Artificial intelligence techniques for the control of cancer cells

NEWCHEM, an artificial intelligence system for the control of cancer cell growth, is described. This system takes into account the most recent advances in molecular and cellular biology and in cell-drug interaction, and aims to develop optimal strategies for the selective control of cancer cell through qualitative reasoning from first principles at cellular level.     

Artificial intelligence techniques for the control of cancer cells

NEWCHEM, an artificial intelligence system for the control of cancer cell growth, is described. This system takes into account the most recent advances in molecular and cellular biology and in cell-drug interaction, and aims to develop optimal strategies for the selective control of cancer cell through qualitative reasoning from first principles at cellular level.     

The dromotropic pacemaker: system analysis and design considerations.

Patients suffering from chronotropic incompetence are generally treated with a rate-responsive pacemaker that stimulates the heart at a rate derived from a strain related sensor signal. The pacemaker concept described here uses a well-defined time interval in the electrogram as sensor parameter (AVCT: atrio-ventricular conduction time). AVCT is directly controlled by the autonomic nervous system. The design of the new algorithm was based on a thorough experimental analysis of AVCT subject to variations of the exercise rate and the pacing frequency. There it was demonstrated that AVCT is disturbed by the respiratory activity. The new rate-responsive algorithm which uses the internal model control principle explicitly takes into account the closed-loop nature of the underlying system. The major design objectives were: a) extended range of the individual heart rate, b) effective attenuation of the respiratory related disturbance and c) dynamic stability. Seven patients undergoing an incremental exercise test were paced with the new AVCT-based algorithm. When paced with this algorithm the paced heart rate was 126 +/- 12 min(-1) whereas the peak intrinsic heart rate was only 100 +/- 20 min(-1). The increase which was significant (26 +/- 13 min(-1); 15.53 min(-1)) clearly demonstrated the potential of this concept to restore chronotropic competence. A reanalysis of the experiments was undertaken in order to facilitate the individual parameterization in clinical practice. It could be demonstrated that a rather simple screening test is sufficient to gain the knowledge necessary for the individual parameterisation.     

Modelling Heart Rate Kinetics

The objective of the present study was to formulate a simple and at the same time effective mathematical model of heart rate kinetics in response to movement (exercise). Based on an existing model, a system of two coupled differential equations which give the rate of change of heart rate and the rate of change of exercise intensity is used. The modifications introduced to the existing model are justified and discussed in detail, while models of blood lactate accumulation in respect to time and exercise intensity are also presented. The main modification is that the proposed model has now only one parameter which reflects the overall cardiovascular condition of the individual. The time elapsed after the beginning of the exercise, the intensity of the exercise, as well as blood lactate are also taken into account. Application of the model provides information regarding the individual’s cardiovascular condition and is able to detect possible changes in it, across the data recording periods. To demonstrate examples of successful numerical fit of the model, constant intensity experimental heart rate data sets of two individuals have been selected and numerical optimization was implemented. In addition, numerical simulations provided predictions for various exercise intensities and various cardiovascular condition levels. The proposed model can serve as a powerful tool for a complete means of heart rate analysis, not only in exercise physiology (for efficiently designing training sessions for healthy subjects) but also in the areas of cardiovascular health and rehabilitation (including application in population groups for which direct heart rate recordings at intense exercises are not possible or not allowed, such as elderly or pregnant women).     

Regulation of respiration during muscular exertion

A brief critical review of literature shows that many authors still follow a classical theory that the respiration control is performed by feedback (by deviation of PCO2, PO2 and pH in blood). This point of view does not account for the exercise hyperpnea. The present paper contains the various data and considerations which show that respiration during muscular exercise is controlled by a combined self-learning system. The system is based on both disturbance (open-loop) control and feedback control. The signals of disturbance (of central origin and from receptors of exercising muscles) cause the increase of respiration during exercise. The signals of deviations (from peripheral and central chemoreceptors) correct the response of respiratory centre to disturbance signals. The self-learning takes place by the formation of conditioned reflexes that ensures the control of respiration (the stability of gaseous composition of blood during exercise).     

Encounters in predator-prey systems: a simple discrete model

Predator-prey systems are often described by exploitation models. These models can mimic experimental data very accurately, but it is sometimes difficult to realize the relationships between the models and the behavior of individual predator and prey animals. A simple discrete model is proposed here that tries to elucidate the connections between: the animals' movements, the predator/prey encounters; and the dynamics in the system as globally represented by the exploitation models. In these models, the term "area of discovery" plays an essential role. This term is shown to be a predictable coefficient that is composed of measurable physical properties of the analyzed predator-prey system. The model takes into account that predators and prey in experimental systems often do not search randomly but prefer some parts of the test area. The model is applied to the mite system Phytoseiulus persimilis/Tetranychus urticae under simple artificial conditions.     

The regulatory principles of glycolysis in erythrocytes in vivo and in vitro. A minimal comprehensive model describing steady states, quasi-steady states and time-dependent processes.

A simple mathematical model for glycolysis in erythrocytes is presented which takes into account ATP synthesis and consumption. The system is described by four ordinary differential equations. Conditions in vivo are described by a stable steady state. The model predicts correctly the metabolite concentrations found in vivo. The parameters involved are in agreement with data on the separate steps. The metabolite changes found in pyruvate kinase-deficient erythrocytes and the species variations among erythrocytes from different animals are described satisfactorily. The roles of the enzymes in the control of metabolites and glycolytic flux are expressed in the form of a control matrix and control strengths [R. Heinrich & T.A. Rapoport (1974) Eur. J. Biochem. 42, 89-95] respectively. Erythrocytes from various species are shown to be adapted to a maximal ATP-consumption rate. The calculated eigenvalues reveal the pronounced time-hierarchy of the glycolytic reactions. Owing to the slowness of the 2,3-bisphospho-glycerate phosphatase reaction, quasi-steady states occur during the time-interval of about 0.5-2h incubation, which are defined by perturbed 2,3-bisphosphoglycerate concentrations. The theoretical predictions agree with experimental data. In the quasi-steady state the flux control is exerted almost entirely by the hexokinase-phosphofructokinase system. The model describes satisfactorily the time-dependent changes after addition of glucose to starved erythrocytes. The theoretical consequences are discussed of the conditions in vitro with lactate accumulation and the existence of a time-independent conservation quantity for the oxidized metabolites. Even in this closed system quasi-steady states occur which are characterized by approximately constant concentrations of all glycolytic metabolites except for the accumulation of lactate, fructose 1,6-bisphosphate and triose phosphate.     

Circular dichroism of polynucleotides: A general method applied to dimers

A method is described which relates the circular dichroism of a polymer to its conformation. The method takes into account near and accidental degeneracies and eliminates the artificial distinction between degenerate and nondegenerate systems. Comparison of this method with perturbation theory indicates that the errors inherent in nondegenerate perturbation theory tend to cancel when a circular dichroism spectrum is calculated. The method is applied to dinucleoside phosphates.     

Analysis and Evaluation of the Functional State of the Cardiovascular System in Cosmonauts during Long-term Spaceflights

Forty-four cosmonauts participating in 28 main long-term (73–438 days) missions on the Mirorbital station performed functional tests with graded physical exercise using a bicycle ergometer. There were two types of this functional load. The cosmonauts that participated in the first eight main missions performed a two-step exercise with a total load power of 1150 W. In the remaining cosmonauts, the exercise was three-step, with a total power of 1350 W. The results obtained during the flight were compared with the results of the same tests performed before the flight, which served as control values for each cosmonaut. To estimate the load tolerance, the heart rate (HR), systolic blood pressure, stroke volume (SV), cardiac output (CO), and cardiac index were analyzed. The data were grouped according to the load, taking into account the type of blood circulation for each group before and during the flight. The ratio between different types of blood circulation was found to change during the flight. The responses to both types of exercises before the flight were less favorable in the cases of the hyperkinetic type of circulation. In these cases, the dominance of the chronotropic function of the heart determined the increase in CO. In the cases of the hypo- and eukinetic types of circulation, the response to the exercise was close to normotonic. In microgravity, irrespective of the circulation type and the exercise, the mechanism of the CO formation changed: the effect of HR was dominant, and there was no increase in SV. Insufficient venous return to the chambers of the heart is the main cause of the decreased response of SV to exercises during spaceflight.     

Computational simulation of vibrationally resolved spectra for spin‐forbidden transitions

In this computational study, we illustrate a method for computing phosphorescence and circularly polarized phosphorescence spectra of molecular systems, which takes into account vibronic effects including both Franck‐Condon and Herzberg‐Teller contributions. The singlet and triplet states involved in the phosphorescent emission are described within the harmonic approximation, and the method fully takes mode‐mixing effects into account when evaluating Franck‐Condon integrals. Spin‐orbit couplings, which are responsible for these otherwise forbidden phenomena, are accounted for by means of a relativistic two‐component time‐dependent density functional theory method. The model is applied to two types of chiral systems: camphorquinone, a rigid organic system that allows for an extensive benchmark, and some members of a class of iridium complexes. The merits and shortcomings of the methods are discussed, and some perspectives for future developments are offered.     

Mathematical modelling of angiogenesis using continuous cell-based models

In this work, we develop a mathematical formalism based on a 3D in vitro model that is used to simulate the early stages of angiogenesis. The model treats cells as individual entities that are migrating as a result of chemotaxis and durotaxis. The phenotypes used here are endothelial cells that can be distinguished into stalk and tip (leading) cells. The model takes into account the dynamic interaction and interchange between both phenotypes. Next to the cells, the model takes into account several proteins such as vascular endothelial growth factor, delta-like ligand 4, urokinase plasminogen activator and matrix metalloproteinase, which are computed through the solution of a system of reaction–diffusion equations. The method used in the present study is classified into the hybrid approaches. The present study, implemented in three spatial dimensions, demonstrates the feasibility of the approach that is qualitatively confirmed by experimental results.     

The left ventricle as confocal prolate spheroids

A model of left ventricle is described which takes into account the physiologic variations of thickness, a function of time and distance prior to and during ejection, by assuming that the prolate spheroids are confocal at a given instant. The hyperbolic segment of arc between innermost and outermost spheroids, confocal with the latter, defines a so-called functional thickness, for which a derivation is given. Results show that this model operates in a range of eccentricity wherein thickness change per unit internal volume change are greatest.     

Central neural correlates of learned heart rate control during exercise: central command demystified

Chefer, Svetlana I., Mark I. Talan, and Bernard T. Engel.Central neural correlates of learned heart rate control during exercise: central command demystified. J. Appl.Physiol. 83(5): 1448-1453, 1997.To identify thebrain areas involved in central command, four monkeys were trained toattenuate the tachycardia of exercise while different brain sitesaffecting heart rate (HR) were simultaneously stimulated electrically.Among 24 brain sites located mostly in the limbic structures, we haveidentified four types of control systems that mediate cardiovascularand motor behavior during exercise. One system increases HRequivalently during both exercise and operantly controlled HR, whereasanother increases HR during both tasks and abolishes operant HRcontrol. In the third system, the effect of brain stimulation on HR is attenuated during exercise and during exercise with operantly controlled HR. The fourth system increases HR in both tasks, but itseffect is significantly attenuated during operant HR control. Webelieve that this last system, which includes the mediodorsal nucleus,nucleus ventralis anterior, and cingulate cortex, plays a significantrole in central command.

     

Cell cycle progression

In this paper we consider cell cycle models for which the transition operator for the evolution of birth mass density is a simple, linear dynamical system with a stochastic perturbation. The convolution model for a birth mass distribution is presented. Density functions of birth mass and tail probabilities in n-th generation are calculated by a saddle-point approximation method. With these probabilities, representing the probability of exceeding an acceptable mass value, we have more control over pathological growth. A computer simulation is presented for cell proliferation in the age-dependent cell cycle model. The simulation takes into account the fact that the age-dependent model with a linear growth is a simple linear dynamical system with an additive stochastic perturbation. The simulated data as well as the experimental data (generation times for mouse L) are fitted by the proposed convolution model.     

Comparison between a 30-s all-out test and a time-work test on a cycle ergometer

The relationship between the amount of work (Wlim) performed at the end of constant-power exhausting exercise and exhaustion time (tlim) has been studied for supramaximal exercise [105%, 120%, 135% and 150% of the individual maximal aerobic power, (MAP)] performed on a Monark cycle ergometer in nine men. The Wlim--tlim relationship was described by a linear relationship (Wlim = a + b . tlim). Intercept a was roughly equivalent to the work produced during a 1-min exercise performed at MAP. Slope b was equal to 79% of MAP. Intercept a has been correlated with the total amount of work (AW) performed during a 30-s all-out test supposed to assess anaerobic capacity. Intercept a was significantly (p less than 0.05) correlated with AW. The anaerobic capacity was not depleted at the end of the all-out test, as the mechanical power at the 30th s of this test was approximately equal to twice MAP. However, AW was significantly higher than intercept a. It was likely that the value of intercept a was an underestimation of the maximal anaerobic capacity because of the inertia of the aerobic metabolism. Indeed, an exponential model of the Wlim--tlim relationship, which takes the interia of the aerobic metabolism into account, shows that a linear approximation of the Wlim--tlim relationship yields a systematic underestimation of the anaerobic capacity. Consequently, intercept a of the Wlim--tlim relationship is not a more accurate estimation of the anaerobic capacity than the AW performed during a 30-s all-out test.(ABSTRACT TRUNCATED AT 250 WORDS)     

The process of gas exchange in the pulmonary circulation incorporating the contribution of axial diffusion

A mathematical model is made to describe the process of gas exchange in the pulmonary circulation incorporating the contribution of axial diffusion. The model takes into account the transport mechanisms of molecular diffusion, convection and facilitated diffusion due to the presence of haemoglobin as a carrier of the gases. The mathematical formulation leads to a coupled system of non-linear elliptic partial differential equations. A numerical scheme is described to solve such a system. It is found that the axial diffusion does not have an appreciable effect on the transport of the species in the blood.     

Optimization of diameters and bifurcation angles in lung and vascular tree structures

An optimization model is described for lung and vascular tree structures. The model extends Murray's model, which is derived from minimal power dissipation due to the frictional resistance of laminar flow and the volume of the duct system. Instead of just laminar flow, it takes into account all types of steady flow, e.g. turbulent and laminar flow, and predicts which structural changes will occur among different parts of trees having different types of flow. The sensitivity of the optimal values is indicated and the model, predictions are compared with literature data.