86 research outputs found

    Interfacing and Verifying ALHAT Safe Precision Landing Systems with the Morpheus Vehicle

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    The NASA Autonomous precision Landing and Hazard Avoidance Technology (ALHAT) project developed a suite of prototype sensors to enable autonomous and safe precision landing of robotic or crewed vehicles under any terrain lighting conditions. Development of the ALHAT sensor suite was a cross-NASA effort, culminating in integration and testing on-board a variety of terrestrial vehicles toward infusion into future spaceflight applications. Terrestrial tests were conducted on specialized test gantries, moving trucks, helicopter flights, and a flight test onboard the NASA Morpheus free-flying, rocket-propulsive flight-test vehicle. To accomplish these tests, a tedious integration process was developed and followed, which included both command and telemetry interfacing, as well as sensor alignment and calibration verification to ensure valid test data to analyze ALHAT and Guidance, Navigation and Control (GNC) performance. This was especially true for the flight test campaign of ALHAT onboard Morpheus. For interfacing of ALHAT sensors to the Morpheus flight system, an adaptable command and telemetry architecture was developed to allow for the evolution of per-sensor Interface Control Design/Documents (ICDs). Additionally, individual-sensor and on-vehicle verification testing was developed to ensure functional operation of the ALHAT sensors onboard the vehicle, as well as precision-measurement validity for each ALHAT sensor when integrated within the Morpheus GNC system. This paper provides some insight into the interface development and the integrated-systems verification that were a part of the build-up toward success of the ALHAT and Morpheus flight test campaigns in 2014. These campaigns provided valuable performance data that is refining the path toward spaceflight infusion of the ALHAT sensor suite

    SLI-1 Cbl Inhibits the Engulfment of Apoptotic Cells in C. elegans through a Ligase-Independent Function

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    The engulfment of apoptotic cells is required for normal metazoan development and tissue remodeling. In Caenorhabditis elegans, two parallel and partially redundant conserved pathways act in cell-corpse engulfment. One pathway, which includes the small GTPase CED-10 Rac and the cytoskeletal regulator ABI-1, acts to rearrange the cytoskeleton of the engulfing cell. The CED-10 Rac pathway is also required for proper migration of the distal tip cells (DTCs) during the development of the C. elegans gonad. The second pathway includes the receptor tyrosine kinase CED-1 and might recruit membranes to extend the surface of the engulfing cell. Cbl, the mammalian homolog of the C. elegans E3 ubiquitin ligase and adaptor protein SLI-1, interacts with Rac and Abi2 and modulates the actin cytoskeleton, suggesting it might act in engulfment. Our genetic studies indicate that SLI-1 inhibits apoptotic cell engulfment and DTC migration independently of the CED-10 Rac and CED-1 pathways. We found that the RING finger domain of SLI-1 is not essential to rescue the effects of SLI-1 deletion on cell migration, suggesting that its role in this process is ubiquitin ligase-independent. We propose that SLI-1 opposes the engulfment of apoptotic cells via a previously unidentified pathway.National Cancer Institute (U.S.) (Award K08CA104890

    Anticoagulants and the Propagation Phase of Thrombin Generation

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    The view that clot time-based assays do not provide a sufficient assessment of an individual's hemostatic competence, especially in the context of anticoagulant therapy, has provoked a search for new metrics, with significant focus directed at techniques that define the propagation phase of thrombin generation. Here we use our deterministic mathematical model of tissue-factor initiated thrombin generation in combination with reconstructions using purified protein components to characterize how the interplay between anticoagulant mechanisms and variable composition of the coagulation proteome result in differential regulation of the propagation phase of thrombin generation. Thrombin parameters were extracted from computationally derived thrombin generation profiles generated using coagulation proteome factor data from warfarin-treated individuals (N = 54) and matching groups of control individuals (N = 37). A computational clot time prolongation value (cINR) was devised that correlated with their actual International Normalized Ratio (INR) values, with differences between individual INR and cINR values shown to derive from the insensitivity of the INR to tissue factor pathway inhibitor (TFPI). The analysis suggests that normal range variation in TFPI levels could be an important contributor to the failure of the INR to adequately reflect the anticoagulated state in some individuals. Warfarin-induced changes in thrombin propagation phase parameters were then compared to those induced by unfractionated heparin, fondaparinux, rivaroxaban, and a reversible thrombin inhibitor. Anticoagulants were assessed at concentrations yielding equivalent cINR values, with each anticoagulant evaluated using 32 unique coagulation proteome compositions. The analyses showed that no anticoagulant recapitulated all features of warfarin propagation phase dynamics; differences in propagation phase effects suggest that anticoagulants that selectively target fXa or thrombin may provoke fewer bleeding episodes. More generally, the study shows that computational modeling of the response of core elements of the coagulation proteome to a physiologically relevant tissue factor stimulus may improve the monitoring of a broad range of anticoagulants

    De novoCIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): A new member of the expanding family of pyrin-associated autoinflammatory diseases

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    Neonatal-onset multisystem inflammatory disease (NOMID; also known as chronic infantile neurologic, cutaneous, articular [CINCA] syndrome) is characterized by fever, chronic meningitis, uveitis, sensorineural hearing loss, urticarial skin rash, and a characteristic deforming arthropathy. We investigated whether patients with this disorder have mutations in CIAS1, the gene which causes Muckle-Wells syndrome and familial cold autoinflammatory syndrome, two dominantly inherited disorders with some similarities to NOMID/CINCA syndrome

    Measurements of top-quark pair differential cross-sections in the eμe\mu channel in pppp collisions at s=13\sqrt{s} = 13 TeV using the ATLAS detector

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    Search for single production of vector-like quarks decaying into Wb in pp collisions at s=8\sqrt{s} = 8 TeV with the ATLAS detector

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    Measurement of the W boson polarisation in ttˉt\bar{t} events from pp collisions at s\sqrt{s} = 8 TeV in the lepton + jets channel with ATLAS

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