96 research outputs found

    Micro-organism extraction from biological samples using DEP forces enhanced by osmotic shock

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    1473-0197International audienceOn the road towards efficient diagnostics of infectious diseases, sample preparation is considered as the key step and remains a real technical challenge. Finding new methods for extraction of micro-organisms from a complex biological sample remains a major challenge prior to pathogen detection and analysis. This paper reports a new technique for capturing and isolating micro-organisms from a complex sample. To achieve the segregation of pathogens and blood cells, dielectrophoretic forces applied to bioparticles previously subjected to an osmotic shock are successfully implemented within a dedicated microfluidic device. Our device involves an electrode array of interdigitated electrodes, coated with an insulating layer, to minimize electrochemical reactions with the electrolyte and to enable long-time use. The electric field intensity inside the device is optimized, considering the insulating layer, for a given frequency bandwidth, enabling the separation of bioparticles by dielectrophoretic forces. Our predictions are based on analytical models, consistent with numerical simulations (using COMSOL Multiphysics) and correlated to experimental results. The method and device have been shown to extract different types of micro-organisms spiked in a blood cell sample. We strongly believe that this new separation approach may open the way towards a simple device for pathogen extraction from blood and more generally complex samples, with potential advantages of genericness and simplicity

    Die Stauchbarkeit von gegossenem Zink in AbhÀngigkeit von dem Winkel zwischen Stauchrichtung und Hauptwachstumsrichtung der Kristalle

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    The compressibility of cast zinc-plates was measured under the drop hammer in temperatures between 20 and 400 degrees C. When perpendicularly compressed this material offers a resistance against deformation by several times higher than when compressed parallel or inclined by 45 degrees to the plain of plate. This observation is derived from the texture of cast zinc bars on the basis of the crystal translation and mechanical twinning

    Approaches for Business Model Representation: An Overview

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    Explicitly representing a business model facilitates the understanding, analysis, and innovation of its underlying logic. For representing business models, numerous approaches have been suggested in the literature. They differ greatly in their understanding of the business model concept, the approach for representation, the terminology, and the notational elements they use. This impedes the diffusion of the representational approaches in business practice and the development of a cumulative research tradition. Our contributions are twofold: Based on a comprehensive literature review, we provide (I) a synthesizing framework for classifying approaches for business model representation, and (II) a terminological and conceptual synthesis of the notational elements. Thereby, practitioners are supported in selecting the most suitable representation for a specific purpose. For researchers, our work provides the basis to develop a more cumulative stream of research

    Bat responses to changes in forest composition and prey abundance depend on landscape matrix and stand structure

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    Despite the key importance of the landscape matrix for bats, we still not fully understand how the effect of forest composition interacts at combined stand and landscape scales to shape bat communities. In addition, we lack detailed knowledge on the effects of local habitat structure on bat-prey relationships in forested landscapes. We tested the assumptions that (i) forest composition has interacting effects on bats between stand and landscape scales; and (ii) stand structure mediates prey abundance effects on bat activity. Our results indicated that in conifer-dominated landscapes (> 80% of coniferous forests) bat activity was higher in stands with a higher proportion of deciduous trees while bats were less active in stands with a higher proportion of deciduous trees in mixed forest landscapes (~ 50% of deciduous forests). Moth abundance was selected in the best models for six among nine bat species. The positive effect of moth abundance on Barbastella barbastellus was mediated by vegetation clutter, with dense understory cover likely reducing prey accessibility. Altogether, our findings deepen our understanding of the ecological processes affecting bats in forest landscapes and strengthen the need to consider both landscape context and trophic linkage when assessing the effects of stand-scale compositional and structural attributes on bats

    Attenuated Leishmania induce pro-inflammatory mediators and influence leishmanicidal activity by p38 MAPK dependent phagosome maturation in Leishmania donovani co-infected macrophages

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    Promastigote form of Leishmania, an intracellular pathogen, delays phagosome maturation and resides inside macrophages. But till date limited study has been done to manipulate the phagosomal machinery of macrophages to restrict Leishmania growth. Attenuated Leishmania strain exposed RAW 264.7 cells showed a respiratory burst and enhanced production of pro-inflammatory mediators. The augmentation of pro-inflammatory activity is mostly attributed to p38 MAPK and p44/42 MAPK. In our study, these activated macrophages are found to induce phagosome maturation when infected with pathogenic Leishmania donovani. Increased co-localization of carboxyfluorescein succinimidyl ester labeled pathogenic L. donovani with Lysosome was found. Moreover, increased co-localization was observed between pathogenic L. donovani and late phagosomal markers viz. Rab7, Lysosomal Associated Membrane Protein 1, Cathepsin D, Rab9, and V-ATPase which indicate phagosome maturation. It was also observed that inhibition of V-type ATPase caused significant hindrance in attenuated Leishmania induced phagosome maturation. Finally, it was confirmed that p38 MAPK is the key player in acidification and maturation of phagosome in attenuated Leishmania strain preexposed macrophages. To our knowledge, this study for the first time reported an approach to induce phagosome maturation in L. donovani infected macrophages which could potentiate short-term prophylactic response in futur

    Malarial Hemozoin Activates the NLRP3 Inflammasome through Lyn and Syk Kinases

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    The intraerythrocytic parasite Plasmodium—the causative agent of malaria—produces an inorganic crystal called hemozoin (Hz) during the heme detoxification process, which is released into the circulation during erythrocyte lysis. Hz is rapidly ingested by phagocytes and induces the production of several pro-inflammatory mediators such as interleukin-1ÎČ (IL-1ÎČ). However, the mechanism regulating Hz recognition and IL-1ÎČ maturation has not been identified. Here, we show that Hz induces IL-1ÎČ production. Using knockout mice, we showed that Hz-induced IL-1ÎČ and inflammation are dependent on NOD-like receptor containing pyrin domain 3 (NLRP3), ASC and caspase-1, but not NLRC4 (NLR containing CARD domain). Furthermore, the absence of NLRP3 or IL-1ÎČ augmented survival to malaria caused by P. chabaudi adami DS. Although much has been discovered regarding the NLRP3 inflammasome induction, the mechanism whereby this intracellular multimolecular complex is activated remains unclear. We further demonstrate, using pharmacological and genetic intervention, that the tyrosine kinases Syk and Lyn play a critical role in activation of this inflammasome. These findings not only identify one way by which the immune system is alerted to malarial infection but also are one of the first to suggest a role for tyrosine kinase signaling pathways in regulation of the NLRP3 inflammasome

    Duodenal Adenomas and Cancer in MUTYH-associated Polyposis: An International Cohort Study

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    Although duodenal adenomas and cancer appear to occur significantly less frequently in autosomal recessive MUTYH-associated polyposis (MAP) than in autosomal dominant familial adenomatous polyposis (FAP),1 current guidelines recommend similar endoscopic surveillance for both disorders.2-4 This involves gastro-duodenoscopy starting at 25 to 35 years of age and repeated at intervals determined by Spigelman staging based on the number, size, histological type and degree of dysplasia of adenomas, and by ampullary staging. Case reports of duodenal cancers in MAP suggest that they may develop in the absence of advanced Spigelman stage benign disease and even without coexisting adenomas.1 Recent molecular analyses suggest thatMAPduodenal adenomashave a higher mutational burden than FAP adenomas and are more likely to harbor oncogenic drivermutations, such as those in KRAS.5 These apparent differences in the biology and natural history of duodenal polyposis in FAP and MAP challenge the assumption that the same surveillance should be applied in both conditions
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