Northeastern 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)

ENDOCANNABINOID ACTIVE SITES AS THERAPEUTIC TARGETS

SENTRY SOFT TARGET ENGINEERING TO NEUTRALIZE THE THREAT REALITY

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

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)

CENTER FOR TRANSLATIONAL CANCER NANOMEDICINE

EPISTORM: CENTER FOR ADVANCED EPIDEMIC ANALYTICS AND PREDICTIVE MODELING TECHNOLOGY

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

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

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

RESOLVING THE BOTTLENECK IN ANTIBIOTIC DISCOVERY

STRUCTURAL DETERMINANTS OF PIP2 REGULATION

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

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

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.

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

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.

SUPER-PERSISTENT CELLS AND THE PARADOX OF UNTREATABLE INFECTIONS

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

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

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

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

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

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.

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)

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.

FIRST IN THE WORLD

AWARENESS & LOCALIZATION OF EXPLOSIVE-RELATED THREATS (ALERT)

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)

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

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.

CANCURE: CANCER NANOMEDICINE CO-OPS FOR UNDERGRADUATE RESEARCH EXPERIENCES

CARDIOPULMONARY RISK ASSESSMENT FROM SMOKE EXPOSURE AT THE WILDLAND URBAN INTERFACE - PROJECT SUMMARY ACUTE AND CHRONIC WILDLAND FIRE SMOKE INHALATION HAVE BEEN LINKED TO INCREASED MORTALITY AS WELL AS RESPIRATORY AND CARDIOVASCULAR MORBIDITY, THOUGH THE EXTENT TO WHICH THE FREQUENCY AND DURATION OF EXPOSURE OR THE CHEMICAL AND PARTICLE PROFILES OF THE SMOKE CONTRIBUTE TO THE OBSERVED HEALTH EFFECTS REMAINS UNKNOWN. AS THE OCCURRENCES OF WILDLAND FIRES AND NUMBER OF PEOPLE LIVING AT THE WILDLAND URBAN INTERFACE (WUI) CONTINUE TO INCREASE, PROLONGED INHALATION OF WILDLAND FIRE SMOKE POSES A SERIOUS THREAT TO PUBLIC HEALTH. DUE TO THIS, THERE IS AN URGENT NEED TO BETTER UNDERSTAND THE ADVERSE CARDIOPULMONARY OUTCOMES ASSOCIATED WITH THE EXPOSURE TO WILDLAND URBAN SMOKE. THE SMOKE THAT ARISES FROM WILDLAND FIRES AT THE WUI IS A COMPLEX MIXTURE OF GASES, TRACE METALS, AND FINE AND ULTRAFINE PARTICLES. THE LATTER ARE PARTICULARLY DANGEROUS FOR HUMAN HEALTH, SINCE THEY DEPOSIT IN THE DEEP REGIONS OF THE LUNGS AND MAY TRANSLOCATE INTO THE BLOOD STREAM, INCREASING THE OXIDATIVE AND INFLAMMATORY BURDEN, BOTH LOCALLY AND SYSTEMICALLY. PROLONGED INFLAMMATION CAN LEAD TO THE DEVELOPMENT OF OBSTRUCTIVE LUNG DISEASE AND ATHEROSCLEROSIS. TO INVESTIGATE THE LINK BETWEEN EXPOSURE TO WUI SMOKE AND DEVELOPMENT OF CARDIOPULMONARY DYSFUNCTION, OUR INTERDISCIPLINARY TEAM BRINGS TOGETHER EXPERTISE IN FIRE GENERATION AND CHARACTERIZATION, RODENT AEROSOL EXPOSURES, RESPIRATORY MECHANICS, LUNG BIOLOGY, AND CARDIOVASCULAR PHYSIOLOGY. TO FULFILL OUR GOALS, WE WILL CREATE LAB-SCALE SMOKE USING MATERIALS REPRESENTATIVE OF WUI REGIONS IN SOUTHERN CALIFORNIA AND WE WILL DELIVER IT TO MICE. IN AIM 1, WE WILL INVESTIGATE THE ROLE OF FREQUENCY AND DURATION OF THE EXPOSURE, AS WELL AS PARTICULATE CONCENTRATION OF THE WILDLAND FIRE SMOKE. IN AIM 2, WE WILL FOCUS ON THE RELATIVE CONTRIBUTION OF DIFFERENT FUEL SOURCES CHARACTERISTIC OF THE WUI. FURTHERMORE, AS PART OF THIS ONES EARLY-STAGE-INVESTIGATOR PROJECT, THE PI AND CO-IS WILL GENERATE AN EXTERNAL ADVISORY PANEL CONSISTING OF INHALATION TOXICOLOGY RESEARCHERS, PUBLIC HEALTH ADVOCATES, AND FIRE PROTECTION EXPERTS. DISSEMINATION OF NEW KNOWLEDGE GAINED FROM THIS PROPOSAL TO THE COMMUNITY WILL BE A VITAL PART OF THIS ENDEAVOR.

IMPACT OF LIPIDS ON COMPOUND ABSORPTION: MECHANISTIC STUDIES AND MODELING

MEDIATORS AND MODERATORS OF PERCEPTUAL LEARNING

YOGA, AEROBIC AND STRETCHING EXERCISE EFFECTS ON NEUROCOGNITIVE PERFORMANCE: A RANDOMIZED CONTROLLED TRIAL

A REDUCED COMPLEXITY CROSS IN BALB/C SUBSTRAINS TO IDENTIFY THE GENETIC BASIS OF OXYCODONE DEPENDENCE PHENOTYPES

NEW COMPUTATIONAL SYSTEMS BIOLOGY METHODS FOR MODELING GENE REGULATORY CIRCUITS

FLUMOD - CENTER FOR THE MULTISCALE MODELING OF PANDEMIC AND SEASONAL FLU PREVENTION AND CONTROL

DIRECT RNA SEQUENCING USING ELECTO-OPTICAL ZERO MODE WAVEGUIDES AND CUSTOM CLICK FLUORESCENT NUCLEOTIDES - ADVANCES IN GENOME TECHNOLOGIES USHERED IN VAST COST REDUCTIONS IN DNA SEQUENCING AND INCREASED READ LENGTHS, THE LATTER AFFORDED BY DEVELOPMENT OF NEW SINGLE-MOLECULE SEQUENCING TECHNOLOGIES. AS A RESULT, MUCH OF THE GENOME’S “DARK MATTER” HAS BEEN ELUCIDATED, AND HIGHER-QUALITY REFERENCE GENOMES WERE MADE AVAILABLE. IN ADDITION TO GENOME SEQUENCING, THESE SINGLE-MOLECULE METHODS HAVE ENABLED NEW APPLICATIONS FOR PROBING CHEMICAL MODIFICATIONS IN DNA, BY EITHER PROBING THE KINETICS OF SEQUENCING-BY-SYNTHESIS USING OPTICAL WAVEGUIDES, OR BY ELECTRICALLY DISTINGUISHING MODIFIED BASES USING NANOPORES. DESPITE PROGRESS, A CRITICAL BARRIER IN GENOMICS IS UNDERSTANDING THE ROLES OF RNA IN BIOLOGY, WHICH DEMANDS METHODS FOR QUANTITATIVE ANALYSIS OF RNA MOLECULES IN A CELL. THE MYRIAD OF TYPES OF RNAS IN A CELL, THEIR DYNAMIC CHEMICAL MODIFICATIONS, AND THEIR ELABORATE STRUCTURAL AND FUNCTIONAL DIVERSITY, ALL HINT AT A TREMENDOUS LEVEL OF REGULATION AND BIOLOGICAL SIGNIFICANCE. TRADITIONAL RNA SEQUENCING METHODS HAVE PRIMARILY RELIED ON CONVERSION TO COMPLEMENTARY DNA (CDNA) FOLLOWED BY CDNA SEQUENCING USING EITHER HIGH-THROUGHPUT SECOND-GENERATION METHODS OR THIRD GENERATION SINGLE-MOLECULE METHODS, THE LATTER OF WHICH OFFERS LONG READS. USING THESE METHODS, SOME RNA MODIFICATIONS CAN BE READ THROUGH PRIOR CHEMICAL FUNCTIONALIZATION OF THE RNA PRIOR TO CONVERSION TO CDNA (FOR EXAMPLE, M6A, PSEUDOURIDINE, A-TO-I EDITING, 1-METHYLURIDINE, AND DIHYDROURIDINE). HOWEVER, THE CHEMICAL REACTIONS INVOLVED IN THESE METHODS ARE NOT 100% QUANTITATIVE OR SPECIFIC, AND FURTHER, DETECTION IS OFTEN DONE THROUGH INCOMPLETE READS DUE TO REVERSE TRANSCRIPTION BLOCKS, WHICH PRECLUDES DETECTION OF MULTIPLE MODIFICATIONS. THE ONLY AVAILABLE METHOD FOR DIRECT RNA SEQUENCING, THE OXFORD NANOPORE TECHNOLOGIES PLATFORM, SUFFERS FROM SEVERAL DRAWBACKS THAT INCLUDE HIGH INPUT REQUIREMENTS, LIMITED ABILITY TO PROBE RNA MODIFICATIONS, AND INCOMPLETE READS, PARTICULARLY NEAR THE RNA 5’ END. WE ADDRESS THESE LIMITATIONS BY DEVELOPING A NEW SINGLE-MOLECULE METHOD THAT CAN BE SCALED TO ALLOW LONG READ DIRECT RNA SEQUENCING AT HIGH THROUGHPUTS, ALL WITH VERY LOW INPUT REQUIREMENTS OF SEVERAL PICOGRAMS. BUILDING ON ZERO-MODE WAVEGUIDES (ZMWS) ORIGINALLY DEVELOPED BY PACIFIC BIOSCIENCES, WE HAVE RECENTLY DEVELOPED ELECTRO-OPTICAL ZMWS (EZMWS) THAT ALLOW LOW-INPUT CAPTURE OF DNA AND RNA MOLECULES. WE DEMONSTRATED USING THESE DEVICES IDENTIFICATION OF DNA FRAGMENTS FROM LOW INPUTS BY RAPID CAPTURE OF SINGLE MOLECULES AND THEIR FLASH SEQUENCING. TOGETHER WITH THE PYLE GROUP, WE ARE DEVELOPING THE INTEGRATION OF MARATHONRT, AN ULTRA- PROCESSIVE REVERSE TRANSCRIPTASE THAT CONVERTS RNA MOLECULES TO CDNA MOLECULES WITH HIGH PROCESSIVITY AND ACCURACY, INTO OUR ELECTRO-OPTICAL EZMWS FOR DIRECT RNA SEQUENCING. WE HAVE ALREADY FUSED MARATHONRT TO A STREPTAVIDIN PROTEIN AND DEMONSTRATED ITS FUNCTIONALITY IN EZMWS. HERE WE WILL BUILD ON THESE DEVELOPMENTS TO DEVELOP A DIRECT RNA SEQUENCING METHOD THAT CAN DETECT SINGLE BASE EDITS AND CHEMICAL MODIFICATIONS, ALL WITH HIGH COVERAGE FROM SINGLE-CELL INPUTS OF A FEW PG PER RUN.

THE NARRATIVE EFFECT OF ACTIVE VIDEO GAMES ON LONG-TERM MODERATE-TO-VIGOROUS PHYSICAL ACTIVITY

PLANNING AND UPDATING IN FRONTOPARIETAL NETWORKS FOR GRASPING

CYBERCORPS SCHOLARSHIP FOR SERVICE (RENEWAL): SECURING THE FUTURE: SCHOLARSHIP FOR SERVICE AT NORTHEASTERN UNIVERSITY -DESPITE THE RECOGNIZED NEED FOR A STRONG CYBERSECURITY WORKFORCE TO COMPLEMENT OUR NATION?S TECHNICAL STRENGTH, THE U.S. SUFFERS FROM A SUBSTANTIAL CYBERSECURITY WORKFORCE GAP. NOWHERE IS THIS GAP MORE KEENLY FELT THAN IN THE PUBLIC SECTOR, WHERE AGENCIES AT ALL LEVELS STRUGGLE TO ACQUIRE AND DEVELOP STRONG CYBERSECURITY TALENT. THIS PROJECT IS A CONTINUATION OF NORTHEASTERN UNIVERSITY?S LONG-STANDING PARTICIPATION IN THE SCHOLARSHIP FOR SERVICE (SFS) PROGRAM SINCE 2009. NORTHEASTERN IS DESIGNATED AS A NATIONAL CENTER OF ACADEMIC EXCELLENCE IN CYBER RESEARCH (CAE-R) BY THE NATIONAL CENTERS OF ACADEMIC EXCELLENCE IN CYBERSECURITY (NCAE-C) AND HAS A LONG TRACK RECORD OF SUCCESS IN PLACING SKILLED CYBERSECURITY WORKERS ACROSS GOVERNMENT AGENCIES AND FEDERALLY FUNDED RESEARCH AND DEVELOPMENT CENTERS (FFRDCS). IN THIS PROJECT, NORTHEASTERN WILL BUILD UPON ITS SUCCESSFUL HISTORY OF TRAINING CYBERSECURITY PROFESSIONALS WITH A THREE-FOLD APPROACH: (I) INCREASE RECRUITMENT FROM NON-TRADITIONAL POPULATIONS, (II) DEEPEN EXPOSURE TO THE CYBERSECURITY COMMUNITY AND CURRENT NEEDS, AND (III) STRENGTHEN SUPPORT FOR PLACING STUDENTS AT FEDERAL EXECUTIVE AGENCIES. WITH THIS APPROACH, THE TEAM BROADLY SEEKS TO SCALE UP ITS SFS PROGRAMMATIC EFFORTS ACROSS THE WORKFORCE RECRUITMENT AND DEVELOPMENT PIPELINE. THE TEAM WILL RAISE AWARENESS OF THE MUTUAL BENEFITS OF THE SFS PROGRAM TO A WIDER POPULATION OF CANDIDATES, INTENSIFYING RECRUITMENT FROM UNDER-REPRESENTED GROUPS ACROSS THE UNIVERSITY?S NETWORK OF CAMPUSES TO WIDEN THE FUNNEL OF POTENTIAL WORKERS. RECOGNIZING THE SIGNIFICANT BENEFIT OF USE-INSPIRED RESEARCH AND EDUCATION, THE PROJECT WILL DEEPEN THE EXPOSURE OF SFS SCHOLARS TO CONTEMPORARY ISSUES AND OPEN NEEDS IN THE SECURITY COMMUNITY. FINALLY, THE PROJECT WILL STRENGTHEN ALREADY-ESTABLISHED MENTORSHIP AND ADVISING FRAMEWORKS, BUILDING ADDITIONAL RECRUITMENT CHANNELS TO PARTICIPATING AGENCIES. THE ULTIMATE OBJECTIVE OF THIS EFFORT IS FOR ALL SFS STUDENTS AT NORTHEASTERN TO EFFICIENTLY FILL OPEN POSITIONS AT AGENCIES ACROSS THE US GOVERNMENT AND OTHER HIRING PARTNERS. THIS PROJECT IS SUPPORTED BY THE CYBERCORPS? SCHOLARSHIP FOR SERVICE (SFS) PROGRAM, WHICH FUNDS PROPOSALS ESTABLISHING OR CONTINUING SCHOLARSHIP PROGRAMS IN CYBERSECURITY AND ALIGNS WITH THE U.S. NATIONAL CYBER STRATEGY TO DEVELOP A SUPERIOR CYBERSECURITY WORKFORCE. FOLLOWING GRADUATION, SCHOLARSHIP RECIPIENTS ARE REQUIRED TO WORK IN CYBERSECURITY FOR A FEDERAL, STATE, LOCAL, OR TRIBAL GOVERNMENT ORGANIZATION FOR THE SAME DURATION AS THEIR SCHOLARSHIP SUPPORT.? 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.

DELINEATING THE ROLE OF SEROTONIN 5-HT2 RECEPTORS IN OPIOID USE DISORDERS:DEVELOPMENT OF NOVEL 5-HT2 MODULATORS WITH TRANSLATIONAL STUDIES IN RODENTS ANDPRIMATES

NORTHEASTERN UNIVERSITY NEW HESTIA AWARD CONTROL NUMBER: 2625-1626 TITLE: CENTURY-SCALE CARBON-SEQUESTRATION IN CROSS-LAMINATED TIMBER COMPOSITE BOLTED-STEEL BUILDINGS THE PROJECT TEAM’S AIM IS TO ACHIEVE WIDESPREAD CONSTRUCTION OF CARBON-NEGATIVE MULTI-STORY BUILDINGS BY 2050. MASS TIMBER BUILDINGS ARE CURRENTLY THE MOST VIABLE PATH TOWARDS THIS END. WHILE CODES NOW PERMIT SUCH BUILDINGS UP TO 18-STORIES, DESIGNERS MAY PREFER TRADITIONAL MATERIALS FOR THEIR LONGER SPANS; ENGINEERS MAY AVOID TIMBER DESIGNS IN SEISMIC AREAS; AND LOCAL TRADES MAY HAVE TO BE UPSKILLED FOR THE SKILLS SPECIFIC TO TIMBER CONSTRUCTION.

EMOTIONS ARE EMERGENT EVENTS CONSTRAINED BY AFFECTIVE AND CONCEPTUAL PROCESSES.

PREDICTABILITY IN COMPLEX OBJECT CONTROL - PROJECT SUMMARY MANIPULATION OF COMPLEX OBJECTS OR TOOL USE IS A HALLMARK OF DAILY LIVING, AND LOSS OF MANUAL DEXTERITY DUE TO MOTOR IMPAIRMENTS LEAD TO LOSS OF INDEPENDENCE. MANIPULATING OBJECTS IS PARTICULARLY CHALLENGING WHEN THE OBJECT HAS INTERNAL DYNAMICS THAT IS NOT DIRECTLY CONTROLLED. EVEN THE SEEMINGLY SIMPLE TASK OF TRANSPORTING A CUP OF COFFEE HAS INTRINSIC DYNAMICS THAT HUMANS NEED TO PREDICT, PREEMPT, AND COMPENSATE FOR TO AVOID SPILLING. CONTROL OF SUCH COMPLEX NONLINEAR SYSTEMS WITH ONLINE ERROR CORRECTIONS BASED ON PRECISE INTERNAL MODELS APPEARS DAUNTING, GIVEN THE SLOW NEURAL PROCESSES AND THE UBIQUITOUS NOISE IN THE SENSORIMOTOR SYSTEM. HENCE, THIS RESEARCH TESTS THE HYPOTHESIS THAT HUMANS LEARN TO SIMPLIFY THE OBJECT INTERACTIONS, I.E., MAKE THE INTERACTIONS PREDICTABLE. THE TASK OF CARRYING A CUP OF COFFEE IS MODELED WITH A CART-AND-PENDULUM SYSTEM THAT IS RENDERED IN A VIRTUAL ENVIRONMENT AND SUBJECTS INTERACT WITH THE VIRTUAL CUP VIA A ROBOTIC MANIPULANDUM. TO GAIN INSIGHT INTO HUMAN CONTROL STRATEGIES, THIS PROPOSAL DEVELOPS A TASK-DYNAMIC APPROACH THAT AFFORDS PRINCIPLED HYPOTHESIS-TESTING BY PARSING THE COMPLEX DYNAMICS INTO EXECUTION AND RESULT VARIABLES, WITH MINIMAL ASSUMPTIONS ABOUT THE HUMAN CONTROLLER. EIGHT EXPERIMENTS TEST THE OVERALL HYPOTHESIS THAT HUMANS SEEK SOLUTIONS THAT ARE PREDICTABLE, BY CORRELATING HAND-OBJECT MOTIONS, AND MAKING THE BEHAVIOR STABLE AND TOLERANT TO ERROR AND RISK TO OBVIATE ERROR CORRECTIONS AND PREVENT FAILURE. AIM-1 TESTS CONTROL OF INTERNAL DYNAMICS IN LINEAR MOVEMENTS AND EXAMINES HOW HUMANS CHOOSE INITIAL CONDITIONS TO MITIGATE PERTURBATIONS, HOW THEY PREEMPT UNDESIRED BALL OSCILLATIONS, HOW THEY EXPLOIT INTERMITTENT CONTACT TO DEVELOP A STABLE RHYTHM, AND HOW THEY MODIFY THE OBJECT PROPERTIES TO FACILITATE STABLE CONTACT BEHAVIOR. TO EXAMINE LEARNING, AIM-2 SCALES UP THE DIMENSIONALITY OF THE TASK BY INTRODUCING MORE REAL-LIFE PLANAR CUP MOVEMENTS, WHICH CREATES AN EXPONENTIAL INCREASE IN COMPLEXITY. FOUR EXPERIMENTS TEST TASK GOALS THAT INTRODUCE NEW DYNAMIC CHALLENGES, SUCH AS COMBINATION OF RHYTHMIC AND DISCRETE MOVEMENTS, COMPLEX BALL DYNAMICS WHEN CHANGING MOVEMENT DIRECTIONS, ADAPTATION AND MODIFICATION OF OBJECT PROPERTIES, ALL TO SHOW HOW HUMANS EITHER EXPLOIT OR OVERRIDE INTERNAL DYNAMICS TO ACHIEVE PREDICTABILITY. AIM-3 INTRODUCES A REAL VERSION OF THE TASK WITH A CUSTOM-DESIGNED DEVICE, THE MAGIC TABLE. FOLLOWING A COMPARISON OF THE REAL AND VIRTUAL SET-UPS, THE MAGIC TABLE IS USED TO LEVERAGE THE THEORETICAL FRAMEWORK TO CREATE NOVEL SENSITIVE METRICS TO QUANTIFY MOTOR FUNCTION FOR CLINICAL APPLICATIONS. SPECIFICALLY, WE ASSESS SEVERITY AND RECOVERY OF MOTOR IMPAIRMENT IN A COHORT OF PATIENTS AFTER STROKE. AS MANUAL DEXTERITY IS COMPROMISED IN MANY INDIVIDUALS WITH NEUROLOGICAL DISORDERS, THE EXPERIMENTAL PARADIGM AND ITS QUANTITATIVE ANALYSES PROMISE TO BECOME A USEFUL PLATFORM TO GAIN INSIGHTS INTO NEUROLOGICAL DISEASES.

MULTIPLEXED AND DYNAMICALLY TARGETED PHOTOIMMUNOTHERAPY OF HETEROGENEOUS, CHEMORESISTANT MICROMETASTASES GUIDED BY ONLINE IN VIVO OPTICAL IMAGING OF CELL-SURFACE BIOMARKERS

SEPARATION AND ANALYTICAL TECHNOLOGIES FOR PROTEOMICS

CARDIOPULMONARY OUTCOMES OF DUAL CIGARETTE AND E-CIGARETTE USE IN ANIMAL MODELS OF CHRONIC EXPOSURE - PROJECT SUMMARY NEW GENERATION POD-STYLE NICOTINE SALT E-CIGARETTES (E-CIGSPOD) ARE POPULAR BECAUSE OF THEIR SLEEK DESIGN AND ABILITY TO DELIVER NICOTINE LEVELS SIMILAR TO THOSE OF CONVENTIONAL TOBACCO CIGARETTES (CIGS). NICOTINE SALTS ARE EASIER TO INHALE THAN THE FREE-BASE FORM OF NICOTINE FOUND IN PREVIOUS GENERATION E-CIGS. WHILE THE LONG-TERM HEALTH IMPACT OF CIG SMOKE IS WELL KNOWN, THE CONSEQUENCES OF CHRONIC E-CIG USE REMAIN IN QUESTION, AND DATA IS NEEDED TO JUSTIFY IMMEDIATE FDA REGULATIONS. A SUBSTANTIAL PORTION OF SMOKERS ARE UNSUCCESSFUL IN USING E-CIGS TO SUPPORT THEIR CESSATION EFFORTS AND INSTEAD BECOME DUAL USERS. THE CHEMICAL PROFILE OF CIG SMOKE AND E-CIGPOD AEROSOLS IS DIFFERENT, WHICH SUGGESTS THAT THE HEALTH EFFECTS OF CHRONIC SMOKING AND VAPING MAY NOT FULLY OVERLAP. BUILDING UPON THIS, WE HYPOTHESIZE THAT CIG SMOKING AND E-CIGPOD VAPING, ARE INDEPENDENT RISK FACTORS FOR CARDIOPULMONARY DISEASE, WHOSE SUPERPOSITION EXACERBATES THE MALADAPTIVE REMODELING OF THE LUNGS, HEART, AND VASCULATURE COMPARED TO EITHER PRACTICE ALONE. TO TEST THIS HYPOTHESIS, WE WILL EXPOSE HYPERCHOLESTEROLEMIC AND WILDTYPE MICE TO NEBULIZED NICOTINE, AEROSOLIZED SOLVENT CARRIER, E-CIGPOD AEROSOLS, AND CIG SMOKE (NAÏVE MICE), OR A COMBINATION OF THE TWO (BOTH NAÏVE AND PREVIOUSLY CIG SMOKE-EXPOSED MICE) AND WE WILL COMPARE THE STRUCTURAL AND FUNCTIONAL REMODELING OF THE CARDIOVASCULAR AND RESPIRATORY SYSTEMS. WE WILL GENERATE E-CIGPOD AEROSOLS FROM PODS IN TOBACCO FLAVOR AT 5% NICOTINE STRENGTH. MOTIVATED BY THE IDEA THAT SMOKERS WHO USE E-CIGS AS CESSATION AIDS MAY VAPE UNTIL THEY SATISFY THEIR NICOTINE CRAVINGS, WE WILL PERFORM EXPERIMENTS TO ACHIEVE EQUAL COTININE BIOAVAILABILITY IN THE MOUSE BLOOD, WHILE MAINTAINING THE SAME DAILY DURATION OF EXPOSURE. WE WILL MEASURE THE MECHANICAL PROPERTIES OF THE OF AORTA (TISSUE STIFFNESS, DISTENSIBILITY, AND ELASTIC STORAGE), HEART (FRACTIONAL SHORTENING AND EJECTION FRACTIONS), AND LUNGS (RESISTANCE AND ELASTANCE). WE WILL CHARACTERIZE TISSUE MICROSTRUCTURE (AIR SPACE SIZES, COLLAGEN CONTENT, AND ELASTIC FIBER INTEGRITY) TO HIGHLIGHT THE FACTORS THAT MOST CONTRIBUTE TO THE OBSERVED FUNCTIONAL CHANGES. KNOWLEDGE GAINED FROM THIS PROJECT WILL PROVIDE SCIENTIFIC EVIDENCE IN SUPPORT OF DATA-DRIVEN E-CIG REGULATION UNDER THE FAMILY SMOKING PREVENTION AND TOBACCO CONTROL ACT (FSPTCA), SPECIFICALLY CONCERNING THE HEALTH RISKS OF DUAL COMBUSTIBLE AND ELECTRONIC CIGARETTE USE.

OURSLEEPKIT: A COUPLE-FOCUSED MHEALTH TOOL TO SUPPORT ADHERENCE TO CPAP TREATMENT - PROJECT SUMMARY POOR ADHERENCE TO CONTINUOUS POSITIVE AIRWAY PRESSURE (CPAP) TREATMENT REMAINS THE SINGLE LARGEST IMPEDIMENT TO EFFECTIVE MANAGEMENT FOR OBSTRUCTIVE SLEEP APNEA (OSA) LEADING TO INCREASED MORBIDITY, MORTALITY, AND HIGHER HEALTH CARE COSTS. EXISTING INTERVENTIONS PROMOTING CPAP ADHERENCE FOCUS ONLY ON THE DIAGNOSED INDIVIDUAL AND ARE DELIVERED MOSTLY BY HEALTH PROFESSIONALS, WITH LIMITED SUCCESS. AS SUPPORTED BY THE FINDINGS OF THE PI’S R15 PROJECT, THE PARTNERS OF PATIENTS PLAY A SIGNIFICANT ROLE – EITHER POSITIVE OR NEGATIVE – IN CPAP ADHERENCE, AND ARE PART OF ALL OF THE MAJOR FACILITATIVE ASPECTS AND BARRIERS TO CPAP USE. A DYADIC APPROACH ENGAGING BOTH THE PATIENT AND PARTNER TO PROMOTE CPAP ADHERENCE REMAINS AN UNTAPPED OPPORTUNITY. OUR INTERDISCIPLINARY TEAM HAS DEVELOPED A PROTOTYPE OF OURSLEEPKIT, WHICH IS AN INNOVATIVE COUPLE-FOCUSED MHEALTH TOOL TO PROMOTE CPAP ADHERENCE. GUIDED BY THE CONCEPTUAL FRAMEWORK OF PARTNER INVOLVEMENT IN CPAP ADHERENCE, THE GOAL OF OURSLEEPKIT IS TO COACH MUTUAL ENGAGEMENT AND MODEL POSITIVE PARTNER INVOLVEMENT IN CPAP TREATMENT, THUS MOTIVATING GREATER CPAP ADHERENCE. RESPONDING TO THE PA-18- 722, THE GOAL OF THIS R01 PROJECT IS TO REFINE AND TEST OURSLEEPKIT TO SUPPORT ADHERENCE TO CPAP TREATMENT. WE WILL REFINE AND DEPLOY OURSLEEPKIT ON AN ESTABLISHED SECURE MHEALTH PLATFORM, NUCOACH. GETTING USERS TO ENGAGE WITH AN MHEALTH INTERVENTION IS CRITICAL TO ITS SUCCESS, AND LOW USER ENGAGEMENT WITH EXISTING MHEALTH TOOLS REMAINS A BIG CONCERN. TO ADDRESS THIS ISSUE, WE WILL USE A PARTICIPATORY APPROACH TO REFINE OURSLEEPKIT AND COMPREHENSIVELY EVALUATE BOTH ITS EFFECT ON CPAP ADHERENCE AND USER ENGAGEMENT. SPECIFICALLY, WE WILL 1) REFINE OURSLEEPKIT USING QUALITATIVE METHODS WITHIN A STANDARDIZED ITERATIVE PARTICIPATORY APPROACH BY WORKING WITH END USERS (OSA PATIENTS AND THEIR PARTNERS); 2) EXAMINE THE EFFECTIVENESS OF OURSLEEPKIT ON CPAP ADHERENCE BY CONDUCTING A 6-MONTH RANDOMIZED PARALLEL GROUP CONTROLLED TRIAL IN 180 COUPLES (NEWLY DIAGNOSED OSA PATIENTS AND THEIR PARTNERS); AND 3) EVALUATE USER ENGAGEMENT IN THE INTERVENTION GROUP BY TRACKING OBJECTIVE OURSLEEPKIT USAGE AND UNDERSTANDING THE SUBJECTIVE USER EXPERIENCE. RESULTS OF THIS PROJECT WILL SUPPORT THE DEVELOPMENT OF AN EFFECTIVE AND ENGAGING MHEALTH TOOL WHICH CAN BE READILY ADOPTED BY OSA PATIENTS AND THEIR PARTNERS TO SUPPORT ADHERENCE TO CPAP TREATMENT. GIVEN THE FREQUENCY AND DEPTH OF INTERACTION THAT MOST PATIENTS HAVE WITH THEIR PARTNER, OURSLEEPKIT IS LIKELY TO SUCCEED WITH A SUSTAINABLE EFFECT ON CPAP ADHERENCE LEADING TO SIGNIFICANT HEALTH BENEFITS. IF SHOWN TO BE SUCCESSFUL, OURSLEEPKIT CAN BE EASILY INTEGRATED WITH OTHER INTERVENTIONS AND EXISTING TECHNOLOGY TO BETTER PROMOTE CPAP USE. THIS NEW MHEALTH INTERVENTION FACILITATES CHANGING THE CURRENT CARE OF OSA FROM A REACTIVE DISEASE-FOCUSED MODEL TO A MORE PROACTIVE SELF-MANAGEMENT MODEL. GOING BEYOND OSA, OURSLEEPKIT CAN BE AN EXEMPLAR OF USING MHEALTH TECHNOLOGY TO OPTIMIZE TREATMENT ADHERENCE AND SELF-MANAGEMENT INVOLVING FAMILY CARE PARTNERS.

IGERT NANOMEDICINE SCIENCE AND TECHNOLOGY

ROBUST ULTRA-HIGH SENSITIVITY PROTEOMIC TECHNOLOGIES FOR LIMITED SAMPLES

EVALUATING DAROBACTINS AS ANTIMICROBIAL AGENTS - THE ANTIMICROBIAL RESISTANCE CRISIS (AMR) HAS BEEN RECOGNIZED FOR YEARS, AND THE SIGNIFICANCE OF THIS GLOBAL HUMAN HEALTH PROBLEM SETS IT APART FROM OTHER TYPES OF DISEASES, BECAUSE IT AFFECTS NOT ONLY INDIVIDUALS, BUT HAS A POTENTIAL TO DISRUPT THE LIFE OF SOCIETY. WE HAVE A STARK REMINDER OF THE ABILITY OF A PATHOGEN TO BRING NORMAL LIFE TO A HALT, AS WE EXPERIENCE THE COVID-19 PANDEMIC. IN THE CASE OF A VIRUS, WE CAN USUALLY COUNT ON A REASONABLY RAPID DEVELOPMENT OF A VACCINE. FOR MULTIDRUG-RESISTANT BACTERIA, WE DO NOT HAVE A SIMILARLY RELIABLE APPROACH, AND THE PIPELINE OF NOVEL COMPOUNDS AGAINST THE MOST PROBLEMATIC PATHOGENS, MDR GRAM- NEGATIVE BACTERIA, IS VERY THIN (LEWIS, CELL 2020). WE RECENTLY DISCOVERED A NOVEL CLASS OF COMPOUNDS ACTING AGAINST IMPORTANT GRAM-NEGATIVE PATHOGENS, THE DAROBACTINS (IMAI ET AL., NATURE 2019). DAROBACTIN A IS A 7- MER MODIFIED PEPTIDE CONTAINING TWO UNUSUAL FUSED RINGS. THIS CREATES A RIGID SS-STRAIN FROM THE PEPTIDE BACKBONE. THE TARGET IS BAMA, AN ESSENTIAL CHAPERONE THAT INSERTS PROTEINS SUCH AS PORINS INTO THE OUTER MEMBRANE. BAMA RECOGNIZES A SIGNAL SEQUENCE OF INCOMING PEPTIDES THAT BIND TO ONE OF ITS SS-STRANDS. DAROBACTIN, WHICH HAS A UNIQUE PREFORMED SS-STRAND, IS A BETTER BINDER AND PREVENTS SUBSTRATES FROM INTERACTING WITH BAMA. IMPORTANTLY, BAMA MUTANTS RESISTANT TO DAROBACTIN A LOSE VIRULENCE. DAROBACTIN A HAS NO CYTOTOXICITY AND SHOWS GOOD EFFICACY IN MOUSE SEPTICEMIA AND THIGH MODELS AGAINST SUCH PATHOGENS AS POLYMYXIN-RESISTANT E. COLI AND KPC K. PNEUMONIAE. DAROBACTIN A IS RIBOSOMALLY TRANSLATED AND CODED BY A RIPP OPERON. BIOINFORMATICS SEARCH OF THE NCBI GENOMES DATABASE RESULTED IN IDENTIFYING 8 ANALOGS WITH THE SAME SCAFFOLD, AND 6 DAROBACTIN-LIKE ANALOGS. THE GOAL OF THIS PROJECT IS TO EVALUATE THE DAROBACTINS AND IDENTIFY THE BEST LEADS. ADDITIONAL ANALOGS WILL BE IDENTIFIED BY SEARCHING THROUGH THE RAW DATA OF THE METAGENOMICS DATABASE. WE WILL SYNTHESIZE THE DAR OPERONS, CLONE THEM INTO E. COLI AND OPTIMIZE PRODUCTION. FOR THIS, WE WILL USE AN APPROACH WE RECENTLY DEVELOPED, SCREENING MUTAGENIZED PRODUCERS IN AGAROSE MICRODROPLETS CONTAINING A YFP-LABELED TEST PATHOGEN. FACS ANALYSIS ALLOWS TO SORT DROPLETS IN WHICH THE TEST STRAIN IS INHIBITED. SPECTRUM OF ACTION WILL BE DETERMINED, RESISTANT MUTANTS WILL EITHER CONFIRM BAMA AS A TARGET, OR POINT TO A NEW ONE. WE WILL ANALYZE VIRULENCE OF RESISTANT MUTANTS IN DETAIL. COMPOUNDS WILL BE TESTED FOR CYTOTOXICITY AND ANIMAL SAFETY AND EFFICACY WITH TARGET PATHOGENS. THIS PROJECT WILL RESULT IN LEADS READY TO ENTER INTO DEVELOPMENT TO TREAT PATHOGENS OF CRITICAL PRIORITY.

NRT-FW-HTF-HDR: PLATFORMS FOR EXCHANGE AND ALLOCATION OF RESOURCES (PEAR) -THE INCREASING DIGITIZATION OF THE ECONOMY AND RESULTING GROWTH OF DIGITAL PLATFORMS LIKE RIDE-HAILING APPS AND ENERGY TRADING PLATFORMS HAVE DRAMATICALLY ALTERED HOW INDIVIDUALS, ORGANIZATIONS AND GOVERNMENTS EXCHANGE AND ALLOCATE RESOURCES. BY 2025 IT IS ESTIMATED OVER $60 TRILLION PER YEAR (~30 PERCENT OF WORLD REVENUE) WILL BE MEDIATED BY DIGITAL PLATFORMS. THESE PLATFORMS HAVE DISRUPTED MULTIPLE INDUSTRIES, UPENDED LABOR ECONOMICS AND PRACTICES, AND FUNDAMENTALLY TRANSFORMED RESOURCE MANAGEMENT, ASSET ALLOCATION AND MARKET DESIGN. WHILE DIGITAL PLATFORMS HAVE DEMOCRATIZED PROVISION AND ACCESS TO SERVICES AND PRODUCTS WITH LOW ENTRY AND TRANSACTION COSTS, THE LARGER IMPACT ON SOCIETY IS NOT FULLY UNDERSTOOD. IT IS CRITICAL THAT THE DEVELOPERS OF NEW PLATFORM TECHNOLOGIES NO LONGER SIMPLY BE TRAINED AS ENGINEERS AND COMPUTER SCIENTISTS, AND THAT POLICY MAKERS AND REGULATORS MUST UNDERSTAND THE ECOSYSTEMS AROUND DIGITAL PLATFORMS. THIS NATIONAL SCIENCE FOUNDATION RESEARCH TRAINEESHIP (NRT) AWARD TO NORTHEASTERN UNIVERSITY, UNIVERSITY OF HOUSTON, AND HAMPTON UNIVERSITY (TWO OF THREE OF WHICH ARE MINORITY-SERVING INSTITUTIONS), ENTITLED PLATFORMS FOR EXCHANGE AND ALLOCATION OF RESOURCES (PEAR), WILL DEVELOP CONVERGENT, TRANSDISCIPLINARY TRAINING PROVIDING STUDENTS WITH (1) THE CAPACITY TO INTEGRATE APPLICABLE FINDINGS AND THEORIES IN BUSINESS, POLICY AND SOCIAL SCIENCE INTO ETHICAL ENGINEERING DESIGN AND PRACTICE AND VICE VERSA, (2) THE ABILITY TO SUCCEED IN EMERGING AND DYNAMIC WORK ENVIRONMENTS THAT ARE YET TO BE REGULATED, AND (3) THE UNDERSTANDING OF HOW TECHNOLOGICAL INNOVATIONS CREATE VALUE FOR DIFFERENT STAKEHOLDERS AND IMPACT SOCIETY AT LARGE. THIS PROJECT ANTICIPATES TRAINING 80+ MS AND PHD STUDENTS, INCLUDING 22 STIPENDED FELLOWS, FROM A RANGE OF DOCTORAL PROGRAMS AT NORTHEASTERN UNIVERSITY (NU) OR UNIVERSITY OF HOUSTON (UH), A NEW MASTER?S IN ENGINEERING ENTREPRENEURSHIP AT HAMPTON UNIVERSITY (HU) ? THE UNIVERSITY?S FIRST ENGINEERING GRADUATE DEGREE ? OR ONE OF THE TWO NEW GRADUATE CERTIFICATE PROGRAMS AT NU OR UH. THE PEAR TRAINING MODEL IS GUIDED BY EVIDENCE-BASED BEST PRACTICES IN TEACHING, MENTORING AND LEARNING, WITH AN EMPHASIS ON BEST PRACTICES FOR INTERDISCIPLINARY LEARNING AND ENGAGEMENT OF UNDERREPRESENTED POPULATIONS. THROUGH CAREFULLY CURATED COURSEWORK AND EXPERIENCES, STRUCTURED MENTORING AND PROFESSIONAL DEVELOPMENT, AND STAKEHOLDER CO-DESIGNED RESEARCH OPPORTUNITIES, PEAR FELLOWS WILL BE TRAINED TO UNDERSTAND AND CONTRIBUTE TO THE FUTURE OF DIGITAL PLATFORMS AND THEIR IMPACT ON EQUITABLE DISTRIBUTION OF ECONOMIC OPPORTUNITIES IN SOCIETY, SUSTAINABLE CONSUMPTION, FAIR ACCESS TO GOODS AND SERVICES, ETHICALLY INFORMED TECHNOLOGY DESIGN, AND THE RE-SHAPING OF LABOR AND BUSINESS PRACTICES. THESE PROFESSIONALS WILL BE READY TO DEFINE AND CONTRIBUTE TO THE FUTURE OF WORK AT THE HUMAN TECHNOLOGY FRONTIER AND TO HARNESS THE DATA REVOLUTION (TWO NSF BIG IDEAS) IN MULTIPLE SECTORS SUCH AS ENERGY, HEALTH, TRANSPORTATION, LOGISTICS, HOUSING, COMPUTING, POLICY, AND BEYOND. PEAR IS A COLLABORATION THAT COMBINES EACH INSTITUTION?S STRENGTHS: NU?S LEADERSHIP IN EXPERIENTIAL LEARNING, HAMPTON?S IN ENGINEERING ENTREPRENEURSHIP AND TEACHING, AND UH?S ENGINEERING PARTNERSHIPS PARTICULARLY IN THE ENERGY SECTOR ? TO DEVELOP THREE NEW GRADUATE PROGRAMS. FORMAL EXTERNAL EVALUATION WILL DOCUMENT OUTCOMES TO CONTRIBUTE TO THE BODY OF KNOWLEDGE ON EFFECTIVE MODELS FOR GRADUATE EDUCATION IN CONVERGENT RESEARCH AREAS SUCH AS DIGITAL PLATFORMS. THE NSF RESEARCH TRAINEESHIP (NRT) PROGRAM IS DESIGNED TO ENCOURAGE THE DEVELOPMENT AND IMPLEMENTATION OF BOLD, NEW POTENTIALLY TRANSFORMATIVE MODELS FOR STEM GRADUATE EDUCATION TRAINING. THE PROGRAM IS DEDICATED TO EFFECTIVE TRAINING OF STEM GRADUATE STUDENTS IN HIGH PRIORITY INTERDISCIPLINARY OR CONVERGENT RESEARCH AREAS THROUGH COMPREHENSIVE TRAINEESHIP MODELS THAT ARE INNOVATIVE, EVIDENCE-BASED, AND ALIGNED WITH CHANGING WORKFORCE AND RESEARCH NEEDS. 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.

IGERT: INTELLIGENT DIAGNOSTICS FOR AGING CIVIL INFRASTRUCTURE (ID-ACI)

TRAINING INTERPRETERS FOR INDIVIDUALS WHO ARE DEAF AND INDIVIDUALS WHO ARE DEAF-BLIND - INTERPRETER TRAINING: DISTANCE EDUCATION

SINGLE-CELL DIRECT RNA SEQUENCING USING ELECTRICAL ZERO-MODE WAVEGUIDES AND ENGINEERED REVERSE TRANSCRIPTASES

FUNDAMENTAL SUBCORTICAL MECHANISMS OF AFFECTIVE PROCESSING

SINGLE MOLECULE HIV-1 NC/GAD-DNA INTERACTIONS

TRANSDISCIPLINARY TRAINING AT THE INTERSECTION OF ENVIRONMENTAL HEALTH AND SOCIAL SCIENCE

DESIGN AND CHARACTERIZATION ON CIGARETTES

GPU-ACCELERATED MONTE CARLO PHOTON TRANSPORT SIMULATION PLATFORM

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 GENERAL MECHANISM OF PERSISTER FORMATION

INDIVIDUAL DIFFERENCES IN EMOTIONAL EXPERIENCE AND COGNITIVE PERFORMANCE

MULTISCALE MECHANISMS OF LINGUAL MECHANICAL FUNCTION

NOVEL MEDICATIONS FOR CANNABIS DEPENDENCE

A RANDOMIZED CLINICAL TRIAL OF CULTURALLY TAILORED MI

SYSTEMS GENETICS OF PREMORBID AND COCAINE USE TRAITS IN A RAT REDUCED COMPLEXITY CROSS - PROJECT SUMMARY STIMULANT USE DISORDERS (E.G., COCAINE, METHAMPHETAMINE) ARE A MAJOR PUBLIC HEALTH CONCERN. DESPITE A HERITABILITY OF ~40-50%, GENOME-WIDE ASSOCIATION STUDIES (GWAS) HAVE IDENTIFIED VERY FEW LOCI, INCLUDING ONE HIT FOR COCAINE (COC) DEPENDENCE THAT MAPS TO FAM53B, A GENE ALSO IDENTIFIED VIA EXPRESSION QUANTITATIVE TRAIT LOCUS (QTL) ANALYSIS TO BE ASSOCIATED WITH COC SELF-ADMINISTRATION IN MICE. THE PRIMARY OBJECTIVE IS TO RAPIDLY IDENTIFY NOVEL GENETIC FACTORS IN RATS THAT CONTRIBUTE TO PREMORBID RISK (COMPULSIVITY, IMPULSIVITY) AND COCAINE USE TRAITS IN A SPONTANEOUSLY HYPERTENSIVE RAT (SHR) REDUCED COMPLEXITY CROSS (RCC). A RODENT SYSTEMS GENETICS APPROACH TRIANGULATES ON DISCOVERY-BASED GENETIC AND MULTI-LEVEL FUNCTIONAL GENOMIC ANALYSIS AND CAN PROVIDE A MORE RAPID GENETIC AND NEUROBIOLOGICAL INSIGHT INTO DRUG ACTION AND NEUROPLASTICITY UNDERLYING ADDICTION. FOR SEVERAL YEARS, THE CONTACT PI HAS BEEN EMPLOYING MOUSE REDUCED COMPLEXITY CROSSES (RCCS) BETWEEN NEAR-ISOGENIC INBRED SUBSTRAINS TO FACILITATE GENE MAPPING, VALIDATION, AND MECHANISMS. BECAUSE RODENT SUBSTRAINS ARE > 99% GENETICALLY IDENTICAL AND CONTAIN SEVERAL ORDERS OF MAGNITUDE FEWER VARIANTS COMPARED TO CLASSICAL INBRED STRAINS, MAPPING QUANTITATIVE TRAIT LOCI (QTLS) IN RCCS YIELDS ORDERS OF MAGNITUDE FEWER CAUSAL CANDIDATE GENES TO CONSIDER. WHEN COMBINED WITH FUNCTIONAL GENOMICS, RCCS CAN RAPIDLY LEAD TO CAUSAL GENE AND VARIANT IDENTIFICATION. OUR PRELIMINARY STUDIES ESTABLISH ROBUST, HERITABLE DIFFERENCES IN PREMORBID IMPULSIVITY AND COMPULSIVITY, SUCROSE REWARD SENSITIVITY, AND MULTIPLE COC USE TRAITS BETWEEN SHR/NCRL AND SHR/NHSD SUBSTRAINS, INCLUDING COC-INDUCED LOCOMOTOR ACTIVITY, COC IVSA TAKING, SEEKING, AND INTAKE CYCLES, DEMONSTRATING FEASIBILITY FOR GENE MAPPING IN AN RCC. IN AIMS 1 AND 2, WE WILL PIONEER THE USE OF A RAT RCC WHERE WE WILL CONDUCT WHOLE GENOME SEQUENCING (WGS) AND MAP BEHAVIORAL QTLS AND EXPRESSION QTLS (EQTLS) FROM NUCLEUS ACCUMBENS (NAC) AND PREFRONTAL CORTEX (PFC) AT THE WHOLE TRANSCRIPT AND EXON LEVELS IN AN F2 CROSS COMPRISING COC-TRAINED VERSUS YOKED SALINE (SAL)-TRAINED RATS. IN AIM 3, WE WILL CONDUCT PROTEOMIC ANALYSIS OF PFC AND NAC FROM COC VS. YOKED SAL-TRAINED RATS TO TRIANGULATE ON HIGH CONFIDENCE CANDIDATE QUANTITATIVE TRAIT GENES (QTGS) AND VARIANTS (QTVS) AS WE BUILD FUNCTIONAL CONNECTIONS BETWEEN DNA VARIANTS, TRANSCRIPTIONAL REGULATION, PROTEIN TRANSLATION, AND CELL SIGNALING ADAPTATIONS UNDERLYING PREMORBID AND COCAINE USE TRAITS. THESE STUDIES PIONEER THE USE OF A RAT RCC COMBINED WITH DEEP BEHAVIORAL PHENOTYPING TO RAPIDLY IDENTIFY HIGH-CONFIDENCE CANDIDATE NOVEL GENETIC FACTORS AND MOLECULAR MECHANISMS INFLUENCING PREMORBID RISK FACTORS AND COCAINE USE TRAITS. FUTURE GENE EDITING OF CANDIDATE CAUSAL GENE VARIANTS WILL BE MODELED ON THE TWO NEAR-ISOGENIC SHR BACKGROUNDS TO DEMONSTRATE NECESSITY (MUTATION CORRECTION; “RESCUE”) AND SUFFICIENCY (MUTATION INDUCTION). DELIVERABLES INCLUDE WGS’S OF SHR SUBSTRAINS FOR FUTURE RCCS FOR COMPLEX TRAIT ANALYSIS AS WELL AS ADAPTIVE RAT TRANSCRIPTOMIC AND PROTEOMIC DATASETS IN KEY BRAIN REGIONS OF THE MESOCORTICOLIMBIC CIRCUITRY THAT CAN BE FURTHER MINED BY INVESTIGATORS AND HOPEFULLY INFORM THERAPEUTICS.

IN VIVO ANALYSIS OF MECHANOTRANSDUCTION

STRONG SEEDLING CA

CONTINUOUS, NON-INVASIVE OPTICAL MONITORING OF CIRCULATING TUMOR CELL-MEDIATED METASTASIS IN AWAKE MICE - PROJECT SUMMARY HEMATOGENOUS METASTASIS IS RESPONSIBLE FOR A LARGE MAJORITY OF CANCER-RELATED DEATHS, WHERE CIRCULATING TUMOR CELLS (CTCS) SHED FROM THE PRIMARY TUMOR INTO THE PERIPHERAL BLOOD (PB). A SMALL NUMBER OF CTCS MAY FORM SECONDARY SITES, WHICH ARE EXTREMELY DIFFICULT TO CONTROL CLINICALLY. MOST METHODS FOR STUDYING CTCS RELY ON DRAWING AND ANALYZING FRACTIONALLY SMALL PB BLOOD SAMPLES (“LIQUID BIOPSY”). ALTHOUGH CTCS AND MULTICELLULAR CTC CLUSTERS (CTCCS) HAVE BEEN STUDIED FOR DECADES, LITTLE IS KNOWN ABOUT THEIR “DYNAMICS” IN VIVO (TRANSIENT CHANGES IN THEIR NUMBERS IN PB), AND HOW THESE MAY AFFECT METASTASIS DEVELOPMENT AND RESPONSE TO ANTI-CANCER TREATMENT. FOR EXAMPLE, IT IS KNOW THAT RADIATION THERAPY MAY ENCOURAGE METASTATIC DISSEMINATION OF CANCER, YET THE MECHANISMS FOR THIS ARE STILL POORLY UNDERSTOOD. OUR TEAM RECENTLY DEVELOPED A NEW METHOD FOR IN VIVO ENUMERATION OF CTCS IN SMALL ANIMALS CALLED “DIFFUSE IN VIVO FLOW CYTOMETRY” (DIFC). DIFC USES DIFFUSE LIGHT TO DETECT FLUORESCENT-PROTEIN EXPRESSING CTCS IN LARGE, DEEPLY-SEATED BLOOD VESSELS. DIFC CAN SAMPLE APPROXIMATELY 100 MICROLITERS OF BLOOD PER MINUTE, PERMITTING DETECTION OF FEWER THAN 1 CTC PER ML OF PB, AND SAMPLING OF THE ENTIRE PERIPHERAL BLOOD VOLUME IN MINUTES. WE PREVIOUSLY USED DIFC TO STUDY RARE CTC AND CTCC DISSEMINATION IN MOUSE XENOGRAFT MODELS. DIFC REVEALED THAT CTC NUMBERS ARE HIGHLY DYNAMIC AND MAY CHANGE BY AN ORDER-OF-MAGNITUDE OR MORE OVER 24 HOUR PERIODS. THESE CHANGES ARE LARGELY MISSED BY CTC ENUMERATION METHODS THAT INVOLVE INFREQUENT BLOOD DRAWS. THE GOAL OF THIS PROJECT IS TO BUILD A “WEARABLE” TETHERED W-DIFC INSTRUMENT THAT WILL ALLOW CONTINUOUS, NON- INVASIVE MONITORING OF CTC NUMBERS OVER EXTENDED PERIODS IN MICE. THE W-DIFC OPTICAL PROBE AND SIGNAL PROCESSING DESIGN WILL PERMIT DATA COLLECTION IN FREELY-MOVING MICE IN AMBIENT LIGHTING CONDITIONS. WE WILL FIRST USE W-DIFC TO STUDY CTC DYNAMICS DURING DISEASE DEVELOPMENT IN AN ORTHOTOPIC XENOGRAFT AND TRANSGENIC MOUSE MODEL OF METASTASIS. WE WILL USE ALSO W-DIFC TO MEASURE CONTINUOUS CTC DYNAMICS AFTER RADIATION THERAPY IN A MEDULLOBLASTOMA (MB) MOUSE MODEL. MB IS A COMMON FORM OF CHILDHOOD BRAIN CANCER THAT AGGRESSIVELY METASTASIZES TO THE LEPTOMENINGEAL SURFACES OF THE BRAIN AND SPINE VIA THE PB. THERE IS SIGNIFICANT EVIDENCE THAT RADIATION MAY EXACERBATE METASTASIS BY TRIGGERING MOBILIZATION OF CTCS INTO THE BLOOD. WE EXPECT THAT THE ABILITY OF W-DIFC TO MEASURE CTCS OVER SHORT-, MEDIUM-, AND LONG-TERM TIMESCALES WILL PROVIDE UNIQUE INSIGHTS INTO THIS PROCESS. WE WILL ALSO USE W-DIFC TO STUDY THE USE OF ANTI-INFLAMMATORY DRUGS TO BLOCK THE PRO-METASTATIC EFFECT. HENCE, THE STUDIES PROPOSED HERE COULD ULTIMATELY LEAD TO BETTER UNDERSTANDING OF METASTASIS AND IMPROVED TREATMENT PROTOCOLS FOR CHILDHOOD MB. WE ANTICIPATE THAT THE UNIQUE TECHNOLOGIES THAT WILL BE DEVELOPED HERE WILL HAVE BROAD APPLICATION TO OTHER CANCERS AND ANTI-CANCER THERAPIES IN THE FUTURE.

THE PURPOSE OF THIS COOPERATIVE AGREEMENT IS TO FUND RESEARCH IN SUPPORT TO MTO IN THE AMOUNT OF 276,310 ON CONTRACT NUMBER HR0011-17-2-0002.

RELATING NEUROIMMUNE AND NEUROVASCULAR ALTERATIONS DURING ALZHEIMER'S DISEASE PROGRESSION

DATING VIOLENCE PREVENTION FOR JUVENILE JUSTICE GIRLS

SCC-LSR: FROM TECHNOLOGY TO HUMANS: PROTECTING USERS OF NEURAL AND MEDICAL IMPLANT TECHNOLOGIES THROUGH RESILIENCE AND SAFETY ENGINEERING -THIS RESEARCH WILL ADVANCE COMMUNITY PRIORITIES IN THE AREAS OF SAFETY, SECURITY, AND HUMAN HEALTH AND WELLNESS PERTAINING TO EXISTING AND FUTURE NEURAL IMPLANT DEVICES. THE TEAM INCLUDES COMPUTER SCIENTISTS, ELECTRICAL ENGINEERS, MDS, NEUROSCIENTISTS, NEURAL IMPLANT COMMUNITY GROUPS, AND MANUFACTURERS. THE PARTNER COMMUNITY GROUPS INCLUDE PATIENTS AND THEIR SUPPORTING FAMILIES AND CAREGIVERS FROM WHOM THE TEAM WILL UNDERSTAND THE PERSONAL IMPACT OF NEURAL IMPLANT TECHNOLOGIES. EXPANDING ENGAGEMENT WITH PARTNERED COMPANIES WHO MANUFACTURE AND MEDICAL DOCTORS WHO USE NEURAL IMPLANTS, THE TEAM WILL ADDRESS THESE COMMUNITY CHALLENGES AND COLLABORATIVELY DELIVER A NEURAL IMPLANT HARDWARE/SOFTWARE CO-DESIGN SOLUTION THAT EMPOWERS THE USE AND FACILITATES THE SAFE ADOPTION OF EMERGING NEURAL IMPLANT TECHNOLOGIES. THE RESEARCH TECHNIQUES DEVELOPED FOR CHIP SECURITY WILL HAVE APPLICABILITY TO OTHER SECURITY RELATED CHIP-BASED DEVICES. THIS PROJECT WILL ADVANCE THE SCIENTIFIC AND TECHNICAL SECURITY AND CHIP HARDWARE DESIGN BY MODELING THE OPERATIONS FROM A SECURE AND DEPENDABLE CONTROL PERSPECTIVE AND DEVELOPING INNOVATIVE DEFENSE MECHANISMS THAT CAN BE APPLIED TO EMERGING SMART HEALTHCARE DEVICES. FINALLY, BY ADDING LOW-RESOURCE CHIP DESIGN, THE TEAM WILL ADVANCE MANUFACTURING TECHNIQUES FOR CHIP-BASED DEVICES ADDING ADDITIONAL SECURITY FEATURES WITHOUT IMPACT TO OVERALL PERFORMANCE OR LIFETIME. RESEARCHERS HAVE DEMONSTRATED THE IMPACT OF ?BRAIN-JACKING? IN MOUSE MODELS BUT HAVE NOT PROVIDED SOLUTIONS. THIS TEAM?S MULTIPRONGED PROJECT RESOLVES THESE CHALLENGES BY LEVERAGING EXPERTISE IN COMPUTER SECURITY, SENSING, MICROELECTRONIC DESIGN, AND STRONG AFFILIATIONS WITH CLINICAL SETTINGS. THE APPROACHES INCLUDE THE DESIGN OF (1) VERIFIABLY RESILIENT CONTROL SYSTEM AND SIMULATIONS AND DESIGN UPGRADES THAT BUILD UPON MODELS OF NEURAL SENSING AND STIMULATION AND EXPLAINABLE AI TECHNIQUES, (2) AUTOMATED CYBERSECURITY AND RESILIENCE TESTBEDS THAT HOST PHYSICAL NEURAL IMPLANT DEVICES FOR FAULT-INJECTION, SIDE-CHANNEL INFORMATION LEAKAGE, AND REMOTE CONNECTION SECURITY ANALYSIS, AND (3) LOW-RESOURCE (I.E., COMPUTATIONAL TIME, POWER, FOOTPRINT) INTRUSION DETECTION WITH ON-CHIP SENSING TO CONTINUOUSLY MONITOR ANOMALIES AND DETER ADVERSARIAL MANIPULATIONS. THE TEAM WILL IMPROVE THE RESILIENCE AND SECURITY OF NEURAL IMPLANTS BY PROTECTING SYSTEM HARDWARE AND AI-IN-THE-LOOP CONTROL SOFTWARE FROM MALICIOUS INFORMATION INJECTION, DISRUPTION IN OPERATION, AND PRIVACY LEAKAGE. A TEST BED WILL BE DEVELOPED TO VALIDATE AND TEST PHYSICAL DEVICES, SEE THE RESULTS FROM MODELING AND MICROELECTRONIC DESIGN CHANGES, WITH REAL WORLD DATA COLLECTED IN LAB AND TRANSLATED BACK TO THE MODEL FOR UPDATING AND CONTROL OF REALISTIC INTERACTIONS. TESTING THE INSERTION OF MALICIOUS INTENT OR UNINTENDED INTERFERENCE WILL ALLOW THE TEAM TO DISCERN IMPACT AND IDENTIFY POTENTIAL DESIGN CHANGES ON THE DEVICE HARDWARE TO PREVENT FUTURE INCIDENTS. 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.

CONGESTED AND CONTESTED RF EMULATIONS WITH COLOSSEUM

A SYNERGY-BASED THERAPY AGAINST C. DIFFICILE

INFLUENCE OF LEGAL CONTEXT ON TOBACCO INDUSTRY BEHAVIOR

CRISP TYPE 2: INTERDEPENDENT NETWORK-BASED QUANTIFICATION OF INFRASTRUCTURE RESILIENCE (INQUIRE)

MOLECULAR BASIS OF CANNABINOID ACTIVITY

NEW COOPERATIVE AGREEMENT: PERCEPTIVE AND REACTIVE AUTONOMOUS NAVIGATION IN CHALLENGING ENVIRONMENTS (PRANCE)

A VERSATILE HIGH-PERFORMANCE OPTICAL MAMMOGRAPHY CO-IMAGER

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

INTRA-CARTILAGE DEPOT DELIVERY OF ELECTRICALLY-CHARGED IL-1RA FOR TARGETING OSTEOARTHRITIS-ASSOCIATED INFLAMMATION AND CATABOLISM IN MULTIPLE JOINT TISSUES

ORIGINS AND FUNCTIONS OF MAMMALIAN FEMALE GERMLINE STEM CELLS

SCC-IRG TRACK 1: COMMON SENSES (STANDARDS FOR ENACTING SENSOR NETWORKS FOR AN EQUITABLE SOCIETY) : COMMUNITY-LED, SCIENCE-DRIVEN CLIMATE RESILIENCE IN BOSTON, MA -COMMUNITIES ACROSS THE WORLD ARE EXPERIENCING A CHALLENGING PARADOX: ACCELERATING DEVELOPMENT IN THE CONTEXT OF CLIMATE CHANGE. OFTEN, THE IMPACTS ARE CONCENTRATED IN DISADVANTAGED COMMUNITIES, REQUIRING NEW APPROACHES TO PURSUING LOCAL AND EQUITABLE SOLUTIONS TO CLIMATE RESILIENCE. COMMON SENSES WILL DEMONSTRATE SUCH AN APPROACH BY INTEGRATING CUTTING-EDGE SCIENCE WITH COMMUNITY PRIORITIES IN CONJUNCTION WITH A CAPITAL REDEVELOPMENT OF BLUE HILL AVE. IN BOSTON, MA, A LONG-NEGLECTED THOROUGHFARE RUNNING THROUGH THE HEART OF THE CITY?S HISTORICALLY BLACK COMMUNITIES. NETWORKS OF SENSORS INSTALLED THROUGHOUT BLUE HILL AVE.?S NEIGHBORHOODS WILL MEASURE THE THREAT OF ENVIRONMENTAL HAZARDS, INCLUDING EXTREME HEAT AND RAINWATER FLOODING, FROM STREET TO STREET. THESE DATA WILL BE EXPLORED COLLABORATIVELY WITH COMMUNITY STAKEHOLDERS IN WORKSHOPS THAT WILL CULMINATE IN PROPOSALS FOR THE PLACEMENT OF GREEN INFRASTRUCTURE (E.G., RAIN GARDENS, GREEN ROOFS) OPTIMIZED TO MITIGATE HAZARDS IN THE NEIGHBORHOOD FOLLOWING THE REDEVELOPMENT. THE PROJECT IS A COMMUNITY-CITY-UNIVERSITY PARTNERSHIP BETWEEN THE DUDLEY STREET NEIGHBORHOOD INITIATIVE (DSNI) AND PROJECT RIGHT, WHICH SERVE COMMUNITIES ALONG THE BLUE HILL AVE. CORRIDOR; THE CITY OF BOSTON?S MAYOR?S OFFICE OF NEW URBAN MECHANICS (MONUM); AND AN INTERDISCIPLINARY TEAM AFFILIATED WITH NORTHEASTERN UNIVERSITY?S BOSTON AREA RESEARCH INITIATIVE (BARI). COMMON SENSES WILL MAKE FOUR MAJOR ADVANCES. (1) IT WILL GENERATE NEW TECHNIQUES FOR MODELING SENSOR DATA TO QUANTIFY DISPARITIES IN HAZARDS FROM BLOCK TO BLOCK WITHIN COMMUNITIES, OR MICROSPATIAL INEQUITIES. (2) IT WILL DEVELOP NEW PRACTICES AND TOOLS FOR PARTICIPATORY MODELING, OR THE PROCESS OF GENERATING SOLUTIONS BY PLACING COMPLEX DATA IN THE HANDS OF COMMUNITY STAKEHOLDERS. (3) IT WILL EVALUATE THE IMPACTS THAT GREEN INFRASTRUCTURE CAN HAVE ON MITIGATING MICROSPATIAL INEQUITIES IN COMMUNITIES. (4) IT WILL DEMONSTRATE HOW SENSOR NETWORKS CAN BE BEST INTEGRATED WITH COMMUNITY NEEDS AND PERSPECTIVES TO HAVE TRUE PUBLIC IMPACT, SOMETHING THAT THIS EMERGENT TECHNOLOGY OFTEN LACKS. THE PROJECT WILL HAVE EXTENSIVE BENEFITS FOR THE BLUE HILL AVE. CORRIDOR AND WILL DEMONSTRATE A MODEL FOR SIMILAR PROJECTS LOCALLY AND GLOBALLY. THE TEAM WILL WORK WITH THE CITY OF BOSTON TO REPLICATE THE APPROACH IN OTHER PROJECTS THROUGHOUT THE GREATER BOSTON REGION. THIS PROJECT WILL ALSO PUBLISH THE COMMON SENSES PLAYBOOK, A NON-ACADEMIC PUBLICATION SUMMARIZING THE INSIGHTS, TOOLS, AND PRACTICES DEVELOPED THROUGHOUT THE PROJECT TO ENABLE OTHER COMMUNITIES TO INCORPORATE IN THEIR OWN PURSUIT OF LOCAL SOLUTIONS TO CLIMATE RESILIENCE. 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.

FW-HTF-RL: CO-WORKER ROBOTS TO IMPACT SEAFOOD PROCESSING (CRISP): DESIGNS, TOOLS AND METHODS FOR ENHANCED WORKER EXPERIENCE

CRISP TYPE 2: IDENTIFICATION AND CONTROL OF UNCERTAIN, HIGHLY INTERDEPENDENT PROCESSES INVOLVING HUMANS WITH APPLICATIONS TO RESILIENT EMERGENCY HEAL

PERSONALIZED THERAPEUTICS FOR INHIBITING BREAST CANCER METASTASIS

MECHANISMS DRIVING THE DEVELOPMENT OF THREAT SENSITIVITY FOLLOWING EARLY LIFE ADVERSITY - EXPOSURE TO EARLY LIFE ADVERSITY (ELA) CONFERS SIGNIFICANT RISK FOR PSYCHIATRIC DISORDERS THAT ARE OFTEN UNRESPONSIVE TO TRADITIONAL TREATMENTS. IMPORTANTLY, MOST ELA-ATTRIBUTABLE PSYCHOPATHOLOGIES INVOLVE HEIGHTENED RESPONSIVITY TO POTENTIAL THREATS, YET OUR MECHANISTIC UNDERSTANDING OF THIS SUSCEPTIBILITY REMAINS INCIPIENT DUE TO INSUFFICIENT KNOWLEDGE ABOUT HOW EXPERIENCE, SEX, AND AGE INTERACT TO AFFECT THE DEVELOPMENT OF THREAT-RESPONSIVE CIRCUITS. THUS, THIS PROJECT AIMS TO IDENTIFY CAUSAL MECHANISMS INITIATED BY ELA THAT DRIVE HEIGHTENED CORTICOLIMBIC CONNECTIVITY AND ENHANCED THREAT RESPONSIVITY. OUR LONG-TERM GOAL IS TO ENABLE TRANSLATION OF THESE FINDINGS INTO INDIVIDUALIZED INTERVENTION STRATEGIES. OUR GROUPS HAVE SHOWN THAT ELA LEADS TO DEVELOPMENT OF HEIGHTENED ANATOMICAL (INNERVATION) AND FUNCTIONAL (BOLD; LOCAL FIELD POTENTIAL) CONNECTIVITY BETWEEN THE BASOLATERAL AMYGDALA (BLA) AND THE PREFRONTAL CORTEX (PFC) IN EARLY ADOLESCENCE, AS WELL AS HIGHER ANXIETY-LIKE BEHAVIORS. SEVERAL OF THESE EFFECTS EMERGED EARLIER IN FEMALES THAN IN MALES, AND OUR PRELIMINARY FINDINGS SUGGEST THAT PUBERTAL SEX HORMONES MAY IMPACT THE SEX-SPECIFIC DEVELOPMENT OF BLA-PFC CONNECTIVITY FOLLOWING ELA. WE WILL THEREFORE TEST THE CENTRAL HYPOTHESIS THAT ELA DISRUPTION OF PERI-PUBERTAL BLA ACTIVITY AND HORMONAL SIGNALING ACCELERATE DEVELOPMENT OF BLA-PFC CONNECTIVITY IN A SEX-SPECIFIC MANNER, ALTERING PFC-REGULATED THREAT RESPONSIVITY ACROSS THE LIFESPAN. OUR STUDIES WILL FIRST USE ELECTROPHYSIOLOGICAL AND CHEMOGENETIC APPROACHES TO REVEAL SEX-SPECIFIC CRITICAL PERIODS OF BLA ACTIVITY THAT DRIVE HYPER-CONNECTIVITY WITH THE PFC (AIM 1), ENHANCED RESPONSIVITY TO POTENTIAL THREAT (AIM 1), AND GLUTAMATE RECEPTIVITY IN THE PFC (AIM 2). AIM 3 WILL INVESTIGATE A PERI-PUBERTAL NEUROENDOCRINE MECHANISM USING RNA SILENCING TO DETERMINE WHETHER ESTROGEN RECEPTOR SIGNALING IN THE BLA DRIVES HYPER-CONNECTIVITY TO THE PFC, GLUTAMATE TRANSMISSION IN THE PFC, AND HEIGHTENED THREAT RESPONSIVITY. TOGETHER, THESE STUDIES WILL FILL CRITICAL GAPS IN KNOWLEDGE ABOUT THE DEVELOPMENTAL AND SEX-SPECIFIC NATURE OF ELA EFFECTS ON BLA-PFC CIRCUITRY AND ARE EXPECTED TO HAVE SIGNIFICANT IMPACT ON THE DEVELOPMENT OF SPECIFIC TARGETS FOR PREVENTION IN ELA-EXPOSED POPULATIONS.

NEW CONDITIONAL AWARD TO NORTHEASTERN UNIVERSITY FOR A PROJECT ENTITLED, “WIRELESS HYDROGEN INTEGRATED SENSING VIA PIEZOELECTRIC RESONATORS AND SWITCHES (WHISPERS)'' FOA NUMBER DE-FOA-0002784 ET: H2SENSE AND CONTROL NUMBER 2784-1893

THE PURPOSE OF THIS AGREEMENT IS TO FUND RESEARCH SUPPORTING THE DEFENSE ADVANCED RESEARCH PROJECTS AGENCY (DARPA) PERCEPTUALLY-ENABLED TASK GUIDANCE (PTG). THIS EFFORT SHALL BE CARRIED OUT GENERALLY AS SET FORTH IN EXHIBIT B, RESEARCH DESCRIPTION DOCUMENT, DATED NOVEMBER 9, 2021, AND IN THE RECIPIENTS PROPOSAL TITLED, AI2ART: ADAPTIVE AND INTERACTIVE AI-AR TASK ASSISTANCE, PROVIDED TO DARPA ON MAY 14, 2021,

ELECTRONIC STRUCTURE, SPECTROSCOPY, AND CORRELATION EFFECTS IN NOVEL MATERIALS

IDENTIFYING AND ADDRESSING SOCIAL DETERMINANTS OF HEALTH TO REDUCE THE NATIONAL BURDEN OF AND INEQUITIES IN DEMENTIA - PROJECT SUMMARY/ABSTRACT ALZHEIMER’S DISEASE AND RELATED DEMENTIAS (ADRD) ARE AN ESCALATING NATIONAL CRISIS THAT SHAPES OVERALL LEVELS OF POPULATION HEALTH INCLUDING AVERAGE LIFE EXPECTANCY. CRITICALLY, IN ORDER TO EFFECTIVELY ADDRESS THIS CRISIS, IT IS IMPERATIVE THAT WE IDENTIFY ITS ROOT CAUSES, WHICH MAY INCLUDE SOCIAL DETERMINANTS OF HEALTH (SDOH) SUCH AS EDUCATION SPENDING AND SOCIAL MOBILITY, AND THAT WE MODIFY THESE ROOT CAUSES THROUGH CORRESPONDING POLICIES. WHILE A HANDFUL OF SDOH HAVE BEEN SHOWN TO PREDICT COGNITIVE DECLINE AND ADRD, IMPORTANT QUESTIONS REMAIN ABOUT WHICH SDOH ARE ROOT SOCIAL DRIVERS I.E., HAVE THE GREATEST IMPACTS. DESPITE INCREASING CALLS FOR COMPARATIVE ASSESSMENTS TO UNPACK AND ADDRESS THE ROOT CAUSES—THE SOCIAL DETERMINANTS—OF ADRD, WE LACK KNOWLEDGE ON THE RELATIVE ADRD BURDEN AND ECONOMIC IMPACTS ASSOCIATED WITH MODIFYING SDOH, INCLUDING POLICIES SUCH AS THE SOCIAL SECURITY BENEFITS TAX. FURTHERMORE, WE HAVE YET TO ESTABLISH WHICH SUBPOPULATIONS ARE MOST AFFECTED BY SDOH. GIVEN THIS INFORMATION, THERE ARE CRITICAL NEEDS TO ACCURATELY ESTIMATE SDOH IMPACTS, INCLUDING BY SUBPOPULATION; AND TO TRANSLATE THESE ESTIMATES INTO PRIORITY-SETTING TOOLS INCLUDING IMPACTS ON ADRD BURDEN AND COSTS. LEFT UNADDRESSED, THESE CRITICAL NEEDS WILL HINDER THE DEVELOPMENT OF POLICIES TO MORE EFFECTIVELY REDUCE ADRD BURDEN AND INEQUITIES. OUR OVERALL OBJECTIVE IS TO USE LARGE MULTILEVEL, LONGITUDINAL DATASETS AND QUASI-EXPERIMENTAL APPROACHES TO CONSTRUCT THE FIRST COMPARATIVE ASSESSMENT EVIDENCE BASE ON THE SOCIAL DRIVERS OF ADRD BURDEN AND INEQUITIES. WE WILL ACCOMPLISH OUR OVERALL OBJECTIVE BY PURSUING THE FOLLOWING SPECIFIC AIMS USING DATA IN ADULTS AGE 50+ FROM: THE NATIONALLY-REPRESENTATIVE MORTALITY DISPARITIES IN AMERICAN COMMUNITIES STUDY, LINKED TO NATIONAL MORTALITY DATABASES; THE NATIONALLY-REPRESENTATIVE HEALTH AND RETIREMENT STUDY, LINKED TO MEDICARE CLAIMS DATA; AND THE NIH’S ALL OF US PROGRAM, A MULTIETHNIC STUDY LINKED TO ELECTRONIC HEALTH RECORDS (EHR) DATA ON DIAGNOSES/TREATMENTS OF HEALTH CONDITIONS: AIM 1) TO ASSESS THE IMPACTS OF AREA-LEVEL SDOH INCLUDING STATE POLICIES AS PROTECTIVE FACTORS AGAINST ADRD MORTALITY, THAT MAY VARY ACROSS HEALTH DISPARITY POPULATIONS; AIM 2) TO EVALUATE THE IMPACTS OF AREA-LEVEL SDOH ON MEMORY DECLINE IN MIDDLE-AGED ADULTS AND INCIDENCE OF COGNITIVE IMPAIRMENT AND DEMENTIA IN OLDER ADULTS; AIM 3) TO EXPLORE THE MECHANISMS THROUGH WHICH AREA-LEVEL SDOH MAY PROTECT AGAINST ADRD INCIDENCE AND COGNITIVE IMPAIRMENT/DECLINE, INCLUDING PHYSICAL/MENTAL HEALTH DISORDERS AND BIOMARKERS; AND AIM 4) TO ASCERTAIN WHICH AREA-LEVEL SDOH, IF MODIFIED, ARE EXPECTED TO YIELD THE GREATEST REDUCTIONS IN LEVELS OF AND INEQUITIES IN ADRD BURDEN AND COSTS. REGARDING IMPACT, WE WILL IDENTIFY THE MOST PROMISING SDOH ON WHICH TO INTERVENE TO YIELD IMPROVEMENTS IN ADRD BURDEN AND INEQUITIES. WE WILL FURTHER ESTABLISH THE PATHWAYS TO DIFFERENTIAL VULNERABILITIES BY SUBPOPULATION. BY TRANSLATING ESTIMATES INTO POPULATION HEALTH METRICS, WE ANTICIPATE OUR PROJECT WILL HAVE HIGH TRANSLATIONAL IMPACT THROUGH GUIDING POLICYMAKERS' EVIDENCE-BASED DECISIONS ABOUT POLICIES TO MORE EFFECTIVELY REDUCE THE BURDEN OF AND INEQUITIES IN ADRD AMONG AMERICANS.

COMMUNITY-BASED DESIGN AND EVALUATION OF A CONVERSATIONAL AGENT TO PROMOTE SARS-COV2 VACCINATION IN BLACK CHURCHES - PROJECT SUMMARY/ABSTRACT COMMUNITY-BASED DESIGN AND EVALUATION OF A CONVERSATIONAL AGENT TO PROMOTE SARS- COV2 VACCINATION IN BLACK CHURCHES AFRICAN AMERICANS HAVE SUFFERED A DISPROPORTIONATE BURDEN FROM COVID-19, WITH SIGNIFICANTLY HIGHER RATES OF INFECTION, HOSPITALIZATION, AND MORTALITY COMPARED TO WHITES. THESE FINDINGS MAY BE COMPOUNDED BY THE FACT THAT AFRICAN AMERICANS ARE ALSO AT HIGHER RISK FOR VACCINE HESITANCY. AS LIMITED HEALTH LITERACY HAS BEEN IDENTIFIED AS A KEY MEDIATOR OF RACIAL AND ETHNIC DISPARITIES, INTERVENTIONS THAT ADDRESS HEALTH LITERACY BARRIERS HAVE THE POTENTIAL TO AMELIORATE THESE DISPARITIES. OVER THE PAST DECADE WE HAVE DEVELOPED AND TESTED EMBODIED CONVERSATIONAL AGENTS (ECA) — COMPUTER CHARACTERS THAT SIMULATE FACE-TO-FACE COUNSELING USING VOICE, HAND GESTURE, GAZE CUES AND OTHER NONVERBAL BEHAVIOR, AND SUCCESSFULLY USED THEM IN HEALTH BEHAVIOR INTERVENTIONS FOR POPULATIONS WITH LOW HEALTH LITERACY. WE HAVE DEVELOPED ECA-BASED INTERVENTIONS TO ADDRESS A WIDE RANGE OF HEALTH PROBLEMS AMONG LOW LITERACY POPULATIONS, INCLUDING PHYSICAL ACTIVITY, DIET, AND MEDICATION ADHERENCE PROMOTION, PROVIDING ACCESS TO AND EXPLANATION OF HEALTHCARE DOCUMENTS, AND COLLECTION OF FAMILY HEALTH HISTORIES. IN THIS PROJECT, WE PROPOSE TO CREATE AN EFFECTIVE AND SUSTAINABLE SMARTPHONE-BASED ECA INTERVENTION DESIGNED TO DELIVER PERSONALIZED AND TAILORED EDUCATION ABOUT SARS-COV-2 AND INFLUENZA VACCINATION. WE WILL COLLABORATE WITH THE BLACK MINISTERIAL ALLIANCE TENPOINT (BMATP) OF GREATER BOSTON TO DEVELOP THE INTERVENTION APP AND EVALUATE IT IN A CLINICAL TRIAL INVOLVING 600 CONGREGANTS FROM 12 PREDOMINATELY AFRICAN AMERICAN CHURCHES. OUR PRIMARY HYPOTHESIS IS THAT PARTICIPANTS WILL HAVE SIGNIFICANTLY GREATER SARS-COV-2 AND INFLUENZA VACCINATION SERIES COMPLETION AT 6 MONTHS (H1) AND 12 MONTHS (H2) IN VERSIONS OF THE APP THAT PROMOTE ENGAGEMENT AND INCORPORATE SPIRITUAL TAILORING. OUR SECONDARY HYPOTHESES ARE THAT, AMONG PARTICIPANTS WHO HAVE NOT BEEN VACCINATED, THOSE IN THE HIGH ENGAGEMENT AND TAILORED CONDITIONS WILL HAVE SIGNIFICANT IMPROVEMENTS IN INTENT TO OBTAIN SARS-COV-2 AND INFLUENZA VACCINATION AND ATTITUDES TOWARDS SARS-COV-2 AND INFLUENZA VACCINATION.

BUILDING A SHARED INFRASTRUCTURE FOR COGNITIVE ASSESSMENT IN THE SERVICE OF COGNITIVE TRAINING RESEARCH - EFFECTIVE MEASUREMENT OF COGNITIVE ABILITIES IS FUNDAMENTAL TO EFFECTIVE DIAGNOSTICS, RISK ASSESSMENT AND EVALUATION OF INTERVENTIONS TARGETED TOWARDS OLDER ADULTS (OA) AND IN PARTICULAR THOSE WITH ALZHEIMER'S DISEASE AND RELATED DEMENTIAS (ADRD). WITH THE UBIQUITOUS AVAILABILITY OF SMARTPHONE/TABLET TECHNOLOGY IN MODERN SOCIETY A PROLIFERATION OF MOBILE COGNITIVE ASSESSMENTS FROM COMPANIES, HEALTHCARE PROVIDERS, AND RESEARCHERS ARE BEING DEVELOPED. HOWEVER, A DIFFICULTY IN EVALUATING SUCH INTERVENTIONS, AND IN PARTICULAR MAKING COMPARISON BETWEEN THEM IS THE LACK OF STANDARDIZATION/INTEROPERABILITY OF ASSESSMENT TOOLS. THIS IS ESPECIALLY THE CASE FOR EARLY STAGE/MECHANISTIC STUDIES WHERE IT IS COMMON FOR INVESTIGATORS TO EACH USE THEIR OWN LABS' TOOLSET TO EVALUATE INTERVENTION OUTCOMES. HERE WE ADDRESS PARTICULAR NEEDS IN THE FIELD OF COGNITIVE TRAINING, AS WELL AS FOR OTHER LONGITUDINAL ASSESSMENTS FOCUSED ON OA, WHERE THE LIMITED STANDARDIZATION AND ACCESSIBILITY OF COGNITIVE OUTCOME MEASURES MAKES IT DIFFICULT TO EVALUATE EFFECTIVENESS OF INTERVENTIONS. THIS R21/R33 INFRASTRUCTURE PROPOSAL SEEKS TO DEVELOP SHARED TOOLS TO FACILITATE EFFECTIVE TRANSLATION AND SHARING OF COGNITIVE ASSESSMENT AND TRAINING PROCEDURES. WE ACCOMPLISH THIS BY LEVERAGING TECHNOLOGIES, EXISTING ASSESSMENT BATTERIES, AND KNOW- HOW FROM 3 GROUPS THAT HAVE EACH INDEPENDENTLY DEVELOPED ROBUST SYSTEMS FOR COGNITIVE ASSESSMENT AND TRAINING THAT CAN RUN ON MOBILE DEVICES (UCR BRAIN GAME CENTER, UCSF NEUROSCAPE CENTER, AND UCI WORKING MEMORY AND PLASTICITY LAB). WE TARGET DEVELOPMENT OF SYSTEMS THAT ALLOW FOR INTEROPERABILITY OF ASSESSMENTS, ENROLLMENT/PARTICIPANT TRACKING SYSTEMS, DATA VISUALIZATION, AND PARTICIPANT COMPLIANCE SYSTEMS. IN THE R21 PHASE, WE AIM TO DEVELOP SUCH SYSTEMS AND DEMONSTRATE THAT THEY CAN BE EFFECTIVELY SHARED ACROSS LABS, AND IN THE R33 PHASE, THESE SYSTEMS WILL BE BOTH TESTED FOR ROBUSTNESS IN LARGE SCALE-RESEARCH PROJECTS THAT WILL NOW BE ABLE TO SHARE OUTCOME MEASURES, AND FOR DEVELOPING PERSONALIZED, PRECISION TRAINING APPROACHES FOR PARTICIPANTS BASED UPON THESE ASSESSMENTS. FURTHER, THESE SYSTEMS WILL BE DOCUMENTED AND WILL BE SHARED WITH OTHER SCIENTISTS GROUPS TO REDUCE THE BARRIER OF ENTRY FOR OTHER GROUPS. THE LONG-TERM IMPACT OF THIS WORK WILL BE AN INFRASTRUCTURE THAT WILL SUPPORT BETTER COMPARISON ACROSS STUDIES OF COGNITIVE TRAINING, AS WELL AS OTHER INTERVENTIONS THAT ARE INCREASINGLY BEING USED TO AMELIORATE COGNITIVE DECLINES IN OLDER ADULTS SUCH AS THOSE RELATED TO ADRD. THE KEY VALUE OF THIS SYSTEM COMPARED TO OTHERS IS THAT IT WILL SIMULTANEOUSLY SUPPORT THE FLEXIBILITY REQUIRED FOR BASIC RESEARCH, BY FACILITATING GROUPS TO CONTINUE TO USE THEIR OWN LAB'S SOFTWARE SYSTEMS, WHILE AT THE SAME TIME PROVIDING THEM WITH A POWERFUL INFRASTRUCTURE FOR SHARING THAT ALLOWS THEM TO INCORPORATE ASSESSMENTS, SERVER INFRASTRUCTURE AND COMPLIANCE TOOLS INTO THEIR OWN STUDIES. THIS WILL FACILITATE COMPARISONS ACROSS STUDIES USING COMMON OUTCOME MEASURES AS WELL AS THE ABILITY TO USE THE SAME ASSESSMENTS IN NUMEROUS OTHER DOMAINS INCLUDING RISK-ASSESSMENT AND LONGITUDINAL TESTING IN OLDER ADULTS AT RISK FOR ADRD.

ARBI - ASSESSMENT AND REHABILITATION OF BINOCULAR SENSORIMOTOR DISORDERS - PROJECT SUMMARY BINOCULAR VISION RELIES ON A SYNERGY BETWEEN SENSORY AND MOTOR FUSIONAL MECHANISMS THAT JOINTLY CONSTRUCT A SINGLE PERCEPT OF THE ENVIRONMENT FROM THE DIFFERING IMAGES FORMED ON THE TWO RETINAE. A STEREOSCOPIC SENSORY REPRESENTATION OF THE ENVIRONMENT IS REQUIRED FOR ACCURATE BINOCULAR EYE MOVEMENTS, WHICH IN TURN ARE REQUIRED FOR STEREOSCOPIC SENSORY VISION. A FAILURE IN EITHER COMPONENT OF THIS SYSTEM, ESPECIALLY DURING DEVELOPMENT, CAN LEAD TO PERMANENT BINOCULAR VISION IMPAIRMENT. SENSORY IMPAIRMENTS CAN INCLUDE AMBLYOPIA, DIPLOPIA AND SUPPRESSION, OCULOMOTOR IMPAIRMENTS CAN INCLUDE STRABISMUS AND VERGENCE INSUFFICIENCY, WHILE SOCIO-ECONOMIC SEQUELAE INCLUDE LOST EDUCATION, SPORT AND JOB OPPORTUNITIES AND ELEVATED ADVERSE HEALTH RISKS. THE CURRENT TREATMENTS FOR AMBLYOPIA (OCCLUSION AND PENALIZATION) ARE PRIMARILY MONOCULAR AND DO NOT PROMOTE BINOCULAR PERCEPTION OR EYE MOVEMENT COORDINATION. SIMILARLY, TREATMENTS FOR STRABISMUS DO NOT TYPICALLY ADDRESS BINOCULAR PERCEPTION. THESE LIMITATIONS ARE AT LEAST PARTLY DUE TO A LACK OF PRACTICAL METHODOLOGIES FOR THE ASSESSMENT OF SENSORY-MOTOR FUNCTION AND PARTLY DUE TO A LACK OF COORDINATED SENSORY-MOTOR THERAPIES. RECENT DATA SHOW THAT THERE IS SIGNIFICANT PLASTICITY IN BOTH SENSORY SYSTEMS AND MOTOR SYSTEMS, EVEN IN ADULTS. MANY GROUPS ARE NOW EXPLORING METHODS TO PROMOTE SENSORY PLASTICITY WITH DIGITALLY MODIFIED IMAGES IN DICHOPTIC GAMES AND MOVIES, BUT CONSIDERABLY LESS ATTENTION HAS BEEN DIRECTED TO MOTOR PLASTICITY OR SENSORY AND MOTOR PLASTICITY TOGETHER. WE HYPOTHESIZE THAT ADDITIONAL THERAPEUTIC GAINS AND A LOWER RISK OF ADVERSE SIDE EFFECTS MAY BE ACHIEVED WITH A COMBINED SENSORY-MOTOR THERAPEUTIC APPROACH THAT IS MONITORED BY EFFECTIVE SENSORY-MOTOR ENDPOINTS. WE ARGUE I) THAT THE PACE OF COMMERCIALIZATION OF VIRTUAL REALITY THERAPIES FOR ANISOMETROPIC AMBLYOPIA INTENSIFIES THE NEED SIMULTANEOUSLY TO UNDERSTAND SENSORY AND OCULOMOTOR DEFICITS IN STRABISMIC AMBLYOPIA AND II) THAT THE HIGH LEVELS OF RECIDIVISM FOLLOWING SURGICAL INTERVENTION MAY BENEFIT FROM COMBINED SENSORIMOTOR REHABILITATION. IN AIM 1, WE DEVELOP AND EVALUATE EFFICIENT METHODS TO MEASURE SENSORY AND MOTOR DEFICITS IN PEOPLE WITH BINOCULAR VISION IMPAIRMENT AND TO PROVIDE A QUANTITATIVE FRAMEWORK FOR EVIDENCE-BASED ASSESSMENT OF SENSORY-MOTOR THERAPY. IN AIM 2, WE MEASURE THE IMPACT ACROSS THE VISUAL FIELD OF STRABISMUS ON THE THREE-DIMENSIONAL REPRESENTATION OF VIRTUAL AND NATURAL ENVIRONMENTS TO UNDERSTAND HOW THE DISTRIBUTION OF NATURALLY OCCURRING DEPTH STATISTICS ACROSS THE VISUAL FIELD MAY IMPACT THE DEVELOPMENT OF BINOCULAR SENSORY AND MOTOR DEFICITS AND MODERATE THEIR RESPONSE TO TREATMENT. IN AIM 3, WE DEVELOP AND EVALUATE FEEDBACK-BASED METHODS THAT AIM TO FACILITATE AND MAINTAIN OCULAR ALIGNMENT AND EXAMINE THE POTENTIAL BENEFIT OF SIMULTANEOUS SENSORY AND MOTOR INTERVENTIONS FOR BINOCULAR VISUAL FUNCTION. IN EACH AIM, WE EMPLOY BOTH LABORATORY STIMULI, BECAUSE OF THEIR HIGH LEVEL OF CONTROL, AND NATURAL AND VIRTUAL 3D SCENES, BECAUSE OF THEIR RICH STRUCTURE AND RELEVANCE TO REAL-WORLD DEFICITS. THE OVERALL GOAL IS TO DEMONSTRATE THE THEORETICAL FOUNDATION FOR COMBINED SENSORY AND MOTOR THERAPEUTIC APPROACHES TO BINOCULAR VISUAL DYSFUNCTION.

RIBOSOME-MEDIATED TRANSLATIONAL REGULATION DURING STEM CELL DIFFERENTIATION

CONFORMATIONAL REGULATION AND THERAPEUTIC TARGETING OF ONCOGENIC KRAS

SEMI-AUTOMATING DATA EXTRACTION FOR SYSTEMATIC REVIEWS

ROLE OF ENDOTHELIAL SOX17 IN EC-SMC CROSSTALK AND HOMEOSTATIC REGULATION OF BLOOD VESSEL ADAPTION TO ARTERIAL HEMODYNAMICS - SUMMARY ARTERIES AND VEINS PLAY DIFFERENT ROLES IN HUMAN PHYSIOLOGY AND VASCULAR DISEASES. NOTABLY, ARTERIAL AND VENOUS ENDOTHELIAL CELLS (ECS) DEMONSTRATE DISTINCT MOLECULAR PROFILES. THE ESTABLISHMENT OF SUCH MOLECULAR DISTINCTION IS ORCHESTRATED BY SERIES OF TRANSCRIPTIONAL PROGRAMS, WHICH HAVE BEEN WELL STUDIED IN DEVELOPMENTAL BIOLOGY. HOWEVER, HOW THESE EC TRANSCRIPTIONAL PROGRAMS CONTROL ADULT BLOOD VESSEL STRUCTURE AND FUNCTION, AND HOW TO TRANSLATE THIS KNOWLEDGE INTO CLINICAL APPLICATION SUCH AS VEIN OR TISSUE ENGINEERED GRAFT ADAPTATION IS UNDER- EXPLORED. TO ADDRESS THIS QUESTION, WE EXAMINED THE TRANSCRIPTION PROFILE OF ARTERIAL VS. VENOUS ECS IN ADULT BLOOD VESSELS AND HAVE IDENTIFIED SEVERAL KEY TRANSCRIPTION FACTORS THAT ARE DIFFERENTIALLY EXPRESSED IN ARTERIAL VS. VENOUS ECS. AMONG THEM, SOX13 AND SOX17 ARE HIGHLY EXPRESSED IN ADULT ARTERIAL ECS BUT NOT IN VENOUS ECS. OUR PRELIMINARY STUDIES DEMONSTRATE THAT OVER-EXPRESSING SOX17 IN VENOUS ECS RECONSTITUTES ALL THE KNOWN ARTERIAL MARKERS, SUGGESTING SOX17 IS A KEY REGULATOR OF ADULT ARTERIAL EC PHENOTYPES. IMPORTANTLY, SOX17 INDUCES THE EXPRESSION OF MULTIPLE FAMILIES OF MOLECULES (NOTCH, EPHRIN, CONNEXINS, PDGF) THAT MAY CONFER SIGNALS FROM ECS TO SMOOTH MUSCLE CELLS (SMCS) TO REGULATE SMC PHENOTYPES IN BLOOD VESSELS. EC SOX17 ALSO PROMOTED SMC CONTRACTILE PHENOTYPE IN EC-SMC CO-CULTURE AND GRAFT REMODELING MODEL. ON THE OTHER HAND, OVER-EXPRESSING SOX13 IN ECS FACILITATES THE RECRUITMENT OF SMCS TOWARD BLOOD VESSELS. BASED ON THESE ENCOURAGING PRELIMINARY DATA, WE HYPOTHESIZE THAT ENDOTHELIAL SOX13/17 PLAY SYNERGISTIC ROLES IN THE HOMEOSTATIC REGULATION OF ADULT ARTERY FUNCTIONS BY MAINTAINING ADULT ARTERIAL EC PHENOTYPE AND ENGAGING EC- SMC CROSSTALK. TO TEST THIS HYPOTHESIS, WE WILL INVESTIGATE HOW THE ENDOTHELIAL SOX13/17 REGULATES EC AND SMC PHENOTYPES AND THEIR ROLE IN BLOOD VESSEL STRUCTURES AND FUNCTIONS USING IN VITRO BIOENGINEERED MODELS AS WELL AS IN VIVO ANIMAL MODELS.

ENGINEERING BIOMIMETIC CORNEAL CONSTRUCTS

INFRALIMBIC CIRCUIT CONTROL OVER A SEX-DEPENDENT SWITCH IN THREAT RESPONDING

DIRECT PICOGRAM DNA AND RNA SEQUENCING USING NANOPORE ZERO-MODE WAVEGUIDES

PERSISTER CELLS OF BORRELIA BURGDORFERI

SHF: LARGE: GRADUAL TYPING ACROSS THE SPECTRUM

BRIDGING ATOMISTIC AND CONTINUUM SCALES IN PHASE-FIELD MODELING OF SOLID-LIQUID...

"CANCER IMMUNOTHERAPY BY TARGETING A2 ADENOSINE RECEPTOR"

INNOVATIVE MAGNETIC MATERIAL SOLUTIONS FOR NAVY HIGH-FREQUENCY POWER SYSTEMS

RTG: ALGEBRAIC GEOMETRY AND REPRESENTATION THEORY

EFRI-ODISSEI: ORIGAMI AND ASSEMBLY TECHNIQUES FOR HUMAN-TISSUE-ENGINEERING (OATH)

ENHANCED RADIATION THERAPY WITH NANOSCALE FREQUENCY MODULATORS

MULTISCALE DEVELOPMENT OF L10 MATERIALS FOR RARE EARTH FREE PERMANENT MAGNETS

CENTER FOR ATYPICAL LANGUAGE INTERPRETING

MECHANICAL CAUSATION OF CORNEAL STROMAL MATRIX SYNTHESIS AND FIBROSIS - PROJECT SUMMARY THE CORNEA AND SCLERA ARE THE PRINCIPAL LOAD BEARING MEMBERS IN THE TOUGH FIBROUS OCULAR TUNIC WHICH WE CONSIDER TO BE AN INTEGRATED MECHANO-BIOLOGICAL STRUCTURE. DURING DEVELOPMENT, THE SHAPE OF THE EYE HAS BEEN TUNED TO CONFORM TO A SPECIFIC MECHANICAL ENVIRONMENT THROUGH A LONG TIME-SCALE INTEGRATION OF ITS LOADING HISTORY WITH ITS INITIAL GENETIC PATTERNING. ALTHOUGH MECHANICS ARE KNOWN TO CONTRIBUTE TO THE DEVELOPMENT OF MANY CONNECTIVE TISSUES, THE OCULAR GLOBE IS PARTICULARLY SENSITIVE TO PRESSURE (TENSILE WALL STRESS) DURING THE EXPANSIVE PHASE OF GROWTH. EVEN IN THE MATURE OCULAR TUNIC, MECHANICAL INSTABILITIES OFTEN MANIFEST AS CONDITIONS WHICH DISRUPT VISION (E.G. MYOPIA, KERATOCONUS, POST-LASIK ECTASIA, TRACTIONAL RETINAL DETACHMENTS AND GLAUCOMA). WHILE THE UNDERLYING CAUSES OF TISSUE STRUCTURAL INSTABILITIES ARE POORLY UNDERSTOOD, WE SUSPECT THAT THEY ARE MECHANOBIOLOGICAL IN NATURE AND POTENTIALLY REFLECT AN IMBALANCE IN THE TENSIONAL HOMEOSTASIS THAT EXISTS BETWEEN MESENCHYMAL CELLS, THEIR LOCAL ECM AND THE GLOBAL MECHANICAL ENVIRONMENT. WE KNOW THAT DURING DEVELOPMENT, DISRUPTION OF THE MECHANICAL CONNECTION BETWEEN FIBROBLASTIC CELLS AND THEIR ECM SEVERELY RETARDS OCULAR GROWTH IN A MANNER ANALOGOUS TO PRESSURE LOSS, SUGGESTING THAT MECHANICAL COMMUNICATION IS CRITICAL TO PROPER OCULAR MORPHOGENESIS. HOWEVER, THE EFFECT OF MECHANICAL FORCES ON THE MECHANISMS WHICH DRIVE TISSUE FORMATION AND GROWTH ARE NOT WELL CHARACTERIZED. IT IS REMARKABLE THAT WE STILL DO NOT FULLY UNDERSTAND HOW THE MOST IMPORTANT STRUCTURAL MOLECULE IN VERTEBRATES, COLLAGEN, IS EFFICIENTLY ASSEMBLED INTO HIGHLY-ORGANIZED, FUNCTIONAL, LOAD-BEARING TISSUES WHICH ARE MASSIVELY EXPANDED INTO MACROSCALE STRUCTURES DURING GROWTH. HOWEVER, IF WE ARE ABLE TO UNCOVER NEW MECHANISMS WHICH CONTROL TISSUE FORMATION AND GROWTH, WE WILL HAVE ACCESS TO INFORMATION WHICH CAN INFORM THERAPIES FOR A VARIETY OF PATHOLOGICAL CONDITIONS INCLUDING FIBROSIS, MYOPIA, KERATOCONUS AND POTENTIALLY, GLAUCOMA. ADDITIONALLY, IF WE UNDERSTAND HOW TISSUE IS PRODUCED, THEN THERE WILL BE IMPLICATIONS FOR ENGINEERING CORNEAS DE NOVO AND FOR IMPROVING APPROACHES TO REGENERATIVE CORNEAL MEDICINE. IN THE PROPOSED WORK, WE PLAN COMBINE OUR HUMAN CELL CULTURE MODEL OF CORNEAL STROMAL TISSUE ELABORATION WITH LIVE-CELL MECHANODYNAMICS IMAGING TO DIRECTLY OBSERVE SINGLE COLLAGEN MOLECULES DURING THEIR TRANSITION FROM SOLUTION TO FIBRILS. WE WILL THUS DIRECTLY TEST A NEW HYPOTHESIS WHICH DIRECTLY COUPLES LOCAL AND GLOBALLY APPLIED FORCES DIRECTLY TO MOLECULAR ASSEMBLY OF COLLAGEN DURING FIBRILLOGENESIS AND GROWTH. THE WORKING HYPOTHESIS FOR THIS PROPOSAL IS THAT FORCE CAUSES CORNEAL STROMAL ECM ELABORATION TO REGULATE FIBRIL ASSEMBLY, REMODELING AND GROWTH. IF THE HYPOTHESIS IS CORRECT, THERE ARE MYRIAD MECHANOTHERAPEUTIC OPPORTUNITIES AND MORE CRITICALLY, OUR BASIC UNDERSTANDING OF COLLAGENOUS TISSUE FORMATION AND GROWTH, WILL BE FUNDAMENTALLY ALTERED.

A NOVEL PHARMACOTHERAPY FOR GLAUCOMA

DRAVET SYNDROME ANTI-EPILEPTIC CONTROL BY TARGETING GIRK CHANNELS - PROJECT SUMMARY DRAVET SYNDROME (DS) IS A DEVASTATING FORM OF EPILEPSY CAUSED BY LOSS OF FUNCTION OF NAV1.1 (80-90% OF CASES), THE PREDOMINANT VOLTAGE-GATED NA+ CHANNEL EXPRESSED IN INHIBITORY (GABAERGIC) INTERNEURONS IN THE HIPPOCAMPUS AND PREFRONTAL CORTEX. THIS CAUSES A DECREASE IN THE RELEASE OF INHIBITORY NEUROTRANSMITTER (GABA), RESULTING IN HYPEREXCITABILITY. THE DISEASE MANIFESTS ITSELF WITHIN THE FIRST YEAR OF LIFE AND IS USUALLY TRIGGERED BY HYPERTHERMIA CAUSING FREQUENT AND PROLONGED SEIZURES THAT RESULT IN A HOST OF HEALTH PROBLEMS INCLUDING DEVELOPMENTAL DELAY, SPEECH IMPAIRMENT, ATAXIA, HYPOTONIA AND SLEEP DISTURBANCES. TWO SMALL MOLECULE MONOTHERAPIES HAVE BEEN APPROVED RECENTLY BY THE FDA: EPIDIOLEX (CANNABIDIOL OR CBD) IN 2018 AND FINTEPLA (FENFLURAMINE OR FA) IN 2020 FOR PATIENTS TWO YEARS OF AGE AND OLDER. EVEN THOUGH THEY REDUCE THE FREQUENCY OF SEIZURES, THESE DRUGS AT THEIR EFFECTIVE DOSAGES CAUSE MULTIPLE SIDE EFFECTS. THEIR MECHANISM(S) OF ACTION TO REDUCE EPILEPTIFORM ACTIVITY REMAIN(S) UNKNOWN. G PROTEIN-GATED INWARDLY RECTIFYING K+ (GIRK) CHANNELS HAVE BEEN STRONGLY IMPLICATED IN EPILEPSY. THEY ARE ACTIVATED BY THE GSS DIMER OF G PROTEINS AND BY [NA+]I IN A SYNERGISTIC MANNER. THE BASIS OF SYNERGISM LIES IN THAT THEY EACH WORK ALLOSTERICALLY TO CONTROL PREDOMINANTLY THE TWO CHANNEL GATES: GSS, THE MEMBRANE GATE AND NA+, THE CYTOSOLIC GATE. IN THE CASE OF THE GABAERGIC INTERNEURONS, WE HYPOTHESIZE THAT NAV1.1 AND GIRK1/2 ARE COUPLED, SUCH THAT THE NA+ ENTERING THROUGH NAV1.1 PROMOTES GIRK1/2 ACTIVITY TO HYPERPOLARIZE THE CELL AND ENSURE REMOVAL OF NAV1.1 INACTIVATION FOR FAST SPIKING. IN DS THIS MECHANISM BECOMES COMPROMISED CAUSING CELL DEPOLARIZATION AND INACTIVATION OF VOLTAGE-GATED CHANNELS AT LARGE PRESENT IN GABAERGIC NEURONS FAILING TO COMPENSATE FOR THE LOSS OF NAV1.1. WE USE GAT1508, A SPECIFIC ACTIVATOR OF GIRK1/2 TO COMPENSATE FOR THE COMPROMISED NA+ ENTRY. SINCE GAT1508 OPENS THE CYTOSOLIC GATE, WE ASK WHETHER IT SYNERGIZES WITH CBD (VIA CB1R) AND FA (VIA 5-HT1DR) TO OPEN MORE FULLY THE MEMBRANE GATES. IN AIM 1, EXPERIMENTS DESIGNED TO TEST THE HYPOTHESIS ARE AIMED AT THE CELLULAR LEVEL IN BOTH HETEROLOGOUS EXPRESSION AND IN NATIVE GABAERGIC NEURONS. IN AIMS 2 AND 3, WE UTILIZE A DS MOUSE MODEL, HETEROZYGOUS FOR THE SCN1A GENE THAT ENCODES NAV1.1, AND IN AIM 2, WE TEST THE HYPOTHESIS AT THE BRAIN SLICE LEVEL, WHERE SYNAPSES AND TRANSMITTER RELEASE REMAIN INTACT, AND COMPARE THE DS MODEL TO A WILD-TYPE ANIMAL MODEL. IN AIM 3, WE PURSUE EXPERIMENTS AT THE WHOLE ANIMAL LEVEL (DS MODEL), USING SIMULTANEOUS EEG AND 2-PHOTON MICROSCOPY TO MONITOR THE NEURONAL CIRCUITS INVOLVED.

VALIDATION AND DEVELOPMENT OF TRYPANOSOMAL PHOSPHODIESTERASE INHIBITORS FOR TREAT

ACCELERATING THE DEVELOPMENT OF NOVEL METHODS TO MEASURE 24-HR PHYSICAL BEHAVIOR

GAMMA-MUSIC BASED INTERVENTION FOR MILD ALZHEIMER'S DISEASE - PROJECT SUMMARY / ABSTRACT ALZHEIMER’S DISEASE (AD) IS CHARACTERIZED BY COGNITIVE DEFICITS SUCH AS MEMORY LOSS, AS WELL AS DEFICITS IN THE MOTIVATION THAT DRIVES DAILY ACTIVITIES. THESE COGNITIVE AND MOTIVATIONAL DEFICITS ARE LINKED TO WIDESPREAD NEURONAL AND SYNAPTIC ATROPHY, COUPLED WITH AGGREGATED EXTRACELLULAR ASS-PLAQUE AND TAU DEPOSITS, AND ATYPICAL NEURAL ACTIVITY ACROSS MULTIPLE FREQUENCIES. RECENT WORK IN MOUSE MODELS OF AD HAVE SHOWN THAT INDUCING GAMMA OSCILLATIONS WITH A NON-INVASIVE GAMMA-FREQUENCY (40 HZ) LIGHT-FLICKERING AND AUDITORY TONE-STIMULATION REGIMES REDUCED ASS PLAQUES AND IMPROVED SPATIAL AND RECOGNITION MEMORY. IN HUMANS, RESTORING GAMMA-FREQUENCY ACTIVITY WHILE PRESERVING ITS PHASE-AMPLITUDE COUPLING WITH THETA-BAND ACTIVITY ARE SHOWN TO RECOVER HUMAN MEMORY PERFORMANCE IN OLDER ADULTS, AND IN PATIENTS WITH MILD AD, THUS OFFERING A PROMISING ROUTE TOWARDS A NOVEL THERAPY THAT CAN PREVENT BRAIN ATROPHY WHILE IMPROVING COGNITION. DESPITE THEIR RECENT SUCCESSES, IT IS A MAJOR CHALLENGE TO TRANSLATE GAMMA-FREQUENCY NEUROSTIMULATION FROM A LABORATORY STUDY TO A BEHAVIORAL INTERVENTION. OUR GOAL IS TO PROMOTE HEALTHY NEUROCOGNITIVE AGING USING LIFESTYLE INTERVENTIONS; IN PARTICULAR, INTERVENTIONS THAT SUSTAINABLY ELEVATE MOOD AND REWARD MOTIVATED BEHAVIOR WHILE ENCOURAGING SOCIAL BONDING MAY BE MOST PROMISING IN SLOWING THE PROGRESSION OF AD. MUSIC LISTENING ENGAGES MULTIPLE BRAIN NETWORKS INVOLVED IN SENSORY PROCESSING, MOVEMENT, LANGUAGE, ATTENTION, LEARNING AND MEMORY, EMOTION AND REWARD, AND SOCIAL CONNECTEDNESS. MUSIC-BASED INTERVENTIONS (MBIS) HAVE THE POTENTIAL TO MANAGE SYMPTOMS, SLOW DISEASE PROGRESSION, AND IMPROVE QUALITY OF LIFE. OUR LAB HAS RECENTLY SHOWN THAT AN EIGHT-WEEK MBI CAN INCREASE AUDITORY FUNCTIONAL CONNECTIVITY TO THE REWARD SYSTEM. HERE WE PROPOSE TO TEST A NOVEL PROTOCOL FOR MUSIC-BASED BRAIN STIMULATION, GAMMA-MBI: GAMMA-LIGHT STIMULATION THAT AUTOMATICALLY ADAPTS TO MUSIC-BASED INTERVENTION. HARNESSING THE FACT THAT MUSIC LISTENING IS AN INTRINSICALLY REWARDING ACTIVITY, WE PROPOSE TO USE MUSIC AS A CARRIER FOR GAMMA SENSORY STIMULATION. AS MUSIC CONTAINS THETA-BAND ACOUSTIC ENERGY, MUSIC LISTENING IS A FORM OF THETA- BAND NONINVASIVE BRAIN STIMULATION. WE WILL TEST AND REFINE A NOVEL BRAIN-STIMULATION TOOL USING GAMMA-FREQUENCY LIGHTS COUPLED WITH SELF-SELECTED MUSIC FOR A GAMMA-MUSIC-BASED INTERVENTION FOR PARTICIPANTS WITH MILD ALZHEIMER’S DISEASE. RESULTS WILL YIELD A GAMMA-STIMULATION PROTOCOL THAT RELIABLY INFLUENCES BRAIN ACTIVITY (AIM 1), IS ADAPTIVE, MOTIVATING AND REWARDING TO USE (AIM 2), AND WILL GENERATE PREDICTIONS AS TO WHO MIGHT BENEFIT THE MOST FROM GAMMA-MBI (AIM 3). BY BRIDGING THE GAP BETWEEN NEUROSTIMULATION AND BEHAVIORAL INTERVENTION BY COMBINING MUSIC THERAPY WITH GAMMA-BAND NEUROSTIMULATION, THE PRESENT PROJECT AIMS TO FIND A SUSTAINABLE INTERVENTION THAT DELAYS THE PROGRESSION OF AD. OUR TEAM IS UNIQUELY QUALIFIED TO ADDRESS ALL ASPECTS OF THIS INNOVATIVE AND AMBITIOUS PROJECT.

VICARIOUS TRAUMA TOOLKIT (VTT): EVIDENCE-BASED SUPPORT FOR VICTIM ASSISTANCE PROFESSIONALS, LAW ENFORCEMENT OFFICERS, AND OTHER FIRST RESPONDERS

A GENOMICS APPROACH TO DRUG TOLERANCE

NEW COMPETITIVE COOPERATIVE AGREEMENT WITH NORTHEASTERN UNIVERSITY UNDER FOA NUMBER DE-FOA-00002459 (OPEN 2021) AND CONTROL NUMBER 2459-4936. PROJECT TITLE: HIGH-PERFORMANCE AND MINIATURIZED GREENHOUSE GAS SENSOR FOR DRONE-BASED REMOTE SENSING. IN THIS PROJECT, WE PROPOSE TO SIMULTANEOUSLY ADDRESS THE CHALLENGES ASSOCIATED WITH SWAP AND SPEED BY DEVELOPING A NEW CLASS OF HIGH-PERFORMANCE AND MINIATURE N2O SENSORS (TABLE 2) BASED ON LASER ABSORPTION SPECTROMETRY (LAS) AND ADVANCED MEMS RESONANT IR DETECTORS WITH ULTRA-HIGH RESOLUTION AND FAST DETECTION SPEED.

SELECTIVE POSITIVE ALLOSTERIC MODULATORS OF A4B2 NICOTINIC RECEPTORS - ABSTRACT TOBACCO ADDICTION REMAINS A LEADING CAUSE OF DISEASE AND DEATH WORLDWIDE, AND AN INCREASING NUMBER OF NEVER- SMOKERS ARE BEING EXPOSED TO NICOTINE VIA E-CIGARETTES. HOWEVER, THE ROLE OF SPECIFIC NICOTINIC ACETYLCHOLINE RECEPTORS (NACHR) IN NICOTINE’S BEHAVIORAL EFFECTS REMAINS POORLY UNDERSTOOD BECAUSE OF THE AVAILABILITY OF VERY FEW SUBTYPE-SELECTIVE PROBES, WHICH LIMIT DRUG DEVELOPMENT POTENTIAL. THUS, THIS PROPOSAL AIMS TO DEVELOP NOVEL PROBES TO BETTER UNDERSTAND THE FUNCTION OF THE DIFFERENT Α4Β2 SUBTYPES, WHICH HAVE BEEN PROPOSED TO UNDERLIE BEHAVIORS CHARACTERISTIC OF NICOTINE DEPENDENCE. THE Α4Β2 NACHR SUBTYPES EXHIBIT TWO DISTINCT ISOFORMS: Α42Β23, WHICH HAS A HIGH AFFINITY FOR ACETYLCHOLINE AND NICOTINE, AND Α43Β22 NACHR, WHICH HAS A LOWER AFFINITY FOR ACETYLCHOLINE AND NICOTINE. OUR RECENT FINDINGS HAVE SUGGESTED THAT PROBES SELECTIVELY TARGETING THE HIGH SENSITIVITY Α42Β23 NACHRS MAY PROVIDE A NOVEL, PREVIOUSLY UNDEFINED UNDERSTANDING OF NICOTINE’S BEHAVIORAL AND PHARMACOLOGICAL ACTIONS. THUS, THESE STUDIES WILL DEVELOP AND OPTIMIZE NOVEL POSITIVE ALLOSTERIC MODULATORS (PAMS) OF THE HIGH SENSITIVITY Α42Β23 NACHRS. SPECIFIC AIM 1 WILL BEGIN BY FOCUSING ON THE SYNTHESIS OF NOVEL ANALOGS OF DESFORMYLFLUSTRABROMINE (DFBR) AND GAT2802 TO DERIVE AN IMPROVED PHARMACOLOGICAL PROFILE. SPECIFIC AIM 2 WILL INVOLVE IN VITRO CHARACTERIZATION OF NOVEL PROBES FROM BOTH STRUCTURAL CLASSES AS Α42Β3 NACHR-SELECTIVE PAMS. THEREAFTER, SPECIFIC AIM 3 STUDIES WILL EVALUATE ADME/PK PROFILING OF KEY Α42Β23 PAMS TO ELIMINATE POTENTIAL LIABILITIES AND IDENTIFY PROBES WITH SUITABLE DRUG-LIKE PROPERTIES. FINALLY, IN SPECIFIC AIM 4, THE MOST PROMISING PROBES WILL BE TESTED FOR THEIR EFFICACY IN INDUCING BEHAVIORS CHARACTERISTIC OF NICOTINE’S 42 NACHR ACTIONS IN ADULT MALE AND FEMALE MICE. TAKEN TOGETHER, THESE STUDIES WILL DEVELOP AND VALIDATE NOVEL HS-SELECTIVE Α42Β23 PAM PROBES TO BETTER UNDERSTAND THE PHARMACOLOGICAL EFFECTS OF Α4Β2 NACHRS IN BEHAVIORS CHARACTERISTIC OF NICOTINE’S ACTIONS, WHICH MAY THEREBY LEAD TO FUTURE THERAPEUTIC IMPLICATIONS.

FIBRILLAR POLYMORPHS IN HUMAN BRAIN TISSUE - FIBRILLAR POLYMORPHS IN HUMAN BRAIN TISSUE PROJECT SUMMARY ALZHEIMER'S DISEASE (AD) IS A NEURODEGENERATIVE DISORDER DEFINED BY THE ACCUMULATION OF PROTEIN DEPOSITS OF ASS PEPTIDE AND TAU PROTEIN. PROGRESSION OF AD INVOLVES SPREAD OF TAU DEPOSITS, CALLED NEUROFIBRILLARY TANGLES, ALONG WELL CHARTED ANATOMICAL PATHWAYS IN THE BRAIN. TAUOPATHIES SUCH AS PICK’S DISEASE, FRONTOTEMPORAL DEMENTIA, PROGRESSIVE SUPRANUCLEAR PALSY (AND OTHERS) ARE ASSOCIATED WITH ALTERNATE PATTERNS OF PATHOLOGY THROUGHOUT THE BRAIN WITH THE CONSEQUENT DIFFERENCES IN CLINICAL PHENOTYPES. THE STRUCTURES OF FIBRILLAR POLYMORPHS OF TAU HAVE BEEN DETERMINED AT HIGH RESOLUTION AND THERE ARE WELL-ESTABLISHED DIFFERENCES IN THE DOMINANT ISOFORM/POLYMORPH OF TAU ASSOCIATED WITH EACH OF THESE DISEASES. IT HAS BEEN SUGGESTED THAT DIFFERENCES IN COMPOSITION, STRUCTURE AND POST-TRANSLATIONAL MODIFICATIONS (PTMS) OF TAU OLIGOMERS/FIBRILS AMONG INDIVIDUALS LEAD TO DIFFERENCES IN BIOACTIVITY THAT IMPACT DISEASE ATTRIBUTES SUCH AS AGE OF ONSET, RATE OF PROGRESSION AND ANATOMICAL DISTRIBUTION OF PATHOLOGY. IN ORDER TO TEST THAT HYPOTHESIS, METHODS WILL BE USED TO OBSERVE TAU IN SITU, IN DIFFERENT BRAIN AREAS AND AT DIFFERENT PHASES OF DISEASE. A CENTRAL HYPOTHESIS OF THIS PROJECT IS THAT INTERROGATING THE STRUCTURE OF TAU AGGREGATES IN THE CONTEXT OF INTACT TISSUE DURING DISEASE PROGRESSION CAN CLARIFY IF HOMOGENEITY OR HETEROGENEITY IS THE PREDOMINANT FEATURE OF TAU DEPOSITS THAT CONTRIBUTE TO AN INDIVIDUAL’S ALZHEIMER PHENOTYPE. ADVANCED TECHNIQUES WILL BE USED TO PREPARE HUMAN BRAIN SAMPLES AND ENABLE SCANNING X-RAY MICRODIFFRACTION (XMD) TO MAP IN SITU THE DISTRIBUTION OF STRUCTURAL VARIATIONS AT THE MOLECULAR LEVEL. MAPPING THE DISTRIBUTION OF FIBRILLAR AND NON-FIBRILLAR STRUCTURE WITHIN AND AMONG TAU LESIONS WILL PROVIDE A MEASURE OF THE DEGREE TO WHICH DISEASE PROGRESSION IS DRIVEN BY PRION-LIKE SPREADING AND CLARIFY THE ROLE OF NON-FIBRILLAR CONDENSATES IN SEED AND FIBRIL NUCLEATION. EVOLUTION OF THE STRUCTURAL ORGANIZATION OF LESIONS WILL BE TRACKED BY STUDIES OF DIFFERENT REGIONS OF THE BRAIN AT BRAAK STAGE II ONWARD. FOR EACH CASE, INDEPENDENT OF DISEASE STAGE, THE ENTIRE TAU-BRAAK PATHWAY WILL BE INVESTIGATED TO DETECT ANY PRE-FIBRILLAR DEPOSITS OR ALTERATIONS IN TISSUE STRUCTURE THAT MAY PRECEDE OR COINCIDE WITH THE EMERGENCE OF FIBRILLAR PATHOLOGY. OBSERVATIONS IN TYPICAL AD CASES WILL BE COMPARED WITH ANALOGOUS STUDIES OF PICK'S DISEASE, PROGRESSIVE SUPRANUCLEAR PALSY (PSP), FTLD-TAU (FRONTOTEMPORAL LOBAR DEGENERATION WITH TAU PATHOLOGY WITH P301L TAU MUTATIONS) AND RESILIENT CASES (IN WHICH HIGH PLAQUE BURDEN IS OBSERVED IN THE ABSENCE OF OVERT CLINICAL DEMENTIA). THIS WILL DEFINE THE BREADTH OF VARIATION IN FIBRILLAR STRUCTURE AND ORGANIZATION IN THESE NEUROPATHIES AND TEST THE HYPOTHESIS THAT DISEASE-SPECIFIC POLYMORPHS INTERACT WITH BRAIN TISSUE IN DISTINCT WAYS THAT LEAD TO DIFFERENT ANATOMICAL DISTRIBUTIONS OF PATHOLOGY AND VARIATION IN DISEASE PHENOTYPE. CORRELATION OF OBSERVATIONS ACROSS BRAIN REGIONS AND AT VARIOUS STAGES OF DISEASE WILL MAKE POSSIBLE DETECTION OF PATTERNS IN THE MOLECULAR STRUCTURE OF PLAQUES AND TANGLES, CONSTRUCTION OF A SEQUENCE OF EVENTS THAT MAY REVEAL CAUSAL RELATIONSHIPS AND CLARIFY THE NATURE OF UNDERLYING MOLECULAR PROCESSES AS A BASIS FOR IDENTIFYING MOLECULAR INTERACTIONS ESSENTIAL TO DISEASE PROGRESSION AND THEREBY SUSCEPTIBLE TO CLINICAL INTERVENTION.

COLLABORATIVE RESEARCH: INTERNATIONAL PHYSICS OF LIVING SYSTEMS GRADUATE RESEARCH NETWORK

DESIGNING STRONG STABILITY IN NON-CRITICAL AND RARE-EARTH-LEAN MAGNETIC MATERIALS

THE CENTER FOR RESEARCH ON EARLY CHILDHOOD EXPOSURE AND DEVELOPMENT IN PUERTO RICO (CRECE) AIMS TO PROVIDE VALUABLE NEW INFORMATION ON THE IMPACTS OF

ENDOGENOUS/EXOGENOUS CANNABINOIDS: A COMPARISON

ROLE OF SOCIAL, BEHAVIORAL, AND ECOLOGICAL PROCESSES IN DATING VIOLENCE

SCC: SMART AND CONNECTED CHURCHES FOR PROMOTING HEALTH IN DISADVANTAGED POPULATIONS

RANDOMIZED CONTROLLED TRIAL OF WHOLE BODY VIBRATION INTERVENTION IN TRUCK DRIVER

INDIVIDUAL DIFFERENCES IN BRAIN NETWORKS SUPPORTING SPEECH UNDERSTANDING IN PATIENTSWITH COCHLEAR IMPLANTS - ABSTRACT LISTENERS WITH HEARING IMPAIRMENT CAN OFTEN UNDERSTAND SPOKEN LANGUAGE, BUT WITH INCREASED EFFORT, TAKING COGNITIVE RESOURCES AWAY FROM OTHER PROCESSES SUCH AS ATTENTION AND MEMORY. AN IMPORTANT CHALLENGE IS THEREFORE TO UNDERSTAND HOW THE BRAIN COPES WITH A DEGRADED SPEECH SIGNAL AND THE COGNITIVE PROCESSES THAT ARE MOST CRITICAL TO SUCCESSFUL COMPREHENSION. ADULT LISTENERS WITH COCHLEAR IMPLANTS ARE A UNIQUE GROUP IN WHICH TO INVESTIGATE EFFORTFUL LISTENING: THEY HAVE TYPICALLY ADAPTED TO AUDITORY DEPRIVATION FOR A PERIOD OF YEARS OF PROFOUND HEARING LOSS, FOLLOWED BY SOME DEGREE OF HEARING RESTORATION FOLLOWING IMPLANTATION. FOLLOWING INCREASED AUDITORY INPUT DUE TO COCHLEAR IMPLANTATION, THE DEGREE TO WHICH INDIVIDUAL LISTENERS ARE ABLE TO SUCCESSFULLY RECOGNIZE SPEECH, ESPECIALLY IN THE PRESENCE OF BACKGROUND NOISE, IS EXTREMELY VARIABLE. PREVIOUS ATTEMPTS TO EXPLAIN THIS VARIABILITY IN THE CONTEXT OF UNDERLYING PATTERNS OF BRAIN ACTIVITY HAVE BEEN UNSUCCESSFUL, IN LARGE PART BECAUSE THE TECHNICAL CHALLENGES ASSOCIATED WITH NEUROIMAGING IN THE PRESENCE OF AN IMPLANTED MEDICAL DEVICE HAVE PREVENTED ADEQUATE LOCALIZATION OF NEURAL RESPONSES TO SPEECH. THE GOAL OF OUR RESEARCH IS TO UNDERSTAND THE COGNITIVE SYSTEMS THAT SUPPORT SPEECH RECOGNITION IN LISTENERS WITH COCHLEAR IMPLANTS AND TO USE KNOWLEDGE ABOUT THESE SYSTEMS TO IMPROVE BEHAVIORAL OUTCOMES. WE DO SO USING CONVERGING EVIDENCE FROM BEHAVIORAL MEASURES AND FUNCTIONAL BRAIN IMAGING. WE MAKE USE OF HIGH-DENSITY DIFFUSE OPTICAL TOMOGRAPHY (HD-DOT), A FORM OF OPTICAL BRAIN IMAGING THAT PRODUCES ANATOMICALLY-LOCALIZED INDICES OF REGIONAL CORTICAL ACTIVITY. WE WILL MAP THE BRAIN NETWORKS SUPPORTING SPEECH COMPREHENSION IN LISTENERS WITH COCHLEAR IMPLANTS, WHICH WE EXPECT TO DIFFER FROM THOSE ENGAGED BY LISTENERS WITH GOOD HEARING. WE WILL THEN EVALUATE THE DEGREE TO WHICH NEURAL MARKERS OF EFFORTFUL LISTENING CAN PREDICT INDIVIDUAL DIFFERENCES IN SPEECH RECOGNITION SUCCESS IN THE PRESENCE OF BACKGROUND NOISE. TOGETHER THE FINDINGS WILL HELP GROUND OUR UNDERSTANDING OF COCHLEAR IMPLANT-AIDED SPEECH RECOGNITION IN A NEUROANATOMICALLY-CONSTRAINED FRAMEWORK AND DEVELOP MORE ACCURATE OUTCOME MEASURES.

MRI: DEVELOPMENT OF X-MILI: AN OPEN, PROGRAMMABLE PLATFORM TO CONQUER THE 5G AND 6G WIRELESS SPECTRUM

MULTIPLEXED IMAGING IN THE NEAR INFRARED WITH INDIUM PHOSPHIDE QUANTUM SHELLS

DEVELOPMENT AND DIVERGENCE OF WHOLE-BRAIN ACTIVITY - PROJECT SUMMARY/ABSTRACT AN ANIMAL’S BRAIN CONSISTS OF INTERCONNECTED NEURONS THAT ARE RESPONSIBLE FOR PROCESSING SENSORY INFORMATION OVER MANY TIMESCALES TO GUIDE BEHAVIOR. THE FUNCTION OF THAT BRAIN IS DETERMINED PARTIALLY BY THE ANIMAL’S CONNECTOME – THE TOPOLOGY, STRENGTH, AND VALENCE OF EVERY CONNECTION IN ITS BRAIN. WHILE A DRAFT OF THE WHOLE CONNECTOME FOR AN ANIMAL (THE WORM CAENORHABDITIS ELEGANS) HAS BEEN AVAILABLE FOR DECADES, RECENT WORK HAS FOUND THAT THIS CONNECTOME VARIES DRAMATICALLY THROUGH DEVELOPMENT AND BETWEEN INDIVIDUALS. IT IS NOT STEREOTYPED AS EXPECTED. WE DO NOT KNOW HOW THIS LARGE VARIABILITY IN CONNECTIVITY MANIFESTS ITSELF IN BRAIN ACTIVITY THROUGH DEVELOPMENT OR BETWEEN INDIVIDUALS. NONETHELESS, THE SINGLE CONNECTOME AN ANIMAL HAS MUST SOMEHOW BE ABLE TO SUPPORT EVERY BEHAVIOR THAT THE ANIMAL MAY PERFORM IN A GIVEN INSTANT. EACH OF THESE BEHAVIORS MAY ENGAGE OVERLAPPING PORTIONS OF THE BRAIN. THIS PROJECT AIMS TO LEVERAGE CALCIUM IMAGING TO STUDY HOW WHOLE-BRAIN ACTIVITY IN C. ELEGANS VARIES THROUGH DEVELOPMENT AND BETWEEN INDIVIDUALS. OUR GOAL IS TO CLARIFY PRECISELY HOW LARGE-SCALE STRUCTURE AND FUNCTION ARE RELATED IN A SIMPLE SYSTEM. TO DO THIS, WE WILL PERFORM WHOLE-BRAIN IMAGING WITH CELLULAR RESOLUTION IN A COLLECTION OF BEHAVING INDIVIDUAL ANIMALS AS THEY PROGRESS FROM NEWLY-HATCHED LARVAE THROUGH A SERIES OF MOLTS AND TURN INTO ADULTS. THESE LONG-TERM CALCIUM RECORDINGS WILL BE COMPLEMENTED BY MICROFLUIDIC MEASUREMENTS OF WHOLE-BRAIN RESPONSES TO CHEMOSENSORY CUES AT MULTIPLE DEVELOPMENTAL STAGES. THROUGHOUT THIS PROCESS, WE WILL FOCUS ON THE FOLLOWING BIG QUESTIONS: (1) HOW DOES THE ACTIVITY OF EVERY NEURON IN A WORM CHANGE THROUGH DEVELOPMENT? (2) HOW DOES BRAIN ACTIVITY VARY BETWEEN GENETICALLY IDENTICAL INDIVIDUALS? (3) HOW ARE EACH OF THE ABOVE QUESTIONS AFFECTED BY CHANGES IN ENVIRONMENTAL CONTEXT? (4) HOW DOES THE RELATIONSHIP BETWEEN BRAIN ACTIVITY AND CONNECTIVITY CHANGE OVER DEVELOPMENT, AND HOW DOES IT VARY BETWEEN INDIVIDUALS? IF SUCCESSFUL, THIS WORK COULD PROVIDE UNPRECEDENTED INSIGHT INTO HOW BRAIN FUNCTION CHANGES AS AN ANIMAL ADDS NEURONS, CONNECTIONS, AND SYNAPSES. IT WILL SHOW HOW INTER-INDIVIDUAL AND INTRA-INDIVIDUAL VARIATION ARE RELATED TO THE BRAIN’S CONNECTOME. THIS WILL HAVE IMMEDIATE VALUE IN GUIDING EXPECTATIONS ABOUT HOW BRAIN ACTIVITY AND BRAIN WIRING ARE RELATED IN OTHER MODEL SYSTEMS AND HUMANS, WHERE DIRECT INFORMATION ABOUT WIRING IS LESS READILY AVAILABLE.

TARGETING ADOLESCENT DEPRESSION SYMPTOMS USING NETWORK-BASED REAL-TIME FMRI NEUROFEEDBACK AND MINDFULNESS MEDITATION - PROJECT SUMMARY ADOLESCENT MAJOR DEPRESSIVE DISORDER (MDD) IS COMMON AND DEBILITATING. PRESENTLY, GOLD-STANDARD TREATMENTS ARE ONLY EFFECTIVE FOR APPROXIMATELY HALF OF PATIENTS, UNDERSCORING THE NEED TO DEVELOP NOVEL INTERVENTIONS, PARTICULARLY TO TARGET CORE UNDERLYING MECHANISMS AND MORE EFFECTIVELY TREAT THIS RECURRENT DISORDER. RUMINATION, THE TENDENCY TO PERSEVERATE ABOUT DEPRESSIVE SYMPTOMS, CONTRIBUTES TO MDD ONSET AND PREDICTS TREATMENT NON-RESPONSE AND RELAPSE. AT THE NEURAL LEVEL, RUMINATION IS CHARACTERIZED BY ELEVATED FUNCTIONAL CONNECTIVITY WITHIN THE DEFAULT MODE NETWORK (DMN), AND PRIOR RESEARCH ALSO HAS CONSISTENTLY DEMONSTRATED PATTERNS OF DMN HYPERCONNECTIVITY IN MDD. INTERESTINGLY, MINDFULNESS MEDITATION, WHICH TRAINS ATTENTIONAL FOCUS TO THE PRESENT MOMENT, REDUCES PERSEVERATIVE THINKING, RUMINATIVE TENDENCIES, AND DEPRESSION SYMPTOMS. FURTHER, OUR RESEARCH AND OTHERS HAVE SHOWN THAT ADOLESCENTS CAN APPLY MINDFULNESS PRACTICES TO DECREASE PERCEIVED STRESS, INCREASE SUSTAINED ATTENTION, AND SUPPRESS DMN ACTIVITY. ALTHOUGH MINDFULNESS HAS PROFOUND MENTAL HEALTH BENEFITS, FOR SOME, MINDFULNESS ALONE MAY NOT BE SUFFICIENT TO MITIGATE RUMINATIVE TENDENCIES DURING A DEPRESSIVE EPISODE. THAT IS, MDD SYMPTOMS, INCLUDING REDUCED MOTIVATION, INATTENTION, AND LACK OF SELF-EFFICACY, MAY IMPEDE A PATIENT’S PROGRESS IN SUCCESSFULLY ACQUIRING AND UTILIZING MINDFULNESS STRATEGIES NECESSARY TO CHANGE PERCEPTIONS ABOUT ONE’S ENVIRONMENT AND RELATIONSHIPS. TO DIRECTLY ADDRESS THIS CHALLENGE, WE PROPOSE USING REAL-TIME FMRI NEUROFEEDBACK TO ENHANCE THE ACQUISITION AND UTILIZATION OF MINDFULNESS SKILLS TO BETTER TARGET DMN HYPERCONNECTIVITY, RUMINATION, AND DEPRESSIVE SYMPTOMS. WE DEVELOPED A NOVEL, 15-MINUTE MINDFULNESS-BASED, REAL-TIME NEUROFEEDBACK (MBNF) PARADIGM WHEREBY PEOPLE OBSERVE A VISUAL DISPLAY OF THEIR BRAIN ACTIVITY AND PRACTICE MINDFULNESS TO VOLITIONALLY REDUCE DMN ACTIVATION. IN THE R61 PHASE, 90 ADOLESCENTS (AGES 13-18) DIAGNOSED WITH MDD WILL COMPLETE A 45-MINUTE MINDFULNESS TRAINING OUTSIDE THE SCANNER. TO TEST TARGET ENGAGEMENT OF REDUCING DMN HYPERCONNECTIVITY AND OPTIMAL DOSING, ADOLESCENTS WILL THEN BE RANDOMIZED TO RECEIVE EITHER A 15- OR A 30-MINUTE MBNF SESSION (N=45/DOSE GROUP). IF WE MEET OUR GO CRITERION (I.E., SIGNIFICANTLY REDUCING DMN HYPERCONNECTIVITY), WE WILL THEN PROCEED TO THE R33 PHASE TO INVESTIGATE WHETHER MINDFULNESS WITH MBNF OUTPERFORMS MINDFULNESS ONLY. THUS, A NEW SAMPLE OF 120 DEPRESSED ADOLESCENTS (AGES 13-18) WILL PARTICIPATE IN A DOUBLE-BLIND RANDOMIZED CLINICAL TRIAL AND RECEIVE MINDFULNESS WITH THE OPTIMAL MBNF DOSE (I.E., PER THE R61) OR MINDFULNESS ONLY (N=60/GROUP). WE WILL TEST–USING CLINICIAN-ADMINISTERED INSTRUMENTS, SELF-REPORTS, AND ECOLOGICAL MOMENTARY ASSESSMENT– WHETHER COMPARED TO MINDFULNESS ONLY, MINDFULNESS WITH MBNF CONTRIBUTES TO A GREATER REDUCTION IN CLINICIAN ASSESSED DEPRESSION SYMPTOMS (PRIMARY OUTCOME) AS WELL AS DECREASED RUMINATION (SECONDARY OUTCOME) ACROSS THE POST-TREATMENT, 1-MONTH, AND 3-MONTH ASSESSMENTS. AS A WHOLE, MBNF IS DIRECTLY IN LINE WITH PRECISION MEDICINE INITIATIVES, AND IF SUCCESSFUL, COULD REVOLUTIONIZE CLINICAL CARE FOR DEPRESSED ADOLESCENTS.

CANNABINERGIC LIGANDS AND DRUGS

EXPERIMENTAL PARTICLE PHYSICS RESEARCH AT HIGH ENERGIES -EXPERIMENTAL PARTICLE PHYSICS RESEARCH AT HIGH ENERGIES NORTHEASTERN UNIVERSITY THE HIGH ENERGY FRONTIER OF PARTICLE COLLISIONS PROVIDES ONE OF THE BEST OPPORTUNITIES TO DISCOVER NEW PARTICLES AND GAIN NEW UNDERSTANDING OF HOW PARTICLES INTERACT AT THE SMALLEST DISTANCE SCALE. THE STANDARD MODEL OF PARTICLE PHYSICS PROVIDES THEORETICAL PREDICTIONS FOR THESE INTERACTIONS, BUT THIS MODEL IS KNOWN TO BE INCOMPLETE, AND EXPERIMENTS ARE NEEDED TO FIND WHAT LIES BEYOND THOSE PREDICTIONS. THE LARGE HADRON COLLIDER (LHC) AT THE CERN LABORATORY HOUSES THE WORLD?S HIGHEST ENERGY HUMAN-MADE PARTICLE COLLISIONS. THE COMPACT MUON SOLENOID (CMS) EXPERIMENT AT THE LHC IS A POWERFUL MULTIPURPOSE PARTICLE DETECTOR THAT ACTS LIKE A COMPLEX CAMERA, WHICH AIMS TO OBSERVE AND RECORD WHAT HAPPENS IN SUCH COLLISIONS. THIS PROJECT SUPPORTS THE WORK OF THREE FACULTY MEMBERS AT NORTHEASTERN UNIVERSITY PLUS SEVERAL POSTDOCTORAL RESEARCHERS AND STUDENTS TO CONDUCT EXPERIMENTAL PARTICLE PHYSICS RESEARCH WITH THE CMS EXPERIMENT. WITH THE COMBINED POWER OF DATA ALREADY RECORDED AND NEW DATA BEING RECORDED, THEY USE MODERN STATISTICAL AND MACHINE-LEARNING TECHNIQUES TO COMPARE THEORETICAL PREDICTIONS WITH THE OBSERVED DATA IN AREAS TAILORED TO THEIR EXPERTISE: STANDARD MODEL PHYSICS, HIGGS STUDIES, AND SEARCH FOR PHYSICS BEYOND THE STANDARD MODEL. THE KNOWLEDGE GAINED FROM THESE STUDIES WILL REFINE THE PREDICTIONS OF PARTICLE THEORY AND FURTHER THE QUEST FOR UNDERSTANDING OUR UNIVERSE AT THE SMALLEST DISTANCE SCALES. THE PROJECT ALSO INCLUDES OPERATION OF THE CMS DETECTOR DURING LHC RUN 3, AS WELL AS DEVELOPMENT OF DETECTOR UPGRADES THAT WILL ADVANCE THE SOPHISTICATED INSTRUMENTATION THAT IS USED IN PARTICLE DETECTION AND HAS BROADER APPLICATIONS. THESE UPGRADES WILL ENABLE CMS TO EXPLOIT FUTURE HIGH LUMINOSITY RUNNING OF THE LHC (HL-LHC) AND ENSURE THAT THE INSTRUMENTS ARE AVAILABLE TO FUTURE GENERATIONS OF SCIENTISTS. IN THE THREE YEARS SPANNED IN THE PROPOSED WORK, THE ANALYSIS OF THE FULL DATA SET FROM CMS FROM RUN 2 WILL REACH COMPLETION, AND SEVERAL ANALYSIS PROJECTS WILL DEVELOP THAT WILL TARGET OR INCLUDE THE DATA ACCUMULATED IN RUN 3. THE NORTHEASTERN UNIVERSITY CMS GROUP WILL PURSUE SOME TARGETED SEARCHES FOR NEW PHYSICS MOTIVATED BY RECENT ANOMALIES OR COMPELLING THEORETICAL QUESTIONS: LEPTOQUARK SEARCHES, WHICH COULD ADDRESS ANOMALIES OBSERVED IN THE MEASUREMENT OF G-2 OF THE MUON; THE PRODUCTION OF PAIRS OF HIGGS BOSONS IN MULTIPLE DECAY CHANNELS, WHICH CAN SIGNAL NEW PHYSICS IN PRODUCTION OR COUPLINGS, AND WILL ULTIMATELY GIVE INSIGHT INTO THE FORM OF THE HIGGS POTENTIAL. AT THE SAME TIME, THE GROUP WILL USE THE WELL-UNDERSTOOD RUN 2 CMS DATA TO INCREASE THE PRECISION AND SCOPE OF MEASUREMENTS OF STANDARD MODEL PRODUCTION OF THE HIGGS BOSON, AS WELL AS W+JETS AND ZZ PAIRS. THE RESULTS OF THESE MEASUREMENTS WILL BE VERY IMPORTANT FOR MAKING PRECISE PREDICTIONS OF BACKGROUND PROCESSES FOR SEARCHES AT THE HL-LHC. CRITICAL SUPPORT PROVIDED BY THE GROUP TO THE CMS EXPERIMENT TO CONTINUE THE HIGH-EFFICIENCY OPERATION OF THE MUON DETECTION AND TRIGGERING, AND OF THE ELECTROMAGNETIC CALORIMETRY SYSTEMS WILL HELP TO PROVIDE DATA USED BY THE ENTIRE CMS COLLABORATION FOR AN EVEN BROADER PROGRAM OF PARTICLE PHYSICS INVESTIGATIONS. IN THE PREPARATION FOR THE HL- LHC, THE WORK OF THE GROUP WILL IMPLEMENT NEW CAPABILITIES FOR EXTRACTING PHYSICS IN THE HIGH-RATE ENVIRONMENT THROUGH UPGRADES TO THE ELECTRONICS OF THE MUON SYSTEM, MUON TRIGGER, AND ELECTROMAGNETIC CALORIMETER TO ACCOMMODATE A MUCH HIGHER RATE OF DATA, AND THROUGH THE REALIZATION OF A NEW TIMING DETECTOR TO DISAMBIGUATE THE LARGE NUMBER OF MULTIPLE INTERACTION VERTICES. THE NORTHEASTERN UNIVERSITY CMS GROUP WILL ALSO PURSUE BROADER IMPACT THROUGH EFFORTS TO IMPROVE DIVERSITY, INCLUSION, AND MENTORING, AND THROUGH OUTREACH AND ENGAGEMENT TO THE WIDER SCIENTIFIC COMMUNITY AND GENERAL PUBLIC. THE GROUP WILL PROVIDE SPECIAL OPPORTUNITIES FOR INTERACTIONS BY BRINGING PHYSICISTS FROM AROUND THE WORLD TO THE LHCP CONFERENCE HOSTED AT THE NORTHEASTERN UNIVERSITY CAMPUS IN 2024. 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.

REDUCING URBAN WOMEN'S HIV RISK: SOAP OPERA VIDEOS ON VIDEO CAPABLE CELL PHONES

SYMPATHETIC NERVOUS SYSTEM MEDIATION OF ACUTE EXERCISE EFFECTS ON CHILDHOOD BRAIN AND COGNITION

EPIDEMIC SURGE MODEL USE TO IMPROVE PATIENT, STAFF, AND SYSTEM SAFETY AND RESILIENCY - PROJECT SUMMARY BROAD AGREEMENT EXISTS THAT FUTURE EPIDEMICS WILL OCCUR, BETTER PREPAREDNESS IS NEEDED FOR MANAGING SURGES, AND MUCH SHOULD BE LEARNED FROM THE COVID-19 PANDEMIC. THE SARS-COV-2 VIRUS TO-DATE HAS CAUSED OVER 46 MILLION INFECTIONS, 3.25 MILLION HOSPITALIZATIONS, AND 745,000 DEATHS IN THE U.S. ALONE, WITH REGIONAL SURGES OF VARIED TIMING, MAGNITUDE, AND DURATION PROFOUNDLY STRAINING HEALTHCARE CAPACITY AND IMPACTING PATIENT, STAFF, AND SYSTEM SAFETY. AS WITH OTHER EPIDEMICS, LOCAL OUTBREAKS AND SURGES CONTINUOUSLY CHANGE, OFTEN RESULTING IN CRISIS MANAGEMENT, MAKESHIFT ROOMING, SUB-STANDARD PERSONAL PROTECTION EQUIPMENT, AND RATIONING OF LIMITED RESOURCES. AMONG OTHER NEEDS, BETTER REAL-TIME METHODS ARE NEEDED TO ANTICIPATE HOSPITAL, EQUIPMENT, AND STAFF CAPACITIES AND SHORTAGES TO ALLOW EARLIER PREEMPTIVE MITIGATION (GAP). WHILE ANALYTIC MODELS ARE INCREASINGLY USED, MOST ARE AT THE MORE MACRO POLICY LEVEL RATHER THAN FACILITY-SPE- CIFIC OPERATIONAL LEVEL (GAP), IN THE LATTER CASE WITH LITTLE KNOWN ABOUT THEIR USE IN PRACTICE, ACCURACY, DECISION- MAKING WORKFLOW, ADOPTION, UTILITY, AND IMPACT ON OPERATIONS, OUTCOMES, AND SAFETY. IN OUR OWN WORK, WE DEVEL- OPED AND WIDELY DEPLOYED INTEGRATED MODELS THAT PREDICT FACILITY-SPECIFIC AND UNIT-SPECIFIC DEMAND, ADAPT TO REAL-TIME CHANGES IN THESE, AND ESTIMATE 4-WEEK AHEAD DAILY CAPACITY, DEMAND, AND SHORTAGES (ROOMS, EQUIP- MENT, STAFF) WITHIN ANY GIVEN FACILITY, DOWNLOADED BY SYSTEMS IN ALL 50 STATES AND 91 COUNTRIES. WHILE USE OF SYSTEMS ENGINEERING MODELS IS WELL-ACCEPTED IN OTHER SETTINGS, THEIR USE, UTILITY, AND IMPACT IS SIGNIFICANTLY UN- DER-STUDIED IN THIS IMPORTANT CONTEXT AND HEALTHCARE MORE GENERALLY, WITH POTENTIALLY IMPORTANT LESSONS FOR THE FUTURE (GAP). THIS PROJECT THUS WILL TAKE A MULTI-METHODS APPROACH TO (AIM 1) CONDUCT MODELING RESEARCH TO FURTHER REFINE RE- SULTS TO-DATE, OPTIMIZE ACCURACY, AND ADDRESS IDENTIFIED TECHNICAL NEEDS, (AIM 2) EVALUATE IMPACTS AND ACCU- RACY OF THE DEVELOPED MODELS ON IMPROVED HOSPITAL CAPACITY AND SAFETY UNDER A WIDE RANGE OF SIMULATED FUTURE AND PAST SURGE SCENARIOS, AND (AIM 3) MAXIMIZE FUTURE UTILITY BY STUDYING HOW OUR MODELS WERE USED IN PRAC- TICE DURING COVID-19, THE MODEL ADOPTION PROCESS, TYPES OF RESULTING ACTIONS, BARRIERS TO USE, AND USER PERCEP- TIONS OF UTILITY, ACCURACY, AND MODEL-BASED DECISION-MAKING. THE PROJECT WILL BE LED BY AN EXPERIENCED INTERDIS- CIPLINARY HEALTHCARE MODELING TEAM, WORKING CLOSELY WITH VARIED HOSPITAL DATA SITES AND AN ADVISORY COMMITTEE WITH EXPERTISE IN PATIENT SAFETY, EPIDEMIC RESPONSE, HOSPITAL SURGES, AND MODELING. ANTICIPATED RESULTS INCLUDE (1) VALIDATED ROBUST MODELS FOR PREEMPTIVELY ANTICIPATING AND RESPONDING TO CARE SURGES, (2) REDUCED UNSAFE HOSPITAL CRISIS MANAGEMENT CONDITIONS DURING FUTURE EPIDEMICS, AND (3) IMPROVED UNDERSTANDING OF HOW TO BEST USE SYSTEMS ENGINEERING MODELS TO ADDRESS EPIDEMIC SURGES AND OTHER IMPORTANT PUBLIC HEALTH AND CARE DELIV- ERY PROBLEMS.

INTERPRETER TRAINING PROGRAM

DEVELOPING INTEGRATIVE MANUFACTURING AND PRODUCTION ENGINEERING CURRICULA THAT LEVERAGE DATA SCIENCE

ASYMMETRIC SINGLE-CHAIN MSPA NANOPORES FOR ELECTROOSMOTIC STRETCHING AND SEQUENCING PROTEINS - PROJECT SUMMARY / ABSTRACT PROTEIN IDENTIFICATION AND/OR SINGLE-MOLECULE PROTEIN SEQUENCING FROM MINUTE AMOUNTS COULD REVOLUTIONIZE OUR UNDERSTANDING OF HEALTH BY PROVIDING A PICTURE OF THE MOLECULAR STATE OF THE CELL AT THE LEVEL OF ITS MOST FUNCTIONAL MOLECULES. THROUGH THIS MULTI-PI PROPOSAL, WE WILL DEVELOP PROTOTYPE TOOLS THAT EMPLOY INNOVATIVE PROTEIN-BASED NANOPORES FOR PROBING THE SEQUENCE OF INDIVIDUAL PROTEIN MOLECULES. THE PROTEIN SEQUENCING TOOL IS BASED ON ENGINEERED MSPA, A PORIN FROM MYCOBACTERIUM SMEGMATIS THAT HAS BEEN UTILIZED IN NANOPORE- BASED DNA SEQUENCING. HOWEVER, OUR PROTEIN DETECTION/SEQUENCING TOOL WILL BE ENGINEERED IN THE FOLLOWING WAYS: 1) EACH OF THE PROTEIN MONOMERS THAT COMPRISE THE OCTAMERIC ASSEMBLY ARE COVALENTLY CONNECTED, ENABLING MUTAGENESIS ALONG THIS SINGLE-CHAIN MSPA (SCMSPA) PROTEIN TO CREATE A SERIES OF MUTANTS WITH ASYMMETRIC CONSTRICTIONS AS HIGH-RESOLUTION NANOPORES FOR READING AMINO ACID SEQUENCES (RECENTLY DEMONSTRATED BY NIEDERWEIS AND WANUNU GROUPS), 2) A DNA-PROCESSING ENZYME WILL BE USED TO MOVE SHORT PEPTIDES AND FULL-LENGTH PROTEINS THROUGH THE PORE BY CONJUGATION OF THESE PEPTIDES TO DNA AND ATP-MEDIATED DNA TRANSLOCATION, 3) THE FULL COMPATIBILITY OF OUR SYSTEM WITH DENATURING ELECTROLYTE CONDITIONS DURING PORE EXPERIMENTS WILL FACILITATE THREE CRITICAL REQUIREMENTS FOR HIGH ACCURACY PEPTIDE/PROTEIN READOUT IN A SEQUENCE- INDEPENDENT MANNER - PROTEIN UNFOLDING, PROTEIN THREADING, AND A DRIVING FORCE TO STRETCH THE PROTEIN SO IT IS PULLED TAUT AT THE PORE (ALL OF THESE RECENTLY DEMONSTRATED BY WANUNU, AKSIMENTIEV, AND CHEN GROUPS). THESE COMBINED INNOVATIONS, COMBINED WITH KEY TECHNOLOGICAL CAPABILITIES OF THE TEAM, WILL ALLOW US TO DEVELOP A PROTEIN SEQUENCING PROTOTYPE. WE PROPOSE TO ACHIEVE OUR GOALS THROUGH RESEARCH IN THREE MAIN AIMS: 1) WE WILL ENGINEER AND TEST VARIOUS ASYMMETRIC SCMSPA MUTANTS TO OPTIMIZE SIGNAL CONTRAST FROM SIMILAR PROTEIN SEQUENCES WITH SINGLE AMINO ACID SUBSTITUTIONS, 2) WE WILL DEMONSTRATE HELICASE-MEDIATED MOTION OF PEPTIDE LIBRARIES THROUGH SCMSPA MUTANTS AND SIGNAL DECODING, AND 3) WE WILL READ SUBSETS OF FULL-LENGTH UNFOLDED PROTEINS IN A COMPLEX SAMPLE THAT CONTAINS MANY PROTEINS, AND TRAIN A MODEL TO RECOGNIZE THIS SETS BASED ON PURE PROTEIN SAMPLES. FOR THE MOST PROMISING MUTANT SCMSPA WE WILL TARGET >90% ACCURACY IN DISTINGUISHING AMONG ALL PEPTIDES/PROTEINS IN THE SAMPLE SET. SUCCESS IN OUR DEVELOPED PLATFORM WILL RESULT IN ADOPTION AND PRODUCT DEVELOPMENT IN ORDER TO REVOLUTIONIZE SINGLE-MOLECULE AND SINGLE-CELL PROTEOMICS.

PURPOSE: THE PURPOSE OF NORTHEASTERN UNIVERSITY'S PROJECT IS TO DEVELOP AND OPERATIONALIZE-IN THE NORTHEASTERN UNIVERSITY OTIC-DIGIRAN, A HIGH-FIDELITY WIRELESS NETWORK DIGITAL TWIN (DT) PLATFORM WITH HARDWARE-IN-THE-LOOP. DIGIRAN IS A FRAMEWORK DESIGNED TO STREAMLINE LOW-COST, REAL-TIME, REPEATABLE, AND AUTOMATED TESTING AND EVALUATION OF THE INTEROPERABILITY, PERFORMANCE, AND SECURITY OF OPEN 5G RADIO ACCESS NETWORKS IN HETEROGENEOUS, EMULATED, TESTING ENVIRONMENTS. ACTIVITIES TO BE PERFORMED: THE PROJECT WILL BE PERFORMED IN 4 DISTINCT INTERTWINED THRUSTS: 1) DEVELOP A PIPELINE TO CREATE AND EVALUATE VIRTUAL WIRELESS WORLDS VIA FAST RAY-TRACING TOOLS WITH NEAR REAL-TIME UPDATES BETWEEN PHYSICAL AND DIGITAL TWINS; 2) DESIGN AN AUTOMATED PROTOCOL STACK TWINING FRAMEWORK FOR CONTINUOUS TESTING OF STANDARDS-BASED 5GRAN; 3) ENABLE REAL-TIME NETWORKING INFRASTRUCTURE BETWEEN REAL AND VIRTUAL WORLDS WITH APIS TO TEST FIDELITY ACROSS THE TWINS AND DEVELOP RAN INTELLIGENT CONTROLLER SOLUTIONS; AND 4) DEVELOP A PLATFORM FOR SEAMLESS INTEGRATION OF COMMODITY OPEN RAN UNITS (CU, DU, RU) TO THE DIGITAL TWIN EMULATION SYSTEM TO PERFORM REQUIRED PERFORMANCE, SECURITY, AND INTEROPERABILITY TESTING. EXPECTED OUTCOMES: THE PRIMARY OUTCOME OF THIS PROJECT IS THE DEVELOPMENT AND USE OF HIGH-FIDELITY DIGITAL TWINS THAT WILL ENABLE EFFICIENT AND REPEATABLE TESTING OF MULTI-VENDOR INTEROPERABILITY, PERFORMANCE, AND SECURITY AT A FRACTION OF THE COST. INTENDED BENEFICIARIES: BENEFICIARIES OF THIS PROJECT INCLUDE STAKEHOLDERS IN O-RAN DEVELOPMENT INCLUDING INSTITUTIONS AND USERS IN THE U.S. AND GLOBALLY SUCH AS TELECOM OPERATORS, VENDORS, AND INTEGRATORS INVOLVED WITH WIOT THAT FOSTERS INNOVATION THROUGH RESEARCH COMMERCIALIZATION LED BY 6 SPINOFFS. SUBRECIPIENT ACTIVITIES: NORTHEASTERN UNIVERSITY IS NOT PROPOSING ANY SUBRECIPIENTS OR SUBRECIPIENT ACTIVITIES.

PURPOSE: NORTHEASTERN UNIVERSITY'S PROJECT PURPOSE IS TO DEVELOP AND OPERATIONALIZE AUTORAN, A NEW TESTING METHODOLOGY BASED ON A COLLECTION OF AUTOMATED AND CONTINUOUS SOFTWARE PIPELINES DESIGNED TO AUTOMATICALLY TEST DISAGGREGATED RADIO ACCESS NETWORK (RAN) COMPONENTS. ACTIVITIES TO BE PERFORMED: THE APPLICANT PROPOSES TO 1.) EXTEND PRIVATE SG CL/CD PIPELINES TO COVER THE TASKS REQUIRED FOR CT, I.E., TESTING AND RAN EQUIPMENT/SERVICES ORCHESTRATION, REPEATABLE BUILDS, INTERFACE CODE GENERATION, AND SYSTEM MONITORING AND ANALYTICS, 2.) MANAGE THE INPUT AND OUTPUT OF THE AUTOMATED TESTING PROCESS AND DEFINE THE SCRIPTING LANGUAGE AND THE NORTHBOUND APLS THAT ARE USED TO INTELLIGENTLY ORCHESTRATE THE TESTING WORKLOADS AND PARSE THEIR RESULTS, 3.) BRING TOGETHER THE CT PIPELINES AND AUTOMATED INPUT/OUTPUT TEST DEFINITION AND ANALYSIS ON THE OPEN6G OTIC INFRASTRUCTURES, AND 4.) COORDINATE EFFORTS ACROSS THE PROJECT, INCLUDING ACTIVITIES OF THE SUB-AWARDEE AND COLLABORATORS, INTERACT WITH THE OTIC INDUSTRIAL STAKEHOLDERS AND THE MEMBER OF THE WLOT INDUSTRY CONSORTIUM, AND DISSEMINATE CAPABILITIES AND STANDARD-RELATED INSIGHTS IN THE RELEVANT FORA. EXPECTED OUTCOMES: AUTOMATED AND CONTINUOUS TESTING WILL INCREASE THE ROBUSTNESS OF THE WIRELESS SUPPLY CHAIN BY ALLOWING SWIFT AND CONTINUOUS INTEGRATION OF NEW EQUIPMENT AND FUNCTIONALITIES FROM MULTIPLE VENDORS IN LARGE MOBILE NETWORK OPERATOR (MNO) NETWORKS BUT ALSO IN SMALLER PRIVATE 5G DEPLOYMENTS FOR NEW VERTICAL MARKETS. IT WILL ALSO ENABLE A CONTINUOUS CYCLE THAT ALLOWS FOR THE VALIDATION OF NEW FEATURE AND CODE AS SOON AS THEY ARE ADDED TO THE NETWORK, BEFORE DEPLOYMENTS ARE AVAILABLE, BUT STILL IN A COMPLETE, END-TO-END OPEN RAN SANDBOX. INTENDED BENEFICIARIES: THIS PROJECT BENEFITS INTEGRATORS, VENDORS, SERVICE PROVIDERS, INSTITUTIONS, RESEARCHERS, CUSTOMERS, AND USERS OF BOTH LARGE MOBILE NETWORK OPERATOR (MNO) NETWORKS AND SMALLER PRIVATE 5G DEPLOYMENTS FOR NEW VERTICAL MARKETS, UNLOCKING SUPPLY CHAIN DIVERSITY, AND DRIVING INNOVATION IN PUBLIC/PRIVATE NETWORKS. SUBRECIPIENT ACTIVITIES: THIS PROJECT DOES NOT ANTICIPATE USING SUBRECIPIENTS OR SUBAWARDS.

NU STEP-UP

PURPOSE: NORTHEASTERN UNIVERSITY WILL CREATE A FINE-GRAIN, END-TO-END, AND ACCURATE ENERGY EFFICIENCY TESTING PLATFORM REFERRED TO AS TENORAN, WHICH WILL ENABLE THE CONSTRUCTION OF SUSTAINABLE AND ENERGY-EFFICIENT WIRELESS NETWORKS. ACTIVITIES TO BE PERFORMED: ADVANCE 5G (AND BEYOND) TESTING CAPABILITIES BY DESIGNING AND DELIVERING A TESTING PLATFORM CAPABLE OF PRODUCING FINE-GRAINED ENERGY CONSUMPTION REPORTS FOR OPEN RAN SYSTEMS, THUS CONTRIBUTING TO SUSTAINABILITY EFFORTS CONTRIBUTE TO THE EVOLUTION OF OPEN RAN BY IDENTIFYING AND RECOMMENDING REPEATABLE AND PROGRAMMATIC TESTING PROCEDURES AND FUNCTIONALITIES TO SUPPORT MULTI-VENDOR AND VERTICAL ENERGY EFFICIENCY OPTIMIZATION. EXPECTED OUTCOMES: TENORAN WILL SERVE AS A PLATFORM FOR BUILDING THE NEXT GENERATION OF SUSTAINABLE AND ENERGY-EFFICIENT WIRELESS NETWORKS. INTENDED BENEFICIARIES: OPEN RAN PRODUCT DEVELOPERS, CELLULAR MOBILE NETWORK OPERATORS (MNOS), ACADEMIC RESEARCHERS.SUBRECIPIENT ACTIVITIES: THE RECIPIENT DOES NOT PLAN TO SUBAWARD FUNDS.

PRISM: ATTRACTING STUDENTS TO MATHEMATICS, PHYSICS, AND BIOLOGY THROUGH INTERDISCIPLINARY RESEARCH AND DISCOVERY

CRCNS RESEARCH PROPOSAL: COLLABORATIVE RESEARCH: NEURAL BASIS OF MOTOR EXPERTISE

ENGINEERING MULTIFACETED 3D HUMAN ORGAN PLATFORMS FOR TOXICITY TESTING - PROJECT SUMMARY THIS AWARD WILL ACCELERATE MY LONG-TERM GOAL TO DEVELOP MICROPHYSIOLOGICAL SYSTEMS TO IMPROVE HUMAN PHARMACOLOGICAL EFFICACY WITH REDUCED TOXICITY AND RELIANCE ON SMALL ANIMAL MODELS. MODELS OF THE CARDIOVASCULAR SYSTEM (VASCULAR, MYOCARDIUM, ADRENAL MEDULLA) IN VITRO HAVE PRIMARILY BEEN LIMITED TO SIMPLIFIED 2D STRUCTURES AND HAVE NOT EVALUATED FOR TISSUE-TISSUE INTERACTIONS. AS SUCH, THE STRUCTURE/FUNCTION RELATIONSHIPS, AND THE CELL-CELL INTERACTIONS DRIVEN BY TISSUE ORGANIZATION AND INNERVATION REMAIN POORLY UNDERSTOOD. THUS, MPS THAT RECAPITULATES KEY COMPONENTS OF THE HUMAN CARDIOVASCULAR SYSTEM, INCLUDING PHYSIOLOGICALLY RELEVANT SHEAR FLOW, OXYGEN SATURATION, BIOELECTRIC STIMULATION, PRIMARY HUMAN ENDOTHELIAL, SMOOTH MUSCLE, CARDIOMYOCYTES, CHROMAFFIN CELLS, AND HUMAN AUTONOMIC NEURONS WOULD BE A VALUABLE TOOL FOR ADVANCING SCIENTIFIC DISCOVERY, HEALTHCARE, COMPOUND SCREENING, AND BIOMEDICAL RESEARCH. CURRENT MPS GENERALLY UTILIZE SPECIALIZED EQUIPMENT AND TRADITIONAL MICROFABRICATION TECHNIQUES VIA SOFT LITHOGRAPHY WITH POLYDIMETHYLSILOXANE (PDMS), MAKING MICROFLUIDIC PLUMBING DIFFICULT AS WELL AS NEARLY IMPOSSIBLE CONTROL OF OXYGEN, AND POTENTIAL FOR ANALYTE LOSS. THEREFORE, NEW FABRICATION APPROACHES THAT DEVIATE FROM PDMS ARE NEEDED. OUR APPROACH HERE DESCRIBES THE APPLICATION OF A LASER-FABRICATED, CUT AND ASSEMBLED MPS FOR A FULLY HUMANIZED SYSTEM. THERE IS A SCIENTIFIC AND CLINICAL URGENCY FOR THE DEVELOPMENT OF NEW TOOLS TO IDENTIFY COMPOUND TOXICITY AND DECREASE NEW COMPOUND ATTRITION DURING CLINICAL TRIALS. BY APPLYING MY STRENGTHS IN BIOMATERIALS, ORGAN-CHIP DESIGN, BIOELECTRONICS, AND NEUROENGINEERING, WE WILL ACCELERATE THE DEVELOPMENT OF ROBUST 3D, INSTRUMENTED MPS PLATFORMS OF THE CARDIOVASCULAR SYSTEM. A FUNDAMENTAL ISSUE ADDRESSED IN THIS PROJECT WILL BE THE ABILITY TO INTEGRATE, IN A SCALABLE PLATFORM, INSTRUMENTATION FOR STIMULATION AND RECORDING OF NEURAL, ADRENAL, AND CARDIAC ACTIVITY TO BETTER ELUCIDATE THE IMPACT OF THE AUTONOMIC NERVOUS SYSTEM AND COMPOUND TOXICITY. WE WILL HARNESS A STATISTICAL MODEL TO IDENTIFY DRIVING FACTORS IN CELL FATE, FUNCTION, AND IDENTIFY SEX-BASED DIFFERENTIAL RESPONSES IN AUTONOMIC BALANCE ON THE MPS. THESE INNOVATIVE MODELS WILL INTEGRATE RECENT ADVANCES IN STEM CELL DIFFERENTIATION AND OUR PROVEN ‘CUT & ASSEMBLE’ FABRICATION METHOD TO BROADLY DISSEMINATE THESE ORGAN PLATFORMS.

CUE-T: A STUDY OF THE CREATION OF INTERDISCIPLINARY COMPUTING MAJORS - THEIR IMPLEMENTATION AND IMPACT ON BROADENING PARTICIPATION IN COMPUTING AT 10 PUBLIC UNIVERSITIES -ACCORDING TO THE OCCUPATIONAL OUTLOOK HANDBOOK, EMPLOYMENT OPPORTUNITIES IN COMPUTING ARE PROJECTED TO GROW MUCH FASTER THAN ALL OTHER DISCIPLINES. THE GOAL OF THIS PROJECT, A COLLABORATION BETWEEN THE CENTER FOR INCLUSIVE COMPUTING AND 10 LARGE PUBLIC UNIVERSITIES LOCATED ACROSS EIGHT DIFFERENT STATES, IS TO IMPLEMENT A SERIES OF INTERDISCIPLINARY COMPUTING MAJORS (ICMS) IN SUCH A WAY THAT STUDENTS WHO ARE NEW TO COMPUTING, AND DID NOT ENTER UNIVERSITY AS COMPUTING MAJORS, ARE ATTRACTED TO DISCOVER AND PERSIST IN THEIR CHOSEN ICM. THE EXPECTED OUTCOME OF THIS PROJECT IS AN INCREASE IN THE NUMBER OF UNIVERSITIES OFFERING ICMS, AND A MORE DIVERSE POOL OF CAREER-READY GRADUATES WHO CAN SATISFY THE GROWING NEED FOR COMPUTING OCCUPATIONS IN THE UNITED STATES. THE PROJECT TEAM WILL EXAMINE THE RESULTS AND IMPACT OF THE IMPLEMENTATION OF THE ICMS AND DOCUMENT THE OUTCOMES IN A SET OF CASE STUDIES THAT EXPLAIN THE IMPLEMENTATION PLAN AND DATA FOR EACH SCHOOL. GIVEN RECENT ADVANCES IN AI, AN ESSENTIAL OUTCOME OF THIS PROJECT WILL BE TO DETERMINE HOW TO BEST INTEGRATE AI AND OTHER DISCIPLINES. THE PROJECT TEAM WILL EXAMINE HOW UNIVERSITIES CAN CREATE ICMS IN WHICH THE COMPUTING SIDE OF THE CURRICULUM INCLUDES AN EMPHASIS ON LEARNING AND ETHICALLY APPLYING AI TO THE OTHER DISCIPLINE. THE ICM CASE STUDIES, COMPLETE WITH DATA MEASURING THE CHANGE IN THE DEMOGRAPHICS OF DECLARED MAJORS, WILL PROVIDE A GENERALIZED ROAD MAP OF BEST PRACTICES FOR OTHER UNIVERSITIES INTERESTED IN IMPLEMENTING INTERDISCIPLINARY COMPUTING MAJORS. THIS WORK WILL BE GUIDED BY AN ADVISORY COUNCIL THAT WILL MEET WITH THE PROJECT TEAM ONCE A QUARTER TO REVIEW LEARNINGS, DATA COLLECTION AND GENERALIZATIONS. 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.