ALBERT

Notizen: Abstract A general mechanism underlying bursting is proposed and described. It consists of two coupled nonlinear oscillators with different frequencies, where the slower oscillator alternatively switches the faster one on and off. This mechanism is shown to work in an extended Bonhoefer-van der Pol oscillator as well as in a modified version of the Hodgkin-Huxley equations.

Notizen: Abstract Pointwise upper and lower bounds for the solution of a class of nonlinear diffusion problems with Michaelis-Menten kinetics are presented. Simple analytical bounding curves are obtained and for an illustrative case the calculated values bound the recent numerical solution of P. Hiltmann and P. Lory, 1983.Bull. math. Biol. 45, 661–664.

Notizen: Abstract The cellular response in terms of steady-state variance of cell mass concentration to fluctuations in incoming nutrient concentration to a chemostat has been examined. A white noise process is assumed to describe incoming nutrient concentration fluctuations and the variance of cell mass concentration has been found to depend on cell yield (a lumped measure of nutrient concentration fluctuation magnitude and lifetime) and two system time constants.

Notizen: Abstract In a well-known collection of his essays in cognitive psychology Miller (The Psychology of Communication. Penguin, 1974) describes in detail a number of experiments aiming at a determination of the limits (if any) of the human brain in processing information. He concludes that the ‘channel capacity’ of human subjects does not exceed a few bits or that the number of categories of (one-dimensional) stimuli from which unambiguous judgment can be made are of the order of ‘seven plus or minus two’. This ‘magic number’ holds also, Miller found, for the number of random digits a person can correctly recall on a row and also the number of sentences that can be inserted inside a sentence in a natural language and still be read through without confusion. In this paper we propose a dynamical model of information processing by a self-organizing system which is based on the possible use of strange attractors as cognitive devices. It comes as an amusing surprise to find that such a model can, among other things, reproduce the ‘magic number seven plus-minus two’ and also its variance in a number of cases and provide a theoretical justification for them. This justification is based on the optimum length of a code which maximizes the dynamic storing capacity for the strings of digits constituting the set of external stimuli. This provides a mechanism for the fact that the ‘human channel’, which is so narrow and so noisy (of the order of just a few bits per second or a few bits per category) possesses the ability of squeezing or ‘compressing’ practically an unlimited number of bits per symbol—thereby giving rise to a phenomenal memory.

Notizen: Abstract Electrical polarization of an artery or an arteriole may be modeled by the use of equations developed for two-dimensional cable theory. Two special cases have previously been solved: those corresponding to the case in which the radius is either zero (one-dimensional cable theory) or infinite. This paper presents the general solution.

Notizen: Abstract The distance geometry approach for computing the tertiary structure of globular proteins emphasized in this series of papers (Goelet al., J. theor. Biol. 99, 705–757, 1982) is developed further. This development includes incorporation of some secondary structure information—the location of alpha helices in the primary sequence—in the algorithm to compute the tertiary structure of alpha helical globular proteins. An algorithm is developed which estimates the interresidue distances between chain-proximate helices. These distances, in conjunction with the global statistical average distances obtainable from a database of real proteins and determined by the primary sequence of the protein under study, are used to determine the tertiary structure. Five proteins, parvalbumin, hemerythrin, human hemoglobin, lamprey hemoglobin, and sperm whale myoglobin, are investigated. The root mean square (RMS) errors between the calculated structures and those determined by X-ray diffraction range from 4.78 to 7.56 Å. These RMSs are 0.21–2.76 Å lower than those estimated without the secondary structure information. Contact maps and three-dimensional backbone representations also show considerable improvements with the introduction of secondary structure information.

Notizen: Abstract If a plane membrane consists of patches, each with a given area and a given diffusion coefficient, then the transient of the total unidirectional flux of a diffusing substance (as defined experimentally by Ussing) is predictable. Here the inverse problem is studied: given only the observed transient of the total unidirectional diffusion flux, the unknown membrane heterogeneity transverse to the flux is to be quantified. The ratio of the arithmetic and of the harmonic means (both area-weighted) of the diffusion coefficients, evaluated over the membrane, is expressed in terms of the observed transient alone and is used to characterize the heterogeneity. A unique exact solution of the inverse problem for two kinds of patches is obtained in closed form. A singular limit of this solution pertains to currently postulated models of endothelial membranes, for which a characteristically shaped transient is predicted.

Notizen: Abstract Major types of sequence similarity searching (often, and incorrectly, called ‘homology’ searching) are reviewed and examples of each are presented. The features and limitations of each type of program, and individual implementations of each type are discussed. Two pairs of sequences are used as examples to show how implementations of each type differ in their results and their presentation. Both local and global alignment programs are examined, and the programs reviewed run on many different types of computer architectures, from laboratory computers such as the IBM PC, minicomputers such as the VAX, to large mainframe computers such as DEC-10/20 series.

Notizen: Abstract Criteria for the existence of globally stable equilibria in classical Volterra predator-prey systems represented by loop graphs are provided by comparing the community matrix with a matrix belonging to matrix classS W .

Notizen: Abstract Ordinary reaction-diffusion mechanisms do not account for size invariance properties of morphogenetic fields. We show that such a failure results from ignoring cell individuality. By considering purely topological factors, such as the number of intercellular contacts or the extent of the cell surface in contact with neighbouring cells, size invariance exists in reaction-diffusion systems. Our results are general, model independent and may be applied to any multi-unit ensemble exhibiting coherent behaviour.

Notizen: Abstract The artery is treated as a thick-walled cylindrical shell. Using the large deformation theory, an analytical expression for the pulse wave speed is obtained and the effect of twist on the wave speed is discussed. Numerical results indicate that although phase velocity increases with pressure, it decreases with increasing twist angle.

Notizen: Abstract The effect of the shape of stenosis on the resistance to blood flow through an artery with mild local narrowing has been studied. It is shown that the resistance to flow decreases as the shape of stenosis changes and the maximum resistance is attained in the case of symmetric stenosis.

Notizen: Abstract A set of 2n−2 relations (edges) and a set ofn−1 hypothetical taxonomic units (HTUs) derive from the estimation of a binary phylogeny of a set ofn operational taxonomic units (OTUs). We propose an easy way for numbering thesen−1 hypothetical taxonomic units, as well as for then−2 interior points of an unrooted binary phylogeny. We also present an alternative method to the one proposed by Rohlf (Bull. math. Biol. 45, 33–40, 1983) for numbering the π i=1 n (2i−3) possible rooted binary phylogenies and the π i=1 n−1 (2i−3) possible unrooted binary phylogenies conerning a set ofn operational taxonomic units. An illustrative example of the method is presented. It is hoped that some studies in phylogenetics will become more accessible, from the viewpoint of computational economy, by the use of this method.

Notizen: Abstract The heterogeneity of rat brain opiate receptors was examined by analyzing competition data. The binding of three prototypical tritiated opioid agonists, [3H]-dihydromorphine ([3H]-DHM), [3H]-D-ala2-D-leu5-enkephalin ([3H]-DADLE), and [3H]-ethylketocyclazocine ([3H]-EKC) was determined in the presence of varying concentrations of each of these unlabeled ligands, generating nine displacement curves. A computer program was then used to find the best fit of a model system to these data, assuming two, three or four independent binding sites. The best fit was a four-site model. One of these sites is specific for DHM; two are relatively selective for DHM and DADLE respectively, but also bind EKC. The remaining site binds only EKC with high affinity. These results, together with displacement data using naloxone, FK33824, and D-ala2-met5-enkephalinamide, are discussed in terms of current opiate receptor models.

Notizen: Abstract This work continues with an examination of capillary exchange models as operators, namely the operatorsO k andK αk relating extravascular and intravascular concentration to input for the Krogh cylinder model of a single capillary, a model basic to many organ models. Fundamental algebraic and analytic properties are presented: the operators belong to a commutative Banach algebra; an addition theorem holdsK αk +K βk =K α+β,k ; the operatorK αk has an inverse;K αk -1 , (as an operator on LebesgueL p space or on the locally integrable functions); partial derivatives are given forK αk [f](t) andO k [f](t) (sensitivity functions); and inequalities are established for the derivatives. Dominance relations between model curves are inferred. Error bound formulas are presented forK andO as bounds on ‖K αk f-K βl f‖ p and ‖O k f-O l f‖ p for allL p . Consequent limitations on relative errors are shown. The implications for operators on a finite time interval are deduced.

Notizen: Abstract The nonlinear nature of the hydraulic permeability, as well as the corresponding pressure and displacement fields, in a soft tissue are studied for steady-state permeation. From a two-phase continuum model analytical expressions are derived that can be used with the results from a permeation experiment to determine the dependence of the permeability on the strain. In the process it is found that, because of the compaction of the tissue arising from fluid flow, it is necessary to distinguish between the apparent and intrinsic permeability. The former, which is an averaged quantity, is the permeability usually obtained in permeation studies. However, as shown from the analysis, it can differ substantially from the latter, which is the local permeability in the tissue.

Notizen: Abstract The analytic, eccentric spheres model of the torso was used to examine the validity of approximating the ‘infinite medium’ potential by integrating ‘finite medium potentials’ over the torso surface. Although idealized, the analytic model is sophisticated enough for all important torso conductivity and geometry parameters to be preserved in the formulation. The model generates both ‘finite medium’ potentials (for which the torso is surrounded by air) and also ‘infinite medium’ potentials (for which the outermost layer of the torso extends outward to infinity). The finite medium torso potentials were integrated over the torso surface in accordance with the approximation used by many investigators in an effort to make the surface distribution more representative of the primary cardiac sources. The resulting potential distribution was compared with the true infinite medium potential, in which the effects of internal inhomogeneities (secondary sources) were taken into account. The difference between the two representations was found to be significant, and caution should be used when interpreting such data.

Notizen: Abstract Environ analysis, an input-output analysis for models of ecological systems, has been previously formulated for linear systems. This note has a twofold purpose: first, we indicate that a variation of parameters technique can be applied, at least in principle, to computeboth input and output environs; and second, we show that this technique may be used for computation of environs in nonautonomous, nonlinear compartment models. This nonlinear theory, obtained as a direct extension of dynamical system developments, allows the traditional environ partitioning of compartmental storages and flows. An example of a nonlinear nutrient-producer-consumer system whose output environs can be computed asymptotically is presented to illustrate these concepts.

Notizen: Abstract Prolonged exposure to cyanide leads to a delayed but reversible disappearance of tetanic hyperpolarization in theXenopus node (G. M. Schoepfle,Am. J. Physiol. 231, 1033–1038, 1976). This effect is attributed to a pronounced decline in the absolute values of the ATP and ADP concentrations, such that the ATP-driven ion translocation is no longer possible, regardless of the existing values for (Na)i, (K)i and the (ATP)/(ADP) ratio. Mathematically, this would imply a vanishing of a constant pump conductance gp in the exression for electrogenic pump current densitityJ p, whereJ p=g p (V m −E p) in whichV m is membrane potential andE p is an ATP-and sodium-dependent e.m.f.

Notizen: Abstract For the two-parameter (A, α) exponentially-stiffening constituitive relation, typical of many biological materials, it is shown that the uniaxial stress-strain behavior of an initially curved strip is significantly changed by the residual bending stresses. Closedform theoretical results depend on the thickness to radius ratio (h/R) and the relative strain level ε(h/R). The bending stresses tend to obscure accurate measurement ofA and α unless care is taken. However, it is shown that by changing co-ordinates to (dℝ/d∈, ℝ)-space, bothA and α can be recovered from the high stress data, and α alone can be recovered from the low stress data. This has practical application to the mechanics of cornea, sclera, and heart muscle.

Notizen: Abstract An axisymmetric flow of a power law fluid through circular tubes under constant pressure gradient with the flow parameters varying radially is analyzed theoretically. The main finding is that for the Fahraeus-Lindqvist (F-L) effect to occur, it is necessary to have at least one of the parametersK (consistency) andn (index) as a discontinuous function ofr in the absence of wall slip; and with slip condition the parameters could be continuous functions ofr under specific conditions. In both the cases the existence of more than one discontinuity cannot be ruled out. The results obtained are consistent with experimental findings of blood flow through narrow tubes.

Notizen: Abstract This is a study of the properties of a zygotic algebra of two linked autosomal loci with different recombination rates in males and females, without selection or mutation and with random mating. The above-mentioned zygotic algebra contains a genetic subalgebra. A canonical basis of this subalgebra is constructed and the train roots are calculated.

Notizen: Abstract Among the conformations which the DNA molecule can adopt, the transition beween the A and B families, controlled by water content (relative humidity), seems to be implicated in the transcription process. Focusing on the main structural difference involved (tilting of base normals with respect to the helix axis), a model is constructed, solitary wave solutions of the resulting equation of motion are demonstrated and possible experimental implications indicated.

Notizen: Abstract Balls are removed one-at-a-time at equal time intervals from an urn initially containingw 0 white balls and a large number b of black balls and each black or white ball is immediately replaced by a black ball. The distribution of the number of white balls remaining aftert iterations (under certain limiting operations) is taken from the literature. The problem is to use this result to find the time required to remove a fixed number of white ballsw 1 from the urn. We then find the mean and variance of this distribution and also look at the special case whenw 1 =w 0.

Notizen: Abstract By studying the behavior of various tracer species in the lungs, one can assess many important characteristics which distinguish normal and abnormal function. Quantitative evaluation of function depends on the use of an appropriate model in conjunction with experimental data. A multi-compartment model is derived from mass balances to describe dynamic as well as (breath-averaged) steady-state transport processes between the environment and pulmonary capillary blood. The breathing cycle is divided into three time periods (inspiration, expiration, and pause) so that the model equations are discrete in time. No other model of tracer species transport in the lungs deals simultaneously with species dynamics, variable breathing pattern, distribution inhomogeneities, and non-equilibrium between alveolar gas and capillary blood. Models currently in the literature are shown to be special cases of the model presented here.

Notizen: Abstract Local stability seems to imply global stability for population models. To investigate this claim, we formally define apopulation model. This definition seems to include the one-dimensional discrete models now in use. We derive a necessary and sufficient condition for the global stability of our defined class of models. We derive an easily testable sufficient condition for local stability to imply global stability. We also show that if a discrete model is majorized by one of these stable population models, then the discrete model is globally stable. We demonstrate the utility of these theorems by using them to prove that the regions of local and global stability coincide for six models from the literature. We close by arguing that these theorems give a method for demonstrating global stability that is simpler and easier to apply than the usual method of Liapunov functions.

Notizen: Abstract The asymptotic behaviour of a logistic equation with diffusion on a bounded region and a diffusionally coupled delay is investigated. An equivelent parabolic system is derived for certain types of delays. Using a Layapunov functional, sufficient conditions for the global asymptotic stability of the constant steady state are obtained. When the global stability is lost, using Hopf's bifurcation theory, existence of travelling waves is shown for ring-like and periodic one dimensional habitats.

Notizen: Abstract It was hypothesized in an earlier work that sensory perception can occur only when the perceiving system is uncertain about the nature of the event being perceived. In the absence of any uncertainty, perception will not take place. The response of the sensory afferent neuron (impulse transmission rate) was calculated using Shannon's measure of uncertainty or entropy. It will now be shown that when the event being perceived is the position and momentum of a particle, Shannon's measure of uncertainty leads to the Heisenberg Uncertainty relationship.

Notizen: Abstract It is not unusual for several classifications to be given for the same collection of objects. We present a method, called majority rule, which can be used to define a consensus of these classifications. We also discuss some mathematical properties of this consensus tree.

Notizen: Abstract The dependence of the spatial concentration profiles of morphogens on a characteristic dimension is obtained by continuation techniques for Gierer and Meinhardt's activator-inhibitor model of morphogenesis. The study of the behaviour of the system during growth, where the linear and exponential increase of the characteristic dimension is considered, revealed that more complex patterns of morphogen spatial concentrations appear regularly in a reproducible way.

Notizen: Abstract Computer models have been used by various authors to simulate both the growth of normal cellular tissue and the development of cancerous cells within normal tissue. As these models were the result of considerable idealization, the purpose of the present paper is to propose a model in which the degree of simplification is relaxed: the features of simultaneous growth, and cell growth whose rate depends on the free absorbing periphery of the cell are introduced. Simulation experiments have been conducted using the model, and the results are presented.

Notizen: Abstract The theory of complementary variational principles is used to obtain maximum and minimum principles for a nonlinear model of heat conduction in the human head. Accurate variational solutions are obtained in illustrative calculations. The effect of nonlinearity is seen to be significant from a comparison with the linearized model.

Notizen: Abstract A model for the nerve impulse due to Zeeman (1972) and based on catastrophe theory is compared with alternative models and criticisms of Zeeman's model by Sussmann and Zahler (1977, 1978) are assessed. The criticisms of Zeeman's motivation for his model are found to carry some weight. Sussmann and Zahler (1977, 1978) list numerous features of Zeeman's model which, they state, are not in agreement with experiment. These statements as they stand are largely erroneous, and the model still remains to be tested by a critical series of experiments. However, a detailed analysis reveals defects in Zeeman's model, not among those claimed by Sussmann and Zahler, showing that the explicit equations of the model cannot be correct. The possibility of a modified approach along similar lines and its ultimate adoption remains open.

Notizen: Abstract The irreversible Michaelis-Menten reaction is studied by the use of the method of multiple scales. Three stages of the reaction are identified, one of which is studied in detail. The results are compared with those of two earlier analyses.

Notizen: Abstract A numerical study of the coupled nerve fibre problem is given which verifies and extends the perturbation theory of Luzader. Pulses on adjacent fibres can couple together with two possible stable pulse separations.

Notizen: Abstract A possible mechanism for effects of microwave radiation on the auditory system is the generation of field-induced forces at interfaces that divide materials of dissimilar electrical properties. A general expression for these “Maxwell stresses” is derived and then used to calculate the approximate magnitude of field-induced force within the organ of Corti during microwave exposure. Comparison of the results with data on the force needed to excite cochlear hair cells indicates auditory responses could be evoked by this mechanism at power densities near the threshold of rf hearing sensations.

Notizen: Abstract A definition of homogeneity for neural networks is given which permits their construction as group quotients. The significance of this for neural dynamics is discussed.

Notizen: Abstract The left ventricle is represented as a cylinder contracting both radially and longitudinally. A simple method is indicated to derive an expression for the rate of change of the kinetic energy of this three-dimensional model, which quantity can be used as an index for the study of the contractile behaviour of the myocardium. An application to the study of muscle mechanics is also indicated.

Notizen: Abstract A perturbation method is proposed to calculate approximately the limit cycle type nonequilibrium steady-state resulting from periodic perturbation of coefficients of stable population systems; the two species Lotka-Volterra competition system is explicity studied and the results are formulated for general multi-species population systems. Avoidance of competitive or other types of exclusion of species in a periodic environment is indicated.

Notizen: Abstract We postulate that the biomass distribution function for an ecological population may be derived from the condition that the biomas diversity functional is maximal subject to an energetic constraint on the total biomass. This leads to a biomass distribution of the form $$p(m) = \bar m^{ - 1} \exp ( - m/\bar m)$$ , where $$\bar m$$ is the mean biomass per individual. The same condition yields a unique value for the biomass diversity functional. These predictions are tested against fishery data and found to be in good agreement. It is argued that the existence of a unique value for biomass diversity may provide a preliminary theoretical foundation for the observed upper limit to species diversity.

Notizen: Abstract Pigment distribution presages hydranth regeneration in the marine hydroidTubularia. We suggest that such a distribution could result from a reaction-diffusion system. A model system based on a practical reaction scheme is studied and spatial structures found which closely resemble this pigment distribution. Finite-amplitude spatial structures in reaction-diffusion systems are considered. Whereas in one spatial dimension the final structures are normally very similar to the transient patterns which emerge from a linear analysis, it is shown that in more than one dimension this is not necessarily the case. The reasons for this are discussed.

Notizen: Abstract An analytical model is used to described the behavior of inhaled particulate matter in the human respiratory tract. Three different geometries, symmetric and asymmetric, are utilized to simultate the tracheobronchial (TB) tree. The suitability of each geometry for representing the human is evaluated by comparing calculated aerosol deposition probabilities with experimental data from inhalation exposure tests. A symmetric, dichotomously branching pattern is found to be a reliable description of the TB tree for studies of factors affecting aerosol deposition in the human lung. Calculations with the theoretical model are in excellent agreement with measured aerosol deposition efficiencies. Furthermore, the model accurately predicts experimentally observed features of inhalation exposure data, such as effects of inter-subject lung morphology differences and relative efficiencies of specific deposition mechanisms, on aerosol deposition patterns in the TB tree.

Notizen: Abstract In this paper we are concerned with problems of the long-term behavior for nonlinear systems in random environment. The general model is assumed to be given by an ordinary differential equation with random parameters or random input. The disturbance process can be taken from a fairly general class of Markov processes having a bounded state space. In terms of the system’s dynamics we give sufficient conditions for the existence and uniqueness of invariant probabilities. Finally, we apply these results to the two-dimensional biochemical model which is known as the Brusselator.

Notizen: Abstract In various applications one faces the problem of estimating a signal from discontinuous observations. For example, in biomedical applications the signal may be the ‘state’ of a given organ and one observes through an external counter the amount of radioactivity sequestered by the organ after injection of a radioactive tracer. Here the problem is studied in the context of nonlinear filtering when the signal can be modelled as either a random variable or a diffusion process, and the observations have a continuous and a purely discontinuous component; both components may be affected by the signal. When the signal is a random variable an explicitly computable solution is obtained; for the diffusion case the solution is given as a sequence of approximating filters that can be computed recursively.

Notizen: Abstract Eigenvalue problems arise in various biological models. We outline a useful comparison method and a technique using Lyapunov functions that can be applied in many cases. An application to lateral diffusion is discussed.

Notizen: Abstract This paper reviews, up to their recent developments, two types of models of the cell cycle: those considering the size controls over the cycle events and the transition probability models. The distribution of inter-mitotic time and the sister-sister and motherdaughter correlations implied by the two approaches are discussed in view of some relevant experimental data.

Notizen: Abstract The development of a blood cell line originating from a pluripotent stem cell pool is modelled by a chain of multidimensional branching processes in which the sojourn times of the cells in certain resting states depend on the size of the following subpopulation. The stability of such a model is discussed qualitatively and some considerations concerning a possible malignant degeneration are presented. The behaviour of models for normal and malignant cell production are illustrated by stochastic stimulations. The model presented here describes the development of a certain line of blood cells (e.g. erythrocytes, monocytes or granulocytes) originating from the pluripotent stem cell up to the functional cell in the blood (for related models see, e.g., Rubinow and Lebowitz,J. math. Biol. 1, 87–225;Biophys. J. 16, 897–910).

Notizen: Abstract This paper reviews some recent advances in single population stochastic differential equation growth models. They are a natural way to model population growth in a randomly varying environment. The question of which calculus, Itô or Stratonovich, is preferable is addressed. The two calculi coincide when the noise term is linear, if we take into account the differences in the interpretation of the parameters. This clarifies, among other things, the controversy on the theory of niche limiting similarity proposed by May and MacArthur. The effects of correlations in the environmental fluctuations and statistical methods for estimating parameters and for prediction based on a single population trajectory are mentioned. Applications to fisheries, wildlife management and particularly to environmental impact assessment are now becoming possible and are proposed in this paper.

Notizen: Abstract A survey is given of the application of (functions of) continuous-time Markov chains in the statistical analysis of behavioural time series.

Notizen: Abstract This paper demonstrates that there is one and only one solution to a non-linear singular two-point boundary-value problem which describes oxygen diffusion in a spherical cell. Previous authors have calculated numerical results that differ substantially. Numerical computations using the multiple shooting method support the results of McElwain.

Notizen: Abstract The mathematics of distance geometry constitutes the basis of a group of algorithms for revealing the structural consequences of diverse forms of information about a macromolecule's conformation. These algorithms are of proven utility in the analysis of experimental conformational data. This paper presents the basic theorems of distance geometry in Euclidean space and gives formal proofs of the correctness and, where possible, of the complexity of these algorithms. The implications of distance geometry for the energy minimization of macromolecules are also discussed.

Notizen: Abstract A fully developed pulsatile flow in a circular rigid tube is analysed by a microcontinuum approach. Solutions for radial variation of axial velocity and cell rotational velocity across the tube are obtained using the momentum integral method. Simplified forms of the solutions are presented for the relevant physiological data. Marked deviations in the results are observed when compared to a Newtonian fluid model. It is interesting to see that there is sufficient reduction in the mass flow rate, phase lag and friction due to the micropolar character of the fluid.

Notizen: Abstract A mathematical model of the transport of fluorescein across the blood-retina barrier in the transient state and the subsequent diffusion of fluorescein in the vitreous body is presented. The function of the barrier is lumped in a single parameter—the permeability. The sensitivity of this parameter due to changes in the other parameters of the model is given. This establishes the foundation for the quantitative assessment of the barrier function through vitreous fluorophotometry.

Notizen: Abstract The objective of this preliminary study was to develop a new quantitative method of setting the initial insulin infusion patterns in treatment of diabetic patients. The method is based upon the mathematical estimation of the insulin profile required to maintain the glucose level within the normal range after glucose loading in diabetic patients. Using our previously developed equivalent circuit model of glucose kinetics and the reported data of an intravenous glucose tolerance test (IVGTT) in two groups of normal and diabetic patients, two important physiological parameters of the model (the peripheral tissue's insulin resistivity and the hepatic sensitivity to glucose level) were computed for two clinical groups. Then the insulin profile was obtained by computing the plasma insulin concentrations required to keep the total glucose utilization rate of the tissue and the liver in the diabetic group equal to that of the normal group. The simulation result indicated that the computed insulin profile produced a plasma glucose profile which was more closely matched to the normal group's glucose profile than with the case of emulating the normal group's insulin profile in the diabetic group.

Notizen: Abstract This paper shows that the Na conductance changes can be explained quantitatively, based on the following assumptions: (1) there exist in nerve membranes the electron transfer (ET) complexes and traps, (2) there is energy migration among them. The gating mechanism is explained in physical terms. Its mathematical expression differs from the Hodgkin-Huxley equations, but resembles the Hoyt formulation. In the present model, the physical parameters for the squid axon can be estimated from currently available experimental data. The density of the ET complexes is on the order of 105/μm2, and the density of the traps is 103/μm2. The magnitude of the energy transfer rate between ET complexes is about 106/sec at large depolarization and decreases with decreasing depolarizations, as does the Na inactivation rate. The energy gap between the two stable states of the transfer electron in the ET complex is estimated to be around 0.1 eV, which is approximately the same as that for the photosynthetic systems.

Notizen: Abstract The role of symmetry in simplifying the theory of complex neural systems is argued. When the structural symmetries of a network are expressed as an ismorphism group, implications emerge for the dynamics. Various qualitative possibilities concerning stability of uniform motion in homogeneous nets are discussed and an approach to neural hierarchies is outlined.

Notizen: Abstract By constructing appropriate Liapunov functionals, asymptotic behaviour of the solutions of various delay differential systems describing prey-predator, competition and symbiosis models has been studied. It has been shown that equilibrium states of these models are globally stable, provided certain conditions in terms of instantaneous and delay interaction coefficients are satisfied.

Notizen: Abstract Sensitivity analyses have been used to examine the flow structure of two hypothetical ecosystem models. These analyses have results which relate to important aspects of ecosystem theory. Cycles are shown to increase the sensitivity of the network, while increased throughflow is shown to decrease the sensitivity. Such results indicate that several factors can be modified to decrease the sensitivity of ecosystems to environmental stress.

Notizen: Abstract A continous, deterministic mathematical model is used to predict population distributions by age at any time, given the initial distribution and the variation of birth and death rates with age and time. Solutions are obtained on a computer using a semi-discretization algorithm in which time derivatives in the partial differential equations are replaced by finite-difference expressions. The resulting sets of ordinary differential equations are solved by a predictor-corrector method. Graphical results are shown for some examples.

Notizen: Abstract A new formula for the complexity of graphs is proposed and applied to the points lines and ‘connections’ of some chemically relevant graphs.

Notizen: Abstract This paper reports general and specialized results on analytical solutions to the governing phenomenological equations for chemotactic redistribution and population growth of motile bacteria. It is shown that the number of bacteria cells per unit volume,b, is proportional to a certain prescribed function ofs, the concentration of the critical substrate chemotactic agent, for steady-state solutions through an arbitrary spatial region with a boundary that is impermeable to bacteria cell transport. Moreover, it is demonstrated that the steady-state solution forb ands is unique for a prescribed total number of bacteria cells in the spatial region and a generic Robin boundary condition ons. The latter solution can be approximated to desired accuracy in terms of the Poisson-Green's function associated with the spatial region. Also, as shown by example, closed-form exact steady-state solutions are obtainable for certain consumption rate functions and geometrically symmetric spatial regions. A solutional procedure is formulated for the initialvalue problem in cases for which significant population growth is present and bacteria cell redistribution due to motility and chemotactic flow proceeds slowly relative to the diffusion of the chemoattractant substrate. Finally, a remarkably simple exact analytical solution is reported for a stradily propagating plane-wave which features motility, chemotactic motion and bacteria population growth regulated by substrate diffusion.

Notizen: Abstract This paper discusses the flow of blood in large artries under the influence of linear periodic acceleration. The governing equations and boundary conditions are established and analytical solutions for the velocity, fluid acceleration, bulk flow and shear stress are obtained. The results for these physical quantitites are computed for the case of an artery the size of a normal human aorta. It is found that the flow field variables are directly proportional to the external accelerating force. The behaviour of the velocity profile along the radial distance at different stages of times at fixed applied acceleration is also shown.

Notizen: Abstract The evolutionary selection circuits model of learning has been specified algorithmically. The basic structural components of the selection circuits model are enzymatic neurons, that is, neurons whose firing behavior is controlled by membrane-bound macromolecules called excitases. Learning involves changes in the excitase contents of neurons through a process of variation and selection. In this paper we report on the behavior of a basic version of the learning algorithm which has been developed through extensive interactive experiments with the model. This algorithm is effective in that it enables single neurons or networks of neurons to learn simple pattern classification tasks in a number of time steps which appears experimentally to be a linear function of problem size, as measured by the number of patterns of presynaptic input. The experimental behavior of the algorithm establishes that evolutionary mechanisms of learning are competent to serve as major mechanisms of neuronal adaptation. As an example, we show how the evolutionary learning algorithm can contribute to adaptive motor control processes in which the learning system develops the ability to reach a target in the presence of randomly imposed disturbances.

Notizen: Abstract In the present paper we discuss the behaviour of solutions of a dynamical system describing the growth of cells in a well-mixed continuous culture where the supply of the growth-limiting nutrient depends on the activity of an enzyme outside the cell membrane. It turns out that for positive dilution rates there exists an exponentially attractive two-dimensional simplex. Furthermore, the reversed system restricted to this simplex is quasimonotone. In every case all trajectories tend to an equilibrium state.

Notizen: Abstract We present a Gause predator-prey model incorporating mutual interference among predators, a density-dependent predator death rate and a time lag due to gestation. It is well known that mutual interference is stabilizing, whereas time delays are destabilizing. We show that in combining the two, a long time-lag usually, but not always, destabilizes the system. We also show that increasing delays can cause a bifurcation into periodic solutions.

Notizen: Abstract The cycle structure of enzymatic neural networks may be characterized in terms of number of cycles exhibited, size of cycle state sets and cycle lengths. Simulation experiments show that the stability properties of these networks have some unusual features which are not exhibited by networks of two-state switching elements or by randomly constructed ecosystem models. The behavioral and structural stability of these systems decreases with their structural complexity, as measured by the number of components. The behavioral and structural stability of enzymatic neural networks also decreases with structural complexity, as measured by the number of excitase types, but only up to the middle level of excitases per neuron. This is the point of highest potential responsiveness of the system to environmental stimuli. Beyond this point the behavioral and structural stability increase. This is due to the fact that the number of possible states increases up to this point and decreases beyond it. The number of possible states, not the number of components, serves as the useful measure of complexity in these types of systems. The selection circuits learning algorithm has been used to evolve networks whose cycle structures have desired features.

Notizen: Abstract Similarity criteria of the functional design of the mammalian cardiovascular system are scant. For the analysis of mammalian cardiac energetics physiological parameters such as mean arterial blood pressure, stroke volume, heart rate, metabolic rate and heart and body weights are considered pertinent. Based on these parameters, a new similarity principle is established via allometric equations, dimensional analysis and Buckingham's pi-theorem. The principle states that the ratio of left ventricular external work to metabolic rate is inversely proportional to resting heart rates of mammals. The proportionality constant is dimensionless and is invariant of mammalian body weights.

Notizen: Abstract The mathematical theory of categories is used as a tool in the description of the structure and function of natural systems. The connections between the category of natural systems, with observables and dynamics, and the phenomenological calculus of response tensors, duality- and adjoint-invariance diagrams are established. The unified theory is applied to the analysis of hierarchies, pattern generation and the structure and dynamics of proteins.

Notizen: Abstract This is an investigation of natural systems from the standpoint of the mathematical theory of categories. It examines the relationships which exist between different descriptions through measurement of observables and dynamical interactions. We begin with a category theory of formal systems with observables, and then proceed to a category theory of dynamical systems. The two categories are then combined to represent natural systems. Topological considerations enter in the study of stability and bifurcation phenomena. Special emphasis is placed on natural systems which model biological processes. The categorical system theory developed is applied to the analysis of several biological problems and biological system theories.

Notizen: Abstract Tetanic hyperpolarization for theXenopus node is simulated by means of iterative solutions of the Frankenhaeuser-Huxley excitation equations together with an active transport current density term which is dependent on sodium and potassium levels as well as the ADP/ATP ratio. All time-dependent variables at the end of one interspike interval are introduced as initial conditions for the next response, whereupon all time-dependent changes in voltage and permeability factors appear identical for the third and fourth responses of a sequence. Net change in internal sodium concentration is zero throughout the third and fourth intervals if sodium loading of the system is initially adjusted to a critical level. Extent of tetanic hyperpolarization is a function of the pump conductance.

Notizen: Abstract The properties of nonlinear equations describing the solute and solvent transport across a simplified Patlak-Goldstein-Hoffman model (two membranes in series without unstirred layers) are investigated both analytically and numerically. The analysis shows that the principal coefficients measured in transport experiments in the presence of active transport are dependent on the experimental conditions. These ‘apparent’ system parameters are extensions of the corresponding parameters determined both in passive systems and in the linear Kedem-Katchalsky theory. Moreover, they are related to the local phenomenological coefficients of the single membranes of the array. Several relationships between measurable quantities and the local system parameters are indicated, allowing the planning of experiments aimed at the measurement of the latter. Data in the literature have been used to check the proposed volume flow equation.

Notizen: Abstract More than 20 years after its proposal, Keller and Segel's model (1971,J. theor. Biol.,30, 235–248) remains by far the most popular model for chemical control of cell movement. However, before the Keller-Segel equations can be applied to a particular system, appropriate functional forms must be specified for the dependence on chemical concentration of the cell transport coefficients and the chemical degradation rate. In the vast majority of applications, these functional forms have been chosen using simple intuitive criteria. We focus on the particular case of eukaryotic cell movement, and derive an approximation to the detailed model of Sherrattet al. (1993,J. theor. Biol.,162, 23–40). The approximation consists of the Keller-Segel equations, with specific forms predicted for the cell transport coefficients and chemical degradation rate. Moreover, the parameter values in these functional forms can be directly measured experimentally. In the case of the much studied neutrophil-peptide system, we test our approximation using both the Boyden chamber and under-agarose assays. Finally, we show that for other cell-chemical interactions, a simple comparison of time scales provides a rapid check on the validity of our Keller-Segel approximation.

Notizen: Abstract The formal structure of evolutionary theory is based upon the dynamics of alleles, individuals and populations. As such, the theory must assume the prior existence of these entities. This existence problem was recognized nearly a century ago, when DeVries (1904,Species and Varieties: Their Origin by Mutation) stated. “Natural selection may explain the survival of the fittest, but it cannot explain the arrival of the fittest.” At the heart of the existence problem is determining how biological organizations arise in ontogeny and in phylogeny. We develop a minimal theory of biological organization based on two abstractions from chemistry. The theory is formulated using λ-calculus, which provides a natural framework capturing (i) the constructive feature of chemistry, that the collision of molecules generates specific new molecules, and (ii) chemistry's diversity of equivalence classes, that many different reactants can yield the same stable product. We employ a well-stirred and constrained stochastic flow reactor to explore the generic behavior of large numbers of applicatively interacting λ-expressions. This constructive dynamical system generates fixed systems of transformation characterized by syntactical and functional invariances. Organizations are recognized and defined by these syntactical and functional regularities. Objects retained within an organization realize and algebraic structure and possess a grammar which is invariant under the interaction between objects. An organization is self-maintaining, and is characterized by (i) boundaries established by the invariances, (ii) strong self-repair capabilities responsible for a robustness to perturbation, and (iii) a center, defined as the smallest kinetically persistent and self-maintaining generator set of the algebra. Imposition of different boundary conditions on the stochastic flow reactor generates different levels of organization, and a diversity of organizations within each level. Level 0 is defined by selfcopying objects or simple ensembles of copying objects. Level 1 denotes a new object class, whose objects are self-maintaining organizations made of Level 0 objects, and Level 2 is defined by self-maintaining metaorganizations composed of Level 1 organizations. These results invite analogy to the history of life, that is, to the progression from self-replication to self-maintaining procaryotic organizations to ultimately yield self-maintaining eucaryotic organizations. In our system self-maintaining organizations arise as a generic consequence of two features of chemistry, without appeal to natural selection. We hold these findings as calling for increased attention to the structural basis of biological order.

Notizen: Abstract A model is developed to describe neuronal elongation as a result of the polymerization of microtubules and elastic stretching of the neurites by force produced by the growth cone. The model for a single segment with a single growth cone revealed a constant elongation rate, while the concentration of tubulin in the soma rises, and the concentration of tubulin becomes constant in the growth cone. Extending the model to a neurite with a single branch point and two growth cones revealed the same results. When the assembly or the disassembly rate of microtubules is unequal in both growth cones, transient retraction of one of the terminal segments occurs, which results in complete retraction of the segment when the difference in (dis)assembly rate between the two growth cones is large enough. When the model is applied to large trees, a maximal sustainable number of terminal segments as a function of the production rate of tubulin appears. Mechanisms to stop outgrowth are discussed in relation to the establishment of synaptical contacts between cells.

Notizen: Abstract We have developed a new model describing the relationship between plasma and red cell tracers flowing through the lung. The model is the result of an analysis of the transport of radiolabeled plasma albumin between two flowing phases and shows that differences between red cell and plasma tracer curves are related to microvascular hematocrit. The model was tested in an isolated, blood-perfused dog lung preparation in which we injected51Cr-labeled red cells and125I-labeled plasma albumin into the pulmonary artery. From the tracer concentration-time curves at the venous outflow, we calculatedh r, the ratio of microvascular hematocrit to large-vessel hematocrit. In 18 baseline experiments,h r=0.92±0.01 (mn±sem) at a blood flow rate of 10.7±0.3 ml s−1. We determined the effects of (a) glass bead embolization, (b) alloxan, and (c) lobe ligation onh r. Embolization attenuated the separation between plasma and red cells (increasedh r), probably as a consequence of passive vasodilation. Alloxan enhanced separation of plasma and red cells (decreasedh r), possibly as a result of arteriolar vasoconstriction. Ligation of a fraction of the perfused tissue at constant flow did not cause significant change inh r in the remaining perfused tissue. The model assumes that large-vessel transit times are uniform and that all dispersion occurs in the microvasculature. A theoretical analysis apportioning dispersion between large and small vessels disclosed that the error associated with these assumptions is likely to be less than 15% of the measuredh r. We conclude from this study that the microvascular hematocrit model describes experimental plasma and red cell curves. The results imply thath r can be readily deduced from tagged red cells and plasma and can be accounted for in calculating permeability-surface area in diffusing tracer experiments.

Notizen: Abstract We present a mathematical model of the cytotoxic T lymphocyte response to the growth of an immunogenic tumor. The model exhibits a number of phenomena that are seenin vivo, including immunostimulation of tumor growth, “sneaking through” of the tumor, and formation of a tumor “dormant state”. The model is used to describe the kinetics of growth and regression of the B-lymphoma BCL1 in the spleen of mice. By comparing the model with experimental data, numerical estimates of parameters describing processes that cannot be measuredin vivo are derived. Local and global bifurcations are calculated for realistic values of the parameters. For a large set of parameters we predict that the course of tumor growth and its clinical manifestation have a recurrent profile with a 3- to 4-month cycle, similar to patterns seen in certain leukemias.

Notizen: Abstract We present a new, practical algorithm to resolve the experimental data in restriction site analysis, which is a common technique for mapping DNA. Specifically, we assert that multiple digestions with a single restriction enzyme can provide sufficient information to identify the positions of the restriction sites with high probability. The motivation for the new approach comes from combinatorial results on the number of mutually homeometric sets in one dimension, where two sets ofn points are homeometric if the multiset ofn(n−1)/2 distances they determine are the same. Since experimental data contain errors, we propose algorithms for reconstructing sets from noisy interpoint distances, including the possibility of missing fragments. We analyse the performance of these algorithms under a reasonable probability distribution, establishing a relative error limit ofr=Θ(1/n 2) beyond which our technique becomes infeasible. Through simulations, we establish that our technique is robust enough to reconstruct data with relative errors of up to 7.0% in the measured fragment lengths for typical problems, which appears sufficient for certain biological applications.

Notizen: Abstract A simple chemical model of the idiotypic network of immune systems, namely the AB model, has been developed by De Boeret al. The complexity of the system, such as the steady states, periodic oscillations and chaotic motions, has been examined by the authors mentioned above. In the present paper, the periodic motions and chaotic behaviours exhibited by the system are intuitively described. To clarify in which parameter domains concerned the system exhibits periodic oscillations and in which parameter domains the system demonstrates chaotic behaviours the Lyapounov exponent is explored. To characterize the strangeness of the attractors, the fractal dimension problem is worked out.

Notizen: Abstract We consider a stochastic mechanism of the loss of resistance of cancer cells to cytotoxic agents, in terms of unstable gene amplification. Two models being different versions of a time-continuous branching random walk are presented. Both models assume strong dependence in replication and segregation of the extrachromosomal elements. The mathematical part of the paper includes the expression for the expected number of cells with a given number of gene copies in terms of modified Bessel functions. This adds to the collection of rare explicit solutions to branching process models. Original asymptotic expansions are also demonstrated. Fitting the model to experimental data yields estimates of the probabilities of gene amplification and deamplification. The thesis of the paper is that purely stochastic mechanisms may explain the dynamics of reversible drug resistance of cancer cells. Various stochastic approaches and their limitations are discussed.

Notizen: Abstract Dextran has been the most commonly employed test molecule for probing the selectivity of glomerular filtration to macromolecules of varying size. The usual theories for hindered transport of solid spheres through pores have limited utility in interpreting clearance data for dextran or other linear polymers because such polymers in solution more closely resemble random, solvent-filled coils than solid spheres. To provide a model for glomerular filtration of random-coil macromolecules, the equilibrium partitioning of random coils between cylindrical pores and bulk solution was simulated using Monte Carlo calculations, and those results were combined with a hydrodynamic theory for restricted motion of solvent-filled polymer coils in pores. The rates of transport predicted for either neutral random coils or for solid spheres of the same Stokes-Einstein radius were significantly lower than observed transport rates of dextran through the glomerular capillary wall or across synthetic porous membranes. This facilitation of dextran transport was modeled by postulating weak, attractive interactions between dextran monomers and the pore wall. The random-coil model with attractive interactions, modeled using a short-range, square-well potential, was found to adequately represent dextran sieving data in normal rats. Various limitations of this approach are discussed.

Notizen: Abstract Method-dependent mechanisms that may affect dynamic numerical solutions of a hyperbolic partial differential equation that models concentration profiles in renal tubules are described. Some numerical methods that have been applied to the equation are summarized, and ways by which the methods may misrepresent true solutions are analysed. Comparison of these methods demonstrates the need for thoughtful application of computational mathematics when simulating complicated time-dependent phenomena.

Notizen: Abstract The regulation of the interactions between the actin binding proteins and the actin filaments are known to affect the cytoskeletal structure of F-actin. We develop a model depicting the formation of actin cytoskeleton, bundles and orthogonal networks, via activation or inactivation of different types of actin binding proteins. It is found that as the actin filament density increases in the cell, a spontaneous tendency to organize into bundles or networks occurs depending on the active actin binding protein concentration. Also, a minute change in the relative binding affinity of the actin binding proteins in the cell may lead to a major change in the actin cytoskeleton. Both the linear stability analysis and the numerical results indicate that the structures formed are highly sensitive to changes in the parameters, in particular to changes in the parameter ϕ, denoting the relative binding affinity and concentration of the actin binding proteins.

Notizen: Abstract To investigate morphogenesis and in particular circularization mechanisms in young mycelia, we observe cultures of the zygomyceteMucor spinosus and develop discrete models of two-dimensional filamental branching growth. The models are based on the hypothesis that the fungus secretes a regulatory substance that diffuses into the surrounding medium and is detected by the growing hyphae. We also present a simple Markovian growth model without such a feedback, but yielding to analytical computations.

Notizen: Abstract In vivo volume growth of two murine tumor cell lines was compared by mathematical modeling to their volume growth as multicellular spheroids. Fourteen deterministic mathematical models were studied. For one cell line, spheroid growth could be described by a model simpler than needed for description of growthin vivo. A model that explicitly included the stimulatory role for cell-cell interactions in regulation of growth was always superior to a model that did not include such a role. The von Bertalanffy model and the logistic model could not fit the data; this result contradicted some previous literature and was found to depend on the applied least squares fitting method. By the use of a particularly designed mathematical method, qualitative differences were discriminated from quantitative differences in growth dynamics of the same cells cultivated in two different three-dimensional systems.

Notizen: Abstract This paper develops and applies a dynamic mathematical model for optimal scheduling of nitrogen fertilization and irrigation that minimizes nitrogen leaching subject to a target level of yield. The analysis assumes a single crop grown during a single growing season of a given length. It is shown that substitution of water for nitrogen along a given plant growth path decreases nitrogen leaching and, therefore, groundwater contamination. It is proved that a minimum leaching solution to the optimization problem is obtained with a single nitrogen application at the beginning of the season and irrigation scheduling that maintains a wet soil throughout the growing period. A numerical example utilizing experimental data for an irrigated summer corn in Israel confirms and quantifies the analytical findings.

Notizen: Abstract We analyse the stochastic properties of dynamical systems with finite populations of a few differentreplicator species. Our main interest is to evaluate the typicallifetime, i.e. the time for the extinction of the first species in the network, for different catalytic structures, as a function of the population size.