Mikhail Drobotenko

Background: The isotopic composition of the body’s internal environment can affect its functional state. Such effects are realized, among other things, by inserting deuterium atoms into hydrogen bonds between pairs of nitrogenous bases of DNA molecules and modifying their mechanical properties. Methods: This study uses a coarse-grained mathematical model of DNA. Results: It has been established that in a certain range of the magnitude of the torque, with the presence of a deuterium atom within it, stabilization of the CAG repeat tract is observed. In addition, it was found that, regardless of which base pair the deuterium atom falls into in the CAG repeat tract, its stability increases and the probability of hairpin formation decreases, which may interfere with the reading of genetic information from the site encoding glutamine. Conclusions: Single H/D substitutions in the CAG repeat tract of the ATXN2 gene increase its stability by reducing the formation of open states, regardless of the position of deuterium.

It is known that a number of neurodegenerative diseases, also called diseases of waiting, are associated with the expansion of the polyQ tract in the first exon of the ATXN2 gene. In the expanded polyQ tract, the probability of occurrence of non-canonical configurations (hairpins, G-quadruplexes, etc.) is significantly higher than in the normal one. Obviously, for their formation, the occurrence of open states (OSs) is necessary. Calculations were made for these processes using the angular mechanical model of DNA. It has been established that the probability of the large OS zones genesis in a DNA segment depends not only on the “strength” of the nucleotide sequence but also on the factors determining the dynamics of DNA; localization of the energy in the DNA molecule and the potential energy of interaction between pairs of nitrogenous bases also depend on environmental parameters. The potential energy of hydrogen bonds does not remain constant, and oscillatory movements lead to its redistribution and localization. In this case, OSs effectively dissipate the energy of oscillations. Thus, mathematical modeling makes it possible to calculate the localization of mechanical energy, which is necessary for the OSs formation, and to predict the places of their origin, taking into account the mechanical oscillations of the DNA molecule.

Thin-film membranes of Pd-Ag and Pd-Cu alloys capable of releasing hydrogen in a wide temperature range have been developed. The surface activation of the membranes with a nanostructured coating made it possible to intensify hydrogen transport through Pd-containing membranes at low temperatures. This effect was achieved by accelerating limiting surface processes by increasing the active area of the membrane. Surface-activated membranes demonstrated the highest values of hydrogen flux over the entire temperature range, which reached up to 49.4 mmol s⁻¹ m⁻² for Pd-Ag membranes and up to 32.9 mmol s⁻¹ m⁻² for Pd-Cu membranes. Membranes modified with filiform nanoparticles demonstrated a hydrogen flux up to 12 times higher than that of membranes with a smooth surface. Based on the results obtained, a theoretical model of hydrogen transport through metal membranes was developed, taking into account the effect of the state of the membrane surface on hydrogen transport at low temperatures. This model makes it possible to predict hydrogen flows in the entire temperature range much more accurately compared to other existing models. The selectivity and stability of the developed membranes over a long period of operation have been confirmed. The study of the effect of the surface activation of Pd-based membranes on the intensification of hydrogen permeability has shown the success of the method developed, which in turn opens up wide opportunities for creating low-temperature, highly efficient membrane hydrogen filters based on palladium and other devices based on them.

Thin-film membranes of Pd-Ag and Pd-Cu alloys capable of releasing hydrogen in a wide temperature range have been developed. Surface activation of the membranes with a nanostructured coating made it possible to intensify hydrogen transport through Pd-containing membranes at low temperatures. This effect was achieved by accelerating limiting surface processes by increasing the active area of the membrane. Surface-activated membranes demonstrated the highest values of hydrogen flux over the entire temperature range, which reached up to 49.4 mmol s–1 m–2 for Pd-Ag membranes and up to 32.9 mmol s–1 m–2 for Pd-Cu membranes. Membranes modified with filiform nanoparticles demonstrated a hydrogen flux up to 12 times higher than that of membranes with a smooth surface. Based on the results obtained, a theoretical model of hydrogen transport through metal membranes was developed, taking into account the effect of the state of the membrane surface on hydrogen transport at low temperatures. This model makes it possible to predict hydrogen flows in the entire temperature range much more accurately compared to other existing models. The selectivity and stability of the developed membranes over a long period of operation have been confirmed. The study of the effect of surface activation of Pd-based membranes on the intensification of hydrogen permeability has shown the success of the method developed, which in turn opens up wide opportunities for creating low-temperature highly efficient membrane hydrogen filters based on palladium and other devices based on them.

Background: Trinucleotide repeats are the cause of many neurodegenerative diseases that are currently incurable. In this regard, the question of the causes of occurrence and methods of prevention or treatment of diseases caused by the expansion of repeats in the CAG tract of the ATXN2 gene remains relevant. Previously, it was shown that the frequency of occurrence of additional OS (open states) zones increases with increasing length of the CAG tract, and the value inverse to the frequency correlates with the age of disease onset. Methods: In this work, the influence of the viscosity of the medium and the external torque on the stability of the CAG tract in the ATXN2 gene was studied using mathematical modeling methods. Results: It has been established that the probability of the appearance of additional OS zones of significant size increases with an increase in the CAG of the tract (k > 40 CAG repeats) for all viscosity values, however, at k ≤ 40, the change in viscosity does not significantly affect the probability of additional OS zones in the tract. Conclusions: It was found that under normal conditions (absence of pathology), viscosity does not have a reliable effect on the stability of the DNA molecule, but when pathology appears, an increase in viscosity contributes to an increase in DNA stability, and, accordingly, a decrease has a negative effect on the stabilization of the DNA molecule. In the zone of close to incomplete penetrance of the disease, viscosity does not have a reliable effect on the stability of the CAG tract.

It is known that the presence of CAA codons in the CAG tract affects the nature and time of disease onset caused by the expansion of trinucleotide repeats. The mechanisms leading to the occurrence of these diseases should be sought not only at the level of the physiological role of the ATXN2 protein, but also at the DNA level. These mechanisms are associated with non-canonical configurations (hairpins) that can form in the CAG tract. The tendency of hairpins to slide along the corresponding threads is usually considered important to explain the expansion of the CAG tract. At the same time, hairpins occur in areas of open states. Previous studies on the role of CAA interruptions have suggested that, under certain conditions, they can stabilize the dynamics of the hairpin, preventing the expansion of the CAG tract. We calculated the probability of additional open state zones occurrence in the CAG tract using an angular mathematical model of DNA. The calculations made it possible to establish that CAA interruptions affect the stability of the CAG tract, and this influence, depending on the localization of the interruption, can both increase and decrease the stability of the CAG tract.

В статье рассматривается физико-математическая модель процесса синтеза наночастиц серебра методом кавитационно-диффузионного фотохимического восстановления. Исследовано влияние мощности ультрафиолетового излучения на скорость синтеза наночастиц. Установлено, что при уменьшении мощности УФ излучения увеличивается общая длительность синтеза наночастиц серебра. Также уменьшается скорость самих химических реакций из-за уменьшения количества ОН^– и, как следствие, уменьшения концентрации е^–.

All the labor market subjects that can influence the labor resources dynamics are interested in employment forecasts by labor market sectors. Such subjects are state employees and municipal employees, employers and workers. The statistical data aggregation degree affects the quality of the labor resources dynamics forecasting. Each labor market indicator combines a set of detailed indicators in a high degree of aggregation case. When building the trends it is impossibile to take into account information on the detailed indicators trends. The labor market indicators for each specific year don’t contain information about the interaction with each other. This fact also negatively affects the forecast quality. The article discusses the use of a balance mathematical model of the labor resources dynamics, which relates the labor market sectoral indicators, to define the intersectoral movements indicators. The authors consider a calculating labor market indicators method that uses only statistical data on sectoral employment and unemployment. Thus, the statistical data on the labor resources dynamics provided by the Federal State Statistics Service is a sufficient condition for the Russian Federation labor market detailing using intersectoral movements’ indicators. The paper shows how a set of intersectoral movements indicators allows building the forecast values of these indicators and using them to calculate the forecast values of labor market indicators. The article considers examples of building employment estimates by Russian Federation economy sectors for 2011–2016 and 2019. The entry into force of the All-Russian classifier of types of economic activity second edition in 2017 is the reason for choosing such research intervals. The purpose of these examples was to determine the impact of the detailed labor market indicators of the sectoral employment estimates reliability. The authors compared the forecast obtained directly from labor market indicators with the forecasts obtained from intersectoral movements indicators. Intersectoral movements indicators are the results of applying balance models with varying degrees of detail. The reliability tables presented in this work to assess the forecasting quality indicate that the detailing of the sectoral employment indicators by using the balance model can increase reliability of the forecast.

The effect of single substitutions of protium for deuterium in hydrogen bonds between pairs of nitrogenous bases on the open states occurrence probability at high critical breaking energies of these bonds has been studied. The study was carried out using numerical methods based on the angular mathematical model of DNA. The IFNA17 gene was divided into three approximately equal parts. A comparison of the open states occurrence probability in these parts of the gene was done. To improve the accuracy of the results, a special data processing algorithm was developed. The developed methods have shown their suitability for taking into account the occurrence of open states in the entire range of high critical energies. It has been established that single ²H/¹H substitutions in certain nitrogenous bases can be a mechanism for maintaining the vital activity of IFNA17 under critical conditions. In general, the developed method of the mathematical modeling provide unprecedented insight into the DNA behavior under the highest critical energy range, which greatly expands scientific understanding of nucleobases interaction.

The formation and dynamics of the open states in a double-stranded DNA molecule are largely determined by its mechanical parameters. The main one is the torque. However, the experimental study of DNA dynamics and the occurrence of open states is limited by the spatial resolution of available biophysical instruments. Therefore, in this work, on the basis of a mechanical mathematical model of DNA, calculations of the torque effect on the process of occurrence and dynamics of open states were carried out for the interferon alpha 17 gene. It was shown that torsion action leads to the occurrence of rotational movements of nitrogenous bases. This influence is nonlinear, and an increase in the amplitude of the torsion action does not lead to an automatic increase in the amplitude of rotational movements and an increase in the zones’ open states. Calculations with a constant torsion moment demonstrate that open states zones are more often formed at the boundaries of the gen and in regions with a predominance of A–T pairs. It is shown, that for the occurrence of open states in the part of the gene that contains a small number of A–T pairs, a large amount of torque is required. When the torque is applied to a certain region of the gene, the probability of the formation of the open state depends on the content of A–T pairs in this region, the size of this region, and on the exposure time. For this mathematical model, open states zones can be closed when the torsion action stops. The simulation results showed that the values of the torsion moment required for the appearance of open states zones, in some cases, are close to experimentally measured (13–15 pN·nm).