3,285 research outputs found

    A study to determine the optimum design of a photographic film for the lunar surface hand-held camera Final report

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    Design, and processing of photographic film for lunar surface hand operated camer

    Tuning of antigen sensitivity by T cell receptor-dependent negative feedback controls T cell effector function inflammed tissues

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    Activated T cells must mediate effector responses sufficient to clear pathogens while avoiding excessive tissue damage. Here we have combined dynamic intravital microscopy with ex vivo assessments of T cell cytokine responses to generate a detailed spatiotemporal picture of CD4+ T cell effector regulation in the skin. In response to antigen, effector T cells arrested transiently on antigen presenting cells, briefly producing cytokine and then resuming migration. Antigen recognition led to PD-1 upregulation of the programmed death-1 (PD-1) glycoprotein by T cells and blocking its canonical ligand, programmed death-ligand 1 (PD-L1), lengthened the duration of migration arrest and cytokine production, showing that PD-1 interaction with PD-L1 is a major negative feedback regulator of antigen responsiveness. We speculate that the immune system employs a mechanism involving T cell recruitment, transient activation, and rapid desensitization, allowing the T cell response to rapidly adjust to changes in antigen presentation and minimize collateral injury to the host

    Targeting protein–protein interactions within the cyclic AMP signaling system as a therapeutic strategy for cardiovascular disease

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    The cAMP signaling system can trigger precise physiological cellular responses that depend on the fidelity of many protein–protein interactions, which act to bring together signaling intermediates at defined locations within cells. In the heart, cAMP participates in the fine control of excitation–contraction coupling, hence, any disregulation of this signaling cascade can lead to cardiac disease. Due to the ubiquitous nature of the cAMP pathway, general inhibitors of cAMP signaling proteins such as PKA, EPAC and PDEs would act non-specifically and universally, increasing the likelihood of serious ‘off target’ effects. Recent advances in the discovery of peptides and small molecules that disrupt the protein–protein interactions that underpin cellular targeting of cAMP signaling proteins are described and discussed

    Aerospace Medicine and Biology: A continuing bibliography with indexes, supplement 144

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    This bibliography lists 257 reports, articles, and other documents introduced into the NASA scientific and technical information system in July 1975

    The Desensitization Gating of the MthK K+ Channel Is Governed by Its Cytoplasmic Amino Terminus

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    The RCK-containing MthK channel undergoes two inactivation processes: activation-coupled desensitization and acid-induced inactivation. The acid inactivation is mediated by the C-terminal RCK domain assembly. Here, we report that the desensitization gating is governed by a desensitization domain (DD) of the cytoplasmic N-terminal 17 residues. Deletion of DD completely removes the desensitization, and the process can be fully restored by a synthetic DD peptide added in trans. Mutagenesis analyses reveal a sequence-specific determinant for desensitization within the initial hydrophobic segment of DD. Proton nuclear magnetic resonance (1H NMR) spectroscopy analyses with synthetic peptides and isolated RCK show interactions between the two terminal domains. Additionally, we show that deletion of DD does not affect the acid-induced inactivation, indicating that the two inactivation processes are mutually independent. Our results demonstrate that the short N-terminal DD of MthK functions as a complete moveable module responsible for the desensitization. Its interaction with the C-terminal RCK domain may play a role in the gating process

    State feedback control of power system oscillations

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    Damping of electromechanical oscillations in power systems is one of the major concerns in the operation of power system since many years. The oscillations may be local to a single generator or generator plant (local oscillations), or they may involve a number of generators widely separated geographically (inter-area oscillations). These oscillations causes improper of the power system incorporating losses. Local oscillations often occur when a fast exciter is used on the generator, and to stabilize these oscillations, Power System Stabilizers (PSS) were developed. Inter-area oscillations may appear as the systems loading is increased across the weak transmission links in the system which characterize these oscillations. If not controlled, these oscillations may lead to total or partial power interruption. Electricité de France developed two state feedback controllers aiming to effectively damp electromechanical oscillations present in power systems. These are Desensitized Four Loop Regulator (DFLR) and Extended Desensitized Four Loop Regulator (EDFLR). The DFLR is designed to damp local lectromechanical oscillations while the EDFLR aims at damping both local and inter-area oscillations. The dynamics of the DFLR and EDLFR are needed to be studies in order to model them. These models are to be incorporated with the generator models to get a power system model with state feedback control. On simulating the system in Simulink with the controllers we will get the power system model with state feedback control and we can observe how these controllers are helpful in damping the oscillations

    You are your Metadata: Identification and Obfuscation of Social Media Users using Metadata Information

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    Metadata are associated to most of the information we produce in our daily interactions and communication in the digital world. Yet, surprisingly, metadata are often still catergorized as non-sensitive. Indeed, in the past, researchers and practitioners have mainly focused on the problem of the identification of a user from the content of a message. In this paper, we use Twitter as a case study to quantify the uniqueness of the association between metadata and user identity and to understand the effectiveness of potential obfuscation strategies. More specifically, we analyze atomic fields in the metadata and systematically combine them in an effort to classify new tweets as belonging to an account using different machine learning algorithms of increasing complexity. We demonstrate that through the application of a supervised learning algorithm, we are able to identify any user in a group of 10,000 with approximately 96.7% accuracy. Moreover, if we broaden the scope of our search and consider the 10 most likely candidates we increase the accuracy of the model to 99.22%. We also found that data obfuscation is hard and ineffective for this type of data: even after perturbing 60% of the training data, it is still possible to classify users with an accuracy higher than 95%. These results have strong implications in terms of the design of metadata obfuscation strategies, for example for data set release, not only for Twitter, but, more generally, for most social media platforms.Comment: 11 pages, 13 figures. Published in the Proceedings of the 12th International AAAI Conference on Web and Social Media (ICWSM 2018). June 2018. Stanford, CA, US

    Aerospace medicine and biology: A continuing bibliography with indexes (supplement 341)

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    This bibliography lists 133 reports, articles and other documents introduced into the NASA Scientific and Technical Information System during September 1990. Subject coverage includes: aerospace medicine and psychology, life support systems and controlled environments, safety equipment, exobiology and extraterrestrial life, and flight crew behavior and performance

    Molecular Rearrangements of the Extracellular Vestibule in NMDAR Channels during Gating

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    AbstractMany N-methyl-D-aspartate receptor (NMDAR) channel blockers that have therapeutic potential can be trapped in the closed state. Using a combination of the substituted cysteine accessibility method and open channel blockers, we found that the M3 segment forms the core of the extracellular vestibule, including a deep site for trapping blockers. The M3 segment, as well as more superficial parts of the extracellular vestibule, undergo extensive remodeling during channel closure, but do not define the activation gate, which is located deeper in the pore. Rather, the pore walls lining the extracellular vestibule constrict during channel closure. This movement is essential for coupling ligand binding to activation gate opening and accounts for the different mechanisms of open channel block, including trapping
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