In recent years, researchers have often encountered the significance of the aberrant metabolism of tumor cells in the pathogenesis of malignant neoplasms. This phenomenon, known as the Warburg ...effect, provides a number of advantages in the survival of neoplastic cells, and its application is considered a potential strategy in the search for antitumor agents. With the aim of developing a promising platform for designing antitumor therapeutics, we synthesized a library of conjugates of 3,5-bis(arylidene)-4-piperidone and sesquiterpene lactones. To gain insight into the determinants of the biological activity of the prepared compounds, we showed that the conjugates of 3,5-bis(arylidene)-4-piperidone and sesquiterpene lactones, which are cytotoxic agents, demonstrate selective activity toward a number of tumor cell lines with glycolysis-inhibiting ability. Moreover, the results of molecular and in silico screening allowed us to identify these compounds as potential inhibitors of the pyruvate kinase M2 oncoprotein, which is the rate-determining enzyme of glycolysis. Thus, the results of our work indicate that the synthesized conjugates of 3,5-bis(arylidene)-4-piperidone and sesquiterpene lactones can be considered a promising platform for designing selective cytotoxic agents against the glycolysis process, which opens new possibilities for researchers involved in the search for antitumor therapeutics among compounds containing piperidone platforms.
This paper presents three-dimensional numerical modeling of the processes occurring in the combustion chamber of a hybrid engine. Numerical simulation using verified author's code was carried out. ...The distributions of temperature, pressure, longitudinal and transverse velocities were analyzed. The characteristic features of the regression rate were studied. The influence of the reaction kinetics on the nature of the processes in the combustion chamber was determined. The obtained numerical results were compared with experimental data.
•Three-dimensional numerical modeling of a rocket engine was presented.•Numerical simulation using verified author's code was carried out.•The distributions of temperature, pressure and velocities were analyzed.•The obtained numerical results were compared with experimental data.
•The correlation graph between attributes provides a tool for studying stress and critical transitions.•We reviewed data that support or refute the hypothesis: both correlations and variance increase ...under stress.•This behavior lasts till some critical intensity of stressors and after that the correlations may decrease.•Several approaches to developing the theory of this effect are reviewed.•New models of adaptation, stress and training are developed using entropy and free energy of adaptation.
The concept of biological adaptation was closely connected to some mathematical, engineering and physical ideas from the very beginning. Cannon in his “The wisdom of the body” (1932) systematically used the engineering vision of regulation. In 1938, Selye enriched this approach by the notion of adaptation energy. This term causes much debate when one takes it literally, as a physical quantity, i.e. a sort of energy. Selye did not use the language of mathematics systematically, but the formalization of his phenomenological theory in the spirit of thermodynamics was simple and led to verifiable predictions. In 1980s, the dynamics of correlation and variance in systems under adaptation to a load of environmental factors were studied and the universal effect in ensembles of systems under a load of similar factors was discovered: in a crisis, as a rule, even before the onset of obvious symptoms of stress, the correlation increases together with variance (and volatility). During 30 years, this effect has been supported by many observations of groups of humans, mice, trees, grassy plants, and on financial time series. In the last ten years, these results were supplemented by many new experiments, from gene networks in cardiology and oncology to dynamics of depression and clinical psychotherapy. Several systems of models were developed: the thermodynamic-like theory of adaptation of ensembles and several families of models of individual adaptation. Historically, the first group of models was based on Selye's concept of adaptation energy and used fitness estimates. Two other groups of models are based on the idea of hidden attractor bifurcation and on the advection–diffusion model for distribution of population in the space of physiological attributes. We explore this world of models and experiments, starting with classic works, with particular attention to the results of the last ten years and open questions.
The motion of a point mass in a vertical plane under the action of gravity, linear viscous friction, support reaction of the curve, and the thrust is considered. The angle of inclination and the ...thrust are considered as control variables. The amount of fuel is indicated. The goal of the control is to maximize the horizontal coordinate of a point in a given time. The novelty of the paper lies in the fact that the structure of the optimal thrust is determined and the optimal synthesis is constructed in the three-dimensional space "slope angle-velocity-mass". For the case of a motion without friction, it is shown that the optimal thrust control takes boundary values, and the trajectory consists of two arcs, at the beginning with maximum thrust, and ending with zero thrust. The optimal synthesis in the three-dimensional space “slope angle-velocity-mass” is constructed for a specific area of the variables. For the case of linear viscous friction, an arc with an intermediate thrust can be included in an extreme trajectory. Assuming that the intermediate (singular) thrust satisfies the constraints, it is shown that the optimal thrust program consists of two arcs, maximum thrust at the beginning and zero thrust at the end, or three arcs: maximum thrust at the beginning, then intermediate thrust and zero thrust at the end. The following combination of arcs is also possible: zero thrust at the beginning, then an intermediate thrust and again zero thrust at the end. The logic of thrust control is similar to the well-known solution of the Goddard problem. The results of numerical simulation illustrating the theoretical conclusions are presented. The results are also valid for the Brachistochrone problem, which is interrelated to the range maximization problem. The results of numerical simulation illustrating the theoretical conclusions are presented.
Aim To study the etiology and the dynamics of prevalence and mortality of CHF; to evaluate the treatment coverage of such patients in a representative sample of the European part of the Russian ...Federation for a 20-year period. Material and methods A representative sample of the European part of the Russian Federation followed up for 2002 through 2017 (n=19 276); a representative sample of the population of the Nizhny Novgorod region examined in 1998 (n=1922).Results During the observation period since 2002, the incidence of major CHF symptoms (tachycardia, edema, shortness of breath, weakness) tended to decrease while the prevalence of cardiovascular diseases has statistically significantly increased. During the period from 1998 through 2017, the prevalence of I-IV functional class (FC) CHF increased from 6.1 % to 8.2 % whereas III-IV FC CHF increased from 1.8 % to 3.1 %. The main causes for the development of CHF remained arterial hypertension and ischemic heart disease; the role of myocardial infarction and diabetes mellitus as causes for CHF was noted. For the analyzed period, the number of treatment components and the coverage of basic therapy for patients with CHF increased, which probably accounts for a slower increase in the disease prevalence by 2007-2017. The prognosis of patients was unfavorable: in I-II FC CHF, the median survival was 8.4 (95 % CI: 7.8-9.1) years and in III-IV FC CHF, the median survival was 3.8 (95 % CI: 3.4-4.2) years.
•Chitosan-chitin composite film are characterized by their oriented structure.•Chitosan macromolecules self-organize on the chitin nanofibrils surface.•Chitin nanofibrils enhances mechanical ...properties, specific conductivity, proliferative activity of fibroblasts on the composite surface.•Optimal concentration of chitin nanofibrils in the composite film is 5 wt.%.
The paper is devoted to the study of influence of chitin nanofibrils on the structure, surface morphology, mechanical properties, and electrical conductivity of chitosan-based composite films intended for use in biomedical technologies. It was demonstrated that the optimal concentration of chitin nanofibrils in the composite film is 5 wt.%. For the films of this composition, we observed orientation of structural elements on film surface, enhanced mechanical properties as well as an increase in both specific conductivity and proliferative activity of skin fibroblasts on film surface. These results are related to the appearance of oriented structure in nanocomposites and to self-organization of chitosan macromolecules on the surface of chitin nanofibrils. It was revealed that increase in surface energy and surface hydrophilicity did not facilitate effective adhesion, viability and proliferative activity of cells during cultivation on the surface of composite films.
A cholesteric liquid crystal (CLC) - cholesteryl tridecylate (X-20) was doped with nanoparticles of shungite carbon (Sh) to effectively improve some physicochemical properties of the CLC matrix for ...the further use in electronic devices. The influence of Sh (concentration of 0.005 and 0.02 wt. %) on phase transition temperatures of X-20 was studied. Addition of 0.005 wt. % of Sh shifts phase transition temperatures upward, while the concentration increase to 0.02 wt. % leads to the opposite effect. These data were taken into account during the study of dielectric properties in different phase states. The dielectric properties were studied in the frequency range from 20 Hz to 10 MHz. Only for the system X-20/Sh (0.02 wt. %), dispersion of the dielectric permittivity was observed. The dispersion was caused by the appearance of additional relaxation processes and it was substantially more extended than the classical Debye theory suggests. The results of the research show that the 'CLC - Sh nanoparticles' composites can be used as promising materials to increase the efficiency of radio electronics devices.
Acute and chronic steroid-refractory graft-versus-host disease (srGVHD) is a life-threatening complication of allogeneic stem cell transplantation. There are a number of reports on case series ...describing efficacy of ruxolitinib in both acute and chronic srGVHD. We conducted a prospective study (NCT02997280) in 75 patients with srGVHD (32 acute, 43 chronic, 41 adults, and 34 children). Patients with chronic GVHD had severe disease in 83% of cases, and acute GVHD patients had grade III-IV disease in 66% of cases. The overall response rate (ORR) was 75% (95% CI 57-89%) in acute GVHD and 81% (95% CI 67-92%) in chronic. Overall survival was 59% (95% CI 49-74%) in acute group and 85% (95% CI 70-93%). The major risk factors for lower survival were grade III-IV gastrointestinal involvement (29% vs 93%, p = 0.0001) in acute form and high disease risk score in chronic (65% vs 90%, p = 0.038). Toxicity was predominantly hematologic with 79% and 44% of grade III-IV neutropenia in acute and chronic groups, respectively. There was no difference between adults and children in terms of ORR (p = 0.31, p = 0.35), survival (p = 0.44, p = 0.12) and toxicity (p > 0.93). The study demonstrated that ruxolitinib is an effective option in acute and chronic srGVHD and can be used both in adults and children.
The features of forming section and projection topography images of an edge dislocation normal to the crystal surface are considered for the case of X-ray anomalous transmission. Experimental images ...are analyzed using numerical simulation of the diffraction experiment. A new mechanism for image formation of defects arranged near the output crystal surface has been proposed. Differences between topography images of dislocations and rosettes of local misorientations of reflecting planes have been established.
The algorithm and the experience of implementing automated systems for monitoring the quality of waste in the pulp and paper industry in the framework of a unified system of industrial environmental ...control are being considered. The required list of wastewater parameters subject to automated control is determined. The main technical and operational characteristics of automated wastewater quality control instruments included in the unified state register of measuring instruments are being considered. The problems of introduction of automated wastewater quality control systems in the Russian Federation are being considered.
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