795 research outputs found

    ACCT 441.01: Auditing

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    BADM 201.03: Financial Accounting

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    Cloning and functional expression of the murine homologue of proteinase 3: implications for the design of murine models of vasculitis

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    AbstractAnti-neutrophil cytoplasmic autoantibodies recognizing conformational epitopes (c-ANCA) of proteinase 3 (PR3) from azurophil granules are a diagnostic hallmark in Wegener's granulomatosis (WG). Because a functional PR3 homologue has not been identified in rodents, it is difficult to assess immunopathological responses in rats or mice immunized with patients' derived c-ANCA or human PR3. Here we report the full length cDNA cloning and functional expression of murine PR3 in HMC-1 cells. Recombinant murine PR3 shows highly similar substrate specificities towards synthetic peptides and is inhibited by human α1-proteinase inhibitor like human PR3. However, neither human c-ANCA, rabbit sera nor mouse monoclonal antibodies to human PR3 recognize the murine homologue. Consequently, it is unlikely that disease observed in mice after immunization with c-ANCA or human PR3 is caused by pathogenic antibodies directed against mouse PR3. Recombinant human-mouse chimaeric variants will be a valuable new tool to localize the disease-specific immunodominant epitopes in human PR3

    Melt-Extrusion-Based Additive Manufacturing of Transparent Fused Silica Glass

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    In recent years, additive manufacturing (AM) of glass has attracted great interest in academia and industry, yet it is still mostly limited to liquid nanocomposite-based approaches for stereolithography, two-photon polymerization, or direct ink writing. Melt-extrusion-based processes, such as fused deposition modeling (FDM), which will allow facile manufacturing of large thin-walled components or simple multimaterial printing processes, are so far inaccessible for AM of transparent fused silica glass. Here, melt-extrusion-based AM of transparent fused silica is introduced by FDM and fused feedstock deposition (FFD) using thermoplastic silica nanocomposites that are converted to transparent glass using debinding and sintering. This will enable printing of previously inaccessible glass structures like high-aspect-ratio (>480) vessels with wall thicknesses down to 250 µm, delicate parts including overhanging features using polymer support structures, as well as dual extrusion for multicolored glasses

    Claimed Co-ethnics and Kin-State Citizenship in Southeastern Europe

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    The paper introduces the often neglected concept of 'claimed co-ethnics' in the analysis of citizenship policies. It argues that this is an interstitial category that further complicates the triadic nexus between national minorities, nationalising states and kin-states. The 'claimed co-ethnics' are defined as people who are recognised by the citizenship (or ethnizenship) conferring state as belonging to its main ethnic group, although they themselves do not embrace that definition. In addition to bringing the issue of claimed co-ethnics into focus, the paper elucidates how citizenship policies can affect groups that challenge the exact fit between ethnicity and nation, showing how national governments through particular citizenship policies and categorisation practices engage in the construction of these groups. The paper shows that the triadic nexus framework, which has had a strong influence on citizenship and minorities scholarship, needs to be revised to include unidirectional relations between the elements of the triadic nexus. The paper is based on the comparison between the cases of ethnic Vlachs (in the context of Albania and Greece) and Bunjevci (in the context of Serbia and Croatia).European Commission - Seventh Framework Programme (FP7

    Kinstate intervention in ethnic conflicts : Albania and Turkey compared

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    Albania and Turkey did not act in overtly irredentist ways towards their ethnic brethren in neighboring states after the end of communism. Why, nonetheless, did Albania facilitate the increase of ethnic conflict in Kosovo and Macedonia, while Turkey did not, with respect to the Turks of Bulgaria? I argue that kin-states undergoing transition are more prone to intervene in external conflicts than states that are not, regardless of the salience of minority demands in the host-state. The transition weakens the institutions of the kin-state. Experiencing limited institutional constraints, self-seeking state officials create alliances with secessionist and autonomist movements across borders alongside their own ideological, clan-based and particularistic interests. Such alliances are often utilized to advance radical domestic agendas. Unlike in Albania's transition environment, in Turkey there were no emerging elites that could potentially form alliances and use external movements to legitimize their own domestic existence or claims

    Features of MOG required for recognition by patients with MOG antibody-associated disorders

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    Antibodies to myelin oligodendrocyte glycoprotein (MOG-Abs) define a distinct disease entity. Here we aimed to understand essential structural features of MOG required for recognition by autoantibodies from patients. We produced the N-terminal part of MOG in a conformationally correct form; this domain was insufficient to identify patients with MOG-Abs by ELISA even after site-directed binding. This was neither due to a lack of lipid embedding nor to a missing putative epitope at the C-terminus, which we confirmed to be an intracellular domain. When MOG was displayed on transfected cells, patients with MOG-Abs recognized full-length MOG much better than its N-terminal part with the first hydrophobic domain (P < 0.0001). Even antibodies affinity-purified with the extracellular part of MOG recognized full-length MOG better than the extracellular part of MOG after transfection. The second hydrophobic domain of MOG enhanced the recognition of the extracellular part of MOG by antibodies from patients as seen with truncated variants of MOG. We confirmed the pivotal role of the second hydrophobic domain by fusing the intracellular part of MOG from the evolutionary distant opossum to the human extracellular part; the chimeric construct restored the antibody binding completely. Further, we found that in contrast to 8-18C5, MOG-Abs from patients bound preferentially as F(ab')(2) rather than Fab. It was previously found that bivalent binding of human IgG1, the prominent isotype of MOG-Abs, requires that its target antigen is displayed at a distance of 13-16 nm. We found that, upon transfection, molecules of MOG did not interact so closely to induce a Forster resonance energy transfer signal, indicating that they are more than 6 nm apart. We propose that the intracellular part of MOG holds the monomers apart at a suitable distance for bivalent binding; this could explain why a cell-based assay is needed to identify MOG-Abs. Our finding that MOG-Abs from most patients require bivalent binding has implications for understanding the pathogenesis of MOG-Ab associated disorders. Since bivalently bound antibodies have been reported to only poorly bind C1q, we speculate that the pathogenicity of MOG-Abs is mostly mediated by other mechanisms than complement activation. Therefore, therapeutic inhibition of complement activation should be less efficient in MOG-Ab associated disorders than in patients with antibodies to aquaporin-4
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