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  • 1
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    Cardiac myosin activation: a potential therapeutic approach for systolic heart failure (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2011-03-19
    Description: Decreased cardiac contractility is a central feature of systolic heart failure. Existing drugs increase cardiac contractility indirectly through signaling cascades but are limited by their mechanism-related adverse effects. To avoid these limitations, we previously developed omecamtiv mecarbil, a small-molecule, direct activator of cardiac myosin. Here, we show that it binds to the myosin catalytic domain and operates by an allosteric mechanism to increase the transition rate of myosin into the strongly actin-bound force-generating state. Paradoxically, it inhibits adenosine 5'-triphosphate turnover in the absence of actin, which suggests that it stabilizes an actin-bound conformation of myosin. In animal models, omecamtiv mecarbil increases cardiac function by increasing the duration of ejection without changing the rates of contraction. Cardiac myosin activation may provide a new therapeutic approach for systolic heart failure.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4090309/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4090309/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Malik, Fady I -- Hartman, James J -- Elias, Kathleen A -- Morgan, Bradley P -- Rodriguez, Hector -- Brejc, Katjusa -- Anderson, Robert L -- Sueoka, Sandra H -- Lee, Kenneth H -- Finer, Jeffrey T -- Sakowicz, Roman -- Baliga, Ramesh -- Cox, David R -- Garard, Marc -- Godinez, Guillermo -- Kawas, Raja -- Kraynack, Erica -- Lenzi, David -- Lu, Pu Ping -- Muci, Alexander -- Niu, Congrong -- Qian, Xiangping -- Pierce, Daniel W -- Pokrovskii, Maria -- Suehiro, Ion -- Sylvester, Sheila -- Tochimoto, Todd -- Valdez, Corey -- Wang, Wenyue -- Katori, Tatsuo -- Kass, David A -- Shen, You-Tang -- Vatner, Stephen F -- Morgans, David J -- 1-R43-HL-66647-1/HL/NHLBI NIH HHS/ -- R01 HL106511/HL/NHLBI NIH HHS/ -- R43 HL066647/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2011 Mar 18;331(6023):1439-43. doi: 10.1126/science.1200113.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Preclinical Research and Development, Cytokinetics, Inc., South San Francisco, CA 94080, USA. fmalik@cytokinetics.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21415352" target="_blank"〉PubMed〈/a〉
    Keywords: Actin Cytoskeleton/metabolism ; Actins/metabolism ; Adenosine Triphosphatases/metabolism ; Adenosine Triphosphate/metabolism ; Adrenergic beta-Agonists/pharmacology ; Allosteric Regulation ; Animals ; Binding Sites ; Calcium/metabolism ; Cardiac Myosins/chemistry/*metabolism ; Cardiac Output/drug effects ; Dogs ; Female ; Heart Failure, Systolic/*drug therapy/physiopathology ; Isoproterenol/pharmacology ; Male ; Myocardial Contraction/*drug effects ; Myocytes, Cardiac/*drug effects/physiology ; Phosphates/metabolism ; Protein Binding ; Protein Conformation ; Protein Isoforms/chemistry/metabolism ; Rats ; Rats, Sprague-Dawley ; Urea/*analogs & derivatives/chemistry/metabolism/pharmacology ; Ventricular Function, Left/drug effects
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Control of facial muscle development by MyoR and capsulin (2002)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2002-12-21
    Description: Members of the MyoD family of basic helix-loop-helix (bHLH) transcription factors control the formation of all skeletal muscles in vertebrates, but little is known of the molecules or mechanisms that confer unique identities to different types of skeletal muscles. MyoR and capsulin are related bHLH transcription factors expressed in specific facial muscle precursors. We show that specific facial muscles are missing in mice lacking both MyoR and capsulin, reflecting the absence of MyoD family gene expression and ablation of the corresponding myogenic lineages. These findings identify MyoR and capsulin as unique transcription factors for the development of specific head muscles.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lu, Jian-Rong -- Bassel-Duby, Rhonda -- Hawkins, April -- Chang, Priscilla -- Valdez, Renee -- Wu, Hai -- Gan, Lin -- Shelton, John M -- Richardson, James A -- Olson, Eric N -- New York, N.Y. -- Science. 2002 Dec 20;298(5602):2378-81.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, University of Texas Southwestern Medical Center at Dallas, 6000 Harry Hines Boulevard, Dallas, TX 75390-9148, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12493912" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis ; Basic Helix-Loop-Helix Transcription Factors ; Branchial Region/embryology/metabolism ; Cell Lineage ; Cleft Palate/embryology ; Crosses, Genetic ; *DNA-Binding Proteins ; Facial Muscles/cytology/*embryology/growth & development ; Female ; Gene Expression Regulation, Developmental ; Gene Targeting ; Head ; Helix-Loop-Helix Motifs ; Hernia, Diaphragmatic/embryology ; Homozygote ; In Situ Nick-End Labeling ; Male ; Masticatory Muscles/cytology/*embryology/growth & development ; Mice ; Muscle Cells/cytology/physiology ; *Muscle Development ; Muscle Proteins/genetics/metabolism ; Muscle, Skeletal/embryology ; Mutation ; MyoD Protein/genetics/metabolism ; Myogenic Regulatory Factor 5 ; Phenotype ; *Trans-Activators ; Transcription Factors/genetics/*physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
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    NRROS negatively regulates reactive oxygen species during host defence and autoimmunity (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-04-18
    Description: Reactive oxygen species (ROS) produced by phagocytes are essential for host defence against bacterial and fungal infections. Individuals with defective ROS production machinery develop chronic granulomatous disease. Conversely, excessive ROS can cause collateral tissue damage during inflammatory processes and therefore needs to be tightly regulated. Here we describe a protein, we termed negative regulator of ROS (NRROS), which limits ROS generation by phagocytes during inflammatory responses. NRROS expression in phagocytes can be repressed by inflammatory signals. NRROS-deficient phagocytes produce increased ROS upon inflammatory challenges, and mice lacking NRROS in their phagocytes show enhanced bactericidal activity against Escherichia coli and Listeria monocytogenes. Conversely, these mice develop severe experimental autoimmune encephalomyelitis owing to oxidative tissue damage in the central nervous system. Mechanistically, NRROS is localized to the endoplasmic reticulum, where it directly interacts with nascent NOX2 (also known as gp91(phox) and encoded by Cybb) monomer, one of the membrane-bound subunits of the NADPH oxidase complex, and facilitates the degradation of NOX2 through the endoplasmic-reticulum-associated degradation pathway. Thus, NRROS provides a hitherto undefined mechanism for regulating ROS production--one that enables phagocytes to produce higher amounts of ROS, if required to control invading pathogens, while minimizing unwanted collateral tissue damage.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Noubade, Rajkumar -- Wong, Kit -- Ota, Naruhisa -- Rutz, Sascha -- Eidenschenk, Celine -- Valdez, Patricia A -- Ding, Jiabing -- Peng, Ivan -- Sebrell, Andrew -- Caplazi, Patrick -- DeVoss, Jason -- Soriano, Robert H -- Sai, Tao -- Lu, Rongze -- Modrusan, Zora -- Hackney, Jason -- Ouyang, Wenjun -- England -- Nature. 2014 May 8;509(7499):235-9. doi: 10.1038/nature13152. Epub 2014 Apr 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Immunology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA [2] Flexus Biosciences, 75 Shoreway Road, Suite D, San Carlos, California 94070, USA (R.N.); American Society for Biochemistry and Molecular Biology, 11200 Rockville Pike, Suite 302, Rockville, Maryland 20852, USA (P.A.V.). ; Department of Immunology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA. ; Department of Antibody Engineering, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA. ; Department of Pathology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA. ; Department of Molecular Biology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA. ; Department of Bioinformatics, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24739962" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autoimmunity/genetics ; Bone Marrow Cells/cytology ; Central Nervous System/metabolism/pathology ; Encephalomyelitis, Autoimmune, Experimental/*immunology/*metabolism/pathology ; Endoplasmic Reticulum/enzymology/metabolism ; Escherichia coli/*immunology ; Female ; Inflammation/immunology/metabolism/pathology ; Listeria monocytogenes/*immunology ; Macrophages/cytology/enzymology/immunology/metabolism ; Male ; Mice ; NADPH Oxidase/metabolism ; Oxidation-Reduction ; Oxidative Stress ; Phagocytes/cytology/immunology/metabolism ; Proteins/genetics/*metabolism ; Reactive Oxygen Species/*antagonists & inhibitors/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 4
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    Thin Film Catalyst Layers for Direct Methanol Fuel Cells (2000)
    In:  CASI
    Details
    Publication Date: 2013-08-31
    Description: One of the primary obstacles to the widespread use of the direct methanol fuel cell (DMFC) is the high cost of the catalyst. Therefore, reducing the catalyst loading well below the current level of 8-12 mg/cm 2 would be important to commercialization. The current methods for preparation of catalyst layers consisting of catalyst, ionomer and sometimes a hydrophobic additive are applied by either painting, spraying, decal transfer or screen printing processes. Sputter deposition is a coating technique widely used in manufacturing and therefore particularly attractive. In this study we have begun to explore sputtering as a method for catalyst deposition. Present experiments focus on Pt-Ru catalyst layers for the anode.
    Keywords: Energy Production and Conversion
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  • 5
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    Low Crossover Polymer Electrolyte Membranes for Direct Methanol Fuel Cells (1996)
    In:  CASI
    Details
    Publication Date: 2013-08-31
    Description: Direct Methanol Fuel Cells (DMFC's) using polymer electrolyte membranes are promising power sources for portable and vehicular applications. State of the art technology using Nafion(R) 117 membranes (Dupont) are limited by high methanol permeability and cost, resulting in reduced fuel cell efficiencies and impractical commercialization. Therefore, much research in the fuel cell field is focused on the preparation and testing of low crossover and cost efficient polymer electrolyte membranes. The University of Southern California in cooperation with the Jet Propulsion Laboratory is focused on development of such materials. Interpenetrating polymer networks are an effective method used to blend polymer systems without forming chemical links. They provide the ability to modify physical and chemical properties of polymers by optimizing blend compositions. We have developed a novel interpenetrating polymer network based on poly (vinyl - difluoride)/cross-linked polystyrenesulfonic acid polymer composites (PVDF PSSA). Sulfonation of polystyrene accounts for protonic conductivity while the non-polar, PVDF backbone provides structural integrity in addition to methanol rejection. Precursor materials were prepared and analyzed to characterize membrane crystallinity, stability and degree of interpenetration. USC JPL PVDF-PSSA membranes were also characterized to determine methanol permeability, protonic conductivity and sulfur distribution. Membranes were fabricated into membrane electrode assemblies (MEA) and tested for single cell performance. Tests include cell performance over a wide range of temperatures (20 C - 90 C) and cathode conditions (ambient Air/O2). Methanol crossover values are measured in situ using an in-line CO2 analyzer.
    Keywords: Energy Production and Conversion
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  • 6
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    A Hydraulic Motor-Alternator System for Ocean-Submersible Vehicles (2012)
    In:  Other Sources
    Details
    Publication Date: 2019-07-13
    Description: An ocean-submersible vehicle has been developed at JPL that moves back and forth between sea level and a depth of a few hundred meters. A liquid volumetric change at a pressure of 70 bars is created by means of thermal phase change. During vehicle ascent, the phase-change material (PCM) is melted by the circulation of warm water and thus pressure is increased. During vehicle descent, the PCM is cooled resulting in reduced pressure. This pressure change is used to generate electric power by means of a hydraulic pump that drives a permanent magnet (PM) alternator. The output energy of the alternator is stored in a rechargeable battery that powers an on-board computer, instrumentation and other peripherals.The focus of this paper is the performance evaluation of a specific hydraulic motor-alternator system. Experimental and theoretical efficiency data of the hydraulic motor and the alternator are presented. The results are used to evaluate the optimization of the hydraulic motor-alternator system. The integrated submersible vehicle was successfully operated in the Pacific Ocean near Hawaii. A brief overview of the actual test results is presented.
    Keywords: Electronics and Electrical Engineering
    Type: AIAA-IEEE International Energy Conversion Engineering Conference; Jul 30, 2012 - Aug 01, 2012; Atlanta, GA; United States
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  • 7
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    A Hydraulic-Alternator System for Ocean Submersible Vehicles (2012)
    In:  Other Sources
    Details
    Publication Date: 2019-07-13
    Description: No abstract available
    Keywords: Energy Production and Conversion
    Type: 10th International Energy Conversion Engineering Conference (IECEC), Atlanta, Georgia,July 30-1 August, 2012; Jul 30, 2012 - Aug 01, 2012; Atlanta, GA; United States|48th AIAA/ASME/SAE/ASEE Joint Propulsion Conference and Exhibit (JPC); Jul 30, 2012 - Aug 01, 2012; Atlanta, GA; United States
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  • 8
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    Power generation in fuel cells using liquid methanol and hydrogen peroxide (2002)
    In:  CASI
    Details
    Publication Date: 2019-08-15
    Description: The invention is directed to an encapsulated fuel cell including a methanol source that feeds liquid methanol (CH.sub.3 OH) to an anode. The anode is electrical communication with a load that provides electrical power. The fuel cell also includes a hydrogen peroxide source that feeds liquid hydrogen peroxide (H.sub.2 O.sub.2) to the cathode. The cathode is also in communication with the electrical load. The anode and cathode are in contact with and separated by a proton-conducting polymer electrolyte membrane.
    Keywords: Energy Production and Conversion
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  • 9
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    Pt-Ni and Pt-Co Catalyst Synthesis Route for Fuel Cell Applications (2013)
    In:  CASI
    Details
    Publication Date: 2019-07-12
    Description: Oxygen reduction reactions (ORRs) at the cathode are the rate-limiting step in fuel cell performance. The ORR is 100 times slower than the corresponding hydrogen oxidation at the anode. Speeding up the reaction at the cathode will improve fuel cell efficiency. The cathode material is generally Pt powder painted onto a substrate (e.g., graphite paper). Recent efforts in the fuel cell area have focused on replacing Pt with Pt-X alloys (where X = Co, Ni, Zr, etc.) in order to (a) reduce cost, and (b) increase ORR rates. One of these strategies is to increase ORR rates by reducing the powder size, which would result in an increase in the surface area, thereby facilitating faster reaction rates. In this work, a process has been developed that creates Pt-Ni or Pt-Co alloys that are finely divided (on the nano scale) and provide equivalent performance at lower Pt loadings. Lower Pt loadings will translate to lower cost. Precursor salts of the metals are dissolved in water and mixed. Next, the salt mixtures are dried on a hot plate. Finally, the dried salt mixture is heattreated in a furnace under flowing reducing gas. The catalyst powder is then used to fabricate a membrane electrode assembly (MEA) for electrochemical performance testing. The Pt- Co catalyst-based MEA showed comparable performance to an MEA fabri cated using a standard Pt black fuel cell catalyst. The main objective of this program has been to increase the overall efficiencies of fuel cell systems to support power for manned lunar bases. This work may also have an impact on terrestrial programs, possibly to support the effort to develop a carbon-free energy source. This catalyst can be used to fabricate high-efficiency fuel cell units that can be used in space as regenerative fuel cell systems, and terrestrially as primary fuel cells. Terrestrially, this technology will become increasingly important when transition to a hydrogen economy occurs.
    Keywords: Energy Production and Conversion
    Type: NPO-47885 , NASA Tech Briefs, May 2013; 17
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  • 10
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    Compact Fuel-Cell System Would Consume Neat Methanol (2007)
    In:  CASI
    Details
    Publication Date: 2019-07-12
    Description: In a proposed direct methanol fuel-cell electric-power-generating system, the fuel cells would consume neat methanol, in contradistinction to the dilute aqueous methanol solutions consumed in prior direct methanol fuel-cell systems. The design concept of the proposed fuel-cell system takes advantage of (1) electro-osmotic drag and diffusion processes to manage the flows of hydrogen and water between the anode and the cathode and (2) evaporative cooling for regulating temperature. The design concept provides for supplying enough water to the anodes to enable the use of neat methanol while ensuring conservation of water for the whole fuel-cell system.
    Keywords: Energy Production and Conversion
    Type: NPO-41661 , NASA Tech Briefs, June 2007; 25-27
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