Restoration of energy homeostasis by SIRT6 extends healthy lifespan

Aging leads to a gradual decline in physical activity and disrupted energy homeostasis. The NAD+-dependent SIRT6 deacylase regulates aging and metabolism through mechanisms that largely remain unknown. Here, we show that SIRT6 overexpression leads to a reduction in frailty and lifespan extension in both male and female B6 mice. A combination of physiological assays, in vivo multi-omics analyses and 13C lactate tracing identified an age-dependent decline in glucose homeostasis and hepatic glucose output in wild type mice. In contrast, aged SIRT6-transgenic mice preserve hepatic glucose output and glucose homeostasis through an improvement in the utilization of two major gluconeogenic precursors, lactate and glycerol. To mediate these changes, mechanistically, SIRT6 increases hepatic gluconeogenic gene expression, de novo NAD+ synthesis, and systemically enhances glycerol release from adipose tissue. These findings show that SIRT6 optimizes energy homeostasis in old age to delay frailty and preserve healthy aging

Crosstalk between Mitochondrial and Sarcoplasmic Reticulum Ca2+ Cycling Modulates Cardiac Pacemaker Cell Automaticity

Mitochondria dynamically buffer cytosolic Ca(2+) in cardiac ventricular cells and this affects the Ca(2+) load of the sarcoplasmic reticulum (SR). In sinoatrial-node cells (SANC) the SR generates periodic local, subsarcolemmal Ca(2+) releases (LCRs) that depend upon the SR load and are involved in SANC automaticity: LCRs activate an inward Na(+)-Ca(2+) exchange current to accelerate the diastolic depolarization, prompting the ensemble of surface membrane ion channels to generate the next action potential (AP).To determine if mitochondrial Ca(2+) (Ca(2+) (m)), cytosolic Ca(2+) (Ca(2+) (c))-SR-Ca(2+) crosstalk occurs in single rabbit SANC, and how this may relate to SANC normal automaticity.Inhibition of mitochondrial Ca(2+) influx into (Ru360) or Ca(2+) efflux from (CGP-37157) decreased [Ca(2+)](m) to 80 ± 8% control or increased [Ca(2+)](m) to 119 ± 7% control, respectively. Concurrent with inhibition of mitochondrial Ca(2+) influx or efflux, the SR Ca(2+) load, and LCR size, duration, amplitude and period (imaged via confocal linescan) significantly increased or decreased, respectively. Changes in total ensemble LCR Ca(2+) signal were highly correlated with the change in the SR Ca(2+) load (r(2) = 0.97). Changes in the spontaneous AP cycle length (Ru360, 111 ± 1% control; CGP-37157, 89 ± 2% control) in response to changes in [Ca(2+)](m) were predicted by concurrent changes in LCR period (r(2) = 0.84).A change in SANC Ca(2+) (m) flux translates into a change in the AP firing rate by effecting changes in Ca(2+) (c) and SR Ca(2+) loading, which affects the characteristics of spontaneous SR Ca(2+) release

Study of adsorption states in ZnO—Ag gas-sensitive ceramics using the ECTV curves method

The ZnO—Ag ceramic system as the material for semiconductor sensors of ethanol vapors was proposed quite a long time ago. The main goal of this work was to study surface electron states of this system and their relation with the electric properties of the material. The quantity of doping with Ag2O was changed in the range of 0,1–2,0% of mass. The increase of the Ag doping leads to a shift of the Fermi level down (closer to the valence zone). The paper presents research results on electrical properties of ZnO-Ag ceramics using the method of thermal vacuum curves of electrical conductivity. Changes in the electrical properties during heating in vacuum in the temperature range of 300—800 K were obtained and discussed. The increase of Tvac leads to removal of oxygen from the surface of samples The oxygen is adsorbed in the form of O2– and O– ions and is the acceptor for ZnO. This results in the lowering of the inter-crystallite potential barriers in the ceramic. The surface electron states (SES) above the Fermi level are virtually uncharged. The increase of the conductivity causes desorption of oxygen from the SES settled below the Fermi level of the semiconductor. The model allows evaluating the depth of the Fermi level in the inhomogeneous semiconductor materials

Study of adsorption states in ZnO—Ag gas-sensitive ceramics using the ECTV curves method

The ZnO–Ag ceramic system as the material for semiconductor sensors of ethanol vapors was proposed quite a long time ago. The main goal of this work was to study surface electron states of this system and their relation with the electric properties of the material. The quantity of doping with Ag2O was changed in the range of 0.1–2.0% of mass. The increase of the Ag doping leads to a shift of the Fermi level down (closer to the valence zone). The paper presents research results on electrical properties of ZnO–Ag ceramics using the method of thermal vacuum curves of electrical conductivity. Changes in the electrical properties during heating in vacuum in the temperature range of 300–800 K were obtained and discussed. The increase of Tvac leads to removal of oxygen from the surface of samples The oxygen is adsorbed in the form of O2– and O– ions and is the acceptor for ZnO. This results in the lowering of the inter-crystallite potential barriers in the ceramic. The surface electron states (SES) above the Fermi level are virtually uncharged. The increase of the conductivity causes desorption of oxygen from the SES settled below the Fermi level of the semiconductor. The model allows evaluating the depth of the Fermi level in the inhomogeneous semiconductor materials

Geometric Modeling IN THE Problems OF Lever Mechanism Kinematics Research

Abstract General information about the elements of lever mechanisms consisting of kinematic pairs is presented. The classification features of pairs are given: constraining conditions imposed by this pair, their graphic images, as well as brief descriptions of some of them. Two main problems of kinematics are highlighted. There are two main methods for solving the first problem of kinematics related to the solution of mechanism positioning questions: analytical and numerical. The second problem is an inverse one. A variety of methods for solving it is shown in the paper. The choice or development of the method is mainly determined by the complexity of the mechanism. The analysis of the documentary flow on the problem of kinematics of lever mechanisms allowed us to identify the main areas of research in this area. One of the promising areas is geometric computer modeling, which has a number of advantages in comparison with others. Its application makes it possible to study not only coordinate spaces formed by geometric elements of the lever mechanisms themselves, but also objects generated by products involved in these mechanisms functioning. The line of such research allows us to improve directly CAD systems used in modeling and obtain new results in various application areas, which is an urgent task.</jats:p

Modeling of shaping process and analysis of gear wheel cutting process by means of AUTOCAD and ANSYS software

Abstract In the present paper methodology of computer aided geometric modeling of formation of workpieces with periodic teeth machined with centroid enveloping method is developed without involving complex mathematical apparatus. During its application, as opposed to already known methods, simultaneous modeling of two objects of formation – wraparound and removed contents – takes place. Analysis of configurations of solid models of cutaway layers and respective removed content volumes allows a design engineer to intentionally set the optimal values of tool advance parameter and number of passes. The key point of the present paper is to establish logical connection between geometric computer simulation of removed contents in CAD environment and analysis of chip formation in the process of cutting using ANSYS software. In the present paper AutoCAD 3D simulations rendering of cutaway layers is shown along with the corresponding realistic simulation of chips, created using metal cutting process finite element analysis software. Due to substantial difficulties of cutting process 3D simulation, it is considered reasonable to perform computer simulation of cutaway layers geometry generation on the first stage of problem solving. This will allow us to choose the optimal cutting parameters and consequently speed up the cutting process simulation.</jats:p