Oset Inc

DEVELOPMENT AND EVALUATION OF ROSETTE ARRAY TECHNOLOGY FOR HUMANNEURODEVELOPMENTAL TOXICITY SCREENING - PROJECT SUMMARY PRE-CLINICAL AND PRE-FIELD TOXICOLOGY TESTING OF NEW DRUGS AND CHEMICALS DOES NOT ROUTINELY INCLUDE DIRECT ASSESSMENT OF HUMAN DEVELOPMENTAL NEUROTOXICITY (DNT). CURRENT STANDARDS FOR DNT TESTING REQUIRE USE OF ANIMAL MODELS WITH LIMITED THROUGHPUT AND SIGNIFICANT DIFFERENCES FROM HUMAN CENTRAL NERVOUS SYSTEM (CNS) DEVELOPMENT. AS SUCH, MANY CHEMICAL PRODUCTS HAVE REQUIRED POST-APPROVAL (EPA/FDA) RESTRICTIONS OR CANCELLATIONS DUE TO HUMAN DNT. SUCH LIMITATIONS OF THE CURRENT REGULATORY DNT TESTING PARADIGM HAVE PROMPTED INCREASED INTEREST IN QUANTITATIVE HIGH-THROUGHPUT SCREENING (QHTS) USING HUMAN PLURIPOTENT STEM CELL (HPSC)-BASED APPROACHES. HERE, WE PROPOSE TO USE ROSETTE ARRAY (RA) TECHNOLOGY TO DEVELOP AN HPSC- DERIVED QHTS PLATFORM (I.E., QHTS-RAS) FOR EFFECTIVE AND EFFICIENT DNT TESTING. ROSETTE ARRAY TECHNOLOGY STANDARDIZES IN VITRO DERIVATION OF HUMAN NEURAL ROSETTES TISSUES THAT ARE MIMETIC OF TRANSVERSE SLICES OF THE HUMAN NEURAL TUBE, THE ANLAGE OF ALL CNS TISSUE. ALTHOUGH NEURAL ROSETTES ARE NOT AN EXACT RECAPITULATION OF IN VIVO PRIMARY NEURULATION, THEY EXHIBIT THE SAME CELL PHENOTYPES, TISSUE CYTOARCHITECTURE, AND ARE DERIVED USING MORPHOGENETIC SIGNALING PATHWAYS ENDOGENOUS TO THE IN VIVO NEURAL TUBE FORMATION PROCESS. ROSETTE ARRAYS ARE THE FIRST IN VITRO TECHNOLOGY TO ENABLE SPATIAL AND TEMPORAL CONTROL OF NEURAL ROSETTE EMERGENCE IN A MICROARRAY FORMAT. THIS ENABLES RAPID ASSESSMENT VIA MICROSCOPE IMAGE ANALYSIS. THIS HIGH-YIELD, STANDARDIZED GENERATION OF IN VITRO NEURAL TUBE ANALOGS ENABLES THE REPEATABILITY NECESSARY TO FEASIBLY INCORPORATE HPSC-BASED CNS MORPHOGENIC READOUTS INTO QUANTITATIVE HIGH-THROUGHPUT TOXICOLOGY SCREENING. THUS, WE HYPOTHESIZE THAT THE QHTS-RA PLATFORM COULD INCREASE THROUGHPUT AND ACCURACY OF HUMAN DNT RISK ASSESSMENT, ALLOWING CONSOLIDATION AND SCALE-UP OF COMMERCIAL DNT SCREENING. PHASE 1 AIMS WILL VALIDATE THE BROAD APPLICABILITY OF THE QHTS-RA PLATFORM, CONFIRMING COMPATIBILITY WITH HUMAN INDUCED PLURIPOTENT STEM CELL (HIPSC) LINES AND ESTABLISHING METHODS FOR AUTOMATED IMAGE ACQUISITION AND BATCH ANALYSIS. PHASE 2 AIMS TO VALIDATE ASSAY FITNESS WITH A 100 COMPOUND DNT REFERENCE LIBRARY SCREEN, IN WHICH AUTOMATED AI IMAGE ANALYSIS IS UTILIZED TO FURTHER INCREASE ACCURACY AND MAXIMIZE THROUGHPUT. IF SUCCESSFUL, THE RESULTING QHTS-RA PLATFORM COULD REPLACE MULTIPLE CURRENT DNT ASSAYS AND INCREASE CONFIDENCE IN TOXICOLOGICAL READOUTS RELEVANT TO OUTCOMES UNIQUE TO HUMAN PHYSIOLOGY. THUS, THE WORK PROPOSED HERE COULD HAVE A TRANSFORMATIVE EFFECT ON DNT RESEARCH, REGULATORY EFFORTS TO PREVENT DNT EXPOSURE, AND FUTURE TRANSLATABILITY OF HPSC-BASED ORGANOID MODELS FOR BROAD STUDY OF HUMAN DEVELOPMENT.

INTEGRATED COMMUNITY BASED HIV/AIDS CARE AND SUPPORT & PREVENTION PROJECT

IDENTIFICATION OF SMALL MOLECULES WITH PAN-ALPHAVIRUS BROAD SPECTRUM ANTIVIRAL ACTIVITY

ADVANCEMENT OF NOVEL SMALL MOLECULES FOR TREATMENT OF RABIES

TARGETING ENDOGENOUS RETROVIRUS GAG GENES FOR BIOMARKER DEVELOPMENT IN TYPE 1 DIABETES - PROJECT SUMMARY: APPROXIMATELY 5-8% OF THE GENOME CONSISTS OF REMNANTS OF ANCIENT RETROVIRUSES THAT WERE INTEGRATED INTO THE HOST GENOME THROUGH GERM LINE INFECTION. THESE RETROVIRUSES ARE KNOWN AS ENDOGENOUS RETROVIRUSES (ERVS). SOME ERV PROVIRUSES HAVE A COMPLETE OR PARTIAL GENOME STRUCTURE AND CAN PRODUCE VIRAL ANTIGENS AND PSEUDO-VIRUSES THAT INTERACT WITH THE IMMUNE SYSTEM. HUMAN ENDOGENOUS RETROVIRUSES (HERVS) HAVE BEEN LINKED TO AUTOIMMUNE DISEASES SUCH AS TYPE 1 DIABETES (T1D). IN OUR STUDY, WHICH FOCUSES ON THE RELATIONSHIP BETWEEN ERVS AND AUTOIMMUNITY USING DEEP SEQUENCING, WE UNEXPECTEDLY DISCOVERED A CONNECTION BETWEEN THE NUMBER OF SEQUENCE VARIANTS ENCODING AN OPEN READING FRAME (ORF) OF THE ERV GENE GAG AND DISEASE PROGRESSION IN BOTH A NON-OBESE DIABETIC (NOD) MOUSE MODEL AND HUMAN T1D PATIENTS. ABNORMAL SEQUENCE VARIANTS OF ERV GAG GENES COULD POTENTIALLY BE ASSOCIATED WITH INCREASED AUTOIMMUNE ACTIVATION. IN THIS STUDY, WE WILL USE DEEP SEQUENCING TO MEASURE THE GAG GENE VARIANTS WITH ORFS AS BIOMARKERS. THE EXPERIMENTS AIM TO FURTHER INVESTIGATE NOD MICE AND VARIOUS T1D-SUSCEPTIBLE AND -RESISTANT MOUSE STRAINS IN ORDER TO UNDERSTAND THE MECHANISM THAT REGULATES THE EXPRESSION OF THESE GENE VARIANTS. FURTHERMORE, WE WILL EXPAND THE STUDY ON T1D PATIENTS BY INCLUDING AUTOANTIBODY-NEGATIVE AND PREDIABETIC CONTROLS TO VALIDATE WHETHER THIS SEQUENCING-BASED BIOMARKER COULD BE USED TO SCREEN HIGH-RISK CHILDREN, STAGE PRE-DIABETIC PATIENTS, AND PREDICT THE ONSET OF DIABETES.

DEVELOPING A NOVEL THERAPEUTIC FOR TREATING TINNITUS

ISOLATION OF RAS-INHIBITORY MIRNA FROM A COMPLETE LIBRARY OF ARRAYED HUMAN MIRNA

REAP RENEWABLE ENERGY SYSTEM (RES) GRANT UNRESTRICTED AMOUNT

REAP RENEWABLE ENERGY SYSTEM (RES) GRANT UNRESTRICTED AMOUNT

THIS GRANT SUPPORTS THE COSTS INCURRED TO IMPLEMENT MEASURES TO RESPOND TO THE NOVEL CORONAVIRUS 2019 (COVID-19), WHICH MAY INCLUDE WORKPLACE SAFETY, MARKET PIVOTS, RETROFITTING FACILITIES, TRANSPORTATION, WORKER HOUSING, AND MEDICAL EXPENSES. IT PROVIDES NEEDED RELIEF TO THE FOOD PROCESSORS, DISTRIBUTORS, FARMERS MARKETS, AND PRODUCERS FOR THEIR COSTS INCURRED BETWEEN JANUARY 27, 2020, THE DATE UPON WHICH THE PUBLIC HEALTH EMERGENCY WAS DECLARED BY THE U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICE (HHS) UNDER SECTION 319 OF THE PUBLIC HEALTH SERVICE ACT, AND DECEMBER 31, 2021. BENEFICIARIES INCLUDE THE EMPLOYEES OF THE FOOD PROCESSORS, DISTRIBUTORS, FARMERS MARKETS, AND PRODUCERS.

COMMUNITY FACILITY GRANTS

COMMUNITY FACILITY GRANTS

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