168 research outputs found

    Innovative method for cutting edge preparation with flexible diamond tools

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    The micro geometry of the cutting edge is of central importance for the performance of cutting tools. It influences all essential parameters in the machining process: chip formation, thermal and mechanical load on the tool and the workpiece, tool wear and the resulting workpiece quality. The effect depends on the size and shape of the cutting edge rounding. Depending on the machining process, asymmetrical roundings often show the greatest potential. In addition to increasing tool life, the quality of the surfaces produced can be improved by a specifically designed asymmetrical rounding. For edge preparation, blasting, brushing and drag finishing are used in industrial applications. However, an economic production of asymmetrical cutting edge geometries on cutting tools with complicated cutting edge geometry, such as solid carbide tools with helical cutting edge, cannot be achieved with these methods. Therefore, a novel method for preparation of the cutting edge rounding using flexible bond diamond polishing tools is introduced. Hence, the conducted research in this study analyzes the basic mechanisms and influencing factors using the new preparation method. For this purpose, polishing tests are carried out on carbide indexable inserts. The results show that the polishing tools can be used to create both asymmetrical and symmetrical roundings in an industrially relevant dimension. © 2019 The Authors. Published by Elsevier B.V

    Generation of helper virus-free adeno-associated viral vector packaging/producer cell lines based on a human suspension cell line

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    The emerging number of clinical trials in the gene therapy field poses the challenge to the industry to produce viral vectors in a scalable, reproducible and cost-efficient manner. To address this issue, our CAP-GT platform comprises high density, serum free suspension cell lines that enable reproducible, scalable transfection and high titer production of viral vectors. An adeno-associated virus (AAV) based vector was the first approved gene therapy product in clinical applications. Attractive features of AAV as a gene therapy vector are e.g. its lack of pathogenicity and its ability to transduce dividing and non-dividing cells. Moving away from mainly targeting ultra-rare diseases and taking more common indications into focus will need to see significant improvements concerning productivity and consistent quality of AAV vector production in order to ensure supply. For this purpose, we are developing a helper virus-free packaging cell line that can easily be turned into a producer cell line by only one additional step of cell line development. Base of this packing cell line is the generation of a cell line with stable Tet-inducible expression of Rep proteins. Extensive screening of Rep expressing single cell clones resulted in clonal cell lines which produced high AAV titers upon induction and transfection of the missing components. In a next step, the adenoviral helper functions E2A and E4orf6 are introduced, due to their toxicity also under the control of a Tet-inducible promoter. In addition, the VA RNA is encoded by the same construct. Finally, a Tet-inducible capsid function and GFP as transgene flanked by the ITRs combined on one construct will be stably integrated resulting in a proof of principle producer cell line. This approach should enable a consistent quality production of AAV vectors that abolishes the drawbacks of transient transfection concerning reproducibility, consistency and high costs for GMP-grade DNA. Process optimization in regard to process duration, feeding strategy etc. is currently ongoing for further improving the vector yields

    Primary prevention of overweight in children and adolescents: A meta-analysis of the effectiveness of interventions aiming to decrease sedentary behaviour

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    The objectives of this meta-analysis were to provide an overview of the evidence regarding the effects of interventions, implemented in the school- and general population setting, aiming to prevent excessive sedentary behaviour in children and adolescents on (1) the amount of sedentary behaviour and (2) BMI. Differences in effects on sedentary behaviour and BMI between single health behaviour interventions (sedentary behaviour only) and multiple health behaviour interventions were explored.A literature search was conducted in PubMed, EMBASE, Web of Science, PsycINFO and Cochrane Database of Systematic Reviews. Thirty-four (R)CT studies evaluating 33 general population interventions, published between 1990 and April 2011, aiming to decrease sedentary behaviour in normal weight children or adolescents (0-18 years) were included. Intervention duration ranged from 7 days to 4 years. Mean change in sedentary behaviour and BMI from baseline to post-intervention was calculated using a random effects model.Results showed significant decreases for the amount of sedentary behaviour and BMI. For sedentary behaviour the post-intervention mean difference was -17.95 min/day (95%CI:-26.61;-9.28); the change-from-baseline mean difference was -20.44 min/day (95%CI:-30.69;-10.20). For BMI the post-intervention mean difference was -0.25 kg/m2 (95%CI:-0.40;-0.09); the change-from-baseline mean difference was -0.14 kg/m2 (95%CI:-0.23;-0.05). No differences were found between single and multiple health behaviour interventions.Interventions in the school- and general population setting aiming to reduce only sedentary behaviour and interventions targeting multiple health behaviours can result in significant decreases in sedentary behaviour. Studies need to increase follow-up time to estimate the sustainability of the intervention effects found

    An integer linear programming approach for finding deregulated subgraphs in regulatory networks

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    Deregulation of cell signaling pathways plays a crucial role in the development of tumors. The identification of such pathways requires effective analysis tools that facilitate the interpretation of expression differences. Here, we present a novel and highly efficient method for identifying deregulated subnetworks in a regulatory network. Given a score for each node that measures the degree of deregulation of the corresponding gene or protein, the algorithm computes the heaviest connected subnetwork of a specified size reachable from a designated root node. This root node can be interpreted as a molecular key player responsible for the observed deregulation. To demonstrate the potential of our approach, we analyzed three gene expression data sets. In one scenario, we compared expression profiles of non-malignant primary mammary epithelial cells derived from BRCA1 mutation carriers and of epithelial cells without BRCA1 mutation. Our results suggest that oxidative stress plays an important role in epithelial cells of BRCA1 mutation carriers and that the activation of stress proteins may result in avoidance of apoptosis leading to an increased overall survival of cells with genetic alterations. In summary, our approach opens new avenues for the elucidation of pathogenic mechanisms and for the detection of molecular key players

    Judicial decision-making within political parties: A political approach

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    How do German intra-party tribunals manage internal conflicts? More specifically, why do they accept some cases for trial but reject others? Required by law to strictly adhere to implement rule of law standards, German intra-party tribunals are designed to insulate conflict regulation from politics. Meanwhile, research on judicial politics highlights the role of political and strategic considerations in accepting cases for trial. Building on the latter, we develop a theory that emphasizes tribunals’ political concerns such as winning elections. We test our hypotheses with a mixed-effects logit model on a novel data set covering 1088 tribunal decisions in six German parties from 1967 until 2015. Our findings indicate that political factors exert a strong effect on tribunal case acceptance. Tribunals are more likely to accept cases when suffering electoral loss and after losing government office. Moreover, tribunals dismiss cases more easily when their parties display relatively high levels of policy agreement

    Adaptability of Millets and Landscapes: Ancient Cultivation in North-Central Asia

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    Millet is a highly adaptable plant whose cultivation dramatically altered ancient economies in northern Asia. The adoption of millet is associated with increased subsistence reliability in semi-arid settings and perceived as a cultigen compatible with pastoralism. Here, we examine the pace of millet’s transmission and locales of adoption by compiling stable carbon isotope data from humans and fauna, then comparing them to environmental variables. The Bayesian modelling of isotope data allows for the assessment of changes in dietary intake over time and space. Our results suggest variability in the pace of adoption and intensification of millet production across northern Asia.</jats:p
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