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  • Articles  (45,607)
  • Springer  (37,774)
  • American Association for the Advancement of Science  (7,833)
  • American Meteorological Society
  • 1995-1999  (45,607)
  • 1990-1994
  • 1999  (21,625)
  • 1995  (23,982)
  • Biology  (45,607)
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  • 1995-1999  (45,607)
  • 1990-1994
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  • 1
    Electronic Resource
    Electronic Resource
    Hypnosis modelling in neural networks (1995)
    Springer
    Bulletin of mathematical biology 57 (1995), S. 1-20 
    Details
    ISSN: 1522-9602
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Mathematics
    Notes: Abstract In the framework of the neural network theory effects similar to hypnotic displays are constructed. They are based on the associative paradigm involving non-linear interaction of excitatory and inhibitory channels with synaptic memory. The non-linearity of long-term memorizing processes may cause effects exhibited by blind spots, which are interpreted as the first stage of hypnosis. More complicated phenomena are discussed in terms of a two-layer network.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02458314
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  • 2
    Electronic Resource
    Electronic Resource
    Dynamics of small autocatalytic reaction networks—II. Replication, mutation and catalysis (1995)
    Springer
    Bulletin of mathematical biology 57 (1995), S. 21-61 
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    ISSN: 1522-9602
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Mathematics
    Notes: Abstract Mutation is introduced into autocatalytic reaction networks. The differential equations obtained are neither of repliator-type nor can they be transformed straightway into a linear equation. Examples of low dimensional dynamical systems —n=2, 3 and 4 — are discussed and complete qualitative analysis is presented. Error thresholds known from simple replication-mutation kinetics with frequency independent replication rates occur here as well. Instead of cooperative transitions or higher order phase transitions the thresholds appear here as supercritical or subcritical bifurcations being analogous to first-order phase transitions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02458315
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  • 3
    Electronic Resource
    Electronic Resource
    Bifurcation and stability analysis of a temperature-dependent mite predator-prey interaction model incorporating a prey refuge (1995)
    Springer
    Bulletin of mathematical biology 57 (1995), S. 63-76 
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    ISSN: 1522-9602
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Mathematics
    Notes: Abstract The non-linear behavior of a differential equations-based predator-prey model, incorporating a spatial refuge protecting a consant proportion of prey and with temperature-dependent parameters chosen appropriately for a mite interaction on fruit trees, is examined using the numerical bifurcation code AUTO 86. The most significant result of this analysis is the existence of a temperature interval in which increasing the amount of refuge dynamically destabilizes the system; and on part of this interval the interaction is less likely to persist in that predator and prey minimum population densities are lower than when no refuge is available. It is also shown that increasing the amount of refuge can lead to population outbreaks due to the presence of multiple stable states. The ecological implications of a refuge are discussed with respect to the biological control of mite pests.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02458316
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  • 4
    Electronic Resource
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    Optimal root/shoot-partitioning of carbohydrates in plants (1995)
    Springer
    Bulletin of mathematical biology 57 (1995), S. 99-107 
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    ISSN: 1522-9602
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Mathematics
    Notes: Abstract In many applications of control theory on plant growth models biomass maximization is postulated to avoid analytically unsolvable problems while fruit maximization is commonly considered to be a more realistic criterion. In a special case, we are able to compare these criteria. Iwasa and Roughgarden (1984,Theor. Pop. Biol. 25, 78–105) have investigated a certain class of plant growth models using a fruit maximization criterion. They proved that, in the vegetative growth period, the organs follow a certain path of balanced growth. We show that this path remains optimal when biomass maximization is postulated. This underlines the importance of the balanced growth path found by Iwasa and Roughgarden. Furthermore, our result suggests that in the vegetative growth period the biomass maximization criterion is a good approximation of fruit maximization. In another theoretical control investigation, Schultzeet al. (1983,Oecologia 58, 169–177) derived a different type of balanced growth path. We apply the theory of Iwasa and Roughgarden to an improved version of the model of Schulzeet al. This leads to a new description of balanced growth between root and shoot that reflects non-linearities in the water uptake process and constitutes an interesting hypothesis for further experimental testing.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02458318
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  • 5
    Electronic Resource
    Electronic Resource
    Ion induced deformation of soft tissue (1995)
    Springer
    Bulletin of mathematical biology 57 (1995), S. 77-98 
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    ISSN: 1522-9602
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Mathematics
    Notes: Abstract In this paper the effects of changing the ion concentration in and around a sample of soft tissue are investigated. The triphasic theory developed by Laiet al. (1990,Biomechanics of Diarthrodial Joints, Vol. 1, Berlin, Springer-Verlag) is reduced to two coupled partial differential equations involving fluid ion concentration and tissue solid deformation. These equations are given in general form for Cartesian, cylindrical and spherical geometries. After solving the two equations quantities such as fluid velocity, fluid pressure, chemical potentials and chemical expansion stress may be easily calculated. In the Cartesian geometry comparison is made with the experimental and theoretical work of Myerset al. (1984,ASME J. biomech. Engng,106, 151–158). This dealt with changing the ion concentration of a salt shower on a strip of bovine articular cartilage. Results were obtained in both free swelling and isometric tension states, using an empirical formula to acount for ion induced deformation. The present theory predicts lower ion concentrations inside the tissue than this earlier work. A spherical sample of tissue subjected to a change in salt bath ion concentration is also considered. Numerical results are obtained for both hypertonic and hypotonic bathing solutions. Of particular interest is the finding that tissue may contract internally before reaching a final swollen equilibrium state or swell internally before finally contracting. By considering the relative magnitude, and also variation throughout the time course of terms in the governing equations, an even simpler system is deduced. As well as being linear the concentration equation in the new system is uncoupled. Results obtained from the linear system compare well with those from the spherical section. Thus, biological swelling situations may be modelled by a simple system of equations with the possibility, of approximate analytic solutions in certain cases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02458317
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  • 6
    Electronic Resource
    Electronic Resource
    Memory capacity in large idiotypic networks (1995)
    Springer
    Bulletin of mathematical biology 57 (1995), S. 109-136 
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    ISSN: 1522-9602
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Mathematics
    Notes: Abstract Many models of immune networks have been proposed since the original work of Jerne [1974,Ann. Immun. (Inst. Pasteur) 125C, 373–389]. Recently, a limited class of models (Weisbuchet al., 1990,J. theor. Biol. 146, 483–499) have been shown to maintain immunological memory by idiotypic network interactions. We examine generalizations of these models when the networks are both large and highly connected to study their memory capacity, i.e. their ability to account for immunization to a large number of random antigens. Our calculations show that in these minimal models, random connectivities with continuously distributed affinities reduce the memory capacity to essentially nil.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02458319
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  • 7
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    A kinetic model of coronary reactive hyperemic response to transient ischemia (1995)
    Springer
    Bulletin of mathematical biology 57 (1995), S. 137-156 
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    ISSN: 1522-9602
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Mathematics
    Notes: Abstract A kinetic model is proposed to delineate the factors that determine the coronary reactive hyperemic response (RHR) to transient ischemia. The model comprises of myocardial-interstitial (M) and vascular (V) compartments. Vasodilator metabolites (VM) are produced in the M compartment during the interval of coronary occlusion. The rate of VM production is dependent on the flow rate during the ischemic period, the ratio of excess flow above the control level (R) to the loss of flow during occlusion period (D), the amount of oxygen stored and the degree of vasodilation in the V compartment prior to occlusion. Following a complete release of occlusion, VM are transported from the M to V compartment and are washed out or degraded with time. The time course of RHR is determined by the coronary patency which is proportional to VM concentration in the V compartment. Based on a set of numerical constants, the model is tested by simulating RHR to the various occlusion manoeuvres: a pair of 10 sec occlusions separated by brief release, a 15 sec release followed by a second brief occlusion, a brief release of an occlusion followed by restriced inflow and a period of restricted inflow after occlusion. The simulated results fit the experimental R/D and RH durations data of canine hearts. Factors that determine the impairment of RH capacity in coronary stenosis are suggested in terms of the model scheme.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02458320
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  • 8
    Electronic Resource
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    Kinetic study of an enzyme-catalysed reaction in the presence of novel irreversible-type inhibitors that react with the product of enzymatic catalysis (1995)
    Springer
    Bulletin of mathematical biology 57 (1995), S. 157-168 
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    ISSN: 1522-9602
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Mathematics
    Notes: Abstract In the present paper a kinetic study is made of the behaviour of a Michaelis-Menten enzyme-catalysed reaction in the presence of irreversible inhibitors rendered unstable in the medium by their reaction with the product of enzymatic catalysis. A general mechanism involving competitive, non-competitive, uncompetitive and mixed irreversible inhibition with one or two steps has been analysed. The differential equation that describes the kinetics of the reaction is non-linear and computer simulations of its dynamic behaviour are presented. The results obtained show that the systems studied here present kinetic co-operativity for a target enzyme that follows the simple Michaelis-Menten mechanism in its action on the substrate, except in the case of an uncompetitive-type inhibitor.
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    URL: http://dx.doi.org/10.1007/BF02458321
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  • 9
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    Book reviews (1995)
    Springer
    Bulletin of mathematical biology 57 (1995), S. 169-173 
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    ISSN: 1522-9602
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Mathematics
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02458322
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  • 10
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    On the estimation of alternative pathways of fatty acid oxidation in the liverIn vivo (1995)
    Springer
    Bulletin of mathematical biology 57 (1995), S. 191-203 
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    ISSN: 1522-9602
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Mathematics
    Notes: Abstract The relative contributions of mitochondrial β-oxidation and peroxisomal β-oxidation and peroxisomal ω-oxidation to the oxidation of a given fatty acidin vivo can be quantitated by an isotopic method. The approach requires infusion of a fatty acid labelled on two specific carbon atoms (e.g. [1-14C] and [11-14C] palmitate) to an isotopic steady state, with subsequent isolation and degradation of an acetylated conjugate as a product of the liver cytosolic acetyl CoA pool and of ketone bodies as a product of the liver mitochondrial acetyl CoA pool.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02460615
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  • 11
    Electronic Resource
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    Correlations of rates of insulin release from islets and plateau fractions for β-cells (1995)
    Springer
    Bulletin of mathematical biology 57 (1995), S. 229-246 
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    ISSN: 1522-9602
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Mathematics
    Notes: Abstract Pancreatic β-cells in intact islets of Langerhans perfused with various glucose concentrations exhibit periodic bursting electrical activity (BEA) consisting of active and silent phases. The fraction of the time spent in the active phase is called the plateau fraction and appears to be strongly correlated with the rate of release of insulin from islets as glucose concentration is varied. Here this correlation is quantified and a theoretical development is presented in detail. Experimental rates of insulin release are correlated with “effective” plateau fractions over a range of glucose concentrations. There are a number of different models for BEA in pancreatic β-cells and a method is developed here to quantify the dependence of a glucose dependent parameter on glucose concentration. As an example, the plateau fractions computed from the Sherman-Rinzel-Keizer model are matched with experimental plateau fractions to obtain a relationship between the model's glucose-dependent parameter, β, and glucose concentration. Knowledge of the relationships between β and glucose concentration and between experimental measurements of rates of insulin release and plateau fractions permits the determination of theoretical rates of insulin release from the model.
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    URL: http://dx.doi.org/10.1007/BF02460617
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  • 12
    Electronic Resource
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    The development of concentration gradients in a suspension of chemotactic bacteria (1995)
    Springer
    Bulletin of mathematical biology 57 (1995), S. 299-344 
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    ISSN: 1522-9602
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Mathematics
    Notes: Abstract When a suspension of bacterial cells of the speciesBacillus subtilis is placed in a chamber with its upper surface open to the atmosphere complex bioconvection patterns are observed. These arise because the cells: (1) are denser than water; and (2) usually swim upwards, so that the density of an initially uniform suspension becomes greater at the top than the bottom. When the vertical density gradient becomes large enough, an overturning instability occurs which ultimately evolves into the observed patterns. The reason that the cells swim upwards is that they are aerotactic, i.e. they swim up gradients of oxygen, and they consume oxygen. These properties are incorporated in conservation equations for the cell (N) and oxygen (C) concentrations, and these are solved in the pre-instability phase of development whenN andC depend only on the vertical coordinate and time. Numerical results are obtained for both shallow- and deep-layer chambers, which are intrinsically different and require different mathematical and numerical treatments. It is found that, for both shallow and deep chambers, a thin boundary layer, densely packed with cells, forms near the surface. Beneath this layer the suspension becomes severely depleted of cells. Furthermore, in the deep chamber cases, a discontinuity in the cell concentration arises between this cell-depleted region and a cell-rich region further below, where no significant oxygen concentration gradients develop before the oxygen is fully consumed. The results obtained from the model are in good qualitative agreement with the experimental observations.
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    URL: http://dx.doi.org/10.1007/BF02460620
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  • 13
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    Topological and phenomenological classification of bursting oscillations (1995)
    Springer
    Bulletin of mathematical biology 57 (1995), S. 413-439 
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    ISSN: 1522-9602
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Mathematics
    Notes: Abstract We describe a classification scheme for bursting oscillations which encompasses many of those found in the literature on bursting in excitable media. This is an extension of the scheme of Rinzel (inMathematical Topics in Population Biology, Springer, Berlin, 1987), put in the context of a sequence of horizontal cuts through a two-parameter bifurcation diagram. We use this to describe the phenomenological character of different types of bursting, addressing the issue of how well the bursting can be characterized given the limited amount of information often available in experimental settings.
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    URL: http://dx.doi.org/10.1007/BF02460633
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  • 14
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    Book reviews (1995)
    Springer
    Bulletin of mathematical biology 57 (1995), S. 499-506 
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    ISSN: 1522-9602
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Mathematics
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02460637
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  • 15
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    Mathematical models for tumour angiogenesis: Numerical simulations and nonlinear wave solutions (1995)
    Springer
    Bulletin of mathematical biology 57 (1995), S. 461-486 
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    ISSN: 1522-9602
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Mathematics
    Notes: Abstract To ensure its sustained growth, a tumour may secrete chemical compounds which cause neighbouring capillaries to form sprouts which then migrate towards it, furnishing the tumour with an increased supply of nutrients. In this paper a mathematical model is presented which describes the migration of capillary sprouts in response to a chemoattractant field set up by a tumour-released angiogenic factor, sometimes termed a tumour angiogenesis factor (TAF). The resulting model admits travelling wave solutions which correspond either to successful neovascularization of the tumour or failure of the tumour to secure a vascular network, and which exhibit many of the characteristic features of angiogenesis. For example, the increasing speed of the vascular front, and the evolution of an increasingly developed vascular network behind the leading capillary tip front (the brush-border effect) are both discernible from the numerical simulations. Through the development and analysis of a simplified caricature model, valuable insight is gained into how the balance between chemotaxis, tip proliferation and tip death affects the tumour's ability to induce a vascular response from neighbouring blood vessels. In particular, it is possible to define the success of angiogenesis in terms of known parameters, thereby providing a potential framework for assessing the viability of tumour neovascularization in terms of measurable quantities.
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    URL: http://dx.doi.org/10.1007/BF02460635
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  • 16
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    Cable analysis of a motor-nerve terminal branch in a volume conductor (1999)
    Springer
    Bulletin of mathematical biology 61 (1999), S. 1-17 
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    ISSN: 1522-9602
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Mathematics
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1006/bulm.1998.0066
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  • 17
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    A mathematical model for simulating virus transport through synthetic barriers (1999)
    Springer
    Bulletin of mathematical biology 61 (1999), S. 113-140 
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    ISSN: 1522-9602
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Mathematics
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1006/bulm.1998.0080
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  • 18
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    Analysis of intra-uterine fluid motion induced by uterine contractions (1999)
    Springer
    Bulletin of mathematical biology 61 (1999), S. 221-238 
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    ISSN: 1522-9602
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Mathematics
    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.
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    URL: http://dx.doi.org/10.1006/bulm.1998.0069
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  • 19
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    Replication potential of cells via the protein kinase C-MAPK pathway: Application of a mathematical model (1999)
    Springer
    Bulletin of mathematical biology 61 (1999), S. 379-398 
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    ISSN: 1522-9602
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Mathematics
    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.
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    URL: http://dx.doi.org/10.1006/bulm.1998.0077
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  • 20
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    Velocity and stability of solitary planar travelling wave solutions of intracellular [Ca]2+ (1999)
    Springer
    Bulletin of mathematical biology 61 (1999), S. 273-301 
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    ISSN: 1522-9602
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Mathematics
    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.
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    URL: http://dx.doi.org/10.1006/bulm.1998.0081
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  • 21
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    Numerical simulations of stochastic circulatory models (1999)
    Springer
    Bulletin of mathematical biology 61 (1999), S. 365-377 
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    ISSN: 1522-9602
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Mathematics
    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.
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    URL: http://dx.doi.org/10.1006/bulm.1998.0094
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  • 22
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    About deterministic extinction in ratio-dependent predator-prey models (1999)
    Springer
    Bulletin of mathematical biology 61 (1999), S. 19-32 
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    ISSN: 1522-9602
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Mathematics
    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.
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    URL: http://dx.doi.org/10.1006/bulm.1998.0072
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  • 23
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    Parkinsonian tremor and simplification in network dynamics (1999)
    Springer
    Bulletin of mathematical biology 61 (1999), S. 157-177 
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    ISSN: 1522-9602
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Mathematics
    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.
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    URL: http://dx.doi.org/10.1006/bulm.1998.0086
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    Computational experience with a parallel algorithm for tetrangle inequality bound smoothing (1999)
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    Bulletin of mathematical biology 61 (1999), S. 987-1008 
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    ISSN: 1522-9602
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    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.
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    URL: http://dx.doi.org/10.1006/bulm.1999.0123
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    Membrane skeleton detachment in spherical and cylindrical microexovesicles (1999)
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    Bulletin of mathematical biology 61 (1999), S. 1019-1030 
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    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.
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    URL: http://dx.doi.org/10.1006/bulm.1999.0128
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    Bulletin of mathematical biology 61 (1999), S. 1209-1210 
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    URL: http://dx.doi.org/10.1006/bulm.1999.0135
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    Controlling chaos in ecology: From deterministic to individual-based models (1999)
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    Bulletin of mathematical biology 61 (1999), S. 1187-1207 
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    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.
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    URL: http://dx.doi.org/10.1006/bulm.1999.0141
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    Persistence in metabolic nets (1999)
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    Bulletin of mathematical biology 61 (1999), S. 573-595 
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    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.
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    Bulletin of mathematical biology 61 (1999), S. 597-600 
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    URL: http://dx.doi.org/10.1006/bulm.1998.0092
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    RNA structures with pseudo-knots: Graph-theoretical, combinatorial, and statistical properties (1999)
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    Bulletin of mathematical biology 61 (1999), S. 437-467 
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    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.
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    A hydrostatic Michell framework supports frog lungs (1999)
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    Bulletin of mathematical biology 61 (1999), S. 683-700 
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    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.
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    Theory of fast neurotransmitter release control based on voltage-dependent interaction between autoreceptors and proteins of the exocytotic machinery (1999)
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    Bulletin of mathematical biology 61 (1999), S. 701-725 
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    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.
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    Bulletin of mathematical biology 61 (1999), S. 799-805 
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    Cellular automaton models for competition in patchy environments: Facilitation, inhibition, and tolerance (1999)
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    Bulletin of mathematical biology 61 (1999), S. 625-649 
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    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.
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    Reaction and diffusion on growing domains: Scenarios for robust pattern formation (1999)
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    Bulletin of mathematical biology 61 (1999), S. 1093-1120 
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    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.
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    On the evolution of pure winner and loser effects: A game-theoretic model (1999)
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    Bulletin of mathematical biology 61 (1999), S. 1151-1186 
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    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.
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    Multiple attractors, saddles, and population dynamics in periodic habitats (1999)
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    Bulletin of mathematical biology 61 (1999), S. 1121-1149 
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    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.
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    Neuronal growth via hybrid system of self-growing and diffusion based grammar rules: I (1995)
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    Bulletin of mathematical biology 57 (1995), S. 205-227 
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    Notes: Abstract The formation of neuronal networks requires axonal growth towards target neutons. A simple set of grammar rules is introduced to describe axonal growth towards target cells situated both at short and long distances from the growing neuron. Growth for short distances is descrbed by growth following the highest gradient of a chemical compound (which is spread by diffusion from the targets). This approach fails to describe long-distance growth, which is addressed by adopting a graph grammar theory for growing trees. With these rules a flexible tool to draw network of neurons by computer can be developed.
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    Interlocking triads of growth control in tumors (1995)
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    Bulletin of mathematical biology 57 (1995), S. 345-366 
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    Notes: Abstract A pair of growth control triads are used to describe coincident tumor growth and liver regeneration after partial hepatectomy. The models are extensions of previous growth control models which describe tumor growth in an unperturbed host (Michelson and Leith, 1991,Bull. math. Biol. 53, 639–656; idem, 1992, Proceedings of the Third International Conference on Communications and Control, Vol. 2, pp. 481–490; idem, 1992,Bull. math. Biol. 55, 993–1011; idem,J. theor. Biol. 169, 327–338). The linkage between the two triads depends upon systemic signals carried by soluble factors, and mathematical descriptors based upon biological first principals are proposed. The sources of the growth factors, their targets and the processing of their signals are investigated. Analyses of equilibrium in the constant coefficients case and simulated growth curves for the dynamic system are presented, and the effects of growth factor-induced mitogenesis and angiogenesis are discussed in particular. A case is made for early and late responses in the coupled control system. The biology of the signal processing paradigm is placed within a new theoretical context and discussed with regard to tumor adaptation, liver differentiation and the development of a tumor hypoxic fraction.
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    Optimal population stabilization and control using the Leslie matrix model (1995)
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    Bulletin of mathematical biology 57 (1995), S. 381-399 
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    Notes: Abstract We consider the problem of optimal stabilization and control of populations which follow the Leslie model dynamics, within state space and control systems theory and methodology. Various types of culling strategies are formulated and introduced into the Leslie model as control inputs, and their effect on global asymptotic stability is investigated. Our new approach provides answers to several unexplored problems. We show that in general it is possible to achieve a desired stable equilibrium population level, through the design of a class ofshifted-proportional stabilizing culling policies. Further, we formulate general non-linear constrained opitmization problems, for obtaining the cost-optimal policy among this generally infinite class of such stabilizing policies. The theoretical findings are illustrated through the solution of the problem over an infinite planning horizon for a numerical example. A comparative study of the costs and dynamic effects of various culling strategies also supports the mathematical results.
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    A data assimilation technique applied to a predator-prey model (1995)
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    Bulletin of mathematical biology 57 (1995), S. 593-617 
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    Notes: Abstract A new approach for data assimilation, which is based on the adjoint method, but allows the computer code for the adjoint to be constructed directly from the model computer code, is described. This technique is straightforward and reduces the chance of introducing errors in the construction of the adjoint code. Implementation of the technique is illustrated by applying it to a simple predator-prey model in a model fitting mode. A series of identical twin numerical experiments are used to show that this data assimilation approach can successfully recover model parameters as well as initial conditions. However, the ease with which these values are recovered is dependent on the form of the model equations as well as on the type and amount of data that are available. Additional numerical experiments show that sufficient coefficient and parameter recoveries are possible even when the assimilated data contain significant random noise. Thus, for biological systems that can be described by ecosystem models, the adjoint method represents a powerful approach for estimating values for little-known biological parameters, such as initial conditions, growth rates, and mortality rates.
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    Building activity and longevity of queenless groups of the Oriental hornet,Vespa orientalis (1995)
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    Bulletin of mathematical biology 57 (1995), S. 441-460 
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    Notes: Abstract The effect of group size on behavioral parameters of the Oriental hornet,Vespa orientalis, was assessed experimentally under laboratory conditions. Hornet groups of various sizes (ranging from 1 to 100 individuals per group) comprised of young individuals (0–24 hr of age) devoid of a queen were placed in artificial breeding boxes (ABBs). The following three quantitative parameters were evaluated: the amount and rate of building as a function of the number of hornets in the group, the rate of oviposition as, related to group size and the longevity of hornets as a function of their group size. The probability for the occurrence of these events was similarly considered and additional behavioral parameters were only assessed qualitatively. Results of this investigation revealed a relation between the three mentioned quantitative behavioral parameters and the number of hornets per group. The number of hornets per group was positively related to the extent of building, the number of cells built by a group is $$2\pi \sqrt {group size} $$ , but negatively related to the rate of building. As for the delay of building, a non-monotone relation was found. The relation between number of hornets per group and the oviposition delay was found to be non-monotone; the number of hornets per group and their longevity were found to be inversely related. Discrepanices were recorded on the very small (1–2 individuals) or very large (100 individuals) hornet groups.
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    Fuzzy classification of nucleotide sequences and bacterial evolution (1995)
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    Bulletin of mathematical biology 57 (1995), S. 527-537 
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    Notes: Abstract A new method for reconstructing evolutionary relationship among bacteria by use of rRNA sequence data is proposed. The method is based on the concept of fuzzy classification of probabilitiesp(i), p(i/j) andp(i/j*) (i=A,G,C,U) of each sequence. The resulting partition tree shares common features of previous works but has some new peculiarities.
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    Bulletin of mathematical biology 57 (1995), S. 619-630 
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    Gyrotaxis: Interaction between algae and flagellates (1995)
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    Bulletin of mathematical biology 57 (1995), S. 631-650 
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    Notes: Abstract We describe the behaviour of motile microorganisms (e.g. flagellates) attracted by “gyrotaxis” to a sinking, non-motile particle (e.g. an algal cell). The model is based on the application of Stokes' solution for the flow field around the settling cell. The volume within which the flagellate is attracted to the sinking particle is determined from the trajectories of the flagellate. The model of gyrotaxis has several applications; these include the colonization of sinking marine snow particles with motile microoganisms and suspension feeding by protozoa.
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    Effect of dimensionality on Lotka-Volterra predator-prey dynamics: Individual based simulation results (1995)
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    Bulletin of mathematical biology 57 (1995), S. 507-526 
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    Notes: Abstract The effect of varying habitat dimensionality on the dynamics of a model predator-prey system is examined using an individual-based simulation. The general results are that in one dimension fluctuations in abundance of prey and predators occur over a large range of spatial scales (extinctions occur over many spatial scales). In two dimensions (and low mobilities of prey and predators) the dynamics become more predictably periodic at local scales and constant at larger scales due to statistical stabilization. In three dimensions, the model can become “phase-locked” with prey and predators displaying oscillations in abundance over large spatial scales.
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    Dicarboxylic acid fluxes during gluconeogenesis. No channelling of mitochondrial oxalacetate (1995)
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    Bulletin of mathematical biology 57 (1995), S. 557-568 
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    Notes: Abstract A rather complete model of the gluconeogenic pathway was used, with the known separate pools of mitochondrial and cytosolic oxalacetate, malate and aspartate. The fumarase, malate dehydrogenase and glutamate oxalacetate transaminase reactions were assumed to be isotopically actively reversible, but none at isotopic equilibrium. Malate was assumed to exchange actively between the mitochondrial and cytosol, while aspartate exchange was more limited, in agreement with the known electrogenic nature of aspartate export from the mitochondria. This model was fit to14C data obtained in hepatocyte studies, and to the whole rat14C data obtained by Heath and Rose (Biochem J. 227, 851–876, 1985). The latter data were easily fit to our model, when a single mitochondrial oxalacetate pool was assumed. However, invoking two mitochondrial oxalacetate pools, as proposed by Heath and Rose, with the oxalacetate formed via pyruvate carboxylase preferentially channelled to gluconeogenesis, could not be fit with the known differences in scrambling in glucose and glutamate produced from L[3-14C]lactate.
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    Mathematical analysis of a proposed mechanism for oscillatory insulin secretion in perifused HIT-15 cells (1995)
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    Bulletin of mathematical biology 57 (1995), S. 569-591 
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    Notes: Abstract Oscillatory secretion of insulin has been observed in many different experimental preparations ranging from pancreatic islets to the whole pancreas. Here we examine the mathematical features underlying a possible model for oscillatory secretion from the perifused, insulin-secreting cell line, HIT-15. The model includes the kinetics of uptake of glucose by GLUT transporters, the rate of glucose metabolism within the cell, and the effect of glucose on the rate of insulin secretion. Putative feedback by insulin on the rate of glucose transport into the cells is treated phenomenologically and leads to insulin oscillations similar to those observed experimentally in HIT cells. The resulting set of ordinary differential equations is simplified by time-scale analysis to a two-variable set of ordinary differential equations. Because of this simplification we can explore, in great detail, the characteristics of the oscillations and their sensitivity to parameter variation using phase plane analysis.
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    Sperm motility in the presence of boundaries (1995)
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    Bulletin of mathematical biology 57 (1995), S. 679-699 
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    Notes: Abstract The fluid dynamics of sperm motility near both rigid and elastic walls is studied using the immersed boundary method. Simulations of both single and interacting organisms are presented. In particular, we find that nearby organisms originally undulating with a 90° phase shift may adjust their relative swimming velocities and phase-lock. Comparisons with previous analytical results are also discussed. The tendency of a near-wall to attract organisms is demonstrated.
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    Contributions of memory B cells to secondary immune response (1995)
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    Bulletin of mathematical biology 57 (1995), S. 713-731 
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    Notes: Abstract The secondary immune response is one of the most important features of immune systems. During the secondary immune response, the immune system can eliminate the antigen, which has been encountered by the individual during the primary invasion, more rapidly and efficiently. Both T and B memory cells contribute to the secondary response. In this paper, we only concentrate on the functions of memory B cells. We explore a model describing the memory contributed by the specific long-lived clone which is maintained by continued stimulation with a small amount of antigens sequestered on the surfaces of the follicular dendritic cells (FDC). The behavior of the secondary response provided by the model can be compared with experimental observations. The model shows that memory B cells indeed play an important role in the secondary response. It is found that a single memory cell in a long-lived clone may not be long-lived. In the present note, the influences of relevant parameters on the secondary response are also explored.
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    Reproduction rate, feeding process, and liebig limitations in cell populations—II (1995)
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    Bulletin of mathematical biology 57 (1995), S. 749-782 
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    Notes: Abstract A biological system consisting of a population of cells suspended in a liquid substrate is considered. The general problem addressed in the paper is the derivation of the kinetic pattern of population growth as a statistical effect of a very large number of elementary interactions between a single cell and the molecules of nutrient in substrate. Solution of the problem is obtained in the form of equation expressing the population growth ratec as a function of substrate concentration,C s. The analytical expression derived is applied to a real bacterial population (Escherichi coli) and kinetic patterns are theoretically computed. The major findings, expressed roughly, without nuances, are: (i) the concentration of nutrient at the cell membrane,C c, can only be equal to either 0 (for theC s below some threshold valueC *) orC s (forC s〉C *); (ii) the Michaelis-Menten-Monod kinetics observed in experiments is an artifact: the pure (not contaminated by foreign factors) dependence ofc onC s is actually such that the functionc=c(C s) has practically linear increase whenC s〈C *, and is constant,c=c(C *)=const, whenC s〉C *; (iii) the Liebig principle is strictly fulfilled: up to a feasible accuracy of observation, under no circumstances can population growth be limited (controlled) by more than one substrate component—replacement of a limiting component for another one is an instant event rather than a gradual process.
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    Idiotypic regulation of B cell differentiation (1995)
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    Bulletin of mathematical biology 57 (1995), S. 841-881 
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    Notes: Abstract We study the equilibrium properties of idiotypically interacting B cell clones in the case where only the differentiation of B cells is affected by idiotypic interactions. Furthermore, we assume that clones may recognize and be stimulated by self antigen in the same fashion as by antiantibodies. For idiotypically interacting pairs of non-autoreactive clones we observe three qualitatively different dynamical regimes. In the first regime, at small antibody production an antibody-free fixed point, the virgin state, is the only attractor of the system. For intermediate antibody production, a symmetric activated state replaces the virgin state as the only attractor of the system. For large antibody production, finally, the symmetric activated state gives way to two asymmetric activated states where one clone suppresses the other clone. If one or both clones in the pair are autoreactive there is no virgin state. However, we still observe the switch from an almost symmetric activated state to two asymmetric activated states. The two asymmetric activated states at high antibody production have profoundly different implications for a self antigen which is recognized by one of the clones of the pair. In the attractor characterized by high autoantibody concentration the self antigen is attacked vigorously by the immune system while in the opposite steady state the tiny amount of autoantibody hardly affects the self antigen. Accordingly, we call the first state the autoimmune state and the second the tolerant state. In the tolerant state the autoreactive clone is down-regulated by its anti-idiotype providing an efficient mechanism to prevent an autoimmune reaction. However, the antibody production required to achieve this anti-idiotypic control of autoantibodies is rather large.
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    The potassium A-current, low firing rates and rebound excitation in Hodgkin-Huxley models (1995)
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    Bulletin of mathematical biology 57 (1995), S. 899-929 
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    Notes: Abstract It is widely believed, following the work of Connor and Stevens (1971,J. Physiol. Lond. 214, 31–53) that the ability to fire action potentials over a wide frequency range, especially down to very low rates, is due to the transient, potassium A-current (I A). Using a reduction of the classical Hodgkin-Huxley model, we study the effects ofI A on steady firing rate, especially in the near-threshold regime for the onset of firing. A minimum firing rate of zero corresponds to a homoclinic bifurcation of periodic solutions at a critical level of stimulating current. It requires that the membrane's steady-state current-voltage relation be N-shaped rather than monotonic. For experimentally based genericI A parameters, the model does not fire at arbitrarily low rates, although it can for the more atypicalI A parameters given by Connor and Stevens for the crab axon. When theI A inactivation rate is slow, we find that the transient potassium current can mediate more complex firing patterns, such as periodic bursting in some parameter regimes. The number of spikes per burst increases asg A decreases and as inactivation rate decreases. We also study howI A affects properties of transient voltage responses, such as threshold and firing latency for anodal break excitation. We provide mathematical explanations for several of these dynamic behaviors using bifurcation theory and averaging methods.
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    Fractals in science (1995)
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    Bulletin of mathematical biology 57 (1995), S. 939-941 
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    Coping with chaos: Analysis of chaotic data and the exploitation of chaotic systems (1995)
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    Bulletin of mathematical biology 57 (1995), S. 945-946 
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    Book review (1999)
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    Bulletin of mathematical biology 61 (1999), S. 207-208 
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    Modelling the internalization of labelled cells in tumour spheroids (1999)
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    Bulletin of mathematical biology 61 (1999), S. 601-623 
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    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.
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    Book reviews (1999)
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    Bulletin of mathematical biology 61 (1999), S. 1009-1013 
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    Modeling the T-cell dynamics and pathogenesis of HTLV-I infection (1999)
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    Bulletin of mathematical biology 61 (1999), S. 935-947 
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    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.
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    Size hierarchy and stability in competitive plant populations (1999)
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    Bulletin of mathematical biology 61 (1999), S. 949-961 
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    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.
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    Comparative dynamics of three models for host-parasitoid interactions in a patchy environment (1999)
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    Bulletin of mathematical biology 61 (1999), S. 141-155 
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    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).
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    Effects of parasitism over two competing host populations leading to persistence (1999)
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    Bulletin of mathematical biology 61 (1999), S. 179-205 
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    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.
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    Parametric-equation representation of biconcave erythrocytes (1999)
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    Bulletin of mathematical biology 61 (1999), S. 209-220 
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    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.
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    A physical-biological coupled model for algal dynamics in lakes (1999)
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    Bulletin of mathematical biology 61 (1999), S. 239-272 
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    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.
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    Zooplankton mortality and the dynamical behaviour of plankton population models (1999)
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    Bulletin of mathematical biology 61 (1999), S. 303-339 
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    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.
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    Use of Bayes theorem to correct size-specific sampling bias in growth data (1999)
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    Bulletin of mathematical biology 61 (1999), S. 355-363 
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    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.
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    Probability density functions useful for parametrization of heterogeneity in growth and allometry data (1999)
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    Bulletin of mathematical biology 61 (1999), S. 1015-1016 
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    Pattern formation of scale cells in lepidoptera by differential origin-dependent cell adhesion (1999)
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    Bulletin of mathematical biology 61 (1999), S. 807-828 
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    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.
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    Modeling epithelial cell homeostasis: Steady-state analysis (1999)
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    Bulletin of mathematical biology 61 (1999), S. 1065-1091 
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    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.
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    On the allometric growth of tissues in fruits (1995)
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    Bulletin of mathematical biology 57 (1995), S. 487-498 
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    Notes: Abstract This paper deals with the relative growth of three different fruit tissues. Their morphogenetic periods and the mathematical constraints involved are described, and more precisely, the paper shows an allometric relationship (Y=nX m ) between the widths (X, Y) of the main tissues in stone fruits such as cherries, peaches and prunes. The mathematical relationships between the growth of the mesocarp and of the endocarp of somePrunus fruits are described, and it is proved that before the formation of the embryo, growth is allometric, in agreement with conclusions drawn from some experimental data. However, according to another study, the growth of the mesocarp and of the endocarp are ruled by autocatalytic and monomolecular functions, before as well as after the formation of the embryo. In this case, it is proved that if allometry exits in stone fruits, it can only be anantiometry (m=−1). To solve the dilemma, two main alternatives are proposed and discussed. We conclude that, while allometry is established on reasonable grounds before the formation of the embryo, after the formation of the embryo the mesocarp and endocarp evolve independently since a center for the coordination of growth no longer exists, and each tissue can grow according to its own independent rules.
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    Reliable segmentation by successive bifurcation (1995)
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    Bulletin of mathematical biology 57 (1995), S. 539-556 
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    Notes: Abstract In many organisms, a reliable number of segments is produced even though important properties of the region involved, especially its size at the time of pattern formation, are apparently not specified with sufficient precision. We show that this can be readily accomplished if segmentation occurs through a sequence of bifurcations rather than all at once, and we provide evidence from developmental studies that indicates that this is typically what actually occurs. Our results strongly suggest that where patterns are formed reliably, this generally happens in stages rather than by the setting up in advance of a complete prepattern.
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    Perturbation of a circadian rhythm by single and periodic signals and its mathematical simulation (1995)
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    Bulletin of mathematical biology 57 (1995), S. 175-189 
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    Notes: Abstract Adaptive characteristics of circadian rhythm are based on their capacity to be synchronized by external signals, particularly light signals. The effect of both single and periodic light signals on the electroretinogram (ERG) circadian rhythm in crayfish is studied. In a previous work (Lara-Aparicioet al., Bull math. Biol. 55, 97–110, 1993) we developed a mathematical model simulating the emergence of the ERG circadian rhythm during the ontogeny of the crayfish. In the present work we have tested the familiar wave-shift behaviour of an oscillator with a single limit cycle. Two new facts, not present in a simpler model, now appear, which simulate adequately the experimental results, i.e. the presence of a transient stage and the shape of the perturbed wave which changes according to the characteristics of the external light signals.
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    Dynamical behaviour of biological regulatory networks—I. Biological role of feedback loops and practical use of the concept of the loop-characteristic state (1995)
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    Bulletin of mathematical biology 57 (1995), S. 247-276 
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    Notes: Abstract In the field of biological regulation, models dictated by expreimental work are usually complex networks comprising intertwined feedback loops. In this paper the biological roles of individual positive loops (multistationarity, differentiation) and negative loops (homeostasis, with or without oscillations, buffering of gene dosage effect) are discussed. The relationship between feedback loops and steady states is then clarified, and the problem: “How can one conveniently disentangle complex networks?” is then considered. Initiated long ago, logical descriptions have been generalized from various viewpoints; these developments are briefly discussed. The recent concept of the loop-characteristic state, defined as the logical state located at the level of the thresholds involved in the loop, together with its application, are then presented. Biological applications are also discussed.
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    Five surprising properties of parsimoniously colored trees (1995)
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    Bulletin of mathematical biology 57 (1995), S. 367-375 
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    Notes: Abstract Trees with a coloration of their leaves have an induced “length” which forms the basis of the widely used maximum parsimony method for reconstructing evolutionary trees in biology. Here we describe five unexpected properties of this length function, including refinements of earlier results.
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    Dynamical behaviour of biological regulatory networks—II. Immunity control in bacteriophage lambda (1995)
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    Bulletin of mathematical biology 57 (1995), S. 277-297 
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    Notes: Abstract A number of bacterial and viral genes take part in the decision between lysis and lysogenization in temperate bacteriophages. In the lambda case, at least five viral genes (cI, cro, cII, N and cIII) and several bacterial genes are involved. Several attempts have been made to model this complex regulatory network. Our approach is based on a logical method described in the first paper of the series which formalizes the interactions between the elements of a regulatory network in terms of discrete variables, functions and parameters. In this paper two models are described and discussed, the first (two-variable model) focused on cI and cro interactions, the second (four-variable model) considering, in addition, genes cII and N. The treatment presented emphasizes the roles of positive and negative feedback loops and their interactions in the development of the phage. The role of the loops between cI and cro, and of cI on itself (which both have to be positive loops) was discovered earlier; this group's contribution to this aspect mainly deals with the possibility of treating these loops as parts of a more extended network. In contrast, the role of the negative loop of cro on itself had apparently remained unexplained. We realized that this loop buffers the expression of genes cro itself, cII, O and P against the inflation due to the rapid replication of the phage. More generally negative auto-control of a gene appears an efficient way to render its expression insensitive (or less sensitive) to gene dosage, whereas a simple negative control would not provide this result.
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    Phyllotaxis: A systemic study in plant morphogenesis (1995)
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    Bulletin of mathematical biology 57 (1995), S. 377-379 
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    The stabilizing role of cannibalism in a predator-prey system (1995)
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    Bulletin of mathematical biology 57 (1995), S. 401-411 
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    Notes: Abstract Cannibalism can have a stabilizing effect in a predator-prey system. Contrary to the intuitive expectation cannibalism of the predator leads to an increase of the standing stocks of both, prey and predator.
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    A universal bifurcation diagram for seasonally perturbed predator-prey models (1995)
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    Bulletin of mathematical biology 57 (1995), S. 701-712 
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    Notes: Abstract The bifurcations of a periodically forced predator-prey model (the chemostat model), with a prey feeding on a limiting nutrient, are numerically detected with a continuation technique. Eight bifurcation diagrams are produced (one for each parameter in the model) and shown to be topologically equivalent. These diagrams are also equivalent to those of the most commonly used predator-prey model (the Rosenzweig-McArthur model). Thus, all basic modes of behavior of the two main predator-prey models can be explained by means of a single bifurcation diagram.
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    A theoretical explanation of “Concomitant resistance” (1995)
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    Bulletin of mathematical biology 57 (1995), S. 733-747 
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    Notes: Abstract Concomitant resistance is a tumor growth dynamic which results when the growth of a second tumor implant is inhibited by the presence of the first. Recently, we modeled tumor growth in the presence of a regenerating liver after partial hepatectomy (Michelson and Leith,Bull. Math. Biol. 57, 345–366, 1995), with an interlocking pair of growth control triads to account for the accelerated growth observed in both tissues. We also modeled tumor dormancy and recurrence as a dynamic equilibrium achieved between proliferating and quiescent subpopulations. In this paper those studies are extended to initially model the concomitant resistance case. Two interlocking model systems are proposed. In one an interactive competition between the tumor implants is described, while in the other purely proportional growth inhibition is described. The equilibria and dynamics of each system when the coefficients are held constant are presented for three subcases of model parameters. We show that the dynamic called concomitant resistance can be real or apparent, and that if the model coefficients are held constant, the only way to truly achieve concomitant resistance is by forcing one of the tumors into total quiescence. If this is the true state of the inhibited implant, then a non-constant recruitment signal is required to insure regrowth when the inhibitor mass is excised. We compare these theoretical results to a potential explanation of the phenomenon provided by Prehn (Cancer Res. 53, 3266–3269, 1993).
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    The mathematics of radiation target analyses (1995)
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    Bulletin of mathematical biology 57 (1995), S. 883-898 
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    Notes: Abstract Radiation target theory has been extended to complex biochemical systems. Mathematical analyses are presented for multiple forms of biological active proteins, for the presence of large inhibitors or activators, for compounds which regulate rate or affinity and for multipe-step reactions. Several predictions of these models have been verified experimentally.
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    Theoretical models in biology: The origin of life, the immune system, and the brain (1995)
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    Bulletin of mathematical biology 57 (1995), S. 935-937 
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    Chaos in dynamical systems (1995)
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    Bulletin of mathematical biology 57 (1995), S. 943-944 
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    Models for embryonic periodicity (1995)
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    Bulletin of mathematical biology 57 (1995), S. 947-948 
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    Density and diffusion limited aggregation in membranes (1995)
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    Bulletin of mathematical biology 57 (1995), S. 651-677 
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    Notes: Abstract Aggregation of membrane molecules is a crucial phenomenon in developing organisms, a classic example being the aggregation of post-synaptic receptors during synaptogenesis. Our understanding of the molecular events involved is improving, but most models of the aggregation or concentration process do not address binding events on the molecular level. An exception is the study of diffusion limited aggregation, in which the aggregation process is simulated on a molecular level. In this analysis, however, important physical parameters such as molecular size, diffusion constant and initial density are not addressed. Thus no predictions about the rate at which such aggregates will form is possible. In the present work the model of diffusion limited aggregation is extended to incorporate these parameters and make the corresponding predictions.
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    An alternative derivation of Fuxman's threshold result (1995)
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    Bulletin of mathematical biology 57 (1995), S. 783-786 
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    Building a structured model of a complex pharmacokinetic system with time delays (1995)
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    Bulletin of mathematical biology 57 (1995), S. 787-808 
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    Notes: Abstract This paper presents a description of the procedure for building a structured model of a complex pharmacokinetic system on using its transfer function. The example employed is that of the pharmacokinetic system based on gentamicin plasma concentrations after intravenous and intratracheal administration to guinea pigs, describing the pathway of the drug into the systemic circulation after the extravascular injection mentioned. The structured model selected consisted of a submodel of a proportional linear subsystem, two submodels of simple linear dynamic subsystems with time constants of 0.135±0.065 hr (95% I.C.) and 0.052±0.288 hr, submodels of parallel subsystems with time delays of 0.254±0.046 hr and 1.135±0.288 hr, connected in serial. Two estimates of the mean residence time of the total amount of gentamicin in the system, i.e. 0.347 and 0.335 hr, were obtained, based on the system frequency and structured model, respectively. From the methodological point of view, our paper demonstrates the efficiency of combination of modelling in the frequency and in the time domain, designed to facilitate studies of pharmacokinetic systems.
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    Deduction of pulmonary microvascular hematocrit from indicator dilution curves (1995)
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    Bulletin of mathematical biology 57 (1995), S. 931-933 
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    Dynamics and bifurcations of two coupled neural oscillators with different connection types (1995)
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    Bulletin of mathematical biology 57 (1995), S. 809-840 
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    Notes: Abstract In this paper we present an oscillatory neural network composed of two coupled neural oscillators of the Wilson-Cowan type. Each of the oscillators describes the dynamics of average activities of excitatory and inhibitory populations of neurons. The network serves as a model for several possible network architectures. We study how the type and the strength of the connections between the oscillators affect the dynamics of the neural network. We investigate, separately from each other, four possible connection types (excitatory→excitatory, excitatory→inhibitory, inhibitory→excitatory, and inhibitory→inhibitory) and compute the corresponding bifurcation diagrams. In case of weak connections (small strength), the connection of populations of different types lead to periodicin-phase oscillations, while the connection of populations of the same type lead to periodicanti-phase oscillations. For intermediate connection strengths, the networks can enter quasiperiodic or chaotic regimes, and can also exhibit multistability. More generally, our analysis highlights the great diversity of the response of neural networks to a change of the connection strength, for different connection architectures. In the discussion, we address in particular the problem of information coding in the brain using quasiperiodic and chaotic oscillations. In modeling low levels of information processing, we propose that feature binding should be sought as a temporally coherent phase-locking of neural activity. This phase-locking is provided by one or more interacting convergent zones and does not require a central “top level” subcortical circuit (e.g. the septo-hippocampal system). We build a two layer model to show that although the application of a complex stimulus usually leads to different convergent zones with high frequency oscillations, it is nevertheless possible to synchronize these oscillations at a lower frequency level using envelope oscillations. This is interpreted as a feature binding of a complex stimulus.
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    Life in moving fluids: The physical biology of Flow (1995)
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    Bulletin of mathematical biology 57 (1995), S. 949-951 
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    Th1/Th2 differentiation and cross-regulation (1999)
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    Bulletin of mathematical biology 61 (1999), S. 403-436 
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    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.
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    A two-dimensional numerical study of spatial pattern formation in interacting Turing systems (1999)
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    Bulletin of mathematical biology 61 (1999), S. 483-505 
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    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.
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    The effect of heterogeneously-distributed RyR channels on calcium dynamics in cardiac myocytes (1999)
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    Bulletin of mathematical biology 61 (1999), S. 651-681 
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    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.
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    Bayesian predictive identification and cumulative classification of bacteria (1999)
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    Bulletin of mathematical biology 61 (1999), S. 85-111 
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    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.
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    Models of classical conditioning (1999)
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    Bulletin of mathematical biology 61 (1999), S. 33-83 
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    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.
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    Book reviews (1999)
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    Bulletin of mathematical biology 61 (1999), S. 399-401 
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    Threshold parameters and metapopulation persistence (1999)
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    Bulletin of mathematical biology 61 (1999), S. 341-353 
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    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.
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    Evolution of migration in a metapopulation (1999)
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    Bulletin of mathematical biology 61 (1999), S. 531-550 
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    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.
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    Determination of the true intraocular pressure and modulus of elasticity of the human cornea in vivo (1999)
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    Bulletin of mathematical biology 61 (1999), S. 551-572 
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    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.
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    A model of survival times for predator populations: The case of the army ants (1999)
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    Bulletin of mathematical biology 61 (1999), S. 469-482 
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    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.
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    Bursting, chaos and birhythmicity originating from self-modulation of the inositol 1,4,5-trisphosphate signal in a model for intracellular Ca2+ oscillations (1999)
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    Bulletin of mathematical biology 61 (1999), S. 507-530 
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    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Mathematics
    Notes: Abstract We investigate the various types of complex Ca2+ oscillations which can arise in a model based on the mechanism of Ca2+-induced Ca2+ release (CICR), that takes into account the Ca2+-stimulated degradation of inositol 1,4,5-trisphosphate (InsP3) by a 3-kinase. This model was previously proposed in the course of an investigation of plausible mechanisms capable of generating complex Ca2+ oscillations (Borghans et al., 1997). Besides simple periodic behavior, this model for cytosolic Ca2+ oscillations in nonexcitable cells shows complex oscillatory phenomena like bursting or chaos. We show that the model also admits a coexistence between two stable regimes of sustained oscillations (birhythmicity). The occurrence of these various modes of oscillatory behavior is analysed by means of bifurcation diagrams. Complex oscillations are characterized by means of Poincaré sections, power spectra and Lyapounov exponents. The results point to the role of self-modulation of the InsP3 signal by 3-kinase as a possible source for complex temporal patterns in Ca2+ signaling.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1006/bulm.1999.0095
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