ALBERT

Notes: Abstract The parameter domain for which the quasi-steady state assumption is valid can be considerably extended merely by a simple change of variable. This is demonstrated for a variety of biologically significant examples taken from enzyme kinetics, immunology and ecology.

Notes: Abstract The ability of random fluctuations in selection to maintain genetic diversity is greatly increased when generations overlap. This result has been derived previously using genetic models with very special assumptions about the population age structure. Here we explore its robustness in more realistic population models, with very general age structure or physiological structure. For a range of genetic models (haploid, diploid, single and multilocus) we find that the condition for maintaining genetic diversity generalizes almost without change. Genetic diversity is maintained by selection if a product of the form (generation overlap)×(selection intensity)×(variability in the selection regime) is sufficiently large, where the generation overlap is measured in units of Fisher's reproductive value. This conclusion is based on a local evolutionary stability analysis, which differs from the standard “protected polymorphism” criterion for the maintenance of genetic diversity. Simulation results match the predictions from the local stability analysis, but not those from the protected polymorphism criterion. The condition obtained here for maintaining genetic diversity requires fitness fluctuations that are substantial but well within the range observed in many studies of natural populations.

Notes: Abstract Premised on relatively simple assumptions, mathematical models like those of Monod, Pirt or Droop inadequately explain the complex transient behavior of microbial populations. In particular, these models fail to explain many aspects of the dynamics of aTetrahymena pyriformis-Escherichia coli community. In this study an alternative approach, an individual-based model, is employed to investigate the growth and interactions ofTetrahymena pyriformis andE. coli in a batch culture. Due to improved representation of physiological processes, the model provides a better agreement with experimental data of bacterial density and ciliate biomass than previous modeling studies. It predicts a much larger coexistence domain than rudimentary models, dependence of biomass dynamics on initial conditions (bacteria to ciliate biomasses ratio) and appropriate timing of minimal bacteria density. Moreover, it is found that accumulation ofE. coli sized particles andE. coli toxic metabolites has a stabilizing effect on the system.

Notes: Abstract At the core of contemporarymorphometrics—the quantitative study of biological shape variation—is a synthesis of two originally divergent methodological styles. One contributory tradition is the multivariate analysis of covariance matrices originally developed as biometrics and now dominant across a broad expanse of applied statistics. This approach, couched solely in the linear geometry of covariance structures, ignores biomathematical aspects of the original measurements. The other tributary emphasizes the direct visualization of changes in biological form. However, making objective the biological meaning of the features seen in those diagrams was always problematical; also, the representation of variation, as distinct from pairwise difference, proved infeasible. To combine these two variants of biomathematical modeling into a valid praxis for quantitative studies of biological shape was a goal earnestly sought though most of this century. That goal was finally achieved in the 1980s when techniques from mathematical statistics, multivariate biometrics, non-Euclidean geometry and computer graphics were combined in a coherent new system of tools for the complete regionalized quantitative analysis oflandmark points together with the biomedical images in which they are seen. In this morphometric synthesis, correspondence of landmarks (biologically labeled geometric points, like “bridge of the nose”) across specimens is taken as a biomathematical primitive. The shapes of configurations of landmarks are defined as equivalence classes with respect to the Euclidean similarity group and then represented as single points in David Kendall'sshape space, a Riemannian manifold with Procrustes distance as metric. All conventional multivariate strategies carry over to the study of shape variation and covariation when shapes are interpreted in the tangent space to the shape manifold at an average shape. For biomathematical interpretation of such analyses, one needs a basis for the tangent space compatible with the reality of local biotheoretical processes and explanations at many different geometric scales, and one needs graphics for visualizing average shape differences and other statistical contrasts there. Both of these needs are managed by thethin-plate spline, a deformation function that has an unusually helpful linear algebra. The spline also links the biometrics of landmarks to deformation analysis of the images from which the landmarks originally arose. This article reviews the history and principal tools of this synthesis in their biomathematical and biometrical context and demonstrates their usefulness in a study of focal neuroanatomical anomalies in schizophrenia.

Notes: Abstract A competition model describing tumor-normal cell interaction with the added effects of periodically pulsed chemotherapy is discussed. The model describes parameter conditions needed to prevent relapse following attempts to remove the tumor or tumor metastasis. The effects of resistant tumor subpopulations are also investigated and recurrence prevention strategies are explored.

Notes: Abstract Increasing attention is being paid to the configuration and development of vascular structures and their possible correlations with physiological events. The study of angiogenesis in normal and pathological states as well as in the embryo and adult has provided new insights into the mechanism of vessel growth and organization of the vasculature. Various mathematical branching models have been developed. These constructions are mainly geometrical and only involve a branching phenomenon. We propose the use of a deterministic non-linear model based on physiological laws and hydrodynamics. Growth, branching and anastomosis, the three actual main events occurring in vascular growth, are included in this model. Space growth, including cells and vessels, is defined by a decreasing transformation. Space density and the length of new sprouts are controlled by a set of parameters. The conditions on these parameters are well established, which allows the production of realistic patterns.

Notes: Abstract The quasi-stationary distribution of a population within a system of interacting populations is approximated by a stochastic logistic process. The parameters of this process can be expressed in the parameters of the full system. Using the diffusion approximation, an expression for the expected extinction time is derived from this logistic process. Since the expected extinction time is expressed in the parameters of the full system, the effect of these parameters on the extinction risk can be easily evaluated, which may be of use for studies in ecology, conservation biology and epidemiology. The outcome is compared with simulation results for the case of a prey-predator system.

Notes: Abstract The cytokines are the information superhighway of the immune system. They are an important component of the integrated behavior of the system. In order to be able to have a good understanding of the immune system, we must be able to model the effect of cytokines and their combined effect. This work is a step in that direction. We study the combined effect of two cytokines: interleukin-2 (IL-2) and interleukin-4 (IL-4) on some cells of the immune system. Interleukin-2 and interleukin-4 are important growth and differentiation factors for B and T cells. Interleukin-4 antagonizes the effect of interleukin-2 on B cells and some T cells while it synergizes with interleukin-2 on other T cells. We build a mathematical model of the interaction of both cytokines on T and B cells as a building block toward a model of the Th1/Th2 cross-regulation. The response of a given cell to the combination of interleukin-2 and interleukin-4 is shown to involve competing dynamical effects which can lead to either antagnostic or synergistic combined effect.

Notes: Abstract We propose a mathematical approach to the modelling of self-organizing hierarchies in animal societies. This approach relies on a basic positive feedback mechanism that reinforces the ability of a given individual to win or to lose in a hierarchical interaction, depending on how many times it won or lost in previous interactions. Motivated by experiments carried out on primitively eusocial waspsPolistes, the model, is based on coupled differential equations supplemented with a small stochastic term. Numerical integrations allow many different hierarchical profiles to be obtained depending on the model parameters: (1) the particular form of the probability for an individual to win or lose a fight given its history, (2) the probability of interaction between two individuals, (3) the forgetting strength, which determines the rate at which events in the past are forgotten and no longer influence the force of an individual and (4) two individual recognition parameters, which set the contribution of individual recognition in the process of hierarchical genesis. We compare the results, expressed in terms of a hierarchical index or of the Landau number that describes the degree of linearity of the hierarchy, with various experimental results.

Notes: Abstract The normal process of dermal wound healing fails in some cases, due to fibro-proliferative disorders such as keloid and hypertrophic scars. These types of abnormal healing may be regarded as pathologically excessive responses to wounding in terms of fibroblastic cell profiles and their inflammatory growth-factor mediators. Biologically, these conditions are poorly understood and current medical treatments are thus unreliable. In this paper, the authors apply an existing deterministic mathematical model for fibroplasia and wound contraction in adult mammalian dermis (Olsenet al., J. theor. Biol. 177, 113–128, 1995) to investigate key clinical problems concerning these healing disorders. A caricature model is proposed which retains the fundamental cellular and chemical components of the full model, in order to analyse the spatiotemporal dynamics of the initiation, progression, cessation and regression of fibro-contractive diseases in relation to normal healing. This model accounts for fibroblastic cell migration, proliferation and death and growth-factor diffusion, production by cells and tissue removal/decay. Explicit results are obtained in terms of the model processes and parameters. The rate of cellular production of the chemical is shown to be critical to the development of a stable pathological state. Further, cessation and/or regression of the disease depend on appropriate spatiotemporally varying forms for this production rate, which can be understood in terms of the bistability of the normal dermal and pathological steady states—a central property of the model, which is evident from stability and bifurcation analyses. The work predicts novel, biologically realistic and testable pathogenic and control mechanisms, the understanding of which will lead toward more effective strategies for clinical therapy of fibro-proliferative disorders.

Notes: Abstract Populations often exhibit abrupt changes in abundance associated with a smooth, continuous change in some component of their environment, with the abruptness usually attributed to inter-specific interactions or physical extremes. This paper presents a spatially explicit single-species population model in which intra-specific interactions alone are responsible for such an abrupt change. The essential mechanism involves cooperation in both colonization (through enhanced recruitment near other individuals) and mortality (protection through a “safety-in-numbers” interaction). Large fluctuations in population density would likely be observable near the transition region.

Notes: Abstract A mathematical model of the nitrogen transformation cycle in an aquatic environment is studied. Using Pontryagin's maximum principle, a preferential utilization of ammonium to nitrate by phytoplankton is explained and verified by experimental data. A multiparameter bifurcation is given. The model was found to have four types of equilibrium sets. It is shown that a Hopf bifurcation may occur.

Notes: Abstract Parallel computation employing a domain decomposition method was used to calculate precisely without approximations the spatio-temporal distribution of Ca2+ in nerve terminals. The results showed, contrary to expectations, that for equal admitted Ca2+ currents at low (one channel open) and high (four channels open) depolarization, the average Ca2+ concentration at the release area is higher at the low depolarization. These calculations provide additional support for the Ca2+-voltage hypothesis for neurotransmitter release.

Notes: Abstract Type I hypersensitivity, which functions to protect the organism from parasites, is caused by binding of antigen to IgE antibodies pre-attached to the cell surface of tissue mast cells and their circulating counterparts, the basophils. In “allergy,” type I hypersensitivity is inappropriately induced by protein-based foreign substances (such as pollen) or protein components of insect stings, which in the normal course of events would be cleared from the organism without causing any damage. Paradoxically, a successful clinical treatment of allergy involves repeated immunization of allergic persons with low doses of the allergen—immunotherapy. Investigation of the available experimental evidence leads to the conclusion that the phenomena of immunotherapy are best addressed in terms of the interplay among the mechanism(s) of immune memory—Th1/Th2 cross-regulation—and the physical compart-mentalization of the immune system. These conclusions are illustrated with a numerical simulation.

Notes: Abstract In the presence of seasonal forcing, predator-prey models with quadratic interaction terms and weak dissipation can exhibit infinite numbers of coexisting periodic attractors corresponding to cycles of different magnitude and frequency. These motions are best understood with reference to the conservative case, for which the degree of dissipation is, by definition, zero. Here one observes the familiar mix of “regular” (neutrally stable orbits and tori) and chaotic motion typical of non-integrable Hamiltonian systems. Perturbing away from the conservative limit, the chaos becomes transitory. In addition, the invariant tori are destroyed and the neutrally stable periodic orbits becomes stable limit cycles, the basins of attraction of which are intertwined in a complicated fashion. As a result, stochastic perturbations can bounce the system from one basin to another with consequent changes in system behavior. Biologically, weak dissipation corresponds to the case in which predators are able to regulate the density of their prey well below carrying capacity.

Notes: Abstract The standard method for measuringin vitro antibiotic efficacy is based on a point observation of bacterial activity 18 hours after inoculation. The method, while simple, forgoes significant information by ignoring the dynamics of the interations between antibiotic and bacteria. This paper proposes a simple dynamic model describing these interactions. The model consists of two non-linear differential equations of the S-system type. Its parameter values are estimated, through the minimization of residual errors, from data on the effect of the carbapenem antibiotic imipenem onPseudomonas aeruginosa. The model adequately describes the dynamic behavior of the bacterial populations in the presence of the antibiotic: beginning with drug administration, then through the decline of the bacterial population and possibly ending with bacterial resurgence.

Notes: Abstract We have studied an ecological system of two species, which we denotestrong andweak, respectively, that compete for a single food resource. This system is modelled as a three component reaction-diffusion process. In the presence of a solitary pulse of increased resources, the weaker competitor can diffuse toward this surplus, gaining a competitive advantage and hence persisting in contraposition with the classical Lotka-Volterra result. An exact analytical solution has been found through a quantum mechanical analogy. A stability analysis of this solution against changes in different parameters has been carried out.

Notes: Abstract Collapsible-tube flow with self-excited oscillations has been extensively investigated. Though physiologically relevant, forced oscillation coupled with self-excited oscillation has received little attention in this context. Based on an ODE model of collapsible-tube flow, the present study applies modern dynamics methods to investigate numerically the responses of forced oscillation to a limit-cycle oscillation which has topological characteristics discovered in previous unforced experiments. A devil's staircase and period-doubling cascades are presented with forcing frequency and amplitude as control parameters. In both cases, details are provided in a bifurcation diagram. Poincaré sections, a frequency spectrum and the largest Lyapunov exponents verify the existence of chaos in some circumstances. The thin fractal structure found in the strange attractors is believed to be a result of high damping and low stiffness in such systems.

Notes: Abstract In this work, we show that a one-dimensional model of the blood flow across the lungs can reproduce the evolution of a bolus versus the time. Solving the differential equation governing the bolus concentration in the framework of this model, we determine the solution which fulfills Gaussian initial boundary conditions. An effective parameter related to the ratio of a diffusion coefficient to the square of the mean speed of the flow is defined. The determination of its numerical values following a semi-empirical approach enables us to know accurately the mean transit time and the cardiac output. The results have been compared to other methods, and were found in good agreement. Such an approach could be of interest in all studies where the knowledge of flow—including micro-circulation—is needed.

Notes: Abstract How two species interact during and after colonization influences which of them will be present in each stage of succession. In the tolerance model of ecological succession in a patchy environment, empty patches can be colonized by any species, but the ability to tolerate reduced resource levels determines which species will exclude the other. Here, we analyze a meta-population model of the possible roles of competition in colonization and succession, using non-linear Markov chains as a mathematical framework. Different kinds of competition affect the final equilibrial, abundances of the species involved in qualitatively different ways. An explicit criterion is given to determine which interactions have stronger effects on the final equilibrial levels of the weaker, species. Precise conditions are stated for the co-existence of both species. Both species are more likely to co-exist in the presence of an intermediate disturbance frequency.

Notes: Abstract An equivalent electrical circuit is given for a branch of an amphibian motor-nerve terminal in a volume conductor. The circuit allows for longitudinal current flow inside the axon as well as between the axon and its Schwann cell sheath, and also for the radial leakage of current through the Schwann cell sheath. Analytical and numerical solutions are found for the spatial and time dependence of the membrane potential resulting from the injection of depolarizing current pulses by external electrodes at one or two separate locations on the terminal. These solutions show that the depolarization at an injection site can cause a hyperpolarization at sites a short distance away. This effect becomes more pronounced in a short terminal with sealed-end boundary conditions. The hyperpolarization provides a possible explanation for recent experimental results, which show that the average quantal release due to a test depolarizing current pulse delivered by an electrode at one site on a nerve terminal is reduced by the application of an identical conditioning pulse at a neighbouring site.

Notes: Abstract Synthetic barriers such as gloves, condoms and masks are widely used in efforts to prevent disease transmission. Due to manufacturing defects, tears arising during use, or material porosity, there is inevitably a risk associated with use of these barriers. An understanding of virus transport through the relevant passageways would be valuable in quantifying the risk. However, experimental investigations involving such passageways are difficult to perform, owing to the small dimensions involved. This paper presents a mathematical model for analyzing and predicting virus transport through barriers. The model incorporates a mathematical description of the mechanisms of virus transport, which include carrier-fluid flow, Brownian motion, and attraction or repulsion via virus-barrier interaction forces. The critical element of the model is the empirically determined rate constant characterizing the interaction force between the virus and the barrier. Once the model has been calibrated through specification of the rate constant, it can predict virus concentration under a wide variety of conditions. The experiments used to calibrate the model are described, and the rate constants are given for four bacterial viruses interacting with a latex membrane in saline. Rate constants were also determined for different carrier-fluid salinities, and the salt concentration was found to have a pronounced effect. Validation experiments employing laser-drilled pores in condoms were also performed to test the calibrated model. Model predictions of amount of transmitted virus through the drilled holes agreed well with measured values. Calculations using determined rate constants show that the model can help identify situations where barrier-integrity tests could significantly underestimate the risk associated with barrier use.

Notes: Abstract Evaluation of the fluid flow pattern in a non-pregnant uterus is important for understanding embryo transport in the uterus. Fertilization occurs in the fallopian tube and the embryo (fertilized ovum) enters the uterine cavity within 3 days of ovulation. In the uterus, the embryo is conveyed by the uterine fluid for another 3 to 4 days to a successful implantation site at the upper part of the uterus. Fluid movements within the uterus may be induced by several mechanisms, but they seem to be dominated by myometrial contractions. Intra-uterine fluid transport in a sagittal cross-section of the uterus was simulated by a model of wall-induced fluid motion within a two-dimensional channel. The time-dependent fluid pattern was studied by employing the lubrication theory. A comprehensive analysis of peristaltic transport resulting from symmetric and asymmetric contractions is presented for various displacement waves on the channel walls. The results provide information on the flow field and possible trajectories by which an embryo may be transported before implantation at the uterine wall.

Notes: Abstract A mechanistically based mathematical model is used to investigate some of the important factors in priming hepatocytes to enter the G1 phase of the cell cycle. The model considers all of the relevant biochemical mechanisms from signal-receptor binding to the elevation of AP-1(activation protein transcription factor) levels. Focus is centered on the chain of biochemical events governing the sequential activation of protein kinase C (PKC), mitogen-activated protein kinase (MAPK) and AP-1. Factors such as amplitude and duration of growth factors signals, the kinetics of guanosine diphosphate (GDP) to guanosine triphosphate (GTP) conversion, and the negative feedback control mechanisms governing initial steps in cellular replication were theoretically examined. The results of our theoretical assessments support the finding that specific mutations along the PKC-AP1 pathways can have a critical effect on the rate at which cells enter the division cycle.

Notes: Abstract Normal cardiac muscle contraction occurs in response to a rapid rise followed by a slower decay in intracellular calcium concentration. When cardiac muscle cells are loaded with calcium, an intracellular store releases calcium into the cytosol by the process of calcium-induced calcium release (CICR). This release contributes to the rise in intracellular calcium which in turn triggers contraction. We use two qualitative piecewise linear reaction-diffusion models of this behaviour to investigate the speed, stability and waveform of plane waves using singular perturbation techniques.

Notes: Abstract Properties of two of the stochastic circulatory models theoretically introduced by Smith et al., 1997, Bull. Math. Biol. 59, 1–22 were investigated. The models assumed the gamma distribution of the cycle time under either the geometric or Poisson elimination scheme. The reason for selecting these models was the fact that the probability density functions of the residence time of these models are formally similar to those of the Bateman and gamma-like function models, i.e., the two common deterministic models. Using published data, the analytical forms of the probability density functions of the residence time and the distributions of the simulated values of the residence time were determined on the basis of the deterministic models and the stochastic circulatory models, respectively. The Kolmogorov-Smirnov test revealed that even for 1000 xenobiotic particles, i.e., a relatively small number if the particles imply drug molecules, the probability density functions of the residence time based on the deterministic models closely matched the distributions of the simulated values of the residence time obtained on the basis of the stochastic circulatory models, provided that parameters of the latter models fulfilled selected conditions.

Notes: Abstract Ratio-dependent predator-prey models set up a challenging issue regarding their dynamics near the origin. This is due to the fact that such models are undefined at (0, 0). We study the analytical behavior at (0, 0) for a common ratio-dependent model and demonstrate that this equilibrium can be either a saddle point or an attractor for certain trajectories. This fact has important implications concerning the global behavior of the model, for example regarding the existence of stable limit cycles. Then, we prove formally, for a general class of ratio-dependent models, that (0, 0) has its own basin of attraction in phase space, even when there exists a non-trivial stable or unstable equilibrium. Therefore, these models have no pathological dynamics on the axes and at the origin, contrary to what has been stated by some authors. Finally, we relate these findings to some published empirical results.

Notes: Abstract We explore the behavior of richly connected inhibitory neural networks under parameter changes that correspond to weakening of synaptic efficacies between network units, and show that transitions from irregular to periodic dynamics are common in such systems. The weakening of these connections leads to a reduction in the number of units that effectively drive the dynamics and thus to simpler behavior. We hypothesize that the multiple interconnecting loops of the brain’s motor circuitry, which involve many inhibitory connections, exhibit such transitions. Normal physiological tremor is irregular while other forms of tremor show more regular oscillations. Tremor in Parkinson’s disease, for example, stems from weakened synaptic efficacies of dopaminergic neurons in the nigro-striatal pathway, as in our general model. The multiplicity of structures involved in the production of symptoms in Parkinson’s disease and the reversibility of symptoms by pharmacological and surgical manipulation of connection parameters suggest that such a neural network model is appropriate. Furthermore, fixed points that can occur in the network models are suggestive of akinesia in Parkinson’s disease. This model is consistent with the view that normal physiological systems can be regulated by robust and richly connected feedback networks with complex dynamics, and that loss of complexity in the feedback structure due to disease leads to more orderly behavior.

Notes: Abstract Determining molecular structure from interatomic distances is an important and challenging problem. Given a molecule with n atoms, lower and upper bounds on interatomic distances can usually be obtained only for a small subset of the $$\frac{{n(n - 1)}}{2}$$ atom pairs, using NMR. Given the bounds so obtained on the distances between some of the atom pairs, it is often useful to compute tighter bounds on all the $$\frac{{n(n - 1)}}{2}$$ pairwise distances. This process is referred to as bound smoothing. The initial lower and upper bounds for the pairwise distances not measured are usually assumed to be 0 and ∞. One method for bound smoothing is to use the limits imposed by the triangle inequality. The distance bounds so obtained can often be tightened further by applying the tetrangle inequality—the limits imposed on the six pairwise distances among a set of four atoms (instead of three for the triangle inequalities). The tetrangle inequality is expressed by the Cayley—Menger determinants. For every quadruple of atoms, each pass of the tetrangle inequality bound smoothing procedure finds upper and lower limits on each of the six distances in the quadruple. Applying the tetrangle inequalities to each of the ( 4 n ) quadruples requires O(n 4) time. Here, we propose a parallel algorithm for bound smoothing employing the tetrangle inequality. Each pass of our algorithm requires O(n 3 log n) time on a CREW PRAM (Concurrent Read Exclusive Write Parallel Random Access Machine) with $$O\left( {\frac{n}{{\log n}}} \right)$$ processors. An implementation of this parallel algorithm on the Intel Paragon XP/S and its performance are also discussed.

Notes: Abstract We observed that amphiphile-induced microexovesicles may be spherical or cylindrical, depending on the species of the added amphiphile. The spherical microexovesicle corresponds to an extreme local difference between the two monolayer areas of the membrane segment with a fixed area, while the cylindrical microexovesicle corresponds to an extreme local area difference if the area of the budding segment is increased due to lateral influx of anisotropic membrane constituents. Protein analysis showed that both types of vesicles are highly depleted in the membrane skeleton. It is suggested that a partial detachment of the skeleton in the budding region is favoured due to accumulated skeleton shear deformations in this region.

Notes: Abstract The possibility of chaos control in biological systems has been stimulated by recent advances in the study of heart and brain tissue dynamics. More recently, some authors have conjectured that such a method might be applied to population dynamics and even play a nontrivial evolutionary role in ecology. In this paper we explore this idea by means of both mathematical and individual-based simulation models. Because of the intrinsic noise linked to individual behavior, controlling a noisy system becomes more difficult but, as shown here, it is a feasible task allowed to be experimentally tested.

Notes: Abstract In an attempt to improve the understanding of complex metabolic dynamic phenomena, we have analysed several ‘metabolic networks’, dynamical systems which, under a single formulation, take into account the activity of several catalytic dissipative structures, interconnected by substrate fluxes and regulatory signals. These metabolic networks exhibit a rich variety of self-organized dynamic patterns, with e.g., phase transitions emerging in the whole activity of each network. We apply Hurst’s R/S analysis to several time series generated by these metabolic networks, and measure Hurst exponents H 〈 0.5 in most cases. This value of H, indicative of antipersistent processes, is detected at very high significance levels, estimated with detailed Monte Carlo simulations. These results show clearly the considered type of metabolic networks exhibit long-term memory phenomena.

Notes: Abstract The secondary structures of nucleic acids form a particularly important class of contact structures. Many important RNA molecules, however, contain pseudo-knots, a structural feature that is excluded explicitly from the conventional definition of secondary structures. We propose here a generalization of secondary structures incorporating ‘non-nested’ pseudo-knots, which we call bi-secondary structures, and discuss measures for the complexity of more general contact structures based on their graph-theoretical properties. Bi-secondary structures are planar trivalent graphs that are characterized by special embedding properties. We derive exact upper bounds on their number (as a function of the chain length n) implying that there are fewer different structures than sequences. Computational results show that the number of bi-secondary structures grows approximately like 2.35n. Numerical studies based on kinetic folding and a simple extension of the standard energy model show that the global features of the sequence-structure map of RNA do not change when pseudo-knots are introduced into the secondary structure picture. We find a large fraction of neutral mutations and, in particular, networks of sequences that fold into the same shape. These neutral networks percolate through the entire sequence space.

Notes: Abstract A braced framework of tubular struts, in the walls and air spaces of frog lungs, suspends the respiratory surface and holds the lung open at zero transmural pressure withstanding imploding forces created by abdominal viscera, much as would the supports of a bell tent. The struts are tubes, having a larger second moment of area than do solid struts of the same cross-sectional area, and so are stronger, and contain pulmonary vessels within a flexible wall. The orthogonal arrangement of the struts in the framework, explained in part by Maxwell’s Lemma and Michell’s Theorem, strengthens the framework and minimizes its weight; orthogonality is maintained as the lungs change size. A model is presented, in which a frog might control pre-and post-pulmonary vascular resistances and, hence, blood volume in the struts, without compromising pulmonary perfusion. Such adjustments could vary the area of lung and the extent of perfused capillaries exposed to pulmonary gas, helping match the lung’s surface area, weight and metabolic load to activity.

Notes: Abstract A molecular-level theory is constructed for the control of fast neurotransmitter release, based on recent experimental findings that depolarization shifts presynaptic autoreceptors to a low affinity state and that an autoreceptor must be bound to a transmitter before it can become associated with the exocytotic apparatus. It is assumed that such an association blocks release; experimental support for this assumption is cited. The theory provides mechanisms for key experimental results concerning the essence of the matter, what controls the time course of evoked release? The same general model can account for both evoked and spontaneous release. The new theory can be regarded as a molecular implementation of the (phenomenological) calcium-voltage hypothesis that was suggested earlier.

Notes: Abstract We have developed cellular automaton models for two species competing in a patchy environment. We have modeled three common types of competition: facilitation (in which the winning species can colonize only after the losing species has arrived) inhibition (in which either species is able to prevent the other from colonizing) and tolerance (in which the species most tolerant of reduced resource levels wins). The state of a patch is defined by the presence or absence of each species. State transition probabilities are determined by rates of disturbance, competitive exclusion, and colonization. Colonization is restricted to neighboring patches. In all three models, disturbance permits regional persistence of species that are excluded by competition locally. Persistence, and hence diversity, is maximized at intermediate disturbance frequencies. If disturbance and dispersal rates are sufficiently high, the inferior competitor need not have a dispersal advantage to persist. Using a new method for measuring the spatial patterns of nominal data, we show that none of these competition models generates patchiness at equilibrium. In the inhibition model, however, transient patchiness decays very slowly. We compare the cellular automaton models to the corresponding mean-field patch-occupancy models, in which colonization is not restricted to neighboring patches and depends on spatially averaged species frequencies. The patch-occupancy model does an excellent job of predicting the equilibrium frequencies of the species and the conditions required for coexistence, but not of predicting transient behavior.

Notes: Abstract We investigate the sequence of patterns generated by a reaction—diffusion system on a growing domain. We derive a general evolution equation to incorporate domain growth in reaction—diffusion models and consider the case of slow and isotropic domain growth in one spatial dimension. We use a self-similarity argument to predict a frequency-doubling sequence of patterns for exponential domain growth and we find numerically that frequency-doubling is realized for a finite range of exponential growth rate. We consider pattern formation under different forms for the growth and show that in one dimension domain growth may be a mechanism for increased robustness of pattern formation.

Notes: Abstract The persistence of linear dominance hierarchies is often attributed to higher probabilities of a win after a win or a loss after a loss in agonistic interactions, yet there has been no theory on the evolution of such prior-experience effects. Here an analytic model, based on the idea that contests are determined by subjective perceptions of resource-holding potential (RHP) which animals may revise in the light of experience, demonstrates that winner and loser effects can evolve through round-robin competition among triads of animals drawn randomly from their population, and that the probability of a hierarchy increases with the strength of the combined effect. The effects are pure, in the sense that a contestant observes neither its own RHP nor its opponent’s RHP or RHP perception or win—loss record; and so the strength of an effect is unmodified by the RHPs of particular individuals, but depends on the distribution of RHP among the population at large. The greater the difference between an individual’s and its opponent’s RHP perception, the more likely it is to win a contest; however, if it overestimates its RHP, then the cost of fighting increases with the overestimate. A winner or loser effect exists only if the fitness gain of the beta individual in a hierarchy, relative to that of the alpha, is less than 0.5. Then a loser effect can exist alone, or it can coexist with a winner effect; however, there cannot exist a winner effect without a loser effect.

Notes: Abstract Mathematical models predict that a population which oscillates in the absence of time-dependent factors can develop multiple attracting final states in the advent of periodic forcing. A periodically-forced, stage-structured mathematical model predicted the transient and asymptotic behaviors of Tribolium (flour beetle) populations cultured in periodic habitats of fluctuating flour volume. Predictions included multiple (2-cycle) attractors, resonance and attenuation phenomena, and saddle influences. Stochasticity, combined with the deterministic effects of an unstable ’saddle cycle’ separating the two stable cycles, is used to explain the observed transients and final states of the experimental cultures. In experimental regimes containing multiple attractors, the presence of unstable invariant sets, as well as stochasticity and the nature, location, and size of basins of attraction, are all central to the interpretation of data.

Notes: Abstract A global kinetic analysis of a model consisting of an autocatalytic zymogen-activation process, in which an irreversible inhibitor competes with the zymogen for the active site of the proteinase, and a monitoring coupled reaction, in which the enzyme acts upon one of its substrates, is presented. This analysis is based on the progress curves of any of the two products released in the monitoring reaction. The general solution is applied to an important particular case in which rapid equilibrium conditions prevail. Finally, we suggest a procedure to predict whether the inhibition or activation route dominates in the steady state of the system. These results generalize our previous analysis of simpler mechanisms.

Notes: Abstract In this work, treating the artery as a thick-walled cylindrical shell made of an incompressible, isotropic and elastic solid, utilizing the large deformation theory and the stress-strain relation proposed by Demiray (1976b,Trans. ASME Ser. E, J. Appl. Mech.,98, 194–197), an explicit expression for the pulse speed is obtained and the effect of lumen pressure and the axial stretch on wave speed is discussed. Numerical results indicate that the wave speed increases with lumen pressure but decreases with the axial stretch. The results of the present model are compared with our previous work (Demiray, 1988,J. Biomech. 21, 55–58) on the same subject.

Notes: Abstract For a one-locus selection model, Svirezhev introduced an integral variational principle by defining a Lagrangian which remained stationary on the trajectory followed by the population undergoing selection. It is shown here (i) that this principle can be extended to multiple loci in some simple cases and (ii) that the Lagrangian is defined by a straightforward generalization of the one-locus case, but (iii) that in two-locus or more general models there is no straightforward extension of this principle if linkage and epistasis are present. The population trajectories can be constructed as trajectories of steepest ascent in a Riemannian metric space. A general method is formulated to find the metric tensor and the surface in the metric space on which the trajectories, which characterize the variations in the gene structure of the population, lie. The local optimality principle holds good in such a space. In the special case when all possible linkage disequilibria are zero, the phase point of then-locus genetic system moves on the surface of the product space ofn higher dimensional unit spheres in a certain Riemannian metric space of gene frequencies so that the rate of change of mean fitness is maximum along the trajectory. In the two-locus case the corresponding surface is a hyper-torus.

Notes: Abstract Most recent models of the immune network are based upon a phenomenological log bell-shaped interaction function. This function depends on a single parameter, the “field”, which is the sum of all ligand concentrations weighted by their respective affinities. The typical behavior of these models is dominated by percolation, a phenomenon in which a local stimulus spreads globally throughout the network. The usual reason for employing a log bell-shaped interaction function is that B cells are activated by cross-linking of their surface immunoglobulin receptors. Here we formally derive a new phenomenological log bell-shaped function from the chemistry of receptor cross-linking by bivalent ligand. Specifying how this new function depends on the ligand concentrations requires two fields: a binding field and a cross-linking field. When we compare the activation functions for ligand-receptor pairs with different affinities, the one-field and the two-field functions differ markedly. In the case of the one-field activation function, its graph is shifted to increasingly higher concentration as the affinity decreases but keeps its width and height. In the case of the two-field activation function, the graph of a low-affinity interaction is nested within the graphs of all higher-affinity interactions. We show that this difference in the relations among activation functions for different affinities radically changes the network behavior. In models that described B cell proliferation using the one-field activation function, network behavior was dominated by low-affinity interactions. Conversely, in our new model, the high-affinity interactions are the most significant. As a consequence, percolation is no longer the only typical network behavior.

Notes: Abstract The dynamics of a microbial community consisting of a eucaryotic ciliateTetrahymena pyriformis and procaryoticEscherichia coli in a batch culture is explored by employing an individual-based approach. In this portion of the article, Part I, population models are presented. Because both models are individual-based, models of individual organisms are developed prior to construction of the population models. The individual models use an energy budget method in which growth depends on energy gain from feeding and energy sinks such as maintenance and reproduction. These models are not limited by simplifying assumptions about constant yield, constant energy sinks and Monod growth kinetics as are traditional models of microbal organisms. Population models are generated from individual models by creating distinct individual types and assigning to each type the number of real individuals they represent. A population is a compilation of individual types that vary in a phase of cell cycle and physiological parameters such as filtering rate for ciliates and maximum anabolic rate for bacteria. An advantage of the developed models is that they realistically describe the growth of the individual cells feeding on resource which varies in density and composition. Part II, the core of the project, integrates models into a dynamic microbial community and provides model analysis based upon available data.

Notes: Abstract Mathematical models are developed for the chemotherapy of AIDS. The models are systems of differential equations describing the interaction of the HIV infected immune system with AZT chemotherapy. The models produce the three types of qualitative clinical behavior: anuninfected steady state, aninfected steady state (latency) and aprogression to AIDS state. The effect of treatment is to perturb the system from progression to AIDS back to latency. Simulation of treatment schedules is provided for the consideration of treatment regimes. The following issues of chemotherapy are addressed: (i) daily frequency of treatment, (ii) early versus late initiation of treatment and (iii) intermittent treatment with intervals of no treatment. The simulations suggest the following properties of AZT chemotherapy: (i) the daily period of treatment does not affect the outcome of the treatment, (ii) treatment should not begin until after the final decline of T cells begins (not until the T cell population falls below approximately 300 mm−3) and then, it should be administered immediately and (iii) a possible strategy for treatment which may cope with side effects and/or resistance, is to treat intermittently with chemotherapy followed by interruptions in the treatment during which either a different drug or no treatment is administered. These properties are revealed in the simulations, as the model equations incorporate AZT chemotherapy as a weakly effective treatment process. We incorporate into the model the fact that AZT treatment does not eliminate HIV, but only restrains its progress. The mathematical model, although greatly simplified as a description of an extremely complex process, offers a means to pose hypotheses concerning treatment protocols, simulate alternative strategies and guide the qualitative understanding of AIDS chemotherapy.

Notes: Abstract A stochastic cellular automata model for the population dynamics of the army antEciton burchelli on Barro Colorado Island in Panama is set up. It is simulated on the computer and shown to give good agreement with biological data. It is analysed using two approximations akin to the mean field approximation in statistical mechanics, and good agreement with the simulations is obtained. Finally, the role of distance between successive statary phase bivouacs is discussed with regard to the rate of colony growth. There are two aspects of the biological system studied here that make it of general importance. First, the population is structured, since the size of each colony of army ants is crucial. Second, the spatial behaviour of the population, as in many others, is not diffusion-like, although it is random. This has implications for the kind of model that is chosen.

Notes: Abstract An analytical model for thermal damage of retinal tissue due to absorption of laser energy by finite-sized melanin granules is developed. Since melanin is the primary absorber of visible and near-IR light in the skin and in the retina, bulk heating of tissue can be determined by superposition of individual melanin granule effects. Granules are modeled as absorbing spheres surrounded by an infinite medium of water. Analytical solutions to the heat equation result in computations that are quick and accurate. Moreover, the model does not rely on symmetric beam profiles, and so arbitrary images can be studied. The important contribution of this model is to provide a more accurate biological description of submillisecond pulse exposures than previous retinal models, while achieving agreement for longer pulses. This model can also be naturally extended into the sub-microsecond domain by including vaporization as a damage mechanism. It therefore represents the beginning of a model which can be applied across the entire pulse duration domain.

Notes: Abstract Most of the elastic tubes found in the mammalian body will collapse from a distended circular cross section and when collapsed may undergo flow-induced oscillations. A mathematical model describing fluid flow in a collapsible tube is analysed using the software package AUTO-86. AUTO-86 is used for continuation and bifurcation problems in systems of non-linear ordinary differential equations. The model is a third-order lumped-parameter type and is based on the classical “Starling resistor”; it describes the unsteady flow behaviour and, in particular, the experimentally observed self-excited oscillations, in a way which is simple enough to give physical understanding, yet still firmly based on fluid mechanical principles. Some of the bifurcation types found in this model bear close resemblance to the types suggested by experimental observations of self-excited oscillations in collapsible tubes; they thus shed some light on the various topological changes which occur in practice, particularly in view of the fact that some of the points found numerically are diffcult to achieve experimentally, while the existence of others can only be inferred indirectly and uncertainly from experiment.

Notes: Abstract A solution algorithm yielding the pressure and flow-rate distributions for steady flow in an arbitrary, tree-like network is provided. Given the tree topology, the conductance of each segment and the pressure distribution at the boundary nodes, the solution is obtained from a simple recursion based on perfect Gauss elimination. An iterative solution method using this algorithm is suggested to solve for the pressure and flow-rate distributions in an arbitrary diverging-converging (arterial-venous) network consisting of two tree-like networks which are connected to each other at the capillary nodes. A number of special solutions for tree-like networks are obtained for which the general algorithm is either simplified or can be replaced by closed form solutions of the pressure and flow-rate distributions. These special solutions can also be obtained for each tree of diverging-converging networks having particular topologies and conductance distributions. Sample numerical results are provided.

Notes: Abstract Previous game-theoretic models of reciprocity have assumed that populations are large and organisms effectively sessile. This paper analyzes an iterated prisoner's dilemma among non-sessile organisms in a finite population, on the assumption that an individual's chance of remaining in one place is not influenced by a partner's behavior. This mode of interaction is suitable for analyzing potentially cooperative behaviors that are secondary to the advantage of group formation, e.g. allogrooming among social mammals. The analysis yields necessary conditions for stable reciprocity in terms of three parameters, namely, a benefit/cost ratio, the probability of further interaction and the probability of partner retention. The results suggest that, in highly mobile organisms such as fish, birds and mammals, reciprocity may be stable only if the population is small and the relative benefit and future interaction probability are both large.

Notes: Abstract We consider the kinetics of an autocatalytic reaction network in which replication and catalytic actions are separated by a translation step. We find that the behaviour of such a system is closely related to second-order replicator equations, which describe the kinetics of autocatalytic reaction networks in which the replicators act also as catalysts. In fact, the qualitative dynamics seems to be described almost entirely be the second-order reaction rates of the replication step. For two species we recover the qualitative dynamics of the replicator equations. Larger networks show some deviations, however. A hypercyclic system consisting of three interacting species can converge toward a stable limit cycle in contrast to the replicator equation case. A singular perturbation analysis shows that the replication-translation system reduces to a second-order replicator equation if translation is fast. The influence of mutations on replication-translation networks is also very similar to the behavior of selection-mutation equations.

Notes: Abstract In this work, we studied the propagation of non-linear waves in a pre-stressed thin elastic tube filled with an inviscid fluid. In the analysis, analogous to the physiological conditions of the arteries, the tube is assumed to be subject to a uniform pressureP 0 and a constant axial stretch ratio λz. In the course of blood flow it is assumed that a large dynamic displacement is superimposed on this static field. Furthermore, assuming that the displacement gradient in the axial direction is small, the non-linear equation of motion of the tube is obtained. Using the reductive perturbation technique, the propagation of weakly non-linear waves in the long-wave approximation is investigated. It is shown that the governing equations reduce to the Korteweg-deVries equation which admits a solitary wave solution. The result is discussed for some elastic materials existing in the literature.

Notes: Abstract The present paper deals with the bifurcation analysis of a simple food chain model consisting of components like detritus, nutrients, microorganisms, phytoplankton and zooplankton in an aquatic environment. The food chain model is described by a system of differential equations. If the length of the food chain (LFCH) is equal to 3 or 4, then an asymptotically stable equilibrium exists. For LFCH=5 or 6 the non-trivial equilibrium is unstable and the food-chain model has periodic orbits.

Notes: Abstract We develop a macroscopic model for delivering drug to brain tumors. The model accounts for bulk convective and diffusive transport across the blood-brain barrier and through the interstitial space. Through mathematical analysis and simulations, we assess the effects of changing parameters (within physiological bounds) on drug delivery. We find that there is an optimal treatment for convective drug delivery to the center of the tumor. We interpret this phenomenon in terms of traffic flow. The implications of our analyses on existing chemotherapeutic protocols are discussed.

Notes: Abstract The concept of shape space proposed by Perelson and Oster (1979,J. Theor. Biol. 81, 645–670) has been a useful tool for theoretical immunologists, who have invoked it to model idiotypic binding, which plays a significant role in mathematical models of immune networks. The actual construction of such a space from its definition requires specialized experimental information, which is not completely available. In this article, we discuss, with illustrative examples, how graphical representations similar to the idea of shape space can be derived by analyzing real affinity matrices, and the relative merits of such representations to approximations that might be obtained by the approach of Perelson and Oster. We also give directions for future research with a view toward applications.

Notes: Abstract A novel intact circular dsDNA supercoil is proposed as an alternative to the conventional DNA supercoil, so that the two complementary strands of ssDNA circles are separable without any covalent bond breakage. This new structure can be visualized by using two tubings: one black and one clear. Twist the black tubing a number of times and connect its two ends. Do the same for the clear tubing. Then wrap the two tubings together. This forms the separable or novel supercoil. On the other hand, the conventional supercoil can be modeled by twisting the black and clear tubings together and then connect their respective ends, so that the two tubings are not separable unless one of them is cut. Experimentally, in the absence of any enzyme, many intact plasmid dsDNA circles give two bands on agarose gel electrophoresis under a certain given condition, while the same plasmid molecules after cutting once by a restriction enzyme give only one band under the same, condition. In the case of intact pUC19 plasmids, these two bands can then be, recovered and sequenced separately, using two primers in opposite directions. Each band gives mostly one sequence which is complementary to that of the other band. The combination of the above theoretical model and experimental results strongly suggests that there is an alternative structure of DNA which does not have the usual difficulty of unwinding, rewinding and requiring numerous covalent bond breakages and ligations during semiconservative replication.

Notes: Abstract In this paper a mathematical model is developed to describe the migration of labelled particles within a multicell spheroid. In the model, spatial variations in cell proliferation and death create an internal velocity field which leads to redistribution of the labelled and unlabelled cells. By applying a range of numerical and analytical techniques to the model equations, it is possible to show that, whilst the speed with which the labelled cells migrate through the tumour is independent of the type of cells that are labelled, their limiting distribution depends crucially on whether inert polystyrene microspheres or live tumour cells are labelled. These predictions are shown to be in good qualitative agreement with independent experimental results.

Notes: Abstract Human T-cell lymphotropic virus type I (HTLV-I) infection in humans causes a chronic infection of CD4+ T cells, and is associated with various disease outcomes, among them with the development of adult T-cell leukemia (ATL). The T-cell dynamics after HTLV-I infection can be described in a mathematical model with coupled differential equations. The infection process is modeled assuming cell-to-cell infection of CD4+ T cells. The model allows for CD4+ T cell subsets of susceptible, latently infected and actively infected cells as well as for leukemia cells. Latently infected T cells may harbor the virus for several years until they become activated and able to infect susceptible T cells. Uncontrolled proliferation of CD4+ T cells with monoclonal DNA-integration of HTLV-I results in the development of ATL. The model describes basic features that characterize HTLV-I infection; the chronic infection of CD4+ T cells, the increasing number of abnormal cells and the possible progression to ATL.

Notes: Abstract A neighbourhood-based competition model for plant individuals is studied to evaluate how a hierarchical structure related to size may emerge in plant communities. It is shown by numerical simulations and linear stability analysis that many stable states exist in the hierarchical structure when both the total number of individuals and the degree of asymmetry of competition are high. When the hierarchical structures are self-organized by the dynamic instability of the homogeneous state due to non-linearity of competition, it is proved that these states are always locally stable. The relevance of the results to size structures in real plant communities (boreal forests vs tropical and temperate forests) is discussed. This is suggested to be the mechanism responsible for the coexistence of species in plant communities.

Notes: Abstract Phenomenological models represent a simplified approach to the study of complex systems such as host-parasitoid interactions. In this paper we compare the dynamics of three phenomenological models for host-parasitoid interactions developed by May (1978), May and Hassell (1981) and May et al. (1981). The essence of the paper by May and Hassell (1981) was to define a minimum number of parameters that would describe the interactions, avoiding the technical difficulties encountered when using models that involve many parameters, yet yielding a system of equations that could capture the essence of real world interactions in patchy environments. Those studies dealt primarily with equilibrium and coexistence phenomena. Here we study the dynamics through bifurcation analysis and phase portraits in a much wider range of parameter values, carrying the models beyond equilibrium states. We show that the dynamics can be either stable or chaotic depending on the location of a damping term in the equations. In the case of the stable system, when host density dependence acts first, a stable point is reached, followed by a closed invariant curve in phase space that first increases then decreases, finally returning to an asymptotically stable point. Chaos is not seen. On the other hand, when parasitoid attack occurs before host density dependence, chaos is inevitably apparent. We show, as did May et al. (1981) and stated earlier byWang and Gutierrez (1980), that the sequence of events in host-parasitoid interactions is crucial in determining their stability. In a chaotic state the size of the host (e.g., insect pests) population becomes unpredictable, frequently becoming quite large, a biologically undesirable outcome. From a mathematical point of view the system is of interest because it reveals how a strategically placed damping term can dramatically alter the outcome. Our study, reaching beyond equilibrium states, suggests a strategy for biological control different from that of May et al. (1981).

Notes: Abstract In this paper we study the uniform persistence (UP) of an association of two competing host species sharing a directly transmitted macroparasite. Like predators, parasites can regulate UP while the hosts are either coexisting or in a dominance relationship without any infections, but cannot regulate UP in case the hosts are in bistability. The regulatory mechanism depends on the relationships between the parameters, such as host intrinsic growth rate, host carrying capacity, susceptibility, parasite pathogenicity and the magnitude of parasite aggregation. In the case of coexistence the parametric space for UP is more than that for global stability of the host-parasite equilibrium, but is less than that for UP in the case of dominance. In the case of dominance, the parasites can alter the competitive outcome locally or can enhance the local exclusion of the inferior competitor and thus, unlike the predation, parasitism has an beneficial effect over competition. We derive explicitly the range of the values of ratios of the rates of reproduction and survivorship of the hosts, and also of the values of the degree of aggregations, with which macroparasites are not effective in maintaining its beneficial effect over competition. Finally our results support the body-size hypothesis of Price et al. (1988), with possible explanations of certain exceptional examples of the hypothesis.

Notes: Abstract The representation of the shape of a biconcave erythrocyte by a set of three parametric equations was achieved by using the expressions that transform the curvilinear coordinates from the disc-cyclide coordinate system [denoted J2R; Moon and Spencer (1988), Field Theory Handbook, Springer-Verlag, Berlin] to Cartesian coordinates. The equations are products of elliptic functions, so the challenge was to relate the three major ’shape-defining’ measurements of the human erythrocyte in Cartesian coordinates to three parameters in the new curvilinear coordinates, to give a realistic representation of the shape of the membrane-surface. The relationships between the coefficients of the Cartesian degree-4 surface that describes the discocyte and the coordinate transformation equations were derived with the aid of Mathematica; and the membrane-surface of the cell was drawn using the ParametricPlot3D function in this ‘package’. By having the erythrocyte shape expressed in its new form it is readily amenable to further transformations that might be used to model those changes in shape that are seen when the cells are immersed in media of various osmolalities, or when they change metabolic ’states’. On the other hand, the relationship between the coefficients of the Cartesian expression for the disc-cyclide surface is relevant to image analysis of erythrocytes, as determined by physical methods that rely on Cartesian imaging ’slices’. These methods include confocal microscopy and various nuclear magnetic resonance microimaging procedures.

Notes: Abstract A coupled model is presented for simulating physical and biological dynamics in fresh water lakes. The physical model rests upon the assumption that the turbulent kinetic energy in a water column of the lake is fully contained in a mixed layer of variable depth. Below this layer the mechanical energy content is assumed to vanish. Additionally, the horizontal currents are ignored. This one-dimensional two-layered model describes the internal conversion of the mechanical and thermal energy input from the atmosphere into an evolution of the mixed layer depth by entrainment and detrainment mechanisms. It is supposed to form the physical domain in which the simulation of the biological processes takes place. The biological model describes mathematically the typical properties of phyto-and zooplankton, their interactions and their response to the physical environment. This description then allows the study of the behaviour of Lagrangian clusters of virtual plankton that are subjected to such environments. The essence of the model is the dynamical simulation of an arbitrary number of nutrient limited phytoplankton species and one species of zooplankton. The members of the food web above and below affect the model only statically. The model is able to reproduce the typical progression of a predator-prey interaction between phyto-and zooplankton as well as the exploitative competition for nutrients between two phytoplankton species under grazing pressure of Daphnia. It suggests that the influence of the biological system on the physical system results in a weak increase of the surface temperature for coupled simulations, but a considerably higher seasonal thermocline in spring and a lower one in autumn.

Notes: Abstract We investigate the dynamical behaviour of a simple plankton population model, which explicitly simulates the concentrations of nutrient, phytoplankton and zooplankton in the oceanic mixed layer. The model consists of three coupled ordinary differential equations. We use analytical and numerical techniques, focusing on the existence and nature of steady states and unforced oscillations (limit cycles) of the system. The oscillations arise from Hopf bifurcations, which are traced as each parameter in the model is varied across a realistic range. The resulting bifurcation diagrams are compared with those from our previouswork, where zooplankton mortality was simulated by a quadratic function—here we use a linear function, to represent alternative ecological assumptions. Oscillations occur across broader ranges of parameters for the linear mortality function than for the quadratic one, although the two sets of bifurcation diagrams show similar qualitative characteristics. The choice of zooplankton mortality function, or closure term, is an area of current interest in the modelling community, and we relate our results to simulations of other models.

Notes: Abstract The bayesian decomposition of posterior distribution was used to develop a likelihood function to correct bias in the estimates of population parameters from data collected randomly with size-specific selectivity. Positive distributions with time as a parameter were used for parametrization of growth data. Numerical illustrations are provided. The alternative applications of the likelihood to estimate selectivity parameters are discussed.

Notes: Abstract We present a model for the formation of parallel rows of scale cells in the developing adult wing of moths and butterflies. Precursors of scale cells differentiate throughout each epithelial monolayer and migrate into rows that are roughly parallel to the body axis. Grafting experiments have revealed what appears to be a gradient of adhesivity along the wing. What is more, cell adhesivity character is maintained after grafting. Thus we suggest that it is a cell’s location prior to migration that determines its interactions during migration. We use nonlinear bifurcation analysis to show that differential origin-dependent cell adhesion can result in the stabilization of rows over spots.

Notes: Abstract Critical to epithelial cell viability is the homeostasis of cell volume and composition during changes in transcellular transport. In this study, two previously developed mathematical models (principal cell of the collecting duct and proximal tubule cell) are approximated by their linearizations about a reference condition. This yields matrices which estimate cell volume, cell composition, and transcellular fluxes in response to perturbations of bath conditions and membrane transporter activity. These approximations are themselves extended with the inclusion of linear dependence of membrane transport coefficients on cell variables (e.g., volume, solute concentrations, or electrical potential). This provides cell models with variable permeabilities, which may be homeostatic, and which can be examined systematically: sequentially testing each membrane permeability and its controlling cell variable. In the proximal tubule approximation, volume-mediated increases in peritubular K—Cl or Na—3HCO3 cotransport, and volume-mediated decreases in Na,K-ATPase activity are homeostatic; modulation of peritubular K permeability has little impact. In the principal cell model, volume homeostasis is afforded by volume-sensitive peritubular Na/H exchange or Cl− conductance. Predictions from the linear analysis are confirmed in the full models. This approach yields a systematic examination of homeostasis in an epithelial model, and identifies candidate control parameters.

Notes: Abstract The length of an alignment of biological sequences is typically longer than the mean length of its component sequences. (This arises from the insertion of gaps in the alignment.) When such an alignment is used as a profile for the alignment of further sequences (or profiles), it will have a bias toward additional sequences that match the length of the profile, rather than the mean length of sequences in the profile, as the alignment of these well entail fewer (or smaller) insertions) so avoiding gap-penalties). An algorithm is described to correct this bias that entails monitoring the correspondence, for every pair of positions, of the mean separations in both profiles as they are aligned. The correction was incorporated into a standard dynamic programming algorithm through a modification of the gap-penalty, but, unlike other approaches, this modification is not local and takes into consideration the overall alignment of the sequences. This implies that the algorithm cannot guarantee to find the optimal alignment, but tests suggest that close approximations are obtained. The method was tested on protein families by measuring the area in the parameter space of the phase containing the correct multiple alignment. No improvement (increase in phase area) was found with a family that required few gaps to be aligned correctly. However, for highly gapped alignments, a 50% increase in area was obtained with one family and the correct alignment was found for another that could not be aligned with the unbiased method.

Notes: Abstract As in Darwinian evolution, population fitness increases among replicating molecules whose propagation rate coefficients form a normal (symmetric) distribution, even when replication kinetics are fractional order.

Notes: Abstract Single-channel recordings from membrane patches frequently exhibit multiple conductance levels. In some preparations, the steady-state probabilities of observing these levels do not follow a binomial distribution. This behavior has been reported in sodium channels, potassium channels, acetylcholine receptor channels and gap junction channels. A non-binomial distribution suggests interaction of the channels or the presence of channels with different open probabilities. However, the current trace sometimes exhibits single transitions spanning several levels. Since the probability of simultaneous transitions of independent channels is infinitesimally small, such observations strongly suggest a cooperative gating behavior. We present a Markov model to describe the cooperative gating of channels using only the all-points current amplitude histograms for the probability of observing the various conductance levels. We investigate the steady-state (or equilibrium) properties of a system ofN channels and provide a scheme to express all the probabilities in terms of just two parameters. The main feature of our model is that lateral interaction of channels gives rise to cooperative gating. Another useful feature is the introduction of the language of graph theory which can potentially provide a different avenue to study ion channel kinetics. We write down explicit expressions for systems of two, three and four channels and provide a procedure to describe the system ofN channels.

Notes: Abstract A theory has been proposed that encompasses pre-replication changes in RNA synthesis and non-gradual variant formation, in addition to competitive replication. Using a fundamental theorem of natural selection and maximum principle scaled to nucleotide condensation, evolutionin vitro was demonstrated to maximally damp both kinetic and thermodynamic forces driving this reaction, from its pre-replication stage. This led to the finding that evolution follows a path of least action. These principles form the framework for a general theory of evolution, whose scope extends beyond evolution modeled by synthesis of non-interacting RNA molecules. It applies, in particular, to standard processes, such as competitive crystallization. In calculations simulatingde novo formation of self-replicating RNA molecules in the Qβ replicase system, spontaneous changes in strand secondary structure promoted the transition from random copolymerization to template-directed polymerization. This finding indicates selection preceded genome self-propagation. Non-gradual species formation was attributed to the presence of heterogeneous thermodynamic forces. Growth unconstrained by competition follows mutation to a variant able to utilize a free energy source alien to its progenitors. Evolution in a heterogeneous system can, therefore, exhibit discontinuous rates of species formation and spawn new species populations. Natural selection among competing self-propagators thus gives way to a principle of wider scope stating that evolution optimally damps the physicochemical forces causing change within an evolving system.

Notes: Abstract A unified approach is presented for the construction and analysis of models for the dynamics of populations and communities in the presence of temporal variability, vague density dependence, chaos or analytical intractability. The approach is based on comparisons involving simpler models which provide ceilings and floors to the densities predicted by the full models. The method is applied to examples of several types of models, including difference equations, ordinary differential equations, non-linear Leslie matrices and reaction-diffusion equations. The models treated describe various ecological phenomena including self-regulation, competition, predator-prey interactions, age structure and spatial structure. Some results needed for the analysis of matrix models and patch models are given in the Appendix.

Notes: Abstract An essentially new method to relate a number of taxa on the basis of a predefined set of dichotomous properties (i.e. either present or not present) is described. The basic step of the analysis is the derivation of a sophisticated distance measure to describe the pairwise dissimilarities quantitatively on the basis of the individual properties. The presentation of the dissimilarity matrix by a tree-like structure is an obvious step implicated by the the distance measure and is related to the widely used method of successive joining of nearest neighbors with respect to the distances. The distance measure makes no use of stochastic or other mathematical models of evolutionary processes and can be interpreted best in terms of discrete information theory.

Notes: Abstract The olfactory receptor neuron provides a good opportunity to analyze a biophysical model of a single neuron because its dendritic structure is simple and even close to a cylinder in the case of the moth sex-pheromone receptor cell. We have considered this cylindrical case and studied two main problems. First, we were concerned with the effect of the neuron's length on the receptor potential for a constant stimulus-induced conductance change. An analytical solution for the receptor potential was determined by using input, resistances. It was shown that the longer the neuron, the greater its ability to code over a wide range of values of the intensity of the stimulus. Second, we studied numerically the passive backpropagation of action potentials into the dendrite and its influence on the firing frequency. While propagating along the dendrite the action potential decreases in amplitude and its shape becomes rounded. The firing frequency in the model with backpropagation was found to be greater than that obtained analytically in the absence of backpropagation. However, for any given conductance change, when normalized with respect to their maxima, both firing frequencies were found to be very similar over a wide range of parameter values. Therefore, the actual firing rate (with backpropagation) may be approximated by the analytical solution without backpropagation if the actual firing rate for a large conductance change is known.

Notes: Abstract The effect of adding density-dependent migration between nearest neighbour populations of a single discrete-generation species in a chain of habitat fragments is investigated. The larger the population on a particular habitat fragment, the greater the fraction of inhabitants who migrate before reproducing. It has previously been shown for similar models with density-independent migration that coupling populations in this way has no effect on the stability of these populations. Here, it is demonstrated that this effect is also generally true if migration is density-dependent. However, if the migration rate is large enough and has density dependence of the correct form, then the steady state (with all the populations remaining at the same constant value through time) can be destabilised. The conditions for this to occur are obtained analytically. When this “destabilisation” occurs, the system settles down to an alternative steady state where half of the populations take one constant value which is below that of an equivalent isolated system, and the other populations all share a population value which is greater than the steady state of the isolated populations. Once this configuration is reached, the population size on each patch remains constant over time. hence the change might more properly be described as a decrease in homogeneity rather than in stability.

Notes: Abstract Yates-Pardee-type metabolic pathways in a heterogenous cell milieu are modeled as a system of coupled non-linear partial differential equations. A numerical solution to this systmm is described and some properties of such a physiological system are studied. Confinement with and without a membrane is considered and it is shown how confinement results in an increase in the stability of the metabolite concentrations. These results suggest that the enzyme organization may contribute to the stability of the cellular metabolism.

Notes: Abstract Modeling the growth of animals as parts of ecosystems often presumes the existence of an asymptotic weight which, when reached by the individual, stops its further growth. We show that the asymptotic weight is influenced by environmental conditions, and that growth is limited because of a trade-off of foraging costs and gain of feeding. We show that the so-called asymptotic mass is a comprehensive value, which also contains an environmental parameter. We develop our model for organisms of neutral buoyancy in an aquatic environment; for terrestrial and aerial animals it has limited validity only. We discuss examples and derive a critical value for resource availability in a habitat, which informs us whether foraging in that habitat is worthwhile or not.

Notes: Abstract Mathematical models for weed dispersal and control are developed, analyzed and numerically simulated. A model incorporating periodic control, e.g. herbicide application, is derived for a plant population in a spatially homogeneous setting. The model is extended to a spatially heterogeneous population where plant dispersal is incorporated. The dispersal and control model involves integrodifference equations, discrete in time and continuous in space. The models are analyzed to determine values of the control parameter that prevent weed spread. The effects of the control on travelling wave solutions are investigated numerically.

Notes: Abstract The T helper (Th) phenotypes, Th1/Th2, are acquired upon interaction of a naive T helper cell and an antigen presenting cell (APC). Naive T helper cells may differentiate into either phenotype, and the actual outcome is determined by the density and avidity of the antigenic determinants presented by the APC, and the APCs inherent costimulatory properties. Until recently it was thought that differentiation is further affected by cytokines. However, Murphy et al. (1996, J. Exp. Med. 183, 901) have demonstrated that the experimental results, formerly interpreted as Th1/Th2 differentiation, in effect comprise an observation of two consecutive processes. (i) An interaction between naive T cells and APC creates a mixture of mature cells irreversibly committed to Th1 or Th2 phenotype. (ii) Subsequent addition of regulatory cytokines, promotes expansion of one phenotype while suppressing the other. The consequent shift in the per culture production of marker cytokines mimics the appearance of a cellular phenotype switch. We present and analyse a mathematical model that extrapolates these experimental facts into systemic behavior during an immune response. Despite the fact that differentiation produces cells of Th1 and Th2 phenotypes with the same receptor specificity, our results indicate that competition for antigenic stimulation, mediated by the APCs, combines with cytokine mediated cross-suppression between phenotypes to yield a response that is eventually dominated by T helper cells that are uniform in both receptor specificity (clonotype) and in cytokine secretion phenotype.

Notes: Abstract For many years Turing systems have been proposed to account for spatial and spatiotemporal pattern formation in chemistry and biology. We extend the study of Turing systems to investigate the rôle of boundary conditions, domain shape, non-linearities, and coupling of such systems. We show that such modifications lead to a wide variety of patterns that bear a striking resemblance to pigmentation patterns in fish, particularly those involving stripes, spots and transitions between them. Using the Turing system as a metaphor for activator—inhibitor models we conclude that such a mechanism, with the aforementioned modifications, may play a rôle in fish patterning.

Notes: Abstract Calcium plays an essential role in excitation-contraction coupling in muscle, and derangements in calcium handling can produce a variety of potentially harmful conditions, especially in cardiac muscle. In cardiac tissue specialized invaginations of the sarcolemma, called T-tubules, penetrate deep into each sarcomere, and depolarization of the SL leads to an influx of calcium through voltage-sensitive channels in the T-tubules that in turn triggers further calcium release from the sarcoplasmic reticulum via ryanodine-sensitive calcium channels. Under certain conditions, such as elevated external Ca2+, cardiac cells can release calcium from the sarcoplasmic reticulum spontaneously, producing a calcium ’spark’ and propagating traveling waves of elevated Ca2+ concentration, without depolarization of the SL (Wier and Blatter, 1991a, Cell Calcium 12, 241–254; Williams, 1993, Cell Calcium 14, 724–735; Cheng et al., 1993a, Science 262, 740–744). However, under normal resting conditions these potentially harmful waves seldom occur. In this paper we investigate the role of the periodic distribution of ryanodine-sensitive channels in determining whether a spark can trigger a wave, using a modification of the kinetic model proposed by Tang and Othmer, 1994b, Biophys. J. 67, 2223–2235, for calcium-induced calcium release. We show that the spatial localization of these channels near the T-tubules has a significant effect on both wave propagation and the onset of oscillations in this system. Spatial localization provides a possible explanation for the differing effects of various experimental protocols on the system’s ability to propagate a traveling wave.

Notes: Abstract In this paper we give a mathematically precise formulation of an old idea in bacterial taxonomy, namely cumulative classification, where the taxonomy is continuously updated and possibly augmented as new strains are identified. Our formulation is based on Bayesian predictive probability distributions. The criterion for founding a new taxon is given a firm theoretical foundation based on prediction and it is given a clear-cut interpretation. We formulate an algorithm for cumulative classification and apply it to a large database of bacteria belonging to the family Enterobacteriaceae. The resulting taxonomy makes microbiological sense.

Notes: Abstract Classical conditioning is a basic form of associative learning in the animal kingdom. Many paradigmatic features of classical conditioning appear to be conserved throughout species and phyla and are independent of stimulus nature. This paper presents an analysis of trial-based and real-time models of classical conditioning which are mathematical abstractions of the underlying processing principles. Various models are reviewed and in a formal analysis, their capability of simulating and explaining classical conditioning is investigated. Since every existing model fails to simulate some particular conditioning phenomena and since some modelling approaches are not appropriate for detailed mathematical analysis, new model components will be introduced that overcome most of the weaknesses observed in the other models.

Notes: Abstract A method is presented to estimate the minimum viable metapopulation size based on the basic reproductive number R 0 and the expected time to extinction τ E for epidemiological models. We exemplify our approach with two simple deterministic metapopulation models of the patch occupancy type and then proceed to stochastic versions that permit the estimation of the minimum viable metapopulation size.

Notes: Abstract In this paper a general deterministic discrete-time metapopulation model with a finite number of habitat patches is analysed within the framework of adaptive dynamics. We study a general model and prove analytically that (i) if the resident populations state is a fixed point, then the resident strategy with no migration is an evolutionarily stable strategy, (ii) a mutant population with no migration can invade any resident population in a fixed point state, (iii) in the uniform migration case the strategy not to migrate is attractive under small mutational steps so that selection favours low migration. Some of these results have been previously observed in simulations, but here they are proved analytically in a general case. If the resident population is in a two-cyclic orbit, then the situation is different. In the uniform migration case the invasion behaviour depends both on the type of the residents attractor and the survival probability during migration. If the survival probability during migration is low, then the system evolves towards low migration. If the survival probability is high enough, then evolutionary branching can happen and the system evolves to a situation with several coexisting types. In the case of out-of-phase attractor, evolutionary branching can happen with significantly lower survival probabilities than in the in-phase attractor case. Most results in the two-cyclic case are obtained by numerical simulations. Also, when migration is not uniform we observe in numerical simulations in the two-cyclic orbit case selection for low migration or evolutionary branching depending on the survival probability during migration.

Notes: Abstract The purpose of this study was to determine the true intraocular pressure and modulus of elasticity of the human cornea in vivo. The cornea was modeled as a shell, and the equations for the deformations of a shell due to applanating and intraocular pressures were combined to model the behavior of the cornea during applanation tonometry. At certain corneal dimensions called the calibration dimensions, the applanating and intraocular pressures are considered to be equal. This relationship was used to determine the modulus of elasticity of the cornea and the relationship between the applanating and intraocular pressures. The true intraocular pressure (IOPT) was found to be related to Goldmann’s applanating pressure (IOPG) as (IOPT = IOPG/K, where K is a correction factor. For the calibration corneal thickness of 0.52 mm, the modulus of elasticity E in MPa of the human cornea was found to be related to the true intraocular pressure IOPT in mmHg as E = 0.0229IOPT. The generalization of the Imbert—Fick law that takes into account the effect of corneal dimensions and stiffness was found to be given by IOPT = 73.5W/(K A), where W is the applanating weight in gf (gram force) and A is the applanated area in mm2. The calculated true intraocular pressure and modulus of elasticity were found to agree with published experimental results. The mathematical model developed may therefore be used to improve results from applanation tonometry and to estimate the mechanical property of the cornea in vivo.

Notes: Abstract We develop a method to estimate the expected time of survival of a predator population as a function of the size of the habitat island on which it lives and the dynamic parameters of the population and its prey. The model may be thought of either as a patch occupancy model for a structured population or as a model of metapopulation type. The method is applied to a keystone predator species, the neotropical army ant Eciton burchelli. Predictions are made as to how many of the islands and habitat islands in and around Gatun Lake in the Panama Canal, most of which were formed when the canal was dug, can be expected to support such a population today, and these are compared with data.