Improvement of protective oxide layers formed by high-frequency plasma electrolytic oxidation on Mg-RE alloy with LPSO-phase

Oxide layers on Mg97Y2Zn1 magnesium alloy with strengthening LPSO-phase were formed by plasma electrolytic oxidation (PEO) in bipolar mode with frequency variation of forming current pulses (50 and 500 Hz) and addition of sodium aluminate or sodium silicate to alkali phosphate fluoride electrolyte. Microstructure, chemical and phase composition, corrosion and mechanical properties of the oxide layers formed were investigated. With increasing current frequency for both electrolytes, an increase in homogeneity of the oxide layers structure and a decrease in their porosity and fracturing at constant thickness were recorded. The oxide layers formed at 500 Hz even with some decrease in hardness have better adhesive strength and 2 orders of magnitude higher short-term corrosion resistance values. PEO of Mg-alloy with LPSO-phase in the electrolyte with addition of sodium aluminate in combination with increased pulse frequency (500 Hz) allows forming the best-quality uniform oxide layer with high hardness, adhesive strength and corrosion resistance properties. The use of electrolyte with addition of sodium silicate reduced the adhesive strength by 1.5 times and brought down the long-term corrosion resistance of oxide layers by an order of magnitude, as compared with the electrolyte with sodium aluminate. The reason for a significant improvement in the complex of protective properties of the oxide layers with an increase in the current pulse frequency is supposed to be a decrease in the power and duration of individual microarc discharges with simultaneous increase in their number per unit oxidized area

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Electrophysiological and Structural Remodeling in Heart Failure Modulate Arrhythmogenesis. 1D Simulation Study

Background: Heart failure is a final common pathway or descriptor for various cardiac pathologies. It is associated with sudden cardiac death, which is frequently caused by ventricular arrhythmias. Electrophysiological remodeling, intercellular uncoupling, fibrosis and autonomic imbalance have been identified as major arrhythmogenic factors in heart failure etiology and progression. Objective: In this study we investigate in silico the role of electrophysiological and structural heart failure remodeling on the modulation of key elements of the arrhythmogenic substrate, i.e., electrophysiological gradients and abnormal impulse propagation. Methods: Two different mathematical models of the human ventricular action potential were used to formulate models of the failing ventricular myocyte. This provided the basis for simulations of the electrical activity within a transmural ventricular strand. Our main goal was to elucidate the roles of electrophysiological and structural remodeling in setting the stage for malignant life-threatening arrhythmias. Results: Simulation results illustrate how the presence of M cells and heterogeneous electrophysiological remodeling in the human failing ventricle modulate the dispersion of action potential duration and repolarization time. Specifically, selective heterogeneous remodeling of expression levels for the Na+ /Ca2+ exchanger and SERCA pump decrease these heterogeneities. In contrast, fibroblast proliferation and cellular uncoupling both strongly increase repolarization heterogeneities. Conduction velocity and the safety factor for conduction are also reduced by the progressive structural remodeling during heart failure. Conclusion: An extensive literature now establishes that in human ventricle, as heart failure progresses, gradients for repolarization are changed significantly by protein specific electrophysiological remodeling (either homogeneous or heterogeneous). Our simulations illustrate and provide new insights into this. Furthermore, enhanced fibrosis in failing hearts, as well as reduced intercellular coupling, combine to increase electrophysiological gradients and reduce electrical propagation. In combination these changes set the stage for arrhythmias.This work was partially supported by (i) the "VI Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica" from the Ministerio de Economia y Competitividad of Spain (grant number TIN2012-37546-C03-01) and the European Commission (European Regional Development Funds - ERDF - FEDER), (ii) the Direccion General de Politica Cientifica de la Generalitat Valenciana (grant number GV/2013/119), and (iii) Programa Prometeo (PROMETEO/2012/030) de la Conselleria d'Educacio Formacio I Ocupacio, Generalitat Valenciana. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Gómez García, JF.; Cardona, K.; Romero Pérez, L.; Ferrero De Loma-Osorio, JM.; Trénor Gomis, BA. (2014). Electrophysiological and Structural Remodeling in Heart Failure Modulate Arrhythmogenesis. 1D Simulation Study. PLoS ONE. 9(9). https://doi.org/10.1371/journal.pone.0106602S9

Clinical-functional and morphological parameters of purulonecrotic foci healing in diabetic foot syndrome using programmable sanitation technologies

Diabetes mellitus is currently characterised by a high progressive prevalence of patients. The purpose of this study is to evaluate the clinical, functional, and morphological parameters of purulonecrotic foci healing in diabetic foot syndrome (DFS) using programmable sanitation technologies. The patients were randomised into two groups. In the comparison group (n=51), patients received conventional local treatment after surgery. In the main group (n=55), after surgical treatment, the wound was sutured, and in the postsurgical period, programmable sanitation was conducted using the AMP-01 device. The cytological smears of the main group identified a higher rate of cellular reactions in the wound. There was a 1.3-fold reduction in the duration of hospitalisation, the number of purulent complications was significantly less (p=0.014). It was possible to preserve the supporting function of the foot in patients of the main group in a larger percentage of cases (p=0.023). There was a statistically significant increase in the frequency of high amputations in the comparison group (p=0.026). As a result, the effectiveness of the use of programmable sanitation technologies for purulent lesions of the diabetic foot has been proven

Comparative Investigation of the Influence of Ultrafine-Grained State on Deformation and Temperature Behavior and Microstructure Formed during Quasi-Static Tension of Pure Titanium and Ti-45Nb Alloy by Means of Infrared Thermography

A comprehensive study was performed of the deformation and temperature behavior during quasi-static tension, as well as the peculiarities of accumulation and dissipation of energy during plastic deformation. Microstructural analysis at the pre-fracture stage of pure titanium and Ti-45Nb alloy in the coarse grain (CG) and ultrafine-grained (UFG) states was also conducted. It was shown that substructural and dispersion hardening leads to a change in the regularities of dissipation and accumulation energies during deformation of the samples of the pure titanium and Ti-45Nb alloy in the UFG state. Some features of structural transformations during deformation of the pure titanium and Ti-45Nb alloy samples in the CG and UFG states were studied. A band and cellular-network and fragmented dislocation structure was formed in the case of the CG state, while large anisotropic fragments were formed in the UFG state, thus specifying a local softening of the material before fracture

Identification and Characterization of EctR1, a New Transcriptional Regulator of the Ectoine Biosynthesis Genes in the Halotolerant Methanotroph Methylomicrobium alcaliphilum 20Z▿ †

Genes encoding key enzymes of the ectoine biosynthesis pathway in the halotolerant obligate methanotroph Methylomicrobium alcaliphilum 20Z have been shown to be organized into an ectABC-ask operon. Transcription of the ect operon is initiated from two promoters, ectAp1 and ectAp2 (ectAp1p2), similar to the σ70-dependent promoters of Escherichia coli. Upstream of the gene cluster, an open reading frame (ectR1) encoding a MarR-like transcriptional regulator was identified. Investigation of the influence of EctR1 on the activity of the ectAp1p2 promoters in wild-type M. alcaliphilum 20Z and ectR1 mutant strains suggested that EctR1 is a negative regulator of the ectABC-ask operon. Purified recombinant EctR1-His6 specifically binds as a homodimer to the putative −10 motif of the ectAp1 promoter. The EctR1 binding site contains a pseudopalindromic sequence (TATTTAGT-GT-ACTATATA) composed of 8-bp half-sites separated by 2 bp. Transcription of the ectR1 gene is initiated from a single σ70-like promoter. The location of the EctR1 binding site between the transcriptional and translational start sites of the ectR1 gene suggests that EctR1 may regulate its own expression. The data presented suggest that in Methylomicrobium alcaliphilum 20Z, EctR1-mediated control of the transcription of the ect genes is not the single mechanism for the regulation of ectoine biosynthesis

Ultrasensitive Detection of 2,4-Dinitrophenol Using Nanowire Biosensor

The method for the detection of 2,4-dinitrophenol (DNP) in solution is proposed. This method employs the sensors based on silicon nanowire field-effect transistors with protective layers of high-k dielectrics, whose surface is functionalized with an amino silane. Direct highly sensitive detection of DNP has been demonstrated, and the lowest detectable concentration of DNP was determined to be 10−14 M. Silicon-on-insulator nanowire (SOI-NW) sensors can well be employed for the rapid detection of a wide range of toxic and explosive compounds by selection of sensor surface modification techniques

Synthesis and Properties of Rubidium Salts of Phosphotungstic Acid

The work is devoted to the study of the influence of synthesis conditions on the properties of water-insoluble rubidium salts of phosphotungstic acid (PTA). Such heteropoly compounds have a wide range of applications, including in the field of electrocatalysts and solid electrolytes for various electrochemical devices. The acid salts of PTA with high activity of acid sites on the particle surface are of particular interest. It is known that the properties of water-insoluble PTA salts strongly depend on synthesis conditions, such as the ratio of reagents, temperature, concentrations, and other parameters. The work examines the influence of the ratio and concentration of reagents on the sizes of crystallites and agglomerates, specific surface area (SSA), porosity, water content, and ionic conductivity of the synthesized PTA salts. The SSA value of the obtained samples varied in the range of 84–123 m2 g−1, and the ionic conductivity was 13–90 mS cm−1 at room temperature and 75% RH. An increase in the acid concentration and the degree of proton substitution led to an increase in SSA, accompanied by an increase in particle sizes without changing the size of crystallites. The results of the work may be useful for the development of new materials based on the obtained salts in many fields, including hydrogen energy

Micro-Raman Spectroscopy for Monitoring of Deposition Quality of High-k Stack Protective Layer onto Nanowire FET Chips for Highly Sensitive miRNA Detection

Application of micro-Raman spectroscopy for the monitoring of quality of high-k (h-k) dielectric protective layer deposition onto the surface of a nanowire (NW) chip has been demonstrated. A NW chip based on silicon-on-insulator (SOI) structures, protected with a layer of high-k dielectric ((h-k)-SOI-NW chip), has been employed for highly sensitive detection of microRNA (miRNA) associated with oncological diseases. The protective dielectric included a 2-nm-thick Al2O3 surface layer and a 8-nm-thick HfO2 layer, deposited onto a silicon SOI-NW chip. Such a chip had increased time stability upon operation in solution, as compared with an unprotected SOI-NW chip with native oxide. The (h-k)-SOI-NW biosensor has been employed for the detection of DNA oligonucleotide (oDNA), which is a synthetic analogue of miRNA-21 associated with oncological diseases. To provide biospecificity of the detection, the surface of (h-k)-SOI-NW chip was modified with oligonucleotide probe molecules (oDVA probes) complementary to the sequence of the target biomolecule. Concentration sensitivity of the (h-k)-SOI-NW biosensor at the level of DL~10−16 M has been demonstrated

Highly Sensitive Detection of CA 125 Protein with the Use of an n-Type Nanowire Biosensor

The detection of CA 125 protein in a solution using a silicon-on-insulator (SOI)-nanowire biosensor with n-type chip has been experimentally demonstrated. The surface of nanowires was modified by covalent immobilization of antibodies against CA 125 in order to provide the biospecificity of the target protein detection. We have demonstrated that the biosensor signal, which results from the biospecific interaction between CA 125 and the covalently immobilized antibodies, increases with the increase in the protein concentration. At that, the minimum concentration, at which the target protein was detectable with the SOI-nanowire biosensor, amounted to 1.5 × 10−16 M