369 research outputs found

    Identifying Operations Research Systems Analysts\u27 Technical Competencies: A Delphi Approach

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    After the attacks of September 11, 2011, the demands for more agile, adaptive, critical-thinking, and multi-talented U.S. Army Operations Research Systems Analysts (FA49s) have only increased. Tomorrow\u27s joint operating environment demands U.S. Army FA49s to be ingenious, proactive, and multi-talented; proficient in their core competencies as military leaders as well as being proficient in their technical competencies as problem solvers in the operations research field. The purpose of this study was to identify the technical competencies and knowledge, skills, and abilities (KSAs) required for future U.S. Army FA49s to perform their duties within the joint operating environment of the next twenty-five years. To identify these technical competencies and KSAs, this study employed a qualitative research design with a quantitative component using a conventional, web-assisted Delphi methodology. The Delphi study engaged 10 experts through a first round of data gathering through a web-based questionnaire. First round data was synthesized and sent to the experts, seeking consensus, during a subsequent second round. Expert consensus was achieved on the second round, precluding the need for subsequent rounds to reach consensus. The study resulted in the experts\u27 identification and consensus on 5 technical competencies, 21 areas of knowledge, 41 skills, and 22 abilities that are required for future U.S. Army FA49s to perform their duties within the joint operating environment of the next twenty-five years. This research made four significant contributions to the engineering management discipline. First, it has added to the existing body of knowledge in engineering management theory and methodology by presenting and substantiating that a Delphi process is capable of identifying future and/or forecasting requirements. Second, it contributed to the literature by providing a basis for the expansion of the domain of competencies and KSAs for operations research. Third, this research contributed to the identification of competencies and KSAs that are germane to the practical development of military FA49 educational curricula and may be germane to the practical development of engineering management curricula. Fourth, this research has suggested directions for future research to enhance understanding of the competencies, knowledge, skills, and abilities for the operations research field

    EphrinB/EphB Signaling Controls Embryonic Germ Layer Separation by Contact-Induced Cell Detachment

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    Tissue boundary formation in the early vertebrate embryo involves cycles of cell attachment and detachment at the boundary, and cell contact-dependent signaling by membrane-bound EphB receptors and ephrinB ligands

    Gulp1 controls Eph/ephrin trogocytosis and is important for cell rearrangements during development

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    Trogocytosis, in which cells nibble away parts of neighboring cells, is an intercellular cannibalism process conserved from protozoa to mammals. Its underlying molecular mechanisms are not well understood and are likely distinct from phagocytosis, a process that clears entire cells. Bi-directional contact repulsion induced by Eph/ephrin signaling involves transfer of membrane patches and full-length Eph/ephrin protein complexes between opposing cells, resembling trogocytosis. Here, we show that the phagocytic adaptor protein Gulp1 regulates EphB/ephrinB trogocytosis to achieve efficient cell rearrangements of cultured cells and during embryonic development. Gulp1 mediates trogocytosis bi-directionally by dynamic engagement with EphB/ephrinB protein clusters in cooperation with the Rac-specific guanine nucleotide exchange factor Tiam2. Ultimately, Gulp1's presence at the Eph/ephrin cluster is a prerequisite for recruiting the endocytic GTPase dynamin. These results suggest that EphB/ephrinB trogocytosis, unlike other trogocytosis events, uses a phagocytosis-like mechanism to achieve efficient membrane scission and engulfment

    Cell Movement patterns during gastrulation in the chick are controlled by positive and negative chemotaxis mediated by FGF4 and FGF8

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    AbstractDuring gastrulation in amniotes, epiblast cells ingress through the primitive streak and migrate away to form endodermal, mesodermal, and extraembryonic structures. Here we analyze the detailed movement trajectories of cells emerging at different anterior-posterior positions from the primitive streak, using in vivo imaging of the movement of GFP-tagged streak cells. Cells emerging at different anterior-posterior positions from the streak show characteristic cell migration patterns, in response to guidance signals from neighboring tissues. Streak cells are attracted by sources of FGF4 and repelled by sources of FGF8. The observed movement patterns of anterior streak cells can be explained by an FGF8-mediated chemorepulsion of cells away from the streak followed by chemoattraction toward an FGF4 signal produced by the forming notochord

    Integrin α5β1 Function Is Regulated by XGIPC/kermit2 Mediated Endocytosis during Xenopus laevis Gastrulation

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    During Xenopus gastrulation α5β1 integrin function is modulated in a temporally and spatially restricted manner, however, the regulatory mechanisms behind this regulation remain uncharacterized. Here we report that XGIPC/kermit2 binds to the cytoplasmic domain of the α5 subunit and regulates the activity of α5β1 integrin. The interaction of kermit2 with α5β1 is essential for fibronectin (FN) matrix assembly during the early stages of gastrulation. We further demonstrate that kermit2 regulates α5β1 integrin endocytosis downstream of activin signaling. Inhibition of kermit2 function impairs cell migration but not adhesion to FN substrates indicating that integrin recycling is essential for mesoderm cell migration. Furthermore, we find that the α5β1 integrin is colocalized with kermit2 and Rab 21 in embryonic and XTC cells. These data support a model where region specific mesoderm induction acts through kermit2 to regulate the temporally and spatially restricted changes in adhesive properties of the α5β1 integrin through receptor endocytosis

    Frizzled-7 is required for Xenopus heart development

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    Wnt signalling regulates cardiogenesis during specification of heart tissue and the morphogenetic movements necessary to form the linear heart. Wnt11 mediated non-canonical signalling promotes early cardiac development whilst Wnt11-R, which is expressed later, also signals through the non-canonical pathway to promote heart development. It is unclear which Frizzleds mediate these interactions. Frizzled-7 (fzd7) is expressed during gastrulation in the mesodermal cells fated to become heart and then in the primary heart field. This expression is complementary to the expression of wnt11 and wnt11-R We further show co-localisation of fzd7 with other early and late heart-specific markers using double in situ hybridisation. We have used loss of function analysis to determine the role of fzd7 during heart development. Morpholino antisense oligonucleotide-mediated knockdown of Fzd7 results in effects on heart development, similar to that caused by Wnt11 loss of function. Surprisingly, overexpression of dominant-negative Fzd7 cysteine rich domain (Fzd7 CRD) results in a cardia bifida phenotype, similar to the loss of wnt11-R phenotype. Overexpression of Fzd7 and activation of non-canonical wnt signalling can rescue the effect of Fzd7 CRD. We propose that Fzd7 has an important role during Xenopus heart development

    A New Austrian Regionalism : Alfons Walde and Austrian Identity in Painting after 1918

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    This essay assesses the role of regionalism in interwar Austrian painting with a focus on the Tyrolean painter and architect Alfons Walde (1891–1958). At a time when painting was seen to be in crisis, eclipsed by the deaths of prominent Viennese artists such as Gustav Klimt and Egon Schiele, regionalism offered an alternative engagement with modern art. As the representative of a wider regionalist movement, Walde paved the way for a clearly identifiable image of rural Austria without foregoing the modernization process that took place in the Alps at the time. Filtering essential elements of local culture and synthesizing them with both a modern formal language and “modern” topics, most significantly ski tourism, he created a regionalism that reverberated beyond the narrow confines of his home province and caught particular momentum during the rise of the Austrian Ständestaat in the 1930s. Moving in between regional and national significance, Walde's work underlines the essential position of the region in Austria after 1918 and conveys that an engaged regionalism that responded to the rapid cultural and political changes taking place became a significant aspect of interwar Austrian painting

    Wnt expression is not correlated with β-catenin dysregulation in Dupuytren's Disease

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    BACKGROUND: Dupuytren's contracture or disease (DD) is a fibro-proliferative disease of the hand that results in finger flexion contractures. Increased cellular β-catenin levels have been identified as characteristic of this disease. As Wnts are the most widely recognized upstream regulators of cellular β-catenin accumulation, we have examined Wnt gene expression in surgical specimens and in DD-derived primary cell cultures grown in two-dimensional monolayer culture or in three-dimensional FPCL collagen lattice cultures. RESULTS: The Wnt expression profile of patient-matched DD and unaffected control palmar fascia tissue was determined by a variety of complimentary methods; Affymetrix Microarray analysis, specific Wnt and degenerative primer-based Reverse Transcriptase (RT)-PCR, and Real Time PCR. Microarray analysis identified 13 Wnts associated with DD and control tissues. Degenerate Wnt RT-PCR analysis identified Wnts 10b and 11, and to a lesser extent 5a and 9a, as the major Wnt family members expressed in our patient samples. Competitive RT-PCR analysis identified significant differences between the levels of expression of Wnts 9a, 10b and 11 in tissue samples and in primary cell cultures grown as monolayer or in FPCL, where the mRNA levels in tissue > FPCL cultures > monolayer cultures. Real Time PCR data confirmed the down-regulation of Wnt 11 mRNA in DD while Wnt 10b, the most frequently isolated Wnt in DD and control palmar fascia, displayed widely variable expression between the methods of analysis. CONCLUSION: These data indicate that changes in Wnt expression per se are unlikely to be the cause of the observed dysregulation of β-catenin expression in DD

    Gene expression analysis in human osteoblasts exposed to dexamethasone identifies altered developmental pathways as putative drivers of osteoporosis

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    BACKGROUND: Osteoporosis, a disease of decreased bone mineral density represents a significant and growing burden in the western world. Aging population structure and therapeutic use of glucocorticoids have contributed in no small way to the increase in the incidence of this disease. Despite substantial investigative efforts over the last number of years the exact molecular mechanism underpinning the initiation and progression of osteoporosis remain to be elucidated. This has meant that no significant advances in therapeutic strategies have emerged, with joint replacement surgery being the mainstay of treatment. METHODS: In this study we have used an integrated genomics profiling and computational biology based strategy to identify the key osteoblast genes and gene clusters whose expression is altered in response to dexamethasone exposure. Primary human osteoblasts were exposed to dexamethasone in vitro and microarray based transcriptome profiling completed. RESULTS: These studies identified approximately 500 osteoblast genes whose expression was altered. Functional characterization of the transcriptome identified developmental networks as being reactivated with 106 development associated genes found to be differentially regulated. Pathway reconstruction revealed coordinate alteration of members of the WNT signaling pathway, including frizzled-2, frizzled-7, DKK1 and WNT5B, whose differential expression in this setting was confirmed by real time PCR. CONCLUSION: The WNT pathway is a key regulator of skeletogenesis as well as differentiation of bone cells. Reactivation of this pathway may lead to altered osteoblast activity resulting in decreased bone mineral density, the pathological hallmark of osteoporosis. The data herein lend weight to the hypothesis that alterations in developmental pathways drive the initiation and progression of osteoporosis
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