ISSN 2410-7751 (Print)
ISSN 2410-776X (Online)
Biotechnologia Acta V. 13, No 3, 2020
Р. 30-44, Bibliography 138, English
Universal Decimal Classification: 519.8.612.007
https://doi.org/10.15407/biotech13.03.030
N. I. Aralova1, O. M. Klyuchko 2, V. I. Mashkin 1 , I. V. Mashkina 1, T. A. Semchyk1
1 Glushkov Institute of Cybernetics of the National Academy of Sciences of Ukraine, Kyiv
2 National Aviation University, Kyiv, Ukraine
The aim of the work was to create a complex mathematical model simulating the course of the disease caused by the SARS-CoV-2 virus on the level of interaction between functional systems of organism and pharmacological correction of organism hypoxic states arising in the complicated course of the disease. In the present work the methods of mathematical modeling and theory of optimal control of moving objects were used. The proposed integrated mathematical model consisted on the mathematical models of functional systems of respiration and blood circulation, thermoregulation, immune response, erythropoesis, and pharmacological correction. Individual patient data were taken for this model, and the disturbing effect in the form of viral disease was simulated. The reactions of functional respiratory and blood circulatory systems were predicted. Partial pressures of respiratory gases in alveolar spaces and their tensions in lung capillaries blood, arterial and mixed venous blood, and tissue fluid were calculated. Further the intravenous injection of antihypoxant was simulated and the values of the same parameters were calculated. In such a way it was possible to choose the most optimal way of hypoxic state correction for any individual. This model is theoretical only for today because the models of respiratory and blood circulation systems were designed for the average person and it does not suppose peculiarities of individual persons infected with SARS-CoV-2. In particular, this concerns the peculiarities of gas exchange in the alveolar space and characteristics of respiratory gases diffusion through the alveolar-capillary and capillary-tissue membranes. However, it is one of possible directions for solving the complex tasks related to treatment of the disease caused by SARS-CoV-2 virus. In the result of the work the complex of information support for the imitation of viral disease course was developed at the level of interaction of organism functional systems, as well as pharmacological correction of caused by it hypoxic states.
Key words: SARS-Cov-2 virus, immune response model, mathematical model of the respiratory system, hypoxic state, infection lesion
© Palladin Institute of Biochemistry of National Academy of Sciences of Ukraine, 2020
References
1. Novel coronavirus (2019-nCoV) . WHO/Europe. World Health Organization (9 March 2020). Available at http://www.euro.who.int/en/health-topics/health-emergencies/novel-coronavirus-2019-ncov_old
2. Nicholas J. Beeching, Tom E. Fletcher, Robert Fowler. COVID-19. BMJ Best Practices. BMJ Publishing Group (17 Rebruary 2020).
3. David L. Heymann, Nahoko Shindo. COVID-19: what is next for public health? The Lancet. Elsevier, 2020.13 February. ISSN 1474-547X 0140-6736, 1474-547X. https://doi.org/10.1016/S0140-6736(20)30374-3
4. Prevention, diagnosis and treatment of new coronavirus infection (COVID-19). Temporal methodical recommendations. Health Ministry of Russia. (March 3, 2020). https://static-0.rosminzdrav.ru/system/attachments/attaches/000/049/629/original/Временные_МР_COVID-19_03.03.2020 (In Russian).
5. Available at https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200128-sitrep-8-ncov-cleared.pdf?sfvrsn=8b671ce5_2
6. Available at https://emcrit.org/ibcc/covid19/CDC, Novel Coronavirus 2019 Situation Summary.
7. WHO recommendations to the public regarding the spread of the new coronavirus (2019-nCoV): myths and misconceptions. Available at https://ru.wikipedia.org.wiki/ Coronaviral infection COVID 19 (In Russian).
8. WHO recommendations to the public regarding the spread of the new coronavirus (2019-nCoV): myths and misconceptions COVID-19. Available at https://www.who.int/ru/emergencies/diseases/novel-coronavirus-2019/advice-for-public/q-a-c (In Russian).
9. How to Protect Yourself & Others. Available at https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/prevention.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-ncov%2Fprepare%2Fprevention.html
10. Srinivas Murthy, Charles D. Gomersall, Robert A. Fowler. Care for Critically Ill Patients With COVID-19. Jama. 2020, 11 March. https://doi.org/10.1001/jama.2020.3633
11. Anthony S. Fauci, H. Clifford Lane, Robert R. Redfield. Covid-19 ? Navigating the Uncharted. New Engl. J. Med. 2020, 28 February. https://doi.org/10.1056/NEJMe2002387
12. Yonghong Xiao, Mili Estee Torok. Taking the right measures to control COVID-19. The Lancet Infectious Diseases. Elsevier. 2020, 5 March. https://doi.org/10.1016/S1473-3099(20)30152-3
13. Rebrova O. Yu., Vlasov V. V., Baschinsky S. E., Aksyonov V. A. TWIMC: SDMX comment on coronavirus infection. OSDM (March 22, 2020). 2020. http://osdm.org/blog/2020/03/22/twimc-kommentarij-osdm-o-koronavirusnoj-infekcii/
14. Xu X. Chen P., Wang J. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission: Science China Life Sciences. https://doi.org/10.1007/s11427-020-1637-5
15. Letko Michael, Munster Vincent. Functional assessment of cell entry and receptor usage for lineage B ?-coronaviruses, including 2019-nCoV. BioRxiv : journal. 2020, 22 January, P. 2020.01.22.915660. https://doi.org/10.1101/2020.01.22.915660
16. Zhou Peng, Shi Zheng-Li. Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin. BioRxiv: journal. 2020, P. 2020.01.22.914952. https://doi.org/10.1101/2020.01.22.914952
17. Gralinski L. E., Menachery V. D. Return of the Coronavirus: 2019-nCoV. Viruses. 2020, 12 (2), 135. https://doi.org/10.3390/v12020135
18. European Centre for Disease Prevention and Control, Novel coronavirus (2019-nCoV) infections, p. 8.
19. Ke Wang, Wei Chen, Yu-Sen Zhou, Jian-Qi Lian, Zheng Zhang, Peng Du, Li Gong, Yang Zhang, Hong-Yong Cui, Jie-Jie Geng, Bin Wang, Xiu-Xuan Sun, Chun-Fu Wang, Xu Yang, Peng Lin, Yong-Qiang Deng, Ding Wei, Xiang-Min Yang, Yu-Meng Zhu, Kui Zhang, Zhao-Hui Zheng, Jin-Lin Miao, Ting Guo, Ying Shi, Jun Zhang, Ling Fu, Qing-Yi Wang, Huijie Bian, Ping Zhu, Zhi-Nan Chen. SARS-CoV-2 invades host cells via a novel route: CD147-spike protein. BioRxiv: journal. https://doi.org/10.1101/2020.03.14.988345
20. Zhonghua Liu Xing Bing Xue Za Zhi Novel Coronavirus Pneumonia Emergency Response Epidemiology Team. [The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China]. 2020, 41 (2), 145?151. https://doi.org/10.3760/cma.j.issn.0254-6450.2020.02.003. PMID 32064853.
21. Li Q., Guan X., Wu P., Wang X., Zhou L., Tong Y., Ren R., Leung K. S., Lau E. H., Wong J. Y., Xing X., Xiang N., Wu Y., Li C., Chen Q., Li D., Liu T., Zhao J., Li M., Tu W., Chen C., Jin L., Yang R., Wang Q., Zhou S., Wang R., Liu H., Luo Y., Liu Y., Shao G., Li H., Tao Z., Yang Y., Deng Z., Liu B., Ma Z., Zhang Y., Shi G., Lam T. T., Wu J. T., Gao G. F., Cowling B. J., Yang B., Leung G. M., Feng Z. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. The New England Journal of Medicine. 2020. January. https://doi.org/10.1056/NEJMoa2001316
22. Charles Calisher, Dennis Carroll, Rita Colwell, Ronald B. Corley, Peter Daszak et al. Statement in support of the scientists, public health professionals, and medical professionals of China combatting COVID-19. The Lancet. Correspondence. Elsevier. 2020, 18 February. https://doi.org/10.1016/S0140-6736(20)30418-9
23. Zhao Shi, Ran Jinjun, Musa Salihu Sabiu, Yang Guangpu, Lou Yijun, Gao Daozhou, Yang Lin, He Daihai. Preliminary estimation of the basic reproduction number of novel coronavirus. BioRxiv. 2019, 24 January.
24.Qun Li, Xuhua Guan, Peng Wu, Xiaoye Wang, Lei Zhou. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia. New England Journal of Medicine. 2020-01-29. https://doi.org/10.1016/S0140-6736(20)30418-9
25. Ji W., Wang W., Zhao X. Homologous recombination within the spike glycoprotein of the newly identified coronavirus may boost cross?species transmission from snake to human. Journal of Medical Virology. Hoboken, New Jersey: Wiley-Blackwell. 2020, January, P. 1?29. ISSN1096-9071. https://doi.org/10.1002/jmv.25682
26. Callaway E. Why snakes probably aren’t spreading the new China virus: One genetic analysis suggests reptilian reservoir ? but researchers doubt that the coronavirus could have originated in animals other than birds or mammals : [англ.] / E. Callaway, D. Cyranoski. Nature ? Nature Publishing Group. 2020, January. https://doi.org/10.1038/d41586-020-00180-8
27. Zhou, Peng, Yang Xing-Lou, Wang Xian-Guang. Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin [preprint]. BioRxivruen: [site]. 2020, January, 18 p. https://doi.org/10.1101/2020.01.22.914952
28. Meerson F. Z. General mechanism of adaptation and role of stress-reaction in it, main stages of the processes. Moskva: Nauka. 1986, P.77–123 (In Russian).
29. Meerson F. Z., Pshennikova M. G. Adaptation to stressed situations and physical loadings. Moskva: Medicina. 1988, 256 p. (In Russian).
30. Onopchuk Yu. N., Beloshitsky P. V., Aralova N. I. To the question of the reliability of functional organism systems. Kibernetika i vy?islitelna? tehnika. 1999, Is. 122, P. 72?82 (In Russian).
31. Beloshitsky P. V., Onopchuk Yu. M., Aralova N. I. Mathematical methods for the investigation of the problem of organism functioning reliability at extreme high mountains conditions. Physiol. Journal. 2003, 49 (3), 47?54 (In Russian).
32. Beloshitsky P. V., Onopchuk Yu. N., Aralova N. I. Mathematical methods for investigating the reliability of organisms functioning under the extreme conditions of high mountains. High Altitude medicine and biolog. 2002, 3 (1), 129.
33. Beloshitsky P. V., Onopchuk Yu. N., Aralova N. I. Investigation the reability of the functioning of organisms systems under high-altitude conditions. Mathematical modelling. Scientific Highlights 1999?2002, International Centre for Astronomical, Medical and Ecological Research. Kyiv. 2002.
34. Onopchuk Yu., Beloshitsskiy P., Aralova N. Stability, adaptation and reliability of an organism’s functional systems under hypoxia. “The 3rd World Congress on Mountain Medicine and High Altitude Physiology and the 18th Japanese Symposium on Mounain Medicine, May 20th?24th”. 1998. Matsumoto, Japan.
35. Aralova N. I. Mathematical model of the mechanism short- and medium-functional adaptation of breath of persons work in extreme conditions high. Kibernetika i vy?islitelna? tehnika. 2015, V. 182, P. 15?25. https://doi.org/10.15407/kvt182.02.045
36. Aralova N. I., Klyuchko O. M., Mashkin V. I., Mashkina I. V. Software for the reliability investigation of operator professional activity for “human-machine” systems. Electronics and control systems. 2017, V. 1, P. 107?115. https://doi.org/10.18372/1990-5548.51.11712
37. Aralova N. I. Mathematical models of functional respiratory system for solving the applied problems in occupational medicine and sports. Saarbr?cken: LAP LAMBERT Academic Publishing GmbH&Co, KG. 2019, 368 p. (In Russian). ISBN 978-613-4-97998-6
38. Gray J. S. The multiple factor theory of respiratory regulation. Science. 1946, V. 103, P. 739–743. https://doi.org/10.1126/science.103.2687.739
39. Grodins F. S., Buell J., Bart A. J. Mathematical analysis and digital sinulation tje respiratory control system. J. Appl. Physiol. 1967, 22 (2), 272. https://doi.org/10.1152/jappl.1967.22.2.260
40. Grodinz F. Theory of regulation and biological systems. Moskva: Mir. 1966, 315 p. (In Russian).
41. Kolchinskaya A. Z., Misyura A. G., Mankovskaya I. N. Respiration and oxygen regimes of dolphins. Kyiv: Nauk. dumka. 1980, 332 p. (In Russian).
42. Lauer N. B., Kolchinskaya A. Z. About the oxygen organism regimeOxygen organism regime and its regulation. Kyiv: Nauk. dumka. 1966, P. 157–200 (In Russian).
43. Marchuk G. I. Mathematic modeling in the problem of environment. Moskva: Nauka. 1982, 320 p. (In Russian).
44. Dickinson C. J. A computer model of human respiration. Lancaster: Medical and Technical Publishing. 1977, 294 p.
45. Amosov N. M., Paletz B. L., Agapov B. T. Theoretical investigations of physiological systems. Kyiv: Nauk. dumka. 1977, 246 p. (In Russian).
46. Amosov N. M., Paletz B. L., Agapov B. T., Ermakova I. I., Liabah E. G., Theoretical investigations of physiological systems. Kyiv: Nauk. dumka. 1977, 246 p. (In Russian).
47. Marchuk G. I. Mathematic models in immunology. Moskva: Nauka. 1991, 304 p. (In Russian).
48. Novoseltsev V. N. Theory of control and biosystems. Moskva: Nauka. 1978, 319 p. (In Russian).
49. Amosov N. M. Regulation of vital functions and cybernetics. Kyiv: Nauk. dumka. 1998, 366 p. (In Russian).
50. Antomonov Yu. G. Modeling of biological systems. Kyiv: Nauk. dumka. 260 p. (In Russian).
51. Secondary tissue hypoxia. Ed. Kolchinskaya A. Z. Kyiv: Nauk. dumka. 1983, 253 p. (In Russian).
52. Shumakov V. N, Novoseltsev V. N., Sacharov V. P., Shtengold. Modeling of organism physiological systems. Moskva: Medicine. 1971, 352 p. (In Russian).
53. Onopchuk Yu. N. Controled models of gases dynamics in organism and their numerical analysis. Theases for the obtaining the scientific degree of doctor of phys.-mat. sciences. Kyiv. 1984, 45 p. (In Russian).
54. Onopchuk Yu. N. Homeostasis of functional respiratory system as a result of intersystem and system-medium informational interaction. Bioecomedicine. Uniform information space. Ed. by V. I. Gritsenko. Kyiv. 2001, P. 59?84 (In Russian).
55. Onopchuk Yu. N. Homeostasis of the functional circulatory system as a result of intersystem and system-medium informational interaction. Bioecomedicine. Uniform information space. Ed. by V. I. Gritsenko. Kyiv. 2001, P. 85?104 (In Russian).
56. Polynkevich K. B., Onopchuk Yu. N. Conflict situations at regulating of the main function of organism respiratory system and mathematical models of their resolution. Cybernetics. 1986, V. 3, P. 100?104 (In Russian).
57. Aralova N. I., Aralova А. А. Mathematical models of conflict controlled processes under functional self- organization of the respiratory system. Cyb. comp. eng. 2019, 3 (197), 65?79. https://doi.org/10.15407/kvt197.03.065
58. Galchyna N. I., Onopchuk Iu. N., Portnichenko V. I., Siemchyk T. A. Game models for the control of the main body functional systems and their analysis. Cybernetics and system analysis. 2014, 50 (1), 77?92. https://doi.org/10.1007/s10559-014-9593-9
59. Galchyna N. I., Onopchuk Iu. N., Portnichenko V. I., Siemchyk T. A. Game models for the control of the main body functional systems and their analysis. Cybernetics and system analysis. 2014, 50 (2), 89?98. https://doi.org/10.1007/s10559-014-9611-y
60. Onopchuk Y. N., Loziychuck N. G. Mathematical model and organism systems for thermoregulation and their analysis. Cybernetic and system analysis. 1995, N 4, P. 152–160 (in Russian).
61. Loziychuk N. G., Marchenko D. I., Onopchuk D. I. About one model of heat exchange in organism and its quantitative and qualitative homeostasis. Kibernetika i vy?islitelna? tehnika. 1987, N 74, P. 80?82 (In Russian).
62. Loziychuk N. G. Mathematical model of control of the level of temperature homeostasis. Kibernetika i vy?islitelna? tehnika. 1989, N 82, P. 77?80 (In Russian).
63. Semchyk T. A. Mathematical model of the hypoxia course process under infectious diseases, the ischemic heart deseases and their analysis. Theases for the obtaining the scientific degreeof Candidate of Technical Sciences on speciality 01.05.02 – mathematical modeling and computational methods.V. M. Glushkov Institute of Cybernetics of the National Academy of Sciences of Ukraine. Kyiv. 2007, 20 p.
64. Semchyk T. A. The mathematical model of immune response on infectious damage to an organism and mechanisms of its interaction with models of respiration, blood circulation and heat exchange. Theory of optimal solution. 2018, V. 17, P. 92?98.
65. Aralova N. I., Shakhlina L. Ya.-G., Futornyi S. M. Mathematical model of the immune system of hight qualification athlete. Journal of Automation and Information Sciences. 2019, V. 2, P. 130?142.
66. Galchina N. I. Mathematical models of energy resource assessment in strenuous activity and post-activity recovery. Cybernetics and system analysis. 2014, 50 (2), 940?944. https://doi.org/10.1007/s10559-014-9684-7
67. Garaschenko F. G., Lanovenko I. I., Grabova N. I. About one mechanism of autoregulation of process of breath in the organism and is mathematical model. Theory of optimal solution. 2008, V. 7, P. 139?145.
68. Galchyna N. I., Korniush I. I., Semchyk T. A. Mathematical models for complex assessment of the functional condition of the human body in extreme conditions. Theory of optimal solutions. 2019, V. 18, P. 13–18.
69. Aralova N. I., Onopchuk Yu. N., Polinkevich K. B. Role of mechanisms of systemic regulation of respiration and blood circulation during intensive operator activity. Kibernetika i vy?islitelna? tehnika. 1995, Is. 106, P.103?108 (In Russian).
70. Onopchuk Yu. N., Navakatikyan A. O., Aralova N. I. Pequliarities of self-organization of cardiovascular system during intensive operator activity. Model studying. Human problems – ecology, health, education: Materials 1st Intern.Counsil, May 18?21, 1995. Uzhgorod, Ukraine. 1996, P. 116?120 (In Russian).
71. Navakatikyan A. O., Marchenko D. I., Onopchuk Yu. N., Aralova N. I. Role of mechanisms of systemic regulation of respiration and blood circulation during intensive operator activity. Hypoxia: destructive and constructive action. Mater. of Intern. Conference and Prielbrussie talks devoted to 50-th anniv.of research activity and 80-th anniv.of birthday of Prof., Dr. Sci. Kolchinskaya A. Z. Kyiv, June 10–12, Terskol Aug. 6?12, 1998 р. (In Russian).
72. Aralova N. I. Mathematical model of reliability of the function operator of the system of continuous interactions during temperature alteration. Wshodnioeuropejskie Czasopismo Naukowe. 2015, V. 1, P. 81?87.
73. Aralova N. I. Software for studing of reliability of operator work under hightened situational stress. Science and Innovation. 2016, 12 (2), 15?25. http://dx.doi.org/10/15407/scin12.02.015 (in Ukrainian).
74. Aralova N. I., Mashkin N. I., Mashkina I. V. Reliability of the work of operators of human-mashine system in conditions of high situational stress and temperature changes in environment. Study at mathematical model. Mater. of 5-th Intern. Conference in Math. Modeling, Optimization and Information Technologies. Kishiney, March 22?25, 2016, P. 22?32 (In Russian).
75. Aralova N. I. Respiratory system’s self-organization parameters of the operator of the system of continuous interaction for decision-making in a complex situational conditions. research on mathematical model. Journal of Automation and Information Sciences. 2020, V. 2, P. 83–98.
76. Bobryakova I. L. Investigation of the task of optimal control with criterion of compromise conflicts resolution in complex situation condition during decisionmaking. Kibernetika i vy?islitelna? tehnika. 2002, Is. 135, P. 84–89 (In Russian).
77. Aralova N. I., Klyuchko O. M., Mashkin V. I., Mashkina I. V. Compromise solution of conflict situations in the problem of optimal control in the desigion making under the complex situational conditions. Electronics and control systems. 2019, V. 2, P. 77?83. https://doi.org/10.18372/1990-5548.60.13818
78. Aralova N. I. Research of role of hypoxia, hypercaphnia and hypometabolism in the regulation of the respiratory sytstem in their internal and external disturbances based on the mathematical model. Kibernetika i vy?islitelna? tehnika. 2017, V. 188, P. 49?64. https://doi.org/10.15407/kvt188.02.049
79. Aralova N. I., Mashkin V. I. The control mechanism's research of the gas-exchange organizms function on the mathematical model of a functional system of respiration. Theory of optimal solutions. 2019, V. 18, P. 40?45.
80. Bobriakova I. L. Mathematical modeling of hypometabolism process with the objective to identify peculiarities of human organism during the work under condition of highlands. Kibernetika i vy?islitelna? tehnika. 2014, V. 178, P. 64?69.
81. Bobriakova I. L., Kornyush I. I., Mashkina I. V. Study of hypometabolism process during the work at highlands. Computer mathematics. 2014, N 2, Р. 34?42.
82. Bobriakova I. L., Mashkina I. V., Semchik T. A. Imitation of compensatory reactions of an organizm for a hipercapnic stimulation. Computer mathematics. 2005, N 2, P. 94?103.
83. Aralova N. I., Beloshitsky P. V. The change of the parameters of athlete's respiratory system during adaptation to the mountain meteorological factors. Research based on the mathematical models. Sports Medicine. 2016, V. 1, P. 111?116.
84. Aralova N. I., Mashkin V. I., Mashkina I. V. Mathematical model of respiratory system short-term adaptation of persons working in extreme high mountain conditions. Informatics and systemic sciences (ІСН-2016): Mater.of VІI All-Ukrainian Sci.-Pract. Conference with Intern.Participation (Poltava, March 10–12, 2016). Ed. Emetz O. O. Poltava: PUET. 2016, P. 29?31. Access: http://dspace.puet.edu.ua/handle/123456789/2968 (In Russian).
85. Aralova N. I., Shakhlina L. Ya.-G., Futornyi S. M., Kalytka S. V. Information technologies of grounding of optimal course of interval hypoxic training in practice of sports training of highly qualified sportsmen. Journal of Automation and Information Sciences. 2020, V. 1, P. 130–142. https://doi.org/10.1615/JAutomatInfScien.v52.i1.50
86. Aralova N. I., Klyuchko O. M., Mashkin V. I., Mashkina I. V.Algorithmic and program support for optimization of modes selection for pilots interval hypoxic training. Electronics and control systems. 2017, V. 2, P. 105?113. https://doi.org/10.18372/1990-5548.52.11882
87. Shakhlina L. Ya-G., Aralova N. I. Forecasting the organism reaction of the athletes on inhibiting hypoxic mixtures on the mathematical model of the functional respiration system. Kibernetika i vy?islitelna? tehnika. 2018, V. 193, P. 64?82. https://doi.org/10.15407/kvt192.03.064
88. Aralova N. I. Klyuchko O. M., Shakhlina L. Ya-G. Parameters Of Athlete Respiratory System Dependence On Organism Hormonal Status During Hypoxic Mixtures Inhalation: Research On Mathematical Models. SF J. Sports Med. 2018, V. 1, P. 2. http://scifedpublishers.com/journals/scifed-journal-of-sports-medicine
89. Aralova N. I., Shakhlina L. Ya-G. The mathematical models of functional self-organization of the human respiratory system with a change pf the hormonal states of organism. Journal of Automation and Information Sciences. 2018, V. 3, P. 132?141.
90. Aralova N. I., Mashkin V. I., Mashkina I. V. Forecasting of fatique development at mathematic model of respiratory system with optimal control. Mater. of VІ All-Ukrainian Sci.-Pract. Conference with Intern. Participation (Poltava, March 10–12, 2016.) Ed. Emetz O. O. Poltava: PUET. 2016, P. 29?31. Access: http://dspace.puet.edu.ua/handle/123456789/2392 (In Russian).
91. Kolchinskaya A. Z., Monogarov V. D., Aralova N. I. About forecasting of fatique development during intensive muscle activity. Oxygen regimes of organism, work ability, fatique during intensive muscle activity (Workshop materials). Part 1.Vilnius. 1989, P. 111–125 (In Russian).
92. Onopchuk Yu. N., Kurdanov H. A., Semchik T. A., Aralova N. I., Beloshitsky P. V. Mathematical research of oxygen insufficiency in an organism under an ischemic heart disease. Computer Mathematics. 2003, N 2, P. 152?159.
93. Beloshitsky P. V., Onopchuk Yu. N., Aralova N. I., Semchik T. A. Mathematic modeling of hypoxic states at heart ischemia. Physiol. J. 2004, 50 (3), 139?143 (In Russian).
94. Semchyk T. A. Models of development and compensation of hypoxic conditions under ischemic heart disease. Theory of optimal solutions. 2017, V. 16, P. 86–91.
95. Aralova N. I., Klyuchko O. M., Mashkin V. I., Mashkina I. V. Mathematical models for development and compensation of hypoxic states during ischemic heart disease in flight crews’ personnel. Electronics and control systems. 2019, V. 1, P. 80?90. https://doi.org/10.18372/1990-5548.59.13644
96. Aralova N. I., Mashkin V. I., Mashkina I. V. Athletes heart hypertrophy as result of long-term adaptation to loadings. Studying at mathematical model. Scientific achievements of modern society. Abstracts of the 5th International scientific and practical conference. Cognum Publishing House. Liverpool, United Kingdom. 2020, P. 286?292. URL: http://sci-conf.com.ua
97. Aralova N. I. Modification of respiration system mathematic model for the investigation of ischemic heart disease. Informatics and systemic sciences (ІСН-2017): Mater. of VІI All-Ukrainian Sci.-Pract. Conference with Intern. Participation (Poltava, March 10–12, 2017) Ed. Emetz O. O. Poltava: PUET. 2017, P. 29?31. Access: http://dspace.puet.edu.ua/handle/123456789/2968 (In Ukrainian).
98. Aralova N. I., Vyschenski V. I., Onopchuck Yu. N. Data models and algorithms for their treatment at the construction of integral of grade and performance of athletes. Computer Mathematics. 2013, V. 1, P. 151?160.
99. Onopchuk Yu. N., Aralova N. I., Beloshitsky P. V., Klyuchko O. M. Mathematic models and integral estimation of organism systems reliability in extreme conditions. Electronics and control systems. 2015, V. 4, P. 109?115. https://doi.org/10.18372/1990-5548.46.9978
100. Aralova N. I., Klyuchko O. M., Mashkin V. I., Mashkina I. V. Algorithms for data models processing for integral estimation of flight crews’ personnel states. Electronics and control systems. 2018, V. 1, P. 99?105. https://doi.org/10.18372/1990-5548.55.12788
101. Onopchuk Yu. N., Aralova N. I., Beloshitsky P. V., Klyuchko O. M. Integral estimation of human reliability and work ability during wrestling. Bulletin of Engineering Academy of Ukraine. 2015, N 3, P. 145?148 (In Russian).
102. Aralova N. I., Onopchuk Yu. N. Dynamics of voluremetric velocity of blood flow at physical loading of trained persons. Analysis of computational experiments with mathematical model. Cybernetics. 1990, N 3, P. 125?127 (In Russian).
103. Onopchuk Yu. N., Aralova N. I., Beloshitsky P. V., Podlivaev B. A., Mastucash Yu. I. Forecasting of wrestler’ state in the combat on the base of mathematic model of functional respiratory system. Computer mathematics. 2005, N 2, P. 69?79 (In Russian).
104. Aralova A. A., Aralova N. I., Kovalchuk-Khimyuk L. A., Onopchuk Yu. N. Automated information system for athletes functional diagnostics. Control systems and machines. 2008, V. 3, P. 73–78 (In Russian).
105. Beloshitsky P. V., Onopchuk Yu. N., Aralova N. I., Podlivaev B. A. Mathematic forecasting of wrestler’ state during combat. Sport medicine. 2009, N 1?2, P. 55?59 (In Ukrainian).
106. Aralova N. I., Onopchuk Yu. N., Podlivaev B. A. Mathematic models for control of sportive combat. International Workshop “Prediction and Decision Making under Uncertainties (PDMU-2004)”, Abstracts. Ternopil, Ukraine. 2004 (In Ukrainian).
107. Aralova N. I. Information technologies of decision making support for rehabilitation of sportsmen engaged in combat sport. Journal of Automation and Information Sciences. 2016, V. 3, P. 160–170.
108. Aralova A. A., Aralova N. I., Beloshitsky P. V., Onopchuk Yu. N. Automated Information System for Functional Diagnostics of Mountaineers. Sports Medicine. 2008, V. 1, P. 163?169.
109. Beloshitsky P. V., Klyuchko O. M., Onopchuk Yu. N. Results of investigations of adaptation problems by Ukrainian scientists in Prielbrussie. Bulletin of NAU. 2008, V. 1, P. 102?108 (In Ukrainian).
110. Onopchuk Yu. N., Beloshitsky P. V., Klyuchko O. M. Creation of mathematic models on the results of investigations of Ukrainian scientists at Elbrus. Bulletin of NAU. 2008, V. 3, P. 146?155 (In Ukrainian).
111. Beloshitsky P. V., Klyuchko O. M., Onopchuk Yu. N., Kolchinskaya A. Z. Results of investigations of high nervous activity by Ukrainian scientists in Prielbrussie. Bulletin of NAU. 2009, V. 2, P. 105?112 (In Ukrainian).
112. Beloshitsky P. V., Klyuchko O. M., Onopchuk Yu. N. Results of some medical and biological investigations of Ukrainian scientists at Elbrus. Bulletin of NAU. 2007, V. 3, P. 10?16 (In Ukrainian).
113. Beloshitsky P. V., Klyuchko O. M., Onopchuk Yu. N. Studying of hypoxia problem by Ukrainian scientists at Elbrus region. Bulletin of NAU. 2007, V. 2, P. 44?50 (In Ukrainian).
114. Beloshitsky P. V., Klyuchko O. M., Onopchuk Yu. N. Results of investigations by Ukrainian scientists of mountain factors influense on the health and life duration in Prielbrussie. Bulletin of NAU. 2008, V. 4, P. 102?108 (In Ukrainian).
115. Beloshitsky P. V., Klyuchko O. M., Onopchuk Yu. N. Results of investigations of structural and functional inter-relations by Ukrainian scientists in Prielbrussie. Bulletin of NAU. 2009, V. 1, P. 61?67 (In Ukrainian).
116. Aralova N. I., Klyuchko O. M., Mashkin V. I., Mashkina I. V. Mathematical models and integral estimation of organism systems reliability in extreme conditions. Electronics and control systems. 2016, V. 1, P. 107?115. https://doi.org/10.18372/1990-5548.47.10295
117. Aralova N. I., Klyuchko O. M., Mashkin V. I., Mashkina I. V. Investigation of reliability of operators work at fluctuating temperature conditions. Electronics and control systems. 2016, V. 2, P. 133?140. https://doi.org/10.18372/1990-5548.48.11227
118. Aralova N. I., Klyuchko O. M., Mashkin V. I., Mashkina I. V. Mathematical model for research of organism restoring for operators of continuously interacted system. Electronics and control systems. 2016, V. 3, P. 100?105. https://doi.org/10.18372/1990-5548.49.11245
119. Aralova N. I., Klyuchko O. M., Mashkin V. I., Mashkina I. V. Technical complex for selection, current medical control and rehabilitation of flight personnel members. Mater. Sci.-Tech. Conference «Problems of development of global system for connections, navigation, monitoring and air flights organization CNS/ATM». November 21?23, 2016. Kyiv: NAU. 2016, P. 114 (In Ukrainian).
120. Aralova N. I., Klyuchko O. M., Mashkin V. I., Mashkina I. V. Mathematic modeling of functional self-organization of pilots’ respiration. «Integrated intellectual robototechnical complexes». «IIRTC-2017»: ХІ Conf. Mater. Kyiv: «NAU-druk». 2018, P. 268?269 (In Ukrainian).
121. Aralova А. А., Aralova N. I., Klyuchko O. M., Mashkin V. I., Mashkina I. V. Information system for the examination of organism adaptation characteristics of flight crews’ personnel. Electronics and control systems. 2018, V. 2, P. 106?113. https://doi.org/10.18372/1990-5548.56.12944
122. Aralova А. А., Aralova N. I. Authomatized information system for the estimation of functional respiratory system. Physiol. J. 2008, 54 (4), P. 57 (In Russian).
123. Klyuchko O. M., Aralova N. I., Aralova A. A.Electronic automated work places for biological investigations Biotechnol. acta. 2019, 12 (2), 5?26. https://doi.org/10.15407 /biotech12/02/005
124. Aralova N. I. Evaluation of respiratory functional system, oxygen regimes of human organisms and the degree of hypoxia (a set of programs for PC). Physiol. J. 1996, 42 (3–4), 96 (In Russian).
125. Aralova N. I., Mashkin V. I. The equations of inert gases dynamics for optimization of decision-making in providing safe decompression of the aquanaut. Theory of optimal solutions. 2018, V. 17, P. 62?68.
126. Aralova N. I., Mashkin V. I., Mashkina I. V. Information technologies for decisionmaking support for providing of aquanauts decompression security in conditions of hyperbaric hypoxia. Mater. of 6-th Intern. Conferense “Mathematic modeling, optimization and information technologies”, Kishiney, Moldova Republic, November 12–16, 2018. Kishiney: Evrika. 2018, P. 248–251 (In Russian).
127. Beloshitskiy P. V., Onopchuk Yu. N., Aralova N. I. Mathematical models of respiratory systems and circulation of the blood systems as well as the estimation of organism’s reserves and of the reliability of system’s function. Eur. J. Physiol. 1995, Supp. to 430 (4). (Abstracts of the of the First FEPS Congress 9?12 Sept., 1995, Maastricht, The Netherland). https://doi.org/10.1007/BF00591375
128. Aralova N. I., Mastykash Yu. I., Mashkina I. V. Information technologies for the studying of work ability reserves of human organism during the work in extreme high mountain conditions. Mater.Conf. «Information problems of computer systems, jurisprudence, energetics, economy, modeling and management Step to the Science. Collection of research works of Buchach Institute of Management. Buchach. 2011, V. 7, P. 195?198 (In Ukrainian).
129. Aralova N. I., Mashkina I. V. Studying at mathematic models of organism adaptation possibilities for changed environmental conditions. Combinatory optimization and fuzzy multitudes: (Конем-2013). Mater. of III All-Ukrainian Sci. Seminar (Poltava, August 30?31, 2013). Ed. Dr. Sci., Prof. O. O. Emetz. Poltava: PUET. 2013, P. 5?7 (In Russian).
130. Aralova N. I. Mathematical models of estimation of depletion of functional systems of human body after exposure to hypoxia hypermetabolic and effectiveness correction. X Intern. Sci.-Pract. Conference «Domestic Science in Epoque of Changes: Postulates of the Past and Theories of New Time», part 7. 2015, V. 10, P. 7?11 (In Russian).
131. Aralova N. I., Beloshitsky P. V., Klyuchko O. M. Mathematical models of system mechanisms of organism adaptation to hypoxia Abstracts 7th Chronic Hypoxia Symposium Feb 23?Mar 2, 2019. La Paz. Bolivia Dedicated to the Late Danish Prof. Poul Erik Paulev. P. 24.
https://zuniv.net/symposium7/Abstracts7CHS.pdf
132. Marchenko D. I., Byts A. V., Semchik T. A. A multicriterial problem of system blood stream distribution in organs and tissues and an algorithm to its solution. Cybernetics and system analysis. 2001, V. 5, P. 132?141.
133. Aralova N. I. Mathematical models of decision support by the training in extreme conditions. IX Intern. Sci.-Pract. Conference «Domestic Science in Epoque of Changes: Postulates of the Past and Theories of New Time», part 7. 2015, V. 9, P. 7?9.
134. Aralova N. I. Information means for optimizing the process of athlete body recovery. Sports Medicine and physical rehabilitation. 2017, V. 1, P. 88?96.
135. Marchuk G. I., Pogozhev I. B., Zuev S. M. Similarity conditions in systems of interacting particles. Doc. RAS. 1995, 345 (5), 605?606.
136. Belykh L. N. Analysis of some mathematical models in immunology. Moskva: OVM AN USSR. 1984, 147 p.
137. Marchuk G. I., Petrov R. V., Romanyukha A. A., Bocharov G. A. Mathematical model of antiviral immune response. I. Data analysis, generalized picture construction and parameters evaluation for Hepatitis B. J. Theor. Biol. 1991, 151 (1), 1–40. https://doi.org/10.1016/S0022-5193(05)80142-0
138. Liashko N. I., Onopchuck G. Yu. Pharmacological correction of organism state. Mathematical model and its analysis. Computer Mathematics. 2005, V. 1, P. 127–134. (In Russian).