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38,696 grants matching “als”
Development of antibody-based cancer therapies
$1,073,044Mitchell Ho · Division Of Basic Sciences - Nci · ZIA · FY2015 · CA
LIQUID WATER IS ESSENTIAL TO LIFE ON EARTH; HOWEVER MOST PLANETS AND MOONS IN OUR SOLAR SYSTEM HAVE SURFACE TEMPERATURES WELL BELOW THE FREEZING POINT OF PURE WATER. EUROPA ENCELADUS CERES TITAN AND OTHER ICY BODIES ARE TARGETS FOR ASTROBIOLOGICAL INVESTIGATION. MARS IS PRESENTLY COLD AND DRY BUT ORBITAL OBSERVATIONS HAVE IDENTIFIED FLOWING LIQUID WATER AND THERE IS ABUNDANT EVIDENCE FOR PAST HABITABLE ENVIRONMENTS. EARTH MAY ALSO HAVE UNDERGONE A SERIES OF GLOBAL GLACIATIONS (SNOWBALL EARTH EVENTS) IN ITS EARLY HISTORY. THE ABUNDANCE OF ICY CONDITIONS IN OUR SOLAR SYSTEM SUGGESTS THAT LIFE IN FROZEN ENVIRONMENTS MAY PROVIDE ANSWERS TO QUESTIONS ABOUT THE ORIGIN EVOLUTION AND ULTIMATE FATE OF MICROBIAL CELLS AND THEIR BIOSIGNATURES. BACTERIA THAT ARE GROWING METABOLICALLY ACTIVE AND/OR SURVIVING IN THE PRESENCE OF ICE MAY HAVE CHARACTERISTICS THAT REFLECT THE EVOLUTION AND NATURE OF PRIMITIVE LIFE. THESE BACTERIA ARE INTERESTING TO ASTROBIOLOGY POLAR ECOLOGY AND CRYOPRESERVATION BUT THEIR ABILITY TO FUNCTION AT TEMPERATURES BELOW -5 DEG C IS POORLY UNDERSTOOD. WE HAVE RECENTLY SHOWN THAT THE MARINE PSYCHROPHILE COLWELLIA PSYCHRERYTHRAEA STR. 34H [CP34H] HAS DISTINCT SHIFTS IN PROTEIN EXPRESSION AND METABOLIC ACTIVITY AT -10 DEG C USING PROTEOMIC MASS SPECTROMETRY (NUNN ET AL. 2015). PRELIMINARY WORK IN OUR LABORATORIES REVEAL THAT THIS ORGANISM IS CAPABLE OF GROWING IN NUTRIENT BROTH WITH MARS ANALOG BRINE CONTAINING PERCHLORATE. THE OBJECTIVES OF THE PROPOSED RESEARCH ARE TO: 1) DEVISE THREE LOW-TEMPERATURE LIQUID-WATER ENVIRONMENTS THAT MIMIC THE KNOWN CHEMISTRY OF BRINES: I) IN SEA ICE ON MODERN EARTH II) ON SNOWBALL EARTH AND III) ON MARS; 2) MEASURE MICROBIAL GROWTH RATE METABOLIC ACTIVITY ABILITY TO SURVIVE WHILE INACTIVE AND LONGEVITY FOR PSYCHROPHILES IN THESE THREE ENVIRONMENTS; 3) REVEAL PROTEOMIC BIOSIGNATURES FOR GROWTH ACTIVITY AND SURVIVAL STRATEGIES AND UNDERSTAND KEY MOLECULAR RESPONSES OF LIFE IN THESE THREE ENVIRONMENTS. METHODOLOGY: WE PROPOSE A 3-YEAR PROJECT TO PERFORM NOVEL PROTEOMIC EXAMINATIONS ON A SUITE OF THREE PSYCHROPHILES (CP34H PSYCHROBACTER SP. STR. 7E AND A MODEL HALOPHILE) HELD FOR 12 MONTHS AT SUBZERO TEMPERATURES (-1 -5 -10 -30 -50 AND -70 DEG C; REPRESENTATIVE OF ICE ABOVE AND BELOW THE EUTECTIC OF SEAWATER AND PUTATIVE MARS BRINES) IN COMPARISON TO OPTIMAL GROWTH TEMPERATURE BENCHMARK DATA (8 DEG C). BACTERIA WILL BE INTRODUCED TO SAMPLES REPRESENTATIVE OF MODERN SEA ICE COLD SEA ICE HYPOTHESIZED TO OCCUR ON SNOWBALL EARTH AND ICE ON MARS. WE WILL SPIKE CULTURES WITH 3H-LEUCINE 3H-THYMIDINE OR 13C-LEUCINE INCUBATED AT SPECIFIED TEMPERATURES AND SAMPLE THROUGH TIME TO TRACK METABOLIC ACTIVITIES VIABILITY CELL DEATH AND PROTEOME CHANGES. WE EXPECT THAT NOVEL 13C-LEUCINE TRACKING AND GLOBAL PROTEOME RESPONSE QUANTIFICATIONS USING MASS SPECTROMETRY WILL ALLOW FOR THE IDENTIFICATION AND MONITORING OF INDIVIDUAL NEWLY SYNTHESIZED PROTEINS AND WILL PROVIDE DOMINANT BIOMARKERS FOR GROWTH AND/OR SURVIVAL. THIS RESEARCH HAS VALUE TO UPCOMING SPACE-EXPLORATION LIFE DETECTION MISSIONS. IDENTIFICATION OF PROTEINS NEWLY SYNTHESIZED IN LOWT EMPERATURE ENVIRONMENTS OR PROTEINS INDICATIVE OF LONG-TERM ICE SURVIVAL WILL PROVIDE BIOSIGNATURES TO TARGET WHEN EXPLORING LIFE IN LOW-TEMPERATURE ECOSYSTEMS RELEVANT TO FUTURE EXPLORATION. IN ADDITION UNDERSTANDING KEY METABOLIC STRATEGIES FOR LONG-TERM SURVIVAL IN ICE WILL PROVIDE CLUES ON EARLY EVOLUTION AND SURVIVAL OF LIFE AS EARTH UNDERWENT EXTENSIVE GLACIATION DURING THE NEOPROTEROZOIC ERA. THIS PROPOSAL DIRECTLY ADDRESSES THE GOALS OF ROSES 2017 AND THE NASA EXOBIOLOGY PROGRAM SOLICITATION TO ADDRESS "THE POTENTIAL FOR THE ORIGIN AND ESTABLISHMENT OF LIFE UNDER CONDITIONS PREVAILING ON OTHER PLANETARY BODIES AND BASIC RESEARCH ON THE FORMATION AND RETENTION OF BIOSIGNATURES UNDER NON-EARTH CONDITIONS."
$1,072,454University Of Washington · · FY2020 · National Aeronautics and Space Administration
Optimization of sigma-2 receptor modulators for the treatment of cognitive dysfunction
$1,072,222Nicholas John Izzo · Cognition Therapeutics, Inc. · R42 · FY2019 · AG
Walking forward - American Indian Participation in Cancer Clinical Trials
$1,072,142Daniel G Petereit · Rapid City Regional Hospital · U54 · FY2011 · CA
Osteoarthritis: Prevention and Treatment
$1,071,918Thomas S Buchanan · University Of Delaware · P30 · FY2013 · GM
PREVENT PRECLINICAL EFFICACY AND INTERMEDIATE BIOMARKER ENDPOINTS TASK ORDER: USE OF CARNOSIC ACID AND VIVOX40 FOR BREAST CANCER PREVENTION
$1,071,582Alex Lyubimov · University Of Illinois At Chicago · N01 · FY2020 · CA
Genetic and environmental risk factors in mestizos and indigenous populations of Peru: the role of Native component in Alzheimer's disease
$1,070,706Giuseppe Tosto · Columbia University Health Sciences · R56 · FY2020 · AG
NICOTINIC CHOLINERGIC SYSTEMS IN MUTANT MICE
$1,068,990Baylor College Of Medicine · P01 · FY2001 · DA
A NOVEL THERAPEUTIC TARGET FOR WIDE-SPECTRUM ANTIPROTEOTOXICITY EFFECTS IN ALS
$1,068,719The Johns Hopkins University · · FY2019 · Department of the Army
Mitochondrial Integrated Stress Response in Neurological Diseases
$1,068,698Giovanni Manfredi · Weill Medical Coll Of Cornell Univ · R35 · FY2024 · NS
Chromatin Remodeling and Gene Activation
$1,067,447David J Clark · Eunice Kennedy Shriver National Institute Of Child Health & Human Development · ZIA · FY2013 · HD
Regulation and functional effects of localized RNAs
$1,067,188Stavroula Mili · Division Of Basic Sciences - Nci · ZIA · FY2014 · CA
Genetically Engineered Mouse Models to Study RTK Function in Melanoma
$1,066,926Glenn T. Merlino · Division Of Basic Sciences - Nci · ZIA · FY2013 · CA
Red Cell Biology
$1,066,618David M. Bodine · National Human Genome Research Institute · ZIA · FY2022 · HG
Hematopoietic Stem Cell Biology
$1,066,618David M. Bodine · National Human Genome Research Institute · ZIA · FY2022 · HG
Behavioral Health Collaborative for Rural American Indian Communities
$1,066,543Sterling M McPherson · Washington State University · P20 · FY2016 · MD
Role of IKK alpha in lung cancer development
$1,066,264Yinling Hu · Division Of Basic Sciences - Nci · ZIA · FY2025 · CA
Molecular Mechanisms of SOD1-linked ALS (P01)
$1,065,987Joan S Valentine · University Of California Los Angeles · P01 · FY2010 · NS
Regulation of Differentiation of Pediatric Embryonal Tumors- Neuroblastoma
$1,065,881Carol Thiele-Galetto · Division Of Basic Sciences - Nci · ZIA · FY2018 · CA
WE PROPOSE TO DEVELOP APERIODIC MULTILAYER COATINGS HAVING HIGH REFLECTANCE AT NORMAL INCIDENCE OVER A BROAD SPECTRAL BAND IN THE EXTREME ULTRAVIOLET (EUV) FOR SPECTROSCOPY OF THE SOLAR ATMOSPHERE. THE SPECTRAL REGION FROM APPROXIMATELY 17 NM TO 35 NM CONTAINS A NUMBER OF SCIENTIFICALLY IMPORTANT EMISSION LINES EMANATING FROM THE SOLAR CORONA AND TRANSITION REGION. THE REALIZATION OF BROADBAND EUV MULTILAYER COATINGS HAVING HIGH REFLECTANCE OVER ALL OR PART OF THIS BAND WILL ENABLE THE CONSTRUCTION OF HIGH-RESOLUTION SPECTROMETERS BASED ON NORMAL-INCIDENCE GRATINGS HAVING WIDE WAVELENGTH COVERAGE AND SENSITIVITY THAT IS SUFFICIENT TO SUPPORT THE EXPOSURE TIMES AND CADENCES NEEDED FOR FUTURE NASA SOLAR PHYSICS AND SPACE WEATHER MISSIONS. THE HINODE/EIS INSTRUMENT TARGETED THE SPECTRAL BAND FROM 25 NM TO 29 NM USING A NORMAL-INCIDENCE GRATING COATED WITH A PERIODIC SI/MO MULTILAYER. APERIODIC COATINGS DEVELOPED IN RECENT YEARS CAN NOW BE DESIGNED TO PROVIDE HIGH REFLECTANCE OVER A MUCH WIDER RANGE OF WAVELENGTHS. FURTHERMORE NEWLY DEVELOPED MG- AND AL-BASED MULTILAYER COATINGS HAVE BEEN DEMONSTRATED TO HAVE SIGNIFICANTLY HIGHER REFLECTANCE THAN SI/ MO MULTILAYERS IN THIS SPECTRAL REGION. WE THUS PROPOSE TO DEVELOP NEW MG- AND AL-BASED APERIODIC MULTILAYERS HAVING NEARLY FLAT RESPONSE OVER A MUCH WIDER WAVELENGTH BAND THAN CAN BE CAPTURED USING PERIODIC MULTILAYERS THEREBY ENABLING SIGNIFICANT INCREASES IN WAVELENGTH COVERAGE IN FUTURE SPECTROSCOPY INSTRUMENTS. THE PROPOSED RESEARCH WILL FOCUS ON SEVERAL NEW MG- AND AL-BASED MULTILAYER MATERIAL SYSTEMS THAT HAVE BEEN DEVELOPED OVER THE PAST DECADE INCLUDING THE THREE-MATERIAL SYSTEMS ZR/CO/MG SIC/MO/AL AND B4C/MO/AL. GOOD EUV PERFORMANCE AND STABILITY HAVE BEEN DEMONSTRATED ALREADY WITH PERIODIC (I.E. NARROW-BAND) COATINGS COMPRISING EACH OF THESE MATERIAL COMBINATIONS. WE WILL DEVELOP APERIODIC BROAD-BAND COATINGS USING THE SAME MATERIAL COMBINATIONS FOLLOWING A SYSTEMATIC EXPERIMENTAL WORK PLAN. CANDIDATE COATINGS WILL BE DEPOSITED BY MAGNETRON SPUTTERING AND COATING MICROSTRUCTURE STRESS ROUGHNESS EUV REFLECTANCE STABILITY AND OTHER RELEVANT PROPERTIES WILL BE FULLY CHARACTERIZED. THE EXPERIMENTAL WORK WILL BE CONDUCTED USING ESTABLISHED FACILITIES AND METHODS AND A SYSTEMATIC ITERATIVE APPROACH WILL BE FOLLOWED TO OPTIMIZE COATING PERFORMANCE. THE ANTICIPATED OUTCOME OF THE PROPOSED RESEARCH IS THE REALIZATION OF NEW BROAD-BAND MULTILAYER COATINGS OPERATING IN THE 17 35 NM BAND THAT WILL ENABLE THE CONSTRUCTION OF HIGH RESOLUTION SPECTROSCOPY INSTRUMENTS TARGETING THIS REGION OF THE EUV IN SUPPORT OF FUTURE NASA MISSIONS.
$1,065,004Reflective X-Ray Optics, Llc · · FY2020 · National Aeronautics and Space Administration
Molecular interception and immunological characterization of age-associated disease
$1,064,798Mark M Davis · Stanford University · P01 · FY2022 · AI
Cannabinoid CB1 and CB2 receptors and drug abuse
$1,064,560Zheng-Xiong Xi · National Institute On Drug Abuse · ZIA · FY2025 · DA
Molecular interception and immunological characterization of age-associated disease
$1,063,964Mark M Davis · Stanford University · P01 · FY2025 · AI
Regulation of Osteoblast Differentiation by Delta FosB
$1,063,933Roland E Baron · Harvard Medical School · R01 · FY2009 · AR
Interventional approaches for restoring vision
$1,063,252Anand Swaroop · National Eye Institute · ZIA · FY2017 · EY