The Relationship Between Psychology and Physiology

A major theoretical problem for Soviety psychophysiologists, many of whom base their work on Pavlovian research and theory, is the integration of Pavlovian doctrine into contemporary knowledge from neurophysiology and the burgeoning theoretical work on cybernetics. Neither modern electrophysiological techniques nor cybernetic ideas were available to Pavlov.     

The digital language of amino acids

Summary. The subject of this paper is a digital approach to the investigation of the biochemical basis of genetic processes. The digital mechanism of nucleic acid and protein bio-syntheses, the evolution of biomacromolecules and, especially, the biochemical evolution of genetic language have been analyzed by the application of cybernetic methods, information theory and system theory, respectively. This paper reports the discovery of new methods for developing the new technologies in genetics. It is about the most advanced digital technology which is based on program, cybernetics and informational systems and laws. The results in the practical application of the new technology could be useful in bioinformatics, genetics, biochemistry, medicine and other natural sciences.     

Bilateral Regulation as a Behavior Mechanism

1. With the appearance of cybernetics there has been a considerable increase in interest in problems of the regulation of processes in various complex systems, including the biological. In psychology and physiology, experience has been accumulated in the investigation of certain nerve and mental phenomena as regulatory. This has included study of the emotions in the total cycle of neurohumoral regulation, and of voluntary attention in the regulation of activity.     

Self-improvement in a complex cybernetic system and its implications for biology

It is commonly accepted by those who consider macroevolution as a process decoupled from microevolution that its apparent jerkiness (and, hence, incompatibility with principles of population genetics) results from the structural complexity of epigenetic systems, since all complex cybernetic systems are expected to behave discontinuously. To analyse the validity of this assumption, the process of self-improvement has been analysed in a complex cybernetic system by means of computer simulations. It turns out that the investigated system tends to develop by accumulation of as small structural changes as possible, while larger changes are likely to result in the collapse of the system rather than in its persistence or improvement. This implies that cybernetic considerations alone cannot justify the claim that the very nature of epigenetic systems induces evolution by discrete steps rather than by gradual accumulation of small changes.     

Confrontation of the Cybernetic Definition of a Living Individual with the Real World

The cybernetic definition of a living individual proposed previously (Korzeniewski, 2001) is very abstract and therefore describes the essence of life in a very formal and general way. In the present article this definition is reformulated in order to determine clearly the relation between life in general and a living individual in particular, and it is further explained and defended. Next, the cybernetic definition of a living individual is confronted with the real world. It is demonstrated that numerous restrictions imposed on the cybernetic definition of life by physical reality imply a number of particular properties of life that characterize present life on Earth, namely: (1) a living individual must be a dissipative structure (and therefore a low-entropy thermodynamic system out of the state of equilibrium); (2) spontaneously-originated life must be based on organic compounds; (3) evolutionarily stable self-dependent, free-living individuals must have some minimal level of complexity of structure and function; (4) a living individual must have a record of identity separated from an executive machinery; (5) the identity of living individuals must mutate and may evolve; (6) living individuals may collect and accumulate information in subsequent generations over very long periods of time; (7) the degree of complexity of a living individual reflects the degree of complexity of its environment (ecological niche) and (8) living individuals are capable of supple adaptation to varying environmental conditions. Thus, the cybernetic definition of a living individual, when confronted with the real physical world, generates most of the general properties of the present life on Earth.     

Application of cybernetic models to metabolic engineering: investigation of storage pathways

A cybernetic model is proposed to examine generic features of storage pathways. This model is capable of describing synthesis of carbon and non-carbon storage polymers. The effect of environmental conditions is evaluated using storage polymer level as a fraction of total biomass as a gauge of pathway performance. The base wild-type pathway is then analyzed to determine the effect of genetic alterations upon system performance. Proposed modifications are tested using the cybernetic model as a diagnostic tool to ascertain the ramifications of potential genetic alterations. A methodology is developed within the cybernetic framework to describe alterations of enzyme activity and over-expression of pathway enzymes. Copyright 1998 John Wiley & Sons, Inc.     

Verification of immune response optimality through cybernetic modeling

An immune response cascade that is T cell independent begins with the stimulation of virgin lymphocytes by antigen to differentiate into large lymphocytes. These immune cells can either replicate themselves or differentiate into plasma cells or memory cells. Plasma cells produce antibody at a specific rate up to two orders of magnitude greater than large lymphocytes. However, plasma cells have short life-spans and cannot replicate. Memory cells produce only surface antibody, but in the event of a subsequent infection by the same antigen, memory cells revert rapidly to large lymphocytes. Immunologic memory is maintained throughout the organism's lifetime. Many immunologists believe that the optimal response strategy calls for large lymphocytes to replicate first, then differentiate into plasma cells and when the antigen has been nearly eliminated, they form memory cells. A mathematical model incorporating the concept of cybernetics has been developed to study the optimality of the immune response. Derived from the matching law of microeconomics, cybernetic variables control the allocation of large lymphocytes to maximize the instantaneous antibody production rate at any time during the response in order to most efficiently inactivate the antigen. A mouse is selected as the model organism and bacteria as the replicating antigen. In addition to verifying the optimal switching strategy, results showing how the immune response is affected by antigen growth rate, initial antigen concentration, and the number of antibodies required to eliminate an antigen are included.     

From the "Modern Synthesis" to cybernetics: Ivan Ivanovich Schmalhausen (1884-1963) and his research program for a synthesis of evolutionary and developmental biology

Ivan I. Schmalhausen was one of the central figures in the Russian development of the "Modern Synthesis" in evolutionary biology. He is widely cited internationally even today. Schmalhausen developed the main principles of his theory facing the danger of death in the totalitarian Soviet Union. His great services to evolutionary and theoretical biology are indisputable. However, the received view of Schmalhausen's contributions to evolutionary biology makes an unbiased reading of his texts difficult. Here we show that taking all of his works into consideration (including those only available in Russian) paints a much more dynamic and exciting picture of what he tried to achieve. Schmalhausen pioneered the integration of a developmental perspective into evolutionary thinking. A main tool for achieving this was his approach to living objects as complex multi-level self-regulating systems. Schmalhausen put enormous effort into bringing this idea into fruition during the final stages of his career by combining evolutionary theory with cybernetics. His results and ideas remain thought-provoking, and his texts are of more than just historical interest.     

Adding artificial feedback to a simple aquatic ecosystem: the cybernetic nature of ecosystems revisited

A cybernetic system can be defined as one controlled by feedback, that is, a system in which input is partially determined by output. I explored the cybernetic properties of a simple planktonic ecosystem by introducing an artificial feedback loop; light energy delivered to the system was linked to the ecosystem's productivity and respiration. Specifically, I programmed a computer to turn lights on and off when dissolved oxygen reached low and high setpoints, respectively. Three treatments were applied that differed in light intensity and in range between high and low setpoints. Experiments were repeated under high and low nutrient conditions. The added feedback did not substantially alter responses to limiting factors from those expected under fixed duration lighting. However, several novel features were observed, including poor coupling between productivity and respiration, similar patterns in energy demand among treatments, and oscillations in primary productivity. These observations can be viewed as support for a holistic, cybernetic view of ecological systems. This view complements the dominant mechanistic-reductionist perspective on causality in ecosystems. The experimental addition of new feedback is apparently a useful means of investigating the self-organizational properties of ecosystems and may also improve our understanding of the consequences of anthropogenically induced feedback in natural and managed systems.     

Integrating cybernetic modeling with pathway analysis provides a dynamic, systems-level description of metabolic control

Cybernetic modeling strives to uncover the inbuilt regulatory programs of biological systems and leverage them toward computational prediction of metabolic dynamics. Because of its focus on incorporating the global aims of metabolism, cybernetic modeling provides a systems-oriented approach for describing regulatory inputs and inferring the impact of regulation within biochemical networks. Combining cybernetic control laws with concepts from metabolic pathway analysis has culminated in a systematic strategy for constructing cybernetic models, which was previously lacking. The newly devised framework relies upon the simultaneous application of local controls that maximize the net flux through each elementary flux mode and global controls that modulate the activities of these modes to optimize the overall nutritional state of the cell. The modeling concepts are illustrated using a simple linear pathway and a larger network representing anaerobic E. coli central metabolism. The E. coli model successfully describes the metabolic shift that occurs upon deleting the pta-ackA operon that is responsible for fermentative acetate production. The model also furnishes predictions that are consistent with experimental results obtained from additional knockout strains as well as strains expressing heterologous genes. Because of the stabilizing influence of the included control variables, the resulting cybernetic models are more robust and reliable than their predecessors in simulating the network response to imposed genetic and environmental perturbations.     

Metabolic modeling of Saccharomyces cerevisiae using the optimal control of homeostasis: a cybernetic model definition

A model is presented to describe the observed behavior of microorganisms that aim at metabolic homeostasis while growing and adapting to their environment in an optimal way. The cellular metabolism is seen as a network with a multiple controller system with both feedback and feedforward control, i.e., a model based on a dynamic optimal metabolic control. The dynamic network consists of aggregated pathways, each having a control setpoint for the metabolic states at a given growth rate. This set of strategies of the cell forms a true cybernetic model with a minimal number of assumptions. The cellular strategies and constraints were derived from metabolic flux analysis using an identified, biochemically relevant, stoichiometry matrix derived from experimental data on the cellular composition of continuous cultures of Saccharomyces cerevisiae. Based on these data a cybernetic model was developed to study its dynamic behavior. The growth rate of the cell is determined by the structural compounds and fluxes of compounds related to central metabolism. In contrast to many other cybernetic models, the minimal model does not consist of any assumed internal kinetic parameters or interactions. This necessitates the use of a stepwise integration with an optimization of the fluxes at every time interval. Some examples of the behavior of this model are given with respect to steady states and pulse responses. This model is very suitable for describing semiquantitatively dynamics of global cellular metabolism and may form a useful framework for including structured and more detailed kinetic models.     

Metabolic engineering from a cybernetic perspective: aspartate family of amino acids

Using the modular cybernetic framework developed by Varner and Ramkrishna (Varner and Ramkrishna; 1998a, b) a cybernetic model is formulated that describes the time evolution of the aspartate family of amino acids in Corynebacterium lactofermentum ATCC 21799. The network model formulation is employed in the role of a diagnostic tool for the overproduction of threonine. More precisely, having determined a parameter set that describes the time evolution of a base strain (lysine producer), the model predicted response to genetic perturbations, designed to enhance the level of threonine, are simulated using an appropriately modified cybernetic model and compared with the experimental results of Stephanopoulos and Sinskey (Colón et al., 1995a, Appl. Environ. Microbiol. 61, 74-78) for identical genetic perturbations. It is found that the model predicted response to enzymatic over-expression in the aspartate pathway agrees, for the most part, with experimental observations within the experimental error bounds. This result lends credence to the hypothesis that cybernetic models can be employed to predict the local response of a metabolic network to genetic perturbation, thereby, affording cognizance of the potential pitfalls of a particular genetic alteration strategy a priori.     

A cybernetic view of microbial growth: modeling of cells as optimal strategists

A cybernetic framework is presented which views microbial response in multiple substrate environments as a judicious investment of cellular resources in synthesizing different key proteins according to an optimal regulatory strategy. A mathematical model is developed within the cybernetic framework for the diauxic growth of Klebsiella pneumoniae on a mixture of D-glucose and D-xylose. The "bang-bang" optimal policy describes well the experimental observations obtained using a fermenter coupled to an Apple II microcomputer. Striking variations in respiratory levels are observed experimentally during the switching of the cell's adaptive machinery for the utilization of the less preferred substrate.     

A simultaneous saccharification and fermentation model for dynamic growth environments

Many mathematical models by researchers have been formulated for Saccharomyces cerevisiae which is the common yeast strain used in modern distilleries. A cybernetic model that can account for varying concentrations of glucose, ethanol and organic acids on yeast cell growth dynamics does not exist. A cybernetic model, consisting of 4 reactions and 11 metabolites simulating yeast metabolism, was developed. The effects of variables such as temperature, pH, organic acids, initial inoculum levels and initial glucose concentration were incorporated into the model. Further, substrate and product inhibitions were included. The model simulations over a range of variables agreed with hypothesized trends and to observations from other researchers. Simulations converged to expected results and exhibited continuity in predictions for all ranges of variables simulated. The cybernetic model did not exhibit instability under any conditions simulated.     

Application of hybrid cybernetic model in simulating myeloma cell culture co-consuming glucose and glutamine with mixed consumption patterns

A dynamic model called hybrid cybernetic model (HCM) based on structured metabolic network is established for simulating mammalian cell metabolism featured with partially substitutable and partially complementary consumption patterns of two substrates, glucose and glutamine. Benefiting from the application of elementary mode analysis (EMA), the complicated metabolic network is decomposed into elementary modes (EMs) facilitating the employment of the hybrid cybernetic framework to investigate the external and internal flux distribution and the regulation mechanism among them. According to different substrate combination, two groups of EMs are obtained, i.e., EMs associated with glucose uptake and simultaneous uptake of glucose and glutamine. Uptake fluxes through various EMs are coupled together via cybernetic variables to maximize substrate uptake. External fluxes and internal fluxes could be calculated and estimated respectively, by the combination of the stoichiometrics of metabolic networks and fluxes through regulated EMs. The model performance is well validated via three sets of experimental data. Through parameter identification of limited number of experimental data, other external metabolites are precisely predicted. The obtained kinetic parameters of three experimental cultures have similar values, which indicates the robustness of the model. Furthermore, the prediction performance of the model is successfully validated based on identified parameters.     

Cybernetic modeling based on pathway analysis for Penicillium chrysogenum fed-batch fermentation

A macrokinetic model employing cybernetic methodology is proposed to describe mycelium growth and penicillin production. Based on the primordial and complete metabolic network of Penicillium chrysogenum found in the literature, the modeling procedure is guided by metabolic flux analysis and cybernetic modeling framework. The abstracted cybernetic model describes the transients of the consumption rates of the substrates, the assimilation rates of intermediates, the biomass growth rate, as well as the penicillin formation rate. Combined with the bioreactor model, these reaction rates are linked with the most important state variables, i.e., mycelium, substrate and product concentrations. Simplex method is used to estimate the sensitive parameters of the model. Finally, validation of the model is carried out with 20 batches of industrial-scale penicillin cultivation.     

Psychological Matters in the Symposium Cybernetics in the Service of Communism

The symposium Kibernetiku — na sluzhbu kommunizmu [Cybernetics in the Service of Communism J contains articles by Soviet experts on matters of application of modern cybernetics to the major fields of science and technology. The articles in this symposium are arranged in the following sections, a listing of which indicates the breadth of the problems covered: 1) The Gathering, Processing and Transmission of Information; 2) Cybernetics and Living Nature; 3) Cybernetics and the Humanities; 4) Cybernetics in Science and Technology. The symposium has a lengthy introduction by A. I. Berg titled "Cybernetics in the Service of Communism," which is programmatic in nature and contains an analysis of all the principal problems of cybernetics.     

A cybernetic model of growth correlation in young apple trees

Growth correlations among lateral shoots of one-year-old apple treesMalus Mill., were described. The existence of a mechanism was postulated through which small original differences between buds or young shoots are quickly augmented, thus leading to differentiation of long shoots and short shoots. Existing hypotheses do not seem sufficient for explaining correlative phenomena of this type; a cybernetic approach was therefore applied. Studying growth correlations in terms of cybernetic revealed that previous hypotheses concerning correlations do not contradict each other as often thought, but depict different links in a more general chain of events. A cybernetic model points out the importance of root influences in interaction among shoots. It also shows that synergism between auxin, gibberellin and cytokinin in xylem and phloem differentiation and in starch metabolism is very important for understanding correlations in apple trees.