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Repressilator with time-delayed gene expression. Part I. Deterministic description
Computer Research and Modeling, 2018, v. 10, no. 2, pp. 241-259Views (last year): 30.The repressor is the first genetic regulatory network in synthetic biology, which was artificially constructed in 2000. It is a closed network of three genetic elements — $lacI$, $\lambda cI$ and $tetR$, — which have a natural origin, but are not found in nature in such a combination. The promoter of each of the three genes controls the next cistron via the negative feedback, suppressing the expression of the neighboring gene. In this paper, the nonlinear dynamics of a modified repressilator, which has time delays in all parts of the regulatory network, has been studied for the first time. Delay can be both natural, i.e. arises during the transcription/translation of genes due to the multistage nature of these processes, and artificial, i.e. specially to be introduced into the work of the regulatory network using synthetic biology technologies. It is assumed that the regulation is carried out by proteins being in a dimeric form. The considered repressilator has two more important modifications: the location on the same plasmid of the gene $gfp$, which codes for the fluorescent protein, and also the presence in the system of a DNA sponge. In the paper, the nonlinear dynamics has been considered within the framework of the deterministic description. By applying the method of decomposition into fast and slow motions, the set of nonlinear differential equations with delay on a slow manifold has been obtained. It is shown that there exists a single equilibrium state which loses its stability in an oscillatory manner at certain values of the control parameters. For a symmetric repressilator, in which all three genes are identical, an analytical solution for the neutral Andronov–Hopf bifurcation curve has been obtained. For the general case of an asymmetric repressilator, neutral curves are found numerically. It is shown that the asymmetric repressor generally is more stable, since the system is oriented to the behavior of the most stable element in the network. Nonlinear dynamic regimes arising in a repressilator with increase of the parameters are studied in detail. It was found that there exists a limit cycle corresponding to relaxation oscillations of protein concentrations. In addition to the limit cycle, we found the slow manifold not associated with above cycle. This is the long-lived transitional regime, which reflects the process of long-term synchronization of pulsations in the work of individual genes. The obtained results are compared with the experimental data known from the literature. The place of the model proposed in the present work among other theoretical models of the repressilator is discussed.
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Modeling thermal feedback effect on thermal processes in electronic systems
Computer Research and Modeling, 2018, v. 10, no. 4, pp. 483-494Views (last year): 22. Citations: 3 (RSCI).The article is devoted to the effect of thermal feedback, which occurs during the operation of integrated circuits and electronic systems with their use. Thermal feedback is due to the fact that the power consumed by the functioning of the microchip heats it and, due to the significant dependence of its electrical parameters on temperature, interactive interaction arises between its electrical and thermal processes. The effect of thermal feedback leads to a change in both electrical parameters and temperature levels in microcircuits. Positive thermal feedback is an undesirable phenomenon, because it causes the output of the electrical parameters of the microcircuits beyond the permissible values, the reduction in reliability and, in some cases, burn out. Negative thermal feedback is manifested in stabilizing the electrical and thermal regimes at lower temperature levels. Therefore, when designing microcircuits and electronic systems with their application, it is necessary to achieve the implementation of negative feedback. In this paper, we propose a method for modeling of thermal modes in electronic systems, taking into account the effect of thermal feedback. The method is based on introducing into the thermal model of the electronic system new model circuit elements that are nonlinearly dependent on temperature, the number of which is equal to the number of microcircuits in the electronic system. This approach makes it possible to apply matrix-topological equations of thermal processes to the thermal model with new circuit elements introduced into it and incorporate them into existing thermal design software packages. An example of modeling a thermal process in a real electronic system is presented, taking into account the effect of thermal feedback on the example of a microcircuit installed on a printed circuit board. It is shown that in order to adequately model the electrical and thermal processes of microcircuits and electronic systems, it is necessary to take into account the effects of thermal feedback in order to avoid design errors and create competitive electronic systems.
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Numerical studies of the parameters of the perturbed region formed in the lower ionosphere under the action of a directed radio waves flux from a terrestrial source
Computer Research and Modeling, 2018, v. 10, no. 5, pp. 679-708Views (last year): 17.The paper presents a physico-mathematical model of the perturbed region formed in the lower D-layer of the ionosphere under the action of directed radio emission flux from a terrestrial stand of the megahertz frequency range, obtained as a result of comprehensive theoretical studies. The model is based on the consideration of a wide range of kinetic processes taking into account their nonequilibrium and in the two-temperature approximation for describing the transformation of the radio beam energy absorbed by electrons. The initial data on radio emission achieved by the most powerful radio-heating stands are taken in the paper. Their basic characteristics and principles of functioning, and features of the altitude distribution of the absorbed electromagnetic energy of the radio beam are briefly described. The paper presents the decisive role of the D-layer of the ionosphere in the absorption of the energy of the radio beam. On the basis of theoretical analysis, analytical expressions are obtained for the contribution of various inelastic processes to the distribution of the absorbed energy, which makes it possible to correctly describe the contribution of each of the processes considered. The work considers more than 60 components. The change of the component concentration describe about 160 reactions. All the reactions are divided into five groups according to their physical content: ionization-chemical block, excitation block of metastable electronic states, cluster block, excitation block of vibrational states and block of impurities. Blocks are interrelated and can be calculated both jointly and separately. The paper presents the behavior of the parameters of the perturbed region in daytime and nighttime conditions is significantly different at the same radio flux density: under day conditions, the maximum electron concentration and temperature are at an altitude of ~45–55 km; in night ~80 km, with the temperature of heavy particles rapidly increasing, which leads to the occurrence of a gas-dynamic flow. Therefore, a special numerical algorithm are developed to solve two basic problems: kinetic and gas dynamic. Based on the altitude and temporal behavior of concentrations and temperatures, the algorithm makes it possible to determine the ionization and emission of the ionosphere in the visible and infrared spectral range, which makes it possible to evaluate the influence of the perturbed region on radio engineering and optoelectronic devices used in space technology.
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Some features of group dynamics in the resource-consumer agent model
Computer Research and Modeling, 2018, v. 10, no. 6, pp. 833-850Views (last year): 32.The paper investigates the features of group dynamics of individuals-agents in the computer model of the animal population interacting with each other and with a renewable resource. This type of dynamics was previously found in [Belotelov, Konovalenko, 2016]. The model population consists of a set of individuals. Each individual is characterized by its mass, which is identified with energy. It describes in detail the dynamics of the energy balance of the individual. The habitat of the simulated population is a rectangular area where the resource grows evenly (grass).
Various computer experiments carried out with the model under different parameter values and initial conditions are described. The main purpose of these computational experiments was to study the group (herd) dynamics of individuals. It was found that in a fairly wide range of parameter values and with the introduction of spatial inhomogeneities of the area, the group type of behavior is preserved. The values of the model population parameters under which the regime of spatial oscillations of the population occurs were found numerically. Namely, in the model population periodically group (herd) behavior of animals is replaced by a uniform distribution over space, which after a certain number of bars again becomes a group. Numerical experiments on the preliminary analysis of the factors influencing the period of these solutions are carried out. It turned out that the leading parameters affecting the frequency and amplitude, as well as the number of groups are the mobility of individuals and the rate of recovery of the resource. Numerical experiments are carried out to study the influence of parameters determining the nonlocal interaction between individuals of the population on the group behavior. It was found that the modes of group behavior persist for a long time with the exclusion of fertility factors of individuals. It is confirmed that the nonlocality of interaction between individuals is leading in the formation of group behavior.
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The key approaches and review of current researches on dynamics of structured and interacting populations
Computer Research and Modeling, 2019, v. 11, no. 1, pp. 119-151Views (last year): 40. Citations: 2 (RSCI).The review and systematization of current papers on the mathematical modeling of population dynamics allow us to conclude the key interests of authors are two or three main research lines related to the description and analysis of the dynamics of both local structured populations and systems of interacting homogeneous populations as ecological community in physical space. The paper reviews and systematizes scientific studies and results obtained within the framework of dynamics of structured and interacting populations to date. The paper describes the scientific idea progress in the direction of complicating models from the classical Malthus model to the modern models with various factors affecting population dynamics in the issues dealing with modeling the local population size dynamics. In particular, they consider the dynamic effects that arise as a result of taking into account the environmental capacity, density-dependent regulation, the Allee effect, complexity of an age and a stage structures. Particular attention is paid to the multistability of population dynamics. In addition, studies analyzing harvest effect on structured population dynamics and an appearance of the hydra effect are presented. The studies dealing with an appearance and development of spatial dissipative structures in both spatially separated populations and communities with migrations are discussed. Here, special attention is also paid to the frequency and phase multistability of population dynamics, as well as to an appearance of spatial clusters. During the systematization and review of articles on modeling the interacting population dynamics, the focus is on the “prey–predator” community. The key idea and approaches used in current mathematical biology to model a “prey–predator” system with community structure and harvesting are presented. The problems of an appearance and stability of the mosaic structure in communities distributed spatially and coupled by migration are also briefly discussed.
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Hybrid models in biomedical applications
Computer Research and Modeling, 2019, v. 11, no. 2, pp. 287-309Views (last year): 25.The paper presents a review of recent developments of hybrid discrete-continuous models in cell population dynamics. Such models are widely used in the biological modelling. Cells are considered as individual objects which can divide, die by apoptosis, differentiate and move under external forces. In the simplest representation cells are considered as soft spheres, and their motion is described by Newton’s second law for their centers. In a more complete representation, cell geometry and structure can be taken into account. Cell fate is determined by concentrations of intra-cellular substances and by various substances in the extracellular matrix, such as nutrients, hormones, growth factors. Intra-cellular regulatory networks are described by ordinary differential equations while extracellular species by partial differential equations. We illustrate the application of this approach with some examples including bacteria filament and tumor growth. These examples are followed by more detailed studies of erythropoiesis and immune response. Erythrocytes are produced in the bone marrow in small cellular units called erythroblastic islands. Each island is formed by a central macrophage surrounded by erythroid progenitors in different stages of maturity. Their choice between self-renewal, differentiation and apoptosis is determined by the ERK/Fas regulation and by a growth factor produced by the macrophage. Normal functioning of erythropoiesis can be compromised by the development of multiple myeloma, a malignant blood disorder which leads to a destruction of erythroblastic islands and to sever anemia. The last part of the work is devoted to the applications of hybrid models to study immune response and the development of viral infection. A two-scale model describing processes in a lymph node and other organs including the blood compartment is presented.
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Simulation equatorial plasma bubbles started from plasma clouds
Computer Research and Modeling, 2019, v. 11, no. 3, pp. 463-476Views (last year): 14.Experimental, theoretical and numerical investigations of equatorial spread F, equatorial plasma bubbles (EPBs), plasma depletion shells, and plasma clouds are continued at new variety articles. Nonlinear growth, bifurcation, pinching, atomic and molecular ion dynamics are considered at there articles. But the authors of this article believe that not all parameters of EPB development are correct. For example, EPB bifurcation is highly questionable.
A maximum speed inside EPBs and a development time of EPB are defined and studied. EPBs starting from one, two or three zones of the increased density (initial plasma clouds). The development mechanism of EPB is the Rayleigh-Taylor instability (RTI). Time of the initial stage of EPB development went into EPB favorable time interval (in this case the increase linear increment is more than zero) and is 3000–7000 c for the Earth equatorial ionosphere.
Numerous computing experiments were conducted with use of the original two-dimensional mathematical and numerical model MI2, similar USA standard model SAMI2. This model MI2 is described in detail. The received results can be used both in other theoretical works and for planning and carrying out natural experiments for generation of F-spread in Earth ionosphere.
Numerical simulating was carried out for the geophysical conditions favorable for EPBs development. Numerical researches confirmed that development time of EPBs from initial irregularities with the increased density is significantly more than development time from zones of the lowered density. It is shown that developed irregularities interact among themselves strongly and not linearly even then when initial plasma clouds are strongly removed from each other. In addition, this interaction is stronger than interaction of EPBs starting from initial irregularities with the decreased density. The numerical experiments results showed the good consent of developed EPB parameters with experimental data and with theoretical researches of other authors.
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The mechanism of dissociation of cytosine pairs mediated by silver ions
Computer Research and Modeling, 2019, v. 11, no. 4, pp. 685-693Views (last year): 2.The development of structured molecular systems based on a nucleic acid framework takes into account the ability of single-stranded DNA to form a stable double-stranded structure due to stacking interactions and hydrogen bonds of complementary pairs of nucleotides. To increase the stability of the DNA double helix and to expand the temperature range in the hybridization protocols, it was proposed to use more stable metal-mediated complexes of nucleotide pairs as an alternative to Watson-Crick hydrogen bonds. One of the most frequently considered options is the use of silver ions to stabilize a pair of cytosines from opposite DNA strands. Silver ions specifically bind to N3 cytosines along the helix axis to form, as is believed, a strong N3–Ag+–N3 bond, relative to which, two rotational isomers, the cis- and trans-configurations of C–Ag+–C can be formed. In present work, a theoretical study and a comparative analysis of the free energy profile of the dissociation of two С–Ag+–C isomers were carried out using the combined method of molecular mechanics and quantum chemistry (QM/MM). As a result, it was shown that the cis-configuration is more favorable in energy than the trans- for a single pair of cytosines, and the geometry of the global minimum at free energy profile for both isomers differs from the equilibrium geometries obtained previously by quantum chemistry methods. Apparently, the silver ion stabilization model of the DNA duplex should take into account not only the direct binding of silver ions to cytosines, but also the presence of related factors, such as stacking interaction in extended DNA, interplanar hydrogen bonds, and metallophilic interaction of neighboring silver ions.
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On the modeling of water obstacles overcoming by Rangifer tarandus L
Computer Research and Modeling, 2019, v. 11, no. 5, pp. 895-910Seasonal migrations and herd instinct are traditionally recognized as wild reindeer (Rangifer tarandus L.) species-specific behavioral signs. These animals are forced to overcome water obstacles during the migrations. Behaviour peculiarities are considered as the result of the selection process, which has chosen among the sets of strategies, as the only evolutionarily stable one, determining the reproduction and biological survival of wild reindeer as a species. Natural processes in the Taimyr population wild reindeer are currently occurring against the background of an increase in the influence of negative factors due to the escalation of the industrial development of the Arctic. That is why the need to identify the ethological features of these animals completely arose. This paper presents the results of applying the classical methods of the theory of optimal control and differential games to the wild reindeer study of the migration patterns in overcoming water barriers, including major rivers. Based on these animals’ ethological features and behavior forms, the herd is presented as a controlled dynamic system, which presents also two classes of individuals: the leader and the rest of the herd, for which their models, describing the trajectories of their movement, are constructed. The models are based on hypotheses, which are the mathematical formalization of some animal behavior patterns. This approach made it possible to find the trajectory of the important one using the methods of the optimal control theory, and in constructing the trajectories of other individuals, apply the principle of control with a guide. Approbation of the obtained results, which can be used in the formation of a common “platform” for the adaptive behavior models systematic construction and as a reserve for the cognitive evolution models fundamental development, is numerically carried out using a model example with observational data on the Werchnyaya Taimyra River.
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Application of mathematical fracture models to simulation of exploration seismology problems by the grid-characteristic method
Computer Research and Modeling, 2019, v. 11, no. 6, pp. 1077-1082In real problems of exploration seismology we deal with a heterogeneity of the nature of elastic waves interaction with the surface of a fracture by the propagation through it. The fracture is a complex heterogeneous structure. In some locations the surfaces of fractures are placed some distance apart and are separated by filling fluid or emptiness, in some places we can observe the gluing of surfaces, when under the action of pressure forces the fracture surfaces are closely adjoined to each other. In addition, fractures can be classified by the nature of saturation: fluid or gas. Obviously, for such a large variety in the structure of fractures, one cannot use only one model that satisfies all cases.
This article is concerned with description of developed mathematical fracture models which can be used for numerical solution of exploration seismology problems using the grid-characteristic method on unstructured triangular (in 2D-case) and tetrahedral (in 3D-case) meshes. The basis of the developed models is the concept of an infinitely thin fracture, whose aperture does not influence the wave processes in the fracture area. These fractures are represented by bound areas and contact boundaries with different conditions on contact and boundary surfaces. Such an approach significantly reduces the consumption of computer resources since there is no need to define the mesh inside the fracture. On the other side, it allows the fractures to be given discretely in the integration domain, therefore, one can observe qualitatively new effects, such as formation of diffractive waves and multiphase wave front due to multiple reflections between the surfaces of neighbor fractures, which cannot be observed by using effective fracture models actively used in computational seismology.
The computational modeling of seismic waves propagation through layers of mesofractures was produced using developed fracture models. The results were compared with the results of physical modeling in problems in the same statements.
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