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The work is devoted to the synthesis of new light-controlled voltage-gated sodium (Nav) channel blockers based on azobenzene and the study of their local anesthetic and antiarrhythmic properties. The effect of ethercaine and two of its new derivatives on native Nav channels was studied in vitro using the patch-clamp method on isolated excitable cells (neurons and cardiomyocytes) of a rat, and local anesthetic activity of the compounds was evaluated on rabbit's eye cornea. Studies of the effect of the obtained compounds on the conductivity of excitation waves in cardiomyocyte cultures using the optical mapping method were performed. The effective light-dependent biological activity of ethercaine and its derivatives allows us to consider the resulting compounds as potential tools for light-controlled local anesthesia, as well as for non-invasive ablation of arrhythmia in the heart in cardiology. [ABSTRACT FROM AUTHOR]

The spread of drug-resistant strains of Mycobacterium tuberculosis is a major threat to the global control of tuberculosis (TB), urging the need to constantly develop new anti-TB drugs. Tryptanthrins are convenient compounds for the development of candidate anti-TB drugs due to the easy synthesis, low toxicity, and antimycobacterial activity on both drug-susceptible and drug-resistant M. tuberculosis strains. Enoyl-acyl carrier protein reductase InhA was previously predicted in silico as a possible target for tryptanthrins, while spontaneous tryptanthrin-resistant M. smegmatis mutants were found to have mutations in the MSMEG_1963, MSMEG_4427, and MSMEG_5597 genes. Using the approaches of reverse genetics, we demonstrate that mutations in the MSMEG_1963 and MSMEG_5597 genes lead to a loss of function of their encoded transcriptional repressors and lead to resistance to tryptanthrins. We show that mutations in MSMEG_1963 and MSMEG_5597 lead to overexpression of MSMEG_1964 and MSMEG_5596, respectively, which encode enzymes potentially involved in redox inactivation of tryptanthrins. We also show that InhA is not a biotarget of tryptanthrins, as its overexpression does not affect susceptibility of mycobacteria to tryptanthrins. [ABSTRACT FROM AUTHOR]

Cyclic thermal analysis is used to study the effect of overheating ΔT+ of a melt on the presolidification supercooling of gallium–indium alloys. The existence of deep supercooling with respect to the liquidus is found for hypoeutectic alloys, whereas, for hypereutectic alloys, the supercooling is found only with respect to solidus TE (eutectic transformation line). The activities and the coefficients of activity of constituents are calculated at the onset of quasi-equilibrium and nonequilibrium explosive solidification. When the composition approaches the eutectic one, the activity of both constituents is found to decrease. [ABSTRACT FROM AUTHOR]

A combination of variational and empirical methods to determine the porosity is used to give a theoretical explanation of the power-law dependence of the dimensionless velocity of the constrained motion of particles during sedimentation. [ABSTRACT FROM AUTHOR]

The explosive solidification of supercooled liquids is analyzed using heating and cooling thermograms of various substances. As proof of the phenomenon of explosive solidification, thermograms in the temperature–time coordinates are presented for tellurium, bismuth, water, and acetic acid. A schematic cooling curve is used to demonstrate the structural changes occurring in a liquid phase and the stages of solidification, namely, the formation of crystal nuclei, their coalescence, and subsequent isothermal solidification. Explosive solidification at the second stage is characterized by a rapid temperature rise from a supercooling region to the melting temperature at the rates exceeding the cooling rate (i.e., heat removal) by 2–3 orders of magnitude. An attempt is made to explain the phenomenon of explosive solidification in terms of the well-known postulates of the cluster-coalescence model of solidification and the theory of chain reactions. The calculations demonstrate that the critical nucleus sizes are comparable with the unit cell sizes of the corresponding crystal lattices and the nucleus formation energy is comparable with the intermolecular bond energies. Based on the calculations of the heat released during nucleus formation and the interfacial surface energy released during the coalescence of crystal nuclei, we advance a hypothesis that crystalline clusters and stable crystal nuclei can serve as the "building blocks" of crystal growth along with molecules. The energy released during the formation of nuclei and their coalescence is shown to be equivalent to electromagnetic radiation quanta and to generate new centers of solidification, multiplication, and coalescence of nuclei. The calculations demonstrate that the energy released during the coalescence of many nuclei is high enough to quickly heat a substance from the supercooling region to the melting temperature. By analogy with the well-known thermal explosion diagram, we plotted and analyzed a similar diagram for the time dependence of the heat release and the heat removal during explosive solidification. The critical values of the beginning of the explosive process and the cooling rate of a liquid phase are found. The final stage of equilibrium solidification after explosive solidification is estimated. [ABSTRACT FROM AUTHOR]

An alternative approach to calculating the critical nucleus size and the nucleus formation energy has been developed. A significant difference between this method and the generally accepted so-called classical method, according to which a nucleation center begins to form at the melting temperature, is noted. The results are illustrated by the dependences of the nucleus size and the nucleus formation energy on the supercooling and by the Gibbs energy plotted as a function of the nucleus size in both the classical and the proposed versions. [ABSTRACT FROM AUTHOR]

The influence of the overheating of the Ga–14.2 mol % In eutectic alloy melt on the presolidification cooling is studied on 2-g samples by cyclic thermal analysis. In the case of the overheating of the liquid eutectic above the eutectic temperature Te = 288.3 by 28–30 K and subsequent cooling, the overheating dependence of the supercooling has a continuously increasing character. The limiting supercooling is ~25 K regardless of the preliminary overheating of the melt, from 30 to 100 K. The solidification from the supercooled state is found to have an "explosive" character at a rate of 40–45 K/s. The supercooling is not affected by long-term (for several hours) isothermal holding of the melt in overheated and supercooled states. The kinetic and thermodynamic parameters of the eutectic solidification are calculated using fusibility thermograms. [ABSTRACT FROM AUTHOR]

Cyclophosphamide (CP) is an anticancer drug, an alkylating agent. Cardiotoxicity of CP is associated with one of its metabolites, acrolein, and clinical cardiotoxicity manifestations are described for cases of taking CP in high doses. Nevertheless, modern arrhythmogenicity prediction assays in vitro include evaluation of beat rhythm and rate as well as suppression of cardiac late markers after acute exposure to CP, but not its metabolites. The mechanism of CP side effects when taken at low doses (i.e., < 100 mg/kg), especially at the cellular level, remains unclear. In this study conduction properties and cytoskeleton structure of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) obtained from a healthy donor under CP were evaluated. Arrhythmogenicity testing including characterization of 3 values: conduction velocity, maximum capture rate (MCR) measurements and number of occasions of re-entry on a standard linear obstacle was conducted and revealed MCR decrease of 25% ± 7% under CP. Also, conductivity area reduced by 34 ± 15%. No effect of CP on voltage-gated ion channels was found. Conduction changes (MCR and conductivity area decrease) are caused by exposure time-dependent alpha-actinin disruption detected both in hiPSC-CMs and neonatal ventricular cardiomyocytes in vitro. Deviation from the external stimulus frequency and appearance of non-conductive areas in cardiac tissue under CP is potentially arrhythmogenic and could develop arrhythmic effects in vivo. [ABSTRACT FROM AUTHOR]

This work analyzes the change in the Gibbs free energy during formation of nuclei with vacancies from melt. Formulas to determine dimensions lk of the critical nuclei and work Ak of their formation with respect to the concentration of vacancies and supercooling are obtained. The difference between lk and Ak for real nuclei and and for ideal nuclei is shown. [ABSTRACT FROM AUTHOR]

The paper presents the results of investigating sputtering by uranium fission fragments of thin carbon films produced by a method of thermal vacuum deposition. In accordance with the investigations carried out, the intensity of sputtering of carbon films does not exceed ~50 atoms per fission fragment, which indicates the possibility of their use as protective coatings for uranium layers. [ABSTRACT FROM AUTHOR]

Overcooling of gallium–tin alloys under normal conditions has been studied by thermal analysis. The following samples have been analyzed: Ga (I); two hypoeutectic alloys: 95% Ga + 5% Sn (II), 90% Ga + 10% Sn (III); eutectic alloy: 96.3% Ga + 13.7% Sn (IV); and five hypereutectic alloys with Sn content of 20% (V), 35% (VI), 50% (VII), 80% (VIII), and pure tin (IX). A nonequilibrium state diagram of this system is constructed. Herewith, the eutectic composition does not vary and the eutectic temperature decreases to 5.5°C, that is, 26°C below that of three-phase eutectic equilibrium. The eutectic temperature does not actually vary upon a variation of cooling rates of eutectic alloy from 0.06 to 60°C/min. It has been detected that a slight decrease in overcooling is expected in the hypoeutectic region, whereas in the hypereutectic region overcooling increases while the alloy composition approaches eutectic. Activities and activity coefficients of components on the lines of equilibrium and nonequilibrium liquidus have been calculated. It is demonstrated that the activities on the lines of both equilibrium and nonequilibrium liquidus decrease in a predictable manner, and the activity coefficients increase while the composition approaches eutectic. Concentration paths of equilibrium and nonequilibrium crystallization are shown in the state diagrams. [ABSTRACT FROM AUTHOR]

Dependences of free Gibbs energies GL and GS on the component content and temperature are analyzed for binary eutectic alloys, which are characterized by terminal solid solubility and are present in liquid (L), liquid–solid (LS), and solid (S) states. Using additional Gibbs energy GLS for the liquid–solid state, conditions for the most stable alloys in this region and melting (and solidification) paths during L → LS → S transitions are determined. [ABSTRACT FROM AUTHOR]

Emergence of drug-resistance to antituberculosis agents is a global challenge that requires development of novel drugs, active against resistant Mycobacterium tuberculosis strains. One of the tasks of drug development is to determine the mechanism of resistance of the pathogen to the drug candidate. The mycobacterial MmpS5-MmpL5 efflux system can provide resistance to a wide range of antibiotics, including bedaquiline, clofazimine, thiacetazones, azoles, and imidazo[1,2-b][1,2,4,5]tetrazines. We were able to construct a recombinant M. smegmatis Δmmp5 strain, which carries a deletion within the mmpS5-mmpL5 operon and is hypersensitive to imidazo[1,2-b][1,2,4,5]tetrazines. Comparing the sensitivity of M. smegmatis mc2 155 and M. smegmatis Δmmp5 to candidate antimycobacterials can be used as a test system for determining the possible role of the MmpS5-MmpL5 efflux system in developing drug resistance at early screening stages. [ABSTRACT FROM AUTHOR]

The laws of changing the presolidification supercooling of bismuth drops during continuous thermal cycling were studied by thermal analysis in the temperature–time coordinates. A sawtooth cyclic dependence of the supercooling on the sequence of heating and cooling cycles, which is described by a Fourier function, is detected. An expression is derived for the energy of coagulation of nuclei, and it is used to find a relation between the experimental and calculated supercoolings. The obtained results are interpreted in terms of a cluster-coagulation solidification model and the anomalous properties of bismuth in melting and solidification. [ABSTRACT FROM AUTHOR]

The processes of melting and solidification of the eutectic Sn-43 mol % Bi alloy are studied by cyclic thermal analysis. It is found that this alloy melts at a temperature T = 412 K (which corresponds to the reference melting temperature of the eutectic) upon heating and solidifies isothermally at a temperature T = 394 K upon cooling; that is, the temperature difference is Δ T = 18 K. A comparison of temperatures T and T reveals a temperature hysteresis (TH). The activities and the activity coefficients of tin and bismuth in the eutectic are calculated at temperatures T and T . The enthalpies of melting at T and solidification at TS are measured. The ways of changing the Gibbs energy during TH are determined. [ABSTRACT FROM AUTHOR]

Cyclic thermal analysis is used to study the effect of overheating of the eutectic Ga-8.5 mol % Sn melt on the presolidification supercooling. It is found that, when the liquid eutectic is overheated above the eutectic temperature ( T = 293.5 K) and is subsequently cooled, the dependence of the presolidification supercooling on the overheating temperature exhibits monotonic ascending behavior. The maximum supercooling after heating of the melt to 339 K is 26 K. The kinetic and thermodynamic parameters of eutectic solidification are calculated using the thermal analysis curves measured during melting. [ABSTRACT FROM AUTHOR]

STR haplotypes of the Y chromosome are widely used as effective genetic markers in studies of human populations and in forensic DNA analysis. The task often arises to compare the spectrum of haplotypes in individuals or entire populations. Performing this task manually is too laborious and thus unrealistic. We propose an algorithm for counting similarity between STR haplotypes. This algorithm is suitable for massive analyses of samples. It is implemented in the computer program Haplomatch, which makes it possible to find haplotypes that differ from the target haplotype by 0, 1, 2, 3, or more mutational steps. The program may operate in two modes: comparison of individuals and comparison of populations. Flexibility of the program (the possibility of using any external database), its usability (MS Excel spreadsheets are used), and the capability of being applied to other chromosomes and other species could make this software a new useful tool in population genetics and forensic and genealogical studies. The Haplomatch software is freely available on our website www.genofond.ru. The program is applied to studying the gene pool of Cossacks. Experimental analysis of Y-chromosomal diversity in a representative set ( N = 131) of Upper Don Cossacks is performed. Analysis of the STR haplotypes detects genetic proximity of Cossacks to East Slavic populations (in particular, to Southern and Central Russians, as well as to Ukrainians), which confirms the hypothesis of the origin of the Cossacks mainly due to immigration from Russia and Ukraine. Also, a small genetic influence of Turkicspeaking Nogais is found, probably caused by their occurrence in the Don Voisko as part of the Tatar layer. No similarities between haplotype spectra of Cossacks and Caucasus populations are found. This case study demonstrates the effectiveness of the Haplomatch software in analyzing large sets of STR haplotypes. [ABSTRACT FROM AUTHOR]

Fine powders with a modified surface have been prepared via treatment of unbleached softwood cellulose with titanium tetrachloride solutions in hexane. Titanium and chlorine have been detected in the composition of the aglomerates adsorbed onto the powder particles surfaces. Physicochemical properties of the samples have been shown to be dependent on Ti(IV) content on the modified surface. [ABSTRACT FROM AUTHOR]

Geometrical thermodynamics is used to analyze the possible dependences of the Gibbs energy on temperature and component concentration in the two-phase region during nonequilibrium solidification of eutectic alloys. [ABSTRACT FROM AUTHOR]

It is established via an X-ray method that the preparation of powdered forms of cellulose under the action of Lewis acids on fibrous hardwood cellulose is accompanied by a change in its crystallographic characteristics. The degrees of crystallinity, the sizes of crystallites, and the periods and monoclinic angles of the unit cells of the obtained powdered celluloses were determined. [ABSTRACT FROM AUTHOR]

The effect of overheating Δ T of the gallium melt on its supercooling Δ T during solidification is studied by cyclic thermographic analysis. The obtained data on Δ T are used to calculate the thermodynamic and kinetic characteristics of gallium solidification. [ABSTRACT FROM AUTHOR]

A review of experimental and analytical investigations of the energy deposition into the cells of nuclear-pumped lasers is presented. Three experimental techniques for energy deposit determination are considered: pressure jump method, interferometric method, and the method of string calorimeters. Comparative analysis of experimental and analytical data on the energy deposit is conducted. [ABSTRACT FROM AUTHOR]

The effects of exogenous ABA on the expression of the cysteine proteinase (CP) gene and its inhibitor cystatin (WC3) in the leaves of winter wheat ( Triticum aestivum L.) seedlings that were hardened for 7 days at 5°C were studied. Seedling cold-hardiness was judged by the temperature causing death of 50% of palisade cells (LT) following 5-min freezing at the temperatures from −5 to −10°C. In the initial period of cooling, when seedling cold tolerance increased, the CP and WC3 gene expression increased considerably, but at the highest cold-hardiness the transcript levels of these genes returned to the control level. When ABA was applied exogenously, the CP gene expression grew by the order of magnitude already in 1-5 h from the onset of low temperature treatment and then abruptly dropped, but it was further maintained at a high level. In cold- and ABA-treated seedlings, the WC3 gene expression initially decreased, but it grew considerably in 3-7 days. It is concluded that the development of wheat cold-hardiness is related to ABA-regulated changes in the CP and WC3 gene expression. [ABSTRACT FROM AUTHOR]

Yu.P. Altukhov suggested that heterozygosity is an indicator of the state of the gene pool. The idea and a linked concept of genetic ecological monitoring were applied to a new dataset on mtDNA variation in East European ethnic groups. Haplotype diversity (an analog of the average heterozygosity) was shown to gradually decrease northwards. Since a similar trend is known for population density, interlinked changes were assumed for a set of parameters, which were ordered to form a causative chain: latitude increases, land productivity decreases, population density decreases, effective population size decreases, isolation of subpopulations increases, genetic drift increases, and mtDNA haplotype diversity decreases. An increase in genetic drift increases the random inbreeding rate and, consequently, the genetic load. This was confirmed by a significant correlation observed between the incidence of autosomal recessive hereditary diseases and mtDNA haplotype diversity. Based on the findings, mtDNA was assumed to provide an informative genetic system for genetic ecological monitoring; e.g., analyzing the ecology-driven changes in the gene pool. [ABSTRACT FROM AUTHOR]

The dynamics of cold resistance and the activity of the photosynthetic apparatus (PSA) of wheat germs at 4°C were studied. It was shown that in the first hours of cold, a certain functional readjustment to the changed conditions takes place in the plant organism. A decrease in the activity of the PSA and cessation of the linear growth of the leaf are registered at this stage along with an increase in resistance, as well as an increase in the coefficient of non-photochemical quenching of the fluorescence of chlorophyll. In one to four days, when resistance reaches its maximum, photosynthesis and the rate of electron transport are stabilized, the chlorophyll content in the lightcollecting complex increases, and the growth recommences. The final stage of adaptation (days 4-7) is characterized not only by the steady level of resistance but also by new functional organization of the PSA, which allows the plants to endure the lowered temperature successfully. [ABSTRACT FROM AUTHOR]

On seedlings of winter wheat ( Triticum aestivum L.) and cucumber ( Cucumis sativus L.), the dynamics of cysteine and serine trypsin-like proteinases and also trypsin inhibitors at cold hardening (5°C for wheat and 10°C for cucumber) was studied. Activation of proteinases and inhibitors coincided in time or preceded an increased tolerance in wheat and cucumber seedlings in the early period of their hardening. After attaining the highest wheat tolerance, activity amidases reduced, whereas the increased activity levels of cysteine proteinases and trypsin inhibitors was maintained during the entire period of hardening. In cucumber, in these period activities of amidases and trypsin inhibitors reduced, whereas the activity of cysteine proteinases was maintained at the level close to the initial one. It is suggested that cysteine proteinases, amidases, and trypsin inhibitors are involved in plant adaptation to cold. [ABSTRACT FROM AUTHOR]

Geometrical thermodynamics is used to analyze the variation of the Gibbs energy with the temperature and concentration of metallic alloy components with unlimited solubility for liquid, liquid-solid, and solid states. [ABSTRACT FROM AUTHOR]

The mixing when gas is injected into liquid metal is theoretically studied. Physical modeling shows that the similarity of the model and sample (scaling and proportionality) must be taken into account in selecting the model. The influence of the injection rate on the batch hydrodynamics and the conditions of bubble motion is established. [ABSTRACT FROM AUTHOR]

The composition of equilibrium solid phases NaCl, NaSO, NaCO · 2NaSO (berkeyite) and NaCl, NaCO · HO, NaCO · 2NaSO (without preparative determination), saturating E and E eutonic solutions respectively, was established via nonvariant area boundary determination in a NaCl-NSO- NaCO-HO system at 50°C with the use of a combined method. [ABSTRACT FROM AUTHOR]

For the first time, an analysis of five Alu insertion loci ( ACE, APOA1, B65, PV92, TPA25) has been carried out in 10 Russian populations (1088 individuals) covering the whole historical area of the Russian ethnos. Depending on the locus, Russian populations exhibit similarity to their Western (European populations) or Eastern (populations of the Ural region) neighbors. Considering the frequencies of the studied Alu-insertions, the Russian gene pool exhibits low variation: average interpopulation variation ( d) was 0.007, whereas on classical markers, mtDNA and Y chromosome, heterogeneity of the Russian gene pool is essentially higher (0.013, 0.033, 0.142, respectively). Therefore, on the intra-ethnic level, this set of five Alu insertions has low variation. However, a clear pattern was obtained in inter-ethnic comparison of 13 East European ethnic groups, which formed three clusters in accordance with their historical and geographical position: East Slavic, Caucasian and South Ural clusters. The obtained data confirm the efficiency of using Alu insertions for studying genetic differentiation and gene pool history of East European populations. [ABSTRACT FROM AUTHOR]

The technology of producing of potassium dihydrophosphate (and potassium metaphosphate) mineral fertilizer in multicomponent system with salting-out is described; this technology is the result of investigation of multicomponent system K+, (C2H5)2NH // Cl−, H2PO-H2O, diagrams of the system condition and technological scheme are given; theoretical estimation of useful product yield agrees with experimental data. [ABSTRACT FROM AUTHOR]

Changes in expression of WRKY transcription factor and stress protein genes ( Wcor15, Wrab17, Wrab19, and Wcs120) were studied on wheat ( Triticum aestivum L., cv. Moskovskaya 39) seedlings exposed to cold hardening for 7 days at 4°C. The high level of WRKY gene expression was noticed already in 15 min after the beginning of cold treatment, but the expression level lowered during longer treatments. Exogenous ABA (0.1 mM) suppressed the WRKY gene expression. The level of Wcor15 gene expression increased gradually, reaching the peak on the second day, and then decreased. Gene expression of Wrab17 remained elevated throughout the period of cold exposure (7 days), and expression of Wrab19 was promoted within the first two days. Exogenous ABA induced expression of Wcor15, Wrab17, and Wrab19 genes both at cold-hardening (4°C) and normal (22°C) temperatures. A significant increase in Wcs120 gene expression during cold hardening was ABA-independent. It is concluded that the increase of wheat plant resistance at the initial stage of cold hardening is related to gene expression of WRKY transcription factor and of stress proteins ( Wcor15, Wrab17, Wrab19, and Wcs120), while the resistance increase during prolonged adaptation is related to gene expression of Wcor15 and Wrab17. [ABSTRACT FROM AUTHOR]

The dynamics of amidase, cysteine protease, and trypsin inhibitor activities were studied in the leaves of wheat ( Triticum aestivum L.) seedlings grown under controlled conditions (25°C, illuminance 10 kLx, 14-h photoperiod) and subjected to cold hardening (5°C, 10 kLx, 14-h photoperiod). Changes in the activity of amidases and cysteine proteases proved to precede an increase in cold resistance during cold hardening and a decrease in cold resistance after the end of cold hardening. The activity of trypsin inhibitors changed only during cold hardening. It is suggested that amidases, cysteine proteases, and trypsin inhibitors are involved in the cold adaptation of plants. [ABSTRACT FROM AUTHOR]

Part of the fission energy released in some volume of fissile substance is removed through the surface of this volume by fission fragments and can efficiently be used to pump gas lasers. The possibility of deducing this energy fraction from the results obtained by directly measuring the yield of alpha particles originating from the alpha decay of fissile substance and escaping through the surface of the volume being considered is examined. The respective estimates were derived in a first approximation on the basis of an extremely simple computational model. [ABSTRACT FROM AUTHOR]

Results of the estimation of dominance for individual species of woody and shrubby vegetation in the coastal phytocenoses of the Vorona River are presented. The data are indicative of a marked expansion of an alien species of ash-leaf maple ( Acer negundo L.) as well as its substantial invasive capacity. Estimates of the structure and degree of dominance expressiveness for the ash-leaf maple in the coastal phytocenoses of the Vorona River are provided. [ABSTRACT FROM AUTHOR]

Discusses the reduction of flake sensitivity of cerium-microalloyed structural steel. Determination of the optimum concentration of cerium; Derivation of commercial alloys of rare-earth metals from the melting of ferrocerium with ferrosilicon; Examination of process of the evolution of free hydrogen in relation to the dependence on cerium concentration.

The crystallization kinetics in 0.5-g droplets of melted copper, silver, and gold (special purity grade metals) cooled in vacuum at a rate of 0.01 K/s was studied. Under these experimental conditions, the physical supercooling observed in all three metals prior to crystallization was virtually zero. An analysis of the values of supercooling obtained in this study together with the data obtained previously under the same conditions showed that supercooling increases in a regular manner with the number of electrons on the outermost p level. [ABSTRACT FROM AUTHOR]