GRK5 deficiency exaggerates inflammatory changes in TgAPPsw mice

<p>Abstract</p> <p>Background</p> <p>Deficiency of membrane G-protein coupled receptor (GPCR) kinase-5 (GRK5) recently has been linked to early AD pathogenesis, and has been suggested to contribute to augmented microglial activation <it>in vitro </it>by sensitizing relevant GPCRs. However, GRK5 deficient mice did not show any signs of microgliosis, except for their moderate increase in axonal defects and synaptic degenerative changes during aging. We have speculated that one possible reason for the absence of microgliosis in these animals might be due to lack of an active inflammatory process involving activated GPCR signaling, since GRKs only act on activated GPCRs. The objective of this study was to determine whether the microgliosis is exaggerated in TgAPPsw (Tg2576) mice also deficient in GRK5, in which fibrillar β-amyloid (Aβ) and an active inflammatory process involving activated GPCR signaling are present.</p> <p>Methods</p> <p>Both quantitative and qualitative immunochemistry methods were used to evaluate the microgliosis and astrogliosis in these animals. </p> <p/> <p>Results</p> <p>We found that inactivation of one copy of the GRK5 gene in the TgAPPsw mice resulted in approximately doubled extent of microgliosis, along with significantly exaggerated astrogliosis, in both hippocampus and cortex of the aged animals. Consistent with previous observations, the activated microglia were located primarily near or surrounding the fibrillar Aβ deposits.</p> <p>Conclusion</p> <p>The results demonstrate that GRK5 deficiency <it>in vivo </it>significantly exaggerates microgliosis and astrogliosis in the presence of an inflammatory initiator, such as the excess fibrillar Aβ and the subsequent active inflammatory reactions in the TgAPPsw mice.</p

Kinetic Monte Carlo simulations of oscillatory shape evolution for electromigration-driven islands

The shape evolution of two-dimensional islands under electromigration-driven periphery diffusion is studied by kinetic Monte Carlo (KMC) simulations and continuum theory. The energetics of the KMC model is adapted to the Cu(100) surface, and the continuum model is matched to the KMC model by a suitably parametrized choice of the orientation-dependent step stiffness and step atom mobility. At 700 K shape oscillations predicted by continuum theory are quantitatively verified by the KMC simulations, while at 500 K qualitative differences between the two modeling approaches are found.Comment: 7 pages, 6 figure

``Electric growth`` of metal overlayers on semiconductor substrates

In this article, the authors present the main results from their recent studies of metal overlayer growth on semiconductor substrates. They show that a variety of novel phenomena can exist in such systems, resulting from several competing interactions. The confined motion of the conduction electrons within the metal overlayer can mediate a surprisingly long-range repulsive force between the metal-semiconductor interface and the growth front, acting to stabilize the overlayer. Electron transfer from the overlayer to the substrate leads to an attractive force between the two interfaces, acting to destabilize the overlayer. Interface-induced Friedel oscillations in electron density can further impose an oscillatory modulation onto the two previous interactions. These three competing factors, of all electronic nature, can make a flat metal overlayer critically, marginally, or magically stable, or totally unstable against roughening. The authors further show that, for many systems, these electronic effects can easily win over the effect of stress. First-principles studies of a few representative systems support the main features of the present electronic growth concept

Mechanical theory of the film-on-substrate-foil structure : curvature and overlay alignment in amorphous silicon thin-film devices fabricated on free-standing foil substrates

Flexible electronics will have inorganic devices grown at elevated temperatures on free-standing foil substrates. The thermal contraction mismatch between the substrate and the deposited device films, and the built-in stresses in these films, cause curving and a change in the in-plane dimensions of the workpiece. This change causes misalignment between the device layers. The thinner and more compliant the substrate, the larger the curvature and the misalignment. We model this situation with the theory of a bimetallic strip, which suggests that the misalignment can be minimized by tailoring the built-in stress introduced during film growth. Amorphous silicon thin-film transistors (a-Si:H TFTs) fabricated on stainless steel or polyimide (PI) (Kapton E®) foils need tensile built-in stress to compensate for the differential thermal contraction between the silicon films and the substrate. Experiments show that by varying the built-in stress in just one device layer, the gate silicon nitride (SiNx), one can reduce the misalignment between the source/drain and the gate levels from ∼400 parts-per-million to ∼100 parts-per-million

Fingering Instability of Dislocations and Related Defects

We identify a fundamental morphological instability of mobile dislocations in crystals and related line defects. A positive gradient in the local driving force along the direction of defect motion destabilizes long-wavelength vibrational modes, producing a ``fingering'' pattern. The minimum unstable wavelength scales as the inverse square root of the force gradient. We demonstrate the instability's onset in simulations of a screw dislocation in Al (via molecular dynamics) and of a vortex in a 3-d XY ``rotator'' model.Comment: 4 pages, 3 figure

Sintering Kinetics of Plasma-Sprayed Zirconia TBCs

A model of the sintering exhibited by EB-PVD TBCs, based on principles of free energy minimization, was recently published by Hutchinson et al. In the current paper, this approach is applied to sintering of plasma-sprayed TBCs and comparisons are made with experimental results. Predictions of through-thickness shrinkage and changing pore surface area are compared with experimental data obtained by dilatometry and BET analysis respectively. The sensitivity of the predictions to initial pore architecture and material properties are assessed. The model can be used to predict the evolution of contact area between overlying splats. This is in turn related to the through-thickness thermal conductivity, using a previously-developed analytical model

High power rechargeable magnesium/iodine battery chemistry

© The Author(s) 2017. Rechargeable magnesium batteries have attracted considerable attention because of their potential high energy density and low cost. However, their development has been severely hindered because of the lack of appropriate cathode materials. Here we report a rechargeable magnesium/iodine battery, in which the soluble iodine reacts with Mg2+ to form a soluble intermediate and then an insoluble final product magnesium iodide. The liquid-solid two-phase reaction pathway circumvents solid-state Mg2+ diffusion and ensures a large interfacial reaction area, leading to fast reaction kinetics and high reaction reversibility. As a result, the rechargeable magnesium/iodine battery shows a better rate capability (180 mAh g-1 at 0.5 C and 140 mAh g-1 at 1 C) and a higher energy density (∼400 Wh kg-1) than all other reported rechargeable magnesium batteries using intercalation cathodes. This study demonstrates that the liquid-solid two-phase reaction mechanism is promising in addressing the kinetic limitation of rechargeable magnesium batteries

Experimental and Simulation Study on the Emissions of a Multi-Point Lean Direct Injection Combustor

Spurred by the world’s attention to pollution emissions from commercial aero-engines, the International Civil Aviation Organization (ICAO) has made more stringent emission regulations for civil aircraft engines, especially the NOx emission.This paper develops a Five-Point lean direct injection (LDI) combustor with three swirler schemes to reduce the emissions of commercial aircraft engines. The flowfield of the combustor is studied numerically. Moreover, the combustion efficiency and gaseous emissions in different inlet conditions and fuel ratios of the main stage (α) are studied experimentally. The corresponding results reveal that, under a fuel-air ratio (FAR) between 0.0130 and 0.0283 and an α value between 30% and 60%, the combustion efficiency is 99.18%, 98.83%, and 99.03% when the pilot stage works alone, and 99.69%, 99.23%, and 99.75% when the pilot and main stage work simultaneously. Furthermore, the experimental results suggest that the NOx emission decreases as α increases, demonstrating that the convergent swirler has a tremendous advantage in reducing NOx emissions over Venturi

Cardiac Substrate Utilization and Relationship to Invasive Exercise Hemodynamic Parameters in HFpEF

We conducted transcardiac blood sampling in healthy subjects and subjects with heart failure with preserved ejection fraction (HFpEF) to compare cardiac metabolite and lipid substrate use. We demonstrate that fatty acids are less used by HFpEF hearts and that lipid extraction is influenced by hemodynamic factors including pulmonary pressures and cardiac index. The release of many products of protein catabolism is apparent in HFpEF compared to healthy myocardium. In subgroup analyses, differences in energy substrate use between female and male hearts were identified

An Inventory-Theory-Based Inexact Multistage Stochastic Programming Model for Water Resources Management

An inventory-theory-based inexact multistage stochastic programming (IB-IMSP) method is developed for planning water resources systems under uncertainty. The IB-IMSP is based on inexact multistage stochastic programming and inventory theory. The IB-IMSP cannot only effectively handle system uncertainties represented as probability density functions and discrete intervals but also efficiently reflect dynamic features of system conditions under different flow levels within a multistage context. Moreover, it can provide reasonable transferring schemes (i.e., the amount and batch of transferring as well as the corresponding transferring period) associated with various flow scenarios for solving water shortage problems. The applicability of the proposed IB-IMSP is demonstrated by a case study of planning water resources management. The solutions obtained are helpful for decision makers in not only identifying different transferring schemes when the promised water is not met, but also making decisions of water allocation associated with different economic objectives