211 research outputs found

    THE NEXT STEP – OPEN PROTOTYPING

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    Software applications in the car are gaining in importance as a driver for innovation and value creation for the car manufacturers and their suppliers. These novel software functions, e.g., mobile services or car-to-car enabled applications, are increasingly designed and developed using early prototypes. Building on open innovation literature, this paper goes beyond extant knowledge on prototyping and proposes a novel paradigm of ‘open prototyping’. It assumes that organizations can and should use external input as well as internal input in form of prototypes, as the firms look to advance their technology. Set in the empirical field of the automotive industry, we follow a design-oriented research approach to design, develop and evaluate an open prototyping approach consisting of a toolkit and process. The open prototyping toolkit, HIMEPP, has a component-oriented architecture. Combined with the open prototyping process, it supports the development of diagonal high-fidelity prototypes together with persons from outside the R&D department. The study allows for generalizations to other industries and points to significant managerial as well as academic implications, which can be expected from opening the next step of the innovation process

    Atrial Natriuretic Peptide Protects against Histamine-Induced Endothelial Barrier Dysfunction in Vivo

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    Endothelial barrier dysfunction is a hallmark of many severe pathologies, including sepsis or atherosclerosis. The cardiovascular hormone atrial natriuretic peptide (ANP) has increasingly been suggested to counteract endothelial leakage. Surprisingly, the precise in vivo relevance of these observations has never been evaluated. Thus, we aimed to clarify this issue and, moreover, to identify the permeability-controlling subcellular systems that are targeted by ANP. Histamine was used as important pro-inflammatory, permeability-increasing stimulus. Measurements of fluorescein isothiocyanate (FITC)-dextran extravasation from venules of the mouse cremaster muscle and rat hematocrit values were performed to judge changes of endothelial permeability in vivo. It is noteworthy that ANP strongly reduced the histamine-evoked endothelial barrier dysfunction in vivo. In vitro, ANP blocked the breakdown of transendothelial electrical resistance (TEER) induced by histamine. Moreover, as judged by immunocytochemistry and Western blot analysis, ANP inhibited changes of vascular endothelial (VE)-cadherin, β-catenin, and p120ctn morphology; VE-cadherin and myosin light chain 2 (MLC2) phosphorylation; and F-actin stress fiber formation. These changes seem to be predominantly mediated by the natriuretic peptide receptor (NPR)-A, but not by NPR-C. In summary, we revealed ANP as a potent endothelial barrier protecting agent in vivo and identified adherens junctions and the contractile apparatus as subcellular systems targeted by ANP. Thus, our study highlights ANP as an interesting pharmacological compound opening new therapeutic options for preventing endothelial leakage

    Acute flaccid myelitis in Switzerland - association with enterovirus D68.

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    Poliomyelitis-like acute flaccid myelitis associated with enterovirus D68 (EV-D68) has emerged globally during the past decade. Here we describe the first documented case reported from Switzerland, and a second, suspected case occurring in temporal association. AFM occurs primarily in children, is usually heralded by a febrile, respiratory prodrome followed by acute-onset, usually asymmetrical, limb weakness with some predilection for the upper extremities, and respiratory muscle compromise in one third of reported cases. There is no specific therapy and the majority of cases result in permanent neurological sequelae. A comprehensive diagnostic workup and timely reporting to the health authorities are essential. Surveillance of respiratory and stool samples for EV-D68 and other neurotropic enteroviruses is in place in several European countries and warrants consideration in Switzerland. This could entail the extension of the poliomyelitis surveillance program of the Federal Office of Public Health by monitoring and enteroviral typing of respiratory samples from patients with acute flaccid paralysis

    Ganzheitlichkeit in der Lebensmittelmittelforschung

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    Ein Grund für die bislang schwierige bis unmögliche anbauspezifische Zuordnung frischer oder verarbeiteter landwirtschaftlicher Erzeugnisse besteht nach Ansicht von Wissenschaftlerinnen und Wissenschaftlern aus privaten und staatlichen Forschungseinrichtungen des Öko-landbaus in der Art der angewendeten analytischen Methoden zur Qualitätsbewertung. Wäh-rend fast alle gängigen chemisch-analytischen Methoden für eine Differenzierung offensicht-lich nicht genügen, scheinen verschiedene, gegenwärtig jedoch naturwissenschaftlich nicht anerkannte, komplementäre Analysenmethoden eine Unterscheidung treffen zu können. Diese schreiben der Lebensmittelstruktur, äußerer Form, Formerhalt und innerer Formation als Qua-litätskriterium eine besondere Bedeutung zu und können so zwischen verschiedenen Produk-tionsverfahren, Sorten, Verarbeitungsgraden u.a. unterscheiden. Die komplementären Methoden sind jedoch im Hinblick auf ihre Spezifität zur Unterschei-dung der Produktionsverfahren, Vergleichbarkeit, Präzision, Robustheit noch umfassend zu validieren. Obwohl die komplementären Methoden auch nach dieser Validierung nicht notwendigerweise Aussagen über die Qualität der Lebensmittel aus unterschiedlichen Produktionsverfahren zulassen, ist die Möglichkeit der Unterscheidung von konventionell erzeugten Lebensmitteln und Bio-Lebensmitteln gleichwohl von hohem Interesse. Die SAG empfiehlt daher ausdrücklich die Validierung der beschriebenen ganzheitlichen Methoden auf naturwissenschaftlich-statistischer Grundlage zu komplementären Methoden der Qualitätserfassung

    Niacin Reverses Migratory Macrophage Foam Cell Arrest Mediated by oxLDL In Vitro

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    Introduction: Niacin reduces vascular oxidative stress and down regulates inducible nitric oxide synthase, an enzyme mediating proatherosclerotic effects in part by increasing oxidative stress. Here, we evaluate whether Niacin reverses the redox sensitive migratory arrest of macrophages in response to oxidised(ox) LDL uptake. Material and Methods: Migration of RAW264.7 cells, a murine macrophage cell line and bone marrow derived macrophages from wildtype and iNOS knockout mice was quantified using a modified Boyden chamber. Unstimulated cells or cells preincubated with oxLDL or non-oxidised (n)LDL were treated with Nicotinic acid or Nicotinamide. Nitric oxide, peroxynitrite and ROS production were assessed using electron paramagnetic resonance (ESR). Additionally, flow cytometry analysis of apoptosis, fokal adhesion kinase (FAK), phalloidin, CD36, F4/80 macrophage marker and iNOS gene expression (PCR) were assessed. Results: Migration of Nicotinic acid, Nicotinamide treated cells or unstimulated cells did not differ (P>0.05). oxLDL treatment significantly reduced migration vs. unstimulated cells (p, 0.05). In contrast, migratory arrest in response to oxLDL treatment was reversed by co-incubation with Nicotinic acid and Nicotinamide. The oxLDL-induced peroxynitrite formation in RAW264.7 cells was abolished by Niacin and glutathion (GSH) oxidation was significantly reduced. However, nitric oxide (NO)- and reactive oxygen species (ROS) production induced by oxLDL were not affected by Niacin treatment of RAW264.7 cells. In addition, Nicotinic acid and Nicotinamide reduced actin polymerization, a marker for migratory arrest. Discussion: Our data shows that oxLDL induced inhibition of macrophage migration in vitro can be reversed by Niacin. Furthermore, Niacin reduces peroxynitite formation and improves antioxidant GSH
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