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

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

WRF‐TEB: implementation and evaluation of the coupled Weather Research and Forecasting (WRF) and Town Energy Balance (TEB) model

Urban land surface processes need to be represented to inform future urban‐climate and building‐energy projections. Here, the single layer urban canopy model Town Energy Balance (TEB) is coupled to the Weather Research and Forecasting (WRF) model to create WRF‐TEB. The coupling method is described generically, implemented into software, and the issue of scientific reproducibility is addressed by releasing all code and data with a Singularity image. The coupling is implemented modularly and verified by an integration test. Results show no detectable errors in the coupling. Separately, a meteorological evaluation is undertaken using observations from Toulouse, France. The latter evaluation, during an urban canopy layer heat island episode, shows reasonable ability to estimate turbulent heat flux densities and other meteorological quantities. We conclude that new model couplings should make use of integration tests as meteorological evaluations by themselves are insufficient, given that errors are difficult to attribute because of the interplay between observational errors and multiple parameterization schemes (e.g. radiation, microphysics, boundary layer)

Synthesis of quasi-free-standing bilayer graphene nanoribbons on SiC surfaces

Scaling graphene down to nanoribbons is a promising route for the implementation of this material into devices. Quantum confinement of charge carriers in such nanostructures, combined with the electric field-induced break of symmetry in AB-stacked bilayer graphene, leads to a band gap wider than that obtained solely by this symmetry breaking. Consequently, the possibility of fabricating AB-stacked bilayer graphene nanoribbons with high precision is very attractive for the purposes of applied and basic science. Here we show a method, which includes a straightforward air annealing, for the preparation of quasi-free-standing AB-bilayer nanoribbons with different widths on SiC(0001). Furthermore, the experiments reveal that the degree of disorder at the edges increases with the width, indicating that the narrower nanoribbons are more ordered in their edge termination. In general, the reported approach is a viable route towards the large-scale fabrication of bilayer graphene nanostructures with tailored dimensions and properties for specific applications

Effects of thermal annealing on the optical properties of InGaNAs/GaAs multiple quantum wells

We present an optical characterization of as-grown and thermally annealed InGaNAs/GaAs multiple quantum well samples. In both samples, from the analysis of the photoluminescence spectra we can infer that the low-temperature photoluminescence emission is related to carriers localized in the alloy potential fluctuations; with increasing temperature, we observe their gradual delocalization and then the transition towards a completely different type of lineshape, typical of free carrier recombinations. The comparison between the photoluminescence spectra of the as-grown and the annealed samples shows that a remarkable improvement of the optical properties occurs after the thermal annealing. This improvement is related to an important reduction in the density of the defects and in the depth of the alloy potential fluctuations

Anisotropic exchange interaction of localized conduction-band electrons in semiconductor structures

The spin-orbit interaction in semiconductors is shown to result in an anisotropic contribution into the exchange Hamiltonian of a pair of localized conduction-band electrons. The anisotropic exchange interaction exists in semiconductor structures which are not symmetric with respect to spatial inversion, for instance in bulk zinc-blend semiconductors. The interaction has both symmetric and antisymmetric parts with respect to permutation of spin components. The antisymmetric (Dzyaloshinskii-Moriya) interaction is the strongest one. It contributes significantly into spin relaxation of localized electrons; in particular, it governs low-temperature spin relaxation in n-GaAs with the donor concentration near 10^16cm-3. The interaction must be allowed for in designing spintronic devices, especially spin-based quantum computers, where it may be a major source of decoherence and errors

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

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

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

Species-specific responses of planktivorous fish to the introduction of a new piscivore: implications for prey fitness

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75539/1/j.1365-2427.2007.01810.x.pd