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We studied the role of JNK in the regulation of the metabolism of xenobiotic venlafaxine by liver cells under in vitro conditions. The inhibitory role of this protein kinase in the biotransformation of this psychotropic agent by hepatocytes was demonstrated. JNK inhibitor added to the liver homogenate containing antidepressant enhanced and accelerated the formation of the only pharmacologically active venlafaxine metabolite O-desmethylvenlafaxine in the cell suspension. The results show the promise of studying modifiers of activity of intracellular signaling molecules (in particular, mitogen-activated protein kinases) to develop a fundamentally new approach to control the transformation of xenobiotics and to create a new class of pharmaceutical, target regulators of drugs metabolism.

We studied the role of JNK in the regulation of the metabolism of xenobiotic venlafaxine by liver cells under in vitro conditions. The inhibitory role of this protein kinase in the biotransformation of this psychotropic agent by hepatocytes was demonstrated. JNK inhibitor added to the liver homogenate containing antidepressant enhanced and accelerated the formation of the only pharmacologically active venlafaxine metabolite O-desmethylvenlafaxine in the cell suspension. The results show the promise of studying modifiers of activity of intracellular signaling molecules (in particular, mitogen-activated protein kinases) to develop a fundamentally new approach to control the transformation of xenobiotics and to create a new class of pharmaceutical, target regulators of drugs metabolism.

Cyclically changing thermomechanical loads causing the stress–strain state of dies are part of the crushing mechanism of surface and crack propagation in stress concentration zones. In order to evaluate the maximum stresses causing the critical strains of a die, a mathematical model is developed making it possible to predict the durability of a die’s working parts. The durability of punches and matrixes is estimated by the average number of loading cycles up to the breakdown of the tool according to the criteria of low-cycle strength and plastic crushing.

A procedure for the determination of dexketoprofen trometamol in human plasma by liquid chromatography–mass spectrometry (HPLC–MS/MS) using ibuprofen as an internal standard was proposed and validated. The matrix effect on the analyte response value was estimated; its short-term and long-term stability in a biological matrix and an aqueous acetonitrile solution was investigated. In addition, the stability of the analyte after freezing and thawing of samples was studied. It was shown that the dilution of samples by one half does not affect the accuracy and precision of the analysis. The limit of detection and the lower limit of quantification were 0.01 µg/mL; the linearity range was 0.01–8.50 µg/mL (R2 = 0.9974); the total analysis time was 3.5 min. Intra- and interday accuracy values were in the ranges 96.66–100.00% and 94.97–97.92%, respectively. Sample preparation, including liquid–liquid extraction with ethyl acetate in an acidic medium, is simple and fast. The developed procedure was successfully tested on real plasma samples from healthy volunteers in the framework of a comparative study of the pharmacokinetics and bioequivalence of a generic drug.

We studied pharmacokinetics of a new analgesic based on a hexaazaisowurtzitane derivative (thiowurtzine, TWZ). A method for measuring TWZ in organs and tissues by HPLC/MS/MS was developed and validated. The sensitivity of the method under conditions of intragastric administration of TWZ to rats in a dose of 100 mg/kg is 0.5 ng/ml (calibration curve 0.5-400 ng/ml). The concentrations of the substance (Cmax) in the plasma, organs, and tissues of animals were 20-100 ng/ml, the time to reach the maximum concentration after a single dose (Tmax) was 2 h. The mean retention time of the substance in the body ranged from 5.67 to 17.15 h after administration. The highest concentrations were found in excretory organs (liver and kidneys), the substance also actively penetrated into muscle tissue. The medium concentrations were found in the brain and adipose tissue. The tropism to the heart tissues was minimal.

The article is designed as a lecture for students of medical universities, as well as for practicing doctors. It shows the periods of childhood with characteristic for each stage features of a growing organism.

The rational use of metal is determined by the use of alternative methods to produce blanks, including forging a crystallizing metal. Application of external pressure to the melt during crystallization completely eliminates gas porosity, which improves the mechanical characteristics of the products, and substantially increases the crystallization rate, which improves the life of dies. The results of mathematical modeling underlie the selection of thermomechanical conditions for forging of metals (iron, steel, and aluminum alloys) that crystallize under pressure. A number of liquid metal forging processes are mastered.

The indices of T-cell immunity are decreased in children of early age with megalothymus: content of T-cells (CD3+), Т-helpers (СD4+ Т-cells), cytotoxic Т-lymphocytes (СD8+ Т-cells), regulatory Т-cells (CD4+CD25hi) and also activated Т-lymphocytes (CD4+CD25lo и CD3+HLA-DR+). The increasing of expression of alterations was observed as degree of megalothymus was progressing. The only exclusion were regulatory T-cells. Their level was decreased under megalothymus degree I and II and was closer to indices of age standard under megalothymus degree III. Also, it was demonstrated that capacity of T-cells to differentiation to cytokine-producing cells type Th1 and Th2 increases as far as increases expression of megalothymus. However, this process remains within framework inherent to comparison group. The T-lymphopenia under megalothymus is conjugated with decreasing of emigration of T-cells from thymus to peripheral section of immune system. These alterations bring on deficiency of T-cell chain of immune system and can favor manifestation of its incapacity especially in conditions of increased load under effect of pathogens.

An important role in the construction industry is played by the robotics of individual processes in construction. However, despite a wide range of scientific and design developments in the field of construction, the level of automation and robotization processes remains quite low. This is due to the need to systematize the performed research and development, to carry out complex research and development activities. The paper presents data on the technological prerequisites for robotization of construction processes in Russia. The factors hindering the use of industrial robots in Russia are identified. The distinctive parameters and characteristics of robots in the construction of unique buildings and structures are considered. The main tasks for robotization of technological processes at construction enterprises are formulated. The analysis of the levels injuries at construction sites is carried out. The possibility of introducing robotic technology in the construction of unique buildings with complex technical features is considered. As a result of the research carried out, the scientific problem of analysis and synthesis specialized robots for the construction of unique buildings and structures has been considered. The solution to this problem is important, since it contributes to the development of highly effective means of complex mechanization and automation of construction processes that increase the productivity and quality of installation, finishing and plastering works, reduce their labor intensity, free people from harmful and dangerous working conditions.

The flow of a thin plastic layer between two rigid plates approaching each other in the normal direction is considered. The kinematics of plastic layer flow is studied. An evolution equation describing the free boundary of the flow region is derived. The similarity solutions to this equation are analyzed. It is shown that the evolution equation can be reduced to a particular case of the nonlinear heat conduction equation. New exact particular solutions to the evolution equation are obtained using the variable separation method and the method of self-similar transformations.

The development of new shaping technologies for pipe blanks requires simulation of the stress and strain fields, which permits assessment of the limiting stress and strain values. The stress–strain state of a pipe blank in expansion (including nonuniform expansion) is analyzed in the present work. Joint solution of the equilibrium equations and plasticity condition is employed here; that is the traditional approach. Analytical dependences of the stress in the wall of the pipe blank on the technological parameters are obtained; the basic formulas for estimating the strain are also presented. Experiments confirm the results.

Excretion of highly lipophilic (log P = 8.14) 4-methyl-2,6-diisobornylphenol (IBP) from rats was evaluated from renal excretion and elimination through the gastrointestinal tract (GIT) with feces and bile. A total of 81% of the administered dose was detected in feces after a single intragastric administration of IBP at a dose of 20 mg/kg in starch paste. The excretion kinetics through the GIT were represented by two elimination phases, i.e., rapid (within 24 h after IBP administration) accounting for elimination of 70% of the administered dose and slow (24 – 96 g) presumably related to elimination of IBP stored in tissues and organs. The bile IBP concentrations were an order of magnitude less than those in blood plasma. However, the times to reach the maximum concentration differed little. Renal excretion turned out to be minor despite the high kidney concentrations. Total elimination of IBP with urine for 4 d was ~0.01% of the administered dose.

The stress state of metal in the plastic region is considered. The type of stress state is characterized. The remaining plasticity of a deformable metal in axisymmetric extension is estimated on the basis of a phenomenological measure of the deformability.

The complex-forming properties of a silica gel-polyaniline composite with 8-hydroxyquinoline covalently immobilized by the Mannich reaction with respect to Pb(II), Cd(II), Cu(II), Ni(II), Co(II), Al(III), Fe(III), and Mo(VI) ions were studied. The resulting adsorbent had a high sorption capacity and satisfactory kinetic characteristics, which allowed us to use it for the separation or preconcentration of transition metal ions. Data on the composition and structure of the test metal complexes with 8-hydroxyquinoline immobilized on the composite surface were obtained from an analysis of electronic diffuse reflectance spectra and corresponding adsorption isotherms.

Covalent bonding of polyhexamethyleneguanidine amides of maleic and o-phthalic acids to the aminated silica surface was performed. The complexing properties of the obtained composite adsorbents with respect to Zn(II), Cu(II), Fe(III), Co(II), Pb(II), Ni(II), Mn(II), Mo(VI), and Cr(VI) ions were studied. The Mo(VI) and Cr(VI) reduction was detected on the modified silica surface bearing polyhexamethyleneguanidine amide with o-phthalic acid. The formation of different-ligand complexes with transition metal cations adsorbed on the synthesized composite surface was studied.

The possibility was determined for covalent binding of amide of maleic acid and polyhexamethyleneguanidine to a silica gel surface previously activated with cyanur chloride. Adsorption of Zn(II), Cd(II), Pb(II), Cu(II), Mn(II), Ni(II), Fe(III), and Co(II) cations from aqueous solution with a modified silica obtained was studied. The possibility of subsequent formation on the surface of mixed ligand complexes

The sorption of polyionene 1,4-MePh on the silica gel surface was studied. The silica gel modified with polyionene sorbed was used for sorption preconcentration of MoO42−, WO42−, Cr2O72−, and VO3− anions from aqueous solutions. The sorption isotherms of these anions on the initial and modified silica gels were obtained and analyzed.

The complexing properties of modified silica with 4-(2-pyridylazo)resorcinol covalently immobilized by the Mannich reaction are studied with respect to heavy metals. This adsorbent can be used for the preconcentration of heavy metal ions due to its satisfactory kinetic characteristics. The structures of the heavy metal complexes with 4-(2-pyridylazo)resorcinol immobilized on the silica gel surface are studied by ESR and diffuse reflectance spectroscopy.

The sorption properties of silica gel with γ-mercaptopropyl groups chemically immobilized on its surface toward Pb(II), Cd(II), and Zn(II) at MPC levels in natural water in Ukraine were studied. The mutual effect of Pb(II), Cd(II), and Zn(II) in the sorption-X-ray fluorescence determination of their trace amounts with preextraction on silica gel with γ-mercaptopropyl groups was examined

We present the results of comprehensive investigations that include remote spectral measurements under field conditions, laboratory experiments, and mathematical simulation of the radiative regime of winter rye sowings.

General ordinal noncooperative games with a finite number of players are considered. Existence of equilibrium points in such games is proved. The definitions of different mixed extensions of these games are discussed, and the corresponding existence theorems are established. A connection between so defined mixed extensions and mixed extensions of noncooperative games with payoff functions is investigated.

First, an axiomatization is given of one class of deterministic social choice rules which are extensions of symmetric majority rules. Secondly, an axiomatization is given for the probabilistic social choice rule such that, for every profile P of individual preferences, the binary relation ϕ(P) on the set of random alternatives is generated by the expected bilinear skew-symmetric preference intensity function on the set of alternatives. Further, it is shown that the set of maximal elements of ϕ(P) coincides with the set of all optimal mixed strategies of every player in the symmetric matrix game with the preference intensity as its payoff function.

The object of the theory of games is the study of conflict s i tuations. The s imp le s t case of confl ict is nantagonism, n or what is known in ~ tme theory as the z e r o s u m t w o . p e r s o n situation, in which two p a r t ic ipants with d i rec t ly opposing in te res t s a re involved. The re la t ionship and d i f fe rences between the ze ro sum two-pe r son concept in game theory and the an tagonism, or conf l i c t -o f in t e res t , s i tuat ion in philosophy a re d i scussed in an a r t i c l e by Vorob ' ev [8].

We consider a class of infinite games with unbounded cores and establish the existence of their value.It is shown that a game with the core \[ K(x,y) = \left\{ \begin{gathered} L(x,y),\quad x y, \hfill \\ \end{gathered} \right. \] where the functions L and M are defined and continuous on the triangles $0 \leqq x \leqq y \leqq 1$, $0 \leqq y \leqq x \leqq 1$, respectively, the function $\varphi $ is arbitrary and $L(0,0) \geqq M(0,0)$, $L(1,1) \leqq M(1,1)$, is a game with value.

Experiments of outbred rats with modeled xenobiotic load with acetylsalicylic acid (250 mg/kg for 7 days) revealed inhibition of mitochondrial respiration rate in states of rest and active phosphorylation, inhibition of succinate-dependent oxidation pathway, and a decrease in energization of organelles in the heart. For correction of the observed changes in energy production, succinic acid was preventively administered in a dose of 50 mg/kg for 7 days, which abolished the negative metabolic shifts in myocardial mitochondria. Comparison of pharmacokinetics of acetylsalicylic acid and acetylsalicylic acid against the background of succinate treatment performed on rabbits revealed complete coincidence of the studied parameters, which attests to the possibility of prevention of mitochondrial dysregulations with this Krebs cycle intermediate.

We studied the effects of ethanol on the energy production system in the brain and liver in acute and chronic intoxications. Ethanol was found to inhibit mitochondrial respiratory chain in the liver. Acute ethanol intoxication results in uncoupling of oxidative phosphorylation. NAD-dependent respiration prevails in chronic intoxication. In the brain, ethanol exposure induces a compensated low-energy shift with activation of fast mitochondrial metabolic cluster and uncoupling of oxidative phosphorylation.