226 research outputs found

    Mega and Consumer Trends – Towards Car-independent Mobile Applications

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    The car industry is confronted with fundamental changes in society, technology and economy and forced to rethink its concept of mobility. Through constant strategic foresight, trend management and a holistic mobility vision, car manufacturers must develop innovative strategies that reflect current and future trends, in order to meet customer needs, technological standards and economic imperatives. Therefore, car manufacturers are shifting their value chain more and more towards the aftermarket and information technology (IT). Used as a tool for image branding and innovation monitoring, a closer look reveals that car manufacturers are constantly increasing their investment activities in technology start-ups. This indicates that the car industry is in the middle of a transformation process, transforming from a car producer to a mobility provider. Based on an analysis of future driving factors in the car industry and in-depth interviews, we identified six crucial megatrends: peak oil and global warming, connectedness, safety regulations, sharing economy, urban mobility and aging society. Furthermore, four shaping consumer trends were revealed: ownerless, simplicity, eco-lifestyle and personalization. In summary, the most successful providers in the mobile market might be those who understand thoroughly the consumers’ needs and behaviour, in order to offer the mobility services they desire

    Time-resolved measurement of the local equivalence ratio in a gaseous propane injection process using laser-induced gratings

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    This paper was published in Optics Express and is made available as an electronic reprint with the permission of OSA. The paper can be found at the following URL on the OSA website: http://www.opticsinfobase.org/abstract.cfm?URI=oe-14-26-12994. Systematic or multiple reproduction or distribution to multiple locations via electronic or other means is prohibited and is subject to penalties under law.Peer reviewedPublisher PD

    Marginality of bulk-edge correspondence for single-valley Hamiltonians

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    We study the correspondence between the non-trivial topological properties associated with the individual valleys of gapped bilayer graphene (BLG), as a prototypical multi-valley system, and the gapless modes at its edges and other interfaces. We find that the exact connection between the valley-specific Hall conductivity and the number of gapless edge modes does not hold in general, but is dependent on the boundary conditions, even in the absence of intervalley coupling. This non-universality is attributed to the absence of a well-defined topological invariant within a given valley of BLG; yet, a more general topological invariant may be defined in certain cases, which explains the distinction between the BLG-vacuum and BLG-BLG interfaces.Comment: 7 pages, 4 figure

    Pastorale Laienmitarbeiter in Seelsorgeeinheiten der Katholischen Kirche des Erzbistums Freiburg

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    Auf den Rückgang der Priesterzahlen reagiert das Erzbistum Freiburg mit der Bildung von Seelsorgeeinheiten, die sowohl aus Pfarreien als auch weiteren Gemeinschaftsformen bestehen. Pastoral- und Gemeindereferenten nehmen dort vorwiegend Aufgaben im Bereich der Maryria wahr (Ausnahme: weibliche Pastoralreferenten). Die Bedeutung der Martyria ist auch unter Bezug auf den zeitlichen Aufwand am höchsten (Ausnahme: männliche Gemeindereferenten). Es liegt auf Basis einer fünf-fach Skalierung für alle Aufgaben eine hohe Motivation, durchschnittlich im Bereich zwischen 3,67 bis 3,91 vor. Die Motivstruktur ist ex- und intrinsisch geprägt, mit meist deutlichem Schwerpunkt auf den intrinsischen Motiven. Die Anreizsituation in den Seelsorgeeinheiten stellt sich beispielsweise mit der „communio-Ekklesiologie“ intrinsisch, mit den hierarchischen Elementen extrinsisch dar. Mit den extrinsischen Elementen besteht die Gefahr der Verdrängung von Motivation. Anreizsysteme sollten durch intrinsische Anreize (z.B. Kommunikation, Partizipation, Kooperation), die auch von der „communio-Ekklesiologie“ vertreten werden, bestimmt sein, ohne die extrinsische Seite z.B. durch Zahlung von Gehältern zu vernachlässigen

    Non-invasive in vivo imaging of tumour-associated cathepsin B by a highly selective inhibitory DARPin

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    Cysteine cathepsins often contribute to cancer progression due to their overexpression in the tumour microenvironment and therefore present attractive targets for non-invasive diagnostic imaging. However, the development of highly selective and versatile small molecule probes for cathepsins has been challenging. Here, we targeted tumour-associated cathepsin B using designed ankyrin repeat proteins (DARPins). The selective DARPin 8h6 inhibited cathepsin B with picomolar affinity (Ki = 35 pM) by binding to a site with low structural conservation in cathepsins, as revealed by the X-ray structure of the complex. DARPin 8h6 blocked cathepsin B activity in tumours ex vivo and was successfully applied in in vivo optical imaging in two mouse breast cancer models, in which cathepsin B was bound to the cell membrane or secreted to the extracellular milieu by tumour and stromal cells. Our approach validates cathepsin B as a promising diagnostic and theranostic target in cancer and other inflammation-associated diseases

    Tuning the drug efflux activity of an ABC transporter in vivo by in vitro selected DARPin binders.

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    ABC transporters use the energy from binding and hydrolysis of ATP to import or extrude substrates across the membrane. Using ribosome display, we raised designed ankyrin repeat proteins (DARPins) against detergent solubilized LmrCD, a heterodimeric multidrug ABC exporter from Lactococcus lactis. Several target-specific DARPin binders were identified that bind to at least three distinct, partially overlapping epitopes on LmrD in detergent solution as well as in native membranes. Remarkably, functional screening of the LmrCD-specific DARPin pools in L. lactis revealed three homologous DARPins which, when generated in LmrCD-expressing cells, strongly activated LmrCD-mediated drug transport. As LmrCD expression in the cell membrane was unaltered upon the co-expression of activator DARPins, the activation is suggested to occur at the level of LmrCD activity. Consistent with this, purified activator DARPins were found to stimulate the ATPase activity of LmrCD in vitro when reconstituted in proteoliposomes. This study suggests that membrane transporters are tunable in vivo by in vitro selected binding proteins. Our approach could be of biopharmaceutical importance and might facilitate studies on molecular mechanisms of ABC transporters

    Immune system and peripheral nerves in propagation of prions to CNS

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    Prions are not only unique in the way they replicate. Also the sequence of events triggered by peripheral prion infection, generically termed ‘peripheral pathogenesis', sets prions aside from all other known pathogens. Whereas most bacteria, parasites, and viruses trigger innate and adaptive immune responses, the mammalian immune system appears to be remarkably oblivious to prions. Transmissible spongiform encephalopathies (TSEs) do not go along with inflammatory infiltrates, and antibodies to the prion protein are not typically raised during the course of the disease. On the other hand, there is conspicuous involvement of lymphoid organs, which accumulate sizeable concentrations of the infectious agent early during disease. Moreover, various states of immune deficiency can abolish peripheral pathogenesis and prevent ‘take' of infection when prions are administered to peripheral sites. Here, we critically re-visit the current evidence for an involvement of the immune system in prion diseases, and will attempt to trace the elaborate mechanisms by which prions, upon entry into the body from peripheral sites, reach the brai
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