Mica Inc

TAS::89 0211::TAS RECOVERY FOSSIL ENERGY - NEW INDUSTRIAL CARBON CAPTURE AND SEQUESTRATION (CCS) AWARD ENTITLED "DEMONSTRATION OF CO2 CAPTURE & SEQUE

THIS PROJECT INTENDS TO DEMONSTRATE THE COMMERCIAL AND TECHNICAL VIABILITY OF CHEMICALLY RECYCLED POLYETHENE TEREPHTHALATE (CRPET) AT A FIRST-OF-A-KIND CHEMICAL RECYCLING FACILITY. THE CRPET MANUFACTURING PROCESS AIMS TO CREATE DEMAND FOR RECYCLABLE WASTE STREAMS AND, THROUGH PARTNERSHIPS, IMPROVE RECYCLING INFRASTRUCTURE, ULTIMATELY ENABLING HIGHER PLASTIC RECYCLING RATES ACROSS THE US. SUCCESSFUL PROJECT DEPLOYMENT WILL INCREASE MATERIAL CIRCULARITY, DEMONSTRATE THE VIABILITY FOR THERMAL BATTERIES TO PROVIDE LOW-CARBON HEAT, AND SPUR FUTURE INVESTMENT BY SETTING A NEW LOW-CARBON MARKET STANDARD FOR A WIDELY USED CHEMICAL PRODUCT. THIS PROJECT WILL PROVIDE SOCIETAL BENEFIT BY DIVERTING PLASTIC WASTE FROM ENTERING LANDFILLS, SUPPORT TWO-WAY ENGAGEMENT WITH THE COMMUNITY VIA A COMMUNITY ADVISORY PANEL, AND DELIVER TANGIBLE BENEFITS TO THE SURROUNDING COMMUNITY INCLUDING CREATING PERMANENT JOBS.

DEVELOPMENT OF ITM OXYGEN TECHNOLOGY FOR INTEGRATION IN IGCC AND OTHER ADVANCED POWER GENERATION SYSTEMS

DEVELOPMENT OF ITM OXYGEN TECHNOLOGY FOR INTEGRATION IN IGCC AND OTHER ADVANCED POWER GENERATION SYS

BIPARTISAN INFRASTRUCTURE LAW (BIL) CARBONATE SOLVENT PRODUCTION FOR LITHIUM-ION BATTERY ELECTROLYTES THE PROJECT GOAL IS TO DEMONSTRATE THE TECHNOECONOMIC VIABILITY OF ONSHORING DOMESTIC MANUFACTURING OF LOW CARBON ELECTROLYTE SOLVENTS. THE PROJECT WILL DEMONSTRATE THE CREATION OF NEW VALUE STREAMS OF ELECTROLYTE SOLVENTS WHILE FURTHERING THE NATION’S SELF-RELIANCE FOR ELECTRIC VEHICLE (EV) ELECTROLYTES.

THE DOW CHEMICAL COMPANY (DOW) WILL CAPTURE 50% TO 90% BYPRODUCT CARBON DIOXIDE (CO2) IN [[FREEPORT, TEXAS]], FROM PURIFIED ETHYLENE OXIDE (PEO) TO PRODUCE HIGH PURITY ELECTROLYTE SOLVENTS REQUIRED FOR DOMESTIC ELECTRIC VEHICLE (EV) LITHIUM-ION BATTERY (LIB) MANUFACTURING. SECURING A DOMESTIC SUPPLY OF THESE ELECTROLYTE SOLVENTS IS CRITICAL TO NATIONAL SECURITY WITH CURRENT PRODUCTION BEING LARGELY LIMITED TO ASIA. THE PROJECT INVESTS IN SUPPLY CHAIN RESILIENCY FOR DOMESTIC BATTERY AND EV MANUFACTURING AND WILL DEMONSTRATE THE TECHNOECONOMIC VIABILITY OF MANUFACTURING ELECTROLYTE SOLVENTS AT A LARGE-SCALE COMMERCIAL PRODUCTION FACILITY. ADDITIONALLY, DOW WILL UNLOCK AMERICAN WORKFORCE CAPABILITY THROUGH EXTENSIVE WORKFORCE DEVELOPMENT, MEANINGFUL COMMUNITY ENGAGEMENT, DECARBONIZATION EDUCATION, AND DIRECT JOB CREATION WITH A FOCUS ON PROVIDING EQUITABLE ACCESS FOR LOCAL RESIDENTS OF UNDERREPRESENTED COMMUNITIES. THIS PROJECT ALSO AIMS TO IMPROVE CLEAN WATER SUPPLY FOR COMMUNITIES IN THIS WATER-STRESSED BASIN.

RAPID ADVANCEMENT IN PROCESS INTENSIFICATION DEPLOYMENT (RAPID)

WORKER HEALTH AND SAFETY COOPERATIVE AGREEMENT

THE AMERICAN INSTITUTE OF CHEMICAL ENGINEERS (AICHE) WILL LEAD A CONSORTIUM THAT INCLUDES INDUSTRY LEADING FUEL CELL/ELECTROLYZER/CATALYST/IONOMER/ANALYSIS INDUSTRY PARTNERS, NATIONAL LABORATORIES, AND UNIVERSITIES. THE EFFORT WILL DEVELOP TECHNOLOGY RELEVANT TO CIRCULAR RECYCLING FOR THE H2 ECONOMY (H2CIRC) TO ADDRESS END-OF-LIFE (EOL) AND CRITICAL SUPPLY CHAIN CHALLENGES FOR LOW TEMPERATURE PROTON EXCHANGE MEMBRANE (PEM) FUEL CELLS AND ELECTROLYZERS (FC/EL) WITH THE GOAL OF SUSTAINABLY RECOVERING AND RECYCLING CATALYSTS, MEMBRANES, IONOMERS, CARBON, AND OTHER COMPONENTS AS DEPICTED IN FIGURE A.1, WITH THE RECOVERY GOALS LISTED IN TABLE A.1. THE RECOVERY OF THESE MATERIALS IS CRITICAL, AND IT MUST BE PERFORMED IN A MANNER THAT LIMITS GREENHOUSE GAS EMISSIONS (GHG) AND OTHER HARMFUL POLLUTANTS, OTHERWISE THE BENEFITS OF THE H2 ECONOMY WILL BE SIGNIFICANTLY DIMINISHED. ADDITIONALLY, WHILE DEVELOPING THE TECHNOLOGY CRITICAL FOR PEM FC/EL RECYCLABILITY, THE CONSORTIUM WILL INTEGRATE KEY OVERARCHING EFFORTS IN DIVERSITY/INCLUSION, WORKFORCE DEVELOPMENT/TRAINING, TECHNO-ECONOMIC ANALYSIS (TEA), AND LIFE-CYCLE ANALYSIS (LCA), AS HIGHLIGHTED IN THE OUTER RING OF FIGURE A.1. H2CIRC BRINGS TOGETHER A STRONG TEAM OF EXPERTS FROM INDUSTRY, NATIONAL LABS, AND ACADEMIA WITH DEEP TECHNICAL EXPERIENCE IN LOW-TEMPERATURE PEM FC/ELS. THERE ARE A TOTAL OF 16 MEMBERS, INCLUDING 8 INDUSTRIAL PARTNERS, 4 UNIVERSITIES, 3 NATIONAL LABS, AND ONE NON-PROFIT. THE BREADTH AND EXPERTISE OF THESE PARTNERS ENABLES MEMBERSHIP TO SPAN THE ENTIRE VALUE CHAIN OF PEM FC/ELS, BUSINESS SIZE (INCLUDING SMALL/MEDIUM-SIZED ENTERPRISES, SMES), AND GEOGRAPHIC LOCATIONS. THE COLLABORATIVE STRENGTHS OF THE TEAM AND THE KNOWLEDGE OF THE CRITICAL MATERIAL NEEDS/QUALITIES WILL ALLOW THE H2CIRC CONSORTIUM TO DRIVE THE DEVELOPMENT OF CIRCULAR RECYCLING TO ADDRESS EOL AND SUPPLY CHALLENGES WITH THE GOAL TO SUSTAINABLY RECOVER AND RECYCLE CATALYSTS, IONOMERS, AND OTHER COMPONENTS FOR SECOND USE OR REMANUFACTURE. ADDITIONALLY, COMMUNITY OUTREACH IS IMPORTANT TO THE SUCCESS OF THE PROGRAM AS IT WILL HELP TO ATTRACT AND DEVELOP/EDUCATE A WORKFORCE AND INFORM THE PUBLIC AS TO ITS IMPORTANCE. THE CONSORTIUM RECOVERY AND REUSE GOALS FOR EACH MEA COMPONENT ARE 95% FOR IR, 99% FOR PT, 75% FOR THE IONOMER, AND 70% FOR CARBON. TO ACHIEVE THESE GOALS THE CONSORTIUM WILL PURSUE FOUR INDEPENDENT MEA RECYCLE PATHWAYS THAT WILL MINIMIZE RISK, DEVELOP ROBUST RECYCLING OPTIONS, AND ALLOW THE MEMBERS TO DEVELOP THEIR OWN IP. CRITICALLY, THE RECYCLING PATHWAYS AIM TO DEVELOP A PROCESS THAT MAINTAINS THE HIGH LEVELS OF RECOVERY OF THE METALS, BUT ALSO ALLOWS THE IONOMER TO BE RECYCLED/RE-USED WITH CARBON RECOVERY GOALS BEING TERTIARY. TO BE INDUSTRIALLY RELEVANT, THE METHODS DEVELOPED WITHIN THE RECYCLE STREAM MUST BE SCALABLE SUCH THAT THE SPEED OF RECYCLING CAN OCCUR AT RATES COMMENSURATE WITH MANUFACTURING. TO ACHIEVE THIS RATE, IT IS NECESSARY TO ALSO DEVELOP A DISASSEMBLY PROCESS THAT IS EXPEDIENT, AND CONSEQUENTLY, A ROBOTIC/AUTOMATED DISASSEMBLY APPROACH WILL BE PURSUED THAT WILL BE BROADLY USEFUL ACROSS INDUSTRY. FINALLY, THE CONSORTIUM AIMS TO MINIMIZE GHG EMISSIONS BY INVESTIGATING GREEN PATHWAYS, AND THUS TEA AND LCA WILL BE DEPLOYED THROUGHOUT. THIS EFFORT IS NOT AN INFRASTRUCTURE PROJECT.

TAS::89 0331::TAS RECOVERY ACT - ELECTRIC DRIVE VEHICLE BATTERY AND COMPONENT MANUFACTURING INITIATIVE AWARD TO FUTUREFUEL CHEMICAL COMPANY

FULL YEAR HEAD START-PART DAY & HANDICAPPED

HEAD START AND EARLY HEAD START

HEAD START AND EARLY HEAD START CONTINUATION

DEVELOPMENT OF THE ITM SYNGAS TECHNOLOGY FOR CONVERTING NATURAL GAS TO HYDROGEN AND SYNTHESIS GAS FOR LIQUID TRANSPORTATION FUELS

MANAGEMENT AND OPERATION OF THE VIRTUAL ASTRONOMICAL OBSERVATORY

HAZMAT TRAINING AT DOE NUCLEAR WEAPONS COMPLEX

ULTRA HIGH SPEED STEM AND RARE CELL SORTING USING ELECTRO-MAGNETIC MEMS FOR CLINICAL APPLICATIONS

HEAD START AND EARLY HEAD START

DEFENSE PRODUCTION ACT (DPA) TITLE III CRITICAL CHEMICALS PRODUCTION

THIS IS A RENEWAL AWARD FOR THE RAPID MANUFACTURING INSTITUTE®, ORIGINAL AWARD NUMBER DE-EE0007888. THE RAPID INSTITUTE ADVANCES THE DECARBONIZATION OF THE PROCESS INDUSTRIES THROUGH THE DEVELOPMENT AND SCALE-UP OF ADVANCED PROCESS TECHNOLOGIES. RAPID WILL CONTINUE LEADING THE TRANSFORMATION OF MANUFACTURING PROCESSES THROUGH THE DEVELOPMENT AND SCALE-UP OF NEW PROCESS TECHNOLOGIES. DURING ITS RENEWAL, RAPID WILL EXTEND ITS INITIAL FOCUS ON PROCESS INTENSIFICATION AND MODULARIZATION TO ADJACENT ADVANCED PROCESS TECHNOLOGY AREAS SUCH AS CONTINUOUS FLOW PROCESSES, ADVANCED PROCESS COMPUTING AND DATA METHODOLOGIES THROUGHOUT INDUSTRIAL APPLICATIONS.

HIGH ENERGY SUPERIOR LITHIUM POLYMER BATTERIES (SLPB) PROGRAM

THERAPEUTICS TARGETING TDP-43 TO TREAT ALZHEIMER'S DISEASE AND RELATED DISORDERS - TDP-43 IS A MIXED PROTEINOPAPTHY IN ALZHEIMER’S DISEASE (AD), AD-TDP, BASED ON SUBSTANTIAL EPIDEMIOLOGICAL DATA CORRELATING TDP-43 INCLUSIONS WITH COGNITIVE DECLINE IN AD PATIENTS. TDP-43 ASSOCIATED AD HAS BEEN TERMED AS LIMBIC-PREDOMINANT AGE-RELATED TDP-43 ENCEPHALOPATHY (LATE) AS WELL AS OTHER ACRONYMS, UNDERLYING THE NEWLY-RECOGNIZED IMPORTANCE OF TDP-43 IN AD (AD-TDP). AD IS THE MOST COMMON CAUSE OF MID- TO LATE-LIFE COGNITIVE IMPAIRMENT AND DEMENTIA, AFFLICTING ~30 MILLION PEOPLE WORLDWIDE BASED ON AN EXTENSIVE REVIEW OF CLINICAL AND PATHOLOGICAL STUDIES, TDP-43 PROTEINOPATHY IS ASSOCIATED WITH AN AMNESTIC DEMENTIA SYNDROME THAT OCCURS IN OLDER ADULTS. A STATISTICAL ANALYSIS OF ATTRIBUTABLE RISK SUGGESTS THAT TDP-43 ASSOCIATED AD IS A MAJOR PUBLIC HEALTH ISSUE ACCOUNTING FOR UP TO 20% OF CASES OF CLINICALLY DIAGNOSED AD DEMENTIA. THIS TDP-43 PROTEINOPATHY IS A DISTINCT CLINICAL AND PATHOLOGICAL ENTITY FROM OTHER TDP-43 ASSOCIATED DISEASES THAT MAY ALSO BE TREATABLE WITH A TDP-43 TARGETED THERAPY, SUCH AS AMYOTROPHIC LATERAL SCLEROSIS (ALS) AND CERTAIN FORMS OF FRONTOTEMPORAL LOBAR DEGENERATION (FTLD-TDP). THEREFORE, SUCCESSFUL COMPLETION OF THIS PROJECT HAS THE POTENTIAL TO IDENTIFY TDP-43-BASED THERAPEUTICS FOR THE TREATMENT OF OTHER DISEASES WHERE TDP-43 PLAYS A MAJOR AND CAUSATIVE ROLE. WE HAVE DISCOVERED SMALL MOLECULES THAT BIND TO TDP-43 IN SUCH A WAY AS TO INHIBIT BINDING OF RNA TO TDP-43 AND PREVENT TDP-43 AGGREGATION, WITH ACTIVITY SUGGESTIVE OF A THERAPEUTIC EFFECT IN THREE MODELS: (1) HUMAN WILD-TYPE AND MUTANT TDP-43 EXPRESSED IN DROSOPHILA, (2) INDUCED MOTOR NEURONS (IMNS) FROM C9ORF72 PATIENT-DERIVED IPSCS, AND (3) MICE EXPRESSING HUMAN TDP-43 (THY1 PROMOTOR). EVIDENCE FROM 2-D NMR STUDIES AND COMPUTATIONAL DOCKING ANALYSIS SUGGESTS THAT THESE INHIBITORS ARE BINDING TO RIBONUCLEOTIDE RECOGNITION MOTIF RRM2 WHICH CONTAINS ONE OF THE AMINO ACIDS INVOLVED IN A CRITICAL AND FUNCTIONALLY-RELEVANT SALT BRIDGE WITH RRM1. A RECENT PET IMAGING STUDY DESCRIBES A METABOLIC MARKER TO POTENTIALLY SELECT AD-TDP PATIENTS FOR CLINICAL TRIALS BASED ON RATIOS OF FDG IMAGING IN DIFFERENT REGIONS OF THE BRAIN. IN THIS PROJECT WE SEEK TO DISCOVER, VALIDATE AND DEVELOP NEW SMALL- MOLECULE INHIBITORS OF NUCLEIC ACID BINDING TO TDP-43 AND TDP-43 AGGREGATION INHIBITORS TO TREAT AD-TDP. AIM 1 IS THE OPTIMIZATION OF IN VITRO POTENCY AND DRUG-LIKE PROPERTIES OF NOVEL TDP-43 LIGANDS INCLUDING PENETRATION INTO THE BRAIN AND ACCEPTABLE HALF-LIFE AND SAFETY MEASURES USING A COMPREHENSIVE BATTERY OF PHARMACEUTICAL INDUSTRY-STANDARD ASSAYS AND CRITERIA. AIM 2 INVOLVES TARGET ENGAGEMENT STUDIES USING HTDP-43 TRANSFECTED IN HEK293T CELLS, PATIENT-DERIVED INDUCED MOTOR NEURONS FROM IPSCS, DYNAMIC LIGHT SCATTERING ANALYSIS OF AGGREGATION, AND X-RAY CRYSTALLOGRAPHY OF LIGANDS BOUND INTO TDP-43. AIM 3 IS EVALUATION IN ANIMAL MODELS OF TDP-43 PATHOLOGY, INITIALLY USING A THY1 PROMOTER FOLLOWED BY A HTDP-43 BASED MOUSE MODEL THAT DEMONSTRATES COGNITIVE IMPAIRMENT IN THE ABSENCE OF LOCOMOTOR DEFICITS. AIM 4 INCLUDES IND-ENABLING STUDIES, SCALE-UP SYNTHESIS, MULTI-SPECIES PK AND RODENT TOXICITY.

TO PROVIDE INCREAMENTAL FUNDING IN THE AMOUNT OF $350 000.00 THEREBY TO THE TOTAL OBLIGATED AMOUNT OF THE AWARD FROM $1 931 468.00. TO $2 281 468.00

OPCW CENTRE FOR CHEMISTRY AND TECHNOLOGY CONSTRUCTION

BALLISTIC ARMOR RESEARCH PROGRAM

DECARBONIZING LIGHT OLEFIN PRODUCTION USING ADVANCED ELECTROMAGNETIC REACTORS

TAS::57 3600::TAS SUPERIOR LITHIUM POLYMER BATTERY DEVELOPMENT

FULLY INTEGRATED BUILDING SCIENCE SOLUTIONS FOR RESIDENTIAL AND COMMERCIAL PHOTOVOLTAIC ENERGY GENERATION

ELECTRONICS AND PHOTONICS RESEARCH WITH POTENTIALLY FAR-REACHING SIGNIFICANT ECONOMIC AND SCIENTIFIC BENEFITS.

TRANSFORMATIONAL APPROACH TO REDUCING THE TOTAL SYSTEM COSTS OF BUILDING INTEGRATED PHOTOVOLTAICS

HAZMAT TRAINING AT DOE NUCLEAR WEAPONS COMPLEX COOPERAT*

TAS::89 0331::TAS RECOVERY ACT NEW AWARD TO THE DOW CHEMICALCOMPANY ENTITLED, "RECOVERY ACT: ADVANCED INSULATION FOR HIGH PERFOMANCE COST-EFFECTIVE

CALIFORNIA HYDROGEN INFRASTRUCTURE PROJECT

DEVELOPMENT OF ION TRANSPORT MEMBRANE OXYGEN TECHNOLOGY FOR LOW-COST AND LOW-EMISSION GASIFICATION AND OTHER INDUSTRIAL APPLICATIONS

MOD 0001 CHANGES INCLUDE UPDATES TO THE FOLLOWING SECTIONS: 1. SECTION I.B. ON PAGE 36, WITHIN TOPIC 4: TECHNOLOGY FOCUS, CORRECT THE NAICS CODE REFERENCE: CHANGE “BASIC ORGANIC CHEMICALS (NAICS 325519)” TO “ALL OTHER ORGANIC CHEMICALS (NAICS 325199)” 2. SECTION III.F. ON PAGE 64, WITHIN LIMITATION ON NUMBER OF CPS AND FULL APPS ELIGIBLE FOR REVIEW, CHANGE LANGUAGE FROM BASE TEMPLATE OPTION C TO BASE TEMPLATE OPTION A, ALTERNATIVE 2 – ALLOWING FOR MULTIPLE CPS AND APPLICATIONS TO BE SUBMITTED TO THE FOA BY A SINGLE ENTITY. THIS FUNDING OPPORTUNITY (FOA), ISSUED BY THE OFFICE OF ENERGY EFFICIENCY AND RENEWABLE ENERGY, ON BEHALF OF THE INDUSTRIAL EFFICIENCY AND DECARBONIZATION OFFICE (IEDO) WILL ADVANCE THE STRATEGIES IDENTIFIED IN THE INDUSTRIAL DECARBONIZATION ROADMAP AND INDUSTRIAL HEAT ENERGY EARTHSHOT AND WILL FOCUS ON CROSS-SECTOR APPROACHES FOR INDUSTRIAL DECARBONIZATION (SUCH AS THERMAL PROCESSING, LOW-CARBON FUELS UTILIZATION, AND EXPLORATORY CROSS-SECTOR TOPICS), ALONG WITH HIGH-GHG-EMITTING SUBSECTORS (SUCH AS CHEMICALS, IRON AND STEEL, FOOD AND BEVERAGE, CEMENT AND CONCRETE, AND FOREST PRODUCTS). BY ACCELERATING THE DEVELOPMENT AND ADOPTION OF SUSTAINABLE TECHNOLOGIES THAT INCREASE EFFICIENCY AND ELIMINATE INDUSTRIAL GHG EMISSIONS, THE RESEARCH, DEVELOPMENT, AND PROTOTYPE OR PILOT-SCALE TECHNOLOGY VALIDATION AND DEMONSTRATION ACTIVITIES TO BE FUNDED UNDER THIS FOA WILL CONTRIBUTE TO A CLEAN AND EQUITABLE ENERGY ECONOMY, BOLSTER THE TECHNOLOGICAL AND ECONOMIC COMPETITIVENESS OF DOMESTIC MANUFACTURING, AND BOOST THE VIABILITY AND COMPETITIVENESS OF U.S. INDUSTRIAL TECHNOLOGY EXPORTS. THIS FOA IS PART OF AN INTEGRATED INDUSTRIAL DECARBONIZATION TECHNOLOGY DEVELOPMENT STRATEGY FOR DOE’S BASIC AND APPLIED RESEARCH OFFICES. ROOTED IN THE PRINCIPLES IDENTIFIED IN THE 2022 INDUSTRIAL DECARBONIZATION ROADMAP, DOE IS BUILDING AN INNOVATION PIPELINE TO ACCELERATE THE DEVELOPMENT AND ADOPTION OF INDUSTRIAL DECARBONIZATION TECHNOLOGIES WITH INVESTMENTS SPANNING FOUNDATIONAL SCIENCE; RESEARCH, DEVELOPMENT, AND DEMONSTRATIONS (RD&D); AND TECHNICAL ASSISTANCE AND WORKFORCE DEVELOPMENT. DOE’S HIGHLY COORDINATED RD&D INVESTMENTS – LEVERAGING RESOURCES AND EXPERTISE FROM THE OFFICES OF ENERGY EFFICIENCY AND RENEWABLE ENERGY, FOSSIL ENERGY AND CARBON MANAGEMENT (FECM), NUCLEAR ENERGY (NE), AND SCIENCE (SC) – ARE DESIGNED TO ACHIEVE DEEP DECARBONIZATION ACROSS THE INDUSTRIAL SECTOR, TARGETING BOTH INDUSTRY-SPECIFIC INNOVATIONS AND CROSSCUTTING TECHNOLOGIES. THIS TECHNOLOGY DEVELOPMENT STRATEGY COMPLEMENTS THE DEMONSTRATION AND DEPLOYMENT EFFORTS LED BY DOE'S OFFICES OF CLEAN ENERGY DEMONSTRATIONS (OCED) AND MANUFACTURING AND ENERGY SUPPLY CHAINS (MESC) AND THE LOAN PROGRAMS OFFICE (LPO). THIS FOA AND ITS ASSOCIATED PROJECTS ARE DISTINCT FROM ANY EXISTING OR FORTHCOMING EFFORTS FUNDED UNDER THE BIPARTISAN INFRASTRUCTURE LAW OR INFLATION REDUCTION ACT, INCLUDING ACTIVITIES RELATED TO INDUSTRIAL DEMONSTRATION PROJECTS. THE TOPICS INCLUDED ARE: TOPIC 1: DECARBONIZING INDUSTRIAL HEAT TOPIC 2: LOW-CARBON FUELS UTILIZATION R&D TOPIC 3A: ENABLING FLEXIBLE INDUSTRIAL ENERGY USE TOPIC 3B: ENHANCED THERMAL CONDUCTIVITY MATERIALS TOPIC 4: DECARBONIZING CHEMICALS TOPIC 5: DECARBONIZING IRON AND STEEL TOPIC 6: DECARBONIZING FOOD AND BEVERAGE PRODUCTS TOPIC 7: DECARBONIZING CEMENT AND CONCRETE THE EXCHANGE SYSTEM IS CURRENTLY DESIGNED TO ENFORCE HARD DEADLINES FOR CONCEPT PAPER AND FULL APPLICATION SUBMISSIONS. THE APPLY AND SUBMIT BUTTONS AUTOMATICALLY DISABLE AT THE DEFINED SUBMISSION DEADLINES. THE INTENTION OF THIS DESIGN IS TO CONSISTENTLY ENFORCE A STANDARD DEADLINE FOR ALL APPLICANTS. APPLICANTS THAT EXPERIENCE ISSUES WITH SUBMISSIONS PRIOR TO THE FOA DEADLINE: IN THE EVENT THAT AN APPLICANT EXPERIENCES TECHNICAL DIFFICULTIES WITH A SUBMISSION, THE APPLICANT SHOULD CONTACT THE EXCHANGE HELPDESK FOR ASSISTANCE (EXCHANGEHELP@HQ.DOE.GOV). THE EXCHANGE HELPDESK AND/OR THE EERE EXCHANGE SYSTEM ADMINISTRATORS (EXCHANGE@EE.DOE.GOV) WILL ASSIST THE APPLICANT IN RESOLVING ALL ISSUES. APPLICANTS THAT EXPERIENCE ISSUES WITH SUBMISSIONS THAT RESULT IN A LATE SUBMISSION: IN THE EVENT THAT AN APPLICANT EXPERIENCES TECHNICAL DIFFICULTIES WITH A SUBMISSION THAT RESULTS IN A LATE SUBMISSION, THE APPLICANT SHOULD CONTACT THE EXCHANGE HELPDESK FOR ASSISTANCE (EXCHANGEHELP@HQ.DOE.GOV). THE EXCHANGE HELPDESK AND/OR THE EERE EXCHANGE SYSTEM ADMINISTRATORS (EXCHANGE@EE.DOE.GOV) WILL ASSIST THE APPLICANT IN RESOLVING ALL ISSUES (INCLUDING FINALIZING THE SUBMISSION ON BEHALF OF, AND WITH THE APPLICANT'S CONCURRENCE). DOE WILL ONLY ACCEPT LATE APPLICATIONS WHEN THE APPLICANT HAS A) ENCOUNTERED TECHNICAL DIFFICULTIES BEYOND THEIR CONTROL; B) HAS CONTACTED THE EXCHANGE HELPDESK FOR ASSISTANCE; AND C) HAS SUBMITTED THE APPLICATION THROUGH EXCHANGE WITHIN 24 HOURS OF THE FOA'S POSTED DEADLINE.

RILUZOLE PRODRUGS FOR MELANOMA AND ALS

TITLE: ACCELERATED MODULAR PROCESS DEVELOPMENT (AMPD) FOR DOMESTIC MANUFACTURING OF CRITICAL ACTIVE PHARMACEUTICAL INGREDIENT CHEMICAL PRECURSORSPURPOSE: THE PURPOSE OF THIS GRANT IS TO DEVELOP A MORE EFFICIENT FRAMEWORK FOR DOMESTIC MANUFACTURING OF ACTIVE PHARMACEUTICAL INGREDIENTS (APIS) CRITICAL TO MORE EFFECTIVE CORONAVIRUS RESPONSE.ACTIVITIES TO BE PERFORMED: THE PROJECT TEAM WILL DEFINE A NEW STREAMLINED APPROACH TO TAKE A CHEMICAL MANUFACTURING PROCESS FROM LAB BENCH TO COMMERCIAL PRODUCTION. THE PROJECT WILL ALSO DEVELOP A WORK PROCESS THAT INCORPORATES HISTORIC BEST PRACTICES, UPDATED WITH STATE-OF-THE-ART TECHNICAL, ECONOMIC, AND SUSTAINABILITY MODELING, AND INTEGRATES THE APPROACHES TO MODULAR MANUFACTURING. A PROCESS DEVELOPMENT CENTER OF EXCELLENCE WILL BE ESTABLISHED AS A TESTBED WHERE RESEARCHERS CAN ACCESS STATE-OF-THE-ART LABORATORY AND MODULAR PILOT PLANT SYSTEMS FOR DEVELOPING AND SCALING CHEMICAL MANUFACTURING PROCESSES. EXPECTED OUTCOMES: THE PROJECT WILL BUILD GREATER RESILIENCE IN SUPPLY CHAINS FOR ACTIVE PHARMACEUTICAL INGREDIENTS (APIS) THROUGH INTENSIFIED, MODULAR PROCESSES.INTENDED BENEFICIARIES: SMALL AND MEDIUM MANUFACTURERS WILL BENEFIT FROM USE OF THE CENTER OF EXCELLENCE TO DEVELOP PROCESSES AND BUILD PRODUCTION CAPACITY FOR ONSHORING OF SELECTED SPECIALTY CHEMICALS, API PRECURSORS, AND APIS.SUBRECIPIENT ACTIVITIES: THE RECIPIENT PLANS TO SUBAWARD FUNDS TO BRING TOGETHER EXPERTS IN CHEMICAL AND PHARMACEUTICAL PROCESS DEVELOPMENT AND MODULAR PROCESSING TECHNOLOGY TO BE AN INTEGRAL PART OF THIS RESEARCH PROJECT.

VALIDATION OF INTEGRATED SYSTEM FOR A HYDROGEN FUELED POWER PARK

ENVIRONMENTAL SCIENCES COOPERATIVE AGREEMENT

INTERDISCIPLINARY TRAINING IN THE CHEMICAL SENSES

EFFICACY OF BITTER TASTE BLOCKERS ON FLAVOR ACCEPTANCE IN PEDIATRIC POPULATIONS

ULTRA-HIGH-SPEED STEM AND RARE CELL SORTING USING ELECTRO-MAGNETIC MEMS FOR CLINICAL APPLICATIONS

DESIGN AND DEVELOPMENT OF NEW CARBON-BASED SORBENT SYSTEMS FOR AN EFFECTIVE CONTAINMENT OF HYDROGEN

NEW ANTIFUNGAL AGENTS AS TOPICAL AND SYSTEMIC THERAPIES FOR WOUND AND INVASIVE INFECTIONS

TAS::89 0331::TAS RECOVERY ACT EERE- NEW COMBINED HEAT AND POWER (CHP) AWARD ENTITLED "WASTE ENERGY PROJECT AT THE AK STEEL CORPORATION MIDDLETOWN WO

LEARNING AND OLFACTION: UNDERSTANDING AND ENHANCING A CRITICAL INFORMATION CHANNEL

DEVELOPMENT OF SMALL ANTIMICROBIAL PEPTIDE MIMICS AS DRUG-RESISTANT AND SUSCEPTIB

FERTILIZER PRODUCTION EXPANSION PROGRAM

FERTILIZER PRODUCTION EXPANSION PROGRAM 2.0

TITLE: SCALE-UP OF CONTINUOUS MANUFACTURING AND PRODUCTIZATION OF GRAPHENE FUNDABLE OUTSTANDING ADVANCED RESPIRATOR AND BIOSENSOR APPLICATIONSPURPOSE: THE PURPOSE OF THIS GRANT IS TO DEVELOP NEW, ADVANCED MANUFACTURING CAPACITY FOR HIGH-QUALITY GRAPHENE AND DEMONSTRATE USE OF GRAPHENE IN A HIGH EFFICIENCY RESPIRATOR MASK (N98+) AND BIOSENSOR APPLICATIONS.ACTIVITIES TO BE PERFORMED: THE PROJECT TEAM WILL DEMONSTRATE THE ELECTROCHEMICAL EXFOLIATION PROCESS TO PRODUCE GRAPHENE IN THE LABORATORY; PILOT A PROCESS TO CONVERT GRAPHITE TO FULLY REDUCED GRAPHENE FLAKE SCALES; DEVELOP A CONTINUOUS MANUFACTURING APPROACH TO PRODUCE GRAPHENE IN LARGER VOLUMES; AND DEMONSTRATE PROOF-OF-CONCEPT USE OF THIS GRAPHENE IN HIGH PERFORMANCE RESPIRATOR MASKS AND NANO-BIOSENSOR APPLICATIONS.EXPECTED OUTCOMES: THIS TECHNOLOGY FROM THIS PROJECT WILL ENABLE THE DEVELOPMENT OF HIGH EFFICIENCY RESPIRATOR MASK (N98+) AND BIOSENSOR APPLICATIONS TO LIMIT EXPOSURE TO AND TRANSMISSION OF CORONAVIRUS AND WILL ALSO ENABLE THE GREATER INDUSTRIAL USE OF GRAPHENE FOR OTHER APPLICATIONS CURRENTLY LIMITED BY MANUFACTURING SCALE UP CHALLENGES.INTENDED BENEFICIARIES: HEALTHCARE WORKERS, GENERAL PUBLIC AND U.S. MANUFACTURERS WILL BENEFIT FROM A RESILIENT DOMESTIC SUPPLY CHAIN FOR HIGH QUALITY AND LOW-COST GRAPHENE. THIS CRITICAL ADVANCED MATERIAL WILL ENABLE MORE BREATHABLE RESPIRATORS THAT PROVIDE HIGH FILTRATION PERFORMANCE (N98+) AND, POTENTIALLY, ANTIMICROBIAL FUNCTIONALITY, TO PREVENT THE SPREAD OF RESPIRATORY VIRUSES; AN ACCURATE, LOW-COST, AND NEAR REAL TIME BIOSENSOR TO DETECT CORONAVIRUS AND ITS VARIANTS ALLOWING CONVENIENT, NON-INVASIVE TESTING IN SITU; AND A WIDELY DISTRIBUTED, MODULAR DOMESTIC MANUFACTURING CAPABILITY FOR HIGH-QUALITY GRAPHENE FLAKES FOR OTHER INDUSTRIAL APPLICATIONS.SUBRECIPIENT ACTIVITIES: THE RECIPIENT PLANS TO SUBAWARD FUNDS TO BRING IN SUBJECT MATTER EXPERTS TO SCALE UP TECHNOLOGY FROM LAB TO CONTINUOUS MANUFACTURING; INCORPORATE GRAPHENE INTO FILTER MEDIA FOR ADVANCED N98/N99 RESPIRATORS; AND INCORPORATE GRAPHENE IN A WI-FI NANO-BIOSENSOR.

GINER ELECTROCHEMICAL SYSTEMS, INC. - TRANSPORT STUDIES AND MODELING IN PEM FUEL CELLS

FULLY INTEGRATED BUILDING SCIENCE SOLUTIONS FOR RESIDENTIAL AND COMMERCIAL PHOTOVOLTAIC ENERGY

TAS::89 0331::TAS RECOVERY RECOVERY ACT: ENHANCED GROWTH RATE AND SILANE UTILIZATION IN AMORPHOUS SILICON AND NANOCRYSTALINE-SILICON SOLAR CELL DE

PHYSIOLOGY OF CALCIUM APPETITE

TRYPANOCIDAL AGENTS THAT KILL MULTIPLE STAGES OF THE TRYPANOSOMA CRUZI LIFE CYCLE - ABSTRACT. CHAGAS DISEASE IS A NEGLECTED TROPICAL DISEASE AND HAS BEEN DESIGNATED AS A RESEARCH PRIORITY BY NIAID AND AN SBIR RESEARCH TOPIC OF INTEREST. SIX MILLION INDIVIDUALS ARE INFECTED AND 8,000 DEATHS WERE CAUSED BY CHAGAS IN 2015 IN MOSTLY CENTRAL AND SOUTH AMERICA BY ADVANCED FORMS OF THE DISEASE SUCH AS CHAGAS HEMORRHAGIC FEVER. THE COST ASSOCIATED WITH CHAGAS DISEASE TREATMENT GLOBALLY IS ESTIMATED TO BE ~$7 BILLION. CHAGAS DISEASE IS CAUSED BY THE PARASITIC PROTIST TRYPANOSOMA CRUZI (T. CRUZI) AND SPREAD BY TRIATOMINAE, OR "KISSING BUGS". WHILE ENDEMIC IN SOUTH AMERICA, IT IS SPREAD TO PEOPLE LIVING ELSEWHERE DUE TO IMMIGRATION OF INFECTED PATIENTS AND TRAVEL TO ENDEMIC REGIONS. NO VACCINE IS CURRENTLY AVAILABLE AND THE ONLY DRUGS USED TO TREAT CHAGAS, THE NITRO ARYL COMPOUNDS NIFURTIMOX AND BENZNIDAZOLE, LOSE EFFECTIVENESS IN THE CHRONIC PHASE AS THE PARASITE DEVELOPS RESISTANCE, AND THEY CAUSE LIMITING ADVERSE EVENTS AS WELL. NEW MEDICATIONS ACTING VIA NOVEL MECHANISMS ARE URGENTLY NEEDED TO ELIMINATE THE PARASITE IN CHRONIC PATIENTS SUFFERING AND DYING FROM CHAGAS DISEASE. NOVEL COMPOUNDS SYNTHESIZED AT FOX CHASE CHEMICAL DIVERSITY CENTER (FCCDC) HAVE BEEN TESTED AT MULTIPLE COLLABORATOR SITES: GSK TRES CANTOS OPEN LAB FOUNDATION IN TRES CANTOS, SPAIN; NEW YORK UNIVERSITY; UNIVERSITY OF DUNDEE, SCOTLAND; AND THE SWISS TROPICAL PUBLIC HEALTH INSTITUTE, ALL RESEARCH FACILITIES DEDICATED TO CURING NEGLECTED TROPICAL DISEASES. THE ANALOGS TESTED DISPLAYED EXCELLENT ACTIVITY AGAINST THE T. CRUZI PARASITE IN BOTH ITS REPLICATIVE (AMASTIGOTE) AND INFECTIVE (TRYPOMASTIGOTE) FORMS AS FOUND IN PHENOTYPIC SCREENING ASSAYS. THE COMPOUNDS DO NOT ACT THROUGH ANY KNOWN MECHANISM OF ACTION AND DISPLAY LITTLE TO NO TOXICITY TO HOST CELLS, UNLIKE THE STANDARDS OF CARE NIFURTIMOX AND BENZNIDAZOLE. FURTHER, IN VIVO TESTING IN A MURINE MODEL FOR CHAGAS DISEASE (NYU) CONFIRMED POTENT ANTIPARASITIC ACTIVITY. THE LEAD COMPOUNDS ARE PROPRIETARY TO FCCDC AND A PROVISIONAL U.S. PATENT APPLICATION HAS BEEN FILED. THE ACTIVITY SEEN FOR THE SERIES HAS GENERATED GREAT INTEREST AT THE NON-PROFIT DRUGS FOR NEGLECTED DISEASES INITIATIVE (DNDI). DNDI EVALUATES MANY POTENTIAL INTERNATIONAL COLLABORATIONS EACH YEAR BUT ONLY SELECTS THE MOST PROMISING FOR RESOURCE INVESTMENT. FOLLOWING EVALUATION OF OUR PROJECT, DNDI HAS COMMITTED ADDITIONAL T. CRUZI TESTING GRATIS AT BOTH THE UNIVERSITY OF DUNDEE AND THE SWISS TROPICAL AND PUBLIC HEALTH INSTITUTE IN ORDER TO EVALUATE POTENCY AND INVESTIGATE MECHANISM OF ACTION. OUR AIMS TO DEVELOP THIS CHEMOTYPE FROM LEAD COMPOUND TO PRECLINICAL CANDIDATE IS (1) OPTIMIZE THE POTENCY BY EXPLORING THE SAR OF OUR NOVEL LEAD USING ITERATIVE MEDICINAL CHEMISTRY SYNTHESI, (2) CHARACTERIZE THE BIOCHEMICAL PROPERTIES OF THE COMPOUNDS TO OPTIMIZE ANTIPARASITIC ACTIVITY (NYU, DNDI), AND (3) PERFORM IN VIVO TESTS IN ACUTE AND CHRONIC CHAGAS DISEASE MOUSE MODELS (NYU) AS WELL AS EVALUATE AND IMPROVE ADME PROPERTIES OF ADVANCED LEADS AS REQUIRED. THE GOAL OF THIS PROGRAM IS TO COMPLETE MANY OF THE STUDIES NECESSARY FOR FILING AN INVESTIGATIONAL NEW DRUG (IND) APPLICATION FOR NEW AGENTS TO TREAT CHAGAS DISEASE AS MONOTHERAPY OR IN COMBINATION WITH EXISTING AGENTS.

OPTIMIZING A STAPLED-PEPTIDE THAT SPECIFICALLY TARGETS HSV-1 TO TREAT HERPES OCULAR KERATITIS - ABSTRACT INFECTION OF THE EYE BY HERPES SIMPLEX VIRUS-1 (HSV-1) CAN RESULT IN HERPES KERATITIS (HK), WHICH IS THE LEADING CAUSE OF INFECTIOUS CORNEAL BLINDNESS WORLDWIDE. IN THE U.S., NEARLY 500,000 INDIVIDUALS EXPERIENCE OCULAR HERPES INFECTIONS THAT ARE OFTEN RECURRENT AND CULMINATE IN PROGRESSIVE CORNEAL SCARRING AND LOSS OF VISION. THE GOLD STANDARD TREATMENT IS ACYCLOVIR (ACV) THAT TARGETS HSV-1 THYMIDINE KINASE (TK). HOWEVER, EMERGENCE OF ACV VIRAL RESISTANT MUTANTS IN 7-14% OF OCULAR HK PATIENTS HAS CREATED THE URGENT NEED TO DISCOVER A SECOND DRUG DIRECTED AGAINST A DIFFERENT HSV-1 TARGET. A NEW CLASS OF ANTIVIRAL TARGETS ARE PROCESSIVITY FACTORS (PFS) THAT ARE ESSENTIAL FOR TETHERING THEIR COGNATE POLYMERASES (POLS) TO THE TEMPLATE TO ENABLE CONTINUOUS DNA SYNTHESIS. DURING HSV-1 REPLICATION, THE DNA-ANCHORED PF BINDS TO THE EXTREME C-TERMINUS OF POL (C-POL) TO KEEP POL FROM DISSOCIATING FROM THE VIRAL TEMPLATE. WHEN CO-CRYSTALLIZED WITH ITS PF, THE C-TERMINUS OF THE VIRAL POL (C-POL) FORMS AN A-HELIX, WITH ONE FACE MAKING MULTIPLE BONDS WITH SEVERAL RESIDUES OF PF WHILE THE OTHER FACE IS SOLVENT EXPOSED. OUR GOAL IS TO DEVELOP A NOVEL ANTIVIRAL DRUG THAT SPECIFICALLY TARGETS HERPES PF FOR THE PURPOSE OF TREATING ACV RESISTANT HK. STAPLED A-HELICAL PEPTIDES HAVE EMERGED FOR USE IN TARGETING PROTEIN-PROTEIN INTERACTIONS THAT OFTEN DISPLAY AS LONG FLAT SURFACES WHICH ARE DIFFICULT FOR SMALL MOLECULES TO BIND EFFICIENTLY. PEPTIDE A-HELICES ARE IDEAL STRUCTURAL MOTIFS FOR INCORPORATING CHEMICAL STAPLES TO PROVIDE RIGIDITY TO MAKE NATURAL BONDS WITH RESIDUES ON THE TARGET PROTEIN. MOREOVER, STAPLES CAN CREATE A PROTEASE SHIELD TO PROLONG RESIDENCE TIME. WE HAVE NOW ENGINEERED A STAPLED PEPTIDE OF C-POL (SPEP7B) THAT BLOCKS THE MECHANISM OF PROCESSIVE DNA SYNTHESIS IN VITRO AND HSV-1 INFECTION IN HUMAN ORGANOTYPIC (3D) CORNEAL EPITHELIAL CELLS; THE UNSTAPLED PEPTIDE IS NON-INHIBITORY. SPEP7B WAS SHOWN TO ELIMINATE HSV-1 VIRAL DNA IN INFECTED CELLS WHILE FAILING TO BLOCK A DIFFERENT VIRUS. IMPORTANTLY, SPEP7B EXHIBITS UNDETECTABLE TOXICITY (CC50>100ΜM) BY TWO DIFFERENT ASSAYS IN HUMAN OCULAR EPITHELIAL CELLS. OUR GOAL IS TO ENTER SPEP7B INTO PRECLINICAL DEVELOPMENT AS A TOPICAL TO TREAT HK. THIS WILL BE ACCOMPLISHED BY CONDUCTING A SERIES OF AIMS THAT INCLUDE SCALEUP OF SPEP7B AND EVALUATING TWO FORMULATIONS FOR DELIVERY OF SPEP7B INTO HUMAN 3D CULTURES AND THEN EX-VIVO EXCISED RABBIT CORNEA FOR PERMEABILITY AND TOXICITY. THESE STUDIES ARE ESSENTIAL TO CONFRONT THE PHYSIOLOGICAL AND ANATOMICAL BARRIERS TO TOPICAL OCULAR DELIVERY. IN VIVO STUDIES WILL EVALUATE SPEP7B FOR TOLERABILITY, GENOTOXICITY, PK, AND REPEAT DOSING. AN EFFICACY STUDY WILL EVALUATE SPEP7B FOR CLINICAL CURE AND VIRAL CLEARING. BACKUP ANALOGS OF SPEP7B WILL BE PREPARED AND EVALUATED FOR RISK MITIGATION. A MODEL FOR NEW ANTIVIRAL DRUGS: CLOSELY ALIGNED WITH THIS APPROACH IS THE POTENTIAL FOR USING PFS AND STAPLED PEPTIDES OF OTHER VIRUSES FOR TREATING UNMET MEDICAL NEEDS CAUSED BY INFECTIONS THAT LEAD TO DELETERIOUS COMPLICATIONS.

DEVELOPMENT OF SMALL MOLECULE THERAPEUTICS TARGETING HEMORRHAGIC FEVER VIRUSES - SUMMARY: THE ULTIMATE GOAL OF THIS PHASE II APPLICATION IS TO DEVELOP NOVEL SMALL MOLECULE, BROAD-SPECTRUM THERAPEUTICS AGAINST VIRAL INFECTIONS CAUSED BY FILOVIRUSES, ARENAVIRUSES, AND OTHER VIRUSES THAT DEPEND ON THE PPXY L-DOMAIN MOTIF FOR EGRESS AND SPREAD OF INFECTION. SOME OF THESE VIRUSES, INCLUDING EBOLA (EBOV), MARBURG (MARV), AND LASSA FEVER (LAFV) VIRUSES, ARE HIGHLY PATHOGENIC AND CLASSIFIED AS CATEGORY A BIOTERROR PATHOGENS. WE AND OTHERS HAVE DETERMINED THAT EFFICIENT BUDDING OF THESE EMERGING HUMAN PATHOGENS DEPENDS ON THE SUBVERSION OF HOST PROTEINS, SUCH AS NEURAL PRECURSOR CELL EXPRESSED DEVELOPMENTALLY DOWN-REGULATED PROTEIN 4 (NEDD4), BY PPXY L-DOMAINS IN THE MATRIX PROTEINS OF THESE RNA VIRUSES. THE IDENTIFICATION AND DEVELOPMENT OF SMALL MOLECULE INHIBITORS THAT INTERFERE WITH THESE VIRUS-HOST INTERACTIONS SHOULD EFFECTIVELY BLOCK VIRUS EGRESS, DISEASE PROGRESSION, AND TRANSMISSION. IN THESE EFFORTS WE HAVE DISCOVERED SEVERAL CHEMICAL SERIES OF SMALL MOLECULE INHIBITORS OF THE HOST NEDD4/VIRUS PPXY COMPLEX IMPORTANT FOR VIRAL EGRESS WHICH LED TO ONE ANALOG POSSESSING PROOF OF CONCEPT IN VIVO ACTIVITY IN A MARBURG VIRUS CHALLENGED MOUSE MODEL. AS FDA APPROVED THERAPEUTIC AGENTS FOR THE TREATMENT OF THESE MOST OF THESE VIRAL INFECTIONS ARE NOT AVAILABLE, OUR IDENTIFICATION OF VIRUS-HOST INHIBITORS THAT MAY PREVENT VIRUS SPREAD WILL FILL A SIGNIFICANT UNMET NEED. MOREOVER, THESE INHIBITORS WILL BE BROAD-SPECTRUM, AND THEREFORE WILL LIKELY BE EFFECTIVE AGAINST NEWLY EMERGING VIRUSES AS WELL AS VIRAL VARIANTS. AS DESCRIBED BELOW, WE WILL USE A RIGOROUS MULTIFACETED APPROACH TO IDENTIFY, DEVELOP, AND VALIDATE PPXY BUDDING INHIBITORS IDENTIFIED IN PHASE I AS POTENT, BROAD-SPECTRUM ANTIVIRALS. THE GOAL OF THIS PHASE II STTR GRANT APPLICATION IS TO OPTIMIZE OUR LEAD INHIBITORS OF VP40 PPXY-NEDD4 INTERACTIONS TO GENERATE FULL- FLEDGED PREDEVELOPMENT DRUG CANDIDATES READY FOR IND DIRECTED STUDIES. THIS WILL BE ACCOMPLISHED BY COMBINING THE PHARMACEUTICAL AND MEDICINAL CHEMISTRY EXPERTISE OF THE SCIENTISTS AT THE FOX CHASE CHEMICAL DIVERSITY CENTER, INC. (FCCDC) WITH THE EXPERTISE AND EXPERIENCE IN THE EXPERIMENTAL ASPECTS OF ANTIVIRAL THERAPY OF THE HARTY LAB AT THE UNIVERSITY OF PENNSYLVANIA. WE WILL REALIZE THIS GOAL BY OPTIMIZING OUR EXISTING SERIES OF INHIBITORS, EXEMPLIFIED BY IN VIVO ACTIVE FC-10696, FOR IMPROVED POTENCY AND ORAL DRUG PROPERTIES (AIM 1), EVALUATING NEW COMPOUNDS BASED ON TWO POTENT SERIES FOR THEIR ABILITY TO SPECIFICALLY INHIBIT PPXY-NEDD4 INTERACTIONS AND SUBSEQUENT VLP AND SURROGATE VIRUS EGRESS (AIM 2), IDENTIFYING COMPOUNDS HAVING SUITABLE DRUG PROPERTIES AND SELECTIVITY USING IN VITRO AND IN VIVO ADMET EVALUATION (AIM 3), AND EVALUATING COMPOUNDS FOR THEIR ANTIVIRAL EFFICACY AGAINST AUTHENTIC BSL-4 VIRUSES IN VITRO AND IN VIVO (AIM 4).

DEVELOPMENT OF TOPICAL ANTIVIRAL AGENTS FOR TREATING MOLLUSCUM CONTAGIOSUM

PRECLINICAL DEVELOPMENT OF OCF001 FOR TREATMENT OF YEAST INFECTIONS

RAIL AND TRANSIT SECURITY GRANT PROGRAM

EVALUATING THE THERAPEUTIC POTENTIAL OF VAGAL CART CIRCUITRY FOR TREATING METABOLIC DISEASE

SMALL MOLECULE ANTAGONISTS OF PF4 FOR THE TREATMENT AND PREVENTION OF HIT

TAS::89 0331::TAS RECOVERY DE-EE0003925 NEW AWARD "RECOVERY ACT: LOW-COST R10/HIGH SHGC HEAT MIRROR WINDOW DEVELOPMENT"

STRONG PARENTS STRONG CHILDREN - FATHERHOOD PROGRAM

FULL-SCALE DEVELOPMENT: MY SKY TONIGHT: EARLY CHILDHOOD PATHWAYS TO ASTRONOMY

IMPACT OF DIET COMPOSITION DURING INFANCY ON ENERGY BALANCE, SATIETY AND GROWTH

ON-THE-SPOT ASSESSMENT TO IMPROVE SCIENTIST ENGAGEMENT WITH THE PUBLIC

MODEL FOR SENSITIVE PERIODS IN EARLY FLAVOR LEARNING

INFLAMMATION AND CHEMOSENSORY LOSS - SUMMARY. OVERVIEW. INFLAMMATION AND CHEMOSENSORY LOSS THIS APPLICATION RESPONDS TO PAR-22-025 AND REQUESTS FUNDS FOR A CLINICAL RESEARCH CENTER TO RESEARCH HOW INFLAMMATION CONTRIBUTES TO THE SUSTAINED LOSS OF TASTE AND SMELL IN THE WAKE OF COVID-19. THREE RESEARCH PROJECTS FOCUS ON THE MOLECULAR MECHANISMS OF SMELL AND TASTE LOSS, AND THE ADMINISTRATIVE AND CHEMOSENSORY CLINICAL SERVICES CORE SUPPORTS THE RESEARCH PROJECT INVESTIGATORS WITH A RANGE OF SERVICES, INCLUDING PARTICIPANT RECRUITMENT STRATEGIES LIKE OUTREACH AND EDUCATION COMPONENTS FOR CLINICIANS, PATIENTS, PATIENT ADVOCACY GROUPS, AND POLICYMAKERS. PROJECT 1 EXAMINES PEOPLE WITH AND WITHOUT SUSTAINED CHEMOSENSORY LOSS, INCLUDING CHILDREN, AND HOW IT IS RELATED TO OLFACTORY AND TASTE EPITHELIUM INFLAMMATION. PROJECT 2 EXAMINES THE OLFACTORY TISSUE IN MORE DEPTH IN A SUBSET OF THE SAME PARTICIPANTS; PROJECT 3 IS SIMILAR BUT FOR TASTE. INVESTIGATORS IN PROJECTS 2 AND 3 WILL DEVELOP ORGANOIDS, AND WE WILL CONDUCT EXPERIMENTS TO SEE HOW THESE ORGANOIDS RESPOND TO VARIANTS OF SARS-COV-2 AND OTHER VIRUSES. THE THEME OF LONG COVID UNITES THE PROJECTS, AND SYNERGIES ARISE BY MEASURING PARTICIPANTS IN EACH PROJECT WITH A STANDARD SET OF TOOLS, ALLOWING FOR DIRECT COMPARISONS ACROSS PROJECTS. ALL THE INVESTIGATORS ARE EXPERTS IN THEIR RESPECTIVE FIELDS, AND THE DIRECTOR HAS YEARS OF EXPERIENCE ADMINISTERING LARGE RESEARCH AND TRAINING PROGRAMS. INNOVATION OF THIS PROJECT IS TWO-FOLD: (A) LEVERAGING THE UNFORTUNATE NATURAL EXPERIMENT OF COVID-19 CHEMOSENSORY DYSFUNCTION TO UNDERSTAND THE CHEMICAL SENSES BETTER AND (B) DISSOLVING BOUNDARIES IN TRADITIONAL RESEARCH AIMED AT UNDERSTANDING AND TREATING THIS DYSFUNCTION. THE INVESTIGATORS OF THE CLINICAL RESEARCH CENTER AIM TO ACCOMPLISH WHAT NO SINGLE INVESTIGATOR CAN DO ALONE AS THEY WORK TOWARD UNDERSTANDING AND TREATING SUSTAINED COVID-ASSOCIATED TASTE AND SMELL LOSS AND ITS HEALTH CONSEQUENCES.

DIVERSITY SUPPLEMENT TO DP2AT011965 - PROJECT SUMMARY OUR MODERN FOOD ENVIRONMENT, WITH ITS WIDESPREAD AVAILABILITY OF ENERGY-DENSE, PALATABLE FOODS AND ASSOCIATED CUES, IS THOUGHT TO INTERACT WITH OUR PHYSIOLOGY TO PROMOTE FOOD INTAKE. THIS HAS CONTRIBUTED TO THE DRASTIC INCREASE IN OBESITY IN THE UNITED STATES OVER THE PAST SEVERAL DECADES. HOWEVER, MOST PHARMACOLOGICAL WEIGHT LOSS STRATEGIES TARGET SATIATION PATHWAYS, NOT SENSORY PATHWAYS, AND THEREFORE MAY BE LESS EFFECTIVE AT ELIMINATING EFFECTS OF ENVIRONMENTAL/SENSORY CUES ON FOOD INTAKE. HERE WE PROPOSE TO TAKE A NOVEL APPROACH TO UNDERSTANDING THE DRIVE TO EAT BY EXAMINING THE NEURAL INTEGRATION OF SENSORY AND NUTRITIVE FOOD SIGNALS. FIRST, WE WILL CREATE SENSORY “ENGRAMS” – FUNCTIONAL MAPS OF NEURONS ACTIVATED BY DISCRETE SENSORY STIMULI – AND DETERMINE HOW ACTIVATING OR INHIBITING THESE CIRCUITS CAN INFLUENCE FOOD PREFERENCE. NEXT, WE WILL MONITOR CALCIUM DYNAMICS IN INDIVIDUAL NEURONS TO REVEAL THE ACTIVITY PATTERNS THAT INTEGRATE SENSORY AND NUTRITIVE INFORMATION IN THE BRAIN ACROSS DIFFERENT BODY WEIGHTS. THESE STUDIES WILL REVEAL FUNDAMENTAL PRINCIPLES OF HOW FOOD INFORMATION IS INTEGRATED IN THE BRAIN TO DRIVE FEEDING BEHAVIOR, REVEALING NEW TARGETS FOR THE DEVELOPMENT OF OBESITY THERAPEUTICS. THIS APPLICATION SEEKS FUNDS TO ENABLE MS. ALEXANDRA VARGAS, A FIRST-GENERATION, LOW INCOME, LATINX U.S. CITIZEN TO PERFORM RESEARCH ON THE NEURAL UNDERPINNINGS OF FEEDING BEHAVIOR, ADD MULTIPLE COMPLEMENTARY NEUROSCIENCE TECHNIQUES TO HER TECHNICAL REPERTOIRE, DEVELOP RECEIVE WRITING, PRESENTATION, AND NETWORKING SKILLS THAT WILL MAKE HER COMPETITIVE FOR M.D./PH.D. PROGRAMS IN NEUROSCIENCE. THESE FUNDS WILL FACILITATE MS. VARGAS’ TRANSITION TO A PRE-DOCTORAL TRAINEE SO THAT SHE CAN RECEIVE ADVANCED TRAINING AND TAKE A LEADERSHIP ROLE ON AN NIH-FUNDED PROJECT. TO THIS END, WE HAVE CAREFULLY CRAFTED A TRAINING PLAN THAT WILL FACILITATE MS. VARGAS’ TECHNICAL, INTELLECTUAL, AND CAREER DEVELOPMENT, AND FUNDING OF THIS SUPPLEMENT WILL TRANSITION HER TO THIS INDEPENDENT ROLE THAT WILL PREPARE HER FOR THE RIGORS OF AN M.D./PH.D. PROGRAM IN FALL 2023. OVERALL, THIS FUNDING WILL FACILITATE THE CAREER OF MS. VARGAS, AN EXTREMELY IMPRESSIVE AND TALENTED RISING SCIENTIST, GIVING HER THE OPPORTUNITY TO MAKE MAJOR ADVANCES IN THE FIELDS OF NEUROSCIENCE AND OBESITY WHILE INCREASING DIVERSITY IN NIH HEALTH-RELATED RESEARCH.

DESIGNING MICROPOROUS CARBONS FOR HYDROGEN STORAGE SYSTEMS

DIET-INDUCED MODIFICATION OF SWEET TASTE PERCEPTION AND PREFERENCE: A POTENTIAL STRATEGY TO AID IN POPULATION-WIDE REDUCTION IN SUGAR INTAKE

CORE CENTER FOR CHEMICAL SENSES

CHEMOSENSORY CLINICAL RESEARCH CENTER

SUSTAINABLE MANUFACTURING OF ACRYLONITRILE

MARSHALLTOWN COMMUNITY SCHOOL PROJECT

FERTILIZER PRODUCTION EXPANSION PROGRAM 2.0

NSF INCLUDES ALLIANCE: INCLUSIVE GRADUATE EDUCATION NETWORK

DEVELOPMENT OF SMALL MOLECULE THERAPEUTICS AGAINST SMALLPOX AND OTHER POXVIRUSES

UNRAVELING THE HOMEOSTATIC AND HEDONIC CIRCUITS UNDERLYING FEEDING BEHAVIOR AND OBESITY - PROJECT SUMMARY THE STRIKING PREVALENCE OF OBESITY AND ITS ASSOCIATED PERSONAL AND PUBLIC HEALTH CONSEQUENCES HIGHLIGHTS THE IMPORTANCE OF UNDERSTANDING WHY INDIVIDUALS OVEREAT AND GAIN WEIGHT. IT IS WIDELY RECOGNIZED THAT OVEREATING RESULTS FROM A COMBINATION OF HOMEOSTATIC (I.E., NUTRIENT NEED, HUNGER) AND HEDONIC (I.E., PLEASURE, REWARD) DRIVES. WHILE THESE HOMEOSTATIC (E.G., HYPOTHALAMIC) AND HEDONIC [E.G., MIDBRAIN DOPAMINE (DA)] SYSTEMS HAVE BEEN CHARACTERIZED AS DISCRETE DRIVERS OF FOOD INTAKE, THERE IS CONSIDERABLE EVIDENCE THAT THESE SYSTEMS OVERLAP. FOR EXAMPLE, DA SIGNALING IN RESPONSE TO FOOD IS POTENTIATED BY HUNGER, INCREASING THE REWARD VALUE OF FOOD DURING TIMES OF HOMEOSTATIC NEED. OUR RECENT FINDINGS IN RODENT MODELS REVEALED A NEURAL CORRELATE FOR THE INTERACTION BETWEEN HOMEOSTATIC AND HEDONIC SYSTEMS. ACTIVITY IN HUNGER-SENSITIVE, HYPOTHALAMIC AGOUTI-RELATED PROTEIN (AGRP)-EXPRESSING NEURONS POTENTIATES THE DA RESPONSE TO FOOD. CONVERSELY, DA SIGNALING ENHANCES THE HOMEOSTATIC AGRP NEURON RESPONSE TO FOOD. WHAT ARE THE CIRCUITS THROUGH WHICH AGRP AND DA NEURONS INTERACT IN RESPONSE TO FOOD? DO THEY HELP EXPLAIN WHY SOME INDIVIDUALS ARE MORE LIKELY TO OVEREAT AND GAIN WEIGHT? THIS PROPOSAL WILL TEST THE OVERARCHING HYPOTHESES THAT DISTINCT AGRP AND DA NEURON SUBPOPULATIONS MEDIATE THE INTERACTION BETWEEN HOMEOSTATIC AND REWARD SIGNALING AND THAT INDIVIDUAL DIFFERENCES IN AGRP AND DA RESPONSES TO FOOD PREDICT FUTURE WEIGHT GAIN. AIM I EXPERIMENTS WILL DETERMINE THE AGRP NEURON PROJECTION SUBPOPULATIONS THAT POTENTIATE DA RESPONSES TO FOOD. WE WILL LEVERAGE THE ANATOMICAL ORGANIZATION OF AGRP NEURONS, AS WELL AS OPTOGENETIC AND CHEMOGENETIC TECHNOLOGIES, TO INDIVIDUALLY TEST HOW EACH AGRP PROJECTION SUBPOPULATION INFLUENCES FOOD-EVOKED DA SIGNALING. AIM II EXPERIMENTS WILL DETERMINE SITES OF ACTION FOR DA MODULATION OF AGRP NEURON ACTIVITY. WE WILL USE GENETIC AND PHARMACOLOGICAL APPROACHES TO EXAMINE HOW DA PROJECTIONS AND NEUROTRANSMITTER SIGNALING INFLUENCE AGRP NEURON ACTIVITY. AIM III WILL DETERMINE HOW AGRP AND DA ACTIVITY PREDICTS FUTURE OVEREATING AND WEIGHT GAIN. TAKING ADVANTAGE OF THE VARIABILITY IN WEIGHT GAIN IN RESPONSE TO A HIGH-FAT, HIGH-SUGAR DIET, WE WILL DETERMINE IF INDIVIDUAL DIFFERENCES IN NEURAL ACTIVITY IN LEAN MICE PREDICT FUTURE OVEREATING AND THE DEVELOPMENT OF OBESITY. OVERALL, THESE EXPERIMENTS TAKE A UNIQUE APPROACH TO UNDERSTANDING WEIGHT GAIN BY (1) DETERMINING THE NEURAL INTERSECTION OF HOMEOSTATIC AND HEDONIC CIRCUITS THAT HAVE CLASSICALLY BEEN CONSIDERED DISCRETE DRIVERS OF INTAKE AND (2) IDENTIFYING NEURAL ACTIVITY BIOMARKERS TO PREDICT OVEREATING AND OBESITY PREDISPOSITION. ULTIMATELY, RESULTS FROM THE PROPOSED STUDIES WILL REVEAL CELLULAR AND MOLECULAR TARGETS THAT CAN BE LEVERAGED TO DEVELOP OBESITY PREVENTION AND MORE EFFECTIVE WEIGHT LOSS STRATEGIES.

GENETICS OF TASTE PERCEPTION

MECHANISMS OF INFLAMMATION-TRIGGERED TASTE LOSS AND ITS RECOVERY - PROJECT SUMMARY TASTE LOSS CAN LEAD TO MALNUTRITION, WEIGHT LOSS, AND DEPRESSION. IN ADDITION, CHANGES IN TASTE ARE A SYMPTOM OF POOR HEALTH. THIS CYCLICAL RELATIONSHIP BETWEEN TASTE AND HEALTH HIGHLIGHTS THE IMPORTANCE OF RESEARCH AIMED AT UNDERSTANDING TASTE LOSS IN BOTH HEALTH AND DISEASE. RESEARCH ON TASTE LOSS WILL PROVIDE NEW APPROACHES IN THE PREVENTION, DIAGNOSIS, AND TREATMENT OF DISEASE. IT IS WELL-DOCUMENTED THAT INFECTIONS AND AUTOIMMUNE CONDITIONS ARE ACCOMPANIED BY CHANGES IN CHEMOSENSORY PERCEPTION INCLUDING CHANGES IN TASTE. HOWEVER, CURRENTLY WE KNOW LITTLE ABOUT HOW TASTE BUD REGENERATION IS REGULATED, AND THERE IS NO EFFECTIVE TREATMENT FOR TASTE LOSS. OUR RECENT RESEARCH INDICATES THAT INFLAMMATION, CHARACTERIZED BY INDUCTION OF INFLAMMATORY CYTOKINES AND INFILTRATION AND ACTIVATION OF IMMUNE CELLS, CONTRIBUTES SIGNIFICANTLY TO TASTE DYSFUNCTION. WE HYPOTHESIZE THAT INFLAMMATION, PARTICULARLY THROUGH THE ACTION OF THE INFLAMMATORY CYTOKINE INTERFERON- (IFN-), CONTRIBUTES TO TASTE LOSS BY INDUCING CELL DEATH AND INHIBITING TASTE BUD CELL RENEWAL, AND THAT RESOLUTION OF INFLAMMATION PROMOTES TASTE BUD REGENERATION. IFN- CAN BE PRODUCED BY VARIOUS TYPES OF IMMUNE AND NONIMMUNE CELLS IN RESPONSE TO INFECTIONS AND AUTOIMMUNITY. ITS LEVELS IN TASTE TISSUES ARE MARKEDLY INCREASED IN AN AUTOIMMUNE DISEASE MODEL WITH TASTE LOSS. YET, WHETHER IFN- DIRECTLY CONTRIBUTES TO TASTE LOSS HAS NOT BEEN DETERMINED. IN THIS PROJECT, WE PROPOSE TO INVESTIGATE THE ROLE OF INFLAMMATION, ESPECIALLY IFN-, IN TASTE LOSS USING BOTH A TRANSGENIC APPROACH AND A CLINICALLY RELEVANT RESPIRATORY VIRAL INFECTION MODEL. WE WILL THEN USE THESE TASTE LOSS MODELS TO STUDY THE MECHANISMS OF TASTE BUD REGENERATION. THIS RESEARCH WILL TEST MECHANISTIC HYPOTHESES OF HOW INFLAMMATION AND INFECTION CAUSE TASTE LOSS, AND HOW TASTE RESPONSES RECOVER. TO UNDERSCORE THE IMPORTANCE OF RESEARCH INVESTIGATING THE LINK BETWEEN INFLAMMATION, DISEASE, AND TASTE LOSS, A CONSIDERABLE NUMBER OF COVID-19 PATIENTS EXPERIENCE TASTE DYSFUNCTION. ALTHOUGH MOST CASES OF TASTE LOSS ARE TEMPORARY, INCLUDING TASTE LOSS ASSOCIATED WITH SARS-COV-2 INFECTION, LONG-TERM TASTE LOSS CAN OCCUR IN SOME PATIENTS. THUS, INSIGHTS FROM THIS RESEARCH WILL BE INFORMATIVE TO BETTER UNDERSTAND TASTE LOSS IN GENERAL, AS WELL AS TASTE LOSS ASSOCIATED WITH COVID-19.

NEO FOLLOW UP PROJECT PHASE VI

THE PRINCIPAL GOALS OF THESE TWO FACILITIES IN PHASE V WILL BE TO 1) PROVIDE RAPID NEOCP MEASURES AND 2) MEASURE MORE THAN 4 000 NEAS FAINTER THAN V22.0 PER YEAR.

THE ROLE OF T1R TASTE RECEPTORS IN GUSTATION

FUNCTIONAL CHARACTERIZATION OF ENDOCRINE TASTE CELLS

NEURONAL REGULATION OF ADULT TASTE STEM CELLS

DECENTRALIZED CLINICAL TRIAL OF CONTINGENCY MANAGEMENT DIGITAL THERAPEUTIC TO TREAT STIMULANT USE DISORDER - ABSTRACT WITH NO FDA-APPROVED MEDICATIONS AVAILABLE TO ADDRESS STIMULANT USE DISORDERS (STUD) AND RISING PREVALENCE OF STIMULANTS NATIONALLY, CONTINGENCY MANAGEMENT (CM) HAS GAINED ATTENTION AS ONE OF FEW EFFECTIVE TREATMENT OPTIONS. DESPITE GROWING CLINICAL INTEREST IN CM, IMPLEMENTATION BARRIERS POSE SUBSTANTIAL CHALLENGES TO MOVING THIS EVIDENCE-BASED INTERVENTION INTO ROUTINE USE. CHIEF AMONG THESE CONCERNS IS LACK OF REIMBURSEMENT PATHWAYS AND DIFFICULTY IMPLEMENTING CM WITH FIDELITY (RASH ET AL., 2012, 2020). PRESCRIPTION DIGITAL THERAPEUTICS, MOBILE APP BASED PRODUCTS THAT ARE FDA-CLEARED FOR THE TREATMENT OF DISEASE, HAVE SHOWN PROMISE IN OVERCOMING REIMBURSEMENT CHALLENGES BY TAKING ADVANTAGE OF EXISTING FORMULARY BILLING PATHWAYS FOR DRUGS AND MEDICAL DEVICES. ALSO, DELIVERY OF CM THROUGH AN APP ADDRESSES MANY OF THE BARRIERS OF DAY-TO-DAY IMPLEMENTATION WITHIN THE CLINICAL WORKFLOW, MAINTAINS PROTOCOL ADHERENCE, AND IMPROVES PATIENT ACCESS–MAKING IT MORE LIKELY TO BE ADOPTED AND IMPACTFUL. THEREFORE, DYNAMICARE HEALTH HAS DEVELOPED AND PILOTED DCH-003, A DIGITAL THERAPEUTIC DELIVERING CM AND OTHER EVIDENCE-BASED MODALITIES FOR THE TREATMENT OF STUD. UNLIKE COMPETITOR PRODUCTS THAT INCLUDE CM SUCH AS THE PDT RESET FROM PEAR THERAPEUTICS, DCH-003 FULLY AUTOMATES CM THROUGH REMOTE, RANDOM, SELF-ADMINISTERED RAPID SALIVA TESTS WITNESSED OVER SELFIE VIDEO, AND IS DESIGNED AS A FULL YEAR PROGRAM (VS. 90 DAYS). DCH-003 ALSO INCORPORATES EVIDENCE-BASED, SELF-GUIDED THERAPY MODULES, APPOINTMENT TRACKING, AND DELIVERS REWARDS VIA A RISK-PROTECTIVE SMART DEBIT CARD. THE PRODUCT PROMISES GREATER ACCESSIBILITY AND FIDELITY TO CM, AND ULTIMATELY GREATER IMPACT ON STUD THAN CURRENTLY AVAILABLE TREATMENTS. THIS STUDY PROPOSES A PHASE II, TWO-GROUP, RANDOMIZED CLINICAL TRIAL (RCT) THAT WILL PROVIDE THE NECESSARY EFFICACY DATA IN ORDER TO SEEK FDA CLEARANCE OF DCH-003 FOR THE TREATMENT OF STUD. PATIENTS WITH STUD (N = 270) WILL BE RANDOMIZED TO: A) INTERVENTION: STANDARD CLINIC CARE PLUS DCH-003 OR B) CONTROL: STANDARD CLINIC CARE PLUS A TIME- AND EFFORT-CONTROLLED SHAM DIGITAL APP (TO CONTROL FOR PLACEBO EFFECT). THE PRIMARY OUTCOME WILL BE THE PERCENT STIMULANT ABSTINENT SAMPLES COLLECTED DURING WEEKS 1-38. SECONDARY OUTCOMES INCLUDE OTHER CLINICALLY RELEVANT INDICATORS (ABSTINENCE FROM OTHER ILLICIT SUBSTANCES, TREATMENT RETENTION, LONG-TERM (WEEKS 39-64) PERCENT NEGATIVE SAMPLES). AIM 1 COMPARES DCH-003 TO SHAM CONTROL, AND WE EXPECT BETTER CLINICAL OUTCOMES IN THE INTERVENTION VS. CONTROL GROUP. AIM 2 COMPARES HEALTHCARE UTILIZATION AND COSTS BETWEEN THE GROUPS, WITH THE GOAL OF PAYER ADOPTION POST-FDA-CLEARANCE. IMPORTANTLY, THIS STUDY WILL BE THE FIRST RCT FOR DCH-003 (ESSENTIAL FOR FDA CLEARANCE), AND, MORE BROADLY, IT ADDRESSES A CRITICAL NEXT STEP IN THE TRANSLATION OF SCIENCE TO CLINICAL PRACTICE THAT IS VITAL FOR DRIVING ADOPTION OF THIS PROVEN, EFFECTIVE PARADIGM INTO ROUTINE CARE AMIDST A U.S. STIMULANT EPIDEMIC.

IN THE MODERN ERA, NASA SMD MISSIONS AND FACILITIES ARE PRODUCING DATA AT A RATE TOO GREAT FOR THE SCIENCE COMMUNITY TO MAXIMALLY UTILIZE. WHILE SOFT

PREDICTING HUMAN OLFACTORY PERCEPTION FROM MOLECULAR STRUCTURE

DEVELOPMENT OF A PEPTIDE-DRUG CONJUGATE FOR TOPICALLY TREATING THE VIRAL SKIN DISEASE MOLLUSCUM CONTAGIOSUM - ABSTRACT MOLLUSCUM CONTAGIOSUM (MC) IS A HIGHLY CONTAGIOUS SKIN DISEASE CAUSED BY THE POXVIRUS, MCV. IT REMAINS AN UNMET MEDICAL NEED DUE TO LACK OF AN APPROVED ANTIVIRAL DRUG. MC APPEARS AS LESIONS ON THE BODY AND FACE THAT CAN SPREAD AND LAST MONTHS-YEARS BEFORE RESOLVING. LESIONS OCCUR MOST FREQUENTLY IN CHILDREN (5%) AND IMMUNE COMPROMISED INDIVIDUALS (5-18%). THE INFECTION IS CONFINED TO THE EPIDERMAL SKIN LAYERS; IT IS NOT SYSTEMIC. TRANSMISSION SPREADS DIRECTLY FROM PERSON-PERSON CONTACT, AUTOINOCULATION, OR INDIRECT CONTACT WITH FOMITES. A PRINCIPAL CONCERN IS INFECTION OF THE EYELIDS BY RUBBING SKIN LESIONS FROM DISTAL SITES. INFECTION OF THE EYELIDS IS ESPECIALLY DISTRESSFUL AND CAN LEAD TO INFLAMMATION OF THE CONJUNCTIVA CAUSING “PINK EYE” AND FOLLICULAR CONJUNCTIVITIS. CURRENT TREATMENTS CAN BE PAINFUL, CAUSE SCARRING, AND PSYCHOLOGICAL DISTRESS. NONE OF THE CURRENT TREATMENTS THAT INCLUDE A RANGE OF PHYSICAL, CHEMICAL, AND MEDICINAL INTERVENTIONS ARE UNIFORMLY ACCEPTED OR FDA APPROVED. NO MC APPROVED DRUG HAS BEEN DEVELOPED BECAUSE THE VIRUS CANNOT BE GROWN IN TISSUE CULTURE FOR TESTING. WE HAVE NOW MADE 4 MAJOR BREAKTHROUGHS: FIRST, WE IDENTIFIED A PROTEIN TARGET (MD4) OF MCV THAT IS SPECIFIC FOR VIRAL REPLICATION. SECOND, WE CONSTRUCTED A SURROGATE VIRUS (MD4-VV), PROVIDING THE FIRST CELL-BASED SYSTEM FOR SCREENING COMPOUNDS AGAINST THE VIRAL TARGET PROTEIN (MD4) IN INFECTED CELLS. THIRD, WE SYNTHESIZED A SMALL MOLECULE (7269) THAT BINDS A PRECISE REGION OF THE MD4 TARGET PROTEIN TO CAUSE UNFOLDING AND LOSS OF FUNCTION. HOWEVER, ALTHOUGH 7269 BLOCKS INFECTION OF THE SURROGATE VIRUS, WE WERE UNABLE TO IMPROVE ITS POTENCY OR ELIMINATE ITS SLIGHT TOXICITY DESPITE AN INTENSE MEDICINAL CHEMISTRY CAMPAIGN. FOURTH, WE OVERCAME THIS IMPASSE BY CONJUGATING A PEPTIDE TO PRODUCE TRIVALINE-7269 THAT INCREASES ANTIVIRAL POTENCY 6.3-FOLD GREATER THAN THAT OF UNCONJUGATED 7269 WITH NO MEASURABLE TOXICITY. SINCE THE INCREASED POTENCY OF TRIVALINE-7269 IS NOT RELATED TO AN INCREASE IN TARGET BINDING, IT IS LIKELY DUE TO CELL UPTAKE OR STABILITY. THE CHALLENGE FOR FUTURE CLINICAL DRUG DEVELOPMENT IS THAT TRIVALINE-7269 HAS NO RELATED CONJUGATED PEPTIDE ANALOGS OF EQUAL OR GREATER POTENCY TO MITIGATE RISK. TO ADDRESS THIS REQUIREMENT, WE HAVE SYNTHESIZED 68 NEW ANALOGS RELATED TO TRIVALINE-7269 (C-PEP1) FROM WHICH EMERGED C-PEP2 & C-PEP3 EXHIBITING EVEN GREATER ANTIVIRAL POTENCY. OUR GOAL IS TO OPTIMIZE THE 3 C-PEPS TO GENERATE A PRE-CLINICAL LEAD WITH THE OTHER TWO AS BACKUPS TO TOPICALLY TREAT MC LESIONS ON ALL AREAS OF THE SKIN INCLUDING THE EYELIDS. OUR AIMS ARE TO: (I) USE MEDICINAL CHEMISTRY TO GENERATE 100 NEW ANALOGS OF THE C-PEPS; (II) SCREEN THE CHEMICALLY MODIFIED C-PEPS FOR: VALIDATION OF MD4-TARGET ENGAGEMENT, ANTIVIRAL POTENCY, CYTOTOXICITY, BINDING THE MD4 TARGET; (III) USE 3D ORGANOTYPIC SKIN CULTURES AND LIPOSOMES FOR DEVELOPING AND DELIVERING ADVANCED C-PEPS TO TREAT ALL LESIONS, INCLUDING EYELIDS; (IV) ASSAY IN VITRO ADME AND MULTIPLE OFF-TARGET ACTIVITIES; (V) INITIATE PRE-CLINICAL DEVELOPMENT FOR NON-GMP API SCALE-UP AND PRE- FORMULATION MANUFACTURING AND STABILITY.

PERFORMANCE-ADVANTAGED CHEMICALS AND MATERIALS MADE FROM LIGNOCELLULOSE AND CO2

SMALL MOLECULE INHIBITORS OF HIV1 NEF VIRULENCE FACTOR FOR TREATMENT OF HIV_AIDS

BIO-SYNGAS FERMENTATION FOR C6-C14 ALCOHOL PRODUCTION AS A PATHWAY TO FUELS

DENDRITIC SIGNALING IN THE OLFACTORY BULB

INCENTIVIZED COLLABORATIVE CARE TO DESSEMINATE CONTINGENCY MANAGEMENT - ABSTRACT CONTINGENCY MANAGEMENT, AN INCENTIVE-BASED INTERVENTION, BOASTS A MASSIVE RESEARCH BASE AND HAS BEEN DEMONSTRATED EFFICACY IN INCREASING DRUG ABSTINENCE AND MEDICATION ADHERENCE IN PEOPLE WITH OPIOID USE DISORDER. THERE IS A HUGE GAP BETWEEN THE EVIDENCE IN SUPPORT OF THIS APPROACH AND ITS DISSEMINATION IN PRACTICE. A DIGITAL HEALTH PROGRAM THAT SURMOUNTS MOST OF THE BARRIERS TO DISSEMINATION HAS BEEN DEVELOPED THAT COLLECTS ALL THE RELEVANT DATA AND IMPLEMENTS ALL OF THE CONTINGENCY MANAGEMENT PROCEDURES AUTOMATICALLY. THIS PROGRAM HAS BEEN SHOWN TO BE EFFICACIOUS IN SEVERAL PEER-REVIEWED STUDIES. HOWEVER, ONE KEY BARRIER TO DISSEMINATION REMAINS. IN ORDER FOR CONTINGENCY MANAGEMENT TO BECOME TRULY IMPACTFUL ON A NATIONAL SCALE, PROVIDERS MUST ACTIVELY ENGAGE PATIENTS BY INFORMING THEM ABOUT IT, ENCOURAGING THEM TO USE IT, ASSISTING THEIR ENROLLMENT, AND THEN USING THE DATA GENERATED BY THE PLATFORM TO INFORM THEIR ONGOING CARE. THE BEST WAY TO SURMOUNT THIS FINAL BARRIER IS TO USE THE MOTIVATIONAL TECHNIQUE OF CONTINGENCY MANAGEMENT ITSELF; INCENTIVIZE THE NECESSARY PROVIDER BEHAVIORS. THUS, THIS SBIR FAST TRACK APPLICATION PROPOSES TO DEVELOP AND EVALUATE A NOVEL INCENTIVIZED COLLABORATIVE CARE MODEL FOR THE DELIVERY OF CONTINGENCY MANAGEMENT SERVICES FOR BUPRENORPHINE PHARMACOTHERAPY PATIENTS WITH OPIOID USE DISORDERS. WE BELIEVE THIS MODEL WILL HAVE THE IMPORTANT SECONDARY EFFECT OF INCREASING ACCESS TO BUPRENORPHINE PHARMACOTHERAPY, AS PRESCRIBERS WILL BE INDIRECTLY INCENTIVIZED TO MAXIMIZE THE NUMBER OF BUPRENORPHINE PATIENTS IN THEIR PRACTICE. PHASE I WILL BEGIN WITH PREPARATORY ACTIVITIES, INCLUDING STREAMLINING THE ENROLLMENT SYSTEM SO THAT ANY BUPRENORPHINE PRESCRIBER CAN USE IT, ADDING DATA COLLECTION SYSTEMS FOR PROVIDER INFORMATION, AND DATA DISPLAY SYSTEMS THAT PROVIDERS CAN USE TO EASILY ACCESS THE PATIENT DATA THEY WISH TO SEE. A PHASE I FEASIBILITY STUDY (N = 10) WILL FOLLOW. THE MILESTONES REQUIRE THE POTENTIAL OF THE INCENTIVIZED COLLABORATIVE CARE MODEL IN DISSEMINATING CONTINGENCY MANAGEMENT TO BE DEMONSTRATED. IF SUCCESSFUL, THE FEASIBILITY STUDY WILL PAVE THE WAY FOR A RANDOMIZED CONTROLLED TRIAL (RCT). THIS RCT WILL BE THE PRIMARY ACTIVITY OF PHASE II OF THIS SBIR AWARD, AND IS DESIGNED TO EVALUATE THE EFFICACY OF INCENTIVIZED COLLABORATIVE CARE IN THE DISSEMINATION OF CONTINGENCY MANAGEMENT. PRIMARY OUTCOME MEASURES WILL INCLUDE THE ENGAGEMENT IN COLLABORATIVE CARE IN RELATION TO THE CONTINGENCY MANAGEMENT INTERVENTION, AS WELL AS BUPRENORPHINE PRESCRIBING TRENDS. SECONDARY ANALYSES WILL BE DESIGNED TO ASSESS THE ECONOMIC EFFECT OF DYNAMICARE ON PROVIDERS. THE RCT WILL ALSO INCLUDE EXPLORATORY ANALYSES OF PATIENT OUTCOMES. OVERALL, THIS PROJECT IS HIGHLY CONSISTENT WITH CURRENT ONDCP PRIORITIES TO, “IDENTIFY AND ADDRESS POLICY BARRIERS RELATED TO CONTINGENCY MANAGEMENT INTERVENTIONS (MOTIVATIONAL INCENTIVES),” AND “EXPLORE REIMBURSEMENT FOR MOTIVATIONAL INCENTIVES AND DIGITAL TREATMENT FOR ADDICTION.” IF SUCCESSFUL, THIS PROJECT COULD LEAD TO RAPID DISSEMINATION OF CONTINGENCY MANAGEMENT AND IMPROVED ACCESS TO BUPRENORPHINE PHARMACOTHERAPY TO PEOPLE WITH OPIOID USE DISORDER THROUGHOUT THE UNITED STATES.

SMALL MOLECULE ANTAGONISTS OF PF4 FOR THE TREATMENT AND PREVENTION OF HIT

REVERSIBLE LIQUID CARRIERS FOR AN INTEGRATED PRODUCTION, STORAGE, AND DELIVERY OF HYDROGEN

MAPPING GENES FOR ADIPOSITY IN MICE

ROLE OF METABOLIC SENSING IN HUMAN SWEET TASTE

PERCEPTUAL EFFECTS OF GENETIC VARIATION IN HUMAN ODORANT RECEPTORS

ATYPICAL ANTIPSYCHOTICS: EFFECTS ON HEPATIC GLUCOSE AND LIPID METABOLISM IN HUMAN

THE ASTRONOMICAL SOCIETY OF THE PACIFIC CO-INVESTIGATORS AT THE SETI INSTITUTE AND PARTNERS AT THE SPACE SCIENCE INSTITUTE PROPOSE ECLIPSE AMBASSADORS PREPARE COMMUNITIES OFF THE PATH FOR TWO SOLAR ECLIPSES

NIMHD SCIENCE EDUCATION INITIATIVE: K-12 SCIENCE EDUCATION INITIATIVE

PORT SECURITY GRANT PROGRAM (ARRA)

BIOTRANSFORMATION OF METHANE INTO N-BUTANOL BY A METHANOTROPHIC CYANOBACTERIUM

THE ROLES AND FUNCTIONS OF OLFACTORY TRANSDUCTION CHANNELS IN THE ODORANT RESPONSE

COMPARATIVE GENETICS OF SWEET TASTE IN CARNIVORA

MECHANISMS OF INFLAMMATION-ASSOCIATED TASTE DISORDERS

PHYSICAL PROPERTY DATA AND MODELS IN SUPPORT OF BIOPROCESSING SEPARATION TECHNOLOGIES FOR ORGANIC ACIDS SEPARATION

"PEM ELECTROLYZER INCORPORATING AN ADVANCED LOW-COST MEMBRANE"

NOVEL SMALL MOLECULE FOR IMPROVED DENTAL IMPLANT OSSEOINTEGRATION - PROJECT SUMMARY/ABSTRACT ORAL IMPLANTS ARE WIDELY ACCEPTED IN DENTAL MEDICINE AS A RECONSTRUCTIVE TREATMENT OPTION FOR REPLACEMENT OF MISSING TEETH BECAUSE OF CONGENITAL TOOTH AGENESIS, PERIODONTAL DISEASES, OR INJURY. ALTHOUGH THE SURVIVAL RATE OF DENTAL IMPLANTS OVER A 10-YEAR OBSERVATION HAS BEEN REPORTED TO BE HIGHER THAN 90% IN TOTALLY EDENTULOUS JAWS, DENTAL IMPLANTS DO FAIL IN SOME PATIENTS DUE TO A VARIETY OF BONE DENSITY PROBLEMS SUCH AS OSTEOPOROSIS. THUS, A MAJOR CLINICAL CHALLENGE FOR DENTAL IMPLANT THERAPY IS IMPROVING AND ACCELERATING THE MECHANICAL ANCHORAGE OF THE TITANIUM IMPLANTS INTO THE JAWBONE TO FACILITATE EARLIER FUNCTIONAL LOADING. WHILE VARIOUS MODIFICATIONS OF IMPLANT SURFACES HAVE HELPED OSSEOINTEGRATION OF IMPLANTS, A BONE ANABOLIC AGENT WOULD INCREASE THE PREDICTABILITY OF A POSITIVE RESPONSE FOR MANY OF THE BONE DENSITY PROBLEMS SEEN ESPECIALLY IN OLDER PATIENTS WITH PARTIAL OR COMPLETE EDENTULISM. CAYMAN CHEMICAL COMPANY, INC. HAD DISCOVERED AND PATENTED A SERIES OF EP4 RECEPTOR AGONISTS DESIGNED, SYNTHESIZED, AND SCREENED FOR TARGET POTENCY AND SELECTIVITY, CELL ACTIVITY, AND METABOLIC AND PHYSICOCHEMICAL PROPERTIES AMENABLE TO THE RAPID SYSTEMIC CLEARANCE DESIRABLE FOR LOCAL ADMINISTRATION. THE LEAD COMPOUND OF THE SERIES, KMN-159, WAS TESTED DURING PHASE I OF THE PROJECT AND DEMONSTRATED ITS IN VITRO OSTEOGENIC DIFFERENTIATION CAPACITY AS WELL AS ITS IN VIVO BONE REGENERATION POTENTIAL IN RAT CRITICAL DEFECT MODELS OF NON-UNION FRACTURE AND CALVARIAL REPAIR. MOREOVER, WE DEMONSTRATED THAT KMN-159 DOES NOT INDUCE ECTOPIC BONE FORMATION IN CONTRAST TO THE STANDARD OF CARE RHBMP-2. DURING PHASE II OF THE PROJECT WE WILL EVALUATE THE EFFECTS OF KMN-159-COLLAGEN HYDROGEL COMBINATION AS AN ACCELERANT OF DENTAL IMPLANT OSSEOINTEGRATION IN 2D AND 3D IN VITRO SYSTEMS (AIM 1A) AND IN VIVO IN A RAT EXPERIMENTAL ALVEOLAR RIDGE BONE DEFECT MODEL (AIM1B). THE MOST EFFICACIOUS FORMULATION DOSE OF KMN-159 WILL BE EMPLOYED IN AIM 2 TO DEMONSTRATE IMPROVED BIOMECHANICAL STRENGTH OF THE IMPLANT. FINALLY, A DEMO BATCH OF KMN-159 PREPARED UNDER GMP CONDITIONS AND FORMULATED IN HELISTAT ABSORBABLE COLLAGEN SPONGES WILL BE USED TO TEST EFFICACY AND SAFETY IN A GLP RABBIT IMPLANT MODEL ACCEPTED BY THE FDA. ALL THE IN VIVO STUDIES WERE DESIGNED TO CONSIDER SEX AS A BIOLOGICAL VARIABLE. IN SUM, CAYMAN’S GOAL IS TO OFFER DENTISTS A NOVEL, EFFECTIVE, SAFE, ECONOMICAL, AND EASY-TO- USE SMALL MOLECULE DRUG (KMN-159)-DEVICE COMBINATION THAT WILL INCREASE THE RATE OF DENTAL IMPLANT OSSEOINTEGRATION AS WELL AS THE STRENGTH OF THE BONE-IMPLANT INTERFACE. THIS STABLE, PREPACKAGED, READY-TO-USE, FLEXIBLE AND EASILY-FITTED OSSEOINTEGRATION ACCELERANT WOULD AUGMENT THE BONE’S NATURAL REPAIR PROCESS AND COULD THUS FACILITATE EARLIER IMPLANT LOADING AND DECREASE THE NUMBER OF IMPLANT FAILURES AS COMPARED TO THOSE RECEIVING IMPLANTS ALONE.

SBIR PHASE II: SCALABLE PRODUCTION OF PLATFORM CHEMICALS FROM INEDIBLE BIOMASS AND CARBON DIOXIDE -THE BROADER IMPACT/COMMERCIAL POTENTIAL OF THIS SMALL BUSINESS INNOVATION RESEARCH (SBIR) PHASE II PROJECT IS TO ENABLE COST-COMPETITIVE, HIGH-VOLUME PRODUCTION OF USEFUL CHEMICALS AND MATERIALS FROM ABUNDANT AND SUSTAINABLE FEEDSTOCKS. THIS PROJECT IS DEVELOPING A PROCESS TO MANUFACTURE A CHEMICAL KNOWN AS FDCA (FURAN-2,5-DICARBOXYLIC ACID) FROM CARBON DIOXIDE AND A COMMODITY FEEDSTOCK MADE FROM INEDIBLE BIOMASS. FDCA IS A NATURALLY OCCURRING SUBSTANCE AND IS USED TO MAKE POLYMERS (I.E., PLASTICS) THAT HAVE SUPERIOR PERFORMANCE COMPARED TO ANALOGOUS POLYMERS PRODUCED TODAY FROM FOSSIL FUEL FEEDSTOCKS. THE OBSTACLE TO PRODUCING THESE POLYMERS IS THAT IT HAS BEEN COMPLICATED AND PROHIBITIVELY EXPENSIVE TO PRODUCE FDCA. THE COMPETING TECHNOLOGIES FOR MAKING FDCA REQUIRE EDIBLE SUGAR AS THE FEEDSTOCK AND A VERY LARGE NUMBER OF PROCESS STEPS, RESULTING IN HIGH MANUFACTURING COSTS. THIS PROJECT PROPOSES TO PRODUCE THIS CHEMICAL USING A DRAMATICALLY SIMPLIFIED PROCESS, WHICH ENABLES COST-COMPETITIVE PRODUCTION. BY ADVANCING THE TECHNOLOGY TOWARD COMMERCIAL APPLICATION, THIS PROJECT WILL HAVE A FAR-REACHING IMPACT ON US ECONOMIC COMPETITIVENESS AND INNOVATION IN THE CHEMICAL INDUSTRY. WITH A SECURE FDCA SUPPLY, US CHEMICAL AND MATERIALS COMPANIES CAN DEVELOP MANUFACTURING CAPACITY FOR POLYMERS WITH AN ULTIMATE MARKET OPPORTUNITY OF >>$100 BILLION. IN ADDITION, REPLACING ENERGY- AND EMISSIONS-INTENSIVE FOSSIL FUEL-DERIVED POLYMERS WITH THESE MORE ENVIRONMENTALLY FRIENDLY POLYMERS WILL REDUCE EMISSIONS OF MULTIPLE ECONOMIC SECTORS. FINALLY, THESE POLYMERS HAVE FAVORABLE END-OF-USE OPTIONS THAT WILL REDUCE PLASTIC WASTE AND ITS ACCUMULATION IN THE ENVIRONMENT. THIS SBIR PHASE II PROJECT PROPOSES TO ADVANCE THE TECHNOLOGY FOR A KEY STEP OF THE FDCA PRODUCTION PROCESS TO A LEVEL THAT ENABLES ITS IMPLEMENTATION IN A PILOT-SCALE DEMONSTRATION. THE REACTION UNDER INVESTIGATION IS THE AEROBIC OXIDATION OF FURFURAL TO FURAN-2-CARBOXYLATE (FUROATE) UNDER AQUEOUS ALKALINE CONDITIONS. OXIDIZING FURFURAL UNDER INDUSTRIALLY RELEVANT CONDITIONS (HIGH CONCENTRATION AND HIGH RATES) IS FUNDAMENTALLY CHALLENGING BECAUSE FURFURAL IS PRONE TO RAPID DEGRADATION PROCESSES. STUDIES OF THE PROCESS IN THE EARLIER PHASE I PROJECT PROVIDED KEY INSIGHTS INTO THE REACTION MECHANISM AND IDENTIFIED TWO POTENTIAL REACTOR DESIGNS FOR CONTINUOUS OPERATION. THE PHASE II PROJECT WILL COMPARE PERFORMANCE IN THESE TWO REACTOR DESIGNS, SCALE UP THE PREFERRED DESIGN, VALIDATE CATALYST LIFETIME, AND DEMONSTRATE INTEGRATION OF THE REACTION PRODUCT INTO THE DOWNSTREAM STEPS OF THIS FDCA PROCESS. SUCCESSFUL COMPLETION OF THE PROJECT WILL FINALIZE THE REACTOR DESIGN FOR THE OXIDATION UNIT OPERATION IN A PILOT DEMONSTRATION. IN ADDITION TO ADVANCING THIS TECHNOLOGY TOWARD COMMERCIALIZATION, THE PROJECT WILL CREATE NEW KNOWLEDGE TO ENABLE BROADER UTILIZATION OF RENEWABLE FEEDSTOCKS FOR CHEMICAL PRODUCTION BY PROVIDING INSIGHTS INTO CATALYST SELECTION, PROCESS CONDITIONS, AND REACTOR DESIGNS FOR AQUEOUS AEROBIC OXIDATION REACTIONS. 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.

ULTRA-CRYOPUMP FOR HIGH-DEMAND TRANSPORTATION FUELING

FUNCTIONAL CHARACTERIZATION OF ADULT TASTE STEM CELLS

MOLECULAR GENETIC INVESTIGATION OF TASTE SENSATION

MOLECULAR GENETICS OF FAT TASTE

OPCW FORENSICS AND ATTRIBUTION CAPABILITIES DEVELOPMENT

ROLES OF ASCL1 FOR GENERATION AND DIFFERENTIATION OF TASTE CELLS

APPLYING TECHNOLOGY-ENABLED CONTINGENCY MANAGEMENT FOR ALCOHOL USE DISORDER AT SCALE IN A MEDICAID POPULATION

SHARING THE UNIVERSE

THIS GRANT WILL FUND THE OPCW TECHNICAL SECRETARIAT NON-ROUTINE EXPENSES FOR SYRIA-FOCUSED MISSIONS AND ACTIVITIES TO THE DAT, FFM, AND IIT.

NEW FOSSIL ENERGY COOPERATIVE AGREEMENT AWARD ENTITLED "ADVANCED ACID GAS SEPARATION TECHNOLOGY FOR THE UTILIZATION OF LOW RANK", STEMMING FROM THE F

PATHWAYS AND GENES OF SWEET TASTE CELLS

GENETIC CONTROLS OF MINERAL CONSUMPTION

HYPERPHOSPHORYLATED TAU AGGREGATION KIT TO IDENTIFY TAUOPATHY RISK FACTOR

GRANT FOR PROD OF ADV BIOFUEL

A NOVEL THERAPEUTIC FOR INVASIVE CANDIDIASIS

LOW COST MODULAR TISSUE MICROARRAY INSTRUMENT

PET IMAGING AGENTS FOR THE IN VIVO DETECTION OF TDP-43

GENETICS OF TASTE PREFERENCES

NEW COOPERATIVE AGREEMENT TO PERLUMI CHEMICALS, INC. UNDER FOA NUMBER DE-FOA-0002459 FOR A PROJECT ENTITLED, ''NOVEL BIOLOGICAL CARBON FIXATION PATHWAY TO INCREASE PLANT YIELD''.

DEVELOPMENT OF A NOVEL SMALL MOLECULE-BASED APPROACH FOR ACCELERATED FRACTURE REPAIR IN THE AGING SKELETON

DYNAMIC ASPECTS OF OLFACTORY SIGNAL TRANSDUCTION

INDUSTRIAL TECHNOLOGIES ON ENERGY EFFICIENCY AND BEST PRACTICES

PEM ELECTROLYZER INCORPORATED AND ADVANCED LOW-COST MEMBRANE

DIMENSIONALLY STABLE HIGH TEMPERATURE MEMBRANES

ARI-R2 - REPAIR AND RENOVATION OF THE PARI RESEARCH AND EDUCATION INFRASTRUCTURE

ROLE OF TASTE SIGNALING ELEMENTS IN ENTEROENDOCRINE CELLS

ORAL COMPLEX CARBOHYDRATE SENSING

SCENTINEL: A RAPID SMELL TEST FOR COVID-19 SURVEILLANCE - PROJECT SUMMARY SMELL LOSS IS A PREDOMINANT SYMPTOM OF COVID-19, AND INITIAL EVIDENCE BASED ON SELF-REPORTS SUGGESTS THAT CHEMOSENSORY LOSS IS A SENSITIVE PREDICTOR OF COVID-19 IN THE GENERAL POPULATION, MORE SO THAN FEVER. HOWEVER, GIVEN THE NATURAL LACK OF AWARENESS OF CHEMOSENSORY CHANGES, SELF-REPORTS UNDERESTIMATE THE TRUE PREVALENCE OF SMELL LOSS IN PATIENTS WITH COVID-19 BY 20% COMPARED TO AN OBJECTIVE TEST. THEREFORE, WE PROPOSE TESTING AND DEPLOYING A RAPID AND OBJECTIVE MEASURE OF SMELL ABILITY, THE SCENTINEL TEST, INSPIRED BY THE NIH TOOLBOX® ODOR IDENTIFICATION TEST THAT OUR TEAM PREVIOUSLY DEVELOPED. SCENTINEL IS AN INEXPENSIVE, AND CONVENIENT SMELL TEST FOR COVID-19 SURVEILLANCE OF THE POPULATION THAT QUICKLY AND EASILY ASSESSES THREE SMELL LOSS FACTORS: ODOR DETECTION, ODOR INTENSITY, AND ODOR IDENTIFICATION. IT IS DESIGNED FOR PRACTICAL USE IN SEVERAL CONTEXTS, INCLUDING HIGH-DENSITY AREAS SUCH AS COMMUNITY MEDICAL SITES, UNIVERSITIES, SUBACUTE CARE FACILITIES, AND BOTH INDUSTRIAL AND NONINDUSTRIAL WORKPLACES. OUR MULTI-DISCIPLINARY TEAM HAS EXPERTISE IN UNDERSTANDING TASTE AND SMELL, DEVELOPING AND VALIDATING CHEMOSENSORY TESTS, AS WELL AS STUDYING THE BROAD SYMPTOMATOLOGY OF COVID-19. THE GROUP IS LED BY MPI DALTON FROM THE MONELL CHEMICAL SENSES CENTER, AN EXPERT IN HUMAN OLFACTION AND DESIGNING OLFACTORY TESTS; MPI PARMA FROM TEMPLE UNIVERSITY IS AN EXPERT IN COVID-19 SMELL LOSS, IS THE CHAIR OF THE GLOBAL CONSORTIUM FOR CHEMOSENSORY RESEARCH, AND HAS EXPERTISE IN CONDUCTING RESEARCH IN RAPIDLY CHANGING SITUATIONS; DR. SCHALET AND HIS TEAM AT NORTHWESTERN UNIVERSITY AND DR. CHUN AND HIS TEAM AT YALE UNIVERSITY, AMONG THE OTHER ESTABLISHED AND INTERESTED PARTNERS (FOX SUBACUTE NURSING HOMES, HORMEL FOOD). OUR TEAM ALSO INCLUDES THE DIRECTOR OF TECHNOLOGY TRANSFER AT THE MONELL CENTER, DR. O’LEARY, TO EXPLORE POTENTIAL PARTNERS AND EXPAND SCENTINEL DEPLOYMENT NATIONWIDE. DR. REED FROM THE MONELL CHEMICAL SENSES CENTER WILL WORK DIRECTLY WITH THE DATA COORDINATION CENTER, DRAWING ON HER EXPERIENCE IN MANAGING LARGE SHARED NIH DATASETS. ALL WILL WORK CLOSELY WITH THE NIH PROJECT SCIENTIST. THIS PROPOSAL AIMS TO A) FINE-TUNE SCENTINEL’S ABILITY TO PREDICT A POSITIVE COVID-19 DIAGNOSTIC TEST; B) EXAMINE MARGINAL SMELL LOSS AS A SIGN OF THE EARLIEST PHASES OF COVID-19, BEFORE A POSITIVE DIAGNOSTIC TEST; AND C) ASSESS THE TEST’S PSYCHOMETRIC VALIDITY WITH TEST-RETEST RELIABILITY MEASURES AND VALIDATION AGAINST THE NIH TOOLBOX® ODOR IDENTIFICATION TEST. TOGETHER, THESE AIMS WILL ESTABLISH A STANDARDIZED PROTOCOL FOR USE OF SCENTINEL AS A RAPID AND OBJECTIVE SMELL TEST THAT CAN EASILY BE INCORPORATED INTO ONSITE COVID-19 TESTING CENTERS, SCHOOLS, AND WORKPLACES NATIONWIDE. FURTHERMORE, IT WILL PROVIDE KEY INSIGHTS INTO EARLY-ONSET CHEMOSENSORY SYMPTOMS IN RELATION TO A CONFIRMED COVID-19 DIAGNOSIS, PROVIDING A CRUCIALLY NEEDED MEANS TO CONTAIN THE SPREAD OF COVID-19.

VOLTAGE-DEPENDENT ION CHANNELS IN GUSTATION

MULTI UNION, NATIONAL EBOLA AND INFECTIOUS DISEASE AWARENESS TRAINING AND TRAINER DEVELOPMENT

SUMMER SCHOOLS IN NUCLEAR CHEMISTRY

TRAVEL: SUPPORT PARTICIPATION IN INTERNATIONAL SCIENTIFIC MEETINGS BY U.S. ASTRONOMERS -THIS AWARD TO THE AMERICAN ASTRONOMICAL SOCIETY WILL FUND U.S. ASTRONOMERS TO TRAVEL TO INTERNATIONAL SCIENTIFIC CONFERENCES TO PRESENT THEIR RESEARCH AND TO ENGAGE WITH THEIR INTERNATIONAL COLLEAGUES. IT WILL PROVIDE TO SELECTED INDIVIDUALS ROUND-TRIP, ECONOMY-CLASS AIRFARE ON U.S. FLAG CARRIERS TO CONFERENCES HELD IN INTERNATIONAL LOCATIONS THROUGH THE AMERICAN ASTRONOMICAL SOCIETY?S INTERNATIONAL TRAVEL GRANT PROGRAM. THE PROGRAM FAVORS EARLIER CAREER ASTRONOMERS, SUCH AS GRADUATE STUDENTS AND THOSE HAVING RECENTLY RECEIVED THEIR PH.D., THOSE FROM SMALLER, LESS-ENDOWED INSTITUTIONS, AND ASTRONOMERS PLAYING IMPORTANT ROLES IN INTERNATIONAL CONFERENCES, SUCH AS INVITED OR PLENARY SPEAKERS. THE FUNDAMENTAL GOAL OF THE PROGRAM IS TO PLACE U.S. SCIENTISTS AT INTERNATIONAL SCIENTIFIC CONFERENCES TO PRESENT THEIR RESEARCH, LEARN FROM OTHERS AT THE CONFERENCE, AND NETWORK WITH INTERNATIONAL SCIENTISTS. THE PROGRAM ALSO HELPS SHINE A SPOTLIGHT ON U.S. RESEARCH ACCOMPLISHMENTS AND ON THE DYNAMIC RESEARCH ENVIRONMENT THAT THE U.S. PROVIDES FOR THE ASTRONOMICAL SCIENCES, AND COULD SERVE AS A RECRUITMENT TOOL FOR INTERNATIONAL SCIENTISTS TO UNDERTAKE RESEARCH PARTNERSHIPS WITH AMERICAN SCIENTISTS OR EVEN TO CONSIDER RELOCATING TO THE U.S. TO PURSUE THEIR RESEARCH CAREER. THE EXPERIENCE OF INTERNATIONAL TRAVEL WILL ALSO BENEFIT THE INDIVIDUAL RESEARCHERS, ALLOWING THEM TO GROW AND PERFECT THEIR PRESENTATION STYLE, WHILE DIRECTLY SHARING THEIR RESEARCH RESULTS WITH OTHERS IN THE ASTRONOMY COMMUNITY AND WITH THE PUBLIC, WHERE AVAILABLE AND APPROPRIATE. 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.

CORTICAL ODOR PROCESSING FOR SOCIAL RECOGNITION - PROJECT SUMMARY THE SENSE OF OLFACTION ALLOWS ANIMALS TO GATHER CRITICAL INFORMATION ABOUT RESOURCES, DANGERS, AND POTENTIAL SOCIAL INTERACTIONS. A PRIMARY GOAL OF OLFACTORY NEUROSCIENCE IS TO UNDERSTAND HOW NEURAL CIRCUIT OPERATIONS IN THE MAIN OLFACTORY SYSTEM PARSE CHEMICAL SIGNALS IN THE ENVIRONMENT AND CONTRIBUTE TO ADAPTIVE BEHAVIOR. NEURAL CIRCUITS IN PIRIFORM CORTEX (PCX), THE PRIMARY OLFACTORY CORTEX, ARE THOUGHT TO TRANSFORM ELEMENTAL ODOR INFORMATION RECEIVED FROM THE OLFACTORY BULB INTO MORE HOLISTIC ‘ODOR OBJECT’ REPRESENTATIONS THAT SIGNAL THE PRESENCE OF UNIQUE ODOR SOURCES IN THE ENVIRONMENT. THE OLFACTORY SYSTEM DEVELOPED THIS ABILITY OVER THE COURSE OF EVOLUTION IN CONTEXTS WHERE INFORMATION ABOUT THE PRESENCE AND IDENTITY OF OTHER ANIMALS, ESPECIALLY CONSPECIFICS, WAS CRITICALLY IMPORTANT. SUBSTANTIAL PROGRESS HAS BEEN MADE IN UNDERSTANDING REPRESENTATIONS OF NEUTRAL MONOMOLECULAR ODORANTS IN PCX. BY CONTRAST, NOTHING IS KNOWN ABOUT OLFACTORY CORTICAL PROCESSING OF SOCIAL SCENTS. IN SUPPORT OF A SPECIALIZED ROLE IN SOCIAL ODOR PROCESSING, PCX DENSELY EXPRESSES RECEPTORS FOR THE NEUROPEPTIDE OXYTOCIN (OT) INVOLVED IN A WIDE RANGE OF SOCIAL BEHAVIORS. HOWEVER, THE POTENTIAL FOR OT MODULATION ALSO SUGGESTS THAT PCX CIRCUITS MAY OPERATE DIFFERENTLY IN SOCIAL AND NONSOCIAL CONTEXTS. THE OBJECTIVE OF THIS PROPOSAL IS TO UNDERSTAND HOW CORTICAL ODOR PROCESSING CONTRIBUTES TO SOCIAL BEHAVIOR. THE CENTRAL HYPOTHESIS IS THAT OT MODULATES PCX CIRCUIT DYNAMICS IN SOCIAL CONTEXTS TO ALLOW DISTINCT CONSPECIFIC IDENTITY CODING AND SUPPORT SOCIAL RECOGNITION. THE APPROACH IS TO USE CALCIUM IMAGING AND MULTI-ELECTRODE RECORDINGS TO OBSERVE PCX POPULATION RESPONSES DURING SOCIAL ODOR PROCESSING AND TO USE TARGETED PERTURBATIONS OF PCX FUNCTION TO TEST ITS ROLE IN SOCIAL BEHAVIOR. THE RATIONALE IS THAT OBSERVING AND PERTURBING THE SYSTEM AS IT PERFORMS ITS NATURAL ROLE IN AN ADAPTIVE BEHAVIOR PROVIDES THE MOST ACCURATE PICTURE OF PCX’S CAPABILITIES AND CONTRIBUTION TO FITNESS. THE FOLLOWING AIMS ADDRESS THESE GOALS: AIM 1: DETERMINE HOW SOCIAL RECOGNITION INFORMATION IS ENCODED IN PIRIFORM CORTEX. WE WILL IMAGE LARGE POPULATIONS OF PCX NEURONS IN FREELY INTERACTING ANIMALS AND COMPARE DYNAMICS AND CODING PROPERTIES DURING SOCIAL OR NONSOCIAL STIMULUS INVESTIGATION TO TEST OUR HYPOTHESIS THAT DISTINCT CIRCUIT DYNAMICS IN SOCIAL CONTEXTS ENABLE RELIABLE DISCRIMINATION OF INDIVIDUAL SOCIAL IDENTITY. AIM 2: DETERMINE HOW OXYTOCIN MODULATES SOCIAL ODOR PROCESSING IN PIRIFORM CORTEX. WE WILL FIRST MEASURE DYNAMICS OF OT NEURON ACTIVITY DURING SOCIAL INTERACTIONS USING FIBER PHOTOMETRY, AND THEN MATCH THESE DYNAMICS WITH OPTOGENETIC STIMULATION OF OT NEURONS WHILE RECORDING PCX POPULATION RESPONSES TO CONTROLLED PRESENTATION OF SOCIAL ODORS. AIM 3: DETERMINE THE ROLE OF PIRIFORM CORTEX IN INDIVIDUALIZED SOCIAL BEHAVIOR. PCX FUNCTION WILL BE PERTURBED BY CHEMOGENETIC INACTIVATION OR BY DELETION OF OT RECEPTORS TO TEST WHETHER CORTICAL PROCESSING AND MODULATION ARE REQUIRED FOR SOCIAL INTERACTIONS THAT DEPEND ON IDENTIFYING INDIVIDUAL SOCIAL PARTNERS IN PAIRWISE AND GROUP SETTINGS. THIS WORK WILL PROVIDE FUNDAMENTAL INSIGHTS INTO HOW THE OLFACTORY SYSTEM CONTRIBUTES TO ADAPTIVE BEHAVIOR IN NATURAL CONTEXTS.

FINE MAPPING OF MOUSE CHR 2 FOR BODY COMPOSITION GENES

STTR PHASE II: SCALABLE THERMOCHEMICAL CONVERSION OF CARBON DIOXIDE TO COMMODITY CHEMICAL INTERMEDIATES -THE BROADER IMPACT/COMMERCIAL POTENTIAL OF THIS SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PHASE II PROJECT IS TO ADVANCE DYNAMIC CHEMICAL REACTOR SYSTEMS THAT REPURPOSES WASTE GASES (PRIMARILY CARBON DIOXIDE (CO2)) FOR USE AS FUELS AND AS CHEMICALS. THIS EFFORT CAN HAVE SUBSTANTIAL COMMERCIAL AND MARKET IMPACTS AS ITS OUTPUT IS COMPATIBLE WITH EXISTING INFRASTRUCTURE. THIS PROJECT LEVERAGES SIGNIFICANT RECENT INVESTMENTS INTO CARBON CAPTURE, RENEWABLE ENERGY GENERATION, AND GREEN HYDROGEN. A PARTICULARLY INTERESTING APPLICATION OF THIS TECHNOLOGY IS THE PRODUCTION OF CHEMICAL FEEDSTOCKS THAT ARE USED TO MAKE PLASTICS AND OTHER COMMODITY CHEMICALS FROM LIVING ORGANISMS. THIS IS INHERENTLY A STEP TOWARDS CARBON NEGATIVE MANUFACTURING. THE PROPOSED PROJECT AIMS TO RE-PURPOSE POLLUTANTS TO A FEEDSTOCK FOR FUELS AND CHEMICALS. ALTHOUGH RENEWABLE ENERGY SOURCES ARE INCREASING AND BECOMING CHEAPER, THESE TECHNOLOGIES ARE NOT READY FOR HEAVY-DUTY TRANSPORTATION AND CHEMICAL SECTORS. NO COMMERCIAL SCALE OPERATION IS IN EXISTENCE IN WHICH CO2 IS CAPTURED FROM THE AIR OR FLUE GAS AND CONVERTED TO VALUE-ADDED FUELS DESPITE MUCH FUNDAMENTAL RESEARCH EFFORT. THE RESEARCH OBJECTIVES ARE TO SCALE UP THE MATERIALS AND SYSTEM FROM THE PHASE I RESULTS AND CONDUCT A DESIGN AND ANALYSIS OF A FULL-SCALE SYSTEM. THE MAIN ADVANCE IS TO ACHIEVE DYNAMIC CHEMICAL REACTOR MODULES THAT ACHIEVE HIGH REACTANT CONVERSIONS. THESE RESULTS WILL PERMIT ANALYSIS OF A PILOT-SCALE FACILITY AS WELL AS TRANSLATION OF THE BENEFITS OF THIS SUSTAINABLE CHEMICAL REACTION TOWARD INDUSTRIAL SCALE PRODUCTION OF CLEAN AND GREEN HYDROCARBON FUELS AND CHEMICALS. 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.

CONTINUOUS FLOW MANUFACTURING OF ENERGETIC PRECURSORS

PUBLICATION AND RETRIEVAL OF COMPUTATIONAL CHEMICAL-PHYSICS DATA VIA THE SEMANTIC WEB

AN OPTIMIZED BIOCATALYST FOR EFFICIENT CONVERSION OF CH4 AND CO2 INTO BIOPRODUCTS

NOVEL FIBER SCAFFOLDING FOR EFFECTIVE REMOVAL OF DIVERSE HAZARDOUS CHEMICALS FROM WATER

TITLE: A VIRTUAL TECHNICIAN & OPERATOR TRAINING PROGRAM (VTOTP) FOR ADVANCED PROCESSES IN THE PHARMACEUTICAL, BIOPHARMACEUTICAL, AND SPECIALTY CHEMICAL INDUSTRIESPURPOSE: THE PURPOSE OF THIS GRANT IS TO SUPPORT EDUCATION AND WORKFORCE DEVELOPMENT GAPS IN MANUFACTURING OF BIO/PHARMACEUTICALS AND SPECIALTY CHEMICALS BY ESTABLISHING A VIRTUAL TECHNICIAN AND OPERATOR TRAINING PROGRAM FOR ADVANCED PROCESSES.ACTIVITIES TO BE PERFORMED: THE PROJECT TEAM WILL DEVELOP AND DEPLOY A VIRTUAL TECHNICIAN AND OPERATOR TRAINING PROGRAM FOR ADVANCED PROCESSES USED BY THE PHARMACEUTICAL AND SPECIALTY CHEMICAL INDUSTRIES; BUILD A ROADMAP FOR TECHNICIAN AND OPERATOR TRAINING FOR THESE INDUSTRIES; AND DEVELOP FIVE E-LEARNING COURSES BASED OFF THE ROADMAP FOR PILOTING WITH 200 PEOPLE.EXPECTED OUTCOMES: THIS PROJECT WILL PROVIDE ACCESS TO A VIRTUAL, ON-DEMAND ARSENAL OF COURSES THAT COULD BE ACCESSED FROM ANYWHERE IN THE U.S. AT ANY TIME AND BRING PROSPECTIVE WORKERS UP-TO-SPEED QUICKLY FOR INDUSTRIES THAT PRODUCE ITEMS CRITICAL TO THE SUPPLY CHAIN INCLUDING MEDICATIONS, VACCINES, AND OTHER CRITICAL CONSUMER GOODS. INTENDED BENEFICIARIES: PHARMACEUTICAL AND SPECIALTY CHEMICAL INDUSTRIES WILL BENEFIT FROM IMPACTFUL EDUCATION AND WORKFORCE DEVELOPMENT PROGRAMS. BROAD ACCESSIBILITY TO ADVANCED MANUFACTURING TRAINING IN A VIRTUAL ENVIRONMENT ENABLES MORE EQUITABLE ACCESS TO PROSPECTIVE EMPLOYEES AND INDIVIDUALS IN THE CURRENT AND FUTURE WORKFORCE PIPELINE, PARTICULARLY THOSE DISPROPORTIONALLY IMPACTED BY CORONAVIRUSES.SUBRECIPIENT ACTIVITIES: THE RECIPIENT DOES NOT PLAN TO AWARD FUNDS TO SUBRECIPIENTS.

SBIR PHASE II: NOVEL SYNTHESIS METHOD FOR IONIC LIQUIDS

AI-DRIVEN DISCOVERY OF IN VIVO CHEMICAL PROBES FOR UNDERSTUDIED TARGETS FOR THE TREATMENT OF ALZHEIMER'S DISEASE AND RELATED DISORDERS (ADRD) - ALZHEIMER’S DISEASE AND RELATED DEMENTIAS (ADRD) ARE DEBILITATING DISEASES THAT ARE INCREASING IN PREVALENCE BEING THE MOST COMMON FORM OF DEMENTIA WORLDWIDE. CURRENT THERAPIES ARE PRIMARILY PALLIATIVE IN NATURE EXCEPT FOR THE RECENT AMYLOID ANTIBODIES WHICH SHOW VARIABLE AND INCREMENTAL EFFICACY IN SLOWING DISEASE PROGRESSION. WE HERE APPLY THE EMERGING TOOLS OF ARTIFICIAL INTELLIGENCE (AI) AND MACHINE LEARNING (ML) TO AID IN THE DISCOVERY OF IN VIVO CHEMICAL PROBES FOR UNDERSTUDIED TARGETS IN AD RESEARCH. THE PROJECT IS CLOSELY ALIGNED WITH THE NIA- FUNDED AD INITIATIVES ACCELERATING MEDICINES PARTNERSHIP IN ALZHEIMER’S DISEASE TARGET DISCOVERY AND PRECLINICAL VALIDATION PROJECT AND THE EMORY-SAGE-SGC-JAX TARGET ENABLEMENT TO ACCELERATE THERAPY DEVELOPMENT FOR AD (TREAT-AD) CENTER. WE WILL EXAMINE ALL 900 PROTEINS CURRENTLY LISTED ON THE TREAT-AD WEBSITE, EVALUATE 15 PER YEAR USING VIRTUAL SCREENING FROM OUR COMPOUND LIBRARIES, AND ADVANCE FIVE OF THESE THROUGH A SERIES OF SAR DEVELOPMENT ACTIVITIES LEADING TO IN VIVO CHEMICAL PROBES WHICH ARE MADE PUBLICLY AVAILABLE THROUGH TREAT-AD AND SHARED WITH THE SCIENTIFIC COMMUNITY. WE WILL LEVERAGE VALIDATED VIRTUAL SCREENING WORKFLOWS FOR NOVEL TARGET DISCOVERY, A PROCESS FOR WHICH WE HAVE EXTENSIVE EXPERIENCE. AIM 1 IS TARGET SELECTION CLOSELY ALIGNED WITH TREAT-AD. AIM 2 IS VIRTUAL SCREENING FOR NOVEL COMPOUNDS WITH DESIRED TARGET BINDING ACTIVITY. AIM 3 IS ASSAY DEVELOPMENT AND TESTING OF TOP HITS FROM AIM 2 PLUS STRUCTURAL ANALOGS. AN AD HOC TARGET PROJECT TEAM WILL BE CREATED FOR EACH TARGET THAT EMERGES FROM AIM 2. AIM 4 INCORPORATES NOVEL AI-DRIVEN ALGORITHM DEVELOPMENT AND TRAINING FOR OPTIMIZING SELECTIVE LEADS FROM AIM 3 HITS. AIM 5 IS MEDICINAL CHEMISTRY REFINEMENT OF THE AI/ML OUTPUTS AND BIOCHEMICAL AND FUNCTIONAL CHARACTERIZATION OF CHMICAL HITS INCLUDING ADME CHARACTERIZATION SUITABLE FOR THE IDENTIFICATION OF PROBES FOR IN VIVO STUDIES. A HIT REVIEW STEERING COMMITTEE (HRSC) WILL REVIEW THE HITS AND LEADS THAT ARE DISCOVERED DURING THE COURSE OF THIS PROJECT TO PROVIDE GUIDANCE AS TO DESIGN AND INTERPRETATION OF STUDIES AS WELL AS WHICH HITS AND CHEMOTYPES TO ADVANCE FURTHER. FINALLY, AIM 6 IS PUBLIC DISSEMINATION OF THE STRUCTURES AND ACTIVITIES OF NEW IN VIVO CHEMICAL PROBES FOR UNDERSTUDIED TARGETS IN AD RESEARCH. SMALL MOLECULE CHEMICAL PROBES ARE VALIDATED FOR FURTHER PROOF OF CONCEPT RESEARCH IF THEY HAVE BINDING OR FUNCTIONAL ACTIVITY AT TARGETS OF INTEREST TO THE EXTENT OF ≤100 NM (PREFERRED) AND IN VIVO PK IN MICE WITH A T1/2 OF ≥60 MINS (PREFERRED), %F (ORAL BIOAVAILABILITY) OF ≥20% AND A BRAIN:PLASMA RATIO OF ≥0.5. IN SUMMARY, 15 TARGETS PER YEAR WILL GO INTO A FULL VIRTUAL SCREEN. BASED ON THE DATA, FIVE TARGETS PER YEAR WILL GO TO EXPERIMENTAL VALIDATION AND SAR DEVELOPMENT. ALL OF THE DATA WILL BE RELEASED ON THE TREAT-AD WEBSITE SO OTHERS CAN PURSUE THE 10 TARGETS PER YEAR THAT WERE NOT FOLLOWED UP ON. WE WILL USE MODERN METHODS IN COMPUTATIONAL CHEMISTRY INCLUDING AI AND ML TO DISCOVER AND CHARACTERIZE NEW IN VIVO CHEMICAL PROBES FOR UNDERSTUDIED TARGETS IN AD RESEARCH. IT IS ANTICIPATED THAT THESE IN VIVO CHEMICAL PROBES WILL BE WIDELY USED BY RESEARCHERS IN THE AD SCIENTIFIC COMMUNITY TO UNDERSTAND THE FUNCTION OF PROMISING NEW TARGETS.

CHEMISTRY CHALLENGE KITS AND OUTREACH AT SCIENCE FESTIVALS FOR THE INTERNATIONAL YEAR OF CHEMISTRY

GRANT FOR PROD OF ADV BIOFUEL

A SOBERING CHOICE DUI PROGRAM

BASE CLOSURE (CL) TO EVALUATE COMMUNITY NEEDS AND CAPABILITIES, AND PROVIDE ASSISTANCE TO MITIGATE THE MAY 2005 DEPARTMENT OF DEFENSE "BASE CLOSURE A

CAUSES OF CAFETERIA-FEEDING OBESITY

SBIR PHASE II: DUAL SUBSTRATE MEMS SWITCH

FLUE GAS PURIFICATION UTILIZING SOX/NOX REACTIONS DURING COMPRESSION OF CO2 DERIVED FROM OXYFUEL COMBUSTION

DEVELOPMENT OF ADVANCED MEMBRANES TECHNOLOGY PLATFORM FOR HYDROCARBON SEPARATIONS

GRANT FOR PROD OF ADV BIOFUEL

INVESTIGATING THE GUT-BRAIN SIGNALING DYNAMICS REGULATING FOOD INTAKE

NEW AWARD; ADVANCED COMBUSTION DIAGNOSTICS AND CONTROL FOR FURNACES, FIRED HEATERS AND BOILERS.

ADVANCED ACID GAS SEPARATION TECHNOLOGY FOR CLEAN POWER AND SYNGAS APPLICATIONS

ANODE CONCEPTS FOR SO2 CROSSOVER REDUCTION IN THE HYS ELECTROLYZER

ARSENIC SELECTIVE LIGAND-ANCHORED FIBER FOR PURIFICATION OF DRINKING WATER

UNNATURAL AMINO ACIDS BY DERACEMIZATION

DEVELOPMENT OF A TWO-PHASE DENSE FLUID EXPANDER FOR ADVANCED CRYOGENIC AIR SEPARATION AND LOW-GRADE HEAT RECOVERY

ASTRONOMICAL RESEARCH PROJECTS

CATALYST-ASSISTED MANUFACTURE OF OLEFINS FROM NATURAL GAS LIQUIDS: PROTOTYPE DEVELOPMENT AND FULL-SCALE TESTING

GOALS AND OBJECTIVESBEGINNING FEBRUARY 2006 THE ASTRONOMICAL RESEARCH INSTITUTE ARI MADE ITS FIRST NEO OBSERVATION AND IN A SINGLE DECADE HAS PRODUCED MORE THAN 129 488 MEASURES EXCEEDING ALL OTHER RESEARCH FACILITIES WORLDWIDE. OUR GOAL IN CONTINUING THIS RESEARCH IS TO PROVIDE A DEDICATED COST EFFECTIVE NEO FOLLOW UP PROGRAM THAT WILL ALLOW NASA TO COMPLETE THEIR GOAL OF CATALOGING POTENTIALLY HAZARDOUS NEAR EARTH OBJECTS TO 100 METERS.ARI HAS BEEN AN INTEGRAL PART OF NASAS NEOO PROGRAM FOR THE PAST NINE YEARS. UTILIZING FOUR TELESCOPES LOCATED AT THE INSTITUTE OUR PRIMARY OBJECTIVE IS TO PROVIDE THE LONGEST POSSIBLE ORBITAL ELEMENTS SPECIFICALLY FOR OBJECTS FAINTER THAN MAGNITUDE 22.0. THE PRINCIPAL GOAL OF THIS FACILITY IN PHASE IV WILL BE TO MEASURE MORE THAN 2 000 NEAS THAT ARE FAINTER THAN 22ND MAGNITUDE IN ORDER TO MAKE THEIR FUTURE RECOVERY MUCH MORE PROBABLE DURING THE OBJECTS NEXT OPPOSITION.APPROACH AND METHODOLOGYARI WILL CONTINUE TO FOCUS ON NEO CONFIRMATION PAGE OBJECTS AS A MAJOR PRIORITY. OUR SECONDARY GOAL IN THIS RESEARCH WILL BE TO CONDUCT FOLLOW UP OBSERVATIONS OF FIRST OPPOSITION NEOS AND THOSE REQUIRING ADDITIONAL OBSERVATIONS AS SPECIFIED BY THE MINOR PLANET CENTER MPC. ARIS LOWEST PRIORITY IN PHASE IV WILL BE TARGETED FOLLOW UP OF MULTIOPPOSITION OBJECTS.AS THE LARGE SKY SURVEYS SUCH AS PANSTARRS AND THE MT. LEMMON SURVEY CONTINUE TO MAKE NEW DISCOVERIES OF OBJECTS FAINTER THAN 22ND MAGNITUDE THE NEED FOR FAINT FOLLOW UP BECOMES MORE IMPERATIVE. DURING PHASE IV ARI PLANS TO REDUCE THE NUMBER OF OBSERVATIONS ON NEAS BRIGHTER THAN 22ND MAGNITUDE DUE TO THE NUMBER OF ACTIVE OBSERVERS THAT ARE FOCUSED ON THESE NEOS. IN 2015 ONLY SIX OBSERVATORIES REPORTED MORE THAN 250 22ND MAGNITUDE MEASURES OF NEOS TO THE MPC. OF THESE SIX ARI WAS RESPONSIBLE FOR 47.5 OF ALL THE OBSERVATIONS THAT WERE FAINTER THAN MAGNITUDE 22.0. IN 2015 H21 CONFIRMED 513 NEOS FOR THE SKY SURVEY DISCOVERY TEAMS AND RECOVERED TWENTY FIVE 22ND MAGNITUDE FIRST OPPOSITION OBJECTS. THREE OF THE FOUR INSTRUMENTS CURRENTLY IN OPERATION AT THE INSTITUTE ARE FULLY CAPABLE OF 22ND MAGNITUDE NEO OBSERVATIONS AND THE 1.3 M TELESCOPE IS CAPABLE OF RECOVERING 23RD MAGNITUDE NEOS. SHORTLY AFTER COMMISSIONING THE 1.3 M TELESCOPE IN SEPTEMBER 2014 NEO 2010 SV3 WAS RECOVERED AT UNFILTERED MAGNITUDE 24.2 WITH THREE MEASURES. THREE WEEKS LATER IT WAS CONFIRMED A SECOND TIME WITH THREE ADDITIONAL MEASURES. DURING THIS TELESCOPES FIRST 18 MONTHS OF OPERATION MORE THAN 105 23RD MAGNITUDE NEOS HAVE BEEN MEASURED.SIGNIFICANCE OF PROPOSED WORKOBSERVATIONS IN PHASE IV WILL BE EXTREMELY IMPORTANT ESPECIALLY DURING THE SUMMER MONTHS WHEN ONLY A FEW FOLLOW UP FACILITIES ARE AVAILABLE DUE TO THE SOUTHWESTERN U.S. ANNUAL MONSOON SEASON. IN 2015 THE INSTITUTE AT WESTFIELD ILLINOIS WORKED 63 NIGHTS DURING THE SUMMER PRODUCING 10 202 NEO MEASURES AND CONFIRMING 170 NEWLY DISCOVERED OBJECTS FOR THE DISCOVERY TEAMS. IN ADDITION H21 RECOVERED 163 NEOS THAT SUMMER FAINTER THAN MAGNITUDE 22.0.IN AN EFFORT TO STEP UP FAINT OBSERVATIONS ARO WILL CLEARLY IMPACT NASAS NEO PROGRAM BY TARGETING AN ESTIMATED 2 000 NEAS FAINTER THAN MAGNITUDE 22.0 EACH YEAR. IN ADDITION ARO ALSO PROJECTS THAT MORE THAN 250 INDIVIDUAL NEAS FAINTER THAN MAGNITUDE 23.0 WILL BE TARGETED EACH YEAR DURING THIS PHASE IV PROGRAM.

GRANT FOR PROD OF ADV BIOFUEL

HIGH RISK ADULT COURT ENHANCEMENT

ANODE CONCEPTS FOR SO2 CROSSOVER REDUCTION IN THE HYS ELECTROLYZER

UNRAVELING THE NEURAL MECHANISMS FOR SATIETY AND WEIGHT LOSS BY GLP1-BASED DRUGS - PROJECT SUMMARY OVER THE LAST SEVERAL DECADES, OBESITY RATES HAVE BEEN RISING, AND RESEARCH HAS FAILED TO SOLVE THIS PUBLIC HEALTH CRISIS. NOW, WE ARE AT THE PRECIPICE OF CHANGE. GLUCAGON-LIKE PEPTIDE-1 (GLP1)-BASED OBESITY DRUGS HAVE EMERGED AS A PROMISING STRATEGY FOR WEIGHT LOSS, AND THEIR UNPRECEDENTED SUCCESS IS TRANSFORMING THE TREATMENT OF OBESITY. DESPITE THEIR POPULARITY, WE HAVE LITTLE UNDERSTANDING OF THE BRAIN MECHANISMS THAT DRIVE THE FOOD INTAKE AND BODY WEIGHT REDUCTION FROM THESE DRUGS. IN OUR PRELIMINARY STUDIES, WE FOUND THAT HINDBRAIN GLP1 RECEPTOR (GLP1R)-EXPRESSING NEURONS ARE NECESSARY AND SUFFICIENT FOR THE EFFECTS OF GLP1-BASED OBESITY DRUGS SUCH AS SEMAGLUTIDE (OZEMPIC®/WEGOVY®). FURTHER, OUR DATA SUGGEST THAT THE NEURAL CIRCUITS THAT MEDIATE THE FOOD INTAKE SUPPRESSION AND THE NAUSEA/AVERSION (THE TOP SIDE EFFECT OF THESE DRUGS) ARE ANATOMICALLY AND FUNCTIONALLY SEPARABLE. SPECIFICALLY, WE IDENTIFIED A POPULATION OF NUCLEUS TRACTUS SOLITARIUS (NTS) GLP1R NEURONS THAT PROJECT TO THE PARAVENTRICULAR HYPOTHALAMUS (PVH) THAT SUPPRESSES FOOD INTAKE AND BODY WEIGHT WITHOUT CAUSING AVERSION. BUILDING ON THESE DATA, THIS PROPOSAL WILL BEHAVIORALLY, PHYSIOLOGICALLY, ANATOMICALLY, AND MOLECULARLY CHARACTERIZE NTSGLP1RPVH NEURONS AS A POTENTIAL TARGET FOR WEIGHT LOSS DRUGS WITH FEWER SIDE EFFECTS. FIRST, WE WILL TEST THE NECESSITY OF NTSGLP1R NEURONS, THEIR RECEPTORS, AND THEIR PROJECTIONS TO THE PVH, IN MEDIATING THE SATIETY AND WEIGHT LOSS EFFECTS OF SEMAGLUTIDE. NEXT, WE WILL DETERMINE THE ENDOGENOUS NEURAL ACTIVITY PATTERNS OF NTSGLP1R NEURONS IN RESPONSE TO GUT-DERIVED SIGNALS AND OBESITY DRUGS, AND HOW THIS ACTIVITY CHANGES IN DIET-INDUCED OBESITY. FINALLY, WE WILL DETERMINE THE INPUTS AND OUTPUTS OF NTSGLP1R NEURONS TO MAP A CIRCUIT FOR NON-AVERSIVE SATIETY. THIS COMPREHENSIVE ANALYSIS OF NTSGLP1RPVH NEURONS WILL UNCOVER A NOVEL NEURAL CIRCUIT FOR FEEDING BEHAVIOR, AND DETERMINE THE SUITABILITY OF THIS POPULATION AS A SELECTIVE TARGET FOR FUTURE DRUG DEVELOPMENT.

SOUTHERN SKY NEO FOLLOW-UP PHASE IISSNEO PHASE II IS A CONTINUATION OF THE SOUTHERN SKY NEO FOLLOW-UP PROGRAM THAT BEGAN OPERATIONS IN 2012 WITH GRAN

TAS::57 3600::TAS ANALYTICAL IDENTIFICATION OF STRESS ODORS IN HUMAN BREATH

CLOSURE (CL)

INFLUENZA VIRUS INDUCED NEUROINFLAMMATION IN THE OLFACTORY SENSORY SYSTEM AND LONG-TERM ANOSMIA - PROJECT SUMMARY RESPIRATORY VIRAL INFECTION IS A LEADING CAUSE OF OLFACTORY LOSS. MANY RESPIRATORY VIRUSES CAN REACH AND INFECT THE OLFACTORY EPITHELIUM. INFLUENZA VIRUS CAN DIRECTLY INFECT OLFACTORY SENSORY NEURONS, AND THIS INFECTION NOT ONLY CAN CAUSE SMELL LOSS BUT ALSO CAN INCREASE THE RISK OF DEVELOPING OTHER NEURODEGENERATIVE DISEASES, SUCH AS PARKINSON’S DISEASE AND DEMENTIA. WHILE SMELL LOSS IN MOST POSTVIRAL PATIENTS IS TEMPORARY, AS THE OLFACTORY EPITHELIUM CAN REGENERATE, A SUBSET OF PATIENTS DEVELOP LONG-TERM LOSS THAT LASTS MORE THAN SEVERAL MONTHS, AND FOR SOME THE LOSS BECOMES PERMANENT. SMELL LOSS IS ASSOCIATED WITH LOW QUALITY OF LIFE, ANXIETY, AND DEPRESSION. THE UNDERLYING MECHANISMS THAT DRIVE LONG-TERM POSTVIRAL SMELL LOSS REMAIN POORLY UNDERSTOOD, AND EFFECTIVE TREATMENTS FOR SMELL LOSS ARE CURRENTLY LACKING. ANTIVIRAL MECHANISMS ARE CRITICAL FOR TISSUE PROTECTION AGAINST VIRUSES. HOWEVER, THESE MECHANISMS CAN BE WEAKENED BY GENETIC AND/OR ENVIRONMENTAL FACTORS. INTRIGUINGLY, INBORN ERRORS IN ANTIVIRAL GENES HAVE BEEN IDENTIFIED IN HUMANS AND CONTRIBUTE TO THE SEVERITY OF VIRAL INFECTIONS. OUR HYPOTHESIS, STRONGLY SUPPORTED BY OUR PRELIMINARY DATA, IS THAT GENETIC ERRORS IN SOME ANTIVIRAL GENES CONTRIBUTE TO SEVERE, LONG-TERM POST-INFLUENZA SMELL LOSS. HERE WE WILL TEST THIS HYPOTHESIS USING PRECLINICAL ANIMAL MODELS OF INFLUENZA-INDUCED SMELL LOSS. WE WILL DETERMINE WHETHER DEFICIENCY IN ANTIVIRAL PATHWAYS LEADS TO INEFFICIENT VIRUS CLEARANCE FROM THE OLFACTORY TISSUE AND RESULTS IN EXCESSIVE AND PROLONGED NEUROINFLAMMATION, LEADING TO DEATH OF OLFACTORY SENSORY NEURONS, AND ULTIMATELY DAMAGE TO THE OLFACTORY SENSORY EPITHELIUM AND THE OLFACTORY BULB, THE FIRST RELAY STATION OF OLFACTORY INFORMATION IN THE BRAIN. WE WILL ALSO INVESTIGATE THE MOLECULAR MECHANISMS CONTRIBUTING TO NEURODEGENERATION AND THE MECHANISMS UNDERLYING INHIBITION OF NEURAL REGENERATION IN THE OLFACTORY EPITHELIUM FOLLOWING INFLUENZA VIRUS INFECTION. THIS RESEARCH WILL PROVIDE THE MUCH-NEEDED MECHANISTIC INSIGHTS INTO LONG- TERM SMELL LOSS AFTER INFLUENZA VIRUS INFECTION AND WILL REVEAL POTENTIAL TARGETS FOR DEVELOPING NEUROPROTECTIVE THERAPIES. RESULTS FROM THIS STUDY MAY ALSO SHED LIGHT ON MECHANISMS OF OTHER NEURODEGENERATIVE DISEASES ASSOCIATED WITH VIRAL INFECTIONS.

** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** SUSTAINABLE CHEMICALS, LLC (SUST-CHEM) WAS ESTABLISHED TO ADDRESS THE GLOBAL PLASTIC POLLUTION CRISIS. ANNUALLY, BETWEEN 19 TO 23 MILLION TONS OF PLASTICS ENTER THE OCEANS AND BY 2050 PLASTICS WILL CONTRIBUTE 13% OF GLOBAL CO2 EMISSIONS. POLYETHYLENE AND POLYPROPYLENE ARE AMONG THE LARGEST VOLUME PLASTICS AND CONSTITUTE 52% OF THE TOXIC MICROPLASTICS FOUND IN SEDIMENTS, WHICH POSE POTENTIAL HEALTH RISKS. CONSUMERS AND BRAND MANUFACTURERS SEEK LOWER CARBON FOOTPRINT MATERIALS WITH REDUCED MICROPLASTIC FORMATION RISKS, YET VIABLE ALTERNATIVES FOR LIGHTWEIGHT PACKAGING ARE SCARCE. DESPITE SUBSTANTIAL INVESTMENTS, EXISTING BIOPLASTICS REMAIN LIMITED TO NICHE MARKETS DUE TO THEIR HIGHER COST AND INFERIOR PERFORMANCE THAN PETROCHEMICAL PLASTICS. THE IMPERATIVE TO REPLACE EVERYDAY PLASTICS WITH ECO-FRIENDLY ALTERNATIVES REMAINS UNMET.SUST-CHEM FOCUSES ON DEVELOPING INNOVATIVE, FULLY COMPOSTABLE, AND RENEWABLE BIOPLASTICS. OUR APPROACH INVOLVES UTILIZING A PLANT-BASED RAW MATERIAL THAT IS 20% CHEAPER THAN PETROCHEMICAL RAW MATERIALS AND CAN BE PRODUCED IN VOLUMES SUFFICIENT TO MEET THE PLASTIC INDUSTRY'S DEMAND. THIS STRATEGIC ADVANTAGE POSITIONS US COMPETITIVELY AGAINST BOTH TRADITIONAL AND BIOBASED PLASTICS. OUR BIOPLASTICS ARE ENGINEERED FOR OPTIMAL CIRCULARITY AND HAVE A BENIGN END-OF-LIFE WHETHER RECYCLED, LANDFILLED, OR LOST IN THE OCEANS.THIS USDA PHASE II SBIR PROJECT AIMS TO DEVELOP A HIGHER PERFORMANCE FORM OF OUR BIOPLASTICS FOR USE IN RIGID APPLICATIONS SUCH AS COSMETIC CONTAINERS, DETERGENT BOTTLES, AND SODA BOTTLE LIDS.THE MARKET ACCEPTANCE OF SUST-CHEM BIOPLASTIC WILL ENHANCE THE AGRICULTURE SECTOR'S ROLE AS A RELIABLE SUPPLIER OF RAW MATERIALS TO THE PLASTIC INDUSTRY, REDUCE THE US DEPENDENCE ON FOREIGN OIL, AND REDUCE THE ENVIRONMENTAL IMPACT OF THERMOPLASTIC MANUFACTURE, USE, AND DISPOSAL.

SOUTHERN SKY NEAR-EARTH OBSERVATIONS (SSNEO) WITH THIS PROPOSAL THE ASTRONOMICAL RESEARCH INSTITUTE (ARI) WILL CONTINUE ITS COLLABORATION WITH THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL (UNC) TO PROVIDE NASA WITH A LOW-COST SOUTHERN HEMISPHERE NEAR-EARTH ASTEROID (NEA) FOLLOW-UP PROGRAM. SCIENTIFIC: THE SOUTHERN SKY NEAR EARTH OBSERVATIONS (SSNEO) BEGAN APRIL 1ST 2012 AND HAS SINCE PROVIDED OVER 80% OF ALL NEA MEASURES BELOW MINUS 20 DECLINATION. THE SOUTHERN HEMISPHERE REMAINS A CRITICAL AREA FOR NEA FOLLOW-UP TO PREVENT MANY ASTEROIDS FROM BEING LOST BY EXTENDING THEIR ORBITAL ARCS. WITH THE INCREASE IN NEA DISCOVERIES FROM PANSTARRS AND THE CATALINA SKY SURVEY (CSS) THE NUMBER OF NEAR-EARTH OBJECT CONFIRMATION PAGE (NEOCP) NEAS IN NEED OF ASTROMETRY HAS NEVER BEEN HIGHER. THEREFORE SSNEO IN PHASE 3 WILL DEDICATE THEIR EFFORTS TO PROVIDE AN EFFICIENT NEA ASTROMETRY AND RECOVERY PROGRAM. PANSTARRS AND CSS ARE CURRENTLY EXPENDING SIGNIFICANT AMOUNTS OF TIME CONDUCTING FOLLOW-UP OF THEIR OWN DISCOVERIES LIMITING THEIR ABILITY TO SEARCH FOR NEW NEAR-EARTH ASTEROIDS. IN PHASE 3 SSNEO WILL DECREASE THE NEED FOR SURVEYS TO FOLLOW-UP THEIR SOUTHERN HEMISPHERE TARGETS BY 25%. THIS WILL BE ACCOMPLISHED BY UTILIZING NEW HARDWARE AND A SCHEDULING SYSTEM WHICH WILL OBTAIN EPHEMERIS AND UNCERTAINTY INFORMATION DIRECTLY FROM JPL S NEASCOUT WEBSITE. TECHNICAL: IN 2015 SSNEO EXPANDED THEIR PROJECT FROM ONE 0.41-M TELESCOPE TO TWO 0.61-M TELESCOPES AND ONE 0.41-M INSTRUMENT INCREASING THE SOUTHERN HEMISPHERE FOLLOW-UP OF NEOS TO MAGNITUDE V23.0. THIS PROPOSAL WILL CONTINUE TO OPERATE THREE TELESCOPES AND WILL REQUEST FUNDS TO UPGRADE THE REMAINING 0.41-M TELESCOPE TO A 0.61-M INSTRUMENT. WITH THIS UPGRADE ALL THREE TELESCOPES WILL BE IDENTICAL WITH THE SAME IMAGE SCALE AND 23.9 ARC-MINUTE FIELD OF VIEW. SINGLE OPPOSITION NEAS TYPICALLY HAVE AN UNCERTAINTY WHICH IS LINEAR WITHIN A RANGE OF RIGHT ASCENSION AND DECLINATION. TO INCREASE THE NUMBER OF RECOVERIES THE THREE TELESCOPES WILL HAVE A NEW FEATURE WHERE EACH TELESCOPE S CAMERA ROTATOR WILL AUTOMATICALLY ORIENT ITS POSITION SO THAT THE SKY ANGLE OF UNCERTAINTY ALIGNS WITH THE CCD S ARRAY DIAGONALLY. BECAUSE EACH TELESCOPE HAS A DIAGONAL IMAGE THAT IS 33.8 ARC-MINUTES ALL THREE TELESCOPES TOGETHER CAN COVER 5 100 ARC-SECONDS OF UNCERTAINTY WORKING TOGETHER. THIS ADDITIONAL FEATURE IN TELESCOPE AUTOMATION TAKES ADVANTAGE OF EACH TELESCOPE'S IDENTICAL PERFORMANCE. THEREFORE A 3 SQUARE DEGREE UNCERTAINTY REGION CAN BE EASILY SEARCHED IN A SINGLE NIGHT. THE JPL NEASCOUT WEBSITE IS A NEW ASSET THAT WILL BE INTEGRATED INTO DAILY OPERATIONS. USING NEASCOUT BOTH NEOCP AND NEA S EPHEMERIS AND UNCERTAINTY OF AN OBJECT CAN BE DIRECTLY LINKED INTO SSNEO S AUTOMATION ROUTINES. THIS WILL ALLOW CALCULATIONS OF THE FIELDS TO BE TARGETED SO THE UNCERTAINTY AREA CAN BE EASILY SEARCHED. MANAGEMENT: FOLLOW-UP OBSERVATIONS WILL CONTINUE TO BE CONTROLLED BY THE ASTRONOMICAL RESEARCH INSTITUTE S SOUTHERN HEMISPHERE CONTROL OFFICE. ARI HAS SIX YEARS OF EXPERIENCE CONTROLLING TELESCOPES AT CTIO REMOTELY. THIS GRANT WILL CONTINUE TO BE MANAGED BY PI ROBERT HOLMES AND CO-I TYLER LINDER. CO-I LINDER WILL MANAGE THE DAILY OPERATIONS AND OVERSEE PROPER AUTOMATION ROUTINES PROVIDING IMPORTANT SUPPORT TO PANSTARRS AND CSS DISCOVERIES AS WELL AS EXTENDING THE ORBITAL ARCS ON AS MANY SOUTHERN HEMISPHERE TARGETS AS POSSIBLE.

HMIT - HAZARDOUS MATERIAL INSTRUCTOR TRAINING - THIS GRANT SUPPORTS THE STATE BY PROVIDING TRAIN-THE-TRAINER PROGRAMS, FOR TRAINING IN HAZARDOUS MATERIALS REGULATIONS. DELIVERABLES/EXPECTED OUTCOMES: IMPROVED TRAINING FOR HAZMAT EMPLOYEES. INTENDED BENEFICIARY: HAZMAT EMPLOYEES. SUBRECIPIENT ACTIVITIES: NO KNOWN SUBRECIPIENTS.

DEVELOPMENT OF A PEPTIDE-DRUG CONJUGATE FOR TOPICALLY TREATING THE VIRAL SKIN DISEASE MOLLUSCUM CONTAGIOSUM - ABSTRACT MOLLUSCUM CONTAGIOSUM (MC) IS A HIGHLY CONTAGIOUS SKIN DISEASE CAUSED BY THE POXVIRUS, MCV. IT REMAINS AN UNMET MEDICAL NEED DUE TO LACK OF AN APPROVED ANTIVIRAL DRUG. MC APPEARS AS LESIONS ON THE BODY AND FACE THAT CAN LAST MONTHS-YEARS BEFORE RESOLVING. LESIONS OCCUR MOST FREQUENTLY IN CHILDREN (5%) AND IMMUNE COMPROMISED INDIVIDUALS (5-18%). THE INFECTION IS CONFINED TO THE EPIDERMAL SKIN LAYERS; IT IS NOT SYSTEMIC. TRANSMISSION SPREADS DIRECTLY FROM PERSON-PERSON CONTACT, AUTOINOCULATION OR INDIRECT CONTACT WITH FOMITES. CURRENT TREATMENTS CAN BE PAINFUL, CAUSE SCARRING, AND PSYCHOLOGICAL DISTRESS. NONE OF THE CURRENT TREATMENTS THAT INCLUDE A RANGE OF PHYSICAL, CHEMICAL AND MEDICINAL INTERVENTIONS ARE UNIFORMLY ACCEPTED OR FDA APPROVED. THE REASON WHY NO APPROVED DRUG AGAINST MCV HAS BEEN DEVELOPED IS BECAUSE THE VIRUS CANNOT BE GROWN IN TISSUE CULTURE FOR TESTING. WE HAVE NOW MADE FOUR MAJOR BREAKTHROUGHS: FIRST, WE HAVE IDENTIFIED A PROTEIN TARGET (MD4) OF MCV THAT IS ESSENTIAL FOR REPLICATION. THE MD4 PROTEIN FUNCTIONS AS A PROCESSIVITY FACTOR (PF) THAT TETHERS THE VIRAL POLYMERASE (POL) TO THE TEMPLATE TO ENABLE CONTINUOUS SYNTHESIS OF DNA. SECOND, WE HAVE CONSTRUCTED A MD4- SURROGATE VIRUS (MD4-VV), PROVIDING THE FIRST CELL-BASED SYSTEM FOR SCREENING COMPOUNDS AGAINST AN ESSENTIAL MCV TARGET PROTEIN (MD4) IN INFECTED CELLS. THIRD, WE HAVE SYNTHESIZED A SMALL MOLECULE (7269) THAT THAT BINDS A PRECISE REGION OF THE MD4 TARGET PROTEIN, CAUSING IT TO UNFOLD AND NO LONGER FUNCTION. WHILE 7269 CAN BLOCK INFECTION BY THE SURROGATE VIRUS, WE WERE UNABLE TO IMPROVE ITS POTENCY OR ELIMINATE ITS SLIGHT TOXICITY DESPITE AN INTENSE MEDICINAL CHEMISTRY CAMPAIGN. FOURTH, WE OVERCAME THIS IMPASSE BY CONJUGATING A PEPTIDE TO PRODUCE TRIVALINE-7269 THAT BINDS THE MD4 WITH A POTENCY THAT IS 6.3-FOLD GREATER THAN THAT OF UNCONJUGATED 7269 AND HAS NO MEASURABLE TOXICITY. SINCE TRIVALINE-7269 DOES NOT ALTER DIRECT BINDING TO THE MD4 TARGET, ITS INCREASED POTENCY IS DUE TO CELLULAR PENETRATION AND/OR STABILITY. THE CHALLENGE THAT IMPEDES FURTHER DRUG DEVELOPMENT IS THAT TRIVALINE-7269 HAS NO RELATED ANALOG OF EQUAL OR GREATER POTENCY TO MITIGATE RISK IN THE NEXT STAGES OF DRUG DEVELOPMENT. THE GOAL IS TO IDENTIFY ANALOGS OF TRIVALINE-7269 OF EQUAL OR GREATER POTENCY AS ESSENTIAL BACKUPS. AIM 1 WILL UTILIZE MEDICINAL CHEMISTRY TO SYNTHESIZE ANALOGS OF TRIVALINE-7269. THE FOCUS WILL BE TO VARY BOTH THE PEPTIDE AND LINKER PORTIONS OF TRIVALINE-7269. THE 7269 PORTION WILL NOT BE MODIFIED SINCE IT HAS ALREADY BEEN OPTIMIZED. WE WILL PRODUCE 30-40 ANALOGS. AIM 2 WILL EVALUATE NEW ANALOGS FOR ANTIVIRAL POTENCY AGAINST THE SURROGATE VIRUS; CYTOTOXICITY; BLOCKING IN VITRO PROCESSIVE DNA SYNTHESIS; BINDING TO THE MD4 TARGET. AIM 3 WILL EVALUATE STRUCTURALLY DISTINCT ANALOGS FOR IN VITRO ADME ACTIVITIES THAT ARE RELEVANT FOR TOPICAL APPLICATION INCLUDING METABOLIC STABILITY, SOLUBILITY AND CELL PERMEABILITY. CONJUGATES WITH CRITERIA THAT EXCEED OR MATCH TRIVALINE-7269 WILL PROVIDE THE MINIMUM NUMBER OF ANALOGS FOR FUTURE DRUG DEVELOPMENT.

PROJECT LIVE ( LAUGH, INSPIRE, VALUE, EDUCATE)

PATHOGEN-SPECIFIC REGULATION OF PROTEIN ASSEMBLY

TRYPANOCIDAL AGENTS THAT KILL MULTIPLE STAGES OF THE TRYPANOSOMA CRUZI LIFE CYCLE

SOUTH COAST YOUTH COURT - SUBSTANCE ABUSE TREATMENT AND REFERRAL SYSTEM (STARS)

INTERNATIONAL YEAR OF ASTRONOMY 2009 IN THE UNITED STATES - A NATIONAL PROGRAM

IGE: IMPACT INDICATORS AND INSTRUMENTS FOR INDIVIDUAL DEVELOPMENT PLANS

DEVELOPMENT OF FOSA INHIBITORS TO POTENTIATE FOSFOMYCIN ACTIVITY IN GRAM-NEGATIVE PATHOGENS - SUMMARY. ANTIMICROBIAL RESISTANCE IS WIDELY RECOGNIZED AS ONE OF THE MOST SIGNIFICANT PUBLIC HEALTH THREATS OF THE CENTURY. MANY BACTERIAL INFECTIONS HAVE BECOME DIFFICULT TO TREAT DUE TO ANTIMICROBIAL RESISTANCE, AND THERE IS AN URGENT NEED TO DEVELOP NEW STRATEGIES TO COMBAT THESE RESISTANT PATHOGENS. ONE SUCH STRATEGY IS TO REPOSITION OLDER ANTIBIOTICS THAT HAVE LONG-TRACK RECORDS OF SAFETY IN HUMAN. FOSFOMYCIN (FOM) IS AN ETABLISHED ANTIBIOTIC WHICH INACTIVATES UDP-N-ACETYLGLUCOSAMINE ENOLPYRUVYL TRANSFERASE IN BOTH GRAM-POSITIVE AND -NEGATIVE PATHOGENS. CURRENTLY, FOM IS EXCLUSIVELY USED AS AN ORAL FORMULATION FOR THE TREATMENT OF URINARY TRACT INFECTIONS GIVEN ITS EXCELLENT ACTIVITY AGAINST ESCHERICHIA COLI. HOWEVER, AN INTRAVENOUS FOM FORMULATION IS USED ELSEWHERE, AND IS CURRENTLY PENDING FDA APPROVAL IN U.S. FURTHERMORE, AN ONGOING NIAID-SPONSORED TRIAL (NCT03910673) IS EXPLORING WHETHER INTRAVENOUS FOM CAN EFFECTIVELY TREAT LUNG INFECTIONS, SUCH AS HOSPITAL-ACQUIRED AND VENTILATOR-ASSOCIATED BACTERIAL PNEUMONIA. FOSA IS A DIMERIC K+- AND MN2+-DEPENDENT GLUTATHIONE S-TRANSFERASE THAT CATALYZES THE NUCLEOPHILIC ADDITION OF GLUTATHIONE TO CARBON-1 IN THE EPOXIDE RING OF FOM, RENDERING THE ANTIBIOTIC INACTIVE. E. COLI LACKS INTRINSIC CHROMOSOMAL FOSA, THUS EXPLAINING ITS ACUTE SUSCEPTIBILITY TO FOM. HOWEVER, FOSA HOMOLOGUES ARE CHROMOSOMALLY ENCODED BY MANY GRAM-NEGATIVE SPECIES INCLUDING PSEUDOMONAS AERUGINOSA AND KLEBSIELLA PNEUMONIAE. OUR PRIOR RESEARCH HAS CLEARLY DEMONSTRATED THAT THIS INTRINSIC PRODUCTION OF FOSA CONFERS FOM RESISTANCE, AND THAT INACTIVATION OF FOSA PROVIDES A NOVEL APPROACH TO INCREASE THE SENSITIVITY OF CARBEPENEM RESISTANT GRAM-NEGATIVE PATHOGENS TO FOM, THUS HIGHLIGHTING A NOVEL PATHWAY TO EXPAND THE USE OF FOM TO A WIDE RANGE OF GRAM-NEGATIVE SPECIES. IMPORTANTLY, AND CENTRAL TO THIS APPLICATION, WE RECENTLY IDENTIFIED AND PATENTED A FIRST-IN-CLASS, COMPETITIVE SMALL MOLECULE INHIBITOR OF FOSA (ANY1) WHICH POTENTIATES FOM ACTIVITY AGAINST GRAM-NEGATIVE PATHOGENS THAT HARBOR THE FOSA GENE. USING INSIGHTS FROM THE ANY1-FOSA X-RAY CRYSTAL STRUCTURE, WE HAVE DESIGNED AND PREPARED AN ANALOG THAT HAS ~10X GREATER POTENCY, SHOWING THAT FURTHER SAR DEVELOPMENT IS POSSIBLE. THE AIMS IN THIS PROPOSAL ARE (1) MEDICINAL CHEMISTRY OPTIMIZATION OF FOSA INHIBITORS, (2) EVALUATION AND OPTIMIZATION OF ADME PROPERTIES, AND (3) BIOLOGICAL EVALUATION AGAINST A BROAD PANEL OF XDR GRAM-NEGATIVE CLINICAL ISOLATES. WE ANTICIPATE THAT SUCH A COMBINATION COULD BE USED TO TREAT INVASIVE INFECTIONS INCLUDING BACTEREMIA, PNEUMONIA, INTRA-ABDOMINAL INFECTIONS AND COMPLICATED UTIS CAUSED BY GRAM-NEGATIVE BACTERIA THAT HARBOR FOSA (E.G., K. PNEUMONIAE, ENTEROBACTER SPP., P. AERUGINOSA), INCLUDING EXTREMELY DRUG RESISTANT STRAINS. IN THIS PHASE I PROPOSAL, WE WILL IDENTIFY AND EVALUATE FOSA INHIBITORS BASED ON ANY1 BY COMBINING THE PHARMACEUTICAL AND MEDICINAL CHEMISTRY EXPERTISE OF THE SCIENTISTS AT THE FOX CHASE CHEMICAL DIVERSITY CENTER, INC. (FCCDC) WITH THE EXPERTISE AND EXPERIENCE OF THE SLUIS-CREMER LAB AT THE UNIVERSITY OF PITTSBURG IN THE EXPERIMENTAL ASPECTS OF FOSA INHIBITION AND ANTIBIOTIC THERAPY.

PROTACS AGAINST NEF AS A FUNCTIONAL CURE FOR HIV INFECTION

DEVELOPMENT OF SMALL MOLECULE THERAPEUTICS TARGETING HEMORRHAGIC FEVER VIRUSES

ASSISTANCE TO FIREFIGHTERS GRANT

THE HMIT GRANT PROGRAM WAS AUTHORIZED UNDER THE HAZARDOUS MATERIALS TRANSPORTATION SAFETY AND SECURITY REAUTHORIZATION ACT OF 2005 (P.L. 109-59, CODIFIED AT 49 U.S.C. ? 5107(E)), WHICH AUTHORIZES THE SECRETARY OF TRANSPORTATION TO MAKE GRANTS FOR THE PURPOSE OF TRAINING INSTRUCTORS AND TO THE EXTENT DETERMINED APPROPRIATE, FOR SUCH INSTRUCTORS TO TRAIN HAZARDOUS MATERIALS (HAZMAT) EMPLOYEES. HMIT GRANT APPLICATIONS WILL BE REVIEWED THROUGH A COMPETITIVE PROCESS.

DEVELOPMENT OF HOST- ORIENTED THERAPEUTICS TARGETING SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2), - THE ULTIMATE GOAL OF THIS PHASE I APPLICATION IS TO DISCOVER AND DEVELOP HOST-ORIENTED SMALL MOLECULE COMPOUNDS TARGETING SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2) INFECTION. SARS-COV-2 IS A NOVEL CORONAVIRUS DRIVING THE CURRENT GLOBAL PANDEMIC OF SEVERE RESPIRATORY SYNDROME IN HUMANS. ANTIVIRAL THERAPEUTICS ARE URGENTLY NEEDED TO COMBAT INFECTION BY SARS-COV-2 AND NEW VARIANTS THAT ARE CONTINUING TO EMERGE. WE HAVE DISCOVERED SEVERAL CHEMICAL SERIES THAT TARGET MODULAR INTERACTIONS BETWEEN SPECIFIC HOST PROTEINS CONTAINING WW-DOMAINS (E.G. NEDD4) AND VIRAL PROTEINS CONTAINING PPXY MOTIFS (E.G. EBOLA VP40). NOTABLY, EMERGING RNA VIRUS PATHOGENS SUCH AS EBOLA, MARBURG, LASSA, AND RABIES VIRUSES ALL ENCODE PPXY MOTIFS THAT RECRUIT HOST WW-DOMAIN CONTAINING PROTEINS TO FACILITATE EFFICIENT VIRUS EGRESS, SPREAD, AND TRANSMISSION. INTERESTINGLY, THE SURFACE-EXPOSED SPIKE GLYCOPROTEIN (S) OF SARS-COV-2 ALSO HAS A PUTATIVE WW-DOMAIN BINDING MOTIF (25PPAY28), THAT IS NOT PRESENT IN THE S PROTEIN OF SARS-COV-1 OR MORE ATTENUATED CORONAVIRUS STRAINS. THE ACQUISITION OF THIS PPAY MOTIF IN THE MAJOR SURFACE PROTEIN OF SARS-COV-2 VIRIONS RAISES THE INTRIGUING POSSIBILITY THAT IT MAY CONTRIBUTE TO THE UNIQUE PATHOGENICITY AND/OR TRANSMISSION OF SARS-COV-2 VIA INTERACTIONS WITH SPECIFIC HOST WW-DOMAIN BEARING PROTEINS. IN OUR ONGOING STUDIES ON FILOVIRUSES AND ARENAVIRUSES, WE HAVE USED EXTENSIVE SAR TO IDENTIFY A LEAD COMPOUND SERIES CAPABLE OF BLOCKING EGRESS AND SPREAD OF LIVE EBOV, MARV, AND LAFV IN CELL CULTURE, AS WELL AS BLOCKING DISEASE PROGRESSION IN VIVO IN A LIVE MARV CHALLENGE MODEL. HERE, WE HYPOTHESIZE THAT “INFORMED” SAR ANALYSES OF OUR IN-HAND PPXY/WW-DOMAIN INHIBITORS (E.G. LEAD CANDIDATE FC-10696) WILL LEAD TO THE DISCOVERY OF ANALOGS CAPABLE OF BLOCKING EGRESS AND DISEASE PROGRESSION OF SARS-COV-2, AS WELL AS RELATED PPXY-CONTAINING VARIANTS THAT MAY EMERGE IN THE FUTURE. IN SUPPORT OF OUR HYPOTHESIS, WE PRESENT STRONG PRELIMINARY DATA SHOWING THAT THE PPXY MOTIF WITHIN THE S PROTEIN OF SARS-COV-2 VIRUS CAN INTERACT WITH HOST WW-DOMAIN CONTAINING PROTEINS THAT ARE KNOWN TO PROMOTE EGRESS AND SPREAD OF EBOV, MARV, AND LAFV. MOREOVER, OUR CURRENT LEAD CANDIDATE PPXY BUDDING INHIBITORS SHOW ACTIVITY IN BLOCKING EGRESS OF LIVE SARS-COV-2 VIRUS INFECTION IN HUMAN LUNG EPITHELIAL CELLS. IN THIS PHASE I PROPOSAL, WE WILL IDENTIFY AND EVALUATE HOST-ORIENTED INHIBITORS AS POTENTIAL THERAPEUTICS FOR SARS-COV-2 AND RELATED CORONAVIRUSES BY COMBINING THE PHARMACEUTICAL AND MEDICINAL CHEMISTRY EXPERTISE OF THE SCIENTISTS AT THE FOX CHASE CHEMICAL DIVERSITY CENTER, INC. (FCCDC) WITH THE EXPERTISE AND EXPERIENCE OF THE HARTY LAB AT THE UNIVERSITY OF PENNSYLVANIA IN THE EXPERIMENTAL ASPECTS OF VIRUS-HOST INTERACTIONS AND ANTIVIRAL THERAPY, AND THE LAB OF OLENA SHTANKO AT TEXAS BIOMEDICAL RESEARCH INSTITUTE FOR EVALUATING COMPOUNDS AGAINST LIVE VIRUSES UNDER BSL-3 CONDITIONS. THE THREE AIMS ARE (1) LEAD FINDING AND OPTIMIZATION MEDICINAL CHEMISTRY INCLUDING ADME PROFILING, (2) EVALUATION FOR THE ABILITY TO SPECIFICALLY INHIBIT EGRESS OF SARS-COV-2 VLPS AND PPXY- MEDIATED S-HOST PROTEIN INTERACTIONS, AND (3) IN VITRO AND IN VIVO ANALYSES AGAINST AUTHENTIC SARS-COV-2 VIRUS.

SBIR PHASE II: INNOVATIVE GREEN TECHNOLOGY FOR ADVANCED, PATIENT-CENTERED HOME HEMODIALYSIS

GRANT FOR PROD OF ADV BIOFUEL