817 research outputs found

    Ceramic applications in turbine engines

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    Development testing activities on the 1900 F-configuration ceramic parts were completed, 2070 F-configuration ceramic component rig and engine testing was initiated, and the conceptual design for the 2265 F-configuration engine was identified. Fabrication of the 2070 F-configuration ceramic parts continued, along with burner rig development testing of the 2070 F-configuration metal combustor in preparation for 1132 C (2070 F) qualification test conditions. Shakedown testing of the hot engine simulator (HES) rig was also completed in preparation for testing of a spin rig-qualified ceramic-bladed rotor assembly at 1132 C (2070 F) test conditions. Concurrently, ceramics from new sources and alternate materials continued to be evaluated, and fabrication of 2070 F-configuration ceramic component from these new sources continued. Cold spin testing of the critical 2070 F-configuration blade continued in the spin test rig to qualify a set of ceramic blades at 117% engine speed for the gasifier turbine rotor. Rig testing of the ceramic-bladed gasifier turbine rotor assembly at 108% engine speed was also performed, which resulted in the failure of one blade. The new three-piece hot seal with the nickel oxide/calcium fluoride wearface composition was qualified in the regenerator rig and introduced to engine operation wiwth marginal success

    Harmonic moment dynamics in Laplacian growth

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    Harmonic moments are integrals of integer powers of z = x+iy over a domain. Here the domain is an exterior of a bubble of air growing in an oil layer between two horizontal closely spaced plates. Harmonic moments are a natural basis for such Laplacian growth phenomena because, unlike other representations, these moments linearize the zero surface tension problem (Richardson, 1972), so that all moments except the lowest one are conserved in time. For non-zero surface tension, we show that the the harmonic moments decay in time rather than exhibiting the divergences of other representations. Our laboratory observations confirm the theoretical predictions and demonstrate that an interface dynamics description in terms of harmonic moments is physically realizable and robust. In addition, by extending the theory to include surface tension, we obtain from measurements of the time evolution of the harmonic moments a value for the surface tension that is within 20% of the accepted value.Comment: 10 pages, 7 figure

    Perforin gene transfer into hematopoietic stem cells improves immune dysregulation in murine models of perforin deficiency

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    Defects in perforin lead to the failure of T and NK cell cytotoxicity, hypercytokinemia, and the immune dysregulatory condition known as familial hemophagocytic lymphohistiocytosis (FHL). The only curative treatment is allogeneic hematopoietic stem cell transplantation which carries substantial risks. We used lentiviral vectors (LV) expressing the human perforin gene, under the transcriptional control of the ubiquitous phosphoglycerate kinase promoter or a lineage-specific perforin promoter, to correct the defect in different murine models. Following LV-mediated gene transfer into progenitor cells from perforin-deficient mice, we observed perforin expression in mature T and NK cells, and there was no evidence of progenitor cell toxicity when transplanted into irradiated recipients. The resulting perforin-reconstituted NK cells showed partial recovery of cytotoxicity, and we observed full recovery of cytotoxicity in polyclonal CD8 + T cells. Furthermore, reconstituted T cells with defined antigen specificity displayed normal cytotoxic function against peptide-loaded targets. Reconstituted CD8 + lymphoblasts had reduced interferon-γ secretion following stimulation in vitro, suggesting restoration of normal immune regulation. Finally, upon viral challenge, mice with >30% engraftment of gene-modified cells exhibited reduction of cytokine hypersecretion and cytopenias. This study demonstrates the potential of hematopoietic stem cell gene therapy as a curative treatment for perforin-deficient FHL

    A Process and Outcome Evaluation of a Shelter for Homeless Young Women

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    To evaluate the processes and outcomes of a short-term shelter, both quantitative and qualitative data were gathered via participant observation, focus group interviews with shelter staff and residents, and individual interviews with a sample of 40 young women who had been homeless prior to using the shelter. The process evaluation showed that the shelter staff strived to utilize an empowerment philosophy in their relationships with residents, but that there were many challenges to implementing this philosophy. The outcome evaluation showed that, at a 3-month follow-up, the participants reported significant improvements in housing, income, independence, and life satisfaction, but most continued to experience poverty and a number of other difficulties. The results were discussed in terms of the implications for future research and the value and limitations of shelters for dealing with homeless youth. The need for more sustained and comprehensive program interventions and supportive social policies was underscored

    Human Amniocytes Are Receptive to Chemically Induced Reprogramming to Pluripotency

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    Restoring pluripotency using chemical compounds alone would be a major step forward in developing clinical-grade pluripotent stem cells, but this has not yet been reported in human cells. We previously demonstrated that VPA_ AFS cells, human amniocytes cultivated with valproic acid (VPA) acquired functional pluripotency while remaining distinct from human embryonic stem cells (hESCs), questioning the relationship between the modulation of cell fate and molecular regulation of the pluripotency network. Here, we used single-cell analysis and functional assays to reveal that VPA treatment resulted in a homogeneous population of self-renewing non-transformed cells that fulfill the hallmarks of pluripotency, i.e., a short G1 phase, a dependence on glycolytic metabolism, expression of epigenetic modifications on histones 3 and 4, and reactivation of endogenous OCT4 and downstream targets at a lower level than that observed in hESCs. Mechanistic insights into the process of VPA-induced reprogramming revealed that it was dependent on OCT4 promoter activation, which was achieved independently of the PI3K (phosphatidylinositol 3-kinase)/ AKT/ mTOR (mammalian target of rapamycin) pathway or GSK3 beta inhibition but was concomitant with the presence of acetylated histones H3K9 and H3K56, which promote pluripotency. Our data identify, for the first time, the pluripotent transcriptional and molecular signature and metabolic status of human chemically induced pluripotent stem cells

    The fetal mouse is a sensitive genotoxicity model that exposes lentiviral-associated mutagenesis resulting in liver oncogenesis

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    This article is available open access through the publisher’s website at the link below. Copyright @ 2013 The American Society of Gene & Cell Therapy.Genotoxicity models are extremely important to assess retroviral vector biosafety before gene therapy. We have developed an in utero model that demonstrates that hepatocellular carcinoma (HCC) development is restricted to mice receiving nonprimate (np) lentiviral vectors (LV) and does not occur when a primate (p) LV is used regardless of woodchuck post-translation regulatory element (WPRE) mutations to prevent truncated X gene expression. Analysis of 839 npLV and 244 pLV integrations in the liver genomes of vector-treated mice revealed clear differences between vector insertions in gene dense regions and highly expressed genes, suggestive of vector preference for insertion or clonal outgrowth. In npLV-associated clonal tumors, 56% of insertions occurred in oncogenes or genes associated with oncogenesis or tumor suppression and surprisingly, most genes examined (11/12) had reduced expression as compared with control livers and tumors. Two examples of vector-inserted genes were the Park 7 oncogene and Uvrag tumor suppressor gene. Both these genes and their known interactive partners had differential expression profiles. Interactive partners were assigned to networks specific to liver disease and HCC via ingenuity pathway analysis. The fetal mouse model not only exposes the genotoxic potential of vectors intended for gene therapy but can also reveal genes associated with liver oncogenesis.Imperial College London, the Wellcome Trust, and Brunel University

    Radiation tolerance of GaAs1-xSbx solar cells

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    High radiation tolerance of GaAs1-xSbx based solar cells is demonstrated for the low-intensity-low-temperature (LILT) conditions of the target planets Saturn, Jupiter, and Mars. The GaAs1-xSbx-based cells are irradiated with high energy electrons to assess the effect of harsh radiation environment on the solar cell and the response of the cell is then investigated in terms of its photovoltaic operation. This system shows significant radiation resistance to the high energy electron environment for the conditions of the planets of interest. An unusual increase of the short circuit current after irradiation is observed at low temperature, which is supported by a simultaneous increase in the external quantum efficiency of the cell under the same conditions. The open circuit voltage and fill factor of the cell are especially tolerant to irradiation, which is also reflected in unchanged dark current-voltage characteristics of the solar cell upon irradiation particularly at LILT

    Inelastic Neutron Scattering Studies of \u3csup\u3e132,134\u3c/sup\u3eXe: Elucidating Structure in a Transitional Region and Possible Interferences for 0vββ Searches

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    Highly enriched (\u3e 99.9%) 132Xe and 134Xe gases were converted to solid 132XeF2 and 134XeF2 and were used as scattering samples for inelastic neutron scattering measurements at the University of Kentucky Accelerator Laboratory (UKAL). Lifetimes of levels up to 3.5MeV in excitation energy in these xenon isotopes were measured using the Doppler-shift attenuation method, allowing the determination of reduced transition probabilities. Gamma rays corresponding to new transitions and levels have been observed. In particular, tentative new excited 0+ states and associated decays have been examined in an effort to elucidate the structure of these nuclei in a transitional region, and comparisons have been drawn with models which seek to describe such nuclei, e.g., the E(5) critical-point symmetry of the IBM. Newly identified potential interferences for neutrinoless double-beta decay searches involving 136Xe are also discussed
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