE GREATEST RETURN ON INVESTMENT. IN RESPONSE TO RFA-MH-21-145, THE PROPOSED 4-YEAR STUDY WITH A HALF FRACTIONAL FACTORIAL DESIGN, “SUPPORTING TREATMENT ACCESS AND RECOVERY FOR CO-OCCURRING OPIOID USE AND MENTAL HEALTH DISORDERS (STAR-COD),” WILL RANDOMIZE 1,000 PATIENTS WITH COD ACROSS 9 MOUD PROGRAMS TO THE FOLLOWING 5 CONDITIONS: 1) MOUD ALONE; 2) FULL MISSION PROTOCOL (CTI & DRT & PS) + MOUD; 3) CTI & DRT + MOUD; 4) PS & DRT + MOUD; OR 5) CTI & PS + MOUD. THERE ARE FOUR SPECIFIC AIMS. AIM 1: TO EVALUATE THE EFFECTIVENESS OF MISSION OR ITS COMPONENTS WITH MOUD VERSUS MOUD ALONE, AS WELL AS THE INCREMENTAL BENEFITS OF MISSION OR BUNDLED PARTS + MOUD TO IMPROVE ENGAGEMENT, SUBSTANCE USE AND MENTAL HEALTH SYMPTOMS. AIM 2: TO EXAMINE MECHANISMS OF ACTION OF MISSION IN COD. AIM 3: TO CONDUCT A COMPREHENSIVE ECONOMIC EVALUATION OF MISSION OR ITS PARTS AND MOUD. EXPLORATORY AIM: 4. TO CONSTRUCT A PREDICTIVE MODEL TO MATCH OPTIMUM COMBINED USE OF MISSION PARTS WITH PATIENT NEEDS TO IMPROVE HEALTH OUTCOMES. THIS PROPOSAL IS ALIGNED WITH NIMH’S STRATEGIC PLAN GOAL 4 “TO INCREASE THE PUBLIC HEALTH IMPACT OF SERVICES STUDIES, INVESTIGATORS TEST WAYS TO ADAPT, IMPLEMENT, AND SCALE EFFECTIVE INTERVENTIONS FOR VARIED POPULATIONS ACROSS MULTIPLE SERVICE SETTINGS IN A COST-EFFECTIVE MANNER.” UPON COMPLETION, IT COULD OFFER MORE COST EFFECTIVE, ROBUST, PERSONALIZED TREATMENTS.

CENTER FOR REPRODUCIBLE NEUROIMAGING COMPUTATION (CRNC)

AIDS EDUCATION AND TRAINING CENTERS PROGRAM

IMPROVING ORTHOPEDIC OUTCOMES THROUGH A NATIONAL TJR REGISTRY

CD4 T CELLS IN ANTI-VIRAL IMMUNITY AND IMMUNE PATHOLOGY

CENTER FOR 3D STRUCTURE AND PHYSICS OF THE GENOME

EMERGENCY DEPARTMENT SAFETY ASSESSMENT AND FOLLOW-UP EVALUATION (EDSAFE) TRIAL

T CELL MEMORY TO PATHOGENS: GENERATION AND FUNCTION

1/2 PROSPECTIVE TREATMENT EFFICACY IN IPF USLNG GENOTYPE FOR NAC SELECTION (PRECISIONS) TRIAL AND MOLECULAR ENDOPHENOTYPING IN IDIOPATHIC PULMONARY FIBROSIS AND INTERSTITIAL LUNG DISEASES STUDY - ABSTRACT DESPITE BEING THE MOST FREQUENT AND DEADLY OF THE INTERSTITIAL LUNG DISEASES (ILD), IDIOPATHIC PULMONARY FIBROSIS (IPF) REMAINS CHALLENGING TO DIAGNOSE AND TREAT. THE DIAGNOSTIC PROCESS FOR IPF RELIES ON SUBJECTIVE INTERPRETATIONS OF CLINICAL DATA WHILE CURRENT ANTIFIBROTIC THERAPIES EMPLOY A “ONE SIZE FITS ALL” PARADIGM. MEMBERS OF OUR TEAM HAVE BEEN AT THE FOREFRONT OF DEVELOPING `OMICS APPROACHES TO DIAGNOSE AND DEFINE PROGNOSIS IN ILDS. IMPORTANTLY, WE IDENTIFIED THE FIRST PHARMACOGENOMIC INTERACTION SUGGESTING THAT IPF PATIENTS WITH TOLLIP RS3750920 T/T GENOTYPE STRONGLY BENEFITED FROM NAC. THERE IS A CRITICAL NEED FOR MOLECULAR CLASSIFICATIONS THAT DEFINE IPF, THUS ALLOWING PRECISION-BASED MANAGEMENT. OUR LONG-TERM GOALS ARE TO MOVE ILD DIAGNOSIS AND THERAPY INTO THE “ERA OF PRECISION MEDICINE.” IN A HIGHLY INNOVATIVE APPROACH WE HAVE PARTNERED WITH THE PULMONARY FIBROSIS FOUNDATION (PFF) CLINICAL CARE NETWORK (CCN) AND REGISTRY. THIS GROUP HAS RECRUITED ILD PATIENTS WHO HAVE PROVIDED EXTENSIVE BASELINE PHENOTYPIC AND LONGITUDINAL OUTCOME DATA, BIOLOGICAL SAMPLES AND HAVE CONSENTED TO BE RE-CONTACTED FOR FUTURE RESEARCH. OUR OVERALL OBJECTIVE IS TO EFFICIENTLY CONDUCT A NOVEL, PRECISION GENOTYPE-BASED TRIAL IN IPF WHILE LEVERAGING THE CCN AND ITS UNIQUE BIOSPECIMEN COLLECTION TO CHARACTERIZE A BROAD RANGE OF ILDS MOLECULARLY AND IDENTIFY GENETIC VARIANTS OF IPF RISK. TO ADDRESS OUR GOAL OF PRECISION-BASED ILD MANAGEMENT, WE WILL COMPLETE THREE COMPLEMENTARY SPECIFIC AIMS. IN AIM 1 WE WILL DETERMINE IF NAC IS AN EFFECTIVE TREATMENT IN IPF PATIENTS CHARACTERIZED BY A PRECISION GENOTYPE APPROACH. IN PARTNERSHIP WITH THE PFF, WE WILL IDENTIFY PFF REGISTRY SUBJECTS WITH THE TOLLIP T/T GENOTYPE TO BEGIN RANDOMIZING 200 IPF PATIENTS FOLLOWED BY ENROLLING NEW SUBJECTS AT THE SAME CLINICAL SITES TO RECEIVE NAC OR PLACEBO IN A DOUBLE-BLIND FASHION. THIS STUDY, THE “PROSPECTIVE TREATMENT EFFICACY IN IPF USING GENOTYPE FOR NAC SELECTION (PRECISIONS)” TRIAL, WILL DOCUMENT THE BENEFITS OF AN INNOVATIVE “PRECISION” GENOTYPE-SPECIFIC STUDY DESIGN OF A WELL-TOLERATED AND INEXPENSIVE THERAPY. IN AIM 2 WE WILL DISTINGUISH IPF FROM NON-IPF ILDS USING UNBIASED COMBINATIONS OF BLOOD TRANSCRIPTOMICS AND PROTEOMICS. WE PROPOSE TO CONDUCT RNA-SEQ AND PROTEOMICS TO CHARACTERIZE GENE EXPRESSION AND PROTEIN BIOMARKERS ON THE ENTIRE PFF REGISTRY COHORT. WE WILL DEFINE “SIGNATURES” FOR DISTINGUISHING IPF FROM NON-IPF ILDS. OUR UNBIASED APPROACHES TO `OMICS TRAITS WILL BE INTEGRATED TO REVEAL `OMICS RISK SCORES THAT DEFINE INDIVIDUAL DISEASES, PREDICT DISEASE COURSE, AND RESPONSE TO THERAPY. IN AIM 3 WE WILL IDENTIFY GENETIC VARIANTS PLAYING A ROLE IN IPF RISK. WE WILL CONDUCT WHOLE GENOME SEQUENCING OF THE ENTIRE PFF COHORT TO DETECT NOVEL GENETIC ASSOCIATIONS FOR IPF AND ILD RISK. WITH SUFFICIENT POWER, WE WILL ASSESS BOTH COMMON AND RARE/INFREQUENT VARIANTS IN COMPARISON TO ETHNICALLY MATCHED UN-AFFLICTED CASES, AND BETWEEN ILD COHORTS TO MEET OUR OBJECTIVE. THIS WILL ESTABLISH THE LARGEST COLLECTION OF ITS KIND AND ESTABLISH QUANTITATIVE TRAIT LOCI FOR ALL `OMICS' DATA. THE RESULTS OF OUR PROPOSED EXPERIMENTS WILL MOVE ILD MANAGEMENT, AND IPF THERAPY, IN PARTICULAR, INTO THE PRECISION MEDICINE ERA.

VECTORED DELIVERY OF OLIGOCLONAL ANTIBODIES FOR PROTECTION AGAINST ENTEROTOXIN MEDIATED DIARRHEAL DISEASES

NEW APPROACHES TO GENE THERAPY FOR ALPHA-1 ANTITRYPSIN DEFICIENCY

UNDERSTANDING THE ORIGINS OF EARLY COPD

SYSTEMS GENETICS OF TUBERCULOSIS

UNIVERSITY OF MASSACHUSETTS CENTER FOR CLINICAL AND TRANSLATIONAL SCIENCE

INNATE IMMUNE ACTIVATION IN MALARIA

QUALITY ASSURANCE REVIEW CENTER

SUSTAINED STRENGTHENING OF PUBLIC HEALTH LABORATORY, TRANSFUSION SERVICES, AND HEALTH CARE WORKER INFECTION CONTROL PRACTICES FOR EBOLA VIRUS DISEASE

VIRAL INFECTION INFLUENCE ON TRANSPLANTATION TOLERANCE

BOSTON PUERTO RICAN HEALTH STUDY - CVD RISK FACTORS

EDAC: ENCODE DATA ANALYSIS CENTER

MASSACHUSETTS JUSTICE COMMUNITY OPIOID INNOVATION NETWORK (JCOIN) CLINICAL RESEARCH CENTER

HIGH ENERGY PHYSICS RESEARCH ON THE ATLAS EXPERIMENT AT THE LARGE HADRON COLLIDER

SPECIFICALLY TRIGGERABLE MULTI-SCALE RESPONSES IN ORGANIZED ASSEMBLIES

RESCUING THE FRAGILE X SYNDROME BY RESETTING TRANSLATIONAL HOMEOSTASIS

COOPERATIVE AGREEMENT - UNIVERSITY OF MASSACHUSETTS

SUSTAINED STRENGTHENING OF PUBLIC HEALTH LABORATORY, TRANSFUSION SERVICES, AND HEALTH CARE WORKER INFECTION CONTROL PRACTICES FOR EBOLA VIRUS DISEASE

COORDINATING CENTER FOR TRANSITION AND POSTSECONDARY PROGRAMS FOR STUDENTS WITH INTELLECTUAL DISABILITIES

ANTICIPATING INFLUENZA RESISTANCE EVOLUTION (AIRE): PATHWAYS AND STRATEGIES

TRANSITION PROGRAMS FOR STUDENTS WITH INTELLECTUAL DISABILITIES COORDINATING CENTER (COORDINATING CENTERS)

EDAC: ENCODE DATA ANALYSIS CENTER

ADVANCEMENT OF CRISPR-BASED ADIPOSE TISSUE THERAPIES FOR TYPE 2 DIABETES TO NONHUMAN PRIMATES

INDUCTION OF NEUTRALIZING ANTIBODIES TARGETING CD4 BINDING REGION OF HIV-1 ENV

CHEMICAL PROBES TO DECIPHER PAD BIOLOGY

TACE

RNA LOCALIZATION AND TRANSLATIONAL CONTROL

FUNCTION/OPTIMIZATION OF A NEMATICIDAL CRY TOXIN ARSENAL

REGULATION OF CHROMATIN DYNAMICS

TRANSCRIPTION NETWORKS IN C ELEGANS ORGANOGENESIS

UNIVERSITY TRANSPORTATION CENTERS

NOVEL THERAPEUTICS FOR FSHD

PRECISION STUDIES OF QCD AND ELECTRO-WEAK INTERACTIONS

SYSTEMS BIOLOGY OF INSULIN RESISTANCE

AIDS EDUCATION AND TRAINING CENTERS PROGRAM

GENE REGULATORY AND METABOLIC NETWORK STRUCTURE, FUNCTION AND EVOLUTION

ADVANCING GERIATRICS INFRASTRUCTURE & NETWORK GROWTH (AGING) INITIATIVE

INTRAFLAGELLAR TRANSPORT PROTEINS IN MICE

2016 WRRI 104B PROGRAM

TOLL-LIKE RECEPTORS IN SYSTEMIC AUTOIMMUNE DISEASE

THE INTERDEPENDENCY OF DRUG RESISTANCE EVOLUTION AND DRUG DESIGN: HIV-1 PROTEASE

ACTIVATION OF INSECT IMMUNITY BY GRAM-NEGATIVE BACTRIA

NEW ENGLAND CENTER OF EXCELLENCE IN VECTOR-BORNE DISEASES

TRAINING LONG TERM - LEND NEURODEVELOPMENTAL DISABILITIES

A BIOSAFETY LEVEL 3 LABORATORY FOR VIRAL PATHOGENS - PROGRAM SUMMARY/ABSTRACT THE UNIVERSITY OF MASSACHUSETTS CHAN MEDICAL SCHOOL (UMASS CHAN) SEEKS NIH C06 FUNDING TO RENOVATE EXISTING SPACE IN THE MEDICAL SCHOOL (S) BUILDING TO CONSTRUCT AN IN VITRO BIOSAFETY LEVEL 3 (BSL-3) LABORATORY FOR VIRAL PATHOGENS. AS AN INTERNATIONALLY RECOGNIZED LEADER IN INFECTIOUS DISEASE RESEARCH, UMASS CHAN HAS MADE PIVOTAL CONTRIBUTIONS TO THIS FIELD, WITH A STRONG FOCUS ON HAZARDOUS PATHOGENS, INCLUDING BOTH VIRAL AND BACTERIAL PATHOGENS. DURING THE COVID-19 PANDEMIC, UMASS CHAN QUICKLY BECAME ONE OF THE LEADING INSTITUTES FOR RESEARCH ON SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS-2 (SARS-COV-2). OUR RESEARCHERS OBTAINED NUMEROUS AWARDS FROM THE NIH, OTHER GOVERNMENTAL AGENCIES, AND PRIVATE FOUNDATIONS FOR THESE STUDIES. SINCE THEN, OUR RESEARCHERS HAVE ALSO OBTAINED FUNDING FOR COLLABORATIVE RESEARCH PROGRAMS TO STUDY OTHER BSL-3-LEVEL VIRUSES OF PANDEMIC POTENTIAL, SUCH AS VIRUSES THAT CAUSE VIRAL HEMORRHAGIC FEVER (VHF) AND ALPHAVIRUSES. C06 FUNDING IS CRITICAL TO CONTINUE THESE IMPORTANT STUDIES. OUR BSL-3 CORE LABORATORIES HAVE BEEN STRAINED BY THE INCREASED USAGE DUE TO THE PANDEMIC AND THE ADDITION OF OTHER BSL-3 VIRAL PATHOGENS, SUCH AS VHF. TO ACCOMMODATE THIS INCREASE, WE HAVE USED THE SATELLITE BSL-3 LAB IN THE BIOTECH TWO BUILDING, WHICH WILL BE LOST WHEN UMASS CHAN REPURPOSES THIS BUILDING IN 2026. THE REMAINING S7 BSL-3 LAB IS ALREADY OPERATING AT CAPACITY FOR MYCOBACTERIUM TUBERCULOSIS AND YERSINIA PESTIS STUDIES AND CANNOT ADEQUATELY ACCOMMODATE THE RESEARCHERS STUDYING RISK GROUP 3 VIRUSES. TO PROACTIVELY ADDRESS THIS ISSUE, WE SEEK NIH C06 FUNDING TO CONVERT EXISTING SPACE ON THE 7TH FLOOR OF THE S-BUILDING INTO A SECOND IN VITRO BSL-3 LAB DEDICATED TO RESEARCH ON VIRAL PATHOGENS. THE PROPOSED NEW FACILITY ADDRESSES INCREASING DEMANDS ON OUR BSL-3 RESOURCES BY UMASS CHAN FACULTY AND OTHER REGIONAL INVESTIGATORS. THERE IS STRONG INSTITUTIONAL SUPPORT FOR THIS PROJECT AND A COMMITMENT TO FULLY EQUIP THE NEW LAB, INCLUDING THE PURCHASE OF ADVANCED IMAGING EQUIPMENT CURRENTLY UNAVAILABLE IN BSL-3. THE PROPOSED FACILITY WILL ENHANCE THE SAFETY AND RESILIENCE OF THE BSL-3 RESEARCH CORE, AND MAINTAIN THE PRODUCTIVITY OF FUNDED AND FUTURE RESEARCH ON RISK GROUP 3 VIRUSES. OUR MEDICAL SCHOOL IS UNIQUELY POSITIONED TO BRIDGE CLINICAL AND BASIC RESEARCH STUDIES. AS A LEADING SITE FOR CLINICAL TRIALS, OUR RESEARCHERS HAVE ACCESS TO PATIENT SAMPLES TO ENHANCE IN VITRO AND IN VIVO STUDIES. OUR FINDINGS CAN BE TRANSLATED TO DEVELOP NOVEL PREVENTION AND THERAPEUTIC STRATEGIES LEVERAGING OUR WORLD-RENOWNED RNA THERAPEUTICS INSTITUTE AND INSTITUTE FOR DRUG RESISTANCE, AS WELL AS OUR PARTNERSHIP WITH MASSBIOLOGICS FOR VACCINE AND BIOLOGIC THERAPY DEVELOPMENT, MAKING UMASS CHAN A POWERHOUSE FOR BENCH-TO-BEDSIDE TRANSLATIONAL RESEARCH. ROBUST BSL-3 LABS ARE NEEDED TO MAINTAIN THIS EXCELLENCE AND ADDRESS CURRENT AND EMERGING PATHOGENS WITH PANDEMIC POTENTIAL.

RNA-BASED STRATEGIES FOR PREVENTION AND TREATMENT OF ALPHAVIRUS AND HEMORRHAGIC FEVER VIRUS INFECTION

PHOTOMECHANICAL MATERIAL SYSTEMS: FROM MOLECULES TO DEVICES

THINK COLLEGE NETWORK (TCN): A NATIONAL TECHNICAL ASSISTANCE AND DISSEMINATION CENTER

UMASS WORCESTER PREVENTION RESEARCH CENTER

SWIFT CA - SUPPORTING WARFIGHTERS THROUGH INNOVATIVE FOOTWEAR TECHNOLOGIES

MULTI-OMICS DACC: THE DATA ANALYSIS AND COORDINATION CENTER FOR THE COLLABORATIVE MULTI-OMICS FOR HEALTH AND DISEASE INITIATIVE - ABSTRACT THE NIH IS ESTABLISHING A NEW MULTI-OMICS FOR HEALTH AND DISEASE CONSORTIUM TO ADVANCE THE APPLICATION OF MULTI-OMIC TECHNOLOGIES TO STUDY HEALTH AND DISEASE IN ANCESTRALLY DIVERSE POPULATIONS. THE CONSORTIUM COMPRISES THREE COMPONENTS: DISEASE STUDY SITES (DSSS), ‘OMICS PRODUCTION CENTERS (OPCS), AND A DATA ANALYSIS AND COORDINATION CENTER (DACC). THE PROJECT AIMS TO ESTABLISH A DACC TO COORDINATE AND SUPPORT THE CONSORTIUM’S ACTIVITIES AND MAXIMIZE ITS SUCCESS. TO BE IMPACTFUL, THE CONSORTIUM’S EXPERIMENTAL PROTOCOLS MUST BE TRANSPARENT AND REPRODUCIBLE, DATA MUST ADHERE TO THE FAIR GUIDING PRINCIPLES (FINDABLE, ACCESSIBLE, INTEROPERABLE, REUSABLE), AND COMPUTATIONAL METHODS AND SOFTWARE TOOLS MUST BE OPEN TO THE PUBLIC. FURTHERMORE, AN INTERACTIVE PORTAL IS NEEDED FOR INTUITIVE ACCESS TO THE DATA, AND DEDICATED OUTREACH EFFORTS ARE REQUIRED TO ASSIST THE COMMUNITY IN DATA USE. WE HAVE ASSEMBLED A UNIQUE TEAM OF INVESTIGATORS, DATA WRANGLERS, SOFTWARE ENGINEERS, BIOINFORMATICIANS, AND POSTDOCS TO FORM A DACC TO MEET THE CHALLENGES OF ENSURING HIGH DATA QUALITY AND MAXIMIZING THE CONSORTIUM’S IMPACT. ALL FIVE DACC INVESTIGATORS HAVE HELD LEADERSHIP POSITIONS IN LARGE CONSORTIA IN THE PAST DECADE AND BRING SUBSTANTIAL EXPERTISE IN DATA COORDINATION, MANAGEMENT, HARMONIZATION, ANALYSIS, AND INTEGRATION. OUR DACC WILL ACCOMPLISH THE GOALS OF THE CONSORTIUM VIA SIX SPECIFIC AIMS: AIM 1. COORDINATING AND CONTRIBUTING TO CONSORTIUM-WIDE PROTOCOL DEVELOPMENT, DATA ANALYSIS, AND METHODS DEVELOPMENT. AIM 2. MANAGING AND SECURING CONSORTIUM DATA BY SPECIFYING METADATA, ESTABLISHING SUBMISSION PROCESSES AND STANDARDS, AND INCORPORATING EXPERIMENTAL DATA AND ANALYSIS RESULTS INTO ANVIL. AIM 3. CREATING A MULTI-DIMENSIONAL DATASET THAT IS AVAILABLE TO THE BROADER RESEARCH COMMUNITY. AIM 4. DESIGNING, DEVELOPING, AND MAINTAINING AN OPEN-ACCESS PORTAL FOR CATALOGING, QUERYING, AND VISUALIZING SUMMARY-LEVEL DATA. AIM 5. COORDINATING CONSORTIUM LOGISTICS BY ORGANIZING AND FACILITATING INTERNAL AND EXTERNAL ACTIVITIES, COMMUNICATIONS, AND COLLABORATIONS. AIM 6. COORDINATING COMMUNITY OUTREACH AND DISSEMINATION OF CONSORTIUM FINDINGS.

RNA THERAPEUTICS FOR INFECTIOUS DISEASES: VIRAL HEMORRHAGIC FEVER

TARGETING ENSEMBLES OF DRUG RESISTANT HIV-PROTEASE

SHARPS INJURIES AND BLOOD EXPOSURE IN HOMES HEALTH CARE

ROLE OF THE EPITRANSCRIPTOME IN CANCER

NO LONGER 'A DREAM DEFERRED:' GREATER MINORITY STEM PARTICIPATION THROUGH ACADEMIC OPPORTUNITY AND INSTITUTIONAL CHANGE

UNVEILING THE OBSCURED FORMATION OF STARS AND GALAXIES: LARGE-SCALE LEGACY SURVEYS WITH A NEW THREE COLOR IMAGING POLARIMETER ON A 50-M MILLIMETER-WA

ANTIMICROBIAL OLIGOMERS FOR BIODEFENSE AND EMERGING FOOD BORNE INFECTIOUS DISEASE

UMASS CENTER FOR HEALTH EQUITY INTERVENTION RESEARCH

UNIVERSITY OF MASSACHUSETTS CENTER FOR CLINICAL AND TRANSLATIONAL SCIENCE

DISABILITY REHABILITATION RESEARCH PROJECTS

ADVANCING RNA THERAPEUTICS FOR HUNTINGTON?S DISEASE

MODEL STATE-SUPPORTED AHEC PROGRAM

RIP PROTEINS IN INNATE IMMUNE SIGNALING

PRECISION EDITING OF GRANULIN MUTATIONS THAT CAUSE FRONTOTEMPORAL DEMENTIA - PROJECT SUMMARY FRONTOTEMPORAL DEMENTIA (FTD) IS THE MOST COMMON FORM OF PRESENILE DEMENTIA BEFORE THE AGE OF 60, AND NO EFFECTIVE TREATMENTS ARE AVAILABLE. 40% OF FTD CASES ARE FAMILIAL AND ONE OF THE MOST COMMON GENES WITH FTD-CAUSING MUTATIONS IS GRANULIN (GRN), WHICH ENCODES PROGRANULIN (PGRN), A SECRETED REGULATORY PROTEIN. GRN MUTATIONS, SUCH AS THE MOST PREVALENT NONSENSE MUTATION C.1477C>T (P.R493X), RESULT IN PGRN HAPLOINSUFFICIENCY, AND ATTEMPTS AT DEVELOPING SMALL MOLECULE, BIOLOGIC, AND GENE REPLACEMENT THERAPIES HAVE PROVEN CHALLENGING DUE TO INHERENT TOXICITIES THAT RESULT FROM PGRN OVEREXPRESSION. PRECISION GENOME EDITING STRATEGIES TO CORRECT THE ENDOGENOUS GENE AND RESTORE NATIVELY REGULATED PROGRANULIN PRODUCTION, EVEN AT <100% EDITING EFFICIENCY, THEREFORE REPRESENT A SUPERIOR THERAPEUTIC PATH. THE TWO BEST-DEVELOPED MODES OF PRECISION EDITING IN VIVO ARE BASE EDITING (BE) AND PRIME EDITING (PE), EACH WITH COMPLEMENTARY SETS OF ADVANTAGES AND DISADVANTAGES FOR ADDRESSING PATHOGENIC C:G-TO-T:A MUTATIONS SUCH AS GRN C. 1477C>T (P.R493X). IN THIS PROPOSAL, WE HAVE ASSEMBLED AN EXPERIENCED, MULTIDISCIPLINARY TEAM TO DEVELOP A MAXIMALLY EFFECTIVE THERAPEUTIC EDITING APPROACH TO TREAT GRN-FTD CAUSED BY THIS MUTATION. WE WILL ASSESS CANDIDATE APPROACHES THAT EMPLOY EITHER BE OR PE, INITIALLY IN GRN-FTD PATIENT INDUCED PLURIPOTENT STEM CELL (IPSC)-DERIVED NEURONS AND GLIAL CELLS TO CORRECT GRNR493X, AND THEN COMPARE THEIR EFFECTIVENESS TO PREVENT DISEASE PROGRESSION IN A HUMANIZED GRNR493X MOUSE THAT FAITHFULLY MODELS SOME ASPECTS OF FTD. OUR PE DEVELOPMENT WILL ALSO TEST THE FEASIBILITY OF REWRITING LARGER EXON SEGMENTS, THEREBY ENABLING CORRECTION OF ADDITIONAL MUTATIONS FROM THE PATIENT POPULATION TO BE ADDRESSED WITH A SINGLE CORRECTIVE REAGENT. SAFE AND EFFECTIVE DELIVERY REPRESENTS ONE IMPORTANT CHALLENGE IN THERAPEUTIC GENOME EDITING, ESPECIALLY IN THE CENTRAL NERVOUS SYSTEM. WE WILL ADDRESS THIS CHALLENGE BY ADVANCING BOTH VIRAL VECTOR DELIVERY AND NOVEL NON-VIRAL DELIVERY STRATEGIES THAT WE ARE DEVELOPING TO DEFINE THE SAFEST AND MOST EFFECTIVE DELIVERY MODALITY FOR THESE EDITING TECHNOLOGIES. THIS WORK PROMISES TO LEAD TO A SPECIFIC, EFFECTIVE THERAPEUTIC INTERVENTION FOR A DEVASTATING AND CURRENTLY UNTREATABLE FORM OF HERITABLE DEMENTIA. OUR STUDIES WILL ALSO ADVANCE PLATFORM TECHNOLOGIES AND ESTABLISH A BLUEPRINT FOR DEVELOPING CLINICAL GENOME EDITING APPROACHES, LEVERAGING THESE TOOLS FOR ADDITIONAL MUTATIONS THAT CAUSE FTD AND OTHER FORMS OF DEMENTIA.

MEMBRANE TOPOGRAPHY OF CELL SIGNALING COMPLEXES

GENETIC CONTROL OF PROGRAMMED CELL DEATH (APOPTOSIS) AND COMPENSATORY PROLIFERATION IN DROSOPHILA

STREAMLINE ASSESSMENT OF EARLY LETHAL PHENOTYPES IN THE MOUSE

DISSECTING FUNCTIONAL AUTOIMMUNITY THROUGH HIGH-RESOLUTION MULTIOMICS IN A VITILIGO CENTER OF RESEARCH TRANSLATION (V-CORT) - OVERALL – PROJECT SUMMARY ORGAN-SPECIFIC AUTOIMMUNITY REQUIRES A SERIES OF PRECISE CELLULAR INTERACTIONS TO COORDINATE TARGET CELL DESTRUC- TION WITHIN COMPLEX TISSUES. VITILIGO IS AN AUTOIMMUNE DISEASE OF THE SKIN IN WHICH CYTOTOXIC CD8+ T CELLS TARGET PIGMENT-MAKING MELANOCYTES, WHICH RESULTS IN DISFIGURING WHITE SPOTS THAT ARE PARTICULARLY DEVASTATING FOR THOSE WITH DARKER SKIN. VITILIGO IS AN IDEAL DISEASE IN WHICH TO INVESTIGATE MECHANISMS OF ORGAN-SPECIFIC AUTOIMMUNITY BECAUSE DISEASE PHENOTYPE CAN BE DIRECTLY CORRELATED TO MOLECULAR PATHWAYS. THAT IS, AFFECTED SKIN CAN BE OB- SERVED AND SAMPLED, TARGET CELLS AND ANTIGENS ARE KNOWN, AND TRANSLATIONAL RESEARCH TOOLS ARE AVAILABLE. VITI- LIGO SHARES GENETIC RISK ALLELES AND OTHER MECHANISMS WITH AUTOIMMUNE DISEASES LIKE TYPE 1 DIABETES AND MUL- TIPLE SCLEROSIS, WHICH ARE MORE DIFFICULT TO STUDY IN HUMAN PATIENTS. THROUGH VITILIGO WE CAN DEVELOP A COMPRE- HENSIVE UNDERSTANDING OF ORGAN-SPECIFIC AUTOIMMUNITY AS IT PROGRESSES WITHIN HUMAN TISSUE. OUR OBJECTIVE IS TO DETERMINE THE MECHANISMS BY WHICH AUTOREACTIVE T CELLS NAVIGATE THE SKIN, COMMUNICATE WITH NEIGHBORING CELLS, ENGAGE AND DESTROY MELANOCYTES, AND CREATE LONG-TERM MEMORY OF AUTOIMMUNITY DI- RECTLY WITHIN VITILIGO LESIONS. WE GENERATED AN EXTENSIVE SET OF HIGH-RESOLUTION, TRANSLATIONAL MULTIOMICS DATA FROM VITILIGO PATIENT SKIN AND ASSEMBLED IT INTO AN INTEGRATED COMMUNICATION NETWORK AMONG MULTIPLE CELL TYPES THAT COORDINATE DISEASE PROGRESSION. THIS PROVIDES CLUES INTO VITILIGO PATHOGENESIS THAT MUST NOW BE VALIDATED, DISSECTED, AND REASSEMBLED TO REVEAL FUNDAMENTAL CONCEPTS OF AUTOIMMUNITY. THUS, WE HYPOTHESIZE THAT AUTO- REACTIVE T CELL FUNCTION IS CAREFULLY COORDINATED BY CELLULAR SIGNALS WITHIN THE MICROENVIRONMENT OF THE EPIDERMIS. TO TEST THIS HYPOTHESIS, WE WILL LEVERAGE EXISTING DATA, A MULTIDISCIPLINARY TEAM OF LEADING INVESTIGATORS, CUTTING EDGE TOOLS DESIGNED FOR DISCOVERY, AND AN INNOVATIVE STRATEGY TO DISCOVER HOW SKIN CELLS COORDINATE AUTOIM- MUNITY DURING VITILIGO. PROJECT 1 WILL INVESTIGATE AUTOREACTIVE T CELL FUNCTION IN VITILIGO TO DETERMINE HOW AUTORE- ACTIVE T CELL CLONAL DIVERSITY AND LOCALIZATION DEFINE THE CLINICAL DISEASE PHENOTYPE AND COORDINATE MELANOCYTE DESTRUCTION. PROJECT 2 WILL FOCUS ON CELL-CELL COMMUNICATIONS AND TISSUE MEMORY IN VITILIGO TO DISSECT THE MECHANISMS BY WHICH LIGAND-RECEPTOR INTERACTIONS COORDINATE T CELL LOCALIZATION, FUNCTION, AND INFLAMMATORY MEMORY. THESE PROJECTS WILL BE SUPPORTED BY THE HIGH-RESOLUTION SPATIAL TRANSCRIPTOMICS RESEARCH CORE US- ING SEQ-FISH+ TO TRANSLATE OUR VITILIGO MULTIOMICS DATA INTO A COMPLETE SPATIAL UNDERSTANDING OF CELLULAR POSITION AND COMMUNICATION WITHIN VITILIGO LESIONS. THE ADMINISTRATIVE CORE WILL PROMOTE COMMUNICATION, ENSURE SCIEN- TIFIC ACHIEVEMENT, AND MONITOR FISCAL MANAGEMENT TO SUPPORT FOCUS ON RESEARCH GOALS AND IMPLEMENTATION. WE EXPECT TO CREATE AN INTEGRATED UNDERSTANDING OF COORDINATED CELLULAR COMMUNICATIONS AND INTERACTIONS THAT DRIVE VITILIGO PATHOGENESIS. THIS WILL REVEAL FUNDAMENTAL MECHANISMS OF AUTOIMMUNITY AND SUPPORT BETTER THERA- PEUTIC APPROACHES FOR THESE DEVASTATING DISEASES. THE UNIQUE CHARACTERISTICS OF VITILIGO AS WELL AS OUR PRELIMI- NARY DATA, INVESTIGATIVE TEAM, AND INNOVATIVE PLAN PROVIDE US WITH AN UNPARALLELED OPPORTUNITY FOR DISCOVERY.

SMALL SILENCING RNA FUNCTION IN GENOME MAINTENANCE AND GAMETE DEVELOPMENT

STRUCTURE AND FUNCTION OF THE EXOCYST COMPLEX

MODEL STATE-SUPPORTED AHEC PROGRAM

A SYSTEM OF SAFETY (SOS): PREVENTING SUICIDE THROUGH HEALTHCARE SYSTEM TRANSFORMATION

NATIONAL CENTER ON PROGRAM MANAGEMENT AND FISCAL OPERATIONS

REGULATION OF CYTOKINESIS IN FISSION YEAST

A KNOWLEDGE ENVIRONMENT FOR NEUROIMAGING IN CHILD PSYCHIATRY

WE PROPOSE A RESEARCH PROGRAM INVOLVING TWO CONVENTIONAL BALLOON FLIGHTS FROM FT. SUMNER NM TO STUDY DEBRIS DISKS OF FIVE STARS.THESE EXPERIMENTS INCREMENTALLY BUILD ON PREVIOUS FLIGHT-PROVEN SUBSYSTEMS WITH A GOAL OF CONDUCTING FUNDAMENTAL SCIENCE WHILEMATURING KEY EXOPLANET TECHNOLOGIES.FLIGHT ONE WILL USE AN 0.6 M OFF-AXIS TELESCOPE SYSTEM IN CONJUNCTION WITH A VISIBLE NULLING CORONAGRAPH TO DIRECTLY IMAGE ALPHA LYR DELTA DRA AND EPSILON ERI. THE FLIGHT-PROVEN WASP GONDOLA ALONG WITH A FINE POINTING SYSTEM FLIGHT-PROVEN ABOARD OUR SOUNDINGROCKET PROGRAM WILL COMPLETE THE EXPERIMENT COMPLEMENT.IN FLIGHT TWO A FIELD-PROVEN VECTOR VORTEX CORNAGRAPH WILL REPLACE THE NULLING CORONAGRAPH AND A FIELD-PROVEN INTEGRAL FIELD DETECTOR THE MKID WILL REPLACE THE SCIENCE CAMERA OF THE FIRST FLIGHT. THE PLANNED TARGETS FOR THE SECOND FLIGHT ARE ALPHA AQL TAU CET ANDEPSILON ERI. WITH CONSERVATIVE PERFORMANCE ESTIMATES WE EXPECT TO OBTAIN AN IMAGE OF EPSILON ERI IN THE SECOND FLIGHT AS WELL ASSOME SPECTRAL CHARACTERISTICS. SEVERAL OTHER TARGETS ARE AVAILABLE AND WILL BE SELECTED IF/AS TIME PERMITS. OUR SIMULATIONS INDICATE THETANTALIZING POSSIBILITY OF OBTAINING A DIRECT IMAGE OF THE SUGGESTED EPSILON ERI B. IF SUCCESSFUL IT WILL PRODUCE ONE OR MORE IMAGES OFJUPITER-LIKE PLANETS AROUND SUN-LIKE STARS.WITH A DELIBERATE APPROACH OF STEPWISE MATURING KEY ENABLING TECHNOLOGIES WHILE DEMONSTRATING IMPORTANT SCIENCE RESULTS PLANETARYIMAGING CONCEPT TESTBED USING A RECOVERABLE EXPERIMENT - CORONAGRAPH (PICTURE C ) WILL FIRMLY PUT US ON THE PATH TOWARDSREALIZING THE GOAL OF CHARACTERIZING PLANETS IN THE HABITABLE ZONE. IN THE SHORT-TERM IT WILL FLIGHT DEMONSTRATE HIGH PRIORITY TECHNOLOGIESENDORSED BY THE AFTA AND STDT STUDIES.

1/2 DISCOVERY AND VALIDATION OF NEURONAL ENHANCERS ASSOCIATED WITH THE DEVELOPMENT OF PSYCHIATRIC DISORDERS

ROLE OF HEAT SHOCK PROTEIN 90 IN ALCOHOLIC LIVER DISEASE

GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP)

REGULATION OF CD8+ T CELL IMMUNITY TO TUBERCULOSIS (PENDING TITLE)

RULES OF GENE EXPRESSION MODELED ON HUMAN DENDRITIC CELL RESPONSE TO PATHOGENS

EXPANDING THE CHEMICAL DIVERSITY OF THERAPEUTIC OLIGONUCLEOTIDES TO TREAT NEURODEGENERATIVE DISORDERS

SINGLE-PARTICLE AND COLLECTIVE PHENOMENA IN NUCLEI

ART: FACILITATING IMPACTFUL NEW ENTREPRENEURS TO ACCELERATE RESEARCH TRANSLATION (FINE ART) -THE FOCUS OF THIS PROJECT IS TO IDENTIFY, FOSTER RELATIONSHIPS WITH, AND FACILITATE THE DEVELOPMENT OF EMERGING ENTREPRENEURS TO INCREASE THE CAPACITY OF THE UNIVERSITY OF MASSACHUSETTS AMHERST TO REALIZE THE TRANSLATIONAL IMPACTS OF ITS WELL-DEVELOPED BASIC RESEARCH ENTERPRISE. THE EXPECTED OUTCOME IS TO CREATE A SUSTAINABLE INNOVATION ENGINE TO PREPARE STUDENTS AND FACULTY TO CONTRIBUTE TO THE INNOVATION ECONOMY, SHORTEN TIMELINES BETWEEN IDEATION AND DE-RISKED ENTERPRISES READY FOR SIGNIFICANT SEED-ROUND AND VENTURE CAPITALIZATION, AND ESTABLISH ENTERPRISES THAT EMBRACE DEI AND DEVELOP TECHNOLOGIES THAT ADDRESS IMPORTANT SOCIETAL NEEDS. THE PROJECT WILL EQUIP DIVERSE GROUPS OF SCIENTISTS AND ENGINEERS FROM UNDERGRADUATES TO SENIOR FACULTY WITH SKILLS TO EXTEND RESEARCH EXCELLENCE TOWARDS IMPACTFUL TRANSLATIONAL OUTCOMES. TO DEVELOP SUCH TRANSLATIONAL SKILLS FACULTY, POSTDOCTORAL, AND STUDENT RESEARCHERS WILL BE EMBEDDED IN A NETWORK OF ART (ACCELERATING RESEARCH TRANSLATION) AMBASSADORS WHO WILL SERVE AS ROLE MODELS, PEER MENTORS AND ADVOCATES FOR SOCIETALLY IMPACTFUL TRANSLATIONAL RESEARCH, TRAINED AND SUPPORTED TO DEVELOP BOTH TECHNICAL AND NON-TECHNICAL OR ?SOFT? TRANSLATIONAL RESEARCH SKILLS, AND PROVIDED WITH RESOURCES, INCLUDING MICROGRANTS AND SEED GRANTS, TO SUPPORT AND ACCELERATE SPECIFIC TRANSLATIONAL RESEARCH MILESTONES. THE ART PROJECT TEAM WILL MANAGE AN UMBRELLA ORGANIZATION TO SERVE AS 1) AN ENABLER OF INTERDISCIPLINARY TEAMWORK ACROSS TRADITIONAL ?SILOS?, 2) FACILITATOR OF NEW ?TEACHERS? IN THE FORM OF INDUSTRY LEADERS/SERIAL ENTREPRENEURS, 3) A HOME AND RESOURCE FOR TRANSLATIONAL INTELLECTUAL DEVELOPMENT, 4) MANAGE SEED TRANSLATIONAL RESEARCH PROJECTS (STRPS) TO ACCELERATE SPECIFIC TECHNOLOGY DEVELOPMENT PROJECTS AND 5) ESTABLISH A SPECIFIC DEI SUB-TEAM THAT ENGAGES WITH ALL OTHER ART WORKING GROUPS. THE PROJECT TEAM WILL ALSO COLLABORATE WITH EXTERNAL PARTNERS AND OTHER ART SITES TO DEVELOP BEST PRACTICES FOR AN INNOVATION ECOSYSTEM ACROSS THE OFTEN-NEGLECTED REGION OF WESTERN MASSACHUSETTS. THIS PROJECT WILL UNLOCK THE TRANSLATIONAL IMPACTS OF THE STRONG BASIC RESEARCH ENTERPRISE AT UMASS AMHERST. 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.

NATIONAL SCIENCE FOUNDATION EXPEDITIONS IN COMPUTING FOR COMPUTATIONAL DECARBONIZATION OF SOCIETAL INFRASTRUCTURES AT MESOSCALES -OUR SOCIETY STANDS AT A CRITICAL INFLECTION POINT WITH ITS RAPIDLY ACCELERATING DEMAND FOR ENERGY DUE TO GROWTH IN DOMESTIC MANUFACTURING, DATACENTERS, ARTIFICIAL INTELLIGENCE (AI), ELECTRIC VEHICLES, AND ELECTRIC HEAT PUMPS. SUSTAINING THIS GROWTH WHILE ALSO REDUCING SOCIETY?S CARBON EMISSIONS WILL REQUIRE US TO UNDERTAKE A RAPID, LARGE-SCALE TRANSITION TO LOW- AND ZERO-CARBON ENERGY SOURCES. ENABLING THIS CHANGE WILL NECESSITATE A SHIFT BEYOND OUR LONG-STANDING FOCUS ON IMPROVING ENERGY-EFFICIENCY TO OPTIMIZING CARBON-EFFICIENCY. THE GOAL OF THIS EXPEDITION IS TO DEVELOP NEW COMPUTATIONAL TECHNIQUES TO UNIFY, TRANSFORM, AND ACCELERATE SOCIETAL DECARBONIZATION ACROSS MULTIPLE USE DOMAINS. TO THIS END, THE EXPEDITION WILL DEVELOP THE NEW FIELD OF COMPUTATIONAL DECARBONIZATION (CODEC), WHICH FOCUSES ON OPTIMIZING AND REDUCING THE LIFECYCLE CARBON EMISSIONS OF COMPLEX COMPUTING AND SOCIETAL INFRASTRUCTURE SYSTEMS. SPECIFICALLY, THE CODEC EXPEDITION WILL ADDRESS AN IMPORTANT CLASS OF DECARBONIZATION PROBLEMS THAT ARISE FROM INTERDEPENDENCIES ACROSS MULTIPLE INFRASTRUCTURE DOMAINS, INCLUDING COMPUTING, TRANSPORTATION, THE BUILT ENVIRONMENT, AND THE ELECTRIC POWER GRID. OVER FIVE YEARS, THE EXPEDITION WILL DEVELOP NOVEL COMPUTATIONAL TECHNIQUES, ALGORITHMS, SYSTEMS, AND AI METHODS THAT SENSE, OPTIMIZE, AND REDUCE THE OPERATIONAL, EMBODIED, AND LIFECYCLE GREENHOUSE GAS EMISSIONS OF SOCIETAL INFRASTRUCTURE OVER LONG TEMPORAL AND SPATIAL SCALES. THIS WORK WILL ENABLE NEW SCIENTIFIC DISCOVERIES IN ADDRESSING DECARBONIZATION CHALLENGES WHILE ENSURING THE SUSTAINABLE GROWTH OF OUR ENERGY CONSUMPTION THAT IS NECESSARY FOR ADVANCING TECHNOLOGY, GROWING OUR ECONOMY, AND STRENGTHENING NATIONAL SECURITY. TO PREPARE OUR NATION?S WORKFORCE IN THIS EMERGING FIELD, THE EXPEDITION WILL DEVELOP NEW EDUCATIONAL PROGRAMS AND DESIGN NEW TEACHING CURRICULA THAT ELEVATES COMPUTATIONAL DECARBONIZATION TO A CORE TOPIC IN COMPUTING. CODEC WILL ESTABLISH AN INDUSTRY CONSORTIUM TO SHARE ITS RESEARCH RESULTS AND TRANSITION THEM TO PRACTICE. IT WILL ALSO UNDERTAKE A RANGE OF ACTIVITIES TO BROADEN PARTICIPATION IN COMPUTING THROUGH UNDERGRADUATE RESEARCH AND K-12 OUTREACH. SINCE THE DECARBONIZATION OF COMPLEX SYSTEMS CAN BE VIEWED AS A SENSE-OPTIMIZE-REDUCE PROBLEM THAT OPERATES OVER LONG TIMES SCALES OF YEARS OR DECADES AND OVER LARGE GEOGRAPHICAL SCALES, IT WILL REQUIRE NEW TYPES OF OPTIMIZATION TECHNIQUES AND ALGORITHMS THAT ARE DESIGNED FOR THESE MESOSCALES. TO ADDRESS THE PROBLEM, CODEC WILL DEVELOP NOVEL (I) SENSING APPROACHES TO PROVIDE VISIBILITY INTO SYSTEMS' OPERATIONAL AND EMBODIED CARBON OVER THEIR LIFETIME, (II) OPTIMIZATION METHODS GROUNDED IN THEORY AND AI TO EXPLOIT NEW DIMENSIONS OF ENERGY FLEXIBILITY, WHICH ARE EMERGING IN MODERN INFRASTRUCTURE, FOR OPTIMIZING CARBON-EFFICIENCY, AND (III) SOFTWARE-DEFINED INTERFACES AND SYSTEMS FOR PROGRAMMATICALLY DEPLOYING THESE OPTIMIZATIONS TO REDUCE CARBON EMISSIONS. THESE TECHNIQUES WILL BE VERIFIABLE, ROBUST TO UNCERTAINTIES IN ENERGY'S SUPPLY AND DEMAND, AND TRANSFERABLE ACROSS MULTIPLE DOMAINS AND ECONOMIC SECTORS THROUGH INTUITIVE INTERFACES, WHILE ALSO RESOLVING HUMAN-IN-THE-LOOP CONCERNS OF PRIVACY, FAIRNESS, EQUITY, INCENTIVES, AND USER PREFERENCE. IN ADDRESSING THESE ISSUES, CODEC WILL LEVERAGE THE UNIQUE ROLE COMPUTING CAN PLAY IN DECARBONIZING SOCIETY BOTH AS A MEANS TO AUTOMATE AND COORDINATE CARBON-EFFICIENCY OPTIMIZATIONS ACROSS TIME, SPACE, AND SECTORS AND AS AN ESSENTIAL ACTIVITY THAT CONSUMES INCREASINGLY SIGNIFICANT AMOUNTS OF ENERGY BUT ALSO HAS SUBSTANTIAL TEMPORAL, SPATIAL, AND PERFORMANCE FLEXIBILITY. 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.

EMBRYONIC ORIGINS OF ENDOTHELIAL HETEROGENEITY

CTSA PROGRAM AT UNIVERSITY OF MASSACHUSETTS - PROJECT SUMMARY/ABSTRACT THE UMCCTS WAS FUNDED IN 2010 WITH THE VISION OF BUILDING HEALTHIER COMMUNITIES TOGETHER THROUGH TRANSLATIONAL INNOVATION. OUR MISSION IS TO ADVANCE LEARNING AND DISCOVERY TO SOLVE TRANSLATIONAL SCIENCE CHALLENGES AND IMPROVE WELL-BEING BY: 1) CATALYZING, RIGOROUSLY TESTING, AND DISSEMINATING EVIDENCE-DRIVEN APPROACHES THAT REMOVE TRANSLATIONAL SCIENCE (TS) ROADBLOCKS TO EFFICIENT, HIGH QUALITY, AND IMPACTFUL TRANSLATIONAL RESEARCH (TR); AND 2) BUILDING A WORKFORCE OF SKILLED PROFESSIONAL STAFF AND INVESTIGATORS CAPABLE OF CHANGING PARADIGMS IN TS AND TR. AS MASSACHUSETTS’ ONLY PUBLIC UNIVERSITY SYSTEM (UMASS) PARTNERED WITH 3 LARGE CLINICAL SYSTEMS (UMASS MEMORIAL HEALTH; BAYSTATE HEALTH; LAHEY HEALTH), WE SHARE AN ENDURING FOCUS ON PUBLIC ENGAGEMENT AND SOCIETAL BENEFIT. THE UMCCTS ENGAGES A BROAD RANGE OF INTEREST HOLDERS (COMMUNITIES, PATIENT GROUPS, FOUNDATIONS, INDUSTRY, NCATS, AND CTSA HUBS) TO ENSURE THAT THE RESEARCH WE SUPPORT AND WORKFORCE WE TRAIN ADDRESS PROBLEMS IMPORTANT TO THE COMMUNITIES WE SERVE. WITH OUR PARTNERS, WE IDENTIFY IMPORTANT PROBLEMS AND NEEDS, DEVELOP AND VALIDATE ENABLING PLATFORMS, AND PROVIDE RESOURCES THAT FACILITATE TRANSDISCIPLINARY TEAM SCIENCE. WE USE DATA AND ANALYTICS TO GENERATE KNOWLEDGE, APPLY THAT KNOWLEDGE TO IMPROVE PERFORMANCE, THEN USE LESSONS LEARNED TO INFORM AND REFINE THE NEXT IMPROVEMENT CYCLE. UMCCTS WORKFORCE DEVELOPMENT PROGRAMS ENSURE THE FUTURE SUSTAINABILITY OF THE TS ENTERPRISE. OUR FOUR SPECIFIC AIMS CORRESPOND TO NCATS STRATEGIC GOALS STATED IN THE NCATS NOFO AND BUILD ON OUR PRIOR SUCCESSES: AIM 1: PROMOTE INDIVIDUAL AND COMMUNITY HEALTH BY BUILDING COMMUNITY-CENTERED SYSTEMS AND APPROACHES THAT EXPAND AND SUSTAIN THE ENGAGEMENT OF PARTICIPANTS, COMMUNITIES, AND RESEARCH TEAMS; AIM 2: DEVELOP A ROBUST SET OF DIGITAL TOOLS AND INFORMATICS SYSTEMS THAT ENGAGE A BROAD RANGE OF STUDY PARTICIPANTS, PROMOTE DATA SHARING, ENABLE ACTIONABLE INSIGHTS, AND THAT EXTEND OUR LEARNING HEALTH SYSTEM ACROSS PARTNERS AND INTO HOME AND COMMUNITY SETTINGS; AIM 3: PROVIDE RESOURCES THAT OVERCOME TS AND OPERATIONAL BARRIERS TO CONTINUOUSLY IMPROVE THE QUALITY, EFFICIENCY, AND IMPACT OF TR ACROSS THE SPECTRUM; AIM 4: ADVANCE THE DEVELOPMENT OF A SKILLED TS WORKFORCE THROUGH INNOVATIVE EDUCATIONAL CURRICULA, TRANSDISCIPLINARY TEAM-BASED TRAINING, AND CAREER DEVELOPMENT PROGRAMS. BY WORKING WITH OUR PARTNERS ON EACH OF THESE AIMS WE WILL ACCOMPLISH OUR OVERARCHING GOAL OF SPEEDING THE DEVELOPMENT OF EVIDENCE-BASED, REAL-WORLD APPROACHES THAT PROMOTE HEALTH, TREAT DISEASE, AND RESPOND TO URGENT PUBLIC HEALTH NEEDS LOCALLY, REGIONALLY, AND NATIONALLY.

ORAL DELIVERY VEHICLES FOR RNAI THERAPIES

DIETARY EFFECTS ON THE SPERM EPIGENOME

GENETIC CONTROL OF DEVELOPMENTAL TIMING

ETIOLOGIC STUDIES OF AGE-RELATED MACULAR DEGENERATION

ROLES OF CHROMATIN REGULATION IN EMBRYONIC STEM CELL SELF-RENEWAL

UMASS CENTER FOR AIDS RESEARCH (CFAR)

IDENTIFYING TRANSCRIPTION FACTOR BINDING SITES IN THE C. ELEGANS GENOME

TRACE-CORE

EARMARKS

FLAGELLAR MOTILITY AND ASSEMLBY

TAS::89 0336::TAS RECOVERY THE UNIVERSITY OF MASSACHUSETTS AMHERST TO ENHANCE THE PRODUCTIVITY OF MICROBIAL ELECTROSYNTHESIS, A TECHNOLOGY IN WHICH M

ADIPOSE TISSUE ANGIOGENESIS AND METABOLIC DISEASE

INTERDISCIPLINARY RESEARCH IN MENTAL RETARDATION

PHASE 1 STUDY OF ORAL EPIGALLOCATECHIN-3-GALLATE (EGCG) IN IPF PATIENTS - PROJECT SUMMARY / ABSTRACT THE DEVELOPMENT OF ADDITIONAL THERAPIES FOR IDIOPATHIC PULMONARY FIBROSIS IS A PRESSING HUMAN HEALTH NEED. WE HAVE IDENTIFIED EPIGALLOCATECHIN-3-GALLATE (EGCG), AS POTENT (IC50 ~ 50-100 NM) BLOCKER OF TGFSS1 RESPONSES EX VIVO AND NEW COLLAGEN DEPOSITION IN VIVO IN THE BLEOMYCIN MODEL OF PULMONARY FIBROSIS. EGCG IS A PRINCIPAL COMPONENT OF GREEN TEA AND HAS BEEN UTILIZED IN MULTIPLE HUMAN STUDIES. WE HAVE ADMINISTERED EGCG TO PATIENTS WITH PULMONARY FIBROSIS FOR TWO WEEKS PRIOR TO UNDERGOING LUNG BIOPSY AND DEMONSTRATED HIGHLY SIGNIFICANT REVERSAL OF PRO-FIBROTIC MARKERS IN LUNG TISSUE AND DECREASES IN BLOOD BIOMARKERS OF TGFSS1 SIGNALING. HOWEVER, EGCG HAS NOT BEEN GIVEN TO PATIENTS WITH IPF IN THE SETTING OF CONCURRENT FDA-APPROVED IPF THERAPIES AND DETERMINATION OF THE SAFETY OF EGCG IN THE SETTING OF NINTEDANIB OR PIRFENIDONE USE IS ESSENTIAL GIVEN INFREQUENT REPORT OF EGCG ASSOCIATED HEPATOTOXICITY. THE OVERARCHING GOAL OF THIS PROPOSAL IS TO DEFINE THE SAFETY AND OPTIMAL DOSE OF EGCG IN IPF PATIENTS. WE WILL USE THE R61/R33 MECHANISM TO CONDUCT A ROBUST RANDOMIZED CONTROLLED PHASE I TRIAL TO OBTAIN ADDITIONAL CRITICAL SAFETY AND BIOMARKER DATA SUFFICIENT TO EMPOWER A PHASE II CLINICAL TRIAL TO ASSESS THE EFFICACY OF EGCG IN IPF PATIENTS. A TOTAL OF 5 COHORTS OF 10 IPF PATIENTS EACH AT 6 CLINICAL SITES WILL BE ENROLLED TO RECEIVE EGCG. IN AIM 1, WE WILL DETERMINE THE SAFETY OF ORAL 400 MG AND 600 MG EGCG GIVEN ONCE DAILY TO IPF PATIENTS FOR 12 WEEKS CONCURRENT WITH NINTEDANIB OR PIRFENIDONE. WE WILL ALSO DETERMINE IF 400 MG OR 600 MG EGCG IMPACTS NINTEDANIB OR PIRFENIDONE BLOOD LEVELS, AND WHETHER THESE ANTIFIBROTICS ALTER THE BLOOD LEVELS OF EGCG. CLINICAL SAFETY, ESPECIALLY HEPATOTOXICITY, WILL BE MONITORED CLOSELY DURING THE 12 WEEK TREATMENT DURATION AND THE 4 WEEKS OF FOLLOW-UP. IN AIM 2, WE WILL MEASURE THE CHANGE IN LEVELS OF PRESPECIFIED SERUM BIOMARKERS INCLUDING COMP, PERIOSTIN, AND PRO-MMP1 WITH EGCG TREATMENT TO DETERMINE IF THERE IS AN IN VIVO SIGNAL FOR EGCG EFFECT. LASTLY, IN AIM 3, WE WILL UTILIZE THE TYPE I COLLAGEN-SPECIFIC PET PROBE, 68GA-CBP8 TO DETERMINE THE IMPACT OF EGCG IN ATTENUATING LUNG ACCUMULATION. THE RESULTS OF AIM 2 AND 3 WILL PROVIDE CRUCIAL INFORMATION AS TO DOSE SELECTION. THIS PROPOSAL LEVERAGES THE EXPERTISE OF A MULTI-PRINCIPAL INVESTIGATOR TEAM THAT ARE LEADERS IN FIBROSIS BIOLOGY AND CLINICAL TRIAL DESIGN, A LOW COST INTERVENTION, AND AN INNOVATIVE MOLECULAR PROBE. THE TOTALITY OF THIS INFORMATION WILL PROVIDE KEY INFORMATION NEEDED TO DESIGN A PHASE II WITH THE ULTIMATE GOAL OF DEVELOPING MUCH NEEDED IPF THERAPIES.

CRISPR-BASED ADIPOSE THERAPIES FOR ACCELERATED AGING IN IRRADIATED NONHUMAN PRIMATES.

IMPACT OF MALARIA ON SHAPING IMMUNITY TO EBV IN THE ETIOLOGY OF BURKITT LYMPHOMA

NOVEL GENE THERAPY STRATEGIES FOR CANAVAN DISEASE

HOST CYCLE II OF THE NORTHEAST CLIMATE ADAPTATION SCIENCE CENTER

US COMMUNITY ACCESS TO THE LARGE MILLIMETER TELESCOPE

THE HUSH COMPLEX IN HIV-1 LATENCY

GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP)

YEAST PHEROMONE SIGNAL TRANSDUCTION

TRANSLATIONAL CONTROL: DISCOVERY AND MECHANISMS

ADAPTISPECT-C: A NEXT-GENERATION, ADAPTIVE BRAIN-IMAGING SPECT SYSTEM FOR DRUG DISCOVERY AND CLINICAL IMAGING

ANALYSIS OF NICOTINIC ACETYLCHOLINE RECEPTOR FUNCTION IN C. ELEGANS

PROTEIN FOLDING IN THE CELL: CHALLENGES AND COPING MECHANISMS

SYSTEMS GENETICS OF TUBERCULOSIS - SYSTEMS GENETICS OF TUBERCULOSIS. OVERALL PROGRAM ABSTRACT: MYCOBACTERIUM TUBERCULOSIS (MTB) INFECTION OUTCOMES ARE HIGHLY VARIABLE. MOST INDIVIDUALS CONTAIN THE INFECTION AND REMAIN ASYMPTOMATIC FOR A LIFETIME. A FRACTION OF THOSE INFECTED DEVELOP DISEASE; AND EVEN AMONG THESE PATIENTS, THE TIMING, LOCATION, AND PRESENTATION OF THE PATHOLOGY IS REMARKABLY DIVERSE. THIS VARIABILITY IS ALSO EVIDENT IN THE EFFICACY OF BOTH CHEMOTHERAPY AND VACCINATION. WHILE THIS HETEROGENEITY REPRESENTS A GREAT CHALLENGE FOR TB CONTROL EFFORTS, THE BIOLOGICAL DETERMINANTS OF MTB INFECTION OUTCOME HAVE BEEN DIFFICULT TO DEFINE DUE TO THE COMPLEXITY OF CONTRIBUTING FACTORS. BOTH HUMAN AND BACTERIAL POPULATIONS ARE GENETICALLY AND PHENOTYPICALLY DIVERSE, AND INTERACTIONS BETWEEN THIS GENETIC COMPLEXITY AND A VARIETY OF ENVIRONMENTAL FACTORS ULTIMATELY DETERMINES CLINICAL COURSE. TO OVERCOME THIS COMPLEXITY, WE LEVERAGED NEW MAMMALIAN AND BACTERIAL GENETIC RESOURCES TO CREATE A MODEL SYSTEM THAT CAN BE USED TO STUDY THE EFFECT OF EACH OF THESE VARIABLES IN ISOLATION AND IN COMBINATION. HOST DIVERSITY IS INCORPORATED USING MICE FROM THE COLLABORATIVE CROSS (CC) AND DIVERSITY OUTBRED (DO) RESOURCES, NEWLY GENERATED REFERENCE PANELS THAT REFLECT THE DIVERSITY OF AN OUTBRED POPULATION. BACTERIAL VARIATION IS INCORPORATED USING LARGE PANELS OF MTB STRAINS THAT REFLECT BOTH NATURALLY- AND EXPERIMENTALLY-GENERATED DIVERSITY. CONTROLLED INTERVENTIONS, SUCH AS VACCINATION, CAN BE OVERLAID ON THIS HOST- PATHOGEN DIVERSITY. USING THIS HIGHLY-TRACTABLE SYSTEM, OUR PROGRAM DISCOVERED THAT THE COMBINATORIAL COMPLEXITY OF THESE INTERACTIONS CONVERGE ON A DISCRETE NUMBER OF BIOLOGICAL PATHWAYS THAT INFLUENCE OUTCOME. SUPPORTED BY THE CUTTING-EDGE MOUSE AND HUMAN GENETIC, GENOMIC, AND ANALYTICAL RESOURCES PROVIDED BY THE CORES, OUR SGTB PROGRAM WILL NOW FOCUS ON PARALLEL STUDIES IN THIS MODEL SYSTEM AND HUMAN CLINICAL SAMPLES TO IDENTIFY AND DISSECT THE PATHWAYS THAT INFLUENCE OUTCOME. THIS STRUCTURE WILL ENSURE THAT MECHANISTIC MOUSE STUDIES ARE LINKED TO RELEVANT HUMAN PHENOTYPES. ULTIMATELY, THESE INSIGHTS WILL BE LEVERAGED TO DEVELOP MORE PRECISE CORRELATES OF RISK, MORE SPECIFIC DIAGNOSTICS BASED ON CLINICAL PHENOTYPES, AND NEW STRATEGIES FOR THE OPTIMIZATION AND PRECLINICAL DEVELOPMENT OF VACCINES.

HORIZON CENTER: HEALTHY OPTIONS, RESEARCH, INTERVENTIONS & COMMUNITY ORGANIZING

NOVEL IMMUNOTHERAPEUTICS AGAINST MULTIDRUG-RESISTANT NEISSERIA GONORRHOEA

INSULIN SIGNALING AND METABOLIC REGULATION IN ADIPOCYTES

BIOCHEMICAL MARKERS IN THE NURSES? HEALTH STUDY COHORT

UNDERSTANDING THE MECHANISM OF RNA INTERFERENCE

RYAN WHITE PART C OUTPATIENT EIS PROGRAM

RNA AND GENOMIC JUNK IN FUNDAMENTAL CHROMOSOME ARCHITECTURE AND REGULATION

UMASS BSL-3 RENOVATION

NONHUMAN PRIMATE ANTIBODY RESOURCE FOR IMMUNE CELL DEPLETION

MECHANISM(S) OF TAL-1/SCL-MEDIATED LEUKEMOGENESIS

EXECUTE A BALANCED SCIENCE PROGRAM BASED ON DISCIPLINE-SPECIFIC GUIDANCE FROM THE NATIONAL ACADEMIES OF SCIENCES ENGINEERING AND MEDICINE ADMINISTRATION PRIORITIES AND DIRECTION FROM CONGRESS. PARTICIPATE AS A KEY PARTNER AND ENABLER IN THE AGENC

NEXT-GENERATION ANTISENSE THERAPEUTICS FOR ALS AND FRONTOTEMPORAL DEMENTIA

REGIONAL AIDS EDUCATION AND TRAINING CENTERS PROGRAM - NEW ENGLAND AIDS EDUCATION AND TRAINING CENTER (NEAETC) UMASS MEDICAL SCHOOL 55 LAKE AVENUE NORTH WORCESTER, MA 01655 WWW.NEAETC.ORG PHONE: 508.723.4012 PI: PHILIP BOLDUC, MD CO-I/PD: VANESSA J. CARSON-SASSO, MSW PHILIP.BOLDUC@FHCW.ORG VANESSA.CARSONSASSO@UMASSMED.EDU GRANT PROGRAM FUNDS REQUESTED: REGIONAL AETC BASE PROGRAM (BASE), MINORITY AIDS INITIATIVE (MAI), AND ENDING THE HIV EPIDEMIC IN THE UNITED STATES (EHE) INITIATIVE FUNDING PREFERENCE: SEE ATTACHMENT 8 SINCE 1988, NEAETC HAS BEEN CONTINUOUSLY FUNDED TO SERVE NEW ENGLAND WHICH INCLUDES VERMONT, NEW HAMPSHIRE, MAINE, MASSACHUSETTS, CONNECTICUT, AND RHODE ISLAND. AS PART OF THE AETC PROGRAM, NEAETC CONSISTS OF A LOCAL NETWORK OF HIV EXPERTS WHO COLLABORATIVELY WORK TO INCREASE AND SUPPORT A WORKFORCE CAPABLE OF, AND WHO INTEND TO, PROVIDE CARE AND TREATMENT TO PEOPLE WITH OR AT-RISK OF HIV. DURING THE NEXT 5-YEAR PERIOD OF PERFORMANCE, NEAETC WILL BUILD ON ITS PREVIOUS WORK AND SUCCESSES AND IMPLEMENT A MODERNIZED AND STRENGTHENED PROGRAM FRAMEWORK BASED ON INDUSTRY STANDARDS. NEAETC’S 35 YEARS OF EXPERIENCE, WELL-DEVELOPED LONG-TERM RELATIONSHIPS AND EXPERT FACULTY ARE ASSETS TO IMPLEMENT AND SUSTAIN THIS WORK. NEAETC’S LOCAL PARTNERS (LPS) ARE AFFILIATED WITH, OR HOUSED IN, A CLINICAL CENTER OF HIV EXCELLENCE. EACH LP LEVERAGES EXPERTS WHO ARE NATIONALLY AND INTERNATIONALLY KNOWN AND FACULTY WHO ARE CLINICIANS WITH PRACTICE EXPERIENCE IN A VARIETY OF SETTINGS AND REPRESENT DIFFERENT DISCIPLINES AND AREAS OF EXPERTISE. IN SUPPORT OF THE NATIONAL HIV/AIDS STRATEGY (NHAS) AND HIV CARE CONTINUUM, NEAETC CONDUCTED A PLANNING PROCESS TO IDENTIFY NEEDS AND DEVELOP GOALS. NEAETC ENGAGED RWHAP PARTS A – D, AND F PROGRAM RECIPIENTS AND OTHER STAKEHOLDERS AND REVIEWED STATE INTEGRATED PREVENTION AND CARE PLANS. THE RESULTS PROVIDE THE FRAMEWORK FOR THIS PROJECT, WHICH INCLUDES THE THREE REQUIRED COMPONENTS AND ASSOCIATED ACTIVITIES LISTED IN THE TABLE BELOW. REGIONAL BASE PROGRAM FH : NEAETC WILL EDUCATE AND TRAIN HEALTH CARE TEAM MEMBERS CURRENTLY NOT INVOLVED IN HIV CARE TO INCREASE THEIR ABILITY TO PREVENT NEW HIV INFECTIONS, IDENTIFY PEOPLE WITH HIV WHO ARE UNDIAGNOSED OR OUT OF CARE, AND LINK PATIENTS NOT ON ANTIRETROVIRALS TO CARE. PT: NEAETC WILL CONTINUE TO IMPLEMENT PROCESS IMPROVEMENT, TRAINING, AND TECHNICAL ASSISTANCE TO INCREASE THE CAPABILITY OF ORGANIZATIONS T O IMPLEMENT SYSTEM-LEVEL CHANGES AND ENHANCE CLINICAL PRACTICE TO IMPROVE THE PROVISION OF CARE AND TREATMENT TO PWH AND PREVENTION OF HIV IN PRIORITY POPULATIONS AT INCREASED RISK. IPE: NEAETC WILL CONTINUE TO ASSIST FACULTY IN HEALTH PROFESSIONS PROGRAMS TO CREATE INTERACTIVE LEARNING ENVIRONMENTS DESIGNED TO INCREASE THE NUMBER OF HEALTH PROFESSIONALS ABLE TO EFFECTIVELY WORK IN A TEAM-BASED APPROACH TO IMPROVE CARE AND TREATMENT OF PEOPLE WITH HIV. CEE: NEAETC WILL INCREASE THE ABILITY OF HEALTH CARE TEAM MEMBERS CURRENTLY INVOLVED IN HIV CARE TO OFFER QUALITY SERVICES BASED ON CURRENT NATIONAL TREATMENT GUIDELINES AND STANDARDS AND TO INCREASE THE SKILLS TO OFFER COMPREHENSIVE CARE TO PWH. MAI: NEAETC WILL CONTINUE TO SUPPORT TARGETED AND SPECIFIC WORKFORCE TRAINING AND CAPACITY-BUILDING ACTIVITIES TO SUPPORT ORGANIZATIONS AND HEALTH CARE TEAM MEMBERS WHO HAVE HISTORICALLY PROVIDED CULTURALLY AND LINGUISTICALLY APPROPRIATE CARE, SERVICES, EDUCATION, OR TRAINING TO RACIAL AND ETHNIC MINORITIES. EHE: NEAETC WILL COLLABORATE WITH RWHAP RECIPIENTS IN SUFFOLK COUNTY, MA (ONLY EHE JURISDICTION IN NE) TO CONDUCT ACTIVITIES TO SUPPORT THE EHE INITIATIVE BY IMPLEMENTING STRATEGIES, INTERVENTIONS, AND APPROACHES TO ADDRESS THE UNIQUE TRAINING NEEDS OF THE HEALTH CARE WORKFORCE AND ORGANIZATIONS IN SUFFOLK COUNTY.

SIALIC ACID ANALOGS AGAINST MULTIDRUG-RESISTANT GONORRHEA - ABSTRACT GONORRHEA IS A MAJOR PUBLIC HEALTH PROBLEM GLOBALLY. ABOUT 87 MILLION NEW CASES OF GONORRHEA OCCUR WORLDWIDE ANNUALLY. IN 2018, 583,405 CASES WERE REPORTED IN THE U.S, AN 82.6% INCREASE IN DISEASE INCIDENCE SINCE THE HISTORIC LOW IN 2009. CONCOMITANT INFECTION WITH HIV AND GONORRHEA CAN INCREASE RATES OF HIV TRANSMISSION 5- FOLD. DYSBIOSIS OF THE VAGINAL MICROBIOME (I.E., BACTERIAL VAGINOSIS (BV)) INCREASES THE RISK OF GONORRHEA AND HIV ACQUISITION AND TRANSMISSION. SERIOUS SEQUELAE OF GONORRHEA IN WOMEN INCLUDE INFERTILITY, ECTOPIC PREGNANCY AND CHRONIC PELVIC PAIN. NEISSERIA GONORRHOEAE (NG) HAS BECOME RESISTANT TO ALMOST EVERY ANTIBIOTIC IN CLINICAL USE. REPORTS OF RESISTANCE TO CEFTRIAXONE AND AZITHROMYCIN FROM ALMOST EVERY CONTINENT PORTENDS AN ERA OF UNTREATABLE GONORRHEA. DEVELOPMENT OF NOVEL THERAPIES AGAINST NG IS A GLOBAL PUBLIC HEALTH PRIORITY. GONOCOCCI DEPLOY A UNIQUE IMMUNE EVASION STRATEGY WHEREIN IT CAPS ITS LIPOOLIGOSACCHARIDE (LOS) BY A SURFACE LOS SIALYLTRANSFERASE (LST) USING HOST-DERIVED CMP-NEU5AC. LOS SIALYLATION ENABLES NG TO EVADE SEVERAL ASPECTS OF HOST IMMUNITY, INCLUDING COMPLEMENT AND CATIONIC ANTIMICROBIAL PEPTIDES (CAMPS). WE DISCOVERED THAT GONOCOCCI FED WITH CMP-NONULOSONATES (CMP-NULOS), SUCH AS CMP-LEGIONAMINIC ACID (CMP- LEG5,7AC2) AND CMP-KETODEOXYNONULOSONATE (CMP-KDN) CAP THEIR LOS WITH THESE NULOS. INCORPORATION OF NULOS INTO NG LOS RENDERS BACTERIA SUSCEPTIBLE TO COMPLEMENT AND CAMPS. IMPORTANTLY, CMP-NULOS SIGNIFICANTLY SHORTEN THE DURATION AND BURDEN OF NG VAGINAL COLONIZATION IN MICE. CATHELICIDIN (A MEMBER OF THE CAMP FAMILY) PLAYED A KEY ROLE IN THE MOA OF CMP-NULOS. OUR EFFICACY, SAFETY AND STABILITY STUDIES HAVE ESTABLISHED CMP-LEG5,7AC2 AND CMP-KDN AS PROMISING CANDIDATES FOR INTRAVAGINAL DELIVERY TO PREVENT NG ACQUISITION. IN YEARS 1-2 OF AIM 1, THE NRC WILL PRODUCE CMP-NULOS FOR ALL WORK IN THIS PROPOSAL, PERFORM A PHARMACOECONOMIC ANALYSIS AND ASSESS SCALE-UP. PROCESS DEVELOPMENT, QUALITY RELEASE ASSAYS, DEVELOPMENT OF POTENCY ASSAYS AND STABILITY IN SIMULATED GENITAL TRACT FLUIDS OF THE IDENTIFIED LEAD WILL FOLLOW IN YEARS 3-5. AIM 2 WILL ELUCIDATE FACTORS THAT MAY AFFECT SAFETY EFFICACY OF CMP-NULOS. THESE INCLUDE EFFECTS OF CMP-NULOS ON GROWTH AND VIABILITY OF FAVORABLE OR UNFAVORABLE VAGINAL BACTERIA, THE EFFECTS OF SIALIDASES ELABORATED BY BV- ASSOCIATED PATHOGENS AND NATURALLY-OCCURRING ANTI-NULO ANTIBODIES ON THE EFFICACY OF CMP-NULOS IN VITRO AND IN VIVO, EXAMINING CERVICOVAGINAL SECRETIONS FOR CMP-NULO HYDROLASE ACTIVITY AND TESTING THE SPECIFICITY OF CAMPS TO BIND NULO-CONTAINING GLYCANS TO REFINE THE MOA OF CMP-NULO AGAINST NG. AIM 3 WILL FORMULATE THE CMP-NULOS INTO INTRAVAGINAL RINGS (IVRS), PERFORM PK STUDIES IN VITRO AND IN A SHEEP MODEL, AND EXAMINE BIOFILM FORMATION BY VAGINAL MICROBIOTA ON IVRS. WORK IN YEARS 1-2 OF THE AIMS 1-3 WILL IDENTIFY A SINGLE LEAD; WORKS IN YEARS 3-5 WILL FOCUS ON FURTHER PRODUCT DEVELOPMENT AND IND-ENABLING ACTIVITIES. AIM 4 WILL VERIFY ACTIVITY OF THE LEAD CMP-NULO AGAINST GENETICALLY AND GEOGRAPHICALLY DIVERSE NG ISOLATES. AIM 5 INCLUDES REGULATORY GUIDANCE AND OVERSIGHT FOR ALL AIMS THAT WILL CULMINATE IN A PRE-IND MEETING WITH THE FDA.

MEMBRANE POTENTIAL AND CAMP CROSSTALK IN SPERM CAPACITATION

BACKGROUND: IN SUPPORT OF NASA'S EARTH SURFACE AND INTERIOR (ESI) FOCUS AREA THE TERRESTRIAL REFERENCE FRAME (TRF) IS THE FOUNDATION FOR VIRTUALLY ALL AIRBORNE SPACE-BASED AND GROUND-BASED EARTH OBSERVATIONS. THIS FRAME IS DEVELOPED BY COMBINING THE OBSERVATIONS FROM SATELLITE LASER RANGING (SLR) VERY LONG BASELINE INTERFEROMETRY (VLBI) THE GLOBAL NAVIGATION SATELLITE SYSTEM (GNSS) AND DOPPLER ORBITOGRAPHY AND RADIOPOSITIONING INTEGRATED BY SATELLITE (DORIS) STATIONS AND IS REALIZED AS AN INTERNATIONAL STANDARD THROUGH THE INTERNATIONAL TERRESTRIAL REFERENCE FRAME (ITRF). COMBINING THE DIFFERENT MEASUREMENT TECHNIQUES IS ONLY POSSIBLE WITH ACCURATE KNOWLEDGE OF THE RELATIVE MEASUREMENT REFERENCE POINTS BETWEEN CO-LOCATED SYSTEMS AND DOING SO IS ESSENTIAL TO TAKE FULL ADVANTAGE OF THE STRENGTHS OF EACH TECHNIQUE. CURRENTLY THE ITRF IS LIMITED IN ACCURACY BY SYSTEMATIC ERRORS IN TYING TOGETHER THE CONTRIBUTIONS FROM THE DIFFERENT GEODETIC TECHNIQUES. SINCE STANDARD GROUND-BASED SURVEYS PROVIDING TIES BETWEEN GEODETIC TECHNIQUES HAVE REACHED THE LIMIT OF THEIR CAPABILITIES A NEW APPROACH IS REQUIRED THAT EXTENDS TECHNIQUE TIES INTO SPACE. MAJOR GOALS: WE PROPOSE TO DEVELOP A NEW SPACE FLIGHT INSTRUMENT AND VERIFY A MEASUREMENT CONCEPT THAT ENABLES THE DETERMINATION OF SYSTEMATIC ERRORS BETWEEN THE VLBI GNSS AND SLR INDEPENDENT MEASUREMENT TECHNIQUES BY EXTENDING SURVEYING TECHNIQUES OUT TO SPACEFLIGHT ASSETS. THE PROPOSED INSTRUMENT FUNCTIONING AS A GNSS L-TO-X-BAND TRANSPONDER ESTABLISHES FREQUENCY COMPATIBILITY BETWEEN VLBI AND GNSS THEREBY FACILITATING A DIRECT SPACE-BASED GEODETIC TIE BETWEEN THESE TWO RADIO-BASED TECHNIQUES IN POST- PROCESSING. SEPARATE LASER RETRO-REFLECTORS FLOWN CONCURRENTLY WITH GRITSS WOULD PROVIDE ADDITIONAL CONNECTION TO THE SLR NETWORK. BECAUSE THE MEASUREMENT CONCEPT BY WHICH THE VLBI/GNSS SYSTEMATIC ERRORS WILL BE DETERMINED ONLY REQUIRES ONE VLBI STATION TO OBSERVE THE SPACE VEHICLE THE SPACE VEHICLE MAY BE IN LOW-EARTH ORBIT. THIS IS ADVANTAGEOUS AS IT OPENS UP THE POSSIBILITY OF USING INEXPENSIVE CUBESATS OR OTHER SMALL SATELLITES MAKING IT POSSIBLE TO IMPLEMENT A COST-EFFECTIVE CONSTELLATION OF SPACECRAFT TO PROVIDE BETTER GLOBAL COVERAGE AND FURTHER IMPROVE THE ACCURACY OF THE GEODETIC SITE TIES. SPECIFIC TASKS: 1) DEVELOP MODIFIED VERSION OF AN EXISTING SPACE FLIGHT GNSS RECEIVER TO SUPPORT GNSS RELAYING FUNCTIONALITY PROCURE COMMERCIAL SPACE FLIGHT UHF (LOW DATA RATE) S AND X-BAND (HIGH DATA RATE) DIGITAL DATA TRANSMITTERS. 2) DESIGN AND FABRICATE A FIT-FORM-FUNCTION INSTRUMENT CAPABLE OF BEING IMPLEMENTED WITHIN A CUBESAT/SMALL SATELLITE. 3) BENCH TEST BREADBOARD CONCEPT OF GNSS-TO-VLBI TRANSPONDER WITH GNSS SYNTHETIC SIGNAL GENERATORS AND SPACE VEHICLE GNSS RECEIVERS. 4) BENCH TEST BREADBOARD CONCEPT OF GNSS-TO-VLBI TRANSPONDER WITH GNSS SYNTHETIC SIGNAL GENERATORS AND SPACE VEHICLE GNSS RECEIVERS. 5) ON SIGHT GROUND TEST OF GNSS-TO-VLBI TRANSPONDER AT GODDARD GEOPHYSICAL ASTRONOMICAL OBSERVATORY. 6) AIRBORNE FLIGHT TEST EVALUATION OF GNSS-TO-VLBI TRANSPONDER AT GODDARD GEOPHYSICAL ASTRONOMICAL OBSERVATORY.

BRIDGING RESEARCH ADVANCEMENT WITH VERSATILE ENGINEERING

EXPANDQISE: TRACK 2: EQUIP-UMB-EXPAND QUANTUM INFORMATION PROGRAMS AT UMASS BOSTON -NON-TECHNICAL DESCRIPTION: UMASS BOSTON IS IN A UNIQUE POSITION TO PERFORM CUTTING-EDGE RESEARCH IN QUANTUM INFORMATION SCIENCE AND ENGINEERING (QISE) AND TO TRAIN A DIVERSE FUTURE QISE WORKFORCE THROUGH ITS STUDENT POPULATION AS THE MOST DIVERSE PUBLIC RESEARCH INSTITUTION IN NEW ENGLAND. THE PROJECT AIMS TO EXPAND UMASS BOSTON?S EXISTING ACADEMIC AND RESEARCH ACTIVITIES IN QISE AND MAKE UMASS BOSTON A LEADING PUBLIC RESEARCH INSTITUTION IN THIS FIELD. IT DELIVERS HIGH-QUALITY RESEARCH PRODUCTS, DEVELOPS ACADEMIC ACTIVITIES, AND ESTABLISHES A WORKFORCE DEVELOPMENT INFRASTRUCTURE AT UMASS BOSTON IN PARTNERSHIP WITH HARVARD UNIVERSITY AND THE MASSACHUSETTS INSTITUTE OF TECHNOLOGY. RESEARCH ACTIVITIES INCLUDE THE EXPLORATION OF QUANTUM CORRELATED AND ENTANGLED STATES, AND THE DEVELOPMENT OF METHODOLOGIES TO MANIPULATE AND MITIGATE ERRORS IN QUANTUM BITS (QUBITS) WHILE INCORPORATING MACHINE LEARNING ASSISTED TECHNOLOGIES. RESULTS DERIVING FROM THIS PROJECT WILL INFORM THE DESIGN OF FUTURE LARGE-SCALE QUANTUM PROCESSORS. THIS PROJECT EXPANDS UMASS BOSTON EFFORTS IN ACADEMICS AND WORKFORCE DEVELOPMENT AND PROMOTES A SYMBIOTIC RELATION WITH BOSTON AREA COMPANIES AND ACADEMIC INSTITUTIONS BY PROVIDING ACCESS TO EXPERIMENTAL CAPACITY FOR THE GROWING LOCAL QUANTUM COMPUTING ECOSYSTEM AND CREATING TRAINING OPPORTUNITIES AND INTERNSHIPS FOR UMASS BOSTON UNDERGRADUATE AND GRADUATE STUDENTS. THIS PROJECT CONTRIBUTES TO WORKFORCE BUILDUP FROM THE GROUND UP THROUGH COMMUNITY OUTREACH ACTIVITIES, WHICH ARE DELIBERATELY DEDICATED TO ENGAGING PARTICIPANTS FROM BROAD AND DIVERSE BACKGROUNDS. TECHNICAL DESCRIPTION: THIS PROJECT IS BUILT AROUND THREE RESEARCH FOCUS AREAS (FAS): (FA-1) QUANTUM FUNDAMENTALS; (FA-2) QUANTUM METROLOGY AND CONTROL; AND (FA-3) CO-DESIGN AND QUANTUM SYSTEMS. FA-1 INCLUDES THE STUDY OF SYMMETRIC INFORMATIONALLY COMPLETE STATES, THEIR MEASUREMENT AND THEIR EXPERIMENTAL IMPLEMENTATION USING THE RYDBERG ATOMS PLATFORM. AN ADDITIONAL DIRECTION INCLUDES THE STUDY OF QUANTUM FLUCTUATION THEOREMS, WHICH ACCOUNT FOR QUANTUM COHERENCE, AND THE DESIGN OF THEIR EXPERIMENTAL VERIFICATION USING NITROGEN-VACANCY (NV)-CENTERS. IN THE CONTEXT OF ULTRACOLD QUANTUM GASES AND CORRELATED QUANTUM MANY-BODY SYSTEMS, THE PROJECT DEVELOPS NUMERICAL TECHNIQUES ADAPTED TO CONTROLLED NON-EQUILIBRIUM DIAGRAMMATIC MONTE-CARLO AND FOR THE STUDY OF THE GRASSHOPPER PROBLEM IN CONNECTION TO BELL INEQUALITIES AND ENTANGLED STATES. STUDIES OF A HYBRID MOLECULAR IONS PLATFORM TO GENERATE ENTANGLED STATES AND TO IMPLEMENT QUANTUM GATES USING CONDITIONAL TRANSFER OF INTERNAL ATOMIC STATES INTO MOLECULAR ION STATES ARE BEING PERFORMED. IN FA-2, THE RYDBERG ATOMS PLATFORM IS USED TO COHERENTLY TRANSPORT ENTANGLED QUBITS WITH DYNAMIC AND NONLOCAL CONNECTIVITY ACROSS TWO SPATIAL DIMENSIONS. RYDBERG INTERACTIONS AND THEIR IMPACT ON OPTICAL TWEEZERS ARE STUDIED. RESULTS FROM THE LATTER STUDY INFORM HARDWARE-EFFICIENT ALGORITHM IMPLEMENTATION. A COMPLEMENTARY DIRECTION ANALYZES NOISY QUANTUM ALGORITHMS, QUANTUM METROLOGY VIA NV-CENTERS AND ERROR CORRECTION IN NOISY SYSTEMS TO ELUCIDATE ASPECTS OF SUPERCONDUCTING QUANTUM CIRCUITS WHICH ARE CRITICAL TO REALIZE SCALABLE ERROR-MITIGATED QUANTUM PROCESSORS. THE LATTER RESEARCH IS COMPLEMENTED BY THE DEVELOPMENT OF MACHINE-LEARNING ENHANCED QUANTUM SENSING TO DEVELOP VARIATIONAL QUANTUM CIRCUITS FOR OPTIMAL STATE PREPARATION AND MEASUREMENT DESIGN, WHICH IS TO BE APPLIED TO THE NV-CENTER SETUP. FA-3 INCLUDES THE DEVELOPMENT OF STABLE AND CONTROLLABLE SUPERCONDUCTING QUBITS. THE SYSTEM DEVELOPED IS USED TO MEASURE AND CONTROL MULTIPLE QUANTUM CIRCUITS SPREAD-OUT ACROSS A CHIP TO INVESTIGATE CORRELATED NOISES AND THEIR IMPACT ON LARGE SCALE QUANTUM PROCESSORS. FINALLY, THE TEAM IS INVOLVED IN ALL ACTIVITIES OF FA-4 ON EDUCATION AND WORKFORCE DEVELOPMENT, RANGING FROM THE QUANTUM INFORMATION CERTIFICATE (QUIC) AND FUTURE QISE GRADUATE COURSES, TO OUTREACH ACTIVITIES, TO INTERNSHIPS AND TRAINING WITH INDUSTRY PARTNERS IN GREATER BOSTON. THIS PROJECT IS JOINTLY FUNDED BY THE OFFICE OF MULTIDISCIPLINARY ACTIVITIES (MPS/OMA) AND TECHNOLOGY FRONTIERS PROGRAM (TIP/TF). 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.

BROADENING ADVANCED TECHNOLOGICAL EDUCATION CONNECTIONS

PARACRINE SIGNALING BY KUPFFER CELLS IN HEPATIC INSULIN RESISTANCE

UNIVERSITY OF MASSACHUSETTS CENTER FOR CLINICAL AND TRANSLATIONAL SCIENCE

4/4: IMPROVING THE PART C EARLY INTERVENTION SERVICE DELIVERY SYSTEM FOR CHILDREN WITH ASD: A RANDOMIZED CLINICAL TRIAL

DEVELOPMENT AND APPLICATION OF A METABOLOMIC PROFILE OF CHRONIC DISTRESS TO CARDIOMETABOLIC RISK

STRENGTHENING TRANSLATIONAL RESEARCH IN DIVERSE ENROLLMENT (STRIDE)

A SYSTEMS IMMUNOLOGY APPROACH TO EVALUATE MALARIA VACCINE PERFORMANCE IN ENDEMIC REGIONS OF KENYA - A HIGHLY EFFECTIVE MALARIA VACCINE REMAINS THE ULTIMATE TOOL FOR MALARIA CONTROL AND ELIMINATION. THE FRONT RUNNER IS RTS,S/AS01, A RECOMBINANT PROTEIN COMPRISING PORTIONS OF PLASMODIUM FALCIPARUM (PF) CIRCUMSPOROZOITE PROTEIN (CSP). HOWEVER, THE OBSERVED VACCINE EFFICACY TO CLINICAL MALARIA IN CHILDREN LIVING IN MALARIA ENDEMIC SETTINGS IS ONLY 36%. IN ORDER TO UNDERSTAND HOW TO IMPROVE UPON THIS VACCINE, A COMPREHENSIVE EVALUATION OF BASELINE AND CUMULATIVE FACTORS THAT IMPEDE MALARIA VACCINE PERFORMANCE, IN DIRECT CONTRAST TO FACTORS ASSOCIATED WITH PROTECTION FROM MALARIA, IS NEEDED. WE HAVE RECENTLY DEFINED STRONGER CORRELATES OF PROTECTION BASED ON FUNCTIONAL ANTIBODY ACTIVITY USING A SYSTEMS SEROLOGY APPROACH. TO DATE, THESE SYSTEM SEROLOGY STUDIES HAVE BEEN CONDUCTED ONLY FOR ADULTS FROM NON-ENDEMIC REGIONS. HERE, WE AIM TO TEST THE OVERALL HYPOTHESIS THAT CHILDREN LIVING IN MALARIA ENDEMIC AREAS WHO HAVE LESS MATURE OR ABERRANT IMMUNE CELLS ARE UNABLE TO DEVELOP THE BREADTH OF FUNCTIONAL ANTIBODIES AND T CELLS ELICITED BY RTS,S IN ORDER TO BECOME PROTECTED AGAINST MALARIA. DRAWING ON THE WHO MALARIA VACCINE IMPLEMENTATION PROGRAM IN A HIGH- TRANSMISSION REGION IN KENYA, WE WILL EMPLOY AN INTENSIVE LONGITUDINAL COHORT STUDY DESIGN TO FOLLOW CHILDREN DURING THEIR 4-DOSE RTS,S VACCINATION SCHEDULE, WITH ACTIVE AND PASSIVE FOLLOW-UP FOR PF INFECTIONS AND EPISODES OF CLINICAL MALARIA UNTIL THEY REACH 4 YEARS OF AGE. OUR OVERALL HYPOTHESIS WILL BE TESTED BY THE FOLLOWING SPECIFIC AIMS: SA1: TO COMPREHENSIVELY CHARACTERIZE BASELINE AND PERI-VACCINATION FACTORS THAT CORRELATE WITH VACCINE HYPORESPONSIVENESS. USING AN INTEGRATED SYSTEMS IMMUNOLOGY AND MACHINE LEARNING APPROACH, WE WILL DETERMINE THE EFFECTS OF ONGOING EXPOSURES TO MALARIA, SYSTEMIC INFLAMMATION, PRE- EXISTING ANTI-MALARIAL IMMUNITY, AND IMMATURITY OF CELLULAR IMMUNE SIGNATURES ON RTS,S VACCINE HYPO- RESPONSIVENESS, DEFINED AS THE INABILITY TO DEVELOP A CORE GROUP OF FUNCTIONAL ANTI-CSP ANTIBODIES. SA2: TO COMPREHENSIVELY CHARACTERIZE THE POST-VACCINATION IMMUNE SIGNATURES IN CHILDREN THAT CORRELATE WITH PROTECTION FROM MALARIA. USING A SYSTEMS IMMUNOLOGY APPROACH, WE WILL DETERMINE THE FUNCTION OF VACCINE- ELICITED ANTI-CSP ANTIBODIES AND THEIR CORRELATION WITH AGE, CELLULAR IMMUNE SIGNATURES, AND PROTECTION FROM MALARIA. FUNCTIONAL IN VITRO STUDIES WILL ASSESS ANTIBODY OPSONIZATION OF SPOROZOITES AND ANTIBODY-DEPENDENT CELLULAR CYTOTOXICITY WITH AND WITHOUT INNATE IMMUNE CELLS; ASSESS THE PHENOTYPE AND FUNCTION OF VACCINE- ELICITED CSP-SPECIFIC T CELLS; AND EXPLORE THE POTENTIAL FOR EPIGENETIC MODIFICATIONS OF MONOCYTES (TRAINED IMMUNITY) TO INFLUENCE VACCINE PERFORMANCE. USING A COMPUTATIONAL MODELING/MACHINE LEARNING APPROACH, WE WILL INTEGRATE DEEP IMMUNOPROFILING FEATURES TO PREDICT CORRELATES WITH PROTECTION FROM MALARIA. TOGETHER, THIS STUDY AIMS TO INFORM THE NEXT GENERATION OF MALARIA VACCINES AND VACCINATION PROGRAMS THAT COULD INCLUDE IMMUNE-MODULATORY COMPONENTS OR RECOMMENDATIONS TO COMBINE ANTIMALARIAL PROPHYLAXIS/TREATMENT WITHIN THE VACCINE SCHEDULE.

REGULATION OF AUTOPHAGY DURING ANIMAL DEVELOPMENT

MICROGLIA-DEPENDENT MECHANISMS GOVERNING NEURAL CIRCUIT PLASTICITY

TARGETING MULTIPLE DISEASES THROUGH GAMMA SECRETASE

POLYADENYLATION AND TRANSLATIONAL CONTROL

EHR ANTICOAGULANTS PHARMACOVIGILANCE

K+ CHANNEL COMPLEXES: ASSEMBLY, TRAFFICKING AND FUNCTION

SPATIAL HEARING IN COMPLEX SOUND FIELDS

INFLUENZA FORECASTING CENTER OF EXCELLENCE AT UNIVERSITY OF MASSACHUSETTS AMHERST

BIO-DIRECTED HIERARCHICAL ASSEMBLY OF MULTIFUNCTIONAL MATERIALS

THE FUNDAMENTALS OF THE REMOTE SENSING TECHNOLOGY DEVELOPMENT ARE THE USE OF HIGH-RESOLUTION VOLUME AND SURFACE SCATTERING SIGNATURES THAT OCCUR IN A DUAL-FREQUENCY KU-BAND REGIME AND CAN BE EXPANDED UPON THROUGH THE USE OF ANCILLARY SENSORS...

RESOURCE FOR NONHUMAN PRIMATE CELL DEPLETING ANTIBODIES