620 research outputs found

    Operational cost drivers

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    To be economically viable, the operations cost of launch vehicles must be reduced by an order of magnitude as compared to the Space Transportation System (STS). A summary of propulsion-related operations cost drivers derived from a two-year study of Shuttle ground operations is presented. Examples are given of the inordinate time and cost of launch operations caused by propulsion systems designs that did not adequately consider impacts on prelaunching processing. Typical of these cost drivers are those caused by central hydraulic systems, storable propellants, gimballed engines, multiple propellants, He and N2 systems and purges, hard starts, high maintenance turbopumps, accessibility problems, and most significantly, the use of multiple, nonintegrated RCS, OMS, and main propulsion systems. Recovery and refurbishment of SRBs have resulted in expensive crash and salvage operations. Vehicle system designers are encouraged to be acutely aware of these cost drivers and to incorporate solutions (beginning with the design concepts) to avoid business as usual and costs as usual

    CIRCA 2000 operations criteria

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    The current Shuttle Program was used as a working model and certified data source in the identification of Space Transportation System (STS) operational cost drivers. Changes to flight hardware, processing methodologies, and identification of automation applications that would reduce costs were derived by reference to that data. The CIRCA 2000 Criteria were developed using these critical analyses of the on-going Shuttle Program. Several innovative suggestions are reviewed

    Paper Session IV-B - Design the Support rather than Support the Design

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    A major portion (73%) of the life cycle cost of the Space Shuttle is related to operations; this paper presents recommendations for reducing that cost. Operational cost drivers at the launch site are identified, based on an examination of Shuttle operational data collected over the past two and one half years. For decades, the launch vehicles of the Free World have been designed for performance, with very little attention given to consideration for support and/or maintainability. Examples are: multiple commodities; toxic materials; complexity; ordnance; inaccessibility; unique systems or components (lack of commonality and multiple function); Flight hardware designs drive Launch Site resources for: test operations to demonstrate hardware/software conformance to design parameters; test personnel—numbers and skill mix; ground support equipment; facilities; assembly; and maintenance. A case is made for incorporating support and maintainability criteria in the design process

    Three-dimensional microCT imaging of mouse development from early post-implantation to early postnatal stages

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    AbstractIn this work, we report the use of iodine-contrast microCT to perform high-throughput 3D morphological analysis of mouse embryos and neonates between embryonic day 8.5 to postnatal day 3, with high spatial resolution up to 3µm/voxel. We show that mouse embryos at early stages can be imaged either within extra embryonic tissues such as the yolk sac or the decidua without physically disturbing the embryos. This method enables a full, undisturbed analysis of embryo turning, allantois development, vitelline vessels remodeling, yolk sac and early placenta development, which provides increased insights into early embryonic lethality in mutant lines. Moreover, these methods are inexpensive, simple to learn and do not require substantial processing time, making them ideal for high throughput analysis of mouse mutants with embryonic and early postnatal lethality

    Expression of Distal-less, dachshund, and optomotor blind in Neanthes arenaceodentata (Annelida, Nereididae) does not support homology of appendage-forming mechanisms across the Bilateria

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    The similarity in the genetic regulation of arthropod and vertebrate appendage formation has been interpreted as the product of a plesiomorphic gene network that was primitively involved in bilaterian appendage development and co-opted to build appendages (in modern phyla) that are not historically related as structures. Data from lophotrochozoans are needed to clarify the pervasiveness of plesiomorphic appendage forming mechanisms. We assayed the expression of three arthropod and vertebrate limb gene orthologs, Distal-less (Dll), dachshund (dac), and optomotor blind (omb), in direct-developing juveniles of the polychaete Neanthes arenaceodentata. Parapodial Dll expression marks premorphogenetic notopodia and neuropodia, becoming restricted to the bases of notopodial cirri and to ventral portions of neuropodia. In outgrowing cephalic appendages, Dll activity is primarily restricted to proximal domains. Dll expression is also prominent in the brain. dac expression occurs in the brain, nerve cord ganglia, a pair of pharyngeal ganglia, presumed interneurons linking a pair of segmental nerves, and in newly differentiating mesoderm. Domains of omb expression include the brain, nerve cord ganglia, one pair of anterior cirri, presumed precursors of dorsal musculature, and the same pharyngeal ganglia and presumed interneurons that express dac. Contrary to their roles in outgrowing arthropod and vertebrate appendages, Dll, dac, and omb lack comparable expression in Neanthes appendages, implying independent evolution of annelid appendage development. We infer that parapodia and arthropodia are not structurally or mechanistically homologous (but their primordia might be), that Dll’s ancestral bilaterian function was in sensory and central nervous system differentiation, and that locomotory appendages possibly evolved from sensory outgrowths

    Somatic Variants in SVIL in Cerebral Aneurysms

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    Publisher Copyright: © American Academy of Neurology.Background and ObjectivesWhile somatic mutations have been well-studied in cancer, their roles in other complex traits are much less understood. Our goal is to identify somatic variants that may contribute to the formation of saccular cerebral aneurysms.MethodsWe performed whole-exome sequencing on aneurysm tissues and paired peripheral blood. RNA sequencing and the CRISPR/Cas9 system were then used to perform functional validation of our results.ResultsSomatic variants involved in supervillin (SVIL) or its regulation were found in 17% of aneurysm tissues. In the presence of a mutation in the SVIL gene, the expression level of SVIL was downregulated in the aneurysm tissue compared with normal control vessels. Downstream signaling pathways that were induced by knockdown of SVIL via the CRISPR/Cas9 system in vascular smooth muscle cells (vSMCs) were determined by evaluating changes in gene expression and protein kinase phosphorylation. We found that SVIL regulated the phenotypic modulation of vSMCs to the synthetic phenotype via Krüppel-like factor 4 and platelet-derived growth factor and affected cell migration of vSMCs via the RhoA/ROCK pathway.DiscussionWe propose that somatic variants form a novel mechanism for the development of cerebral aneurysms. Specifically, somatic variants in SVIL result in the phenotypic modulation of vSMCs, which increases the susceptibility to aneurysm formation. This finding suggests a new avenue for the therapeutic intervention and prevention of cerebral aneurysms.Peer reviewe
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