University Of Notre Dame Du Lac

RADIATION AND PHOTOCHEMISTRY IN THE CONDENSED PHASE AND AT INTERFACES

TAS::89 0227::TAS RECOVERY; RECOVERY ACT - MATERIALS SCIENCE OF ACTINIDES -- EFRC; PI - PETER BURNS

RAFIATION AND PHOTOCHEMISTRY IN THE CONDENSED PHASE

SUPPORTING HOLISTIC AND ACTIONABLE RESEARCH IN EDUCATION (SHARE)

SII-CENTER: SPECTRUMX ? AN NSF SPECTRUM INNOVATION CENTER

HARNESSING THE POWER OF EXPERIMENTAL GENETIC CROSSES AND SYSTEMS GENETICS TO PROBE DRUG RESISTANCE IN MALARIA

NSF CENTER FOR COMPUTER-ASSISTED SYNTHESIS -THE NSF CENTER FOR COMPUTER ASSISTED SYNTHESIS (CCAS) IS A NEXUS OF COLLABORATION, INNOVATION, AND EDUCATION THAT BRINGS TOGETHER DATA SCIENCE AND CHEMICAL SYNTHESIS. THE HIGHLY INTERDISCIPLINARY CCAS TEAM, COMPOSED OF SYNTHETIC ORGANIC CHEMISTS, COMPUTATIONAL CHEMISTS, AND COMPUTER SCIENTISTS, IS DEVELOPING DATA SCIENCE TOOLS AND COMPUTATIONAL WORKFLOWS THAT WILL LIKELY SHAPE THE FUTURE OF SYNTHETIC CHEMISTRY AND THE FIELDS IT ENABLES, SUCH AS MEDICINE, MATERIALS SCIENCE, AND ENERGY RESEARCH. THIS SITE?S IMPACTS ARE BEING FURTHER AMPLIFIED BY AN EXTENSIVE NETWORK OF ACADEMIC, INDUSTRIAL AND NON-PROFIT PARTNERS AND RESEARCH CENTERS, AND ITS DATA CHEMISTRY TOOLS ARE BEING SHARED WITH THE RESEARCH COMMUNITY THROUGH OPEN-SOURCE CLEARINGHOUSES. ALL OF THIS PROVIDES CCAS WITH A UNIQUE OPPORTUNITY TO DEVELOP, EXCHANGE, AND EVALUATE IDEAS IN THE FIELD OF DATA CHEMISTRY, AND ITS SHARED TOOLS AND TRAINING WILL EMPOWER STUDENTS, PRACTICING CHEMISTS, AND THE CHEMICAL INDUSTRY TO EFFECTIVELY APPLY DATA SCIENCE TO THEIR OWN CHEMICAL RESEARCH. LED BY ORGANIC CHEMISTS AT EVERY STAGE, CCAS FOCUSES ON USE-INSPIRED DATA SCIENCE RESEARCH THAT DRIVES THE DEVELOPMENT OF NEW DATA TYPES AND MACHINE LEARNING (ML) METHODS THAT ENABLE THE DISCOVERY OF NOVEL REACTIONS AND YIELD NEW SCIENTIFIC INSIGHTS. THE FOUR SCIENTIFIC THRUSTS INCLUDE (I) DEVELOPING EFFECTIVE ML TOOLS FOR OPTIMIZING CHEMICAL REACTIONS, (II) GAINING MECHANISTIC UNDERSTANDING THROUGH INTERPRETABLE STATISTICAL MODELS AND ELECTRONIC STRUCTURE CALCULATIONS, (III) PREDICTING REACTION OUTCOMES TO ANTICIPATE AND DISCOVER NEW REACTIVITY AND (IV) INTEGRATING THESE TOOLS FOR THE EFFICIENT PLANNING AND EXECUTION OF MULTISTEP SYNTHESES OF COMPLEX MOLECULES. TO ACCOMPLISH THESE GOALS, THREE THEMES ARE INTERWOVEN INTO EACH OF THE THRUSTS: (A) NEW STRUCTURED DATA TYPES THAT ARE AMENABLE TO HIGH-THROUGHPUT EXPERIMENTATION AND PREDICTIVE MODELS FROM THE GROUND UP, GOING BEYOND THE INFORMATION FROM COMMONLY USED DATABASES, (B) MOLECULAR AND REACTION REPRESENTATIONS THAT BRIDGE DESCRIPTOR-BASED AND STRUCTURE-BASED DEEP LEARNING PARADIGMS, AND (C) ALGORITHMS SPECIFICALLY DESIGNED FOR THE LOW DATA REGIMES PREVALENT THROUGHOUT CHEMISTRY. THROUGH THESE INTEGRATED RESEARCH THEMES AND THRUSTS, CCAS CONSTRUCTS AND SHARES DATA CHEMISTRY PLATFORMS THAT ARE EXPECTED TO ENABLE CHEMISTS TO TACKLE AMBITIOUS CHALLENGES THAT THE FIELD IS CURRENTLY UNDER-EQUIPPED TO PURSUE. THE DATA CHEMISTRY PLATFORM ALSO WILL OPEN UP NEW OPPORTUNITIES IN UNDERGRADUATE AND GRADUATE EDUCATION, AND THROUGH PARTNERSHIPS WITH THE DATA CHEMISTS NETWORK AND RESEARCH OPPORTUNITIES FOR CHEMISTS WITH DISABILITIES, CCAS SEEKS TO BROADEN THE PARTICIPATION OF RESEARCHERS FROM UNDERREPRESENTED GROUPS. 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.

PFC: JOINT INSTITUTE FOR NUCLEAR ASTROPHYSICS, JINA

UNIVERSITY OF NOTRE DAME SSAA PROGRAM: ''ACTINIDE CENTER OF EXCELLENCE'' MOD 0000 INCREMENTALLY FUNDS BUDGET PERIOD 1.

MERLIN - EXPANDING THE REACH OF IMPACT EVALUATION

CENTER FOR SHOCK WAVE-PROCESSING OF ADVANCED REACTIVE MATERIALS (C-SWARM)

WOU-MMA: NUCLEAR PHYSICS AT THE NOTRE DAME NUCLEAR SCIENCE LABORATORY PROVIDING A WINDOW ON THE UNIVERSE -THIS AWARD CONTINUES THE RESEARCH PROGRAM OF EIGHT FACULTY MEMBERS AND THEIR STUDENTS IN NUCLEAR STRUCTURE PHYSICS AND NUCLEAR ASTROPHYSICS AT THE UNIVERSITY OF NOTRE DAME. THE PROGRAM FOCUSES ON DIRECT MEASUREMENTS OF NUCLEAR REACTION AND DECAY PROCESSES THAT DETERMINE THE LIFE OF STARS, THE ORIGIN OF THE ELEMENTS, AND PRODUCTION OF MULTI MESSENGERS THAT PROVIDE A WINDOW ON THE UNIVERSE. THIS PROGRAM ADDRESSES KEY NUCLEAR PROCESSES THAT DEFINE THE TIMESCALES OF STELLAR EVOLUTION AND EXPLOSION PROCESSES. ANOTHER COMPONENT IS THE STUDY OF LOW ENERGY FUSION REACTIONS DURING THE LAST DAYS OF A STELLAR LIFE PRIOR TO SUPERNOVA EXPLOSION. THE PROGRAM ALSO EXPLORES THE NUCLEAR STRUCTURE EFFECTS THAT ARE GUIDING LARGE SCALE NUCLEOSYNTHESIS PROCESSES. THE RESEARCH IS PERFORMED PRIMARILY BY USING THE ACCELERATORS OF THE NUCLEAR SCIENCE LABORATORY (NSL) AT THE UNIVERSITY OF NOTRE DAME, WHICH ARE UNIQUELY DESIGNED TO PROBE STELLAR REACTIONS THROUGH A NUMBER OF EXPERIMENTAL TECHNIQUES. THE EXPERIMENTAL RESULTS EXPAND OUR KNOWLEDGE OF THE FUNDAMENTAL STRUCTURE OF THE NUCLEUS AS A MULTI-BODY QUANTUM SYSTEM; THEY ALSO PROVIDE NEW INSIGHT FOR THE ASTROPHYSICS COMMUNITY ON THE ORIGIN OF THE ELEMENTS AND THE CHEMICAL EVOLUTION OF THE COSMOS FROM THE BIG BANG TO THE PRESENT. THE NSL IS UNIQUELY EQUIPPED FOR PERFORMING THIS KIND OF RESEARCH IN A UNIVERSITY ENVIRONMENT. THE AWARD WILL SUPPORT THE TRAINING OF A LARGE NUMBER OF GRADUATE (APPROXIMATELY 25) AND UNDERGRADUATE STUDENTS (APPROXIMATELY 20) IN EXPERIMENTAL AND THEORETICAL TECHNIQUES TO BE READY TO JOIN THE NUCLEAR WORKFORCE OF THE NATION. THE EXPERIMENTAL PROGRAM IS BASED ON THE USE OF TWO ACCELERATORS AT THE NSL. INTENSE STABLE ION BEAMS FROM THE SINGLE ENDED 5U PELLETRON ARE USED FOR THE DIRECT STUDY OF LOW-ENERGY CAPTURE AND FUSION REACTIONS. HEAVY ION BEAMS ARE USED TO INVESTIGATE SUCH REACTIONS IN INVERSE KINEMATIC TECHNIQUE USING THE ST. GEORGE RECOIL SEPARATOR. THIS SEPARATOR IS UNIQUE AND SERVES AS A BLUEPRINT FOR THE DESIGN OF THE SECAR SEPARATOR AT FRIB. THE FN TANDEM ACCELERATOR IS USED AS A MULTI-PURPOSE INSTRUMENT. IT IS OPERATED AS A DRIVER FOR THE PRODUCTION OF RADIOACTIVE BEAMS AT THE NEWLY-EXPANDED TRISOL FACILITY, THE NATION'S FIRST DEDICATED INSTRUMENT FOR PRODUCING LOW ENERGY RADIOACTIVE BEAMS. THESE BEAMS ALLOW DIRECT REACTION MEASUREMENTS WITH AND THE TRAPPING OF LIGHT RADIOACTIVE PARTICLES AT LEVELS NOT POSSIBLE AT LARGE NATIONAL FACILITIES. THE FN ALSO SERVES THE ACCELERATOR MASS SPECTROMETRY (AMS) PROGRAM AT THE NSL, TESTING GEOLOGICAL AND COSMOLOGICAL SAMPLES FOR LONG-LIVED RADIOACTIVITIES. A LARGE NUMBER OF NUCLEAR STRUCTURE EXPERIMENTS ARE BASED ON THE OPERATION OF THIS MACHINE USING A VARIETY OF PARTICLE AND GAMMA SPECTROSCOPY TECHNIQUES. A SMALLER FRACTION OF THE PROGRAM RELIES ON THE USE OF OTHER NATIONAL AND INTERNATIONAL FACILITIES TO TAKE ADVANTAGE OF HIGHER ENERGY AND MORE EXOTIC BEAMS NOT AVAILABLE AT THE NSL. THIS PROJECT ADVANCES THE OBJECTIVES OF WINDOWS ON THE UNIVERSE: THE ERA OF MULTI-MESSENGER ASTROPHYSICS, ONE OF THE 10 BIG IDEAS FOR FUTURE NSF INVESTMENTS. 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.

STRONG BEGINNINGS: LEVERAGING THE HOME, SCHOOL, AND CHURCH TO DEVELOP THE WHOLE CHILD IN HAITI.

WOU-MMA: NUCLEAR PHYSICS AT THE NOTRE DAME NUCLEAR SCIENCE LABORATORY PROVIDING A WINDOW ON THE UNIVERSE

FATIMA: FOG AND TURBULENCE INTERACTIONS IN THE MARINE ATMOSPHERE

MOUNTAIN TERRAIN ATMOSPHERIC MODELING AND OBSERVATIONS (MATERHORN)PROGRAM

INDUCIBLE ANTIBIOTIC RESISTANCE IN METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS

QUARKNET

NUCLEAR STRUCTURE AND NUCLEAR ASTROPHYSICS

GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP)

NUCLEAR STRUCTURE AND NUCLEAR ASTROPHYSICS

READ HAITI: SCALING EARLY GRADE READING IMPROVEMENT IN HAITI

III-N DEVICES AND ARCHITECTURES FOR TERAHERTZ ELECTRONICS

NUCLEAR STRUCTURE AND NUCLEAR ASTROPHYSICS

TAS::89 0336::TAS RECOVERY GLOBAL WARMING POTENTIAL (GWP) OF CURRENT REFRIGERANTS IS MORE THAN 1000 TIMES THE GWP OF CO2. THIS MAKES CO2 VERY ATTR

21-ULI STEP-B-0052 A SAFETY-AWARE ECOSYSTEM OF INTERCONNECTED AND REPUTABLE SUAS

NEW START GRANT

TAS::89 0336::TAS RECOVERY A RECENT DISCOVERY BY NOTRE DAME HAS IDENTIFIED A CLASS OF IONIC LIQUID MATERIALS WHICH UNDERGO A PHASE TRANSITION FROM

NOVEL OXADIAZOLS FOR THE TREATMENT OF DRUG-RESISTANT GRAM-POSITIVE BACTERIA

BROAD AGENCY ANNOUNCEMENT (BAA) UNDER THE MEDIA LITERACY FOR NEW DIGITAL ARRIVALS

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.

"(HEL-MRI FY07) AIRBORNE AERO-OPTICS LABORATORY (AAOL)"

NUCLEAR STRUCTURE AND NUCLEAR ASTROPHYSICS

THE PURPOSE OF THIS AWARD IS TO INITIATE A LOW FORCE FRICTION WELDING PROJECT SUBMITTED BY THE UNIVERSITY OF NOTRE DAME IN COLLABORATION WITH MANUFACTURING TECHNOLOGY, INC. (MTI). THE PROJECT GOAL IS TO DEMONSTRATE THE SUPERIOR JOINT PERFORMANCE OF THE LOW FORCE FRICTION WELDING TECHNOLOGY, AS COMPARED TO CURRENT THERMITE AND EFB WELDING TECHNOLOGIES, WHEN APPLIED TO CONTINUOUSLY WELDED 136LB AREMA RAIL. THE PROJECT OBJECTIVES ARE TO 1) EVALUATE THE CURRENT STATE OF THE ART IN RAIL WELDING, 2) CONDUCT A FEASIBILITY STUDY OF LOW FORCE FRICTION WELDING USING PRISMATIC COUPONS, 3) STUDY THE PERFORMANCE OF LOW FORCE FRICTION WELDING ON 60LB AREMA RAIL USING AN EXISTING MACHINE AT MTI, 4) DESIGN, BUILD, AND RUN-OFF A LOW FORCE FRICTION WELDING MACHINE CAPABLE OF FABRICATING 136LB AREMA RAIL, 5) STUDY THE PERFORMANCE OF LOW FORCE FRICTION WELDING ON 136LB AREMA RAIL USING THIS NEW MACHINE, AND 6) DISSEMINATE KNOWLEDGE OF LOW FORCE FRICTION WELDING TO THE FRA TRANSPORTATION TECHNOLOGY CENTER TO POTENTIALLY INITIATE AN IN-TRACK TESTING IN A PHASE AFTER THE END OF THIS GRANTS PERIOD OF PERFORMANCE. THE RAIL COMMUNITY AT-LARGE WILL BENEFIT FROM THIS PROJECT.

(R)-ND-336 FOR THE TREATMENT OF DIABETIC FOOT ULCERS

NUCLEAR PROPERTIES AT EXTREME DENSITY, TEMPERATURE, SPIN AND ISOSPIN

DECODING THE REGULATION OF PROTEIN FOLDING BY SYNONYMOUS CODON USAGE - PROJECT SUMMARY - DECODING THE REGULATION OF PROTEIN FOLDING BY SYNONYMOUS CODON USAGE SYNONYMOUS MUTATIONS ARE WIDESPREAD IN COMPLEX, POLYGENIC DISEASES BUT ARE TYPICALLY REGARDED AS PHENOTYPICALLY SILENT, AS THEY PRESERVE THE AMINO ACID SEQUENCE OF THE ENCODED PROTEIN. YET, SYNONYMOUS MUTATIONS CAN SIGNIFICANTLY PERTURB PROTEIN HOMEOSTASIS THROUGH A VARIETY OF MECHANISMS, INCLUDING PERTURBING THE FOLDING MECHANISM OF THE ENCODED PROTEIN. RECENTLY, MY LAB DISCOVERED THAT SYNONYMOUS CODON-INDUCED CHANGES TO PROTEIN FOLDING CAN BE LARGE ENOUGH TO (A) EXCEED THE PROTEIN HOMEOSTATIC BUFFERING PROVIDED BY MOLECULAR CHAPERONES AND (B) LEAD TO A DRAMATIC TWO-FOLD DECREASE IN CELL GROWTH RATE. FOR THESE PROTEINS, CHANGING THE CODON USAGE PATTERN PRODUCES A FOLDED PROTEIN WITH AN ALTERED STRUCTURE, WHICH LEADS TO CHANGES IN ACTIVITY AND/OR SUSCEPTIBILITY TO DEGRADATION BY CELLULAR PROTEASES. THE PROFOUND IMPLICATION OF THESE RESULTS IS THAT CODON USAGE REPRESENTS ANOTHER LEVEL OF INFORMATION ENCODED WITHIN GENOMES, LINKING TOGETHER “SILENT” GENETIC DIFFERENCES WITH PROPER PROTEIN FUNCTION AND REGULATION OF A POTENTIALLY BROAD RANGE OF CELLULAR MECHANISMS. HISTORICALLY, HOWEVER, STUDYING PERTURBATIONS TO PROTEIN FOLDING MECHANISMS IN VIVO HAS PRESENTED IMMENSE TECHNICAL CHALLENGES. FOR THIS REASON, TO DATE ONLY A FEW EXAMPLES HAVE BEEN IDENTIFIED OF CONNECTIONS BETWEEN CODON USAGE AND PROTEIN FOLDING. AS A RESULT, WE LACK A COMPREHENSIVE PICTURE OF THE EXTENT TO WHICH SYNONYMOUS CODON USAGE CONTRIBUTES TO THE PRODUCTION OF A FUNCTIONAL PROTEOME AND HOW SYNONYMOUS MUTATIONS PERTURB PROTEIN HOMEOSTASIS. THIS PIONEER AWARD PROJECT IS DESIGNED TO BREAK THROUGH EXISTING TECHNICAL CHALLENGES, DEVELOPING A NOVEL APPROACH TO (I) BROADLY MEASURE FOR THE FIRST TIME THE NUMBER AND TYPES OF PROTEINS WITH FOLDING MECHANISMS SENSITIVE TO SYNONYMOUS CODON USAGE, ACROSS AN ENTIRE PROTEOME AND (II) DEEPLY INTERROGATE WHICH CODON USAGE PATTERNS AND FEATURES BEST SUPPORT PROPER PROTEIN FOLDING IN VIVO. THE AMBITIOUS, OVERARCHING GOAL OF THIS PROJECT IS TO ENABLE A NEXT GENERATION OF GENOMIC INFERENCE BY DEVELOPING A PREDICTIVE UNDERSTANDING OF THE SYNONYMOUS CODON USAGE PATTERNS THAT BEST SUPPORT PRODUCTION OF A FUNCTIONAL PROTEOME AND THE DYSREGULATION THAT LEADS TO HUMAN GENETIC DISEASE.

NOTRE DAME STUDY OF RESILIENCY IN LATER LIFE

CHARACTERIZATION OF BIOFILMS BY CORRELATED MASS SPECTROMETRIC AND RAMAN IMAGING

TAS::57 3600::TAS "AIRBORNE AERO-OPTICS LABORATORY-TRANSONIC (AAOL-T)" DATED, 01 FEB 2012 AND REVISED BUDGET 14 SEP 2012"

PLASMINOGEN AND PLASMIN: STRUCTURE AND FUNCTION

DESIGN, SYNTHESES AND STUDIES OF NOVEL ANTITUBERCULOSIS AGENTS

INTEGRATING CIVIL DISCOURSE INTO THE CURRICULUM AT PUBLIC, PRIVATE, COMMUNITY AND HISTORICALLY MINORITY-SERVING COLLEGES AND UNIVERSITIES

HIGH CAPACITY PROTEIN PURIFICATION FOR STRUCTURAL IMMUNOLOGY

TO MAXIMIZE IMPLEMENTATION OF COLOMBIA'S PEACE ACCORD AND IMPROVE THE LIKELIHOOD FOR SUSTAINABLE PEACE.

MOLECULAR PROBES FOR BIOMEMBRANE RECOGNITION

BIOLOGICALLY-INSPIRED CNN IMAGE PROCESSORS WITH DYNAMICALLY-INTEGRATED HYPERSPECTRAL NANOSCALE SENSORS

BUILDING BETTER T CELL RECEPTORS FOR TARGETED IMMUNOTHERAPY

ROLE OF N-ALPHA ACETYLATION IN MYCOBACTERIAL SECRETION AND VIRULENCE

REPURPOSING GRAM-POSITIVE ANTIBIOTICS FOR GRAM-NEGATIVE BACTERIA USING ANTIBIOTIC ADJUVANTS - MULTI-DRUG RESISTANT (MDR) ACINETOBACTER BAUMANNII INFECTIONS PRESENT AN ENORMOUS ONGOING CHALLENGE TO PUBLIC HEALTH. DUE TO THE FREQUENT OCCURRENCE OF MULTIDRUG RESISTANCE, CURRENT TREATMENT OPTIONS FOR A. BAUMANNII INFECTIONS ARE LIMITED. SS-LACTAM ANTIBIOTICS, ESPECIALLY CARBAPENEMS, REPRESENT THE TREATMENT OF CHOICE FOR SUSCEPTIBLE INFECTIONS. HOWEVER, CARBAPENEM RESISTANCE IS INCREASINGLY COMMON, AND FOR SUCH INFECTIONS THERE IS NO CONSENSUS ON THE OPTIMAL ALTERNATIVE TREATMENT. BECAUSE RESISTANCE HAS HITHERTO BEEN RELATIVELY UNCOMMON, COLISTIN HAS BECOME A FAVORED TREATMENT IN SPITE OF THE FACT THAT DELETERIOUS SIDE EFFECTS ARE COMMON. HOWEVER, RESISTANCE TO COLISTIN IN A. BAUMANNII IS BECOMING MORE FREQUENT WITH THE RECENT DISSEMINATION OF PLASMID-BORNE COLISTIN RESISTANCE GENES (MCR-1-10) INTO HEALTHCARE FACILITIES. UNFORTUNATELY, THE RECENT TRACK RECORD OF DISCOVERY OF NEW ANTIBIOTICS THAT ARE ACTIVE AGAINST GRAM-NEGATIVE BACTERIA IS EXCEEDINGLY POOR, WHICH, COUPLED WITH THE EXIT OF BIG PHARMA FROM ANTIBIOTIC DISCOVERY, HAS MADE THE DEVELOPMENT OF NEW THERAPIES AND NON-TRADITIONAL THERAPEUTIC APPROACHES VITAL. TO COMBAT THIS GROWING THREAT, WE INITIATED A RESEARCH PROGRAM TO IDENTIFY SMALL MOLECULES, TERMED ANTIBIOTIC ADJUVANTS, THAT POTENTIATE THE ACTIVITY OF MACROLIDES AGAINST MDR A. BAUMANNII. TO THIS END, WE HAVE SUCCESSFULLY IDENTIFIED MOLECULES THAT LOWER THE MINIMUM INHIBITORY CONCENTRATION (MIC) OF CLARITHROMYCIN UP TO 512-FOLD AGAINST ALL MEMBERS OF A PANEL OF PRIMARY CLINICAL A. BAUMANNII ISOLATES FROM THE WALTER REED ARMY INSTITUTE OF RESEARCH (WRAIR) THAT ENCOMPASSES NEARLY ALL CLINICALLY RELEVANT A. BAUMANNII CLADES. ADJUVANTS ALSO POTENTIATE THE ACTIVITY OF VANCOMYCIN UP TO 256-FOLD. BOTH MACROLIDES AND VANCOMYCIN ARE TYPICALLY VIEWED AS “GRAM-POSITIVE” SELECTIVE ANTIBIOTICS DUE TO THEIR INABILITY TO CROSS THE OUTER MEMBRANE OF GRAM-NEGATIVE BACTERIA, MECHANISTIC STUDIES HAVE LED TO A WORKING HYPOTHESIS THAT THESE COMPOUNDS OVERCOME THIS BARRIER BY INCREASING PERMEABILITY OF THE OUTER MEMBRANE THROUGH INHIBITING LIPOOLIGOSACCHARIDE (LOS) PRODUCTION. COMBINATIONS OF ADJUVANT WITH CLARITHROMYCIN ARE EFFECTIVE IN A GALLERIA MELLONELLA MODEL OF INFECTION, WHICH HAS BEEN SHOWN TO PREDICT OUTCOME IN MURINE MODELS OF INFECTION IN THE CONTEXT OF MDR A. BAUMANNII. THEREFORE, COMBINATIONS OF SUCH ADJUVANTS WITH EITHER CLARITHROMYCIN OR VANCOMYCIN MAY FORM THE BASIS FOR AN EFFICACIOUS APPROACH TO TREATING MDR A. BAUMANNII INFECTIONS FOR WHICH THERE ARE NO EFFECTIVE ANTIBIOTICS.

INTERACTIONS REGULATING TRANSLATION AND PROTEIN BIOGENESIS IN VIVO

GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP)

RECEPTOR CROSS-TALK IN EARLY METASTATIC DISSEMINATION

MURI SASCWATCH: STUDY ON AIR-SEA COUPLING WITH WAVES, TURBULENCE, AND CLOUDS AT HIGH WINDS 23-000005369

PENICILLIN-BINDING PROTEINS, MECHANISM AND INHIBITION

QUARKNET

CHEMISTRY-BIOCHEMISTRY-BIOLOGY INTERFACE TRAINING PROGRAM AT NOTRE DAME

MASTERS AND STEM PROGRAMS IN HYPERSONIC SYSTEMS

RESEARCH WITH THE CMS DETECTOR AT THE LHC -PARTICLE PHYSICS FOCUSES ON UNDERSTANDING THE MOST BASIC BUILDING BLOCKS OF NATURE AND THE RULES THAT BIND THEM. THE CERN LARGE HADRON COLLIDER (LHC), LOCATED NEAR GENEVA, SWITZERLAND IS THE WORLD'S MOST POWERFUL PARTICLE ACCELERATOR, ABLE TO REACH THE HIGHEST PARTICLE ENERGIES IN A LABORATORY SETTING. THE CMS DETECTOR AT THE LHC IS A POWERFUL AND SOPHISTICATED CAMERA, OBSERVING THE COLLISIONS OF PROTONS AND RECORDING THE BYPRODUCTS FOR DETAILED STUDY BY CMS EXPERIMENTALISTS. ONE OF THEIR PRIMARY OBJECTIVES WAS TO FIND THE HIGGS BOSON, THE LAST PARTICLE IN THE HISTORICALLY SUCCESSFUL STANDARD MODEL (SM) THAT ACCOUNTS FOR SO MUCH OF THE EXISTENCE OF, AND FORCES BETWEEN, KNOWN PARTICLES FORMING THE MATTER IN THE UNIVERSE. THIS EFFORT HAS BEEN SUCCESSFUL. THE NEXT STEP IN THE EXPERIMENTS IS TO LOOK FOR EVIDENCE FOR PHYSICS BEYOND THE STANDARD MODEL (BSM) THAT MIGHT, FOR INSTANCE, ACCOUNT FOR THE PRESENCE OF THE MYSTERIOUS DARK MATTER THAT MAKES UP SO MUCH OF THE MASS OF THE UNIVERSE. THE LHC IS CURRENTLY IN THE ONSET OF RUN 3 WITH SIGNIFICANTLY INCREASED EVENT SAMPLES. IT IS POSSIBLE THAT EVIDENCE FOR BSM PHYSICS COULD EMERGE AT THIS HIGHER ENERGY AND WITH THE HIGHER EVENT STATISTICS. THROUGH THIS PROJECT, THE HIGH ENERGY PHYSICS GROUP AT NOTRE DAME UNIVERSITY WILL MAXIMIZE THE DISCOVERY POTENTIAL OF THE CMS EXPERIMENT THROUGH CONTRIBUTIONS TO DATA ANALYSIS, PREPARATIONS AND OPERATIONS FOR THE NEXT LHC RUN AS WELL AS DATA ANALYSIS AND MAJOR CONTRIBUTIONS TO THE HIGH LUMINOSITY UPGRADES OF THE LHC. THE NEXT THREE YEARS WILL BE A CHALLENGING PERIOD AS THE CMS EXPERIMENT PRESSES FORWARD ON THREE SEPARATE FRONTS: CONTINUING THE ANALYSIS OF THE DATA COLLECTED DURING THE PAST RUN, PREPARING FOR AND THEN BEGINNING TO ANALYZE TWICE AS MUCH DATA FROM THE UPCOMING RUN, AND BEGINNING THE CONSTRUCTION FOR THE HIGH LUMINOSITY LHC UPGRADES. NOTRE DAME ACTIVITIES INCLUDE CONTRIBUTIONS ACROSS SEVERAL AREAS OF THE CMS DETECTOR INCLUDING THE ELECTROMAGNETIC CALORIMETER, THE HADRONIC CALORIMETER, TRIGGER, COMPUTING, AND OFFLINE SOFTWARE. THEIR PHYSICS ANALYSIS PLANS LEVERAGE PAST INVESTMENTS IN HIGGS AND TOP QUARK PHYSICS, WHILE ALSO ESTABLISHING NEW DIRECTIONS FOR DIRECTLY AND INDIRECTLY PROBING FOR NEW PHYSICS. THE NOTRE DAME GROUP WILL CONTINUE TO LEVERAGE THEIR EXPERTISE IN CALORIMETRY IN SEVERAL HIGGS ANALYSES AND SEARCHES FOR NEW PHENOMENA, INCLUDING HIGGS DECAYS TO TWO TAU LEPTONS, TWO PHOTONS, OR A MUON LEPTON AND A TAU LEPTON. ADDITIONALLY, THEY WILL EXPLOIT THEIR CONTRIBUTIONS TO THE PHASE 1 UPGRADES OF CMS CALORIMETRY FOR IMPROVED PERFORMANCE DURING THE NEXT LHC RUN. THEY WILL ALSO CONTINUE TO COORDINATE AND MANAGE THE OPTICAL READOUT AND DECODING FOR ENDCAP AND BARREL HADRON CALORIMETRY. THE GROUP HAVE LEADERSHIP ROLES IN HIGH-LUMINOSITY LHC UPGRADE PROJECTS, INCLUDING THE ELECTROMAGNETIC AND HADRONIC BARREL CALORIMETER UPGRADES, THE ENDCAP CALORIMETER UPGRADE, AND THE ADDITION OF A NEW TIMING LAYER DETECTOR FOR CMS. THIS PROJECT ALSO INCLUDES CONTRIBUTIONS TO THE LEVEL 1 TRACK TRIGGER UPGRADE AND CONTINUING CONTRIBUTIONS TO HIGH LEVEL TRIGGER OPERATIONS, OFFLINE AND COMPUTING, AND DATA PRESERVATION. THE GROUP WILL ENGAGE BROADLY IN EDUCATION AND OUTREACH THROUGH QUARKNET AND MANY OTHER PUBLIC-FACING INITIATIVES. NOTRE DAME IS LEAD AND THE MANAGING INSTITUTION OF QUARKNET, WHICH CURRENTLY CONSISTS OF 52 CENTERS IN 25 STATES AND PUERTO RICO AND HAS BEEN EXPANDED TO INCLUDE EXPERIMENTAL PROGRAMS AT NATIONAL AND FOREIGN LABORATORIES. THEIR OUTREACH EFFORTS INCLUDE DEVELOPMENT AND IMPLEMENTATION OF ELECTRONIC LABORATORIES (E-LABS) FOR LHC DATA AND COSMIC RAY DATA, MASTERCLASSES BASED ON PARTICLE PHYSICS AND ASTROPHYSICS, AND PARTICIPATION IN PROGRAMS THAT SUPPORT SUMMER RESEARCH FOR UNDERGRADUATES, HIGH SCHOOL TEACHERS AND HIGH SCHOOL STUDENTS. THROUGH THESE EFFORTS, THEY CONTINUE TO DEVELOP AND BUILD UPON A SUITE OF OUTREACH MATERIALS AND DEMONSTRATION PROJECTS THAT BRING PARTICLE PHYSICS TO THE PUBLIC ON A NUMBER OF LEVELS, FROM REAL PHYSICS ANALYSIS ON LHC HIGGS DATA IN THE CLASSROOM TO A PARTICLE DETECTOR DISPLAY AT THE SMITHSONIAN. 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.

DESIGNING SELECTIVE INHIBITORS OF IGE-MEDIATED MAST CELL DEGRANULATION

RESEARCH WITH THE CMS DETECTOR AT THE LHC

RESISTANCE TO CARBAPENEM ANTIBIOTICS IN ACINETOBACTER BAUMANNII

CARBAPENEMASE-STABLE CARBAPENEM ANTIBIOTICS FOR TREATMENT OF MULTIDRUG-RESISTANT ACINETOBACTER BAUMANNII INFECTIONS - ACINETOBACTER BAUMANNII IS LISTED BY THE CDC AS A CLINICAL PATHOGEN THAT POSES A SERIOUS ANTIBIOTIC RESISTANCE THREAT IN THE UNITED STATES, DUE TO ITS RESISTANCE TO THE LAST RESORT CARBAPENEM ANTIBIOTICS (CARBAPENEM-RESISTANT A. BAUMANNII OR CRAB), WHICH WERE THE DRUGS OF CHOICE FOR TREATMENT OF INFECTIONS CAUSED BY THIS MICROORGANISM. IN ADDITION, CRAB IS OFTEN RESISTANT TO ANTIMICROBIAL AGENTS OF DIFFERENT CLASSES (MULTI-DRUG-RESISTANT A. BAUMANNII OR MDRAB), WHICH SEVERELY LIMITS AVAILABLE THERAPEUTIC OPTIONS. THE MAJOR MECHANISM OF RESISTANCE OF A. BAUMANNII TO CARBAPENEMS IS PRODUCTION OF ANTIBIOTIC-INACTIVATING ENZYMES, CARBAPENEM-HYDROLYZING CLASS D SS- LACTAMASES OR CHDLS. IN ADDITION, CARBAPENEMASES OF CLASSES A AND B, SENSITIVITY OF CARBAPENEM TARGETS (BACTERIAL PENICILLIN-BINDING PROTEINS OR PBPS), RATES OF ANTIBIOTIC PENETRATION INTO THE BACTERIAL CELL AND THEIR EXPULSION BY EFFLUX PUMPS CAN ALSO CONTRIBUTE TO RESISTANCE. LEVELS OF RESISTANCE TO CARBAPENEMS REACH UP TO 90% IN SOME PARTS OF THE WORLD, AND MORTALITY RATES FROM INFECTIONS CAUSED BY SUCH BACTERIA ARE STAGGERINGLY HIGH, UP TO 50%. OUR LONG-TERM GOAL IS TO DEVELOP NOVEL ANTIBIOTICS FOR TREATMENT OF DEADLY MDRAB INFECTIONS. OVER THE LAST DECADE, THE VAKULENKO GROUP HAS PERFORMED IN-DEPTH CHARACTERIZATION OF CLINICALLY IMPORTANT CHDLS, WHICH PROVIDES GUIDANCE FOR DEVELOPMENT OF A NEW GENERATION OF CARBAPENEMS CAPABLE OF INHIBITING THESE ENZYMES. CONCURRENTLY, DR. JOHN BUYNAK’S (CO-PI) GROUP DEVELOPED DOZENS OF NOVEL ATYPICALLY-MODIFIED CARBAPENEM ANTIBIOTICS. WE EVALUATED THESE ANTIBIOTICS FOR THEIR ACTIVITY AGAINST MDRAB AND DEMONSTRATED THAT THREE OF THEM POSSESS SUPERIOR ACTIVITY (WHEN COMPARED TO COMMERCIAL CARBAPENEMS) AGAINST MDRAB. ALL THREE INHIBITED THE MOST PREVALENT A. BAUMANNII CHDL, OXA-23, AND HAD VARYING SPECTRA OF INHIBITORY ACTIVITY AGAINST OTHER CHDLS AND CARBAPENEMASES OF OTHER CLASSES. ONE OF THESE COMPOUNDS HAD AN UNPRECEDENTED WIDE SPECTRUM OF ACTIVITY AND RESISTED HYDROLYSIS BY A WIDE RANGE OF CLINICALLY IMPORTANT CARBAPENEMASES OF ALL MOLECULAR CLASSES. IN THIS GRANT APPLICATION, WE PROPOSE TO PERFORM DETAILED CHARACTERIZATION OF OUR NOVEL CARBAPENEM ANTIBIOTICS. WE WILL DETERMINE ACTIVITY OF OUR COMPOUNDS AGAINST A. BAUMANNII STRAINS EXPRESSING MAJOR CHDLS AND OTHER CARBAPENEMASES AND UNVEIL KINETIC AND STRUCTURAL FEATURES RESPONSIBLE FOR THEIR ABILITY TO INHIBIT THESE ENZYMES (AIM 1). WE WILL STUDY INTERACTION OF OUR NOVEL CARBAPENEMS WITH THEIR TARGETS, PBPS, AND DETERMINE TO WHAT EXTENT EFFLUX PUMPS AND PORINS INFLUENCE BACTERIAL RESISTANCE TO THESE ANTIBIOTICS (AIM 2). WE WILL DESIGN AND CHARACTERIZE SEVERAL DOZEN NOVEL CARBAPENEM ANTIBIOTICS TO FURTHER IMPROVE THEIR ANTIMICROBIAL ACTIVITY BY ENHANCING THEIR INHIBITORY POTENCY AGAINST VARIOUS CARBAPENEMASES, IMPROVING AFFINITY FOR PBPS AND INCREASING PENETRATION RATES AND RESISTANCE TO EFFLUX (AIM 3). WE WILL PERFORM IN VITRO CHARACTERIZATION OF OUR BEST NOVEL CARBAPENEMS TO ASSESS THEIR SOLUBILITY, STABILITY AND TOXICITY. FINALLY, OUR BEST COMPOUNDS WILL BE EVALUATED IN ANIMAL STUDIES TO APPRECIATE THEIR POTENTIAL AS NOVEL THERAPEUTIC AGENTS AGAINST MDRAB (AIM 4).

QUARKNET

TRAFFICKING SIGNALS IN P. FALCIPARUM

COMPARATIVE TRANSCRIPTOMIC AND EPIGENOMIC ANALYSES OF MULLER GLIA REPROGRAMMING

THE QUINAZOLINONE CLASS OF ANTIBACTERIAL AGENTS

MECHANISMS AND MANIPULATION OF FORCE DEPENDENT BEHAVIOR IN T CELL BIOLOGY - SUMMARY TCR RECOGNITION OF PEPTIDES BOUND AND PRESENTED BY MHC PROTEINS UNDERLIES CELLULAR IMMUNITY. TCR RECOGNITION OF PMHC IS MOST OFTEN VIEWED THROUGH THE LENS OF TRADITIONAL RECEPTOR-LIGAND THEORY, WHERE CELLULAR RESPONSES ARE PRESUMED TO BE GOVERNED BY SOLUTION BINDING AFFINITIES OR KINETICS. WHILE THIS IS OFTEN THE CASE, WORK OVER THE PAST SEVERAL YEARS HAS SHOWN THAT COMPLEXITIES FROM MECHANICAL FORCES EXERTED ON MEMBRANE BOUND TCR AND PMHC CAN PROFOUNDLY INFLUENCE T CELL SIGNALING. OF NOTABLE INTEREST ARE CATCH BONDS: FORCE DEPENDENT ENHANCEMENTS OF THE LIFETIMES OF TCR-PMHC COMPLEXES FORMED BETWEEN INTERACTING CELLS. CATCH BONDS CAN LEAD TO LARGE CHANGES IN SIGNALING OUTPUT AND CAN GREATLY ENHANCE T CELL SENSITIVITY. DEMONSTRATING THE IMPORTANCE OF MECHANICAL FORCES IN TUNING T CELL RESPONSES, LIGANDS THAT ARE RECOGNIZED WITH STRONG AFFINITY BUT FAIL TO RESULT IN CATCH BONDS YIELD ALTERED OR EVEN NO T CELL SIGNALING. FORCE-DEPENDENT BEHAVIOR HAS BEEN IMPLICATED IN A WIDE RANGE OF T CELL BIOLOGICAL PROCESSES, INCLUDING THYMIC EDUCATION, RESPONSES TO VIRAL OR TUMOR ANTIGENS, AND VIRAL ESCAPE. ALTHOUGH THE IMPORTANCE OF MECHANICAL FORCE IN TCR RECOGNITION HAS BEEN DEMONSTRATED, WE HAVE ONLY A RUDIMENTARY UNDERSTANDING OF HOW TCRS FORM CATCH OR REVERT TO SLIP BONDS. WE (PI EVAVOLD) HAVE HAD RECENT SUCCESS IN MANIPULATING TCR CATCH BONDS (PUBLISHED IN SCIENCE THIS YEAR) BUT THIS WAS ACHIEVED THROUGH SCREENING LIBRARIES AND WITHOUT AN UNDERSTANDING OF MECHANISM. WE THUS LACK PREDICTIVE MODELS FOR FORCE DEPENDENT BEHAVIOR IN TCRS AND IN TURN HOW THIS AFFECTS BIOLOGY, WHICH IN TURN IMPACTS OUR ABILITY TO PREDICT IMMUNOGENICITY, ASSESS THE CONSEQUENCES OF MUTATIONS, AND HINDERS OUR ABILITY TO UNDERSTAND T CELL SPECIFICITY. RECENTLY, HOWEVER, WE DEVELOPED A COMPREHENSIVE FRAMEWORK TO IDENTIFY, MANIPULATE, AND PREDICT FORCE DEPENDENT BEHAVIOR IN TCR-PMHC INTERACTIONS. UNLIKE PRIOR EFFORTS, OUR FRAMEWORK DIRECTLY ADDRESSES MECHANISM. HERE, WE WILL FURTHER DEVELOP, REFINE, AND APPLY OUR FRAMEWORK. OUR DRIVING HYPOTHESIS IS THAT VIEWING FORCE DEPENDENT BEHAVIOR THROUGH THE LENS OF ENERGY WILL PROVIDE THE MISSING MECHANISTIC DETAIL OF HOW AND WHY CATCH BONDS EMERGE IN TCRS, ALLOW THEIR RATIONAL PREDICTION AND MANIPULATION, AND PERMIT FORCE CONSIDERATIONS TO BE INCLUDED IN ASSESSMENTS OF T CELL RECOGNITION OF ANTIGEN. OUR THREE AIMS ARE TO 1) FURTHER DEVELOP OUR MECHANISTIC FRAMEWORK FOR FORCE DEPENDENT TCR BEHAVIOR; 2) EXPLAIN HOW CHANGES TO CATCH BONDS EMERGE FROM NATURAL VARIATIONS IN TCR INTERFACES AND HOW CATCH BONDS REGULATE T CELL BIOLOGY; AND 3) USE RATIONAL CATCH BOND ENGINEERING TO BETTER CONTROL VIRAL INFECTION IN MICE. OVERALL, THE WORK IN THIS PROPOSAL WILL ILLUMINATE THE OPAQUE MECHANISMS THAT UNDERLIE T CELL MECHANOBIOLOGY, PLACE CATCH BONDS ON A FORMAL MECHANISTIC FOOTING, AND PROVIDE THE MEANS TO PREDICT AND PRODUCTIVELY MANIPULATE TCR CATCH BONDS AND ULTIMATELY T CELL BIOLOGY.

AIRBORNE AERO-OPTICS LABORATORY-BEAM CONTROL

DEVELOPMENT OF ANTIBIOTIC ADJUVANTS FOR GRAM-NEGATIVE BACTERIA

DIAPAUSE IN CULEX MOSQUITOES

FOSTERING HEALTHY DEVELOPMENT AMONG MALTREATED PRESCHOOL-AGED CHILDREN

NETHEALTH: MODELING THE CO-EVOLUTION OF SOCIAL NETWORKS AND HEALTH BEHAVIORS

TAS::89 0222::TAS; NEW; METASTABLE VORTEX LATTICES-PROPERTIES AND APPLICATIONS; PI-MORTEN ESKILDSEN

RESEARCH WITH THE CMS DETECTOR AT THE LHC

E2CDA: TYPE I: EXTREMELY ENERGY EFFICIENT COLLECTIVE ELECTRONICS (EXCEL)

AIR-SEA COUPLING IN MONSOON INTRASEASONAL OSCILLATIONS

AMINOGLYCOSIDE RESISTANCE IN ENTEROCOCCI

CHAPERONE THERAPEUTICS FOR THE TREATMENT OF DPN

MECHANISMS OF ERYTHROCYTIC INFECTION & ANEMIA IN MALARIA

DEVELOPING ANTI-VIRAL RIBOZYMES TO SUPPRESS ARBOVIRUSES IN TRANSGENIC MOSQUITOES

NEW COOPERATIVE AGREEMENT IONIC LIQUIDS: BREAKTHROUGH ABSORPTION TECHNOLOGY FOR POST COMBUSTION CO2 CAPTURE

THE COOPERATIVE AGREEMENT SHALL BE PERFORMED IN ACCORDANCE WITH STATEMENT OF WORK (ATTACHMENT 2), ENTITLED "ADVANCED TECHNOLOGY BOOSTERS TO ENABLE LOW TEMPERATURE LOGIC TECHNOLOGY ON A CMOS PLATFORM.

BIOMATERIALS AND FIXATION METHODS DEVELOPMENT FOR TRAUMATIC ORTHOPAEDIC INJURIES

NEW GK-12: THE NOTRE DAME EXTENDED RESEARCH COMMUNITY (NDERC)

CHILDREN AND POLITICAL VIOLENCE IN NORTHERN IRELAND

DESIGN/SYNTHESES/STUDIES/NOVEL ANTITUBERCULOSIS AGENTS

MRI: DEVELOPMENT OF THE GEMINI PLANET IMAGER UPGRADE

BEST DATA COLLECTION VALIDATION AND RESEARCH

RESEARCH IN COLLIDER PHYSICS

TALENT SEARCH PROJECT FOR SOUTH BEND

A LIFE COURSE PERSPECTIVE ON GUT MICROBIOME AGING AND HEALTH IN A NON-HUMAN PRIMATE MODEL - PROJECT SUMMARY THE GUT MICROBIOME HAS REPEATEDLY BEEN LINKED TO MAJOR DISEASES OF AGING, INCLUDING FRAILTY, OSTEOPOROSIS, AND DIABETES. HOWEVER, AFTER MORE THAN A DECADE OF SEARCHING, THERE IS STILL NO CONSENSUS ON WHICH MICROBIAL SPECIES OR TAXONOMIC FEATURES PROVIDE RELIABLE HALLMARKS OF AGING IN ADULTS OR THE ELDERLY. DIFFERENT PEOPLE HARBOR DIFFERENT COLLECTIONS OF MICROBES WITH DENSITIES AND DYNAMICS THAT VARY CONSIDERABLY FROM ONE PERSON TO THE NEXT. THIS PERSONALIZATION ARISES, IN PART, BECAUSE A GIVEN MICROBE MAY PERFORM DIFFERENT FUNCTIONS IN DIFFERENT PEOPLE, AND EVEN IN THE SAME PERSON AT DIFFERENT TIMES. THIS VARIABILITY CONSTRAINS THE UTILITY OF MICROBIOME TAXA (E.G. SPECIES, PHYLA, BIODIVERSITY) TO MEASURE HEALTH AND HEALTHY AGING. OVERCOMING THIS HURDLE REQUIRES A SHIFT IN STRATEGY, AWAY FROM TAXONOMIC DATA AND TOWARDS DATA TYPES THAT REFLECT THE GUT MICROBIOME’S FUNCTIONAL CAPACITIES, INCLUDING THE MICROBIAL GENES AND METABOLIC PATHWAYS FOUND IN THE GUT MICROBIOME’S METAGENOME. DEVELOPING GUT MICROBIOME MARKERS OF HEALTHY AGING WILL ALSO REQUIRE PROSPECTIVE, LONGITUDINAL POPULATION-BASED RESEARCH. HOWEVER, WE LACK PROSPECTIVE DATA SETS THAT TRACK LONGITUDINAL CHANGES IN INDIVIDUAL GUT MICROBIOME FUNCTION AND HEALTH OUTCOMES ACROSS ADULTHOOD AND OLD AGE. OUR OBJECTIVES IN THIS PROPOSAL ARE TO USE A PROSPECTIVE, FULL LIFE COURSE, NONHUMAN PRIMATE MODEL TO: (I) IDENTIFY CHANGES IN THE MICROBIOME’S FUNCTIONAL CAPACITIES ACROSS THE LIFE COURSE; (II) TEST HOW SOCIAL AND ENVIRONMENTAL FACTORS AFFECT THE NATURE AND PACE OF MICROBIOME AGING; (III) TEST HOW TAXA-FUNCTION RELATIONSHIPS CHANGE AT DIFFERENT LIFE STAGES; AND (IV) LEARN WHICH MICROBIOME FEATURES PREDICT PHYSICAL/BEHAVIORAL AGING AND ALL-CAUSE MORTALITY. OUR SYSTEM, THE WELL-STUDIED AMBOSELI BABOON POPULATION IN KENYA, CAPTURES THE COMPLEXITY OF HUMAN BEHAVIORAL AND SOCIAL CONDITIONS BETTER THAN OTHER ANIMAL MODELS. WE HAVE ALREADY PROFILED GUT MICROBIAL TAXONOMIC COMPOSITION IN 17,277 FECAL SAMPLES COLLECTED OVER 14 YEARS FROM 501 BABOONS. THESE DATA REVEAL PERSONALIZED MICROBIOME DYNAMICS AND AGING TRAJECTORIES THAT ARE SHAPED BY INDIVIDUAL SOCIAL AND ENVIRONMENTAL CONDITIONS. WE PROPOSE TO EXPAND THIS DATA SET FOR 10 MORE YEARS TO INCLUDE 800 TOTAL INDIVIDUALS AND ANALYZE MICROBIOME FUNCTIONAL CAPACITY IN 12,000 SAMPLES. BY IDENTIFYING DRIVERS AND PATTERNS OF MICROBIOME FUNCTIONAL AGING, WE WILL IDENTIFY TARGETS FOR INTERVENTIONS AIMED AT BUILDING AND SUSTAINING HEALTHY AGING. OUR RESULTS WILL HELP HARNESS THE PROMISE OF THE GUT MICROBIOME TO PREDICT AND IMPROVE HUMAN HEALTH.

DIAGONAL CAPILLARY ELECTROPHORESIS FOR PHOSPHORYLATION AND SIALYLATION ANALYSIS

LEVERAGING NONINVASIVE TRANSCUTANEOUS VAGUS NERVE STIMULATION AND SMARTPHONE TECHNOLOGY TO REDUCE SUICIDAL BEHAVIORS AND SUICIDE AMONG HIGHLY VULNERABLE ADOLESCENTS - PROJECT SUMMARY / ABSTRACT OVER THE PAST TWO DECADES, SUICIDE RATES HAVE INCREASED NEARLY 35% IN THE U.S., WITH UP- WARD TRENDS IN NEARLY ALL DEMOGRAPHIC GROUPS. FURTHER INCREASES HAVE OCCURRED SINCE THE COVID-19 PANDEMIC BEGAN. DESPITE AMBITIOUS GOALS FOR REDUCING SUICIDES AND SIGNIFICANT FED- ERAL AND PRIVATE INVESTMENT, SUICIDE RATES CONTINUE TO RISE UNABATED. TO DATE, THE PREDOMINANT APPROACH TO MITIGATING SUICIDE RISK IN THE U.S. IS SECONDARY PREVENTION. TYPICALLY, THESE PRO- GRAMS IDENTIFY RISK OF RECURRENCE AMONG THOSE WHO HAVE ALREADY ATTEMPTED SUICIDE AT LEAST ONCE. ALTHOUGH SECONDARY PREVENTION IS CRUCIAL, THE MAJORITY OF DEATHS BY SUICIDE OCCUR ON FIRST ATTEMPT. THUS, TARGETED PRIMARY PREVENTION EARLIER IN DEVELOPMENT IS ESSENTIAL. MOST CURRENT PRI- MARY PREVENTION PROGRAMS ARE INTENSIVE, EXPENSIVE, AND DELIVERED BY HIGHLY TRAINED MENTAL HEALTH PROVIDERS, WHO ARE IN SHORT SUPPLY. TRADITIONAL FACE-TO-FACE THERAPY IS ALSO UNAVAILABLE TO MANY WHO LIVE IN UNDERSERVED COMMUNITIES, AND DISLIKED BY ADOLESCENTS, WHO MUCH PREFER DIGI- TAL DELIVERY ON THEIR DEVICES. THIS HIGH-RISK, HIGH-REWARD PROPOSAL ADDRESSES THESE LIMITATIONS AND NEEDS. WE USE AN EXPERIMENTAL THERAPEUTICS APPROACH TO EVALUATE THE INDEPENDENT AND COMBINED EFFICACIES OF TWO UNCONVENTIONAL BUT SCALABLE INTERVENTIONS: TRANSCUTANEOUS VAGUS NERVE STIMULATION (TVNS) TO TARGET EMOTION DYSREGULATION, AND A PEER-SUPPORT SMARTPHONE APP TO COMBAT SOCIAL ISOLATION. THESE LOW-COST INTERVENTIONS, WHICH HOLD STRONG PROMISE BUT HAVE NOT BEEN USED BEFORE, CAN REACH LARGE NUMBERS OF ADOLESCENTS, WITH MUCH POTENTIAL TO REDUCE PRO- SPECTIVE SUICIDE RISK. WE WILL ENROLL 212 ADOLESCENTS, AGES 13-17 YEARS, WHO SHOW ELEVATIONS ON AT LEAST TWO PROMINENT RISK FACTORS FOR SUICIDE (E.G., SELF-INJURY, MALTREATMENT). USING A 2 × 2 DE- SIGN, ADOLESCENTS WILL BE ASSIGNED RANDOMLY TO RECEIVE 30 DAYS OF TREATMENT WITH (1) TVNS TO TAR- GET EMOTION DYSREGULATION, (2) A PEER-SUPPORT PHONE APP TO TARGET SOCIAL ISOLATION, (3) TVNS + A PEER-SUPPORT PHONE APP, OR (4) ENHANCED TREATMENT AS USUAL WITH MONITORING AND ACCESS TO RE- SOURCES. INTERVENTION EFFECTS ON MECHANISMS (EMOTION DYSREGULATION, SOCIAL ISOLATION) PROXIMAL EFFICACY SIGNALS (E.G., PHYSIOLOGICAL REACTIVITY, SELF-HARM) AND TARGET OUTCOMES (SUICIDAL IDEATION, SUICIDAL BEHAVIORS) WILL BE EVALUATED IMMEDIATELY POST-INTERVENTION AND AT ONE-YEAR FOLLOW-UP. TREATMENT DATA WILL BE MONITORED DAILY TO FINE-TUNE DOSING OF BOTH INTERVENTIONS. THIS TRANSFORMA- TIVE AND INNOVATIVE PROPOSAL TESTS TWO NOVEL, SCALABLE PREVENTIVE INTERVENTIONS DESIGNED TO “MEET ADOLESCENTS WHERE THEY ARE" BY USING DIGITAL TECHNOLOGIES TO ADDRESS CORE MECHANISMS OF SUICIDE RISK.

QUIC-TAQS: DETERMINISTICALLY PLACED NUCLEAR SPIN QUANTUM MEMORIES FOR ENTANGLEMENT DISTRIBUTION

IDENTIFYING LOCAL-TO-GLOBAL WIN-WIN SOLUTIONS FOR HUMAN HEALTH AND SUSTAINABILITY THROUGH INFECTIOUS DISEASE CONTROL

PROBING LOCAL, HYBRID PEROVSKITE PHOTOPHYSICS THROUGH SPATIALLY- AND TEMPORALLY-RESOLVED ABSORPTION/EMISSION MICROSCOPY

FORECASTING SPREAD AND BIOECONOMIC IMPACTS OF AQUATIC INVASIVE SPECIES FROM MULTIPLE PATHWAYS TO IMPROVE MANAGEMENT AND POLICY IN THE GREAT LAKES.

MRI: ACQUISITION OF AN ACCELERATOR FOR STELLAR NUCLEOSYNTHESIS MEASUREMENTS

RESEARCH IN COLLIDER PHYSICS

EFFECTS OF AGRICULTURAL EXPANSION AND INTENSIFICATION ON INFECTIONS

EFFICACY OF FAMILY PROGRAMS FOR IMPROVING CHILD AND FAMILY HEALTH AND DEVELOPMENT.

UPWARD BOUND SOUTH BEND

PHYSICAL BASIS FOR T CELL RECEPTOR BINDING AND ACTIVITY

DIANA, A NOVEL NUCLEAR ACCELERATOR LAB UNDERGROUND

BULGECIN TEMPLATE FOR POTENTIATION OF BETA-LACTAM ANTIBIOTICS

FUNCTIONAL GENOMICS OF INVERSION 2LA IN ANOPHELES GAMBIAE

ROLES FOR INCREASED INTRACELLULAR PH AND HETEROGENEITY IN CA

AN INTEGRATIVE APPROACH TO ELUCIDATE GLIAL DIVERSITY AND ITS ROLE IN BRAIN FUNCTIONALITY

GOLD NANOCRYSTAL ANTIBIOTICS FOR THE TREATMENT OF MULTIDRUG-RESISTANT GRAM NEGATI

PHARMACOLOGICAL BLOCKAGE OF XBP-1S EXPRESSION IN CANCER

AN INTEGRATIVE SCIENCE APPROACH TO RESILIENCE: THE NOTRE DAME STUDY OF HEALTH & WELL-BEING

BLOOD COAGULATION PROTEIN-METAL ION-LIPID INTERACTIONS

FAMILIES OF YOUTH WITH DEVELOPMENTAL DISABILITIES: A THEORY-BASED INTERVENTION

ELUCIDATING AND BYPASSING MOLECULAR MECHANISMS THAT SUPPRESS MULLER GLIA-DEPENDENT REGENERATION OF CONES IN TWO ZEBRAFISH MODELS OF CHRONIC RETINAL DAMAGE - PROJECT SUMMARY: RETINAL DEGENERATIVE DISEASES ARE A MAJOR MEDICAL ISSUE FOR SOCIETY. ONE POTENTIALLY EXCITING APPROACH TO RESTORE VISION IS THE REGENERATION OF LOST RETINAL NEURONS FROM AN ENDOGENOUS POPULATION OF RETINAL CELLS, THE MÜLLER GLIA. WE ARE STUDYING THIS PROCESS IN ZEBRAFISH, WHICH UNLIKE MAMMALS, EXHIBITS A NATURAL MÜLLER GLIA- DEPENDENT RETINAL REGENERATION RESPONSE. HOWEVER, THERE ARE TWO MAJOR GAPS IN OUR UNDERSTANDING OF THIS RETINAL REGENERATION RESPONSE. THE FIRST IS WHY RAPID ACUTE DAMAGE EXHIBITS A REGENERATION RESPONSE AND A SLOW CHRONIC DAMAGE, WHICH IS WHAT IS OFTEN OBSERVED IN HUMAN RETINAL DEGENERATIVE DISEASES, DOES NOT INDUCE A REGENERATION RESPONSE IN ZEBRAFISH. THE SECOND GAP IN OUR UNDERSTANDING IS THE ROLE OF THE MICROGLIA, THE IMMUNE CELLS OF THE CENTRAL NERVOUS SYSTEM, WHICH ARE THE MAJOR SOURCE OF INFLAMMATION RESULTING FROM DAMAGE AND A KNOWN REGULATOR OF THE MÜLLER GLIA-DEPENDENT RETINAL REGENERATION. WE WILL ADDRESS THESE TWO GAPS IN THREE SPECIFIC AIMS. AIM 1 WILL DETERMINE THE POTENTIAL OF TWO DIFFERENT CHRONIC ZEBRAFISH RETINAL DEGENERATION MUTANTS (GOSH, AN EARLY ONSET RAPID CONE PHOTORECEPTOR DEGENERATION MUTANT AND CEP290, A LATE ONSET SLOW CONE DEGENERATION MUTANT) TO INDUCE MÜLLER GLIA PROLIFERATION AND REGENERATE LOST CONES USING DIFFERENT STIMULI. WE WILL DETERMINE TO WHAT EXTENT EITHER A SECONDARY ACUTE DAMAGE OR THE INTRODUCTION OF MOLECULES THAT STIMULATE MÜLLER GLIA PROLIFERATION CAN INDUCE CONE REGENERATION IN CHRONICALLY DAMAGED FISH AND HOW COMPLETE THE REGENERATION PROCESS IS. IN AIM 2, WE WILL CONDUCT A COMPREHENSIVE AND UNBIASED, COMPARATIVE ANALYSIS OF GENE EXPRESSION AND CHROMATIN ACCESSIBILITY IN MÜLLER GLIA AND MICROGLIA USING A MULTIOMIC SINGLE-NUCLEAR RNA- SEQ AND ATAC-SEQ ANALYSIS IN THESE TWO CHRONIC DEGENERATION MUTANTS, ALONG WITH TWO MOUSE CHRONIC RETINAL DEGENERATION MUTANTS. WE WILL DETERMINE THE SIMILARITIES AND DIFFERENCES IN GENE EXPRESSION AND CHROMATIN ACCESSIBILITY IN THE MÜLLER GLIA AND MICROGLIA BETWEEN THE ACUTELY AND CHRONICALLY DAMAGED RETINAS. THESE BIOINFORMATIC ANALYSES WILL REVEAL TRANSCRIPTION FACTORS AND SIGNALING (CYTOKINE, GROWTH FACTORS, LIGAND/ RECEPTOR PAIRS) MOLECULES THAT ARE ESSENTIAL FOR REGENERATION FOLLOWING ACUTE DAMAGE AND BLOCKING REGENERATION IN THE CHRONICALLY DAMAGED ZEBRAFISH RETINA. WE WILL ALSO DETERMINE THE DIFFERENCES AND SIMILARITIES BETWEEN THE CHRONICALLY DAMAGED ZEBRAFISH AND MOUSE RETINAS TO DETERMINE HOW SIMILAR THESE REGULATORY COMPONENTS ARE BETWEEN THE ZEBRAFISH AND MOUSE. AIM 3 WILL THEN FUNCTIONALLY TEST THE ROLES OF THE CANDIDATE REGULATORS PREVIOUSLY IDENTIFIED IN OUR SCRNA-SEQ DATASETS OR IN AIM 2 BY EITHER MODIFYING THEIR EXPRESSION OR THEIR ACTIVITY IN THE CHRONICALLY AND ACUTELY DAMAGED ZEBRAFISH RETINA. THIS WORK WILL BE THE FIRST MOLECULAR ANALYSIS OF HOW RETINAL REGENERATION IS REGULATED IN THE CHRONICALLY DAMAGED ZEBRAFISH RETINA AND WILL BE CRITICAL IN THE TRANSLATION OF MÜLLER GLIAL-DEPENDENT RETINAL REGENERATIVE THERAPIES INTO HUMAN RETINAL DEGENERATIVE DISEASES.

IDENTIFICATION OF KIDNEY REGENERATION MECHANISMS USING THE ZEBRAFISH

DESIGN AND USE OF NOVEL BACTERIOCINS

UPWARD BOUND

PATHWAYS LINKING EARLY ADVERSITY AND SUPPORT TO BEHAVIORAL AND PHYSICAL HEALTH

AIRBORNE AERO-OPTICS LABORATORY - TRANSONIC (AAOL-T)

AN EVIDENCE-BASED FAMILY SUPPORT PROGRAM FOR PARENTS AND CHILDREN IN PALESTINE: A THEORY-BASED INTERVENTION - PROJECT SUMMARY/ABSTRACT FEW EVIDENCE-BASED PROGRAMS EXIST TO SUPPORT CHILDREN AND FAMILIES AFFECTED BY SOCIOPOLITICAL CONFLICT, DESPITE DOCUMENTED EVIDENCE OF THEIR HEIGHTENED RISK FOR EMOTIONAL AND BEHAVIORAL ADJUSTMENT PROBLEMS ASSOCIATED WITH EXPOSURE TO CONFLICT AND VIOLENCE AT MULTIPLE LEVELS OF THE SOCIAL ECOLOGY (E.G., POLITICAL, COMMUNITY, AND FAMILY). THUS, A CRITICAL NEED EXISTS FOR AN EVIDENCE-BASED PROGRAM TO AMELIORATE THE IMPACT OF POLITICAL VIOLENCE ON THE OVERALL WELL-BEING OF CHILDREN AND FAMILIES. THE CURRENT STUDY WILL CONDUCT A RIGOROUS EVALUATION OF A THEORETICALLY-DRIVEN, FAMILY-BASED INTERVENTION PROGRAM IN PALESTINE, INCLUDING BOTH THE WEST BANK AND GAZA. FIRMLY GROUNDED IN THE CULTURAL CONTEXT OF PALESTINE BUT WITH BROAD IMPLICATIONS FOR INDIVIDUALS EXPOSED TO SOCIOPOLITICAL VIOLENCE, THE LONG-TERM GOAL OF THIS PROJECT IS TO PROVIDE A FAMILY-FOCUSED INTERVENTION PROGRAM (PROMOTING POSITIVE FAMILY FUTURES; PPFF) THAT MAY FACILITATE INDIVIDUALS’ SENSE OF SAFETY AND SUPPORT IN THE CONTEXT OF CHRONIC ADVERSITY. THE OBJECTIVE IS TO EVALUATE THIS INTERVENTION PROGRAM IN THE CONTEXT OF A RANDOMIZED CLINICAL TRIAL (RCT) IN THE WEST BANK AND GAZA (N=300). THE CENTRAL HYPOTHESIS IS THAT THE PROGRAM WILL HAVE DIRECT POSITIVE EFFECTS ON FAMILY CONFLICT, PARENT PSYCHOPATHOLOGY AND PARENTAL SECURITY IN THE FAMILY AS WELL AS ON ADOLESCENT EMOTIONAL SECURITY IN THE FAMILY, WITH CASCADING EFFECTS ON ADOLESCENT ADJUSTMENT. CONSISTENT WITH FAMILY SYSTEMS THEORY, WE FURTHER HYPOTHESIZE THAT TREATMENT EFFECTS ON PARENTS WILL MEDIATE ON THE EFFECTS OF THE TREATMENT ON ADOLESCENT ADJUSTMENT. THE RATIONALE IS THAT BOLSTERING RESILIENCE IN FAMILY SYSTEMS IS A KEY APPROACH TO PROMOTING POSITIVE FUNCTIONING IN FAMILIES EXPOSED TO CHRONIC VIOLENCE. THE HYPOTHESIS WILL BE EVALUATED WITH THREE SPECIFIC AIMS: 1) EVALUATE THE EFFICACY OF AN EVIDENCE-BASED FAMILY SUPPORT PROGRAM; 2) EXAMINE PROCESS MODELS OF TREATMENT CHANGE, AND 3) EXAMINE INTERRELATIONS BETWEEN PARENT AND CHILD FUNCTIONING. TO ACHIEVE THESE AIMS, THE STUDY WILL BE AN RCT EMPLOYING A LONGITUDINAL DESIGN (N=300) WITH MULTI-METHOD ASSESSMENTS AT BASELINE (T1), POST-TEST (T2), 6-MONTH FOLLOW-UP (T3) AND 12-MONTH FOLLOW-UP (T4). FAMILIES INCLUDED IN THE STUDY WILL BE EVENLY DIVIDED BETWEEN THE WEST BANK (N=150) AND GAZA STRIP (N=150). FAMILIES WILL BE RANDOMIZED INTO THE INTERVENTION CONDITION (PPFF) OR TREATMENT AS USUAL (TAU). EACH TERRITORY WILL HAVE AN IMPLEMENTING PARTNER, AND IMPLEMENTING PARTNERS AND INVESTIGATORS WILL WORK TOGETHER TO ENSURE THE STUDY PROCEDURES ARE IMPLEMENTED IN PARALLEL ACROSS SITES. DATA COLLECTION WILL BE CONDUCTED BY TRAINED RESEARCH STAFF FROM A THIRD-PARTY SURVEY AND POLICY RESEARCH ORGANIZATION. THE PROPOSAL SEEKS TO SHIFT CURRENT RESEARCH AND CLINICAL PARADIGMS IN THESE CONTEXTS BY EMPLOYING NOVEL THEORETICAL CONCEPTS, APPROACHES, AND METHODOLOGIES. THE CONTRIBUTION WILL BE SIGNIFICANT BY 1) FURTHER DEVELOPING NEW DIRECTIONS FOR EMPIRICALLY-BASED INTERVENTIONS IN THESE HIGH-RISK CONTEXTS, AND 2) ADVANCING A RELATIVELY BRIEF, COST-EFFECTIVE PROGRAM THAT CAN BE READILY IMPLEMENTED TO HELP CHILDREN AND FAMILIES EXPOSED TO CONTINUING CONFLICT IN PALESTINE, WITH THE POTENTIAL TO BE BROUGHT TO SCALE IN OTHER CONTEXTS.

UPWARD BOUND SOUTH BEND

DETERMINATION OF STRUCTURE, DYNAMICS AND ENERGETICS OF ENZYME REACTIONS

LONG-COHERENCE HIGH-FIDELITY ELECTRON QUBITS ON QUANTUM SOLIDS

JOINT INSTITUTE FOR NUCLEAR ASTROPHYSICS - JINA

EFFECTIVENESS OF AN EMPIRICALLY SUPPORTED FAMILY INTERVENTION: MENTAL HEALTH OUTCOMES, MECHANISMS OF EFFECT, AND ORGANIZATIONAL FACTORS - PROJECT SUMMARY/ABSTRACT COST-EFFECTIVE, BRIEF PROGRAMS TO SUPPORT FAMILY COMMUNICATION AND IMPROVE MENTAL HEALTH IN YOUTH ARE A PRESSING NEED; YET FEW EVIDENCE-BASED PROGRAMS EXIST. OUR GROUP HAS DEVELOPED AND RIGOROUSLY TESTED AN EMPIRICALLY-SUPPORTED FAMILY-SYSTEMS APPROACH TO IMPROVING COMMUNICATION AND CONFLICT IN FAMILIES, THEREBY IMPROVING MENTAL HEALTH IN YOUTH. BENEFICIAL EFFECTS FOR YOUTH MENTAL HEALTH AND OTHER INDICES OF ADJUSTMENT ASSOCIATED WITH THE HAPPY FAMILIES CURRICULUM HAVE BEEN SUPPORTED IN SEVERAL EFFICACY TRIALS WITH FAMILIES FROM A VARIETY RISK CONTEXTS. HOWEVER, THE VALUE OF EFFICACY RESEARCH IS LIMITED UNLESS IT IS SUBSEQUENTLY TESTED IN THE CONTEXT OF AN EFFECTIVENESS TRIAL. GIVEN THE POTENTIAL LARGE-SCALE BENEFITS OF BROAD IMPLEMENTATION OF THE HAPPY FAMILIES CURRICULUM, A CRITICAL NEED EXISTS FOR AN EFFECTIVENESS TRIAL TO EVALUATE THE PROGRAM WHEN IT IS IMPLEMENTED IN COMMUNITY SETTINGS BY FACILITATORS WHO WOULD PROVIDE THE PROGRAM IN “REAL WORLD” SETTINGS. OUR OBJECTIVE IN THIS PROPOSAL IS TO TEST THE EFFECTIVENESS FOR A LARGE SAMPLE, IN DIFFERENT CONTEXTS OF RISK, OF THE BRIEF (I.E. 4 SESSION) PSYCHO-EDUCATIONAL AND COMMUNICATION TRAINING APPROACH USED IN OUR EFFICACY TRIALS, AND TO EXAMINE THE MECHANISMS ASSOCIATED WITH CHANGE PROCESSES THAT OCCUR AS A RESULT OF THE PROGRAM, INCLUDING EMOTIONAL SECURITY AS A MEDIATOR OF PROGRAM EFFECTS AND MODERATORS OF EFFECTS ASSOCIATED WITH PARTICIPANTS’ SOCIOECONOMIC AND CONTEXTUAL RISKS AS WELL AS ORGANIZATIONAL FACTORS THAT MAY IMPACT PROGRAM EFFECTIVENESS. OUR CENTRAL HYPOTHESIS IS THAT PARTICIPATION IN THE PROGRAM WILL IMPROVE PATTERNS OF COMMUNICATION AND CONFLICT IN FAMILIES, THEREBY IMPROVING YOUTH MENTAL HEALTH. THIS HYPOTHESIS IS SUPPORTED BY EXTENSIVE EFFICACY RESEARCH ON THE HAPPY FAMILIES CURRICULUM AND CONCLUSIONS BASED ON A RECENTLY CONDUCTED FEASIBILITY STUDY OF THE PROPOSED EFFECTIVENESS TRIAL. OUR RATIONALE IS THAT PROVIDING A FAMILY-SYSTEMS APPROACH TO IMPROVING THE FAMILY ENVIRONMENT WILL SUPPORT YOUTH MENTAL HEALTH OVER TIME. THE SPECIFIC AIMS ARE: (1) EVALUATING PROGRAM EFFECTIVENESS FOR IMPROVING COMMUNICATION, REDUCING DESTRUCTIVE CONFLICT IN FAMILIES AND ENHANCING MENTAL HEALTH IN YOUTH, (2) TESTING PROCESS MODELS, GUIDED BY THE EMOTIONAL SECURITY THEORY (EST; DAVIES & CUMMINGS, 1994), TO EXPLAIN HOW, WHY, FOR WHOM AND WHEN, CHANGES OCCUR AS A RESULT OF THE PROGRAM, AND (3) EVALUATING ORGANIZATIONAL FACTORS ASSOCIATED WITH PROGRAM EFFECTIVENESS, INCLUDING THE IMPACT OF ORGANIZATION STRUCTURE AND FACILITATOR TYPE, AND ORGANIZATIONS’ SUBJECTIVE EVALUATION OF THE PROGRAM. THIS APPROACH IS INNOVATIVE BECAUSE IT UTILIZES AN RCT DESIGN TO TEST THE EFFECTIVENESS OF A PROVEN FAMILY-SYSTEMS APPROACH THAT REPRESENTS A BRIEF, INEXPENSIVE AND READILY SCALABLE APPROACH TO FOSTER CHANGE IN FAMILIES’ COMMUNICATION PATTERNS AND IMPROVE MENTAL HEALTH. THE PROGRAM IS BASED ON A WELL-ESTABLISHED THEORETICAL MODEL FOR “MECHANISMS OF EFFECT” AND BACKED BY EVIDENCE FOR PROGRAM EFFICACY. THIS RESEARCH IS SIGNIFICANT BECAUSE IT WILL RESULT IN AN INEXPENSIVE MODEL PROGRAM FOR FAMILY-SYSTEM-LEVEL INTERVENTIONS THAT IS SUSTAINABLE IN THE ORGANIZATIONS IT IS TESTED IN, AND READILY ADJUSTED TO OTHER CONTEXTS.

M. AVIUM GPLS IN MACROPHAGE ACTIVATION AND VIRULENCE

INTERVENING DURING THE PRENATAL PERIOD WITH WOMEN EXPOSED TO INTIMATE PARTNER VIOLENCE TO IMPROVE MATERNAL FUNCTIONING AND INFANT ADJUSTMENT

CONTROL OF VECTOR-BORNE DISEASES: DEVELOPMENT OF HUMAN-SAFE INSECTICIDES FOR US MILITARY PROTECTION AND IMPROVING GLOBAL HEALTH II

DATA AND SOFTWARE PRESERVATION FOR OPEN SCIENCE (DASPOS)

REGULATION OF OVARIAN CARCINOMA PROTEINASES

TALENT SEARCH PROGRAM

TALENT SEARCH PROGRAM

ADAPTING A POINT OF USE TEST CARD, THE CHEMOPAD, FOR PROTECTING CHEMOTHERAPY DRUG QUALITY IN SUB-SAHARAN AFRICA - ADAPTING A POINT OF USE TEST CARD, THE CHEMOPAD, FOR PROTECTING CHEMOTHERAPY DRUG QUALITY IN SUB-SAHARAN AFRICA PROJECT SUMMARY/ABSTRACT GOAL: VALIDATE A NEW TECHNOLOGY FOR DETECTING BAD QUALITY CHEMOTHERAPY PRODUCTS AT THE POINT OF USE. MOTIVATION: CHEMOTHERAPY MEDICINES FORM THE BACKBONE OF AFFORDABLE CANCER TREATMENT IN LOW- AND MIDDLE- INCOME COUNTRIES (LMICS), YET LMICS OFTEN LACK TECHNICAL AND REGULATORY CAPACITY TO EVALUATE THE QUALITY OF CHEMOTHERAPY PRODUCTS. THERE IS CURRENTLY NO COMMERCIAL TECHNOLOGY TO SCREEN FOR BAD QUALITY CHEMOTHERAPY PRODUCTS AT THE POINT OF USE IN LMIC SETTINGS, AND THE DRUG REGULATORS IN ETHIOPIA, MALAWI, KENYA, AND CAMEROON DO NOT CONDUCT POST-MARKET SURVEILLANCE TESTING ON CHEMOTHERAPY PRODUCTS. ACTIVITIES: THE TECHNOLOGY THAT WILL BE VALIDATED, CALLED SPOTCHECK, CONSISTS OF AN INEXPENSIVE PAPER TEST CARD (THE CHEMOPAD) AND A CELL PHONE APP. WE WILL FIRST ADAPT THE CHEMOPAD TO SCREEN EIGHT TYPES OF INJECTABLE CHEMOTHERAPY DRUGS. THE PHONE APP’S NEURAL NETWORK WILL BE TRAINED TO IDENTIFY PRODUCTS THAT ARE FALSIFIED OR CONTAIN LESS THAN 65% OF THE STATED API CONTENT. CLINICAL, ACADEMIC, AND SUPPLY CHAIN PARTNERS IN ETHIOPIA, MALAWI, CAMEROON, AND KENYA WILL CONDUCT ANNUAL SITUATION AWARENESS AND QUALITY SURVEYS OF 320 CHEMOTHERAPY PRODUCTS PER YEAR; THE RESULTS WILL ENABLE A TEAM OF RESEARCHERS AT U. NORTH CAROLINA TO MODEL THE MARKETS FOR CHEMOTHERAPY PRODUCTS AND EVALUATE THE COST-EFFECTIVENESS OF THE SPOTCHECK SYSTEM. AFTER A TECHNICAL PERFORMANCE MILESTONE IS PASSED, WE WILL TAILOR THE CLINICAL VALIDATION OF SPOTCHECK TO SUIT THE LOCAL NEEDS, CLINICAL WORKFLOWS, AND REGULATORY CAPACITY IN EACH SITE. THE VALIDATION OF THE SPOTCHECK SYSTEM WILL PROCEED THROUGH A PLANNING AND ETHICAL APPROVAL MILESTONE (Y3 IN ETHIOPIA AND MALAWI AND Y4 IN KENYA AND CAMEROON) AND THREE CLINICAL PHASES: PROFICIENCY STUDY, CLINICAL VALIDATION, AND IMPLEMENTATION PILOT. PROFICIENCY TESTING WILL DEMONSTRATE THAT ONCOLOGY PHARMACISTS AND NURSES CAN USE SPOTCHECK WITH ACCURACY >85% TO DETECT SF PRODUCTS. CLINICAL VALIDATION WILL ESTABLISH WHETHER SPOTCHECK WORKS CORRECTLY IN A CLINICAL SETTING ON AUTHENTIC PRODUCTS, RATHER THAN PROFICIENCY SAMPLES. THE IMPLEMENTATION PILOT STUDY WILL PROBE SPOTCHECK’S ABILITY TO TEST THE DROPS LEFT OVER IN PRODUCT VIALS AFTER PATIENT TREATMENTS ARE PREPARED IN THE HOSPITAL; THIS METHOD OF USE WOULD ALLOW SUSTAINABLE IMPLEMENTATION OF SPOTCHECK IN MANY HOSPITALS AND CLINICS IN LOW-RESOURCE SETTINGS. TECHNOLOGY TRANSFER EFFORTS WILL EMPOWER LMIC PARTNERS TO PRODUCE THE CHEMOPAD LOCALLY AND INTEGRATE THE CELL PHONE APP INTO REGULATORY REPORTING SYSTEMS. IMPACT: THIS PROJECT WILL HELP TO FILL THE HUGE EVIDENCE GAP ABOUT THE QUALITY OF CHEMO DRUGS IN LMICS, MAKE IT HARDER FOR MANUFACTURERS AND DISTRIBUTORS TO SELL BAD QUALITY PRODUCTS, AND IMPROVE THE QUALITY OF PRODUCTS THAT ARE USED TO TREAT PATIENTS IN LMICS. 1

NORTHWEST INDIANA COMPUTATIONAL GRID (NWIC-GRID)

EFRI BEGIN OI: IMPLANTATION OF DENSE ASSOCIATIVE MEMORY THROUGH CARDIAC MUSCLE CELL-BASED REPROGRAMMABLE BIO-OSCILLATORY NEURAL NETWORKS -ALL ORGANISMS COLLECT AND STORE INFORMATION. THIS HOLDS TRUE FOR SINGLE- AND MULTI-CELLED ORGANISMS. THE INFORMATION IS USED TO INFORM DECISION-MAKING. THIS INSIGHT LED TO THE NOTION OF BIOCOMPUTING. A PROMISING BIOCOMPUTING SYSTEM COULD INVOLVE CARDIAC MUSCLE CELLS. THEY NATURALLY TRANSMIT ELECTRICITY. THIS PROJECT IS DESIGNED TO EXPLORE THE PROGRAMMING OF ARRAYS OF CARDIAC MUSCLE CELLS. IF THESE ARRAYS ARE PROGRAMMABLE AND CAN STORE INFORMATION, THEY WOULD OFFER AN ENERGY-EFFICIENT COMPUTATIONAL SYSTEM. THE PROJECT WILL ALSO INVOLVE INTERDISCIPLINARY STUDENT MENTORING AND WORKSHOPS FOR UNDERGRADUATE AND HIGH SCHOOL STUDENTS. ONE WORKSHOP WILL BE DEDICATED TO ETHICAL, PHILOSOPHICAL, AND SOCIAL SCIENCE DIMENSIONS OF THE PROJECT. THE GOAL OF THIS PROJECT IS TO EXPLORE THE POTENTIAL OF USING HEART MUSCLE CELLS AS THE BASIS FOR A RECURRENT (HOPFIELD) NEURAL NETWORK. THE HYPOTHESIS IS THAT CARDIAC MUSCLE CELL-BASED REPROGRAMMABLE BIOOSCILLATOR NEURAL NETWORKS (CARBON) CAN IMPLEMENT SCALABLE AND HIGH-CAPACITY ASSOCIATIVE MEMORY. THE CARDIAC MUSCLE CELLS WILL BE CONNECTED BY FIBROBLASTS. A KEY COMPONENT OF THE PROJECT IS MODIFYING THE FIBROBLAST CELL LINES WITH OPTOGENETICALLY TUNABLE ION CHANNELS. THESE CHANNELS WOULD BE USED TO ADJUST THEIR CAPACITIVE (C), RESISTIVE (R) AND HYBRID-RC FILTER CHARACTERISTICS. THIS ENABLES THEIR APPLICATION AS PROGRAMMABLE WEIGHTS IN THE HOPFIELD RNN. THE RESEARCH HAS ETHICAL, LEGAL, AND SOCIAL IMPLICATIONS THAT WILL BE STUDIED BY EXPLORING QUESTIONS THAT WERE NEVER ANSWERED BEFORE. IN A HIGHLY CONVERGENT ENDEAVOR, THIS PROJECT WILL AIM TO STUDY QUESTIONS PERTAINING TO SYSTEMS CAPABLE OF DISPLAYING ASPECTS OF INTELLIGENCE, ESPECIALLY NOT IN TRADITIONAL ?REGULATORY ETHICS? WAY, BUT AROUND QUESTIONS THAT EXPLORE THE TOPIC FROM A CULTURAL AND TRADITIONAL STANDPOINT TO PHILOSOPHY OF MIND AND TO METAPHYSICAL QUESTIONS AROUND ?WHAT PROPERTIES DOES A ?COMPUTING? DEVICE OR SYSTEM NEED TO HAVE TO BE CALLED AN ?ENTITY,? ?LIVING? OR ?INTELLIGENT??, TO HISTORY AND PHILOSOPHY OF SCIENCE QUESTIONS SUCH AS ?WHAT IS THE HISTORY AND FUTURE OF BIOCOMPUTING?? NONE OF WHICH HAS BEEN ASKED BEFORE IN THE CONTEXT OF BIOCOMPUTING USING LIVING CELLS. THIS PROJECT IS JOINTLY FUNDED BY THE EMERGING FRONTIERS IN RESEARCH AND INNOVATION PROGRAM (BEGIN OI), THE DIRECTORATE FOR BIOLOGICAL SCIENCES, AND THE DIRECTORATE FOR MATHEMATICAL AND PHYSICAL SCIENCES. 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.

EFRI 2-DARE: MONOLAYER HETEROSTRUCTURES: EPITAXY TO BEYOND-CMOS DEVICES

EMPOWERING FUNCTIONAL GENOMICS OF AN. GAMBIAE THROUGH INVERSION GENOTYPING

CHEMICAL APPROACHES TO SELECTIVELY TARGET BETA-RICH AMYLOIDS - PROJECT ABSTRACT PROTEIN-PROTEIN INTERACTIONS ARE GOVERNED BY RECOGNITION EVENTS BETWEEN PEPTIDE SECONDARY STRUCTURES (A- HELICES, B-SHEETS, LOOPS), WHICH IN TURN PROVIDE DESIGN CUES FOR THE DEVELOPMENT OF SELECTIVE CHEMICAL PROBES. HOWEVER, REMOVAL OF ORDERED PEPTIDE DOMAINS FROM THE CONTEXT OF THE SURROUNDING TERTIARY STRUCTURE COMPROMISES FOLDING AND CONFORMATIONAL STABILITY. MIMICRY AND DISRUPTION OF B-STRAND/SHEET INTERACTIONS REMAINS A CONSIDERABLE CHALLENGE. THIS IS LARGELY DUE TO THE INHERENT FLEXIBILITY OF SHORT PEPTIDE SEQUENCES, THE PROPENSITY FOR B-STRANDS TO AGGREGATE, AND THE LARGE SURFACE AREAS AND DIVERSE MODES OF B-SHEET PACKING. THE EARLY OLIGOMERIZATION OF SEVERAL AMYLOIDOGENIC PROTEINS INVOLVES CONFORMATIONAL REORGANIZATION INTO PARALLEL B-SHEET STRUCTURES, FOLLOWED SUPRAMOLECULAR ASSEMBLY INTO TOXIC FIBRILS. RECENT ATOMIC-LEVEL STRUCTURAL DATA USING PATIENT-DERIVED EXTRACTS HAS REVEALED THAT NEUROTOXIC AMYLOIDS MAY BE CHARACTERIZED BY UNIQUE STRUCTURAL POLYMORPHS, OR ‘STRAINS’, DEPENDING ON THE DISEASE. DESPITE THE NEED FOR AMYLOID- AND STRAIN-SPECIFIC LIGANDS, B-RICH AMYLOID ASSEMBLIES REPRESENT PARTICULARLY CHALLENGING TARGETS. WE RECENTLY ESTABLISHED PEPTIDE BACKBONE N-AMINATION AS A SUBTLE YET REMARKABLY EFFECTIVE APPROACH TO B-STRAND/SHEET STABILIZATION. THE CONFORMATIONAL AND NON-AGGREGATING CHARACTERISTICS OF N-AMINO PEPTIDES (NAPS) RENDER THEM UNIQUELY SUITED FOR CAPPING THE GROWTH OF SHEET FIBRILS WHILE MAINTAINING THE FACIAL PACKING AND SIDECHAIN INTERDIGITATION IMPORTANT FOR AMYLOID RECOGNITION. HERE, WE WILL FURTHER DEVELOP SOLUBLE MIMICS OF DIVERSE B-SHEET-LIKE FOLDS TO DISRUPT AMYLOID AGGREGATION IN A SEQUENCE AND STRAIN-SPECIFIC MANNER. AS A PROOF-OF-CONCEPT, WE WILL TARGET THE ASSEMBLY AND CELLULAR TRANSMISSION OF TAU FIBRILS THAT CHARACTERIZE NUMEROUS SPORADIC AND HEREDITARY NEURODEGENERATIVE DISORDERS. OUR OVERARCHING HYPOTHESIS IS THAT THE STRUCTURAL FEATURES OF PEPTIDE N-AMINATION WILL ENABLE THE DEVELOPMENT OF LIGANDS THAT SELECTIVELY TARGET B-RICH AMYLOID FOLDS. IN AIM 1 WE WILL EXPAND THE UTILITY OF NAP MODIFICATION IN PURSUIT OF HYPERSTABLE B-STRANDS AND AMYLOID MIMICS BASED ON PARALLEL B-SHEET MACROCYCLES. A LIBRARY OF NAP-BASED TAU MIMICS WILL BE SYNTHESIZED IN AIM 2. THESE COMPOUNDS WILL BE EVALUATED FOR THEIR ABILITY TO BLOCK AGGREGATION AND CELLULAR TRANSMISSION OF RECOMBINANT TAU FIBRILS AS WELL THOSE EXTRACTED FROM AD PATIENTS. IN AIM 3, WE WILL SYNTHESIZE A SERIES OF AGGREGATION-RESISTANT NAP MACROCYCLES THAT MIMIC THE CROSS-B PACKING OBSERVED IN PATHOGENIC TAU STRAINS. THESE WILL BE EVALUATED FOR THEIR CAPACITY TO SPECIFICALLY INHIBIT CELLULAR SEEDING BY TAU FIBRILS DERIVED FROM AD AND CBD BRAINS. WE ANTICIPATE THAT LIGANDS EMERGING FROM THIS STUDY WILL ENABLE A ROBUST EXAMINATION OF THE THE PATHOGENIC STRAIN MODEL OF TAU TRANSMISSION. MORE BROADLY, THESE STUDIES WILL HAVE A SIGNIFICANT IMPACT ON THE DESIGN OF OTHER SELECTIVE DISRUPTORS OF B-SHEET AND AMYLOID ASSEMBLIES THAT ARE INHERENTLY DIFFICULT TO TARGET.

DIMENSIONS US-CHINA: INTEGRATING THE DIMENSIONS OF BIODIVERSITY TO UNDERSTAND TREE PERFORMANCE IN A CHANGING WORLD

INFLUENCE OF TRANSLATION ON PROTEIN FOLDING

AN INTEGRATED HUMAN ORGAN-ON-CHIP ULTRASENSITIVE MIRNA DETECTION PLATFORM FOR NOVEL BIOMARKER DISCOVERY

QUARKNET -THIS AWARD SUPPORTS THE CONTINUATION OF QUARKNET, A PROGRAM WHICH PROVIDES VALUABLE RESEARCH EXPERIENCE TO HIGH SCHOOL TEACHERS, ENABLING THEM TO TEACH THE BASIC CONCEPTS OF INTRODUCTORY PHYSICS IN A CONTEXT THAT STUDENTS FIND EXCITING. QUARKNET HAS CREATED AN ONGOING NATIONAL COMMUNITY OF RESEARCHERS THAT INCLUDE HIGH SCHOOL TEACHERS AND STUDENTS AS WELL AS PHYSICISTS. QUARKNET'S GOALS ARE TO MAINTAIN AND ENHANCE THIS COMMUNITY, TO ATTRACT YOUNG STUDENTS TO CAREERS IN SCIENCE AND TECHNOLOGY, TO HELP DEVELOP SCIENTIFIC LITERACY IN SOCIETY, AND TO DEVELOP LINKS BETWEEN THE HIGH SCHOOL CLASSROOM AND EXPERIMENTS AND TECHNIQUES USED TO EXPLORE THE SCIENTIFIC FRONTIER. KEY FEATURES OF QUARKNET ARE THE ESTABLISHMENT OF MENTOR RELATIONSHIPS BETWEEN TEACHERS AND SCIENTISTS, SUMMER RESEARCH EXPERIENCES FOR TEACHERS, AND THE DEVELOPMENT OF A SCIENTIFIC AND LEARNING COMMUNITY WITHIN AND AMONG CENTERS. QUARKNET PROVIDES OPPORTUNITIES FOR TEACHERS TO BECOME MORE PROFESSIONAL, RESULTING IN THE DEVELOPMENT OF PROGRAMMING FOR PEERS IN THE CENTER, IN THEIR SCHOOLS AND DISTRICTS AND BEYOND. QUARKNET PROVIDES A CENTRALLY HOSTED, SCALABLE, PARALLEL CYBERLEARNING ENVIRONMENT AS A CLOUD-LIKE SERVICE. HELD AT UNIVERSITY AND LABORATORY CENTERS, MASTERCLASSES ARE INSTITUTES FOR TEAMS OF STUDENTS WHO BECOME PHYSICISTS FOR A DAY, ANALYZING REAL EXPERIMENTAL DATA AND DISCUSSING RESULTS IN VIDEOCONFERENCES WITH PEERS AND PHYSICISTS. UNDER THIS THREE-YEAR AWARD, QUARKNET WILL SUPPORT MORE THAN 50 CENTERS PARTICIPATING IN A VARIETY OF EXPERIMENTS AT CERN, FERMILAB AND IN NON-ACCELERATOR AND ASTROPHYSICS PROGRAMS. IN THIS THREE-YEAR PERIOD, THE QUARKNET PROGRAM WILL SUPPORT: (1) THE LOCAL PROGRAMS OF THE LONG-TERM QUARKNET CENTERS FOR ~400 TEACHERS PER YEAR WHO RECEIVE STIPENDS; (2) A FEW TEACHERS WITH MULTI-WEEK SUMMER RESEARCH APPOINTMENTS TO WORK UNDER THE GUIDANCE OF PHYSICISTS FROM A UNIVERSITY OR LABORATORY NEAR THEIR HOMES SHOULD NEW CENTERS JOIN THE COLLABORATION; (3) 72 TEACHERS WHO WILL ATTEND A ONE-WEEK PARTICLE PHYSICS DATA CAMP AT FERMILAB TO BE IMMERSED IN AN INTENSIVE EXPERIENCE TO LEARN MORE PARTICLE PHYSICS AND ONE THAT MODELS AN INVESTIGATION APPROACH TO INQUIRY TEACHING AND LEARNING; (4) 72 TEACHERS WILL ATTEND A ONE-WEEK CODING CAMP. CODING CAMPS PUT AUTHENTIC EXPERIMENTAL DATA INTO THE HANDS OF TEACHERS AND PROVIDE THE APPROPRIATE BACKGROUND, IT TOOLS, TRAINING AND SUPPORT THAT ALLOWS THEM TO SUCCESSFULLY GUIDE THEIR STUDENTS IN CLASSROOM RESEARCH INVESTIGATIONS. (5) 32 FELLOWS WITH CONTINUING TRAINING THAT GIVES THEM THE KNOWLEDGE AND SKILLS TO OFFER PROFESSIONAL DEVELOPMENT EXPERIENCES FOR OTHER TEACHERS; AND (6) 60 TEACHERS WHO WILL BE INVOLVED WITH MASTERCLASSES. OVER THE THREE YEARS (2023-2026) THIS PROJECT IS EXPECTED TO REACH, IN ADDITION TO THE TEACHERS, MORE THAN 150 PHYSICISTS, AND EVENTUALLY WELL OVER 60,000 STUDENTS. A PORTION OF THIS EFFORT IS SUPPORTED THROUGH THE NSF ATLAS AND CMS OPERATIONS AWARDS. 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.

COLLABORATIVE RESEARCH: CSSI FRAMEWORKS: FROM NOTEBOOK TO WORKFLOW AND BACK AGAIN -COMPUTATIONAL NOTEBOOKS HAVE BECOME A CORNERSTONE OF THE SCIENTIFIC COMPUTING ENTERPRISE, PROVIDING AN INTERACTIVE MEANS TO ACQUIRE AND COMMUNICATE INSIGHTS, SHARE DISCOVERIES, AND VISUALIZE EXPERIMENTAL OUTCOMES. HOWEVER, COMPUTATIONAL NOTEBOOKS TODAY ARE MOST SUITED FOR SMALL-SCALE EXPLORATIONS CARRIED OUT ON A SINGLE COMPUTER, AND ARE QUITE DIFFICULT TO USE FOR LARGE-SCALE COMPUTATIONS ON HIGH PERFORMANCE COMPUTING CLUSTERS OR COMMERCIAL CLOUDS. THIS PROJECT WILL DEVELOP NBFLOW, A SOFTWARE TOOLKIT FOR CONVERTING NOTEBOOK COMPUTATIONS INTO WORKFLOWS THAT ARE FEASIBLE TO EXECUTE EFFICIENTLY ON CLUSTERS OR CLOUDS. THIS WILL MAKE IT POSSIBLE TO USE NOTEBOOK TECHNOLOGIES IN CONJUNCTION WITH HIGH PERFORMANCE CLUSTERS TO ENABLE NEW DISCOVERIES IN SCIENTIFIC FIELDS SUCH AS HIGH ENERGY PHYSICS AND GEOSCIENCES. THESE TECHNOLOGIES WILL BE USED TO DEVELOP NEW EDUCATIONAL CURRICULA, OUTREACH ACTIVITIES FOR K-12 STUDENTS, AND RESEARCH EXPERIENCES FOR COLLEGE STUDENTS. NBFLOW WILL SUPPORT AND ADVANCE THE USE OF COMPUTATIONAL NOTEBOOKS IN SCIENTIFIC RESEARCH AND DATA ANALYSIS BY BRIDGING THE GAP BETWEEN INTERACTIVE COMPUTATION AND DISTRIBUTED CYBERINFRASTRUCTURE DEVELOPED FOR DATA-INTENSIVE SCIENCES. TODAY'S NOTEBOOK ENVIRONMENTS PROVIDE EASY ACCESS TO STANDARD ARTIFICIAL INTELLIGENCE AND MACHINE LEARNING TOOLKITS FOR PROCESSING VAST DATASETS WITH GREATER EFFICIENCY AND ACCURACY COMPARED TO CONVENTIONAL METHODS. HOWEVER, MIGRATING A NOTEBOOK FROM A SCRATCHPAD-LIKE ANALYSIS TO A ROBUST PIPELINE, WHICH MUST BE DISTRIBUTED ACROSS A CLUSTER OR CLOUD INFRASTRUCTURE, CURRENTLY REQUIRES SIGNIFICANT EFFORTS BY DEVELOPERS AND SCIENTISTS. NBFLOW WILL BUILD UPON EXISTING NSF INVESTMENTS IN THE AREAS OF CONTAINERIZATION AND WORKFLOWS THAT WILL RECORD NOTEBOOK EXECUTIONS AND SCHEDULE TASKS FOR CONCURRENT EXECUTION. BY EXPERIMENTING WITH AN INTEGRATED NOTEBOOK-WORKFLOW SYSTEM, THIS CUTTING-EDGE RESEARCH WILL ADVANCE UNDERSTANDING IN DATA MANAGEMENT AND DISTRIBUTED COMPUTING SUB-FIELDS. AT THE SAME TIME, THE PROJECT WILL PRODUCE NOVEL TECHNIQUES TO ROBUSTLY CAPTURE PROVENANCE FROM NOTEBOOK-BASED WORKFLOWS, A RICH SOURCE OF DATA IN ITSELF, AS WELL AS PUT TECHNIQUES DEVELOPED FOR INCREMENTAL COMPUTATION TO PRACTICE. THESE TECHNOLOGIES WILL BE DEPLOYED WITH ACTIVE USER COMMUNITIES IN HIGH ENERGY PHYSICS AT MULTIPLE FACILITIES AND IN GEOSPATIAL AND SUSTAINABILITY SCIENCES THROUGH THE I-GUIDE CYBERINFRASTRUCTURE. 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.

IONIC LIQUIDS FOR THE UTILIZATION OF GEOTHERMAL ENERGY

A LIFE COURSE PERSPECTIVE ON THE EFFECTS OF CUMULATIVE EARLY ADVERSITY ON HEALTH

TUBOVESICULAR TRAFFIC INDUCED IN RED CELLS IN PLASMODIA

THIS AWARD APPROVES FUNDING FOR THE 2023-24 VOLUNTEER GENERATION FUND PROGRAM DESCRIBED IN THE APPROVED PROGRAM NARRATIVE AND BUDGET. YOUR 2023-24 REGULATORY MATCH IS 20%, AND YOUR BUDGETARY MATCH IS 36.67%.

RESEARCH IN COLLIDER PHYSICS

IGERT: GLOBAL LINKAGES OF BIOLOGY, ENVIRONMENT, AND SOCIETY (GLOBES)

DRI: THE ARABIAN SEA TRANSITION LAYER (ASTRAL): EXCHANGE ACROSS THE AIR-SEA INTERFACE

MATURATION OF BACTERIAL CELL WALL

RTG: GEOMETRY AND TOPOLOGY

DETERMINANTS OF GROWTH AND FITNESS IN DRUG RESISTANT MALARIA PARASITES

CLASS A CARBAPENEMASES

OPTIMIZING ADDITIVE MANUFACTURING OF THERMOELECTRIC MATERIALS USING BAYESIAN OPTIMIZATION-ENHANCED TRANSFER LEARNING

NEW; TITLE: IN SITU CORRELATED MOLECULAR IMAGING OF CHEMICALLY COMMUNICATING MICROBIAL COMMUNITIES; PI: PAUL BOHN

CONFOCAL MICROSCOPY FOR ENGINEERING STEM CELL MICROENVIRONMENT IN LYMPHATIC REGENERATION - PROJECT SUMMARY THE SUPPLEMENT FUND IS REQUESTED UNDER PA-18-591 AND NOT-GM-20-013 TO PURCHASE A CONFOCAL MICROSCOPY SYSTEM, WHICH WILL SUPPORT NIGMS MIRA AWARD R35GM143055-01. THE RESEARCH PROGRAM SUPPORTED BY THIS AWARD LIES AT THE INTERFACE BETWEEN ENGINEERING AND MEDICINE, WITH A MOTIVATION ON MAKING STEM CELLS AND MOLECULAR THERAPIES AS AN EFFECTIVE METHOD TO MODEL AND TREAT LYMPHATIC DISEASES. TOWARD THIS GOAL, THE RESEARCH PROGRAM IS WORKING AT THE FOREFRONT OF DEVELOPING TRANSDISCIPLINARY APPROACHES BY COMBINING STEM CELL AND BIOENGINEERING, BIOMATERIALS, AND MICROFLUIDICS, AS WELL AS LYMPHATIC AND SYSTEMS BIOLOGY TECHNIQUES TO DEVELOP THE NECESSARY COMPONENT IN THERAPEUTIC LYMPHANGIOGENESIS. MAJOR AMOUNT OF THE WORK IN THE PROJECT NOW RELIES ON ENGINEERING STEM CELLS AND HYDROGELS FOR IN VITRO AND IN VIVO MODELS OF LYMPHATIC VASCULATURES IN HEALTH AND DISEASES. THE WORKFLOW RELIES ON A RAPID AND RELIABLE CONFOCAL MICROSCOPE SYSTEM, CAPABLE OF IMAGING THICK AND LARGE SAMPLES. TECHNOLOGY CURRENTLY AVAILABLE TO THE LABORATORY IS AGING, INCOMPATIBLE FOR IMAGING BIOMATERIALS, REQUIRES ADVANCE SCHEDULING, AND NECESSITATES PAYING COSTLY USER FEES. THE STATE-OF-THE-ART, STREAMLINED, AND SINGLE LABORATORY CONFOCAL MICROSCOPY SYSTEM REQUESTED HERE WILL PERMIT A MORE RAPID ADVANCE TOWARD THE PROJECT GOALS. THE SUPPLEMENT FUND IS REQUESTED FROM NIGMS TO COVER 65% OF THE SYSTEM COST. THE REMAINING 35% WILL BE CONTRIBUTED BY THE UNIVERSITY OF NOTRE DAME AS INSTITUTIONAL SUPPORT.

DIANA, AN UNDERGROUND ACCELERATOR FACILITY FOR NUCLEAR ASTROPHYSICS

CCI PHASE I: NSF CENTER FOR COMPUTER ASSISTED SYNTHESIS

TAS::89 0321::TAS CDP TO NOTRE DAME UNIVERSITY FOR PASSIVE NOX REMOVAL CATALYST RESEARCH.

DISCIPLINARY IMPROVEMENTS: THE SEEKCOMMONS RESEARCH COORDINATION NETWORK -THE ?SOCIO-ENVIRONMENTAL KNOWLEDGE COMMONS? (SEEKCOMMONS) RESEARCH COORDINATION NETWORK WILL DISSEMINATE AND STUDY OPEN SCIENCE TOOLS AND METHODOLOGIES TO ADVANCE COLLABORATIVE SOCIO-ENVIRONMENTAL RESEARCH. SEEKCOMMONS WILL BUILD BRIDGES BETWEEN DOMAINS OF SCIENTIFIC, TECHNICAL, AND ENVIRONMENTAL EXPERTISE THROUGH COMMUNITY-BUILDING WORKSHOPS AND SUPPORT ACTIVITIES THAT ENABLE THE SHARING OF SKILLS, RESOURCES, AND SOCIO-ENVIRONMENTAL RESEARCH PRODUCTS AS PUBLIC GOODS. THE PROJECT SEEKS TO BRIDGE LONG-STANDING DIVIDES BETWEEN THE SOCIAL AND ENVIRONMENTAL SCIENCES THROUGH THE ADAPTATION AND APPLICATION OF OPEN TOOLS AND METHODOLOGIES IN WAYS THAT WILL OVERCOME DISCIPLINARY BARRIERS TO ACCEPTANCE. SEEKCOMMONS WILL DRAW PRIMARILY FROM THREE AREAS OF RESEARCH AND DEVELOPMENT: SCIENCE AND TECHNOLOGY STUDIES (STS), OS, AND SOCIO-ENVIRONMENTAL RESEARCH. EACH OF THESE COMPONENT AREAS WILL BE INTEGRATED AND COORDINATED WITH THE OTHERS BY USING STS AS A ?TRANSLATIONAL COMPONENT? THAT WILL MEDIATE BETWEEN OPEN SCIENCE PRACTITIONERS AND SOCIO-ENVIRONMENTAL RESEARCHERS WORKING WITH COMMUNITIES AFFECTED BY ENVIRONMENTAL AND CLIMATE ISSUES. FIVE MAJOR ACTIVITIES WILL BE CONDUCTED TO ESTABLISH THE SEEKCOMMONS RCN: (1) EMPIRICAL STS RESEARCH ON COMMON PROBLEMS AND CAPACITY GAPS RELATED TO ?OPENNESS? IN SOCIO-ENVIRONMENTAL RESEARCH; (2) REGULAR CONVENINGS TO SHARE RESEARCH FINDINGS AND CHALLENGES, AND TO BUILD CONSENSUS ON HOW TO ADVANCE COLLABORATIVE WORK; (3) FELLOWSHIPS FOR STUDENTS AND EARLY-CAREER RESEARCHERS TO INVESTIGATE EMERGING PROBLEMS AND OPPORTUNITIES IN THE APPLICATION OF OS TO SOCIO-ENVIRONMENTAL RESEARCH; (4) A DATA FACILITATION CONSORTIUM; AND (5) CREATION OF A RESOURCE HUB AND CURRICULUM BUILDER TO DISSEMINATE OPEN RESEARCH OUTPUTS AND HIGHLIGHT THE WORK OF OUR NETWORK PARTNERS. THIS AWARD BY THE OFFICE OF ADVANCED CYBERINFRASTRUCTURE IS JOINTLY SUPPORTED BY THE DIRECTORATE FOR SOCIAL, BEHAVIORAL AND ECONOMIC SCIENCES. 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.

ENGINEERING THE NEXT GENERATION OF SAFER HSP90 INHIBITORS - SUMMARY: HSP90 IS A MOLECULAR CHAPERONE THAT IS RESPONSIBLE FOR THE CONFORMATIONAL MATURATION OF SIGNALING PROTEINS ASSOCIATED WITH ALL TEN HALLMARKS OF CANCER, MAKING IT A PROMISING TARGET FOR THE TREATMENT OF CANCER, AS MULTIPLE SIGNALING NODES CAN BE SIMULTANEOUSLY DERAILED AS A CONSEQUENCE OF HSP90 INHIBITION. MOREOVER, RESEARCHERS HAVE SHOWN THAT HSP90 INHIBITORS ACCUMULATE IN TUMORS WITH HIGH DIFFERENTIAL SELECTIVITY, MAKING HSP90 A HIGHLY SOUGHT AFTER TARGET FOR CANCER. UNFORTUNATELY, CLINICAL TRIALS WITH 17 SMALL MOLECULE INHIBITORS HAVE LED TO MULTIPLE DETRIMENTS THAT HAVE SIGNIFICANTLY DAMPENED ENTHUSIASM FOR HSP90 INHIBITORS, AS INCREASED LEVELS OF HSP90 WERE OBSERVED IN THE CLINIC, WHICH LED TO DOSE-ESCALATING TOXICITIES AMONG OTHER CONCERNS. CONSEQUENTLY, HSP90 REMAINS A DESIRABLE TARGET FOR THE DEVELOPMENT OF CANCER CHEMOTHERAPEUTICS, BUT NEW APPROACHES TO INHIBIT THE PROTEIN MACHINERY ARE NEEDED THAT DO NOT INDUCE HSP90 LEVELS. THROUGH A NUMBER OF SEMINAL STUDIES, IT HAS BEEN SHOWN THAT INHIBITORS OF THE HSP90 C-TERMINAL DOMAIN CAN SEGREGATE HSP90 INHIBITION FROM INDUCTION OF HSP90 LEVELS, AND THEREFORE, WE PROPOSE IN THIS APPLICATION TO OPTIMIZE THESE COMPOUNDS AND TO PERFORM A NUMBER OF PRE-IND STUDIES ON THE BEST MOLECULES IN AN EFFORT TO MOVE THEM TOWARD CLINICAL EVALUATION.

NON-COVALENT MOLECULAR RECOGNITION FOR DRUG TARGETING IN THE BODY

PATHOPHYSIOLOGIES INVOLVING HEMOSTASIS-RELATED GENES

MULTI-SCALE SEPARATION AND ANALYSIS OF HETEROGENEOUS TRINITE PHASES ANTONIO SIMONETTI, P.I.

PROTEOSTATIC MECHANISMS OF RESISTANCE IN MALARIA

GENERATION OF NOVEL MODELS OF KIDNEY DEFECTS USING THE ZEBRAFISH

MOLECULAR DIAGNOSTICS USING A NANOPORE TO ANALYZE SECRETIONS FROM SINGLE CELLS

TOPOLOGICAL STRUCTURAL RELATIONSHIPS, PROPERTIES, AND NANO-STRUCTURES...

** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** FOOD ACCESS IS AN UNFORTUNATE BUT VERY REAL PROBLEM FOR THE MANY AMERICANS THAT LIVE IN FOOD DESERTS WHERE THE COMBINATION OF DISTANCE TO FULL SERVICE SUPERMARKETS AND ACCESS TO TRANSPORTATION MAKES HEALTHY, AFFORDABLE FOOD LESS ATTAINABLE. TODAY'S TECHNOLOGICAL INNOVATIONS HAVE THE POTENTIAL TO ADDRESS THIS PROBLEM, HOWEVER THEY MUST BE ADAPTED TO APPLY TO THE CHALLENGING SOCIO-ECONOMIC CONDITIONS OF THESE COMMUNITIES. THE PROPOSED WORK WILL EXPLORE THE DEVELOPMENT OF HETEROGENEOUS NETWORK MODELS, INFORMATION VISUALIZATION, AND DELIVERY SERVICES FOR ADDRESSING THE PROBLEM OF FOOD ACCESS IN TWO LOW-INCOME COMMUNITIES IN SOUTH BEND, INDIANA AND DETROIT, MICHIGAN. THE PROPOSED WORK WILL DEEPLY INTEGRATE SOCIAL RESEARCH WITH TECHNOLOGICAL INNOVATION IN A USER-CENTERED DESIGN-THINKING FRAMEWORK IN ORDER TO IDENTIFY, UNDERSTAND, AND MEET THE NEEDS OF THE COMMUNITY STAKEHOLDERS. IN PARTICULAR THE PROPOSED WORK ADDRESSES FOUR OVERARCHING QUESTIONS:WHAT ARE THE CRITICAL-USER NEEDS FOR A TECHNOLOGY-ENABLED FOOD RECOMMENDER AND ACCESS SYSTEM?HOW DO WE MODEL THE COMPLEX FOOD INFORMATION LANDSCAPE AND MAKE CONTEXT-RELEVANT RECOMMENDATIONS FOR TARGET USERS LIVING UNDER THE CONSTRAINTS OF POVERTYHOW DO WE PRESENT ACCESSIBLE EXPLANATIONS OF RECOMMENDATIONS MADE OVER THIS COMPLEX LANDSCAPE OF DETERMINANTS INCLUDING, FOR EXAMPLE, PREFERENCE, COST, AND NUTRITIONAL VALUE.HOW FEASIBLE IS A DELIVERY HUB MODEL FOR ADDRESSING BRIDGING THE PHYSICAL ACCESS GAP?THROUGH A SERIES OF ITERATIVE USE RESEARCH AND DESIGN/DEVELOPMENT ACTIVITIES WITH COMMUNITY PARTNERS AND COMMUNITY MEMBERS, THE PROJECT WILL DEVELOP A PROTOTYPE RECOMMENDATION ENGINE THAT TAKES INTO ACCOUNT THE BROADER CONTEXT OF POVERTY TO MAKE STAKEHOLDER-RELEVANT RECOMMENDATIONS FOR MEAL PLANNING. THIS SYSTEM WILL BE EVALUATED USING A MIXED METHODS APPROACH TO UNDERSTAND THE EFFECTS OF THE INTERVENTION ON HEALTHY FOOD CHOICE.

MITOPHAGY-MEDIATED CELL DEATH IN MAMMARY TUMORIGENESIS - PROJECT SUMMARY BACKGROUND: THE METASTASIS OF CANCEROUS CELLS TO DISTANT AND VITAL ORGANS IS RESPONSIBLE FOR IN EXCESS OF 90% OF CANCER MORTALITIES. GIVEN THIS EXTRAORDINARILY HIGH MORTALITY RATE, THERE IS A SIGNIFICANT NEED FOR THE DEVELOPMENT OF NOVEL THERAPEUTIC APPROACHES THAT EITHER ELIMINATE METASTATIC CANCER CELLS OR ERADICATE INCIPIENT CANCER CELLS PRIOR TO METASTATIC DISSEMINATION. AN IMPORTANT BARRIER TO TUMOR PROGRESSION AND METASTASIS IS ANOIKIS, A CASPASE- DEPENDENT CELL DEATH PROGRAM INDUCED BY LOSS OF INTEGRIN-MEDIATED ATTACHMENT TO EXTRACELLULAR MATRIX (ECM). HOWEVER, IT HAS BECOME CLEAR THAT ECM-DETACHMENT CAN INDUCE ANOIKIS-INDEPENDENT MECHANISMS THAT CAN COMPROMISE CELL VIABILITY. MORE SPECIFICALLY, WE HAVE DISCOVERED THAT DETACHMENT OF NON-CANCEROUS EPITHELIAL CELLS FROM ECM TRIGGERS A SIGNIFICANT ELEVATION IN THE LEVELS OF REACTIVE OXYGEN SPECIES (ROS) WHICH COMPROMISES CELL SURVIVAL IN AN ANOIKIS-INDEPENDENT FASHION. THE UNDERSTANDING OF THE CELLULAR CHANGES THAT CONTRIBUTE TO THE ELEVATION OF ROS DURING ECM-DETACHMENT REMAINS RUDIMENTARY AND THE STRATEGIES UTILIZED BY CANCER CELLS TO COMBAT ROS DURING ECM-DETACHMENT ARE INSUFFICIENTLY EXPLORED. THEREFORE, THESE POINTS REPRESENT SIGNIFICANT KNOWLEDGE GAPS THAT THIS GRANT PROPOSAL AIMS TO ADDRESS. DISCERNMENT OF MECHANISTIC INFORMATION REGARDING THE LINKS BETWEEN ECM-DETACHMENT, ROS, AND CELL SURVIVAL COULD PROVIDE TARGETS FOR THE DESIGN OF THE THERAPEUTIC APPROACHES AIMED AT SPECIFICALLY ELIMINATING ECM-DETACHED CANCER CELLS; AN OUTCOME THAT MAY HAVE SIGNIFICANT IMPACT FOR PATIENTS WITH METASTATIC DISEASE. OBJECTIVE/HYPOTHESIS: IN AGGREGATE, OUR PRELIMINARY STUDIES HAVE UNVEILED A NOVEL CELL DEATH MECHANISM (WITH A TUMOR SUPPRESSIVE FUNCTION) THAT COMPROMISES THE VIABILITY OF ECM-DETACHED CELLS: THE INDUCTION OF MITOPHAGY AS CONSEQUENCE OF RIPK1 SIGNALING. AS SUCH, THESE DATA HAVE MOTIVATED OUR CENTRAL HYPOTHESIS THAT RIPK1- MEDIATED MITOPHAGY DURING ECM-DETACHMENT FUNCTIONS AS A BARRIER TO BREAST CANCER PROGRESSION. SPECIFIC AIM I: TO ELUCIDATE THE MOLECULAR MECHANISM BY WHICH ECM-DETACHMENT PROMOTES RIPK1-DEPENDENT MITOPHAGY AND INITIATES CELL DEATH. SPECIFIC AIM II: TO ASSESS THE CAPACITY OF RIPK1-MEDIATED MITOPHAGY TO ANTAGONIZE TUMOR FORMATION IN VIVO AND TO EVALUATE ANTIOXIDANT INHIBITION AS A NOVEL STRATEGY TO LIMIT TUMORIGENESIS IN CANCERS THAT ARE DEFICIENT IN RIPK1-MEDIATED MITOPHAGY ANTICIPATED OUTCOMES: FOLLOWING THE COMPLETION OF THESE STUDIES, WE WILL HAVE ACCUMULATED SIGNIFICANT MECHANISTIC KNOWLEDGE REGARDING THE RELATIONSHIP BETWEEN ECM-DETACHMENT, RIPK1 MITOPHAGY, AND CELL DEATH. THUS, THE COMPLETION OF THESE STUDIES WILL UNVEIL FUNDAMENTAL BIOLOGICAL INSIGHTS REGARDING CANCER CELL SURVIVAL DURING ECM-DETACHMENT THAT MAY ULTIMATELY LEAD TO THE DEVELOPMENT OF THERAPEUTIC APPROACHES TO LIMIT THE DISSEMINATION OF BREAST CANCER CELLS.

UPWARD BOUND PROGRAM

DEVELOPMENT AND EVALUATION OF PURINE AND COUMARIN BASED HSP90 INHIBITORS

STRUCTURAL EXTREME EVENTS RECONNAISSANCE (STEER): DATA TO KNOWLEDGE FRAMEWORK FOR COORDINATED RECONNAISSANCE FOLLOWING NATURAL HAZARD EVENTS

MOLECULAR ASPECTS OF TRANSPORT IN THIN FILMS OF CONTROLLLED ARCHITECTURE

MASTERS AND STEM PROGRAMS IN HYPERSONIC SYSTEMS

NEB: PHYSICS-INSPIRED NON-BOOLEAN COMPUTATION BASED ON SPATIAL- TEMPORAL WAVE EXCITATIONS

COLLABORATIVE RESEARCH AND NEON: MSB CATEGORY 2: PALEON - A PALEOECOLOGICAL OBSERVATORY NETWORK TO ASSESS TERRESTRIAL ECOSYSTEM MODELS

MOLECULAR PROBES FOR BIOMEMBRANE RECOGNITION

QUANTITATIVE PROTEOMICS OF XENOPUS OOCYTES, EGGS, BLASTOMERES, AND NUCLEAR TRANSPLANTS

AN ENGINEERED TISSUE MODEL OF AGED MAMMARY MICROENVIRONMENT

COMPUTATIONAL BIOMECHANICS MODELING OF INFLAMMATION - PROJECT SUMMARY/ABSTRACT THE PHYSICAL LAWS THAT GOVERN THE UNIVERSE ALSO GOVERN THE HEALTHY FUNCTIONING OF LIVING TISSUES, AS WELL AS THE GENESIS AND DEVELOPMENT OF DISEASES. HISTORICALLY, THE BIOMEDICAL RESEARCH COMMUNITY HAS OVERLOOKED THE ROLE OF MECHANICS IN MANY DEVELOPMENTAL, PATHOLOGICAL, AND ADAPTIVE PROCESSES. IN MY RESEARCH GROUP, THE COMPU- TATIONAL MECHANICS OF MORPHOLOGY AT NOTRE DAME (COMMAND LAB), WE WORK AT THE INTERSECTION OF MECHANICS, COMPUTATION, AND BIOLOGY, TO INVESTIGATE THE COUPLED BIO-MECHANICAL BEHAVIORS OF TISSUES AND ORGANS, PARTICULARLY DURING GROWTH AND REMODELING. IN THIS PROPOSAL, WE AIM TO EXTEND OUR WORK TO THE STUDY OF INAMMATORY SWELLING. SIMILARLY TO GROWTH, INAMMATION AND SWELLING INVOLVE LOCAL CHANGES IN MASS (FOR INSTANCE, DUE TO AN INUX OF CELLS) WHICH CAN MANIFEST AS CHANGES IN VOLUME. WHILE EXTERNAL SWELLING IS OFTEN USED AS AN INDICATOR OF UNDER- LYING INAMMATION, CONSTRAINTS FROM SURROUNDING TISSUE CAN ALSO RESTRICT SWELLING AND INSTEAD RESULT IN INCREASES IN PRESSURE. IN ADDITION, INAMMATION CAN DRASTICALLY CHANGE THE CELLULAR COMPOSITION OF A TISSUE. INAMMATION IS WIDESPREAD AMONG DIFFERENT TISSUES, AND THESE SEQUELAE CAN HAVE IMPORTANT IMPLICATIONS FOR THE DIAGNOSIS, DE- VELOPMENT, AND TREATMENT OF DIFFERENT DISEASES. WE WILL DEVELOPING NOVEL COMPUTATIONAL MODELS OF INAMMATION AND SWELLING THAT 1) ALLOW FOR CELL BEHAVIOR TO VARY SPATIALLY, TEMPORALLY, AND BY CELL TYPE; 2) ACCOUNT FOR MECHANICAL INTERACTIONS BETWEEN THE SWELLING TISSUE AND SURROUNDING TISSUES; AND 3) REPORT RESULTS IN A WAY THAT FACILITATES CALIBRATION, VALIDATION, AND COMPARISONS WITH EXPERIMENTAL. THIS WORK WILL PROVIDE TOOLS FOR PROBING SMALL-SCALE PHENOMENA BEYOND LARGE-SCALE SWELLING, EXPLORING THE EFFECTS OF INDIVIDUAL PARAMETERS, AND TESTING HYPOTHESES REGARDING THE BIOMECHANICS OF INAMMATION IN SILICO. 1

MODEL-BASED INFERENCE AND FORECASTING OF CO-CIRCULATING PATHOGEN DYNAMICS - PROJECT SUMMARY PUBLIC HEALTH FACES THREATS FROM A MULTITUDE OF PATHOGENS ON AN ONGOING BASIS, YET PATHOGENS ASSOCIATED WITH DIFFERENT DISEASES ARE TYPICALLY COMPARTMENTALIZED WITH RESPECT TO SURVEILLANCE, MANAGEMENT, AND RESEARCH. THIS COMPARTMENTALIZED APPROACH IGNORES THE MANY WAYS THAT PATHOGENS INTERACT, IN SOME CASES LEADING TO THE EXACERBATION OF THEIR COLLECTIVE BURDEN ON PUBLIC HEALTH. THESE INTERACTIONS CAN BE BIOLOGICAL (E.G., CROSS-REACTIVE IMMUNITY), BEHAVIORAL (E.G., PROMPTING ADHERENCE TO GOOD HYGIENE), OR CLINICAL (E.G., MISDIAGNOSIS). MODERN, DATA- DRIVEN APPROACHES TO MATHEMATICAL MODELING HAVE THE POTENTIAL TO RESOLVE THE DYNAMICS OF CO- CIRCULATING PATHOGENS BY ACCOUNTING FOR THESE INTERACTIONS. IN DOING SO, MODELING ALSO HAS THE POTENTIAL TO IMPROVE PATHOGEN-SPECIFIC DISEASE FORECASTS BY BORROWING INFORMATION ACROSS SURVEILLANCE DATA FOR DIFFERENT DISEASES. TO DATE, THIS POTENTIAL REMAINS LARGELY UNTAPPED. IN THIS PROJECT, I WILL DEVELOP A GENERALIZABLE FRAMEWORK FOR MODELING THE DYNAMICS OF CO-CIRCULATING PATHOGENS. THE FIRST COMPONENT OF THIS FRAMEWORK WILL USE BAYESIAN HIERARCHICAL MODELING TO FUSE MECHANISTIC DESCRIPTIONS OF PATHOGEN TRANSMISSION DYNAMICS WITH STATISTICAL DESCRIPTIONS OF SURVEILLANCE PROCESSES, ALLOWING FOR MAXIMAL LEVERAGING OF HETEROGENEOUS DATA STREAMS TO INFORM BIOLOGICAL INFERENCES. THE SECOND COMPONENT OF THIS FRAMEWORK WILL INVOLVE VALIDATING MODEL INFERENCES THROUGH FORECASTS OF FUTURE DISEASE DYNAMICS. BOTH COMPONENTS OF THIS FRAMEWORK WILL INVOLVE THE USE OF MULTIPLE MODELS THAT REPRESENT COMPETING HYPOTHESES ABOUT PATHOGEN INTERACTION, AS WELL AS OTHER FORMS OF MODEL UNCERTAINTY. THIS FRAMEWORK WILL BE APPLIED IN TWO SETTINGS: MOSQUITO-BORNE VIRUSES IN BRAZIL AND RESPIRATORY PATHOGENS IN INDIANA. IN BOTH OF THESE SETTINGS, CO-CIRCULATION OF RECENTLY EMERGED AND ENDEMIC PATHOGENS POSES NEW CHALLENGES FOR SURVEILLANCE AND CONTROL ACTIVITIES, MAKING THE DEVELOPMENT OF NEW MODELING TOOLS TO ADDRESS THESE CHALLENGES ESPECIALLY TIMELY.

HOST AND FUNGAL FACTORS IMPORTANT FOR THE CRYPTOCOCCAL INTRACELLULAR NICHE - PROJECT SUMMARY / ABSTRACT UNDERSTANDING HOW INTRACELLULAR PATHOGENS SURVIVE IN THEIR HOST CELLS HAS LED TO BETTER MANAGEMENT/PRE- VENTION OF THEIR DISEASES, AS WELL AS DISCOVERY OF FUNDAMENTAL BIOLOGY. IN THIS APPLICATION, WE AIM TO START ELUCIDATING THE STRATEGIES AND MECHANISMS USED BY ONE OF THE COMMONEST FUNGAL PATHOGENS, CRYPTOCOCCUS NEOFORMANS, TO SURVIVE INSIDE MACROPHAGES. THE TREATMENT OF CRYPTOCOCCAL DISEASE IS SUBPAR, RESULTING IN MOR- TALITIES THAT RANGE FROM 20% TO ALMOST 90%, DEPENDING ON THE GEOGRAPHICAL REGION. THE ABILITY OF THIS FUNGUS TO SURVIVE INSIDE HOST CELLS IS ONE OF THE MAIN DRIVERS OF DISEASE PROGRESSION, AND CLINICAL STUDIES SHOW THAT INTRA- CELLULAR SURVIVAL IN MACROPHAGES CORRELATES WITH PATIENT’S MORTALITY. HOWEVER, THE MOLECULAR MECHANISMS THAT GOVERN INTERNALIZATION AND THE ABILITY TO SURVIVE INTRACELLULARLY ARE NOT KNOWN, HAMPERING THE DEVELOPMENT OF MORE EFFECTIVE THERAPEUTICS. OUR LONG-TERM GOAL IS TO UNDERSTAND THE CELLULAR AND MOLECULAR MECHANISMS BEHIND INTRA- CELLULAR SURVIVAL, A SIGNIFICANT GAP IN KNOWLEDGE IN THE FIELD. MOVING TOWARDS THAT GOAL, THE OBJECTIVES OF THIS APPLICATION ARE TO DEFINE AND CHARACTERIZE THE CRYPTOCOCCAL-CONTAINING PHAGOSOME (CCP) IN MACROPHAGES, AND UNDERSTAND THE ROLE OF HOST AND FUNGAL FACTORS IN THE GENERATION OF THIS INTRACELLULAR NICHE. WE HYPOTHESIZE THAT CRYPTOCOCCUS ACTIVELY TARGETS RAB GTPASES AND PHOSPHOINOSITIDES TO DELAY THE NORMAL MATURATION OF ITS PHAG- OSOME. THIS ALLOWS FUNGAL FACTORS, SUCH AS CAPSULAR HYALURONIC ACID AND GLUCURONIC ACID, TO MODULATE ACIDIFICATION OF THE CCP, RESULTING IN A FUNGAL PERMISSIVE NICHE. PRO-INFLAMMATORY SIGNALS, MEDIATED IN PART BY RAB20 EFFECTS ON PHAGOSOMAL MATURATION, COUNTER THIS FUNGAL MANIPULATION AND PREVENT NICHE ESTABLISHMENT. WE PLAN TO TEST THIS HYPOTHESIS BY (1) DEFINING AND CHARACTERIZING THE INTRACELLULAR NICHE OF C. NEOFORMANS IN NAÏVE AND ACTIVATED MACROPHAGES; AND (2) IDENTIFY AND EXPLORE THE ROLE OF FUNGAL FACTORS IN NICHE ESTABLISHMENT. IF COMPLETED, WE WILL HAVE IDENTIFIED THE GENETIC (FUNGAL GENES), PHENOTYPIC (CCP PROPERTIES) AND IMMUNOLOGICAL (HOST’S IMMUNE STA- TUS) CHARACTERISTICS THAT ENABLE CRYPTOCOCCUS TO LIVE INTRACELLULARLY, ALLOWING US TO PINPOINT POTENTIAL AREAS OF INTERVENTION TO BLOCK INTRACELLULAR REPLICATION. COMPLETION OF THESE AIMS WILL HAVE A POSITIVE IMPACT IN THE FIELD BY GENERATING A DETAILED MOLECULAR DESCRIPTION OF THE STRATEGIES CRYPTOCOCCUS USES TO SURVIVE IN MACROPHAGES AND HOW HOST CELLS RESPOND. MOREOVER, GIVEN THE SCARCITY OF WELL CHARACTERIZED INTRACELLULAR SURVIVAL STRATEGIES IN FUNGI, THE KNOWLEDGE CREATED HERE WILL IMPACT THE UNDERSTANDING AND STUDIES OF OTHER PATHOGENIC FUNGI AS WELL.

OVERCOMING BREAST CANCER METASTASIS TO BONE BY CXCR2 INHIBITION

ADVANCES IN BIOANALYSIS

CDI-TYPE II: BUILDING AND STUDYING A VIRTUAL ORGANIZATION FOR ADAPTATION TO CLIMATE CHANGE

SP-MIMO RADAR STUDIES

NEB: NANOELECTRONICS WITH MIXED-VALENCE MOLECULAR QCA

CHEMISTRY-BIOCHEMISTRY-BIOLOGY INTERFACE (CBBI) PROGRAM AT NOTRE DAME - ABSTRACT THE CHEMISTRY-BIOCHEMISTRY-BIOLOGY INTERFACE (CBBI) PROGRAM AT THE UNIVERSITY OF NOTRE DAME IS AN ESTABLISHED NIH-FUNDED PROGRAM THAT SUPPORTS THE TRAINING OF DIVERSE POOL OF SCIENTISTS WHO CONDUCT MULTIDISCIPLINARY RESEARCH AT THE INTERFACE OF CHEMISTRY AND BIOLOGY-RELATED DISCIPLINES. THE GOAL OF THE CBBI PROGRAM IS TO PRODUCE PHD SCIENTISTS WHO WORK EFFECTIVELY AT THE INTERFACE OF CHEMISTRY AND BIOLOGY AND WHO ARE ABLE TO SPEAK THE LANGUAGE OF TWO OR MORE DISCIPLINES. THE CBBI PROGRAM HAS ESTABLISHED AN OUTSTANDING TRAINING ENVIRONMENT FOR OUR PREDOCTORAL TRAINEES. SINCE 2007 WE HAVE TRAINED 84 STUDENTS, 57 OF WHOM HAVE COMPLETED PHD DEGREES IN AN AVERAGE OF 5.14 YEARS (TIME TO PHD DEGREE FROM CBBI TRAINEES IS 4.98 IN THE PAST 10 YEARS) WITH 19 STILL IN TRAINING. OF THESE 84, 16 ARE UNDERREPRESENTED MINORITIES (URMS), 10 OF WHOM HAVE ALREADY RECEIVED PHD DEGREES. OUR 84 TRAINEES HAVE 362 PUBLICATIONS, OF WHICH 159 ARE FIRST-AUTHOR PUBLICATIONS. THIS REPRESENTS 4.3 PUBLICATIONS PER TRAINEE AND 1.9 FIRST-AUTHOR PUBLICATIONS PER TRAINEE. THE 16 URMS HAVE PRODUCED 79 PUBLICATIONS, OF WHICH 31 ARE FIRST-AUTHOR PUBLICATIONS; THIS REPRESENTS 4.9 PUBLICATIONS PER URM AND 1.9 FIRST- AUTHOR PUBLICATIONS PER URM. DURING THE PAST 14 YEARS, OUR ATTRITION RATE HAS BEEN LOW, WITH ONLY EIGHT OF 84 TRAINEES (9.5%) WHO DID NOT COMPLETE A PHD DEGREE. THE KEY HIGHLIGHTS OF THE CBBI PROGRAM ARE: 1) A LARGE AND DIVERSE POOL OF HIGHLY QUALIFIED CANDIDATES; 2) A STRONG TRACK RECORD OF COLLABORATIVE AND MULTIDISCIPLINARY RESEARCH BY BOTH TRAINEES AND MENTORS; 3) A DIVERSE FACULTY GROUP THAT SERVES AS RESEARCH MENTORS AND ARE EXPERIENCED, PRODUCTIVE, AND FEDERALLY-FUNDED; 4) AN INTENSIVE, CROSS-DISCIPLINARY RESEARCH INTERNSHIP IN THE OTHER FIELD OUTSIDE THE MENTOR’S LABORATORY; 5) MULTIDISCIPLINARY SEMINARS THAT SUPPLEMENT TRAINING; 6) INDIVIDUAL AND GROUP MEETINGS WITH TRAINEES; 7) THE ANNUAL CBBI SYMPOSIUM THAT FEATURES BOTH ORAL AND POSTER PRESENTATIONS AT THE CHEMISTRY- BIOLOGY INTERFACE; 8) PROGRAM ADMINISTRATION WITH AN ESTABLISHED TRACK RECORD OF TRAINING STUDENTS AT THE CHEMISTRY- BIOLOGY INTERFACE; 9) A PLAN AND MECHANISM FOR CONTINUOUS EVALUATION AND REFINEMENT OF THE TRAINING PROGRAM; 10) PROFESSIONAL DEVELOPMENT AND CAREER PLACEMENT; 11) OUTSTANDING RESEARCH FACILITIES; AND 12) A STRONG INSTITUTIONAL COMMITMENT. WE PROPOSE TO CONTINUE TO TRAIN PHD SCIENTISTS WITH THE SKILLS AND EXPERTISE TO SOLVE CHALLENGING BIOMEDICAL PROBLEMS, REGARDLESS OF DISCIPLINE. THE UNIVERSITY OF NOTRE DAME ENTHUSIASTICALLY SUPPORTS THIS TRAINING PROGRAM, AND WILL CONTINUE TO PROVIDE A GENEROUS FELLOWSHIP MATCH TO THE CBBI PROGRAM AND ADDITIONAL RESOURCES, INCLUDING THE COST OF THE RESEARCH INTERNSHIP FOR ALL TRAINEES, UPON RENEWAL OF FUNDING BY THE NIH.

CHARACTERIZATION OF A MODEL SYSTEM TO ADVANCE TRIPLE-STRANDED RNA BIOLOGY

DEVELOPMENT OF HSP90 INHIBITORS FOR THE TREATMENT OF CANCER

BRINGING MODERN DATA SCIENCE TOOLS TO BEAR ON ENVIRONMENTAL MIXTURES

CELL-WALL RECYCLING AND NEXUS TO ANTIBIOTIC RESISTANCE

ENGINEERING OF OXIDE/NITRIDE STRUCTURES (EONS)

REGULATION AND FUNCTION OF MULTICELLULAR CALCIUM SIGNALING IN EPITHELIAL GROWTH AND REGENERATION

HYBRID ENCAPSULATED IONIC LIQUIDS FOR POST-COMBUSTION CARBON DIOXIDE CAPTURE

AS-PHYS DEVELOPMENT OF ADVANCED, RADIATION RESISTANT, OPTICAL-BASED DETECTOR TECHNOLOGY FOR FUTURE HEP EXPERIMENTS

SCC-IRG TRACK 1: A NEW AI-DRIVEN PARADIGM TO PROMOTE COMMUNITY RESILIENCE FOR TEENAGERS AND YOUNG ADULTS IN PREVENTING OPIOID MISUSE AND ADDICTION -COMBATING THE DEADLY OPIOID EPIDEMIC IS A NATIONAL PRIORITY. SPECIFICALLY, TEENAGERS AND YOUNG ADULTS (TYAS) ARE DISPROPORTIONATELY AFFECTED BY AND PARTICULARLY VULNERABLE TO OPIOID MISUSE AND ADDICTION. UNFORTUNATELY, RESEARCH ON HOW TO PROVIDE EFFECTIVE YET AFFORDABLE SOLUTIONS TO GENERATE AND PROMOTE TAILORED MESSAGES FOR THE DISTINCT YET VULNERABLE TYA COMMUNITY AGAINST THE OPIOID CRISIS IS LACKING. TO FILL THIS GAP, THE ?SMART AND CONNECTED (S&CC) COMMUNITY? IN THIS PROJECT IS DEFINED AS THE COMMUNITY OF AT-RISK TYAS WHO ARE PARTICULARLY VULNERABLE TO OPIOIDS AND CONNECTED VIA ONLINE SOCIAL MEDIA, WITHIN WHICH INTELLIGENT TECHNOLOGIES WILL BE SYNERGISTICALLY INTEGRATED TO IMPROVE THEIR RESILIENCE AND WELL-BEING AGAINST THE LETHAL OPIOID EPIDEMIC. BY ENGAGING WITH REPRESENTATIVE COMMUNITY STAKEHOLDERS, THIS PROJECT WILL DESIGN AND DEVELOP A NEW AI-DRIVEN PARADIGM TO FACILITATE PERSONALIZED MESSAGES TAILORED TO TYA COMMUNITY?S CHARACTERISTICS AND CIRCUMSTANCES TO PROMOTE THEIR RESILIENCE AGAINST OPIOID MISUSE AND ADDICTION, AND THUS HELP ENHANCE NATIONAL PUBLIC HEALTH, SAFETY, AND WELFARE. THE DEVELOPED FRAMEWORK CAN BE SCALED AND EASILY TRANSFERRED TO OTHER COMMUNITIES IN PREVENTING AND REDUCING CORRESPONDING HARMS, SUCH AS PEOPLE WITH DIFFERENT TYPES OF SUBSTANCE MISUSE AND ADOLESCENTS AT-RISK FOR SUICIDE. THE PROPOSED WORK WILL ADVANCE SCIENTIFIC THEORY IN RELATED RESEARCH COMMUNITIES AND BENEFIT MULTIDISCIPLINARY DOMAINS, INCLUDING EPIDEMIOLOGY, ECONOMICS, AND SOCIAL AND BEHAVIORAL SCIENCES. THIS RESEARCH WILL ACCELERATE PERSONALIZED INTERVENTIONS FOR THE AT-RISK TYA COMMUNITY IN REDUCING OPIOID MISUSES AND OVERDOSE DEATHS. FIRST, BASED ON THE LARGE-SCALE DATA GENERATED BY TYAS ON SOCIAL MEDIA, THE TEAM WILL DEVELOP GRAPH NEURAL NETWORKS WITH NOVEL SELF-SUPERVISED AND PROMPT LEARNING TECHNIQUES TO DETECT AT-RISK TYAS, BY ADDRESSING THE CHALLENGES OF HETEROGENEITY, MULTI-MODALITY, AND LIMITED LABELING OF THE ONLINE DATA. SECOND, TO DERIVE AND INTERPRET KEY FACTORS FROM DIVERSE CONTEXTS PRESENTED BY AT-RISK TYAS, THE TEAM WILL DEVELOP A NOVEL CAUSAL ANALYSIS FRAMEWORK BY BRIDGING KNOWLEDGE GRAPH AND LARGE LANGUAGE MODEL FOR INTRICATE REASONING. THIRD, GIVEN THE DETECTED AT-RISK TYAS WITH RELATED CAUSAL ANALYSES, THE TEAM WILL DEVELOP A SAFETY-ENHANCED MULTI-MODAL LEARNING FRAMEWORK AIMING TO GENERATE MESSAGES TAILORED TO AT-RISK TYAS IN PREVENTING OPIOID MISUSE AND ADDICTION. FOURTH, THE TEAM WILL FURTHER DEVELOP AN ADAPTIVE REINFORCEMENT LEARNING FRAMEWORK ENABLING USER-IN-THE-LOOP TO FACILITATE AN INTERACTIVE PROCESS THAT COULD INFORM USERS? FEEDBACK, CALIBRATE THE GENERATED MESSAGES, AND THUS PRODUCE ADAPTIVE INTERVENTIONS FOR AT-RISK TYAS. THIS PROJECT WILL INTEGRATE RESEARCH WITH EDUCATION AND THE OUTCOMES WILL BE MADE PUBLICLY ACCESSIBLE AND BROADLY DISTRIBUTED. 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.