64 research outputs found

    Geohydrologic Conditions at the Nuclear-fuels Reprocessing Plant and Waste-management Facilities at the Western New York Nuclear Service Center, Cattaraugus County, New York

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    A nuclear-fuel reprocessing plant, a high-level radioactive liquid-waste tank complex, and related waste facilities occupy 100 hectares (ha) within the Western New York Nuclear Service Center near West Valley, N.Y. The facilities are underlain by glacial and postglacial deposits that fill an ancestrial bedrock valley. The main plant facilities are on an elevated plateau referred to as the north plateau. Groundwater on the north plateau moves laterally within a surficial sand and gravel from the main plant building to areas northeast, east, and southeast of the facilities. The sand and gravel ranges from 1 to 10 m thick and has a hydraulic conductivity ranging from 0.1 to 7.9 m/day. Two separate burial grounds, a 4-ha area for low-level radioactive waste disposal and a 2.9-ha area for disposal of higher-level waste are excavated into a clay-rich till that ranges from 22 to 28 m thick. Migration of an organic solvent from the area of higher level waste at shallow depth in the till suggests that a shallow, fractured, oxidized, and weathered till is a significant pathway for lateral movement of groundwater. Below this zone, groundwater moves vertically downward through the till to recharge a lacustrine silt and fine sand. Within the saturated parts of the lacustrine unit, groundwater moves laterally to the northeast toward Buttermilk Creek. Hydraulic conductivity of the till, based on field and laboratory analyses , ranges from 0.000018 to 0.000086 m/day. (USGS

    Final Report of the AFIT Quality Initiative External Discovery Committee

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    This report summarizes the findings of the Air Force Institute of Technology’s (AFIT’s) Quality Initiative - External Discovery Team. The overarching purpose of the Quality Initiative is to create a detailed, executable investment strategy for modernizing AFIT’s instructional capabilities across five thrust areas. These activities were completed over the course of one year, beginning in June of 2016 and concluding in June of 2017. The data gathered were evaluated and several recommendations for further review were decided upon by the External Discovery Team. The following report briefly covers those recommendations and provides sources from which the recommendations were gleaned. These recommendations are meant to serve as a baseline for ways in which AFIT could begin to program resources to help improve teaching and instruction across the institution as a whole. The data presented here are meant to serve as a compliment to the Internal Discovery Team’s report that focuses on data and feedback gathered from institutions internal to AFIT

    Pluralism about Knowledge

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    In this paper I consider the prospects for pluralism about knowledge, that is, the view that there is a plurality of knowledge relations. After a brief overview of some views that entail a sort of pluralism about knowledge, I focus on a particular kind of knowledge pluralism I call standards pluralism. Put roughly, standards pluralism is the view that one never knows anything simpliciter. Rather, one knows by this-or-that epistemic standard. Because there is a plurality of epistemic standards, there is a plurality of knowledge relations. In §1 I argue that one can construct an impressive case for standards pluralism. In §2 I clarify the relationship between standards pluralism, epistemic contextualism and epistemic relativism. In §3 I argue that standards pluralism faces a serious objection. The gist of the objection is that standards pluralism is incompatible with plausible claims about the normative role of knowledge. In §4 I finish by sketching the form that a standards pluralist response to this objection might take

    Type inference in flexible model-driven engineering using classification algorithms

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    Flexible or bottom-up model-driven engineering (MDE) is an emerging approach to domain and systems modelling. Domain experts, who have detailed domain knowledge, typically lack the technical expertise to transfer this knowledge using traditional MDE tools. Flexible MDE approaches tackle this challenge by promoting the use of simple drawing tools to increase the involvement of domain experts in the language definition process. In such approaches, no metamodel is created upfront, but instead the process starts with the definition of example models that will be used to infer the metamodel. Pre-defined metamodels created by MDE experts may miss important concepts of the domain and thus restrict their expressiveness. However, the lack of a metamodel, that encodes the semantics of conforming models has some drawbacks, among others that of having models with elements that are unintentionally left untyped. In this paper, we propose the use of classification algorithms to help with the inference of such untyped elements. We evaluate the proposed approach in a number of random generated example models from various domains. The correct type prediction varies from 23 to 100% depending on the domain, the proportion of elements that were left untyped and the prediction algorithm used

    Interleukin-22 Protects Intestinal Stem Cells from Immune-Mediated Tissue Damage and Regulates Sensitivity to Graft versus Host Disease

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    SummaryLittle is known about the maintenance of intestinal stem cells (ISCs) and progenitors during immune-mediated tissue damage or about the susceptibility of transplant recipients to tissue damage mediated by the donor immune system during graft versus host disease (GVHD). We demonstrate here that deficiency of recipient-derived IL-22 increased acute GVHD tissue damage and mortality, that ISCs were eliminated during GVHD, and that ISCs as well as their downstream progenitors expressed the IL-22 receptor. Intestinal IL-22 was produced after bone marrow transplant by IL-23-responsive innate lymphoid cells (ILCs) from the transplant recipients, and intestinal IL-22 increased in response to pretransplant conditioning. However, ILC frequency and IL-22 amounts were decreased by GVHD. Recipient IL-22 deficiency led to increased crypt apoptosis, depletion of ISCs, and loss of epithelial integrity. Our findings reveal IL-22 as a critical regulator of tissue sensitivity to GVHD and a protective factor for ISCs during inflammatory intestinal damage

    A comprehensive candidate gene approach identifies genetic variation associated with osteosarcoma

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    <p>Abstract</p> <p>Background</p> <p>Osteosarcoma (OS) is a bone malignancy which occurs primarily in adolescents. Since it occurs during a period of rapid growth, genes important in bone formation and growth are plausible modifiers of risk. Genes involved in DNA repair and ribosomal function may contribute to OS pathogenesis, because they maintain the integrity of critical cellular processes. We evaluated these hypotheses in an OS association study of genes from growth/hormone, bone formation, DNA repair, and ribosomal pathways.</p> <p>Methods</p> <p>We evaluated 4836 tag-SNPs across 255 candidate genes in 96 OS cases and 1426 controls. Logistic regression models were used to estimate the odds ratios (OR) and 95% confidence intervals (CI).</p> <p>Results</p> <p>Twelve SNPs in growth or DNA repair genes were significantly associated with OS after Bonferroni correction. Four SNPs in the DNA repair gene <it>FANCM </it>(ORs 1.9-2.0, <it>P </it>= 0.003-0.004) and 2 SNPs downstream of the growth hormone gene <it>GH1 </it>(OR 1.6, <it>P </it>= 0.002; OR 0.5, <it>P </it>= 0.0009) were significantly associated with OS. One SNP in the region of each of the following genes was significant: <it>MDM2</it>, <it>MPG</it>, <it>FGF2</it>, <it>FGFR3</it>, <it>GNRH2</it>, and <it>IGF1</it>.</p> <p>Conclusions</p> <p>Our results suggest that several SNPs in biologically plausible pathways are associated with OS. Larger studies are required to confirm our findings.</p

    Ceacam1 separates graft-versus-host-disease from graft-versus-tumor activity after experimental allogeneic bone marrow transplantation.

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    BACKGROUND: Allogeneic bone marrow transplantation (allo-BMT) is a potentially curative therapy for a variety of hematologic diseases, but benefits, including graft-versus-tumor (GVT) activity are limited by graft-versus-host-disease (GVHD). Carcinoembryonic antigen related cell adhesion molecule 1 (Ceacam1) is a transmembrane glycoprotein found on epithelium, T cells, and many tumors. It regulates a variety of physiologic and pathological processes such as tumor biology, leukocyte activation, and energy homeostasis. Previous studies suggest that Ceacam1 negatively regulates inflammation in inflammatory bowel disease models. METHODS: We studied Ceacam1 as a regulator of GVHD and GVT after allogeneic bone marrow transplantation (allo-BMT) in mouse models. In vivo, Ceacam1(-/-) T cells caused increased GVHD mortality and GVHD of the colon, and greater numbers of donor T cells were positive for activation markers (CD25(hi), CD62L(lo)). Additionally, Ceacam1(-/-) CD8 T cells had greater expression of the gut-trafficking integrin α(4)β(7), though both CD4 and CD8 T cells were found increased numbers in the gut post-transplant. Ceacam1(-/-) recipients also experienced increased GVHD mortality and GVHD of the colon, and alloreactive T cells displayed increased activation. Additionally, Ceacam1(-/-) mice had increased mortality and decreased numbers of regenerating small intestinal crypts upon radiation exposure. Conversely, Ceacam1-overexpressing T cells caused attenuated target-organ and systemic GVHD, which correlated with decreased donor T cell numbers in target tissues, and mortality. Finally, graft-versus-tumor survival in a Ceacam1(+) lymphoma model was improved in animals receiving Ceacam1(-/-) vs. control T cells. CONCLUSIONS: We conclude that Ceacam1 regulates T cell activation, GVHD target organ damage, and numbers of donor T cells in lymphoid organs and GVHD target tissues. In recipients of allo-BMT, Ceacam1 may also regulate tissue radiosensitivity. Because of its expression on both the donor graft and host tissues, this suggests that targeting Ceacam1 may represent a potent strategy for the regulation of GVHD and GVT after allogeneic transplantation

    Promotion of avian endothelial cell differentiation by GATA transcription factors

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    AbstractIn the avian embryo, endothelial cells originate from several sources, including the lateral plate and somite mesoderm. In this study, we show that Gata transcription factors are expressed in the lateral plate and in vasculogenic regions of the avian somite and are able to promote a vascular endothelial fate when ectopically expressed in somite precursors. A fusion of GATA4 to the transcriptional activator VP16 promoted endothelium formation, indicating that GATA transcription factors promote vasculogenesis via activation of downstream targets, while a fusion of GATA4 to the transcriptional repressor engrailed repressed expression of Vascular Endothelial Growth Factor Receptor 2, a marker of endothelial precursors. These findings indicate a role for GATA transcription factors in the differentiation of the endothelium
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