Europas Krise und Zukunftsperspektiven: 10. März 2019

Der Historiker und Schriftsteller Ian Kershaw analysiert in seiner Rede 'Europas Krise und Zukunftsperspektiven' die große Geschichte Europas. Für Kershaw gleicht diese Geschichte einer „Achterbahn“, die niemals aufhört: Europa befindet sich in einer ernsthaften Krise. Das ‚europäische Projekt‘ der engeren Integration hat bei vielen Bürger*innen seine Überzeugungskraft verloren. Demgegenüber ist der Nationalismus wieder stärker geworden. Der nationale Populismus gewinnt an Zustimmung und grassiert mittlerweile in fast allen europäischen Staaten. Die europäische Verständigung ist offenkundig in Gefahr. Und international sieht die Lage düster aus. Wie ist es dazu gekommen? Wo liegen die Wurzeln dieser besorgniserregenden Situation? Wie sieht die Zukunft der EU aus? Kann sie Reformen einführen und damit den Bedrohungen erfolgreich begegnen? Antworten auf diese wichtigen Fragen sucht er in dieser Dresdner Rede

Spatial decision support system for the selection of an overhead electrical transmission line corridor.

This dissertation presents research into the possibility of using GIS Spatial Analysis and Multi-Criteria Decision Making to determine a corridor for electric overhead transmission power line routing. The research described in this dissertation examines the feasibility of developing a spatial decision support system to select an overhead transmission line corridor. This support system could also be used to perform scenario analysis. The selection model evaluates multiple environmental, ecological, electrical, aesthetic, engineering and socio-economic criteria spatially. Each criterion is weighted using a pair-wise comparison and is presented as a GIS layer. A suitability map is derived from the weighted layers using a weighted linear combination. A least cost path that represents the corridor most likely to contain the optimum route for an overhead electrical transmission line is derived from the suitability map

Problems and Solutions in Laboratory Testing for Hemophilia

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From digital resources to historical scholarship with the British Library 19th Century Newspaper Collection

It is increasingly acknowledged that the Digital Humanities have placed too much emphasis on data creation and that the major priority should be turning digital sources into contributions to knowledge. While this sounds relatively simple, doing it involves intermediate stages of research that enhance digital sources, develop new methodologies and explore their potential to generate new knowledge from the source. While these stages are familiar in the social sciences they are less so in the humanities. In this paper we explore these stages based on research on the British Library’s Nineteenth Century Newspaper Collection, a corpus of many billion words that has much to offer to our understanding of the nineteenth century but whose size and complexity makes it difficult to work with

Performance of factor IX extended half-life product measurements in external quality control assessment programs

Background: Patients with hemophilia B are increasingly treated with extended half-life (EHL) factor IX (FIX) concentrates. For the laboratory, introduction of these EHL concentrates presents a major challenge. To understand the variation in FIX activity levels, all available diagnostic assays need to be directly compared. Methods: The ECAT, UKNEQAS, and RCPAQAP have collaboratively performed a global survey to evaluate the quality of FIX measurements using FIX deficient plasma samples spiked with recombinant FIX (rFIX), rFIXFP, rFIXFc, and N9-GP to levels at typical FIX trough (6 IU/dL) and peak levels (60 IU/dL). Participants were asked to use their routine protocols, using one-stage assays (OSA) or chromogenic assays (CA). Results: In samples spiked with 6 IU/dL product, median (25%-75% range) FIX activity levels (OSA), were 8.0 IU/dL (7.0-9.2) for rFIX, 6.0 IU/dL (4.0-7.1) for rFIXFP, 6.6 IU/dL (5.5-8.0) for rFIXFc, and 4.9 IU/dL (3.5-8.4) for N9-GP. In samples spiked with 60 IU/dL, FIX activity levels measured (using OSA) was 63.0 IU/dL (59.9-67.0) for rFIX, 42.5 IU/dL (28.2-47.0) for rFIXFP, 50.0 IU/dL (45.0-55.0) for rFIXFc, and 34.0 IU/dL (24.8-67.5) for N9-GP. Considerable differences were observed between reagents for all samples. With CA, there was also quite some variation, but no differences between reagents. Conclusion: Large variation is observed in the measurement of FIX activity levels after administration of rFIX and EHL FIX products. For N9-GP, most silica-based assays show especially high levels. It is essential to standardize and improve reliability of measurements of these concentrates as diagnosis and treatment monitoring is based on these results

Attenuation of AMPK signaling by ROQUIN promotes T follicular helper cell formation

T follicular helper cells (Tfh) are critical for the longevity and quality of antibody-mediated protection against infection. Yet few signaling pathways have been identified to be unique solely to Tfh development. ROQUIN is a post-transcriptional repressor of T cells, acting through its ROQ domain to destabilize mRNA targets important for Th1, Th17, and Tfh biology. Here, we report that ROQUIN has a paradoxical function on Tfh differentiation mediated by its RING domain: mice with a T cell-specific deletion of the ROQUIN RING domain have unchanged Th1, Th2, Th17, and Tregs during a T-dependent response but show a profoundly defective antigen-specific Tfh compartment. ROQUIN RING signaling directly antagonized the catalytic α1 subunit of adenosine monophosphate-activated protein kinase (AMPK), a central stress-responsive regulator of cellular metabolism and mTOR signaling, which is known to facilitate T-dependent humoral immunity. We therefore unexpectedly uncover a ROQUIN–AMPK metabolic signaling nexus essential for selectively promoting Tfh responses

IFNs Modify the Proteome of <i>Legionella</i>-Containing Vacuoles and Restrict Infection Via IRG1-Derived Itaconic Acid

Macrophages can be niches for bacterial pathogens or antibacterial effector cells depending on the pathogen and signals from the immune system. Here we show that type I and II IFNs are master regulators of gene expression during Legionella pneumophila infection, and activators of an alveolar macrophage-intrinsic immune response that restricts bacterial growth during pneumonia. Quantitative mass spectrometry revealed that both IFNs substantially modify Legionella-containing vacuoles, and comparative analyses reveal distinct subsets of transcriptionally and spatially IFN-regulated proteins. Immune-responsive gene (IRG)1 is induced by IFNs in mitochondria that closely associate with Legionella-containing vacuoles, and mediates production of itaconic acid. This metabolite is bactericidal against intravacuolar L. pneumophila as well as extracellular multidrug-resistant Gram-positive and -negative bacteria. Our study explores the overall role IFNs play in inducing substantial remodeling of bacterial vacuoles and in stimulating production of IRG1-derived itaconic acid which targets intravacuolar pathogens. IRG1 or its product itaconic acid might be therapeutically targetable to fight intracellular and drug-resistant bacteria