Eastern University

PUERTO RICO TESTSITE FOR EXPLORING CONTAMINATION THREATS (PROTECT)

APPLICATION FOR INSTITUTIONAL ALLOCATION OF HEERF UNDER CARES ACT, SECTION 18004(A)(1) AND 18004(C).

UNDER THE CARES ACT, THE UNIVERSITY WILL DISBURSE EMERGENCY STUDENT GRANTS FROM THE HIGHER EDUCATION EMERGENCY RELIEF FUND (HEERF).

ENGINEERED MATERIALS AND MATERIALS DESIGN OF ENGINEERED MATERIALS (EMMDEM)

NEW CA: COGNITIVE DISTRIBUTED SENSING IN CONGESTED RADIO FREQUENCY ENVIRONMENTS

PAWR PLATFORM POWDER-RENEW: A PLATFORM FOR OPEN WIRELESS DATA-DRIVEN EXPERIMENTAL RESEARCH WITH MASSIVE MIMO CAPABILITIES

ENVIRONMENTAL INFLUENCES ON CHILD HEALTH OUTCOMES IN PUERTO RICO (ECHO-PRO)

NOVA SOUTHEASTERN UNIVERSITY - CARES ACT HIGHER EDUCATION EMERGENCY RELIEF INSTITUTIONAL FUNDS

ENDOCANNABINOID ACTIVE SITES AS THERAPEUTIC TARGETS

NOVA SOUTHEASTERN UNIVERSITY - CARES ACT HIGHER EDUCATION EMERGENCY RELIEF FUND

SENTRY SOFT TARGET ENGINEERING TO NEUTRALIZE THE THREAT REALITY

RECIPIENT IS ALLOWED TO USE UP TO 50 PERCENT OF THE REMAINING CARES ACT FUNDS TO COVER ANY COSTS ASSOCIATED WITH SIGNIFICANT CHANGES TO THE DELIVERY OF INSTRUCTION DUE TO THE CORONA VIRUS.

MID-SCALE RI-1 (M1:IP): OBSERVATORY FOR ONLINE HUMAN AND PLATFORM BEHAVIOR

NEW COOPERATIVE AGREEMENT (DAC): TESTING & EVALUATION FOR SOLDIER-DEVICE TEAMING COMPATIBILITY, VULNERABILITY, AND DURABILITY IN EMERGENT SITUATIONS

DESIGN AND CONSTRUCTION OF THE CENTER OF EXCELLENCE FOR CORAL REEF ECOSYSTEM SCIENCE RESEARCH FACILITY AT NOVA SOUTHEASTERN UNIVERSITY.

PAWR PLATFORM AERPAW: AERIAL EXPERIMENTATION AND RESEARCH PLATFORM FOR ADVANCED WIRELESS

PROGRAM IN MATERIALS, ADDITIVE AND SECURE MANUFACTURING, AND MULTISCALE MATERIALS ENGINEERING (3ME)

NSEC: CENTER FOR HIGH-RATE NANOMANUFACTURING

ENVIRONMENTAL INFLUENCES ON CHILD HEALTH OUTCOMES IN PUERTO RICO (ECHO-PRO)

RELIEF FUNDS FOR STUDENTS UNDER THE CARES ACT

CENTER FOR TRANSLATIONAL CANCER NANOMEDICINE

EPISTORM: CENTER FOR ADVANCED EPIDEMIC ANALYTICS AND PREDICTIVE MODELING TECHNOLOGY

NEW CO-OP: OPEN 6G: ORAN COMPLIANT OPEN-SOURCE PROTOCOL STACKS FOR SOFTWARIZED DYNAMIC NETWORKING AT THE EDGEE

PAWR PLATFORM ARA: WIRELESS LIVING LAB FOR SMART AND CONNECTED RURAL COMMUNITIES

AN ENGINEERING RESEARCH CENTER FOR SUBSURFACE SENSING AND IMAGING SYSTEMS - CENSSIS

HAZARDOUS MATERIAL WORKER HEALTH AND SAFETY TRAINING (U45), COOPERATIVE AGREEMENT

STRUCTURAL DETERMINANTS OF PIP2 REGULATION

NSF INCLUDES ALLIANCE: ENGINEERING PLUS (PARTNERSHIPS LAUNCHING UNDERREPRESENTED STUDENTS)

RESOLVING THE BOTTLENECK IN ANTIBIOTIC DISCOVERY

THE GULF WAR ILLNESS CLINICAL TRIALS AND INTERVENTIONS CONSORTIUM (GWICTIC)

NATIONAL DEEP INFERENCE FABRIC FOR VERY LARGE LANGUAGE MODELS -THE NATIONAL DEEP INFERENCE FABRIC THE NATIONAL DEEP INFERENCE FABRIC (NDIF) IS A RESEARCH COMPUTING PROJECT THAT WILL ENABLE RESEARCHERS TO CRACK OPEN THE MYSTERIES INSIDE LARGE-SCALE ARTIFICIAL INTELLIGENCE (AI) SYSTEMS. MODERN LARGE-SCALE AI SYSTEMS SUCH AS LARGE LANGUAGE MODELS HAVE SHOWN STRONG CAPABILITIES, PASSING A RANGE OF BENCHMARK TESTS IN MATHEMATICAL, MEDICAL, AND LEGAL REASONING. HOWEVER, BECAUSE LARGE-SCALE AI SYSTEMS ARE TRAINED AUTOMATICALLY USING MASSIVE AMOUNTS OF DATA?INSTEAD OF BEING DESIGNED LINE-BY-LINE BY A PROGRAMMER?THE INTERNAL WORKINGS OF THE CURRENT GENERATION OF AI ARE INSCRUTABLE TO HUMANS. UNDERSTANDING HOW THESE SYSTEMS WORK IS AN EMERGING SCIENCE. BUT PERFORMING SCIENCE ON THE INTERNALS OF SUCH LARGE-SCALE AI SYSTEMS REQUIRES SUBSTANTIAL COMPUTATIONAL RESOURCES THAT ARE NOT PRACTICAL AT INSTITUTIONAL SCALE, BECAUSE A PLATFORM REQUIRED TO STUDY THE DETAILED COMPUTATIONS OF AI DIFFERS FROM THE COMPUTING SYSTEMS USED FOR ORDINARY COMMERCIAL DEPLOYMENT OF AI. NDIF ADDRESSES THIS CRITICAL NEED BY PLANNING TO DEVELOP A UNIQUE NATIONWIDE RESEARCH COMPUTING FABRIC THAT ENABLES SCIENTISTS TO PERFORM TRANSPARENT AND REPRODUCIBLE EXPERIMENTS ON THE LARGEST-SCALE OPEN AI SYSTEMS, IN ORDER TO ADVANCE OUR NATION?S UNDERSTANDING OF THEIR CAPABILITIES, AS WELL AS THEIR LIMITATIONS, ROBUSTNESS, SAFETY ISSUES, AND IMPACTS ON HUMAN SOCIETY. LED BY NORTHEASTERN UNIVERSITY IN PARTNERSHIP WITH THE NSF DELTA AI HIGH-PERFORMANCE COMPUTING CLUSTER AT THE NATIONAL CENTER FOR SUPERCOMPUTING APPLICATIONS, UNIVERSITY OF ILLINOIS URBANA-CHAMPAIGN, NDIF PLANS TO CONSIST OF THREE MAJOR COMPONENTS. (1) A NATIONWIDE HIGH-PERFORMANCE COMPUTING FABRIC HOSTING THE LARGEST OPEN PRETRAINED MACHINE LEARNING MODELS FOR TRANSPARENT DEEP INFERENCE. THIS NATIONAL DEEP INFERENCE FABRIC IS A UNIQUE COMBINATION OF GPU HARDWARE WITH THE CREATION OF A DEEP NETWORK AI INFERENCE SOFTWARE TO PROVIDE A REMOTELY-ACCESSIBLE COMPUTING RESOURCE FOR SCIENTISTS TO PERFORM DETAILED AND REPRODUCIBLE EXPERIMENTS ON LARGE AI SYSTEMS ON THE FABRIC. ONCE DEVELOPED, THE FABRIC WILL ALLOW MANY SCIENTISTS TO EFFICIENTLY AND SIMULTANEOUSLY SHARE THE SAME AI COMPUTING CAPACITY TO MAKE EFFICIENT USE OF RESOURCES. (2) A NOVEL OPEN-SOURCE RESEARCH SOFTWARE LIBRARY TO BE CREATED THAT ENABLES SCIENTISTS TO DEVELOP AND DEPLOY NEW RESEARCH METHODS ON AI MODELS BY CREATING INTERVENTION CODE THAT INSPECTS, MODIFIES AND CUSTOMIZES AI MODEL COMPUTATIONS. THIS LIBRARY WILL HELP ENABLES REPRODUCIBLE SCIENTIFIC EXPERIMENTS TO BE DEFINED AND EXECUTED ON BOTH THE SHARED LARGE-SCALE FABRIC AND ON A SCIENTIST?S OWN SMALLER-SCALE COMPUTERS. (3) A NATIONWIDE TRAINING PROGRAM TO EQUIP RESEARCHERS AND STUDENTS IN EVERY PART OF THE COUNTRY TO UTILIZE NDIF TO UNLOCK CRITICAL RESEARCH PROBLEMS IN EVERY FIELD IMPACTED BY LARGE-SCALE AI. DEVELOPED TOGETHER WITH THE PUBLIC INTEREST TECHNOLOGY UNIVERSITY NETWORK, A CONSORTIUM OF 63 UNIVERSITIES AND COLLEGES, THE NDIF TRAINING PROGRAM WILL CONSIST OF ONLINE MODULES, COURSE MATERIALS, AND IN-PERSON WORKSHOPS HOSTED AT MULTIPLE SITES THROUGHOUT THE UNITED STATES. IT WILL CREATE A NETWORK OF EXPERTS IN A RANGE OF FIELDS IMPACTED BY AI, PROVIDE EMBEDDED EXPERTISE WITHIN THEIR OWN INSTITUTIONS, AND HELP CREATE A NEXT-GENERATION WORKFORCE EQUIPPED TO UNDERSTAND AND HARNESS THE MECHANISMS AND CAPABILITIES OF THE SYSTEMS AT THE FOREFRONT OF ARTIFICIAL INTELLIGENCE. 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.

CB1 NEUTRAL ANTAGONISTS FOR ALCOHOL USE DISORDER

ADVANCED TERRAIN ANALYTICS TO SUPPORT TACTICAL SCALE PLANNING AND OPERATIONS OVER VARIED ENVIRONMENTS

VOTERS: VERSATILE ONBOARD TRAFFIC EMBEDDED ROAMING SENSORS

CCRI: GRAND: COLOSSEUM: OPENING AND EXPANDING THE WORLD'S LARGEST WIRELESS NETWORK EMULATOR TO THE WIRELESS NETWORKING COMMUNITY

SCALING DEEP TECH INNOVATION THROUGH INTERNATIONAL PARTNERSHIPS -ADVANCING U.S. LEADERSHIP IN CRITICAL AND EMERGING TECHNOLOGIES, INCLUDING SEMICONDUCTORS, ADVANCED MATERIALS, QUANTUM COMPUTING, AND ADVANCED MANUFACTURING, IS ESSENTIAL FOR NATIONAL SECURITY, LONG-TERM ECONOMIC COMPETITIVENESS, AND DOMESTIC JOB GROWTH. DEEP TECHNOLOGY STARTUPS PLAY A CENTRAL ROLE IN THIS LEADERSHIP, YET THEIR PROGRESS TOWARD COMMERCIALIZATION IS OFTEN HINDERED BY LIMITED ACCESS TO SPECIALIZED FABRICATION FACILITIES, PILOT-SCALE MANUFACTURING CAPABILITIES, COSTLY CAPITAL EQUIPMENT, AND INTERNATIONAL INDUSTRY PARTNERS. THESE RESOURCES ARE INCREASINGLY CONCENTRATED IN TECHNOLOGICALLY ADVANCED NATIONS OUTSIDE THE U.S., WHILE U.S. FOUNDERS FACE SIGNIFICANT BARRIERS IN IDENTIFYING POTENTIAL PARTNERS AND NAVIGATING FOREIGN INNOVATION ECOSYSTEMS. AS A RESULT, THE ABSENCE OF STRUCTURED, SECURE, AND STRATEGICALLY ALIGNED PATHWAYS TO VETTED INTERNATIONAL RESOURCES SLOWS THE TRANSLATION OF HIGH-IMPACT U.S. RESEARCH INTO DOMESTIC ECONOMIC VALUE. THIS PROJECT PILOTS AND EVALUATES A SCALABLE MODEL FOR STRATEGIC INTERNATIONAL DEEP TECH PARTNERSHIP FACILITATION WITH JAPAN AND SOUTH KOREA, EXPANDING STRUCTURED ENGAGEMENT OPPORTUNITIES THAT ULTIMATELY STRENGTHEN THE U.S. INNOVATION BASE. THE EFFORT BEGINS WITH TARGETED BILATERAL WORKSHOPS THAT CONVENE U.S. STARTUP FOUNDERS, INCUBATOR LEADERS, GOVERNMENT OFFICIALS, AND CORPORATE PARTNERS ALONGSIDE COUNTERPARTS IN PARTNER NATIONS TO SURFACE COLLABORATION OPPORTUNITIES AND DOCUMENT AVAILABLE CAPABILITIES OF DIRECT RELEVANCE TO U.S. COMMERCIALIZATION GOALS. THE PROJECT ADDITIONALLY PROVIDES DIRECT SUPPORT TO U.S. DEEP TECH STARTUPS PURSUING PARTNERSHIPS WITH TAIWAN, SINGAPORE, JAPAN, AND SOUTH KOREA, SELECTED THROUGH A RIGOROUS TWO-STAGE REVIEW PROCESS ASSESSING TECHNICAL MERIT, PARTNERSHIP STRENGTH, COMMERCIAL POTENTIAL, AND FEASIBILITY. QUARTERLY REVIEWS, IN PERSON CONVENINGS, AND LONGITUDINAL DATA COLLECTION WILL GENERATE EMPIRICAL INSIGHTS INTO WHICH INTERNATIONAL PARTNERSHIP STRUCTURES MOST EFFECTIVELY ACCELERATE U.S. TECHNOLOGY DEVELOPMENT, REDUCE COMMERCIALIZATION RISK, AND SUSTAIN LONG-TERM COLLABORATION BENEFICIAL TO THE U.S.. OUTCOMES WILL BE SYNTHESIZED INTO REPLICABLE FRAMEWORKS AND DISSEMINATED BROADLY TO STRENGTHEN U.S. ENTREPRENEURIAL CAPACITY, ENHANCE STRATEGIC COMPETITIVENESS, AND ENSURE THAT EARLY-STAGE RESEARCH SUPPORTED BY U.S. TAXPAYERS IS TRANSLATED INTO DOMESTIC ECONOMIC AND NATIONAL SECURITY ADVANTAGE. 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.

CONTROL AND LEARNING ENABLED VERIFIABLE ROBUST AI (CLEVR-AI)

SCALABLE HEALTHCARE SYSTEMS ENGINEERING REGIONAL EXTENSIONS

BIOENGINEERING TO MAP STRESS PROPAGATION IN CYTOSKELETON

AN INTRANASAL GDNF GENE THERAPY FOR OPIOID RELAPSE REDUCTION - THERE ARE CURRENTLY NO EFFECTIVE NON-OPIOID-BASED PHARMACOTHERAPIES FOR TREATMENT OF OPIOID USE DISORDER (OUD). CURRENT MEDICATION ASSISTED TREATMENTS DO NOT ADDRESS THE NEUROADAPTIVE CHANGES THAT PERPETUATE COMPULSIVE DRUG USE, LEAVING THE PRIMARY PATHOPHYSIOLOGY UNTREATED. THIS PROPOSAL WILL TEST A NOVEL, NON-OPIOID APPROACH FOR TREATMENT OF OUD DESIGNED TO CORRECT THE UNDERLYING DOPAMINE DEFICIENCY AND NORMALIZE THE REWARD DEFICIT, RESULTING IN REDUCED CRAVING AND A DECREASED RISK OF RELAPSE. WE HYPOTHESIZE THAT AN INTRANASAL GLIAL CELL LINE-DERIVED NEUROTROPHIC FACTOR (GDNF) GENE THERAPY WILL CORRECT THESE DEFICITS AND PROMOTE LONG-TERM RECOVERY. WE WILL TEST INTRANASAL PLASMID DNA NANOPARTICLES (NPS) ENCODING GDNF IN A RAT MODEL OF OUD TO ASSESS WHETHER INCREASING BRAIN GDNF CAN REDUCE CRAVING AND PREVENT RELAPSE. IN THE UG3 PHASE OF THE PROJECT, AIM 1 WILL DETERMINE IF INTRANASAL ADMINISTRATION OF PGDNF NPS SUPPRESSES OPIOID CRAVING AND REINSTATEMENT IN A RAT SELF-ADMINISTRATION MODEL OF OUD. AIM 2 WILL DETERMINE IF INTRANASAL PGDNF NPS REDUCE THE DOPAMINE DEFICIENCY STATE IN THE MESOLIMBIC DOPAMINE REWARD SYSTEM IN THIS MODEL. IF BOTH OCCUR SIMULTANEOUSLY, THE LATTER MAY BE MECHANISTICALLY RESPONSIBLE FOR THE FORMER. AIM 3 WILL BE LARGE ANIMAL DOSE-RESPONSE AND TIME COURSE STUDIES TO DETERMINE IF INTRANASAL NPS CAN GENERATE 2-3- FOLD INCREASES IN BRAIN GDNF IN NON-HUMAN PRIMATES (NHPS), AND TO SELECT A DOSE FOR A GLP TOXICOLOGY STUDY. THE MILESTONES FOR THE UG3 PHASE ARE AS FOLLOWS: IF ALL AIMS YIELD POSITIVE RESULTS, OR IF AIM1 AND 3 PRODUCE POSITIVE RESULTS, BUT NOT AIM 2, THE PROJECT WILL CONTINUE TO THE UH3 PHASE. (THE LATER OUTCOME WOULD INDICATE THAT THE APPROACH HAS THERAPEUTIC POTENTIAL FOR OUD BUT NOT BY THE MECHANISM PROPOSED.) THE PROJECT WILL END AFTER THE UG3 IF AIM 2 YIELDS POSITIVE RESULTS BUT NOT AIM 1, WHICH WOULD MEAN CORRECTING THE DOPAMINE DEFICIT DOES NOT REDUCE RELAPSE POTENTIAL. IF BOTH AIMS 1 AND 2 YIELD NEGATIVE RESULTS, A HIGHER DOSE OF THE NPS WOULD BE TESTED TO SEE IF THIS COULD CORRECT THE DOPAMINE DEFICIENCY AND REWARD DEFICIT. FINALLY, THE PROJECT WILL END IF AIM 3 DOES NOT RESULT IN 2-FOLD INCREASES IN BRAIN GDNF SINCE THE APPROACH IS UNLIKELY TO SUCCEED IN HUMANS. IN THE UH3 PHASE OF THE PROJECT, THE FOLLOWING AIMS WILL BE PURSUED FOR A SUCCESSFUL IND APPLICATION: AIM 4. HOLD A PRE-IND MEETING WITH THE FDA TO DETERMINE WHICH IND-ENABLING STUDIES (ESPECIALLY THE GLP TOXICOLOGY PROTOCOL) WOULD BE NECESSARY FOR APPROVAL OF AN IND APPLICATION BY THE END OF UH3 FUNDING. AIM 5. DRAFT CLINICAL PROTOCOL FOR FDA TO DETERMINE IF GLP TOXICOLOGY STUDY DESIGN IS ADEQUATE. AIM 6. DESIGN GLP TOXICOLOGY STUDY AND SUBMIT FOR FDA APPROVAL. PREPARE GMP-GRADE NPS FOR THIS STUDY. AIM 7. PERFORM GLP TOXICOLOGY STUDY AND DNA BIODISTRIBUTION STUDY. AIM 8. SCALE UP PRODUCTION METHODS FOR MANUFACTURING OF PGDNF NPS UNDER GLP/GMP GUIDELINES. AIM 9. LOAD GDNF NPS INTO NASAL SPRAYER AND CONDUCT LONG-TERM STABILITY STUDIES. AIM 10. SUBMIT IND APPLICATION FOR A PILOT CLINICAL STUDY IN PATIENTS WITH OUD.

ASSISTANCE FOR COSTS AND OTHER LOSSES SUSTAINED BY THE INSTITUTION DUE TO SIGNIFICANT CHANGES TO THE DELIVERY OF INSTRUCTION, AND OTHER DISRUPTION OF CAMPUS OPERATIONS RESULTING FROM THE CORONAVIRUS.

PAWR PLATFORM COSMOS: CLOUD ENHANCED OPEN SOFTWARE DEFINED MOBILE WIRELESS TESTBED FOR CITY-SCALE DEPLOYMENT

TAS::89 0321::TAS NORTHEASTERN UNIVERSITY - DEVELOPMENT OF NOVEL NON PT GROUP METAL ELECTROCATALYSTS FOR PEM FUEL CELL APPLICATIONS

CANNABINERGIC MEDICATIONS FOR METHAMPHETAMINE ADDICTION

ELECTROMAGNETIC RESEARCH IN THE STRAITS OF FLORIDA: OCEANOGRAPHIC PERSPECTIVE.

REGULATORY B CELLS IN THE AMELIORATION OF IMMUNE-MEDIATED PERIODONTAL DISEASE

ASSISTANCE TO STUDENTS SUBJECTED TO DISRUPTIONS OF CAMPUS OPERATIONS DUE TO COVID-19

SUPER-PERSISTENT CELLS AND THE PARADOX OF UNTREATABLE INFECTIONS

GUMI: NEW IN VITRO PLATFORMS TO PARSE THE HUMAN GUT EPITHELIAL-MICROBIOME-IMMUNE AXIS

UNDERSTANDING MEDIATING AND MODERATING FACTORS THAT DETERMINE TRANSFER OF WORKING MEMORY TRAINING

NSEC: THE CENTER FOR HIGH-RATE NANOMANUFACTURING (CHN)

STUDENT PATHWAYS OPENING WORLD ENERGY RESOURCES (S-POWER)

MULTI-DISCIPLINARY PREPARATION OF NEXT GENERATION INFORMATION ASSURANCE PRACTITIONERS - RENEWAL

U.S. GEOLOGICAL SURVEY FLORIDA WATER SCIENE CENTER

U.S. GEOLOGICAL SURVEY SOUTH FLORIDA SCIENCE CENTER

NEW; TITLE: TRAINING PROGRAM IN RADIOCHEMISTRY AND RADIOTRACER DEVELOPMENT; PI: ROBERT HANSON

POSTDOCTORAL TRAINING IN GENERAL PEDIATRIC AND PUBLIC HEALTH DENTISTRY AND DENTAL HYGIENE

RENEWAL: SFS @ NORTHEASTERN - A MULTI-DISCIPLINARY APPROACH

HIT-TO-LEAD DISCOVERY FOR SLEEPING SICKNESS VIA INDUSTRY-ACADEMIC PARTNERSHIP

MILLS COLLEGE UPWARD BOUND PROGRAM CONTINUATION

VERTEBRATE PRIMARY MOUTH FORMATION

DISCOVERING ANTIMICROBIALS ACTING AGAINST MDR PATHOGENS - ABSTRACT WE ARE EXPERIENCING AN ANTIMICROBIAL RESISTANCE CRISIS (AMR), A DIRECT RESULT OF A DECLINE IN ANTIBIOTIC DISCOVERY. THE WHO DESIGNATED A LIST OF PRIORITY PATHOGENS, AND OF THESE, MDR GRAM- NEGATIVE ENTEROBACTERIACEAE (E. COLI, S. TYPHIMURIUM, KLEBSIELLA PNEUMONIAE, ENTEROBACTER), PSEUDOMONAS AERUGINOSA, AND ACINETOBACTER BAUMANNII) ARE OF “CRITICAL PRIORITY”. THESE PATHOGENS ARE THE FOCUS OF THE PRESENT PROPOSAL AIMED AT DEVELOPING A PLATFORM FOR EFFICIENT DISCOVERY OF NOVEL ANTIMICROBIALS. THE FIELD ONCE ENJOYED A GOLDEN ERA OF DISCOVERY, FUELED MAINLY BY SCREENING OF SOIL ACTINOMYCETES. ALL MAJOR CLASSES OF BROAD-SPECTRUM ANTIBIOTICS ACTIVE AGAINST GRAM-NEGATIVE PATHOGENS WERE DISCOVERED BY THE 1960S. OVERMINING OF ACTINOMYCETES RESULTED IN THE COLLAPSE OF THE DISCOVERY PLATFORM. NOVEL ANTIBIOTICS DISCOVERED SINCE THEN ONLY ACT AGAINST GRAM-POSITIVE SPECIES. WE DEVELOPED METHODS TO ACCESS A BROADER RANGE OF BACTERIA, WITH A FOCUS ON UNCULTURED SPECIES THAT MAKE UP 99% OF TOTAL BIODIVERSITY. A NUMBER OF NOVEL COMPOUNDS CAME FROM THIS SOURCE, INCLUDING TEIXOBACTIN, REPRESENTING A NEW CLASS OF CELL- WALL ACTING COMPOUNDS WITHOUT DETECTABLE RESISTANCE (LING ET AL., 2015). TEIXOBACTIN IS UNDERGOING IND-ENABLING STUDIES; IT IS ALSO A NARROW-SPECTRUM COMPOUND. WE PROPOSE TO DEVELOP A PLATFORM FOR EFFICIENT DISCOVERY OF NOVEL ANTIMICROBIALS. THE MAIN PROBLEM IS THE ENORMOUS BACKGROUND OF TOXIC, AND TO A LESSER EXTENT, KNOWN COMPOUNDS. WE HYPOTHESIZE THAT THE BOTTLENECK OF DEREPLICATION CAN BE RESOLVED BY DIFFERENTIAL SCREENING THAT DETECTS THE PRESENCE OF A PROMISING COMPOUND PRIOR TO DEREPLICATION. USING THIS APPROACH, WE RECENTLY DISCOVERED DAROBACTINS THAT HAVE A NOVEL SCAFFOLD AND TARGET THE ESSENTIAL OUTER MEMBRANE PROTEIN BAMA (IMAI ET AL., 2019), AND SEVERAL ADDITIONAL NOVEL COMPOUNDS. IN THE PROPOSED PROJECT, WE WILL DEVELOP AN ULTRA-HIGH THROUGHPUT SCREEN BASED ON ENCAPSULATING PRODUCING BACTERIA TOGETHER WITH DIFFERENT FLUORESCENTLY LABELED REPORTERS IN MICRODROPLETS CREATED IN A MICROFLUIDICS DEVICE. OUR PRELIMINARY DATA SHOW THAT SORTING DROPLETS CAN BE PERFORMED AT A RATE OF 106 A DAY, AND LEADS TO DETECTION OF PRODUCERS OF DESIRABLE ANTIMICROBIALS. WE WILL EVALUATE SEVERAL MODALITIES OF THIS SCREEN, AIMED AT DISCOVERING SELECTIVE AS WELL AS BROAD-SPECTRUM COMPOUNDS ACTING AGAINST GRAM-NEGATIVE BACTERIA; AND ANTI-PERSISTER COMPOUNDS. THE PLATFORM IS LIKELY TO BE OF USE TO THE FIELD OF ANTIBIOTIC DISCOVERY. LEADS THAT COME OUT OF THIS SCREEN WILL BE EVALUATED IN VITRO AND IN ANIMAL MODELS OF INFECTION. NOVEL LEADS THAT COME OUT OF THIS PROJECT WILL BE READY TO ENTER IND-ENABLING STUDIES.

AN ACCELERATED PATHWAY FROM ASSOCIATES TO MASTER'S DEGREE IN BIOTECHNOLOGY

NAME OF EFFORT: "GNOSYS: RAISING THE LEVEL OF DISCOURSE IN PROGRAMMING SYSTEMS" TYPE OF AWARD: COOPERATIVE AGREEMENT

GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP)

AFFECT REGULATION AND BETA AMYLOID: MATURATIONAL FACTORS IN AGING AND AGE-RELATED PATHOLOGY

FULLY INTEGRATED ACOUSTO OPTICAL ELECTRONIC PHOTONIC SYSTEM FOR REAL TIME IN VIVO 3D PHOTOACOUSTIC IMAGING BY NORTHEASTERN UNIVERSITY AND SUBAWARDEES UNIVERSITY OF WASHINGTON JOHNS HOPKINS UNIVERSITY AND MASSACHUSETTS GENERAL HOSPITAL.ENDOSCOPIC AND INTRAVASCULAR PHOTOACOUSTIC IMAGING SYSTEMS THAT NAVIGATE THE BODY TO DIAGNOSE AND EVALUATE DISEASE ARE A KEY ELEMENT OF THE FUTURE OF MEDICINE ADDRESSING MALFUNCTION IN CANCER CARDIOVASCULAR AND OTHER DISEASE AREAS. AT PRESENT HOWEVER WIDE DEPLOYMENT OF THESE SYSTEMS HAVE BEEN LIMITED BY LOW IMAGING SPEED AND LARGE SIZE FREQUENTLY CAUSING POST OPERATIVE COMPLICATIONS. EMERGING SYSTEMS ON THE OTHER HAND SUFFER FROM POOR IMAGE QUALITY DUE TO THEIR INHERENT LIMITATIONS OF LOW SIGNAL TO NOISE RATIO AND SPATIAL RESOLUTION. TO ADDRESS THESE CORE LIMITATIONS WE NEED TO BREAK AWAY FROM THE CONVENTIONAL SCHEME OF RECORDING AND RELAYING PHOTOACOUSTIC SIGNALS USING ELECTRICAL ULTRASOUND TRANSDUCERS AND CABLES.WE PROPOSE A DISRUPTIVE APPROACH BASED ON ADVANCEMENTS IN MICROELECTRONICS NANOFABRICATION AND OPTIONS TO DEVELOP AN INNOVATIVE ELECTRONIC PHOTONIC PHOTOACOUSTIC IMAGING SYSTEM BASED ON ACOUSTO OPTIC DETECTION. THE SYSTEM CORE ELEMENT IS A MINIATURE PROBE IN WHICH PHOTOACOUSTIC WAVES FROM THE TISSUE OF INTEREST ARE DETECTED AND TRANSDUCED TO OPTICAL SIGNALS. THE RESULTING OPTICAL SIGNALS ARE ROUTED USING A DENSE OPTICAL FIBER BUNDLE TO A MODULE OUTSIDE THE BODY. THE MODULE EMBODIES APPLICATION SPECIFIC ELECTRONIC PHOTONIC INTEGRATED CIRCUITS AND COMPUTATIONAL ALGORITHMS FOR DATA DECODING AND PROCESSING. OUR UNIQUE DESIGN APPROACH WILL RESULT IN AN ALMOST ORDER OF MAGNITUDE REDUCTION IN PROBE AREA WITH A SIMULTANEOUS ORDER OF MAGNITUDE IMPROVEMENT IN SPATIAL RESOLUTION AT CLINICALLY RELEVANT DEPTHS OVER THE STATE OF THE ART.THE RESULT OF OUR EFFORT WILL BE A RADICALLY NEW MINIATURE OPTICAL PHOTOACOUSTIC IMAGING PLATFORM WITH ADVANCE IMAGE RECONSTRUCTION ALGORITHMS. SUCH A SYSTEM CAN TRANSFORM THE LANDSCAPE OF THE PHOTOACOUSTIC IMAGING FIELD BY PROVIDING REAL TIME HIGH CONTRAST VOLUMETRIC IMAGES THAT CAN ASSIST THE DIAGNOSIS AND TREATMENT OF WIDESPREAD DISEASES RANGING FROM CANCER TO VASCULAR DISEASES. THE COMMERCIALIZATION OF OUR TECHNOLOGY WILL HAVE BROAD SOCIETAL IMPACTS SINCE IT CAN PROVIDE OPPORTUNITIES WITH LOW INVASIVENESS TO PERSONALIZE THERAPIES AND IMPROVE OUTCOMES FOR PATIENTS.

UNDERSTANDING GULF WAR ILLNESS: AN INTEGRATIVE MODELING APPROACH

AWARENESS AND LOCALIZATION OF EXPLOSIVE RELATED THREATS (ALERT)

INTERDISCIPLINARY EXPEDITIONARY CYBER RESEARCH

CENTER OF EXCELLENCE - CENTER FOR EXPLOSIVES (CER) CENTER LEAD

EFFECT OF METHODOLOGICAL AND BIOLOGICAL VARIABILITY ON MOLECULAR PROFILING OF EXTRACELLULAR VESICLES IN CANCER DETECTION

STRUCTURE AND FUNCTION OF CB2 RECEPTOR

ALERT - CENTER OF EXCELLENCE FOR EXPLOSIVES DETECTION MITIGATION AND RESPONSE

AWARENESS & LOCALIZATION OF EXPLOSIVES-RELATED THREATS (ALERT)

DEVELOPING HISPANIC-SERVING INSTITUTIONS PROGRAM

GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP) -THE NATIONAL SCIENCE FOUNDATION (NSF) GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP) IS A HIGHLY COMPETITIVE, FEDERAL FELLOWSHIP PROGRAM. GRFP HELPS ENSURE THE VITALITY AND DIVERSITY OF THE SCIENTIFIC AND ENGINEERING WORKFORCE OF THE UNITED STATES. THE PROGRAM RECOGNIZES AND SUPPORTS OUTSTANDING GRADUATE STUDENTS WHO ARE PURSUING RESEARCH-BASED MASTER'S AND DOCTORAL DEGREES IN SCIENCE, TECHNOLOGY, ENGINEERING, AND MATHEMATICS (STEM) AND IN STEM EDUCATION. THE GRFP PROVIDES THREE YEARS OF FINANCIAL SUPPORT FOR THE GRADUATE EDUCATION OF INDIVIDUALS WHO HAVE DEMONSTRATED THEIR POTENTIAL FOR SIGNIFICANT RESEARCH ACHIEVEMENTS IN STEM AND STEM EDUCATION. THIS AWARD SUPPORTS THE NSF GRADUATE FELLOWS PURSUING GRADUATE EDUCATION AT THIS GRFP INSTITUTION. 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.

THIS AWARD OF $3,841,000 IN CONGRESSIONALLY MANDATED FY23 FEDERAL FUNDING WILL SUPPORT THE RE-ESTABLISHMENT OF THE NATIONAL CORAL REEF INSTITUTE (NCRI) AT NOVA SOUTHEASTERN UNIVERSITY (NSU) INCLUDING THE ESTABLISHMENT OF A GOVERNANCE STRUCTURE; CREATION OF AN ADVISORY BOARD AND TECHNICAL ADVISORY COMMITTEE; THE ESTABLISHMENT OF FORMAL COOPERATION MECHANISMS WITH LABORATORIES AT THE FEDERAL, STATE, AND LOCAL LEVEL, AS WELL AS WITH ACADEMIA; AND HIRING OF FIVE POSTDOCTORAL RESEARCHERS AS WELL AS GRADUATE STUDENTS. UPON RE-ESTABLISHMENT OF NCRI THE PROPOSAL SUPPORT THE IMPLEMENTATION OF TARGET RESEARCH PROJECTS TO ACHIEVE THE FOLLOWING FIVE GOALS: 1. EVALUATE CHALLENGES RESULTING FROM UPSTREAM IMPACTS AND OTHER ENVIRONMENTAL STRESSES; 2. DEVELOP A DETECTION ALGORITHM FOR PREDICTION OF DISEASE HOTSPOTS IN THE CARIBBEAN AND PACIFIC; 3. UNDERSTAND, MODEL, AND PREDICT OUTBREAKS AND LEGACY EFFECTS OF CORAL DISEASE EPIZOOTICS TO INFORM QUANTITATIVELY JUSTIFIABLE RESTORATION ACTION; 4. INVESTIGA

POSTDOCTORAL TRAINING IN GENERAL, PEDIATRIC AND PUBLIC HEALTH DENTISTRY AND DENTAL HYGIENE

PRESCRIPTION DRUG ABUSE AMONG CLUB DRUG USERS

FIRST IN THE WORLD

AWARENESS & LOCALIZATION OF EXPLOSIVE-RELATED THREATS (ALERT)

COOPERATION AND ALIGNMENT OF SERVICES TO ENGAGE HISPANIC AND LOW INCOME TRANSFER AND NATIVE STUDENTS PURSUING HIGH INTEREST/HIGH DEMAND STEM FIELDS

GERIATRICS WORKFORCE ENHANCEMENT PROGRAM

ADVANCE INSTITUTIONAL TRANSFORMATION AWARD: ADVANCING WOMEN WITHIN INTERDISCIPLINARY AND INTERNATIONAL NETWORKS

MEDIATORS AND MODERATORS OF AUDITORY TRAINING - THIS PROPOSAL SEEKS TO UNDERSTAND MECHANISMS OF AUDITORY TRAINING (AT) AND POTENTIAL OF AT TO MITIGATE HEARING ISSUES THAT PROMOTE RISK OF DEVELOPMENT OF ALZHEIMER’S DISEASE AND RELATED DEMENTIAS (ADRD). REPORTS FROM THE LANCET COMMISSION (LIVINGSTONE AND COLLEAGUES, 2020), AND OTHERS, SHOW MIDLIFE HEARING LOSS IS ONE OF THE GREATEST PREDICTORS OF LATE-LIFE DEMENTIA, AND HEARING AIDS PROTECT AGAINST DEVELOPMENT OF ADRD. WHILE THIS HAS PROMOTED A PUSH FOR GREATER DISTRIBUTION OF HEARING AIDS, RESEARCH FROM GATES AND COLLEAGUES (2011) SUGGESTS THAT CENTRAL HEARING PROCESSES MAY BE GREATER PREDICTORS OF ONSET OF ADRD THAN PERIPHERAL HEARING (AS ADDRESSED THROUGH HEARING AIDS). CENTRAL AUDITORY PROCESSING ABILITIES ARE FUNDAMENTAL TO UNDERSTAND SPEECH, APPRECIATE MUSIC, AND SEPARATE COMPETING ENVIRONMENTAL SOUND SOURCES. HEARING CHALLENGES EXPERIENCED WITH INCREASING AGE, ESPECIALLY UNDERSTANDING SPEECH IN NOISY AMBIENT ENVIRONMENTS, CAUSE FRUSTRATION WITH INTERPERSONAL VERBAL COMMUNICATION AND DETRIMENTAL LONG-TERM EFFECTS ON FUNCTIONAL INDEPENDENCE, COGNITIVE ABILITIES, AND OVERALL QUALITY OF LIFE, INCLUDING INCREASED RISK FOR ADRD. NEVERTHELESS, DESPITE EXTENSIVE RESEARCH CONDUCTED ACROSS MULTIPLE FIELDS, CLINICIANS AND RESEARCHERS STILL DISAGREE ABOUT THE BEST WAYS TO ADDRESS THE DIVERSITY OF HEARING DIFFICULTIES INDIVIDUALS FACE THROUGHOUT THEIR LIVES. THE GUIDING PREMISE OF THE CURRENT PROPOSAL IS THE NEED FOR ROBUST AND RELIABLE DATA SETS TO CLARIFY THE UNDERLYING MECHANISMS OF AT AND TO IDENTIFY THE MEDIATORS AND MODERATORS THAT IMPACT TRAINING OUTCOMES. THE OVERARCHING GOAL OF THIS PROPOSAL IS THAT BETTER UNDERSTANDING OF MECHANISMS OF AT, WITH FOCUS ON SPEECH IN COMPETITION, CAN ADDRESS THE MOST PREVALENT HEARING COMPLAINTS REPORTED BY PEOPLE AS THEY AGE, AND IN TURN MITIGATE TRANSITION TO ADRD. TO ADDRESS THIS, WE WILL RECRUIT A LARGE AND DIVERSE SAMPLE OF OLDER ADULTS, INCLUDING THOSE WITH PRODROMAL ADRD, AND A COMPARISON GROUP OF YOUNGER ADULTS (1260 PARTICIPANTS ACROSS TRAINING CONDITIONS, INCLUDING SEPARATE SAMPLES OF YOUNG AND OLDER ADULTS). WE WILL RESEARCH HOW BASELINE COGNITIVE AND HEARING MEASURES PREDICT TRAINING OUTCOMES (MODERATORS) AND HOW THESE INTERACT WITH TRAINING METHODS (MEDIATORS). TO ENHANCE RIGOR AND REPRODUCIBILITY, WE WILL RELEASE DATA SETS AND TRAINING/ASSESSMENT TOOLS TO ENABLE OTHER RESEARCHERS TO CONDUCT ANALYSES, REPLICATE OUR STUDIES, AND TEST THEIR OWN TRAINING METHODS USING COMMON OUTCOME MEASURES. THE PROPOSED RESEARCH WILL ADDRESS FOUR SPECIFIC AIMS. AIM 1 – DETERMINE THE RELATIONSHIP OF STIMULUS COMPLEXITY AND AT OUTCOMES. AIM 2 – DETERMINE THE RELATIONSHIP OF AT TRAINING STRUCTURES AND AT OUTCOMES. AIM 3 – DETERMINE RELATIONSHIPS BETWEEN PARTICIPANT CHARACTERISTICS (MODERATORS) AND AT APPROACHES (MEDIATORS) ON TRAINING OUTCOMES. AIM 4 – CREATE AN AT PLATFORM THAT FACILITATES FAITHFUL REPLICATION AND MODELLING. THROUGH THE COLLECTION AND DISSEMINATION OF A LARGE, UNIQUE, AND COMPREHENSIVE DATASET, THIS PROPOSAL HAS POTENTIAL FOR TRANSFORMATIVE IMPACT BY CLARIFYING MODERATORS AND MEDIATORS OF AT, AND WILL AFFORD TRANSLATIONAL OPPORTUNITIES TO CONTRIBUTE TO THE MITIGATION OF HEARING AND COGNITIVE DECLINE IN INDIVIDUALS WHO MAY BE AT RISK FOR THE DEVELOPMENT OF ADRD.

MAKING OLIGONUCLEOTIDES BETTER BIOPHARMACEUTICALS BY STERIC PROTECTION

TAS::97 0400:: TAS CONTINUUM: FINDING SPACE AND TIME VULNERABILITIES IN JAVA PROGRAMS

CENTER FOR RESEARCH ON EARLY CHILDHOOD EXPOSURE AND DEVELOPMENT IN PUERTO RICO (CRECE)

EPIGENETIC MARKS OF COCAINE ADDICTION

AWARENESS & LOCALIZATION OF EXPLOSIVE RELATED THREATS (ALERT)

ORALLY BIOAVAILABLE 4(1H)-QUINOLONES WITH MULTI-STAGE ANTIMALARIAL ACTIVITY

USING INFANT NON-NUTRITIVE SUCK AS A DIAGNOSTIC MEASURE OF FUTURE SPEECH FUNCTION - PROJECT SUMMARY PEDIATRIC FEEDING DISORDERS ARE ON THE RISE AND ARE PRESENT IN 20-50% OF TYPICALLY DEVELOPING CHILDREN (1-8) AND IN 33-80% OF CHILDREN WITH DEVELOPMENTAL DELAY (9, 10). FURTHERMORE, INFANTS WHO ARE BORN PRETERM ARE PARTICULARLY AT-RISK FOR SUCKING AND FEEDING DIFFICULTIES (11, 12). EARLY NON-NUTRITIVE SUCK (NNS) – OR SUCKING WITHOUT NUTRIENTS BEING DELIVERED – AND FEEDING SKILLS HAVE BEEN SHOWN TO BE RELIABLE INDICATORS OF CENTRAL NERVOUS SYSTEM (CNS) INTEGRITY (18). IN FACT, DELAYS IN SUCKING AND FEEDING HAVE BEEN REPORTED IN APPROXIMATELY 35-48% OF INFANTS WITH DIFFERENT TYPES OF NEONATAL BRAIN INJURY (18). SUCKING, FEEDING, SPEECH, AND LANGUAGE ALL DEVELOP IN PARALLEL IN THE FIRST YEAR OF LIFE AND RELY HEAVILY ON SENSORIMOTOR INTEGRATION. HOWEVER, THE LINK BETWEEN SUCKING AND FEEDING SKILLS, CNS FUNCTION, AND DEVELOPMENT EXTENDS BEYOND THE NEONATAL PERIOD. EMERGING RETROSPECTIVE RESEARCH LINKS NEONATAL SUCKING AND FEEDING PATTERNS TO SUBSEQUENT SPEECH (13) AND LANGUAGE (14-17) DEVELOPMENT IN EARLY CHILDHOOD. ALTHOUGH THESE BEHAVIORS EMERGE ON A SIMILAR TIMELINE AND SHARE NEURAL RESOURCES AND MUSCULATURE, THEY ARE RARELY STUDIED TOGETHER AND THE LINKS BETWEEN THEM REMAIN UNKNOWN. WE PROPOSE A LONGITUDINAL STUDY TO SAMPLE NNS DATA AT 3, 6, 9, AND 12 MONTHS OF AGE AND SPEECH OUTCOMES AT 12, 24, AND 36 MONTHS OF AGE ACROSS FULL-TERM (N=85) AND MODERATE TO LATE PRETERM (32-37 WEEKS’ GESTATIONAL AGE; N=85) INFANTS. THE SPECIFIC GOALS OF THE PROPOSED RESEARCH ARE AS FOLLOWS: (AIM 1) TO ESTABLISH TYPICAL PATTERNS OF NNS ACROSS INFANTS BORN FULL-TERM AND PRETERM IN THE FIRST YEAR OF LIFE AND UTILIZE A FUNCTIONAL DATA ANALYSIS TO EXAMINE INFANTS’ NNS BURST WAVEFORMS, AND (AIM 3) TO DETERMINE THE ABILITY OF NNS TO PREDICT SUBSEQUENT SPEECH DEVELOPMENT ACROSS PRETERM AND FULL-TERM INFANTS UNTIL AGE THREE. WE HYPOTHESIZE THAT INFANT SUCK WILL CHANGE SIGNIFICANTLY ACROSS THE FIRST YEAR OF LIFE WITH INFANTS BORN PREMATURE PERFORMING WORSE ON THESE MEASURES COMPARED TO FULL-TERM INFANTS. IN ADDITION, WE HYPOTHESIZE THAT NEONATAL SUCK WILL PREDICT SPEECH DEVELOPMENT ACROSS PRETERM AND FULL-TERM INFANTS. THIS STUDY PROVIDES AN UNPRECEDENTED LEVEL OF POWER IN IDENTIFYING THE CONNECTION BETWEEN NEONATAL SUCKING AND SUBSEQUENT SPEECH EMERGENCE FOR SEVERAL REASONS: WE WILL USE OUR (1) INNOVATIVE, CUSTOM AND QUANTITATIVE NNS DEVICE TO SAMPLE SUCK ACROSS (2) TWO GROUPS OF INFANTS AND WILL (3) UTILIZE FUNCTIONAL DATA ANALYSES TO BETTER UNDERSTAND NNS DEVELOPMENT AND ITS IMPLICATIONS FOR SPEECH DEVELOPMENT LATER IN LIFE. (4) WE WILL USE STANDARDIZED AND NON- STANDARDIZED APPROACHES TO LONGITUDINALLY STUDY SPEECH DEVELOPMENT, WHICH WILL ALLOW FOR A MORE ROBUST AND NUANCED UNDERSTANDING OF HOW NNS AND SPEECH ARE CONNECTED IN INFANTS AND CHILDREN. OVERALL, THIS PROJECT CAPTURES THREE YEARS OF IN-DEPTH ORAL MOTOR COORDINATION USING STATE-OF-THE-ART METHODS AND COLLABORATORS TO ANSWER IMPORTANT THEORETICAL QUESTIONS. RESULTS GENERATED BY THIS CLINICALLY RELEVANT AND THEORETICALLY DRIVEN STUDY WILL CREATE A PARADIGM SHIFT IN HOW CLINICIANS APPROACH FEEDING AND SPEECH THERAPIES IN EARLY CHILDHOOD.

DESIGN, CONTROL AND APPLICATION OF NEXT-GENERATION QUBITS

INTERPRETER TRAINING: NATIONAL INTERPRETER EDUCATION CENTER

ROBUST ULTRA-HIGH SENSITIVITY PROTEOMIC TECHNOLOGIES FOR LIMITED SAMPLES

SUPPORTING IGVF BY MODELING GENETICS, FUNCTION, AND PHENOTYPE WITH MACHINE LEARNING - PROJECT SUMMARY LEVERAGING THE POWER OF THE HUMAN GENOME TO UNDERSTAND THE RISKS, CAUSES, AND TREATMENTS OF HUMAN DIS- EASE REMAINS A GRAND CHALLENGE FOR ALL OF BIOLOGY AND MEDICINE. WHILE SEQUENCING COSTS HAVE PLUMMETED, AND CLINICAL IMPLEMENTATION HAS BECOME COMMONPLACE, INTERPRETING HUMAN GENOMES REMAINS A HIGHLY CHALLENGING TASK. IT IS OUR HYPOTHESIS THAT UNDERSTANDING THE FUNCTION OF THE GENOME AND ITS PRODUCTS AT A MOLECULAR, TISSUE, AND PHENOTYPIC LEVEL USING ADVANCED MACHINE LEARNING WILL HELP UNLOCK THE DOOR TO BETTER INTERPRETATION FOR SCI- ENTIFIC DISCOVERY AND BETTER CLINICAL OUTCOMES BASED ON GENOMIC MEDICINE. TO THAT END, OUR TEAM HAS SPENT THE PAST TWO DECADES WORKING TO DEVELOP COMPUTATIONAL MODELS OF BIOLOGY, TO PREDICT HOW THOSE MODELS ARE PERTURBED THROUGH CHANGES IN THE GENOME, AND TO USE THOSE PERTURBATIONS TO MODEL PHENOTYPE AND DISEASE. WE HAVE HAD MANY RESEARCH OUTPUTS IN THIS AREA, HAVING DEVELOPED AND PUBLISHED A NUMBER OF WIDELY USED METHODS THAT PREDICT BIOCHEMICAL AND PHENOTYPIC CHANGES CAUSED BY GENETIC VARIANTS TO INFER PHENOTYPE AND PATHOGENICITY. HOWEVER, WE BELIEVE THAT THERE IS A COMING CONVERGENCE BETWEEN THE VARIABILITY IN CLINICAL INTER- PRETATION, HIGH-THROUGHPUT BIOTECHNOLOGY ASSAYS, AND MODERN MACHINE LEARNING METHODOLOGY THAT WILL RESULT IN MORE ACCURATE CLINICAL ASSESSMENTS AND IMPROVED CLINICAL CARE. THEREFORE, IN THIS AMBITIOUS PROPOSAL, WE ARE ADDRESSING IMPORTANT QUESTIONS IN VARIANT AND GENOME INTERPRETATION CONSISTENT WITH THIS VIEW AND THE MISSION OF THE IGVF CONSORTIUM. OUR MAJOR GOALS INCLUDE (1) DEVELOPING ADVANCED SEMI-SUPERVISED APPROACHES TO PREDICT VARIANTS THAT DISRUPT MOLECULAR FUNCTION AND/OR ARE CAPABLE OF ALTERING PHENOTYPES; (2) IDENTIFYING IN- FORMATIVE ASSAYS, VARIANTS, AND GENES TO AUTOMATE EXPERIMENTAL DESIGN WITH AN EMPHASIS ON RESOURCE ALLOCA- TION AND REDUCTION OF ASCERTAINMENT BIAS IN THE CONSORTIUM; AND (3) DEVELOPING MACHINE LEARNING APPROACHES TO INTEGRATE THESE MODELS INTO A WORKFLOW OF THE IGVF CONSORTIUM AND ENABLE THE INTERACTION BETWEEN COMPU- TATION AND EXPERIMENT IN ORDER TO CATALYZE ADVANCES IN BOTH GENETIC VARIANT INTERPRETATION AND PREDICTIVE MODEL DEVELOPMENT.

A PROTOTYPE FLIGHT FOR THE GRAMS PROJECT

THE PURPOSE OF THIS AGREEMENT IS TO FUND RESEARCH SUPPORTING THE DEFENSE ADVANCED RESEARCH PROJECTS AGENCYS DARPA OPTOMECHANICAL THERMAL IMAGING OPTIM PROGRAM. THIS EFFORT SHALL BE CARRIED OUT GENERALLY AS SET FORTH IN EXHIBIT B, RESEARCH DESCRIPTION DOCUMENT, DATED JUNE 9, 2023, AND IN THE RECIPIENTS, PROPOSAL TITLED, NANO OPTO MECHANICAL PIEZOELECTRIC RESONANT INFRARED SENSITIVE METAMATERIALS NPRIME FOR QUANTUM LIMITED PHOTODETECTION, DATED NOVEMBER 1, 2022, COPIES OF WHICH ARE IN THE POSSESSION OF BOTH PARTIES.

SYNTHETIC MRNA CONTROL SET FOR NANOPORE-BASED PSEUDOURIDINE MODIFICATION PROFILING IN HUMAN TRANSCRIPTOMES - PROJECT SUMMARY/ABSTRACT MAMMALIAN CELLS EXPEND LARGE AMOUNTS OF ENERGY INTO GENERATING ENZYME-MEDIATED RNA CHEMICAL MODIFICATIONS THAT CAN CHANGE THE BASE-PAIRING, RNA STRUCTURE, OR RECRUITMENT OF RNA-BINDING PROTEINS, AMONG OTHER ELUSIVE ROLES. PSEUDOURIDINE ()-MODIFIED MRNAS ARE MORE THERMODYNAMICALLY STABLE, MORE RESISTANT TO RNASE-MEDIATED DEGRADATION, AND HAVE THE POTENTIAL TO MODULATE IMMUNOGENICITY AND ENHANCE TRANSLATION IN VIVO. HOWEVER, DETECTION IS EXTREMELY CHALLENGING: MODIFICATIONS DO NOT AFFECT WATSON-CRICK BASE PAIRING AND ARE INDISTINGUISHABLE FROM URIDINE WHEN USING HYBRIDIZATION-BASED METHODS. FURTHER, SINCE IS AN ISOMER OF URIDINE, DETECTION USING MASS SPECTROMETRY REQUIRES NON-QUANTITATIVE CHEMICAL DERIVATIZATION METHODS. WHILE RECENT STUDIES HAVE SHOWN THAT RNA MODIFICATIONS CAN BE DETECTED THROUGH DIRECT RNA NANOPORE SEQUENCING BY MONITORING BASECALLING ERRORS, WE HAVE RECENTLY SHOWN THAT THE ACCURACY AND FIDELITY OF THIS APPROACH IS RELATIVELY LOW AND SEQUENCE DEPENDENT. OUR TEAM HAS RECENTLY USED A LIGATION APPROACH TO PRODUCE SYNTHETIC MRNA CONTROLS THAT CONTAIN SINGLE SITES WITHIN RELEVANT TRANSCRIPTS MAMMALIAN CELLS. USING THESE SYNTHETIC CONTROLS WE PERFORMED NANOPORE-BASED RNA SEQUENCING AND DEVELOPED COMPUTATIONAL TOOLS THAT INCREASE THE ACCURACY OF -CALLING TO 90+%, DEPENDING ON THE SPECIFIC SEQUENCE. WE ARE BASING OUR WORK ON OUR RECENT FINDING THAT ACHIEVING QUANTIFICATION REQUIRES SEQUENCE-SPECIFIC TRAINING USING UNIQUE SIGNAL PARAMETERS. THE INITIAL SUCCESS OF OUR TEAM HAS LAID THE FOUNDATION TO 1) GENERATE AN EXPANDED SET OF BARCODED SYNTHETIC RNA CONSTRUCTS THAT CONTAIN SINGLE SITES, 2) OBTAIN A RIGOROUS SET OF QUADRUPLICATE NANOPORE RUNS WITH ~50,000 SINGLE-MOLECULE READS PER CONSTRUCT, 3) DEVELOP COMPUTATIONAL TOOLS TO ALLOW HIGHLY ACCURATE SEQUENCE-SPECIFIC -CALLING. WE WILL DEVELOP A GOLD-STANDARD SET OF SYNTHETIC MRNA TRANSCRIPTS AS A TRAINING MOLECULAR SET FOR QUANTITATIVE PROFILING IN DIRECT RNA NANOPORE SEQUENCING OF HUMAN TRANSCRIPTOMES. THE MOLECULAR SET WILL ALLOW QUANTITATIVE PROFILING OF HUNDREDS OF PUTATIVE SITES ACROSS MAMMALIAN SAMPLES. THIS PROPOSAL WILL SERVE AN UNMET NEED BY ADDRESSING A CRITICAL BOTTLENECK: THE LACK OF AVAILABLE MODIFIED RNA MODIFICATION GOLD STANDARDS, I.E., RNA MOLECULES THAT CONTAIN A SITE-SPECIFIC AND STRUCTURE-SPECIFIC MODIFICATION. IN THIS COLLABORATIVE PROJECT WE WILL DEVELOP A COMPLETE PIPELINE FOR SYNTHESIS OF GOLD STANDARD MOLECULES; USE THESE MOLECULES TO MEASURE THE NANOPORE SIGNALS THAT MODIFICATIONS PRODUCE; DEVELOP A MACHINE-LEARNING TOOL TO ACCURATELY QUANTIFY THESE MODIFICATIONS; PROFILE SITE-SPECIFIC MODIFICATIONS IN VARIOUS CELL LINES TO OBTAIN -MAPS THAT CAN BE USED TO ASSESS RELATIONSHIPS OF MODIFICATIONS WITH PHENOTYPES.