Thaw Inc

TAS::89 0328::TAS RECOVERY ACT. OBLIGATE FY 10 ARRA FUNDING IN THE AMOUNT OF $137,877,906.00

DE-EE0007997 PROJECT TITLE: WESTSMARTEV: WESTERN SMART PLUG-IN ELECTRIC VEHICLE COMMUNITY PARTNERSHIP

A TIERED-APPROACH TO TRAUMA- AND GRIEF-FOCUSED EVIDENCE-BASED PRACTICE DELIVERY IN RESIDENTIAL AND INTENSIVE PROGRAMS - THE PROPOSED PROJECT, ENTITLED “A TIERED APPROACH TO TRAUMA- AND GRIEF-FOCUSED EVIDENCE- BASED PRACTICE DELIVERY IN RESIDENTIAL AND INTENSIVE PROGRAMS,” IS FOCUSED ON INCREASING AND IMPROVING IDENTIFICATION AND DIRECT SERVICE DELIVERY TO THE DISPROPORTIONATE NUMBER OF TRAUMA-EXPOSED AND BEREAVED YOUTH HATHAWAY-SYCAMORES CHILD AND FAMILY SERVICES (HSCFS) SERVES IN OUR RESIDENTIAL AND COMMUNITY-BASED INTENSIVE PROGRAMS (CBIPS) ACROSS SIX OF THE EIGHT SERVICE AREAS IN LOS ANGELES COUNTY (LAC). YOUTH IN THESE PROGRAMS HAVE HAD LIMITED ACCESS TO TRAUMA-AND GRIEF-FOCUSED EVIDENCE-BASED ASSESSMENTS (EBAS) AND EVIDENCE-BASED PRACTICES (EBPS) LARGELY DUE TO FUNDING AND POLICY BARRIERS, DESPITE REPRESENTING THE MOST VULNERABLE YOUTH ACROSS OUR GEOGRAPHIC CATCHMENT AREA (I.E., DISPROPORTIONATELY BLACK [10-79%] AND HISPANIC [33-68%] POPULATIONS, LOW SOCIOECONOMIC STATUS [18-40% BELOW POVERTY LINE], UNDERSERVED COMMUNITIES IN TERMS OF ACCESS TO CARE). HSCFS IS A LARGE, NON-PROFIT COMMUNITY MENTAL HEALTH CENTER LOCATED IN LOS ANGELES COUNTY (LAC), CALIFORNIA. HSCFS SERVES A HIGHLY DIVERSE YOUTH POPULATION, WITH 9 LOCATIONS SPANNING SIX OF THE EIGHT SERVICE AREAS ACROSS LAC. OUR RESIDENTIAL AND CBIPS SERVE MANY YOUTH WHO ARE INVOLVED IN CHILD WELFARE AND/OR JUVENILE JUSTICE SYSTEMS, AND THE DEGREE OF TRAUMA EXPOSURE AND GRIEF/LOSS EXPERIENCES IN THIS POPULATION IS SUBSTANTIAL AND REPRESENTS A SIGNIFICANT SERVICE GAP. THE PROPOSED PROJECT INCLUDES A SUSTAINABLE, TIERED PLAN FOR INCREASING AND IMPROVING IDENTIFICATION, ASSESSMENT, AND TREATMENT OF YOUTH IN OUR POPULATION OF NEED BY IMPLEMENTING (A) TRAUMA- AND GRIEF-FOCUSED SCREENING INSTRUMENTS, (B) COMPREHENSIVE ASSESSMENT MEASURES, (C) TWO TRAUMA- AND GRIEF-FOCUSED EBPS (TRAUMA AND GRIEF COMPONENT THERAPY FOR ADOLESCENTS [TGCT-A]; TRAUMA-FOCUSED COGNITIVE BEHAVIORAL THERAPY [TF-CBT]), (D) TRAINING FOR ALL STAFF ROLES ACROSS OUR RESIDENTIAL AND CBIPS IN TRAUMA-INFORMED CARE (TIC) FOUNDATIONAL MODELS TO DEVELOP SHARED, TRAUMA-INFORMED LANGUAGE, AWARENESS, AND CASE CONCEPTUALIZATION FOR DIRECT SERVICE. IN ADDITION, TECHNOLOGY-BASED TOOLS WILL ALSO BE DEVELOPED AND IMPLEMENTED TO ENHANCE IDENTIFICATION AND TRACKING EFFORTS OF YOUTH RECEIVING OUR SERVICES. PREDICTED MEASURABLE OUTCOMES INCLUDE (A) INCREASED IDENTIFICATION AND LINKAGES OF YOUTH WHO SCREEN POSITIVE FOR TRAUMA AND GRIEF/LOSS REACTIONS WITH COMPREHENSIVE TRAUMA AND GRIEF ASSESSMENTS, (B) INCREASED YOUTH ENROLLMENT IN TRAUMA- AND GRIEF-FOCUSED EBPS, (C) REDUCTION IN TRAUMATIC STRESS AND BEREAVEMENT SYMPTOMS AS MEASURED BY CLINICAL OUTCOME MEASURES, AND (D) IMPROVED ATTITUDES AND PRACTICES RELATED TO TIC ORGANIZATIONAL PRINCIPLES. APPROXIMATELY 755 UNDUPLICATED YOUTH WILL BE SERVED BY THE CONSTELLATION OF SERVICES INCLUDED IN THE PROPOSED PROJECT ACROSS THE LIFE OF THE GRANT.

INSTITUTE OF TEACHER EDUCATION AND DEVELOPMENT-TRANSFORMING INTO A MEMBERSHIP-BASED ORGANIZATION TO IMPACT EDUCATORS AND MARGINALIZED YOUTH ACROSS WEST AFRICA

MULTIFAMILY HOUSING SERVICE COORDINATORS

ANTIOXIDANT FUNCTIONALIZED POLYMERS FOR EXTENDED HD POLYMER ELECTROLYTE MEMBRANE LIFETIMES

PARTNERSHIPS IN AWARENESS: MENTAL HEALTH FIRST AID FOR COMMUNITIES - THE PROPOSED PROJECT, ENTITLED “PARTNERSHIPS IN AWARENESS: MENTAL HEALTH FIRST AID FOR COMMUNITIES,” IS FOCUSED ON PROVIDING TRAINING TO INCREASE MENTAL HEALTH AWARENESS, REDUCE STIGMA, AND CONNECT INDIVIDUALS WITH REFERRAL AND RESOURCE SUPPORTS. HATHAWAY-SYCAMORES CHILD AND FAMILY SERVICES (HSCFS) WILL OFFER MENTAL HEALTH FIRST AID (MHFA) TRAINING TO PREPARE FRONT LINE WORKERS, PARENTS, AND COMMUNITY MEMBERS TO ASSIST THOSE WITH MENTAL HEALTH NEEDS. HSCFS, A LARGE NON-PROFIT COMMUNITY MENTAL HEALTH CENTER LOCATED IN LOS ANGELES COUNTY, CALIFORNIA, WILL PROVIDE THE MHFA TRAININGS. THIS HIGHLY INTERACTIVE EVIDENCED-BASED PRACTICE WILL BE USED TO TARGET PARTICIPANT GROUPS MOST LIKELY TO HAVE CONTACT WITH INDIVIDUALS WHO MAY BE DEVELOPING A MENTAL HEALTH CONDITION OR ARE IN NEED OF MENTAL HEALTH SERVICES AND SUPPORT. HSCFS WILL PROVIDE MHFA TRAINING FOCUSED ON ADULTS TO FIRST RESPONDERS (LAW ENFORCEMENT, EMERGENCY MEDICAL TECHNICIANS, FIRE-FIGHTERS, ETC.) AND THOSE WORKING WITH OUR VETERAN POPULATION. YOUTH MENTAL HEALTH FIRST AID (YMHA), A CURRICULUM DEVELOPED TO ADDRESS MENTAL HEALTH WITH YOUTH WILL BE OFFERED TO SCHOOL PERSONNEL, PARENTS AND CAREGIVERS (RESOURCE PARENTS). TRAINING PARTICIPANTS WILL LEARN HOW TO RESPOND DURING A MENTAL HEALTH CRISIS, AND HOW TO ACCESS RESOURCES IN THEIR COMMUNITIES. THEY WILL LEARN TO RECOGNIZE MENTAL HEALTH DISORDERS; HOW TO INTERVENE WHEN IN CONTACT WITH A PERSON WITH MENTAL HEALTH SIGNS AND SYMPTOMS AND SUBSTANCE USE DISORDERS; AND HOW TO DE-ESCALATE A PERSON HAVING A MENTAL HEALTH CRISIS. PARTICIPANTS WILL DEVELOP AN UNDERSTANDING OF HOW TO FIND AND ACCESS RECOURSES SUCH AS REFERRAL LINKAGES, SUPPORT GROUPS, EDUCATIONAL RESOURCES, AND MENTAL HEALTH SERVICES. COMMUNITIES SERVED WILL INCLUDE UNDERSERVED AND REMOTE REGIONS THROUGHOUT THE STATE OF CALIFORNIA AND TO ORGANIZATIONS IN OTHER STATES THAT HAVE HAD LESS ACCESS TO MHFA/YMHFA TRAINING AND SUPPORT RESOURCES. REGIONS THAT ARE DENSELY POPULATED AND/OR HIGHLY UNDERSERVED DUE TO RACIAL, ETHNIC AND SOCIOECONOMIC DISPARITY WILL BE PRIORITIZED FOR THIS TRAINING OPPORTUNITY. FOR EXAMPLE, THE COUNTIES OF LOS ANGELES, RIVERSIDE, IMPERIAL, SAN BERNARDINO, ORANGE, TULARE, FRESNO, KINGS, KERN, SANTA BARBARA, MONTEREY, SAN MATEO, ALAMEDA, CONTRA COSTA, SANTA CRUZ, SAN JOAQUIN, MERCED, SACRAMENTO, AMADOR, HUMBOLDT, SAN LUIS OBISPO, YUBA, SISKIYOU, SHASTA, TEHAMA, EL NORTE, SIERRA, SAN DIEGO, BUTTE, SAN FRANCISCO, TRINITY, SAN BENITO, LASSEN, LAKE, SUTTER, INYO, MADERA, MARIN, MARIPOSA, MENDOCINO, MODOC, PLUMAS, SOLANO, EL DORADO, AND GLENN HAVE A HIGH RACIAL/ETHNIC MINORITY POPULATIONS AND ARE CONSIDERED MEDICALLY UNDERSERVED.1 WE WILL FOCUS MARKETING EFFORTS TOWARDS RECRUITING TRAINING PARTICIPANTS OUTSIDE OF CALIFORNIA AS WELL VIA VARIOUS PROFESSIONAL NETWORKS. THUS, THE GOALS OF THIS PROJECT ARE TO INCREASE THE NUMBER OF COMMUNITY PARTICIPANTS TRAINED IN MHFA (N = 364 IN YEAR 1 AND N = 494 IN EACH SUBSEQUENT GRANT YEAR), AND TO INCREASE PARTICIPANTS’ CAPACITY FOR IDENTIFYING COMMUNITY REFERRAL LINKAGES AND KNOWLEDGE FOLLOWING TRAINING.

AN IGF-1R-TARGETING PEPTIDE DRUG CONJUGATE FOR TARGETED TREATMENT OF ATYPICAL TERATOID/RHABDOID TUMORS - PROJECT SUMMARY ATYPICAL TERATOID/RHABDOID TUMORS (AT/RT) ARE RARE EMBRYONAL CENTRAL NERVOUS SYSTEM MALIGNANCIES THAT OCCUR IN EARLY CHILDHOOD AND ARE LETHAL. CURRENT TREATMENT STRATEGIES FOR CHILDREN DIAGNOSED WITH AT/RT ARE LIMITED TO SURGERY, RADIATION, AND CHEMOTHERAPY, BUT TO DATE, NONE OF THESE HAVE SUCCESSFULLY IMPROVED SURVIVAL BEYOND 18 MONTHS, AND MOST ARE ASSOCIATED WITH SIGNIFICANT TOXICITIES GIVEN THE YOUNG AGE OF PATIENTS. GENETIC INACTIVATION OF THE SWI/SNF CHROMATIN REMODELING COMPLEX UNDERLIES AT/RT TUMORIGENESIS; THUS, TARGETED THERAPIES THAT CAN CORRECT THE EPIGENETIC DYSREGULATION IN AT/RT PRESENT A COMPELLING THERAPEUTIC STRATEGY IF THESE AGENTS CAN BE SELECTIVELY DELIVERED TO TUMOR CELLS IN THE BRAIN. PEPTIDE-DRUG CONJUGATES (PDCS) ARE ONE TREATMENT MODALITY THAT CAN ACCOMPLISH THIS BY LINKING TARGET-SPECIFIC PEPTIDES TO STRONG CYTOTOXIC DRUGS TO ENHANCE SITE-SPECIFIC DELIVERY AND TUMOR-SPECIFIC THERAPEUTIC EFFECTS, WHILE LIMITING EXPOSURE OF THE DRUG TO HEALTHY SURROUNDING TISSUES. TO LEVERAGE THIS APPROACH FOR AT/RT, NIGHTHAWK BIOSCIENCES, INC. HAS DEVELOPED A PDC STRATEGY THAT COMBINES A NOVEL BINDING PEPTIDE (“429”) AGAINST THE INSULIN-LIKE GROWTH FACTOR 1 RECEPTOR (IGF-1R), WHICH IS HIGHLY EXPRESSED ON THE SURFACE OF AT/RT CELLS, WITH POTENT CYTOTOXIC DRUGS FOR TARGETED TREATMENT OF AT/RT. IN THIS PHASE I STTR, NIGHTHAWK WILL PARTNER WITH DR. NADIA DAHMANE’S LABORATORY AT WEILL CORNELL MEDICINE TO TEST TWO INVESTIGATIONAL ANTI-IGF-1R PDCS, ONE CONJUGATED TO THE ANTIMITOTIC TOXIN MONOMETHYL AURISTATIN E (MMAE), AND A SECOND CONJUGATED TO THE PAN-HDAC INHIBITOR PANOBINOSTAT, IN CELL AND ANIMAL MODELS OF AT/RT. IN PRELIMINARY STUDIES, ANTI-IGF-1R PDCS ARE EFFICACIOUS AGAINST IGF-1R-EXPRESSING AND AT/RT CELL LINES IN VITRO. FURTHER, A SINGLE INTRATUMORAL INJECTION OF 429-MMAE SIGNIFICANTLY REDUCED TUMOR VOLUMES FOLLOWING FLANK IMPLANTATION OF A431, AN IGF-1R-EXPRESSING EPITHELIAL CARCINOMA. TO VALIDATE THE POTENTIAL OF THIS APPROACH FOR AT/RT AND DEFINE THE OPTIMAL DRUG TO BE USED IN THE FINAL PDC FORMAT, WE PROPOSE TO EXAMINE ANTI-IGF-1R PDCS FOR THERAPEUTIC EFFICACY AGAINST HUMAN AT/RT CELLS AND IN AN IN VIVO ORTHOTOPIC TUMOR MODEL. IN AIM 1, ANTI-IGF-1R PDC CANDIDATES WILL BE TESTED AGAINST AN EXPANDED PANEL OF HUMAN AT/RT CELL LINES FOR EFFECTS ON CELL VIABILITY, APOPTOSIS, CYTOTOXICITY, AND CELL MIGRATION AND INVASION. IN AIM 2, SYSTEMIC (INTRAVENOUS) AND DIRECT (INTRATUMORAL) DRUG DELIVERY STRATEGIES WILL BE EXPLORED TO DEFINE DOSE-EXPOSURE RESPONSE RELATIONSHIPS AND TO DETERMINE THE MAXIMUM TOLERATED DOSE. AIM 3 WILL EVALUATE IN VIVO EFFICACY OF THE ANTI-IGF- 1R PDCS ON TUMOR INHIBITION AND SURVIVAL IN AN ESTABLISHED ORTHOTOPIC MOUSE MODEL OF AT/RT. WE EXPECT THAT COMPLETION OF THE PROPOSED AIMS WILL DETERMINE POTENTIAL FOR ACHIEVING THERAPEUTIC BENEFIT IN AT/RT AND IDENTIFY A LEAD PDC CANDIDATE TO ADVANCE TO IND-ENABLING STUDIES.

FY 2011 TRANSIT SECURITY GRANT PROGRAM

DEVELOPMENT OF ANTI-HUMAN TL1A MONOCLONAL ANTIBODY FOR THE TREATMENT OF HUMAN AST

REAP RENEWABLE ENERGY SYSTEM (RES) GRANT UNRESTRICTED AMOUNT

MICROFLUIDIC TECHNOLOGY PLATFORM AS A CONTINUOUS END-LINE PROCESS TO INACTIVATE PHARMACEUTICALS - PROJECT SUMMARY TO ACHIEVE THE FDA’S REQUIRED STERILITY ASSURANCE LEVEL FOR USE IN HUMANS, PHARMACEUTICAL PRODUCTS MUST UNDERGO TERMINAL STERILIZATION OR ASEPTIC MANUFACTURING. THIS CAN BE ACCOMPLISHED USING PHYSICAL OR CHEMICAL METHODS SUCH AS HEAT OR FORMALDEHYDE FOR SIMPLE DRUG FORMULATIONS; HOWEVER, FOR PHARMACEUTICAL PRODUCTS THAT HAVE MORE COMPLEX DRUG FORMULATIONS OR THAT CONTAIN BIOLOGICALLY ACTIVE MATERIAL IMPORTANT FOR DOWNSTREAM APPLICATIONS (CELL-CONTAINING THERAPEUTICS, VACCINES, ETC.), GAMMA IRRADIATION IS THE PREFERRED METHOD OF STERILIZATION. GAMMA IRRADIATION DESTROYS NUCLEIC ACIDS TO INACTIVATE PATHOGENS OR RENDER ANY CELLS REPLICATION INCOMPETENT BUT LEAVES STRUCTURAL COMPONENTS LIKE PROTEINS INTACT. THE LOGISTICAL CHALLENGES OF RELIANCE ON GAMMA IRRADIATION FOR TERMINAL STERILIZATION ARE, HOWEVER, SIGNIFICANT. GAMMA IRRADIATION REQUIRES HIGH DOSES OF RADIATION, NECESSITATING SIGNIFICANT REGULATORY RESTRICTIONS AND SPECIALIZED INFRASTRUCTURE, DRIVING UP COSTS AND PROCESSING TIMES TO MANUFACTURE A FINISHED DRUG. AS SUCH, FEW BIOMEDICAL RESEARCH AND PRODUCTION FACILITIES ARE ABLE TO ADOPT GAMMA-IRRADIATION PROCESSES IN-HOUSE TO EXPEDITE MANUFACTURING TIMELINES, AND THEY REMAIN RELIANT ON CENTRALIZED SHIELDED FACILITIES. LOW ENERGY ELECTRON IRRADIATION (LEEI) REPRESENTS A PRACTICAL AND INEXPENSIVE ALTERNATIVE TO GAMMA IRRADIATION; HOWEVER, A LOW PENETRATION DEPTH LIMITS ITS UTILITY FOR LIQUID SUSPENSIONS. TO OVERCOME THESE OBSTACLES, HEAT BIOLOGICS HAS PARTNERED WITH GEORGIA INSTITUTE OF TECHNOLOGY AND TEXAS A&M UNIVERSITY TO DEVELOP A MICROFLUIDICS-ENABLED IN-LINE CONTINUOUS PROCESS FOR HIGH-THROUGHPUT LEEI STERILIZATION OF PHARMACEUTICALS. THIS STRATEGY USES MICROFLUIDIC MANIFOLDS TO BRING A CONTINUOUSLY FLOWING PRODUCT INTO THE WORKING DEPTH OF AN LEEI BEAM AT A SUFFICIENT VOLUMETRIC FLOW RATE TO ALLOW FOR SCALING TO COMMERCIAL CAPACITY. SINCE THE PRODUCT IS TERMINALLY STERILIZED BY THIS PROCESS, IT ENABLES END-TO-END CONTROL AS AN ALTERNATIVE TO CENTRALIZED STERILIZATION AT A SHIELDED FACILITY. IN PRELIMINARY STUDIES, RAPID PROTOTYPING RESULTED IN THE DESIGN OF A CONSUMABLE CHIP MANIFOLD. COMPUTATIONAL MODELING FOLLOWED BY EXPERIMENTAL VALIDATION OF THE MICROFLUIDIC CHIP DESIGN DEMONSTRATED FLOW UNIFORMITY AND GOOD E-BEAM PENETRATION THROUGH THE CHANNELS WITHOUT COMPROMISING BIOLOGICAL MATERIAL. IN THIS PHASE I STTR PROJECT, THIS INTERDISCIPLINARY TEAM WILL FINALIZE THE MICROFLUIDICS DESIGN AND TEST THE PROTOTYPE SYSTEM IN TWO PHARMACEUTICAL CELL THERAPY PRODUCTS TO CONFIRM INACTIVATION EFFICIENCY AND ACTIVE AGENT BIOAVAILABILITY FOLLOWING IRRADIATION. A CONSUMABLE COMMERCIAL SET WILL BE BUILT TO ACHIEVE 30L/HOUR PROCESSING TO ENSURE THAT THE SYSTEM CAN BE APPROPRIATELY SCALED TO ACCOMMODATE COMMERCIAL SCALE PRODUCTION. COMPLETION OF THESE OBJECTIVES WILL VALIDATE A HIGH-THROUGHPUT MICROFLUIDICS DEVICE THAT WHEN COMBINED WITH E- BEAM IRRADIATION WILL PROVIDE STANDARD BIOLOGICAL RESEARCH AND PRODUCTION LABORATORIES WITH THE ABILITY TO PRODUCE AND IRRADIATE BIOLOGICALLY ACTIVE PHARMACEUTICAL PRODUCTS AT THE SITE OF MANUFACTURE.

RCDG - VALUE-ADDED PRODUCT MARKET DEVELOPMENT GRANTS

MENTAL HEALTH AND EMOTIONAL SUPPORT FOR CHILDREN OF THE TERMINALLY ILL.

PRIDE PROGRAM (PEER COACHING SAFETY IMPROVEMENT)

A NEXT GENERATION CROSS-SEROTYPE BINDING ANTITOXIN FOR TREATMENT OF POST-EXPOSURE BOTULINUM POISONING - PROJECT SUMMARY BOTULINUM POISONING IS A RARE NEUROTOXIN-MEDIATED SYNDROME THAT RESULTS IN PROGRESSIVE RESPIRATORY AND MUSCULAR PARALYSIS AND LEADS TO DEATH IF UNTREATED. AEROSOLIZED BOTULINUM NEUROTOXINS (BONT) ARE PARTICULARLY LETHAL AND OF MAJOR CONCERN AS POTENTIAL BIOLOGICAL WEAPONS. GIVEN THIS CONCERN, THE U.S. HAS STOCKPILED THE ONLY APPROVED ANTIDOTE FOR BONT POISONING, BAT®, TO BE USED IN CASE OF INTENTIONAL OR UNINTENTIONAL RELEASE OF INFECTIOUS BONT. BAT® CONSISTS OF A POLYCLONAL MIXTURE OF ANTIBODIES AGAINST BOTULINUM TOXIN TYPES A-G THAT IS DERIVED FROM EQUINE SERUM FOLLOWING A COMPLICATED AND TIME-CONSUMING MANUFACTURING PROCESS. WHILE EFFECTIVE IN ABSTRACTING BONT IN CIRCULATION, BAT® IS ASSOCIATED WITH A NUMBER OF PRIMARY SAFETY CONCERNS THAT LIMIT ITS USE TO PATIENTS WITH A CONFIRMED BOTULISM DIAGNOSIS. AS THE EARLIEST SYMPTOMS OF BOTULISM POISONING ARE NON-SPECIFIC, BAT® TREATMENT IS OFTEN ADMINISTERED WELL INTO THE DISEASE COURSE WHEN MANY PATIENTS REQUIRE ADDITIONAL AGGRESSIVE SUPPORTIVE CARE MEASURES SUCH AS MECHANICAL VENTILATION FOR SURVIVAL. AS SUCH, A NEXT GENERATION BONT ANTITOXIN THAT IS HUMAN-COMPATIBLE, CONFERS PROTECTION AGAINST MULTIPLE SEROTYPES, DEMONSTRATES RAPID CLEARANCE OF CIRCULATING TOXIN, AND CAN BE SAFELY ADMINISTERED AS AN EARLY INTERVENTION UPON SUSPICION OF BONT EXPOSURE IS CRITICALLY NEEDED TO REPLACE BAT®. TO ADDRESS THIS NEED, NIGHTHAWK BIOSCIENCES, INC. (NHB) IS DEVELOPING A MULTIVALENT BOTULINUM ANTITOXIN PRODUCT BASED ON THEIR NOVEL TERMINATOR TECHNOLOGY, WHICH SEQUESTERS TARGET PATHOGENS BY BINDING THEM TO CIRCULATING RED BLOOD CELLS (RBCS) VIA RECEPTOR TYPE I (CR1) AND DELIVERS THEM TO FIXED-TISSUE MACROPHAGES FOR ENGULFMENT. TO DATE, EXPERIMENTAL RESULTS INDICATE THAT THE TERMINATOR SYSTEM CAN BE USED TO INDUCE RBC IMMUNE ADHERENCE TO EFFECTIVELY REMOVE A VARIETY OF PATHOGENS FROM CIRCULATION, DRASTICALLY REDUCING THE BLOOD CONCENTRATION OF PATHOGENIC PARTICLES WITHIN MINUTES OF TREATMENT. CRITICALLY, TERMINATOR HAS DEMONSTRATED GOOD SAFETY AND TOLERABILITY IN HUMANS, POSITIONING IT POTENTIALLY AS A DRUG OF LOW REGRET THAT CAN BE SAFELY ADMINISTERED PRIOR TO CLINICAL CONFIRMATION OF DIAGNOSIS. IN THIS PHASE I SBIR, NHB WILL ADVANCE A TERMINATOR BONT ANTITOXIN CANDIDATE CONSISTING OF A UNIQUE ANTIBODY COMPLEX IN WHICH A HUMAN CR1 ANTIBODY IS FUSED TO AN ANTIBODY TARGETING THE BONT SEROTYPES ASSOCIATED WITH HUMAN DISEASE (A, B, E, AND F). TO ADEQUATELY DE-RISK THIS CANDIDATE FOR IND-ENABLING STUDIES, THIS PROPOSAL WILL 1) DEMONSTRATE SELECTIVE AND HIGH- AFFINITY CROSS-SEROTYPE BINDING AND SPECIFIC UPTAKE INTO MACROPHAGES; 2) DEFINE THE KINETICS OF TERMINATOR- MEDIATED CLEARANCE OF BONTS IN VIVO; AND 3) DEMONSTRATE EFFICACY TO PROTECT AGAINST BONT POISONING IN A POSTEXPOSURE MOUSE MODEL. PHASE II STUDIES WILL EXPAND EFFICACY EVALUATIONS INTO AEROSOL CHALLENGE MODELS AND INITIATE IND-ENABLING TOXICOLOGY AND DOSE-REFINING STUDIES.

CHANGE ATTITUDES AGAINST GIRLS AND WOMEN IN SECONDARY EDUCATION. IMPROVE CLASSROOM LEARNING/PROMOTE LEADERSHIP ROLES FOR FEMALE STUDENTS AND TEACHERS

ASSISTANCE TO FIREFIGHTERS GRANTS

SEC. 9007 REAP-ENERGY EFFICIENCY IMPROVEMENTS GRANTS (MAN)

SEC 9007 REAP-RENEW ENERGY SYSTEMS GRANTS, $20,000 OR LESS (MAN)

NORTH HOOPS CRK FISH SCREEN PROJECT

NORTH HOOPS CREEK FISH SCREEN PROJECT

RAIL AND TRANSIT SECURITY GRANT PROGRAM

A VISION OF AN ELECTROCHEMICAL CELL TO PRODUCE CLEAN TITANIUM