Test fixture design for boron-aluminum and beryllium test panels

A detailed description of the test fixture design and the backup analysis of the fixture assembly and its components are presented. The test fixture is required for the separate testing of two boron-aluminum and two beryllium compression panels. This report is presented in conjunction with a complete set of design drawings on the test fixture system

Evaluation of a Liquid Amine System for Spacecraft Carbon Dioxide Control

The analytical and experimental studies are described which were directed toward the acquisition of basic information on utilizing a liquid amine sorbent for in use in a CO2 removal system for manned spacecraft. Liquid amine systems are successfully used on submarines for control of CO2 generated by the crew, but liquid amines were not previously considered for spacecraft applications due to lack of development of satisfactory rotary phase separators. Developments in this area now make consideration of liquid amines practical for spacecraft system CO2 removal. The following major tasks were performed to evaluate liquid amine systems for spacecraft: (1) characterization, through testing, of the basic physical and thermodynamic properties of the amine solution; (2) determination of the dynamic characteristics of a cocurrent flow absorber; and (3) evaluation, synthesis, and selection of a liquid amine system concept oriented toward low power requirements. A low weight, low power system concept was developed. Numerical and graphical data are accompanied by pertinent observations

Size--sensitive melting characteristics of gallium clusters: Comparison of Experiment and Theory for Ga17+_{17}{}^{+} and Ga20+_{20}{}^{+}

Experiments and simulations have been performed to examine the finite-temperature behavior of Ga$_{17}{}^{+}$ and Ga$_{20}{}^{+}$ clusters. Specific heats and average collision cross sections have been measured as a function of temperature, and the results compared to simulations performed using first principles Density--Functional Molecular--Dynamics. The experimental results show that while Ga$_{17}{}^{+}$ apparently undergoes a solid--liquid transition without a significant peak in the specific--heat, Ga$_{20}{}^{+}$ melts with a relatively sharp peak. Our analysis of the computational results indicate a strong correlation between the ground--state geometry and the finite--temperature behavior of the cluster. If the ground--state geometry is symmetric and "ordered" the cluster is found to have a distinct peak in the specific--heat. However, if the ground--state geometry is amorphous or "disordered" the cluster melts without a peak in the specific--heat.Comment: 6 figure

Src Binds Cortactin Through An Sh2 Domain Cystine-Mediated Linkage

Tyrosine-kinase-based signal transduction mediated by modular protein domains is critical for cellular function. The Src homology (SH)2 domain is an important conductor of intracellular signaling that binds to phosphorylated tyrosines on acceptor proteins, producing molecular complexes responsible for signal relay. Cortactin is a cytoskeletal protein and tyrosine kinase substrate that regulates actin-based motility through interactions with SH2-domain-containing proteins. The Src kinase SH2 domain mediates cortactin binding and tyrosine phosphorylation, but how Src interacts with cortactin is unknown. Here we demonstrate that Src binds cortactin through cystine bonding between Src C185 in the SH2 domain within the phosphotyrosine binding pocket and cortactin C112/246 in the cortactin repeats domain, independent of tyrosine phosphorylation. Interaction studies show that the presence of reducing agents ablates Src-cortactin binding, eliminates cortactin phosphorylation by Src, and prevents Src SH2 domain binding to cortactin. Tandem MS/MS sequencing demonstrates cystine bond formation between Src C185 and cortactin C112/246. Mutational studies indicate that an intact cystine binding interface is required for Src-mediated cortactin phosphorylation, cell migration, and pre-invadopodia formation. Our results identify a novel phosphotyrosine-independent binding mode between the Src SH2 domain and cortactin. Besides Src, one quarter of all SH2 domains contain cysteines at or near the analogous Src C185 position. This provides a potential alternative mechanism to tyrosine phosphorylation for cysteine-containing SH2 domains to bind cognate ligands that may be widespread in propagating signals regulating diverse cellular functions

Proximal tubular cell–specific ablation of carnitine acetyltransferase causes tubular disease and secondary glomerulosclerosis

© 2019 by the American Diabetes Association. Proximal tubular epithelial cells are highly energy demanding. Their energy need is covered mostly from mitochondrial fatty acid oxidation. Whether derailments in fatty acid metabolism and mitochondrial dysfunction are forerunners of tubular damage has been suggested but is not entirely clear. Here we modeled mitochondrial overload by creating mice lacking the enzyme carnitine acetyltransferase (CrAT) in the proximal tubules, thus limiting a primary mechanism to export carbons under conditions of substrate excess. Mice developed tubular disease and, interestingly, secondary glomerulosclerosis. This was accompanied by increased levels of apoptosis regulator and fibrosis markers, increased oxidative stress, and abnormal profiles of acylcarnitines and organic acids suggesting profound impairments in all major forms of nutrient metabolism. When mice with CrAT deletion were fed a high-fat diet, kidney disease was more severe and developed faster. Primary proximal tubular cells isolated from the knockout mice displayed energy deficit and impaired respiration before the onset of pathology, suggesting mitochondrial respiratory abnormalities as a potential underlying mechanism. Our findings support the hypothesis that derailments of mitochondrial energy metabolism may be causative to chronic kidney disease. Our results also suggest that tubular injury may be a primary event followed by secondary glomerulosclerosis, raising the possibility that focusing on normalizing tubular cell mitochondrial function and energy balance could be an important preventative strategy

Evaluating how agent methodologies support the specification of the normative environment through the development process

[EN] Due to the increase in collaborative work and the decentralization of processes in many domains, there is an expanding demand for large-scale, flexible and adaptive software systems to support the interactions of people and institutions distributed in heterogeneous environments. Commonly, these software applications should follow specific regulations meaning the actors using them are bound by rights, duties and restrictions. Since this normative environment determines the final design of the software system, it should be considered as an important issue during the design of the system. Some agent-oriented software engineering methodologies deal with the development of normative systems (systems that have a normative environment) by integrating the analysis of the normative environment of a system in the development process. This paper analyses to what extent these methodologies support the analysis and formalisation of the normative environment and highlights some open issues of the topic.This work is partially supported by the PROMETEOII/2013/019, TIN2012-36586-C03-01, FP7-29493, TIN2011-27652-C03-00, CSD2007-00022 projects, and the CASES project within the 7th European Community Framework Program under the grant agreement No 294931.Garcia Marques, ME.; Miles, S.; Luck, M.; Giret Boggino, AS. (2014). Evaluating how agent methodologies support the specification of the normative environment through the development process. Autonomous Agents and Multi-Agent Systems. 1-20. https://doi.org/10.1007/s10458-014-9275-zS120Cossentino, M., Hilaire, V., Molesini, A., & Seidita, V. (Eds.). (2014). Handbook on agent-oriented design processes (Vol. VIII, 569 p. 508 illus.). Berlin: Springer.Akbari, O. (2010). A survey of agent-oriented software engineering paradigm: Towards its industrial acceptance. 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