Computational Modeling Methods Research Articles

Editorial: Computational modeling and machine learning methods in neurodevelopment and neurodegeneration: from basic research to clinical applications

Editorial: Computational modeling and machine learning methods in neurodevelopment and neurodegeneration: from basic research to clinical applications

Synthesis of a parametrically robust controller with an extended state observer

This paper considers the problem of control of a parametrically uncertain dynamic system using an extended state observer. The control system is implemented using a two-loop scheme, where the outer loop ensures the fulfillment of the selected criterion for controlling the state vector, and the inner loop compensates for or reduces the influence of the vector of the total equivalent disturbance. The goal of the study is to develop a procedure for synthesizing an extended state observer taking into account the parametric uncertainty of the plant and the requirements for the closed loop of the combined control system specified in the frequency domain. Methods of control theory, robust control, and computer modeling are used for this study. The effect of the parametric uncertainty of the plant on its controlled motion is presented as a structured disturbance described in the form of a block-diagonal matrix. The concept of structured singular values is used to determine the measure of the system's robustness. Using the methodology of optimization of structured singular values, a procedure is proposed for synthesizing the extended state observer when considering a closed loop of a combined control system taking into account the parametric uncertainty of its mathematical model. The requirements ensuring the specified performance and stability of the closed loop of the control system taking into account the spectral properties of disturbances and sensor noise are formulated in the frequency domain using frequency-dependent weighting functions. For the synthesis of combined controllers based on the minimization of structured singular values, a D-G-L-K iteration algorithm is developed. The efficiency of the proposed approach is illustrated by a numerical example. Recommendations are given for the synthesis of parametrically robust combined controllers. The practical value of the obtained results lies in the fact that the procedure developed reduces the conservatism of robust combined control systems and, as a result, improves the control performance in the case of parametric uncertainty of the plant.

Analytical justification of the thermochemical interaction between blast reagents and carbon-containing products under the influence of magnetic fields

Purpose. To justify and develop a model that describes the effect of magnetic treatment of blast reagents and carbon-containing products on the gasification process for predicting the intensification of gas formation. Methodology. The study involves theoretical modeling based on experimental data to investigate the influence of magnetic fields on the underground coal gasification process and co-gasification of coal and carbon-containing products. The Arrhenius equation was used to estimate the rate constants of gasification reactions in the temperature range of 800–1,000 °C. The effect of the magnetic field was incorporated by adjusting the activation energy (Ea). The results of analytical and experimental studies were processed using methods of computer and mathematical modeling. Findings. The results show that the application of magnetic fields significantly intensifies the gasification process of carbon containing products. Increasing the reactivity of the blast reagents, particularly water and oxygen, leads to a higher overall yield of combustible gases. The use of magnetic fields in the gasification process substantially increases the reaction rate (k) due to the reduction in activation energy (Ea), improving the overall efficiency of gasification. Originality. For the first time, an analytical model has been developed to describe the effect of magnetic treatment of blast reagents and carbon-containing products on the gasification process in the temperature range of 800–1,000 °C. The obtained reaction rates follow an exponential trend. The established and correlation-validated pattern shows the relationship between changes in the approximation coefficient (F ) and the change in the carbon fraction (C, %) during the magnetic treatment of blast components within the specified temperature range. Practical value. The results of this study can be applied to enhance the efficiency of industrial gasification processes, particularly underground coal gasification and co-gasification of coal and carbon-containing productss.

Pipe production cost management model based on graph theory

The pipe production process is a complex dynamical system with a significant number of production operations and interconnected cost localization centres. Purpose. To develop a mathematical model of the process of handling analytical information of a pipe enterprise using graph theory for the needs of cost management at each production stage. Methodology. Technological flow charts of the production job, where the list of mandatory activities and routing of the operating process are indicated, were used to organize cost accounting by operational centres of their localization with the help of computer modelling elements, namely the graph theory. The work used a complex of research methods, including analysis and scientific synthesis of scientific and technical information; theoretical studies; methods of mathematical and computer modelling, engineering developments. Findings. The cost accounting process is represented by a directed hypergraph. Each production operation is associated with a graph vertex. Each vertex is assigned to a series of interrelated marks: type of technological operation; weight factor; the value of direct costs for the operation; the value of indirect costs for the operation; the expense factor. The initial state of the hypergraph is specified by means of its initial marking, which corresponds to the set cipher of the batch of pipes and its weight. Further execution of the marked hypergraph is performed by running the allowed vertices. Marking of the graph ends if all the information from the technological flow charts of pipe products has been used. Originality. A model of cost management by operational centres is proposed which will allow dividing the prime cost of pipes which differ according to the production technology. It is recommended to rank pipe products within each technologically similar group for an economically feasible allocation of costs between batches of pipes. The proposed process model of processing analytical information of the pipe enterprise using graph theory will allow providing data governance as for the prime cost of each individual batch of pipe products, will contribute to the improvement in the order generation procedure taking into account the acquired information, and will allow making the appropriate adjustments when making management decisions. Practical value. Calculation of expenses for production operations allows one to identify the most cost-intensive of them. Relying on the results of the calculation, the enterprise management has the opportunity to manage costs at any stage of the production process. Moreover, the model allows determining the amount of consumed metal for each production operation, which is relevant for pipe enterprises. It is appropriate to focus further scientific developments in this direction on the possibility of managing non-manufacturing cost with the help of mathematical models in economics to optimize the supply and sales activities of the enterprise.

Assessment of the efficiency of functioning of the environmental management system of enterprises

Purpose. A multifactor model is developed to assess the efficiency level of an enterprise’s environmental management system, depending on the effectiveness of organizational environmental measures. Methodology. The authors’ method for determining a comprehensive criterion for monitoring the effectiveness of the environmental management system, which characterizes the efficiency of operation and determines the level of environmental safety of enterprises, is proposed and used. To solve the tasks, a complex research method was also used, which included the analysis and generalization of literary and patent sources, and analytical, experimental research using computer and mathematical modeling methods. Findings. According to the studies and calculations of the generalized environmental quality indicator – 0.64, 0.66 and 0.66, the largest negative impact on the environment is caused by the activities of enterprises in the Pecherskyi, Podilskyi, and Solomianskyi districts of Kyiv, respectively. The obtained data testify to the relationship between the effectiveness of the implemented environmental measures (saving and rational use of resources, application of environmental technologies, advanced training, and environmental competence of employees) and the level of efficiency of the environmental management system of enterprises. Originality. As a result of the studies conducted using actual data, a system of indicators of the generalized environmental quality indicator has been proposed for the first time, which allows determining the environmental efficiency and effectiveness of the implemented environmental measures to assess the effectiveness of the functioning of the implemented environmental management system of the enterprise. Practical value. Based on the research results, a technique is proposed to assess the effectiveness of the environmental management system of enterprises by determining a generalized environmental quality indicator in terms of reducing the negative impact of the enterprise’s activities on the environment. Such an assessment system will help the management of the enterprise to promptly introduce corrective actions to improve the efficiency of the environmental management system and increase the level of environmental safety.

Modeling of drilling tool vibration in the process of drilling blast wells

Purpose. To determine the characteristic features and model bit vibration during its interaction with rock in the process of drilling technical (blast) wells in open pit mines. Methodology. The following methods were used in the work: analysis of scientific and practical solutions; statistical methods for processing the results of experimental studies; methods of analytical synthesis; computer modeling methods for synthesis and analysis of mathematical models. Findings. The process of interaction between a drill bit and a rock was analyzed. The conditions and causes of vibration of drilling equipment are determined. The spectral analysis of the vibration signal, the formation and analysis of the map of the order of rotation of the rotating parts of the drilling rig during the drilling of technical (blast) wells were performed to identify the bit in the frequency domain of the measured concomitant integrated vibration signal as a source of high-amplitude vibration. The modulated signal measured in the time domain at the specified frequency carries information about the physical and mechanical characteristics of the drilled rock and the state of the bit. The analysis of the experimental studies and modeling of the process of interaction of the bit with the rock allows us to conclude that the obtained statistical indicators of the accompanying vibration signal really adequately characterize the process of well drilling. Originality. A method for determining the characteristics of the interaction of a drill bit with rock in the process of drilling technical (blast) wells based on measuring the parameters of the accompanying vibration signal is proposed. The method differs from the known ones in the fact that in the process of changing the operating mode of the drive of the rotating parts of the drilling rig, an order map is formed over the entire range of its revolutions, the frequency of high-amplitude vibration of the bit is determined, which corresponds to a certain peak order of revolutions, and at this frequency the statistical parameters of changes are measured. Practical value. This approach to the process of drilling wells in open pit mines makes it possible to quickly determine the physical and mechanical characteristics of the drilled rock and adjust the process parameters accordingly to increase its productivity and energy saving.

Чисельно-експериментальне дослідження високотемпературної багатоциклової втомної міцності монокристалічних лопаток газових турбін

The subject of the research is anisotropic single-crystal turbine blades of aircraft gas turbine engines (AGTE), as well as their multi-cycle fatigue strength characteristics at high temperatures. The goal of this study was to determine the endurance limit of single-crystal high-pressure turbine blades of an AGTE at high temperatures of 820°C. The objective of the study is to develop a method for calculating and experimentally investigating the characteristics of high-temperature multi-cycle fatigue strength of gas turbine blades made of single-crystal nickel heat-resistant alloys. The research methods used are: method of computer modelling, which was used to create a 3D model of a cooled high-pressure turbine blade; finite element method, which was used to determine the stress-strain state of the blade according to the selected form of resonant vibrations; strain and resonance methods, which were used to determine the fatigue strength characteristics of single-crystal turbine blades under high-temperature loading. The following results were obtained. Literary sources describing theoretical and experimental methods for determining the strength characteristics of blades under combined dynamic and high-temperature loading were analyzed. The developed special installation for testing turbine blades under conditions of temperature and dynamic (resonant) loading was described. A combined method for assessing the multi-cycle fatigue strength at high temperatures is proposed, which includes studies on full-scale turbine blades and finite element calculations. The dynamic and temperature characterization of single-crystal turbine blades selected for the study was carried out and described. Fatigue tests were performed to determine the endurance limit of the blades at a high temperature equal to T = 820 °C. Conclusions. The scientific novelty of the obtained results is as follows. A specialized experimental setup was developed to study the endurance limit of single-crystal AGTE blades under high-temperature loading. A method for combining numerical (ANSYS) and experimental (field tests) study of high-temperature multi-cycle fatigue strength of turbine blades made of single-crystal heat-resistant alloys was developed. The direction of further research is presented.

Attention mechanism‐assisted recurrent neural network for well log lithology classification

AbstractLithology classification is a fundamental aspect of reservoir classification. Due to the limited availability of core samples, computational modelling methods for lithology classification based on indirect measurements are required. The main challenge for standard clustering methods is the complex vertical dependency of sedimentological sequences as well as the spatial coupling of well logs. Machine learning methods, such as recurrent neural networks, long short‐term memory and bidirectional long short‐term memory, can account for the spatial correlation of the measured data and the predicted model. Based on these developments, we propose a novel approach using two distinct models: a self‐attention‐assisted bidirectional long short‐term memory model and a multi‐head attention‐based bidirectional long short‐term memory model. These models consider spatial continuity and adaptively adjust the weight in each step to improve the classification using the attention mechanism. The proposed method is tested on a set of real well logs with limited training data obtained from core samples. The prediction results from the proposed models and the benchmark one are compared in terms of the accuracy of lithology classification. Additionally, the weight matrices from both attention mechanisms are visualized to elucidate the correlations between depth steps and to help analyse how these mechanisms contribute to improved prediction accuracy. The study shows that the proposed multi‐head attention‐based bidirectional long short‐term memory model improves classification, especially for thin layers.

Computational Models of Dynamic Load Sources for Modeling of Construction Structures Operation Used in Monitoring of Technical Condition of Buildings and Structures

This research aims to develop principles for assessing the impact of mega-cyclic vibrodynamic loads on the reliability of construction structures. The relevance of the reasons for the development and improvement of algorithms for numerical modeling of multicycle dynamic loads on building structures is due to the steadily increasing intensity of such loads on buildings and structures in megacities, as well as the acute practical problem of significant differences in the dynamic characteristics of buildings and structures obtained as a result of mathematical modeling and determined by experimental methods. The article presents research materials on computational equivalent models of dynamic load sources for numerical modeling of the behavior of construction structures under their influence, using the method of vibroacoustic analogies. The article examines models of sources of dynamic impact on construction sites. Algorithms and final formulas for computational modeling of the simplest sources of dynamic load are developed using the method of vibroacoustic analogies. The dynamic properties of the simplest dynamic load sources were analyzed. A significant difference between the computational models of real and ideal dynamic load sources. The article presents research and development results intended for calculating the distribution of dynamic loads on elements of construction structures in industrial and civil engineering projects located in areas with high levels of transport vibrodynamic impacts. An important property of the proposed computational equivalent models of sources of dynamic impact on building structures is the possibility of computational verification of critical elements, points, or nodes of load-bearing structures of buildings and structures under dynamic overloads. The position of these critical elements, points, and nodes of load-bearing structures under dynamic loads can differ significantly from their position determined using static and quasistatic computational modeling methods.

Mathematical model for constructing a matrix of coefficients thermal conductivity under low-temperature influence on the multilayer epidermis of biological tissue

Objective. The purpose of the study is to develop a mathematical model for constructing a matrix of thermal conductivity coefficients under low-temperature exposure to the multilayer epidermis of biological tissue. Method. The research is based on methods of thermo dynamic analysis, full-scale and computational modeling of processes under low-temperature influence. Result. A mathematical model of the matrix of thermal conductivity coefficients under low-temperature effects on biological tissue has been developed. Heat transfer in a multilayer medium under low-temperature influence on biological tissue is presented as a process with a discrete step in time and coordinate. Thermal properties are evenly distributed throughout the volume of layers of biological tissue. For exposure to cold, layers of the epidermis of biological tissue were used, divided into uniform identical cells, where the cell area of the biological tissue was taken to be equal to one. Conclusion. The results obtained in this work can be useful to specialists who deal with modeling problems with free boundaries.

Thermoelectric installation for lifting objects from shallow reservoirs using the freezing method

Objective. The purpose of the study is to develop the design of a thermoelectric installation for lifting objects from shallow reservoirs using the freezing method, as well as its calculation, analysis of parameters and electrical and thermophysical characteristics. Method. The research is based on the use of methods of thermodynamic analysis, full-scale and computational modeling of cryogenic equipment in order to find optimal solutions for the reliability and service life of low-temperature installations. Result. The installation includes a waterproof probe, on the end surface of which, facing the bottom of the reservoir, thermoelectric modules are installed, heat is removed from the hot junctions of which by means of a heat removal system made in the form of an all-metal heat pipe or in the form of a thermal thermosiphon. The connection between the object lifted from the reservoir and the thermoelectric installation is carried out through a cold wall by freezing. The thermoelectric installation was calculated and its parameters were determined. Graphs were constructed and dependencies were obtained describing the main characteristics of TEMs included in the thermoelectric installation. The graphs are presented at a temperature of the hot junctions of the TEM of 300 K and the achievement of such values of the thickness of frozen water ice on the cold wall of the technical device that would allow lifting objects from a reservoir up to 4 m deep. Conclusion. The installation parameters have been determined: the number of TEMs of the DRIFT-1.2 type is 8, the operating power range of a single TEM of the DRIFT-1.2 type is from 14 to 40 W with an average temperature difference between the junctions of 45 K, the supply current is from 3.8 to 7 .6 A with power consumption from 50 to 200 W, coefficient of performance - from 0.1 to 0.45, minimum temperature of the cold wall of the TU - 248 K, a domestically produced thermal thermosyphon is used as a heat removal system from the hot junctions of the TEM.

Development of an imitation learning method for a neural network system of mobile robot’s movement on example of the maze solving

Objectives. To develop a new method for training a mobile robot control system to use a maze solver algorithm based on reinforcement learning and the right-hand algorithm.Methods. The work uses the method of computer modeling in the MATLAB/Simulink environment.Results. A new method for training a mobile robot control system capable of implementing the right-hand algorithm for finding an exit from a maze is proposed. The proposed method is based on the work of two agents interacting with each other: the first directly implements the search algorithm and searches for an exit from the maze, and the second, following it, tries to learn using the imitation learning method. The expert agent, implementing a discrete algorithm for moving through the maze, makes precise discrete steps and moves almost independently of the second agent. The only limitation is its speed, which is directly proportional to the distance between the agents. The second agent, the student agent, tries to reduce the distance to the first agent by trial and error. The learning process was implemented using the reinforcement learning method, which was used in the imitation mode and for which a corresponding reward function was developed, allowing the robot's center of mass to be kept in the center of the corridor and, if necessary, to turn, following the expert agent. The agents move along a virtual polygon consisting of branched corridors wide enough to implement various movement maneuvers.Conclusion. It was proven that, thanks to the proposed method of imitative learning, the student agent is able not only to adopt the required behavior patterns from the expert agent – to search for an exit in a previously unknown labyrinth using the right-hand algorithm, but also to independently acquire new ones (changing speed on a turn, bypassing small dead-end corridors), which positively influence the performance of the assigned task.

ANALYSIS OF I-BEAM WITH CORRUGATED WEB AND TECHNOLOGICAL PERFORATIONS UNDER STATIC LOAD

The article is aimed at studying the operation of welded I-beams with corrugated web and technological perforations under static loading. The relevance of the study is due to the lack of specific instructions on the pitch, diameter and methods of strengthening technological perforations in the Republic of Kazakhstan and other countries. In this study the method of computer modeling with the help of the program complex LIRA-SAPR-2022 was used. The study was carried out for the beam, taking into account different sizes of perforations in the beam web, distances between the perforations, with and without perforation. The beam deformability and the beam stability with and without perforations under static concentrated load was analyzed. Twenty-nine beam models were analyzed, three circular perforations with diameters of 0,25 , 0,5 , 0,75 were formed in the webs of the beam models, where is the height of the corrugated web. The center of the perforations was located in the middle of the web height. The distance between the centers of the perforations were taken 2d, 3d and 4d, where d is the diameter of the perforation. Analysis of the performance of beam models with perforations under load showed that the bearing capacity of the beam decreases with increasing perforation pitch and perforation diameter. The most optimum perforation diameter for design may be perforation diameter 0,25 and 0,5 with perforation pitch 2d.

Action enhancement of antimicrobial peptides by their combination with enzymes hydrolyzing fungal quorum molecules

Recently, the lactonase activity of several enzymes (lactonase AiiA, organophosphate hydrolase (His6-OPH) and New Delhi metallo-β-lactamase (NDM-1)) was revealed in the hydrolysis of lactone-containing fungal Quorum Sensing molecules (FQSM). This study was aimed at the investigation of possible use of these enzymes as components of antifungal combinations with antimicrobial peptides (AMPs) to increase their action efficiency against various fungi. For this, the interaction of various AMPs with AiiA, NDM-1 or His6-OPH, as well as the effect of AMPs on the catalytic characteristics of these enzymes in the hydrolysis of FQSM in enzyme/AMP combinations, were studied using in silico computer modeling methods. Enzymes combinations with 3 AMPs Bacitracin, Colistin and Polymyxin B were selected as the most rational in terms of maintaining the effectiveness of AMP and the catalytic activity of enzymes. The antifungal action of the selected combinations against cells of mycelial fungi and yeast was studied in vitro. It was found that combinations of the enzymes AiiA, His6-OPH and NDM-1 with Bacitracin, Colistin and Polymyxin B provide a significant increase in the action efficiency (up to 5000 times) of both AMPs and enzymes against fungi. The most effective variants were obtained for Polymyxin B in multicomponent combinations with enzymes.

Reconstructing of the geometry of Atg13 and Atg101 molecules while assembling the complex

Aim. Associated subproteins which constitute the ATG1 multi-protein complex in plants and mammals, including ULK1 in humans, are orchestral protein kinase atg-units in resistance to stress stimuli across their different nature. The goals of this endeavour were to characterize the molecular nature of the interaction of ATG13 with ATG101, followed by in silico docking to catch the plausible ensuing integration into a multimeric complex ULK1/ATG1, which initiates the assembly of a PAS-preautophagosomal structure in the first step of autophagy initiation. Methods. Protein structures were modeled by homology using AlphaFold, and molecular dynamics (MD) was performed using GROMACS 5.0 with the Charmm36. Results. By implementing computer modeling methods, a complex of protein kinase atg-units for both ATG13 and ATG101 proteins, reflecting the interaction interface and conformational properties, was constructed for detailed interpretation while forming the forthcoming assembly of the ULK1/ATG1 multi-protein platform. Conclusions. This study provides a high-quality model platform for further sequential studies of protein-protein docking and protein-protein interactions with the possibility of reconstructing a model of the full ULK1/ATG1 complex to identify ATG8 binding sites.

Computational Study of Molecular Mechanism for the Involvement of Human Serum Albumin in the Renin–Angiotensin–Aldosterone System

Human serum albumin (HSA) is an endogenous inhibitor of angiotensin I-converting enzyme (ACE) and, thus, plays a key role in the renin–angiotensin–aldosterone system (RAAS). However, little is known about the mechanism of interaction between these proteins, and the structure of the HSA–ACE complex has not yet been obtained experimentally. The purpose of the presented work is to apply computer modeling methods to study the interaction of HSA with ACE in order to obtain preliminary details about the mechanism of their interaction. Ten possible HSA–ACE complexes were obtained by the procedure of macromolecular docking. Based on the number of steric and polar contacts between the proteins, three leading complexes were selected, the stabilities of which were then tested by molecular dynamics (MD) simulation. Based on the results of MD simulation, the two most probable conformations of the HSA–ACE complex were selected. The analysis of these conformations revealed that the processes of oxidation of the thiol group of Cys34 of HSA and the binding of albumin to ACE can reciprocally affect each other. Known point mutations in the albumin molecules Glu82Lys, Arg114Gly, Glu505Lys, Glu565Lys and Lys573Glu can also affect the interaction with ACE. According to the result of MD simulation, the known ACE mutations, albeit associated with various diseases, do not affect the HSA–ACE interaction. A comparative analysis was performed of the resulting HSA–ACE complexes with those obtained by AlphaFold 3 as well as with the crystal structure of the HSA and the neonatal Fc receptor (FcRn) complex. It was found that domains DI and DIII of albumin are involved in binding both ACE and FcRn. The obtained results of molecular modeling outline the direction for further study of the mechanisms of HSA–ACE interaction in vitro. Information about these mechanisms will help in the design and improvement of pharmacotherapy aimed at modulation of the physiological activity of ACE.

Exploring flavonoids as potential inhibitors for Enterococcus faecium nicotinate nucleotide adenylyltransferase: An integration of in silico with empirical studies

Nicotinate nucleotide adenylyltransferase (NNAT) emerges as a promising target for drug development, given its pivotal role in the nicotinate nucleotide biosynthesis pathway crucial for bacterial survival. Using computational modelling and fluorescence methods, this study screened a library of 1427 compounds from MedChemExpress as potential inhibitors against Enterococcus faecium NNAT (EfNNAT). We employed Maestro's Glide HTVS, SP, and XP docking protocols to identify compounds with high binding affinity. The screening utilised two models of the EfNNAT crystal structure: energy-minimised and 100-ns MD-simulated model, hypothesising conformational change that may influence ligand selectivity in the HTVS study. Our findings revealed variations between the minimised versus MD-simulated models, impacting ligand selectivity by each model post-HTVS. However, quercetin 3-O-beta-d-glucose-7-O-beta-d-gentiobioside (QGG) appeared to be the top inhibitor selected by both models after more rigorous docking using Maestro-implemented SP and XP. A 500-ns all-atom MD simulation of the EfNNAT:ligand complex revealed that the compound interacts mainly through hydrogen bonding and water bridges. Validation of the in-silico studies via molecular spectroscopy confirmed QGG's binding to EfNNAT by displacing the fluorescent probes from the protein binding site. Although the binding demonstrated minimal impact on the thermal stability of EfNNAT as deduced from the thermal shift assay, ITC showed that QGG exhibits moderate binding affinity for EfNNAT, with the interaction being spontaneous and thermodynamically favourable. Insights gleaned from this study offer a mechanistic basis that could be leveraged to develop new leads. Expansion of the compound library holds promise for identifying inhibitors with enhanced affinity for EfNNAT.

Some Aspects and Convergence of Human and Veterinary Drug Repositioning.

Drug innovation traditionally follows a de novo approach with new molecules through a complex preclinical and clinical pathway. In addition to this strategy, drug repositioning has also become an important complementary approach, which can be shorter, cheaper, and less risky. This review provides an overview of drug innovation in both human and veterinary medicine, with a focus on drug repositioning. The evolution of drug repositioning and the effectiveness of this approach are presented, including the growing role of data science and computational modeling methods in identifying drugs with potential for repositioning. Certain business aspects of drug innovation, especially the relevant factors of market exclusivity, are also discussed. Despite the promising potential of drug repositioning for innovation, it remains underutilized, especially in veterinary applications. To change this landscape for mutual benefits of human and veterinary drug innovation, further exploitation of the potency of drug repositioning is necessary through closer cooperation between all stakeholders, academia, industry, pharmaceutical authorities, and innovation policy makers, and the integration of human and veterinary repositioning into a unified innovation space. For this purpose, the establishment of the conceptually new "One Health Drug Repositioning Platform" is proposed. Oncology is one of the disease areas where this platform can significantly support the development of new drugs for human and dog (or other companion animals) anticancer therapies. As an example of the utilization of human and veterinary drugs for veterinary repositioning, the use of COX inhibitors to treat dog cancers is reviewed.

Design and Technological Aspects of Integrating Multi-Blade Machining and Surface Hardening on a Single Machine Base

Modern mechanical engineering faces high competition in global markets, which requires manufacturers of process equipment to significantly reduce production costs while ensuring high product quality and maximum productivity. Metalworking occupies a significant part of industrial production and consumes a significant share of the world’s energy and natural resources. Improving the technology of manufacturing parts with an emphasis on more efficient use of metalworking machines is necessary to maintain the competitiveness of the domestic machine tool industry. Hybrid metalworking systems based on the principles of multi-purpose integration eliminate the disadvantages of monotechnologies and increase efficiency by reducing time losses and intermediate operations. The purpose of this work is to develop and implement a hybrid machine tool system and an appropriate combined technology for manufacturing machine parts. Theory and methods. Studies of the possible structural composition and layout of hybrid equipment at integration of mechanical and surface-thermal processes were carried out, taking into account the basic provisions of structural synthesis and componentization of metalworking systems. Theoretical studies were carried out using the basic provisions of system analysis, geometric theory of surface formation, design of metalworking machines, methods of finite elements, and mathematical and computer modeling. The mathematical modeling of thermal fields and structural-phase transformations during HEH HFC was carried out in ANSYS (version 19.1) and SYSWELD (version 2010) software packages using numerical methods of solving differential equations of unsteady heat conduction (Fourier equation), carbon diffusion (2nd Fick’s law) and elastic–plastic behavior of the material. The verification of the modeling results was carried out using in situ experiments employing the following: optical and scanning microscopy; and mechanical and X-ray methods of residual stress determination. Formtracer SV-C4500 profilograph profilometer was used in the study for simultaneous measurement of shape deviations and surface roughness. Surface topography was assessed using a Walter UHL VMM 150 V instrumental microscope. The microhardness of the hardened surface layer of the parts was evaluated on a Wolpert Group 402MVD. Results and discussion. The original methodology of structural and kinematic analysis for pre-design studies of hybrid metalworking equipment is presented. Methodological recommendations for the modernization of multi-purpose metal-cutting machine tool are developed, the implementation of which will make it possible to implement high-energy heating with high-frequency currents (HEH HFC) on a standard machine tool system and provide the formation of knowledge-intensive technological equipment with extended functionality. The innovative moment of this work is the development of hybrid metalworking equipment with numerical control and writing a unique postprocessor to it, which allows to realize all functional possibilities of this machine system and the technology of combined processing as a whole. Special tooling and tools providing all the necessary requirements for the process of surface hardening of HEH HFC were designed and manufactured. The conducted complex of works and approbation of the technology of integrated processing in real conditions in comparison with traditional methods of construction of technological process of parts manufacturing allowed to obtain the following results: increase in the productivity of processing by 1.9 times; exclusion of possibility of scrap occurrence at finishing grinding; reduction in auxiliary and preparatory-tasking time; and reduction in inter-operational parts backlogs.

DEFORMATION MECHANISMS IN CASE OF DESTRUCTION OF THE TUBING NOZZLE MADE OF FERRITE-PEARLITE STEEL

In the work by methods of experimental studies and computer modeling, deformation mechanisms were analyzed during the destruction of the steel suspended branch pipe of the tubing. Tubing rupture occurred during production well operation for 306 days as a result of hydrogen sulfide stress corrosion cracking (SSCC), which was preceded by hydrogen embrittlement of the metal and cyclic action of external forces. Scanning electron microscopy (SEM) shows that the suspended branch pipe is characterized by a ferrite-pearlite structure, and in the area of its fracture, which occurred in the threaded part, there is an increased content of degenerated pearlite grains and traces of hydrogen blisters. Analysis of the crystallographic texture of the original nozzle showed the presence of Br {110} < 112 >, G {110} < 001 >, TG1 {111} < 110 >, TG2 {111} < 011 >, RG {110} < 110 > and RC {001} < 110 > grain texture components. It was found that after operation of the nozzle in well conditions, in the area far from the fracture, the grain orientations related to Cube {001} < 100 >, TG1 {111} < 110 >, TG2 {111} < 011 >, TB3 {331} < 136 > texture components increase. It was found that in the fracture area, in addition to the grain orientations characteristic of the nozzle body, there are also Br {110} < 112 >, G {110} < 001 >, RC {001} < 110 >, RG {110} < 110 >, TC {112} < 110 >, TB1 {111} < 112 > and TB2 {554} < 225 > texture components It is shown that Cube and grain orientation TB3 in the branch pipe after operation accelerate the process of hydrogen embrittlement of metal, and the presence of TB1 orientation indicates the process of return and/or recrystallization in the product. It was found that the process of hydrogen embrittlement led to a decrease in the strength properties and ductility of the steel of the branch pipe. Within the framework of viscoplastic self-consistent (VPCC) model, textures and deformation behavior of samples cut from different sections of the nozzle (before and after operation) were simulated. It was found that at the initial stages of tension the samples of the new branch pipe, the most active is the operation of {110} < 111 > slip systems. In samples of the nozzle after operation, the activity of {110} < 111 > slip systems decreases. At the same time, the activity of {123} < 111 > slip systems increases, and the nature of the operation < 112 > {111} of the slip system does not change. It was found that in all studied states before destruction the activity of {123} < 111 > systems increases ~ 1.4 times. It was concluded that the growth of TG2 {111} < 011 >, {332} < 110 > and {557} < 110 > texture components, as well as the activity of < 123 > {111} slip systems are associated with the effect of shear deformations that generate microcracks in pearlitic grains, and the applied forces contribute to the development of cracks and subsequent destruction of the product. It has been shown that by controlling the crystallographic texture and, accordingly, deformation mechanisms, it is possible to produce new pipeline steels that are more resistant to SSCC.