463 research outputs found

    Reliability improvement of electronic circuits based on physical failure mechanisms in components

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    Traditionally the position of reliability analysis in the design and production process of electronic circuits is a position of reliability verification. A completed design is checked on reliability aspects and either rejected or accepted for production. This paper describes a method to model physical failure mechanisms within components in such a way that they can be used for reliability optimization, not after, but during the early phase of the design process. Furthermore a prototype of a CAD software tool is described, which can highlight components likely to fail and automatically adjust circuit parameters to improve product reliability

    New craftsmanship in industrial design towards a transformation economy

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    Historically, design focused on ‘the giving of form and meaning,’ taking place in design studios, workshops or laboratories. Grown from a traditional craft (artisan) activity, design was often about creative problem solving. Meanwhile technology has been advancing, allowing designers to create highly complex interactive and intelligent products and systems in our everyday life. Through these new technological possibilities, new design opportunities can be explored. In our society we are currently facing a number of complex major challenges e.g., healthy living, the economic recession, safety and attaining a sustainable level of energy and material consumption. Disruptive innovations are needed to create structural and sustainable societal change to face these challenges. In many cases these innovations cannot be obtained through traditional problem-solving design approaches. This brings new challenges for modern designers and inevitably entails questions about design, the role of the designer and the design process. In this conceptual paper, we describe our proposal for a new craftsmanship of the designer, based on taking the design process into the wild towards real people in their own environments. By using a Research through-Design approach we see new roles for designers and accompanying crafts, competencies and design processes

    The role of interleukin-4 receptor alpha on smooth muscle cells during helminth infection

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    Includes abstract.Includes bibliographical references (leaves 101-111).Interleukin-4 receptor alpha (IL-4Ra) signaling, mediated by the ligands IL-4 and IL- 13, is important for effective host protection during murine Nippostrongylus brasiliensis (N. brasiliensis) and Schistosoma mansoni (S. manson!) infection. Among other cell types, IL-4Ra responsive smooth muscle cells influence immunological responses and are needed for host protection during N. brasiliensis and S. mansoni infection

    IL-4 Mediated Resistance of BALB/c Mice to Visceral Leishmaniasis Is Independent of IL-4Rα Signaling via T Cells

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    Previous studies infecting global IL-4Rα-/-, IL-4-/-, and IL-13-/-mice on a BALB/c background with the visceralizing parasite Leishmania donovani have shown that the T helper 2 cytokines, IL-4, and IL-13, play influential but not completely overlapping roles in controlling primary infection. Subsequently, using macrophage/neutrophil-specific IL-4Rα deficient BALB/c mice, we demonstrated that macrophage/neutrophil unresponsiveness to IL-4 and IL-13 did not have a detrimental effect during L. donovani infection. Here we expand on these findings and show that CD4+ T cell-(Lckcre), as well as pan T cell-(iLckcre) specific IL-4Rα deficient mice, on a BALB/c background, unlike global IL-4Rα deficient mice, are also not adversely affected in terms of resistance to primary infection with L. donovani. Our analysis suggested only a transient and tissue specific impact on disease course due to lack of IL-4Rα on T cells, limited to a reduced hepatic parasite burden at day 30 post-infection. Consequently, the protective role(s) demonstrated for IL-4 and IL-13 during L. donovani infection are mediated by IL-4Rα-responsive cell(s) other than macrophages, neutrophils and T cells

    Simvastatin enhances protection against Listeria monocytogenes infection in mice by counteracting Listeria-induced phagosomal escape

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    Statins are well-known cholesterol lowering drugs targeting HMG-CoA-reductase, reducing the risk of coronary disorders and hypercholesterolemia. Statins are also involved in immunomodulation, which might influence the outcome of bacterial infection. Hence, a possible effect of statin treatment on Listeriosis was explored in mice. Statin treatment prior to subsequent L. monocytogenes infection strikingly reduced bacterial burden in liver and spleen (up to 100-fold) and reduced histopathological lesions. Statin-treatment in infected macrophages resulted in increased IL-12p40 and TNF-α and up to 4-fold reduced bacterial burden within 6 hours post infection, demonstrating a direct effect of statins on limiting bacterial growth in macrophages. Bacterial uptake was normal investigated in microbeads and GFP-expressing Listeria experiments by confocal microscopy. However, intracellular membrane-bound cholesterol level was decreased, as analyzed by cholesterol-dependent filipin staining and cellular lipid extraction. Mevalonate supplementation restored statin-inhibited cholesterol biosynthesis and reverted bacterial growth in Listeria monocytogenes but not in listeriolysin O (LLO)-deficient Listeria . Together, these results suggest that statin pretreatment increases protection against L. monocytogenes infection by reducing membrane cholesterol in macrophages and thereby preventing effectivity of the cholesterol-dependent LLO-mediated phagosomal escape of bacteria

    IL-4Rα Signaling in Keratinocytes and Early IL-4 Production Are Dispensable for Generating a Curative T Helper 1 Response in Leishmania major-Infected C57BL/6 Mice.

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    Experimental infection with the protozoan parasite Leishmania major has been extensively used to understand the mechanisms involved in T helper cell differentiation. Following infection, C57BL/6 mice develop a small self-healing cutaneous lesion and they are able to control parasite burden, a process linked to the development of T helper (Th) 1 cells. The local presence of IL-12 has been reported to be critical in driving Th1 cell differentiation. In addition, the early secretion of IL-4 was reported to potentially contribute to Th1 cell differentiation. Following infection with L. major, early keratinocyte-derived IL-4 was suggested to contribute to Th1 cell differentiation. To investigate a putative autocrine role of IL-4 signaling on keratinocytes at the site of infection, we generated C57BL/6 mice deficient for IL-4Rα expression selectively in keratinocytes. Upon infection with L. major, these mice could control their inflammatory lesion and parasite load correlating with the development of Th1 effector cells. These data demonstrate that IL-4 signaling on keratinocytes does not contribute to Th1 cell differentiation. To further investigate the source of IL-4 in the skin during the first days after L. major infection, we used C57BL/6 IL-4 reporter mice allowing the visualization of IL-4 mRNA expression and protein production. These mice were infected with L. major. During the first 3 days after infection, skin IL-4 mRNA expression was observed selectively in mast cells. However, no IL-4 protein production was detectable locally. In addition, early IL-4 blockade locally had no impact on subsequent Th1 cell differentiation and control of the disease. Taken together, the present data rule out a major role for skin IL-4 and keratinocyte IL-4Rα signaling in the development of a Th1 protective immune response following experimental infection with L. major

    Resolved-sideband cooling of a single 9^9Be+^+ ion in a Penning trap

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    Manipulating individual trapped ions at the single quantum level has become standard practice in radio-frequency ion traps, enabling applications from quantum information processing to precision metrology. The key ingredient is ground-state cooling of the particle's motion through resolved-sideband laser cooling. Ultra-high-presicion experiments using Penning ion traps will greatly benefit from the reduction of systematic errors offered by full motional control, with applications to atomic masses and gg-factor measurements, determinations of fundamental constants or related tests of fundamental physics. In addition, it will allow to implement quantum logic spectroscopy, a technique that has enabled a new class of precision measurements in radio-frequency ion traps. Here we demonstrate resolved-sideband laser cooling of the axial motion of a single 9^9Be+^+ ion in a cryogenic 5 Tesla Penning trap system using a two-photon stimulated-Raman process, reaching a mean phonon number of nˉz=0.10(4)\bar{n}_z = 0.10(4). This is a fundamental step in the implementation of quantum logic spectroscopy for matter-antimatter comparison tests in the baryonic sector of the Standard Model and a key step towards improved precision experiments in Penning traps operating at the quantum limit.Comment: 6 pages, 5 figure

    Optical stimulated-Raman sideband spectroscopy of a single 9Be+ ion in a Penning trap

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    We demonstrate optical sideband spectroscopy of a single 9Be+ ion in a cryogenic 5 tesla Penning trap using two-photon stimulated-Raman transitions between the two Zeeman sublevels of the 1s22s ground state manifold. By applying two complementary coupling schemes, we accurately measure Raman resonances with and without contributions from motional sidebands. From the latter we obtain an axial sideband spectrum with an effective mode temperature of (3.1±0.4) mK. These results are a key step for quantum logic operations in Penning traps, applicable to high-precision matter-antimatter comparison tests in the baryonic sector of the standard model
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