67 research outputs found

    The nodal structure of doubly-excited resonant states of helium

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    The authors examine the nodal structure of accurate helium wavefunctions calculated by direct diagonalization of the full six-dimensional problem. It is shown that for fixed interelectronic distance R (or hyperspherical radius R) the symmetric doubly-excited resonant states have well defined lambda , mu nodal structure indicating a near separability in prolate spheroidal coordinates. For fixed lambda , however, a clear mixing of R, mu nodes is demonstrated. This corresponds to a breakdown of the adiabatic approximation and can be understood in terms of the classical two-electron motion

    Identification of BACE1 cleavage sites in human voltage-gated sodium channel beta 2 subunit

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    <p>Abstract</p> <p>Background</p> <p>The voltage-gated sodium channel Ī²2 subunit (NavĪ²2) is a physiological substrate of BACE1 (Ī²-site APP cleaving enzyme) and Ī³-secretase, two proteolytic enzymes central to Alzheimer's disease pathogenesis. Previously, we have found that the processing of NavĪ²2 by BACE1 and Ī³-secretase regulates sodium channel metabolism in neuronal cells. In the current study we identified the BACE1 cleavage sites in human NavĪ²2.</p> <p>Results</p> <p>We found a major (147-148 Lā†“M, where ā†“ indicates the cleavage site) and a minor (144145 Lā†“Q) BACE1 cleavage site in the extracellular domain of human NavĪ²2 using a cell-free BACE1 cleavage assay followed by mass spectrometry. Next, we introduced two different double mutations into the identified major BACE1 cleavage site in human NavĪ²2: 147LM/VI and 147LM/AA. Both mutations dramatically decreased the cleavage of human NavĪ²2 by endogenous BACE1 in cell-free BACE1 cleavage assays. Neither of the two mutations affected subcellular localization of NavĪ²2 as confirmed by confocal fluorescence microscopy and subcellular fractionation of cholesterol-rich domains. Finally, wildtype and mutated NavĪ²2 were expressed along BACE1 in B104 rat neuroblastoma cells. In spite of Ī±-secretase still actively cleaving the mutant proteins, NavĪ²2 cleavage products decreased by ~50% in cells expressing NavĪ²2 (147LM/VI) and ~75% in cells expressing NavĪ²2 (147LM/AA) as compared to cells expressing wildtype NavĪ²2.</p> <p>Conclusion</p> <p>We identified a major (147-148 Lā†“M) and a minor (144-145 Lā†“Q) BACE1 cleavage site in human NavĪ²2. Our <it>in vitro </it>and cell-based results clearly show that the 147-148 Lā†“M is the major BACE1 cleavage site in human NavĪ²2. These findings expand our understanding of the role of BACE1 in voltage-gated sodium channel metabolism.</p

    Spectral data for doubly excited states of helium with non-zero total angular momentum

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    A spectral approach is used to evaluate energies and widths for a wide range of singlet and triplet resonance states of helium. Data for total angular momentum L=1,...,4L=1,...,4 is presented for resonances up to below the 5th single ionization threshold. In addition the expectation value of cosā”(Īø12)\cos(\theta_{12}) is given for the calculated resonances.Comment: 35 pages, 16 tables, to be published in Atomic Data and Nuclear Data Table

    Treatment intensification in HIV-infected Patients is associated With reduced Frequencies of regulatory T cells

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    In untreated HIV infection, the efficacy of T cell responses decreases over the disease course, resulting in disease progression. The reasons for this development are not completely understood. However, immunosuppressive cells are supposedly crucially involved. Treatment strategies to avoid the induction of these cells preserve immune functions and are therefore the object of intense research efforts. In this study, we assessed the effect of treatment intensification [= 5-drug antiretroviral therapy (ART)] on the development of suppressive cell subsets. The New Era (NE) study recruited patients with primary HIV infection (PHI) or chronically HIV-infected patients with conventional ART (CHI) and applied an intensified 5-drug regimen containing maraviroc and raltegravir for several years. We compared the frequencies of the immune suppressive cells, namely, the myeloid-derived suppressor cells (MDSCs), regulatory B cells (Bregs), and regulatory T cells (Tregs), of the treatment intensification patients to the control groups, especially to the patients with conventional 3-drug ART, and analyzed the Gag/Nef-specific CD8 T cell responses. There were no differences between PHI and CHI in the NE population (p > 0.11) for any of the studied cell types. Polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC), monocytic myeloid-derived suppressor cell (M-MDSC), and the Breg frequencies were comparable to those of patients with a 3-drug ART. However, the Treg levels were significantly lower in the NE patients than those in 3ART-treated individuals and other control groups (p = 0.0033). The Gag/Nef-specific CD8 T cell response was broader (p = 0.0134) with a higher magnitude (p = 0.026) in the NE population than that in the patients with conventional ART. However, we did not find a correlation between the frequency of the immune suppressive cells and the interferon-gamma+ CD8 T cell response. In the treatment intensification subjects, the frequencies of the immune suppressive cells were comparable or lower than those of the conventional ART-treated subjects, with surprisingly broad HIV-specific CD8 T cell responses, suggesting a preservation of immune function with the applied treatment regimen. Interestingly, these effects were seen in both treatment intensification subpopulations and were not attributed to the start of treatment in primary infection

    Untersuchung und Vergleich von Open Source Plattformen fĆ¼r das Smart Home

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    Ziel dieser Bachelor-Thesis war es, sich mit den vier Open Source Smart Home Plattformen OpenHAB, ioBroker, Home Assistant und Node-RED auseinanderzusetzen, Vergleichskriterien zu entwickeln und die Plattformen in einem exemplarischen Smart Home Szenario miteinander zu vergleichen

    Analyse von automatisierten Testverfahren fĆ¼r die Barrie-refreiheitsprĆ¼fung von Apps im Hinblick auf den EuropƤischen Standard EN 301 549

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    Viele Menschen mit Behinderungen stoƟen immer noch auf Barrieren, die es ihnen er-schweren, Smartphone-Anwendungen zu nutzen. Die harmonisierte europƤische Norm EN 301 549 legt die Anforderungen an die funktionale Barrierefreiheit von ICT-Produk-ten und -Dienstleistungen fest und beschreibt Testverfahren und Bewertungsmetho-den fĆ¼r jede Anforderung. Analysetools und automatisierte Testverfahren versprechen Entwickler bei der Erstellung barrierefreier Anwendungen zu unterstĆ¼tzen. Diese Werkzeuge unterscheiden sich in ihrer Funktionsweise, ihrer Zielgruppe und dem Zeit-punkt, an dem sie in den Entwicklungsprozess eingebunden werden kƶnnen. Ziel dieser Arbeit ist es, einen Leitfaden zu erstellen, der aufzeigt, welche Kriterien nach EN 301 549 mit Hilfe von Analysewerkzeugen Ć¼berprĆ¼ft werden kƶnnen und die Frage zu be-antworten "Wie kƶnnen Analysewerkzeuge und automatisierte Testverfahren einge-setzt werden, um Barrierefreiheitstests im Hinblick auf die europƤische Norm EN 301 549 zu automatisieren?"
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