MIREA - Russian Technological University

Contents 1. Introduction 2. Molecular mechanisms of the cellular NRF2 antioxidant system function 3. Activation of the NRF2 antioxidant system in cancer cells under oxidative stress caused by ionizing irradiation 4. Activation of NRF2 as a factor of radioresistance 5. NRF2 antioxidant system of the cell as a target of targeted therapy to increase radiosensitivity of cancer cells 6. Conclusion

Understanding protein–drug complex structures is crucial for elucidating therapeutic mechanisms and side effects. Blind docking facilitates site identification but is hindered by computational complexity and imprecise scoring, causing ambiguity. Dipolar electron paramagnetic resonance (EPR) provides spin–spin distances but struggles to determine relative positions within complexes. We present a novel approach combining GPU-accelerated blind docking with EPR distance constraints to enhance binding site detection. Our algorithm uses a single EPR distance distribution to filter and validate docking results. Ligand poses from blind docking are clustered, filtered by expected distances, and refined through focused docking. To illustrate our approach, we investigated human serum albumin binding with porphyrin-based photosensitizers used in photodynamic therapy. Combining docking and EPR, we identified possible binding sites, demonstrating that EPR data significantly reduce possible configurations and provide experimentally validated information. This strategy produces a detailed map of photoligand binding sites, revealing that binding may occur away from standard albumin sites and often involves multiple locations. Furthermore, it overcomes key limitations of fluorescence-based methods, which are prone to misinterpretation in albumin studies due to non one-to-one donor–acceptor relationships. By resolving ambiguities in both blind docking and EPR, our framework provides a versatile platform for investigating EPR-active ligands.

One of the urgent and key problems of the transport industry is considered. This is the problem of planning the routes of vehicles. The given problem can be described and formalized as the Traveling Salesman Problem (TSP) for many applications. This problem consists in finding of the optimal route for a traveling salesman passing through the indicated cities at least once and with returning to the source city. In general, when planning such routes, it is necessary to solve the multiple traveling salesman problem (MTSP), which allows for more than one traveling salesman and more than one depot, their base point, where routes begin and end. As a combinatorial optimization problem, MTSP belongs to the class of NP-hard problems. This article presents a heuristic method for its solving on the basis of geospatial clusterization of the initial set of cities. First, an MTSP with a single depot is considered. A two-index mathematical formalization of this problem is given and the Miller-Tucker-Zemlin method is described. It reduced to the problem of integer linear programming. Metaheuristic methods for solving MTSP are discussed. A more complex problem an MTSP with several depots is being considered. A comprehensive two-stage method for solving this problem is described — the CFRS ("Cluster First — Route Second") method, which allows reducing it to the MTSP family with a single depot. Here, at the first stage, geospatial clustering of cities is carried out, for which it is possible to use various clustering methods, including the K-means method. At the second stage, for each built cluster, a depot is selected for its maintenance and routes are built to bypass all cities in this cluster. The clustering methodology is discussed as an effective tool for solving MTSP. A numerical example of aviation logistics is given — the routing of flights of UAV group.

Objectives . The problem of restoring defocused and/or linearly blurred images using a Tikhonov-regularized inverse filter is considered. A common approach to this problem involves solving the Fredholm integral equation of the first convolution type by means of discretization based on quadrature formulas. The work sets out to obtain an expression of the point scattering function (PSF) taking into account pixel size finiteness and demonstrate its utility in application. Methods . The research is based on signal theory and the method of digital image restoration using Tikhonov regularization. Results . Taking into account the finiteness of the pixel size, discrete PSF formulas are obtained both for the case of a defocused image and for the case of a linearly blurred image at an arbitrary angle. It is shown that, while differences between the obtained formulas and those traditionally used are not significant under some conditions, under other conditions they can become significant. Conclusions. In the case of restoring images at the resolution limit, i.e., when the pixel size cannot be considered negligibly small compared to the details of the image, the proposed approach can slightly improve the resolution. In addition, the derived formula for the discrete PSF corresponding to linear blur in an arbitrarily specified direction can be used to solve the problem without the need for prior image rotation and account for the blur value with subpixel accuracy. This offers an advantage in terms of improving the resolution of extremely fine details in the image, allowing the obtained formula to be used in solving the adaptive deconvolution problem, where precise adjustment of PSF parameters is required.

The aim was to characterize morphological and functional changes in the placenta in midpregnancy when modeling experimental preeclampsia and evaluate the model for validity. Material and methods . The study was conducted on 12–14-week-old mice of the inbred CBA, DBA/2, Balb/c lines. Uncomplicated pregnancy was modeled using the ♀CBA×♂Balb/c combination, preeclampsia was reproduced by the ♀CBA×♂DBA/2 combination and the introduction of 0.1 ml of 0.9% NaCl solution of beta-heptylglycoside muramyl dipeptide (C7MDP) intraperitoneally at the dose of 25 μg per 1 animal on days 5 and 7 of gestation (DG). On day 14 of gestation, the frequency of fetal resorption and the level of proteinuria were determined, and the placentas were dissected. Placenta preparations were stained with hematoxylin and eosin. Freshly isolated placenta was also examined using scanning electron microscopy, placenta homogenate was used to measure ex vivo cytokine production using flow cytofluorimetry. After birth of the offspring, the fetuses were weighed on the 1st day of life and the crown-rump length was measured. The obtained results were statistically processed using the Sigma Stat 3.5 program. Results . The proteinuria level was 0.1 (0.0; 0.1) g/l in cases of uncomplicated pregnancy and 1.0 (1.0; 3.0) g/l in pregnancy complicated by preeclampsia. On the 14th day of pregnancy, the resorption rate in cases of the uncomplicated pregnancy group was 12.9%, in group of experimental preeclampsia we revealed 39.34% ones. Morphometric study showed intrauterine growth retardation of the fetuses in the experimental preeclampsia group. Our study of cytokines estimating in placental homogenates showed that pregnancy complicated by experimental preeclampsia was accompanied by significant increase in the level of the proinflammatory cytokine IL-1, as well as decrease in the pleiotropic cytokines IL-4 and IL-6 and anti-inflammatory IL-10. Using light and scanning electron microscopy we found morphological and functional changes in the placenta in experimental preeclampsia reflecting the signs of placental insufficiency. Conclusion . The changes we observed allow us to classify the considered model of preeclampsia as one of the most adequate at present. Having high reproducibility and validity, it can contribute to the search for new diagnostic and therapeutic targets for this pregnancy complication.

The objective of the study described in the article was to analyse the features of application of ontologies in the field of transport and transportation. It referred to the exploration of the methods of building ontologies as well as to the information uncertainty hampering building ontologies, based on introduced terms of «transport and transportation ontologies», «ontological management» and «ontological information uncertainty». The main research methods comprised system, ontological, qualitative and comparative analysis. Since the use of ontologies for transport management has been practiced for the last twenty years, the accumulated experience in that field, development of ontologies and the current state of transport infrastructure technology provide grounds for introducing the concepts of «transport and transportation ontology» and «ontological management». The approaches based on those concepts are critically important for further development of transport system, digital transport, efficient management of transport infrastructure objects. A brief analysis of the application of ontologies in the field of transport and transportation refers also to the building of applied ontologies that embrace among others transport and transportation ontology. The study highlights the significance of semantic relationships for building applied ontologies, describes problems of information integration and offers rationale for the use of ontological units of information for building ontologies. It is noted that since a generally shared method of building ontologies is missing, transport and transportation field is now characterised by prevalence of private ontologies, some of them are listed in the article. While highlighting labelling method to build ontologies and describing application of graph databases for modelling semantics, it is shown that building of ontologies is hindered by the diversity of information systems and by a large amount of factual data used in modern transport management that objectively entail information uncertainty, the types there-of as well as methods of their elimination being described.

Objectives . Despite the wide application of the term “ontology” in philosophy and social sciences, ontological modeling in the fields of computer science and information theory remains poorly studied. The purpose of the work is to develop a methodology for the ontological modeling of information and to clarify the theory of information retrieval technology both in a broad sense and as part of ontological modeling. Relevant problems in ontological modeling include the necessity of demonstrating the difference between regularity and functional dependence. Methods . To achieve the stated goal, a logically structural approach is used, including the construction of conceptual schemes and their description in terms of logical formalism. The logically structural approach includes the construction of conceptual schemes that serve to apply logical formalism. The basis of logical modeling involves the selection of related models. The extended information retrieval technology proposed for this purpose searches not for individual objects, but for groups of objects. Since ontological research is based on a transition from qualitative to quantitative description, the methods used include quantitative-qualitative transitions. Results . A new concept of ontological modeling of information is introduced. The conditions of ontological modeling are substantiated. Relationships between the concepts of regularity and functionality are investigated. On this basis, an interpretation of regularity and functional dependence is given. Structural and formal differences between information modeling, information retrieval technologies, and ontological modeling are demonstrated. Three information retrieval tasks are described, of which the second and third tasks involving the search for a group of related objects and the search for relationships or connections within a group of related objects, respectively, are solved using ontological modeling. Formal schemes of ontological modeling are provided. The transition from relations to connections in the case of ontological modeling is demonstrated. Conclusions . Ontological modeling is shown to be applicable only to related models or to models between which there is a commonality. A technology of ontological modeling is proposed, in which version information retrieval is the initial part, while the second option involves the use of cluster analysis technology. Since ontological modeling uses qualitatively quantitative transitions, the proposed variant can be used to extract implicit knowledge.

Objectives . In contemporary software development practice, version control systems are often used to manage the development process. Such systems allow developers to track changes in the codebase and convey the context of these changes through commit messages. The use of such messages to provide relevant and high-quality descriptions of the changes generally requires a high level of competence and time commitment from the developer. However, modern machine learning methods can enable the automation of this task. Therefore, the work sets out to provide a statistical and comparative analysis of the collected data sample with sets of changes in the program code and their descriptions in natural language. Methods . In this study, a comprehensive approach was used, including data collection from popular GitHub repositories, preliminary data processing and filtering, as well as statistical analysis and natural language processing method (text vectorization). Cosine similarity was used as a means of assessing the semantic proximity between the first sentence and the full text of commit messages. Results . A comprehensive study of the structure and quality of commit messages encompassed data collection from GitHub repositories and preliminary data cleansing. The research involved text vectorization of commit messages and evaluation of semantic similarity between the first sentences and full texts of messages using cosine similarity. The comparative analysis of message quality in the collected dataset and several analogous datasets used classification based on the CodeBERT model. Conclusions . The analysis revealed a low level of cosine similarity (0.0969) between the first sentences and full texts of commit messages, indicating a weak semantic relationship between them and refuting the hypothesis that first sentences serve as summaries of message content. The low proportion of empty messages in the collected dataset at 0.0007% was significantly lower than expected, indicating high-quality data collection. The results of classification analysis showed that the proportion of messages categorized as “poor” in the collected dataset was 16.82%, substantially lower than comparable figures in other datasets, where this percentage ranged from 34.75% to 54.26%. This fact underscores the high quality of the collected dataset and its suitability for further application in automatic commit message generation systems.

Interchain exchange, proceeded by the transesterification mechanism, allows one to obtain polyethylene terephthalate-based polyester products, bypassing the stage of molecular weight reduction and polycondensation used in classical methods of chemical recycling. A kinetic model is presented, which describes the change in the concentrations of bound and terminal units of ethylene glycol from PET and glycol from another polyester, as well as free molecules of ethylene glycol and another glycol, during transesterification reactions for the first time. Experimental data on the dependence of the degree of randomness and conversion on timeduring the interaction of polyethylene terephthalate and oligodiethylene terephthalate with terminal hydroxyl groups with a number-average molecular weight of 860 g/mol in different ratios were obtained. Molecular weight characteristics of the products of PET and oligoesters with hydroxyl end group interchain exchange, with number-average molecular weights from 610 to 860 g/mol, were also investigated. The simulation results were also compared with published data on the dependence of the degree of randomness and conversion on time during ether exchange in PET/PEN blends. The developed kinetic model was found to be in agreement with the experimental data.

The main optical characteristic of pyrometers is the dependence of the diameter of the circle of the pyrometer’s field of view on the distance between the pyrometer and the object being measured. This dependence is not possible to be calculated strictly currently, so it has to be measured experimentally. The diameter of the field of view circle can be determined using circular (iris) and slit diaphragm methods. In the first method, the results of measurements of the diameter of a variable iris diaphragm, fitted near the emitter outlet, are used, and in the second method the results of measurements of the width of a slit diaphragm, also fitted near the emitter outlet and moved in a plane which is perpendicular to the optical axis of the pyrometer, are used. The results obtained using these two methods somewhat differ from each other because of difference of areas of the iris diaphragm and in the surface cut by the slit diaphragm, the width of the slit being equal to the diameter of the iris diaphragm. The relationship has been established linking the results obtained by the mentioned methods of a circular diaphragm and a slit diaphragm. This enables to correctly measure the diameter of the field of view circle using the slit diaphragm method, which is faster and less labor-intensive than the iris diaphragm method. The obtained results are relevant for contactless temperature measurements performed in technological processes as well as in research and development work.

We have systematically examined various parameters of t - (tetragonal) and h - (hexagonal) lattices of transition metal nitride (TMN) monolayers through first-principles calculations, emphasising their structural and magnetic properties. Our study...