Qualitative analysis of motion properties of semistate models of large-scale systems

This paper studies the behavior of motions of large-scale (LS) semistate systems (SSS) governed byP _i (t)x _i =M _i (t,x _i )x _i +f _i (t)+h _i (t, x), i=1,2,...,s, =(x ₁ ^T x ₂ ^T x _s ^T )^T, where matricesP _i (t) are singular. Using Lyapunov's approach and the tools for LS system analysis, a variant of attractivity and ultimate boundedness of appropriate time-variable sets are investigated. The results are based on a specific choice of the aggregate functions. It is assumed that the reduction of equations to a normal form of lower order is inconvenient. The aggregation-decomposition approach used in this paper reduces the dimensionality of an aggregate matrix of the system to the number of its systems. Motion properties of LS systems are deduced from the properties of its isolated subsystems, the character of interconnections, and the conditions imposed on the system aggregate matrix. Sufficient algebraic conditions for the above-mentioned motion properties are developed.     

Early Lipid Raft-Related Changes: Interplay between Unilateral Denervation and Hindlimb Suspension

Muscle disuse and denervation leads to muscle atrophy, but underlying mechanisms can be different. Previously, we have found ceramide (Cer) accumulation and lipid raft disruption after acute hindlimb suspension (HS), a model of muscle disuse. Herein, using biochemical and fluorescent approaches the influence of unilateral denervation itself and in combination with short-term HS on membrane-related parameters of rat soleus muscle was studied. Denervation increased immunoexpression of sphingomyelinase and Cer in plasmalemmal regions, but decreased Cer content in the raft fraction and enhanced lipid raft integrity. Preliminary denervation suppressed (1) HS-induced Cer accumulation in plasmalemmal regions, shown for both nonraft and raft-fractions; (2) HS-mediated decrease in lipid raft integrity. Similar to denervation, inhibition of the sciatic nerve afferents with capsaicin itself increased Cer plasmalemmal immunoexpression, but attenuated the membrane-related effects of HS. Finally, both denervation and capsaicin treatment increased immunoexpression of proapoptotic protein Bax and inhibited HS-driven increase in antiapoptotic protein Bcl-2. Thus, denervation can increase lipid raft formation and attenuate HS-induced alterations probably due to decrease of Cer levels in the raft fraction. The effects of denervation could be at least partially caused by the loss of afferentation. The study points to the importance of motor and afferent inputs in control of Cer distribution and thereby stability of lipid rafts in the junctional and extrajunctional membranes of the muscle.     

Prediction of Functional Consequences of Missense Mutations in ANO4 Gene

The anoctamin (TMEM16) family of transmembrane protein consists of ten members in vertebrates, which act as Ca²⁺-dependent ion channels and/or Ca²⁺-dependent scramblases. ANO4 which is primarily expressed in the CNS and certain endocrine glands, has been associated with various neuronal disorders. Therefore, we focused our study on prioritizing missense mutations that are assumed to alter the structure and stability of ANO4 protein. We employed a wide array of evolution and structure based in silico prediction methods to identify potentially deleterious missense mutations in the ANO4 gene. Identified pathogenic mutations were then mapped to the modeled human ANO4 structure and the effects of missense mutations were studied on the atomic level using molecular dynamics simulations. Our data show that the G80A and A500T mutations significantly alter the stability of the mutant proteins, thus providing new perspective on the role of missense mutations in ANO4 gene. Results obtained in this study may help to identify disease associated mutations which affect ANO4 protein structure and function and might facilitate future functional characterization of ANO4.     

The dynamic evolution of aggregated lithium dendrites in lithium metal batteries

Lithium (Li) metal anodes promise an ultrahigh theoretical energy density and low redox potential,thus being the critical energy material for next-generation batteries.Unfortunately,the formation of Li den-drites in Li metal anodes remarkably hinders the practical applications of Li metal anodes.Herein,the dynamic evolution of discrete Li dendrites and aggregated Li dendrites with increasing current densities is visualized by in-situ optical microscopy in conjunction with ex-situ scanning electron microscopy.As revealed by the phase field simulations,the formation of aggregated Li dendrites under high current den-sity is attributed to the locally concentrated electric field rather than the depletion of Li ions.More specif-ically,the locally concentrated electric field stems from the spatial inhomogeneity on the Li metal surface and will be further enhanced with increasing current densities.Adjusting the above two factors with the help of the constructed phase field model is able to regulate the electrodeposited morphology from aggregated Li dendrites to discrete Li dendrites,and ultimately columnar Li morphology.The methodol-ogy and mechanistic understanding established herein give a significant step toward the practical appli-cations of Li metal anodes.     

Cardioinotropic Effects in Subchronic Intoxication of Rats with Lead and/or Cadmium Oxide Nanoparticles

Subchronic intoxication was induced in outbred male rats by repeated intraperitoneal injections with lead oxide (PbO) and/or cadmium oxide (CdO) nanoparticles (NPs) 3 times a week during 6 weeks for the purpose of examining its effects on the contractile characteristics of isolated right ventricle trabeculae and papillary muscles in isometric and afterload contractions. Isolated and combined intoxication with these NPs was observed to reduce the mechanical work produced by both types of myocardial preparation. Using the in vitro motility assay, we showed that the sliding velocity of regulated thin filaments drops under both isolated and combined intoxication with CdO–NP and PbO–NP. These results correlate with a shift in the expression of myosin heavy chain (MHC) isoforms towards slowly cycling β–MHC. The type of CdO–NP + PbO–NP combined cardiotoxicity depends on the effect of the toxic impact, the extent of this effect, the ratio of toxicant doses, and the degree of stretching of cardiomyocytes and muscle type studied. Some indices of combined Pb–NP and CdO–NP cardiotoxicity and general toxicity (genotoxicity included) became fully or partly normalized if intoxication developed against background administration of a bioprotective complex.     

Pre-Senescence Induction in Hepatoma Cells Favors Hepatitis C Virus Replication and Can Be Used in Exploring Antiviral Potential of Histone Deacetylase Inhibitors

Recent evidence suggests that fibrotic liver injury in patients with chronic hepatitis C correlates with cellular senescence in damaged liver tissue. However, it is still unclear how senescence can affect replication of the hepatitis C virus (HCV). In this work, we report that an inhibitor of cyclin-dependent kinases 4/6, palbociclib, not only induced in hepatoma cells a pre-senescent cellular phenotype, including G1 arrest in the cell cycle, but also accelerated viral replicon multiplication. Importantly, suppression of HCV replication by direct acting antivirals (DAAs) was barely affected by pre-senescence induction, and vice versa, the antiviral activities of host-targeting agents (HTAs), such as inhibitors of human histone deacetylases (HDACi), produced a wide range of reactions—from a dramatic reduction to a noticeable increase. It is very likely that under conditions of the G1 arrest in the cell cycle, HDACi exhibit their actual antiviral potency, since their inherent anticancer activity that complicates the interpretation of test results is minimized.     

Molecular Mechanisms of the Deregulation of Muscle Contraction Induced by the R90P Mutation in Tpm3.12 and the Weakening of This Effect by BDM and W7

Point mutations in the genes encoding the skeletal muscle isoforms of tropomyosin can cause a range of muscle diseases. The amino acid substitution of Arg for Pro residue in the 90th position (R90P) in γ-tropomyosin (Tpm3.12) is associated with congenital fiber type disproportion and muscle weakness. The molecular mechanisms underlying muscle dysfunction in this disease remain unclear. Here, we observed that this mutation causes an abnormally high Ca²⁺-sensitivity of myofilaments in vitro and in muscle fibers. To determine the critical conformational changes that myosin, actin, and tropomyosin undergo during the ATPase cycle and the alterations in these changes caused by R90P replacement in Tpm3.12, we used polarized fluorimetry. It was shown that the R90P mutation inhibits the ability of tropomyosin to shift towards the outer domains of actin, which is accompanied by the almost complete depression of troponin’s ability to switch actin monomers off and to reduce the amount of the myosin heads weakly bound to F-actin at a low Ca²⁺. These changes in the behavior of tropomyosin and the troponin–tropomyosin complex, as well as in the balance of strongly and weakly bound myosin heads in the ATPase cycle may underlie the occurrence of both abnormally high Ca²⁺-sensitivity and muscle weakness. BDM, an inhibitor of myosin ATPase activity, and W7, a troponin C antagonist, restore the ability of tropomyosin for Ca²⁺-dependent movement and the ability of the troponin–tropomyosin complex to switch actin monomers off, demonstrating a weakening of the damaging effect of the R90P mutation on muscle contractility.     

Direct Synthesis and Sintering of Silicon Nitridenitanium Nitride Composite

Electrical discharge machining is an attractive machining technique which requires electrically conductive ceramic materials. Silicon nitride based composites with 35–40% of TiN possess electrical conductivity high enough to use this machining technique. The composite powder was prepared by combustion synthesis and densified by pressure sintering (sintering aids 6 wt% of Y₂O₃ and 4 wt% of A1,0₃). High fracture toughness, K _c 10.5 MPa^.m^1/2, is typical for the composite. It can be expected that this material can compete with pure silicon nitride in applications requiring complex machining.     

Optical–microphysical properties of smoke haze from Siberian forest fires in summer 2012

A comprehensive experiment on the study of dynamics of optical and microphysical characteristics of submicron aerosols in the near-ground air layer was carried out in June–August of 2012 under conditions of extremely strong smoke haze originating from vast forest fires in Siberia. Variations of the spectral angular scattering coefficients and the degree of linear polarization in the visible wavelength range are studied, as well as the mass concentrations of dry fractions of aerosol and black carbon, relative content of black carbon (BC fraction), single scattering albedo, particle size distribution function, complex refractive index of the particulate matter, and parameter of condensation activity of aerosol. Peculiarities of differences between optical and microphysical characteristics of near-ground aerosol in smoke haze and under smokeless conditions are revealed. This study is important for validation of results of remote sensing of the composition of smoke haze and background atmosphere obtained from satellite data and sun photometric measurements at the Aerosol Robotic Network (AERONET).