275 research outputs found

    PRAS40 suppresses atherogenesis through inhibition of mTORC1-dependent pro-inflammatory signaling in endothelial cells

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    Endothelial pro-inflammatory activation plays a pivotal role in atherosclerosis, and many pro-inflammatory and atherogenic signals converge upon mechanistic target of rapamycin (mTOR). Inhibitors of mTOR complex 1 (mTORC1) reduced atherosclerosis in preclinical studies, but side effects including insulin resistance and dyslipidemia limit their clinical use in this context. Therefore, we investigated PRAS40, a cell type-specific endogenous modulator of mTORC1, as alternative target. Indeed, we previously found PRAS40 gene therapy to improve metabolic profile; however, its function in endothelial cells and its role in atherosclerosis remain unknown. Here we show that PRAS40 negatively regulates endothelial mTORC1 and pro-inflammatory signaling. Knockdown of PRAS40 in endothelial cells promoted TNFα-induced mTORC1 signaling, proliferation, upregulation of inflammatory markers and monocyte recruitment. In contrast, PRAS40-overexpression blocked mTORC1 and all measures of pro-inflammatory signaling. These effects were mimicked by pharmacological mTORC1-inhibition with torin1. In an in vivo model of atherogenic remodeling, mice with induced endothelium-specific PRAS40 deficiency showed enhanced endothelial pro-inflammatory activation as well as increased neointimal hyperplasia and atherosclerotic lesion formation. These data indicate that PRAS40 suppresses atherosclerosis via inhibition of endothelial mTORC1-mediated pro-inflammatory signaling. In conjunction with its favourable effects on metabolic homeostasis, this renders PRAS40 a potential target for the treatment of atherosclerosis

    Metal - Insulator transition driven by vacancy ordering in GeSbTe phase change materials

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    Phase Change Materials (PCMs) are unique compounds employed in non-volatile random access memory thanks to the rapid and reversible transformation between the amorphous and crystalline state that display large differences in electrical and optical properties. In addition to the amorphous-to-crystalline transition, experimental results on polycrystalline GeSbTe alloys (GST) films evidenced a Metal-Insulator Transition (MIT) attributed to disorder in the crystalline phase. Here we report on a fundamental advance in the fabrication of GST with out-of-plane stacking of ordered vacancy layers by means of three distinct methods: Molecular Beam Epitaxy, thermal annealing and application of femtosecond laser pulses. We assess the degree of vacancy ordering and explicitly correlate it with the MIT. We further tune the ordering in a controlled fashion attaining a large range of resistivity. Employing ordered GST might allow the realization of cells with larger programming windows

    Metal - Insulator transition driven by vacancy ordering in GeSbTe phase change materials

    Get PDF
    Phase Change Materials (PCMs) are unique compounds employed in non-volatile random access memory thanks to the rapid and reversible transformation between the amorphous and crystalline state that display large differences in electrical and optical properties. In addition to the amorphousto-crystalline transition, experimental results on polycrystalline GeSbTe alloys (GST) films evidenced a Metal-Insulator Transition (MIT) attributed to disorder in the crystalline phase. Here we report on a fundamental advance in the fabrication of GST with out-of-plane stacking of ordered vacancy layers by means of three distinct methods: Molecular Beam Epitaxy, thermal annealing and application of femtosecond laser pulses. We assess the degree of vacancy ordering and explicitly correlate it with the MIT. We further tune the ordering in a controlled fashion attaining a large range of resistivity. Employing ordered GST might allow the realization of cells with larger programming windows

    Ein mehrkanaliges Biosensormesssystem zur Überwachung der Nitrifikation in Abwasserreinigungsanlagen

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    Bei der biologischen Abwasserreinigung treten häufig Störungen der Nitrifikationsstufe (biochemische Oxidation von Ammonium über Nitrit zu Nitrat) auf, die durch Hemmstoffe sowie durch Stossbelastungen hoher Stickstofffrachten (N-BSB) verursacht werden. Dadurch gelangen erhöhte Mengen an sauerstoffzehrenden reduzierten Stickstoffverbindungen in die Oberflächengewässer. Dies ist besonders kritisch bei Vorflutern mit einem bereits niedrigem Sauerstoffgehalt, da durch diese reduzierten Stickstoffverbindungen die Konzentration an gelöstem Sauerstoff in Folge mikrobieller Oxidation stark absinken kann und somit die Biocönose im Gewässer nachhaltig gestört wird. Da es sich bei Nitrit und Ammoniak zudem um starke Fischgifte handelt, ist die Elimination dieser Stickstoffverbindungen aus dem Abwasser nicht zuletzt auch gesetzlich vorgeschrieben. Zur Erfassung von Störungen der Nitrifikationsstufe wurde deswegen in den vergangenen Jahren am ISWA ein Nitrifikanten-Einzelbiosensor entwickelt. Dabei wird über den Sauerstoffverbrauch des Immobilisates die bakterielle Stoffwechselaktivität überwacht, wobei dies ein Maß für das Vorhandensein von Hemmstoffen bzw. Nitrifikationssubstraten in einer Probe ist. Der Vorteil dieses Systems ist vor allem darin zu sehen, dass die damit durchgeführten Messungen sowohl schnell als auch reproduzierbar durchführbar sind. So ist mit diesem Geräteprototyp über die Durchführung von ca. 10 – 15 Einzelmessungen verschiedener Probenverdünnungen die Quantifizierung der Hemmwirkung von einer Probe pro Messtag möglich. Schlussfolgerung und Ausblick Die Untersuchungen zur Bestimmung der nitrifikationshemmenden Wirkung von Standardhemmstoffen, Abwasserproben und des N-BSB ergaben, dass die neu entwickelten Nitrifikanten-Biosensoren schnell und mit hoher Signalstabilität auf sich ändernde Hemmstoff- und Substratkonzentrationen reagieren und somit für die Klärwerksüberwachung prinzipiell einsetzbar sind

    Polarized recombination of acoustically transported carriers in GaAs nanowires

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    The oscillating piezoelectric field of a surface acoustic wave (SAW) is employed to transport photoexcited electrons and holes in GaAs nanowires deposited on a SAW delay line on a LiNbO3 crystal. The carriers generated in the nanowire by a focused light spot are acoustically transferred to a second location where they recombine. We show that the recombination of the transported carriers occurs in a zinc blende section on top of the predominant wurtzite nanowire. This allows contactless control of the linear polarized emission by SAWs which is governed by the crystal structure. Additional polarization-resolved photoluminescence measurements were performed to investigate spin conservation during transport
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