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  • Springer  (139,107)
  • 2015-2019
  • 1985-1989  (52,321)
  • 1980-1984  (86,786)
  • 1986  (52,321)
  • 1982  (44,622)
  • 1980  (42,164)
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  • 2015-2019
  • 1985-1989  (52,321)
  • 1980-1984  (86,786)
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  • 1
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    Bulletin of mathematical biology 42 (1980), S. 131-135 
    ISSN: 1522-9602
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Mathematics
    Notes: Abstract The theory of complementary variational principles is used to obtain maximum and minimum principles for diffusion problems with Michaelis-Menten kinetics. In an illustrative calculation we obtain an extremely accurate variational solution in good agreement with the numerical solution of McElwain (1978).
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  • 2
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    Bulletin of mathematical biology 42 (1980), S. 137-141 
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  • 3
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    Bulletin of mathematical biology 42 (1980), S. 181-189 
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    Notes: Abstract Necessary and sufficient conditions for primitivity of a product of two Leslie matrices are given. Such a product could be used in modeling the growth of a population governed alternately by two different sets of fertility and survival parameters.
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  • 4
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    Bulletin of mathematical biology 42 (1980), S. 173-180 
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    Notes: Abstract Zadeh's transfer function method for linear time-variable systems is used to apply frequency-domain analysis to a periodically time-varying elastance model of the left ventricle. Left ventricular pressure computed from the system function of the time-varying elastance and the phasors of aortic flow shows a typical waveform of the measured ventricular pressure.
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    Bulletin of mathematical biology 42 (1980), S. 901-901 
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  • 6
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    Bulletin of mathematical biology 48 (1986), S. 29-57 
    ISSN: 1522-9602
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    Notes: Abstract Approximate equations for epithelial solute and water transport have been combined with the relations of mass conservation to yield a single differential equation representing volume flow along the proximal tubule. This flow equation is first order, quasilinear and may be integrated directly. For the steady state, the result is an implicit relation between volume flow and distance along the tubule. For two time-dependent problems (step change of tubule inlet velocity or osmolality) the trajectories (distance as a function of transit time) of a fluid element starting at the inlet are obtained. Differentiation of the steady-state relation with respect to the inlet velocity yields a first-order differential equation relating inlet and outlet velocity. This equation is considered in detail, particularly with regard to the influence of solute-linked water reabsorption. Model calculations with parameters representing rat proximal tubule indicate that it will be difficult to discern coupled water flux in this epithelium from only outlet and inlet flows. Calculations using lower transport rates and lower permeabilities suggest that this equation may be useful in quantifying coupled water flow in proximal tubules from other species.
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  • 7
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    Bulletin of mathematical biology 48 (1986), S. 105-105 
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  • 8
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    Bulletin of mathematical biology 48 (1986), S. I 
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    Bulletin of mathematical biology 48 (1986), S. 97-103 
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    Notes: Abstract The branching characteristic of the arterial system is such that blood pressure pulses propagate with minimum loss. This characteristic depends on the geometric and elastic properties of branching vessels. In the current investigation, mathematical relations of branching geometry and elastic properties are formulated and their relative contributions to pulse reflection at an arterial junction are analyzed. Results show that alteration of pulse transmission through the junction is more significantly affected by changes in branching vessel radii and wall thickness than by corresponding percentage changes in vessel wall elastic moduli.
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    Bulletin of mathematical biology 48 (1986), S. 125-136 
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    Notes: Abstract Galerkin's finite element-Laplace transform technique (GAFELTTE) has been used to study transient temperature distribution in human skin and subcutaneous tissues. This study incorporates heat conduction, heat carried by perfusion of blood in the capillary beds and metabolic heat generation in the tissues. Different values of various quantities have been considered in all three parts, namely epidermis, dermis and subcutaneous tissues, depending on physiological considerations. The GAFELTTE provides interface temperatures for a wide range of the values of skin surface temperatures. These values have been used to obtain temperature profiles in the region considered. Steady-state temperature distribution has been deduced from the solution obtained by GAFELTTE and has been compared with the results obtained by using different methods.
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    Bulletin of mathematical biology 48 (1986), S. 137-148 
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    Notes: Abstract Necessary and sufficient conditions are given for three equilibria to occur in a predatorprey model and conditions are given for two of these to be stable. The existence of two stable equilibria requires predator intraspecific competition for either space or food, and the lower the prey growth rate the stronger this predator self-regulation must be. A prey growth rate that is skewed to the right, the ability of a few predators to survive at low prey densities, and predators with high searching effectiveness, long handling times, and large maximum per capita rate of increase all make two stable equilibria more likely.
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    Bulletin of mathematical biology 48 (1986), S. 107-124 
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    Notes: Abstract Drawing evidence from a variety of cardiovascular studies on the heart rate in homeothermic animals, the author establishes the following thesis. The servocontrol (i.e. the autonomic and reflex control) by the medulla oblongata of the heart (rate) is a negative feedback dynamic which is isomorphic (i.e. ‘diffeomorphic’) to the dyamic underlying the heat rate control in those animals (cf. Kuyk,Bull. math. Biol. 46, 81–102, 1984). In fact, unlike in the heat rate case, the qualitative evidence supporting this thesis can not be fully complemented by quantitative data stemming from experiments, because of a lack of pertinent experiments—which, indeed, should measuresimultaneously the heart rate state parameter and thefour control parameters at the input side of the medulla. The results of some of the existing experiments on animal preparations can nevertheless be adduced to recognize that this dynamic can be graphed by the five-dimensional butterfly catastrophe type. The theory leads to new ways of looking at experiments in the field and/or setting up such experiments in the future.
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  • 13
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    Notes: Abstract A model based upon minimization of surface energy is proposed as an explanation for compaction and internalization of cells during mammalian embryo development. The model is used to simulate and graphically display these phenomena on a computer.
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    Bulletin of mathematical biology 48 (1986), S. 197-211 
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    Notes: Abstract This paper describes a growth model for binary topological trees. The model defines the branching probability of all segments in the tree. The branching probability of a segment is formulated as a function of two variables, one indicating its type (intermediate or terminal), the other representing its order, i.e. the topological distance to the root segment. The function is determined by two parameters, namely the ratio of branching probabilities of intermediate and terminal segments and the strength of the order dependency, implemented in an exponential form. Expressions are derived for the calculation of symmetry properties of the partitions and it is indicated which part of the parameter domain results in predominantly symmetrical trees.
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    Bulletin of mathematical biology 48 (1986), S. 213-228 
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    Notes: Abstract The problem of cellular differentiation and consequent pattern generation during embryonic development has been mathematically investigated with the help of a reaction-diffusion model. It is by now a well-recognized fact that diffusion of micromolecules (through intercellular gap junctions), which is dependent on the spatial parameter (r), serve the purpose of ‘positional information’ for differentiation. Based on this principle the present model has been constructed by coupling the Goodwin-type equations for RNA and protein synthesis with the diffusion process. The homogeneous Goodwin system can exhibit stable periodic solution if the value of the cooperativity as measured by the Hill coefficient (ρ) is greater than 8, which is not biologically realistic. In the present work it has been observed that inclusion of a negative cross-diffusion can drive the system into local instability for any value of ρ and thus a time-periodic spatial solution is possible around the unstable local equilibrium, eventually leading to a definite pattern formation. Inclusion of a negative cross-diffusion thus makes the system biologically realistic. The cross-diffusion can also give rise to a stationary wave-like dissipative structure.
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    Bulletin of mathematical biology 48 (1986), S. I 
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  • 17
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    Notes: Abstract A nes software system is described for building simulation programs on micro- and minicomputers. Model equations are written as C subroutines, compiled and linked to the SCoP package to produce a menu-driven, interactive program. The system maintains a database of names, values, and units for all model parameters and variables. Run-time options include several methods for interactive parameter modification and both graphic and tabular outputs, with output values presented as they are calculated. Simulation output values can be compared with experimental data graphically and a companion program SCoPFit is provided for formal optimization of parameter values.
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    Bulletin of mathematical biology 48 (1986), S. 455-468 
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    Notes: Abstract We consider the existence and global stability of aq-member equilibrium (1≤q≤n) in partially closed food-chains of lengthn having an abiotic component as resource. We observe that such existence demands bounds of resource supply rate and these bounds are weighted sums of interaction coefficients. Particular results of global sector-stability of partially feasible equilibria of simple food-chains obeying Lotka-Volterra dynamics are shown. Lastly the elasticity of such food-chains when a new species is introduced at the highest trophic level is investigated.
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    Bulletin of mathematical biology 48 (1986), S. 485-492 
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    Notes: Abstract Criteria are established for three classes of models of single-species dynamics with a single discrete delay to have a globally asymptotically stable positive equilibrium independent of the length of delay.
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    Bulletin of mathematical biology 48 (1986), S. 493-508 
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    Notes: Abstract The main concern of this paper is with survival or extinction of predators in models of predator-prey systems exhibiting group defence of the prey. It is shown that if there is no mutual interference among predators, enrichment could result in their extinction. However, if there is mutual interference, the predator population survives (at least deterministically).
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    Bulletin of mathematical biology 48 (1986), S. 509-523 
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    Notes: Abstract In this paper a general class of semi-Markov compartmental systems is studied. Two models for different input processes are analysed. Attention has been paid to the recurrence times associated with each compartment and to the distribution of the number of particles in each compartment. As an example, a three-compartment system is discussed to study the movement between three health states of patients with chronic diseases.
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    Bulletin of mathematical biology 48 (1986), S. 569-583 
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    Notes: Abstract A strategy is presented for searching the gene and protein sequence data banks which combines the use of two previously described algorthms. The implementation of this strategy is thoroughly evaluated with respect to sensitivity, specificity and speed. The establishment of standard benchmarks for comparing programs that rearch the sequence data banks for homology is proposed.
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    Bulletin of mathematical biology 48 (1986), S. 545-567 
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    Notes: Abstract During functional linkage, ligand receptors are coupled to other receptors and to the cell's metabolic-transport apparatus. The linkage guides the cellular processing of matter, energy and information. Previous conceptions of functional linkage have used the ideas of classical physics appropriate to macroscopic objects. This study presents an initial quantum mechanical model of functional linkage in the case of ligands moving through lipid bilayers and hydrophilic transmembrane channels (‘pores’) of molecular dimensions. On the basis of permeability data, energy surfaces consisting of piecewise-constant potential regions are used to model the lipid bilayers and transmembrane channels. The centre-of-mass wavefunction for a ligand on such energy surfaces is analysed and the permeability coefficients calculated from the wavefunction's transmission characteristics. It is found that quasi-bound states in the several ligand-binding regions of a bilayer or pore system can functionally link to facilitate the passage of the molecule across the permeability barrier. Appearance of the linkage is a sensitive function of the ligand's energy. If the centre-of-mass energies are distributed as in a thermalized fluid, the flux via the quantum functional linkage can equal or exceed that of a classical flux for proton transport through rigid pores in which the intrasite barriers are relatively high (0.25–1 eV) and narrow (0.1–1 Å). The functional linkage plays a less important role in bilayer (rather than pore) energy surfaces and at higher molecular weights. If the ligand-receptor interaction is accompanied by energy transfer to or from ligands, the flux via the quantum functional linkage can equal or exceed the classically expected flux at all relevant ligand molecular weights. These findings are discussed in relation to earlier work and the limitations of the model emphasized.
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    Bulletin of mathematical biology 48 (1986), S. 617-632 
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    Notes: Abstract A new measure of subalignment similarity is introduced. Specifically, similaritys(l,c) is defined as the logarithm to the basep of the probability of findingc or fewer mismatches in a subalignment of lengthl, wherep is the probability of a match. Previous algorithms can not use this measure to find locally optimal subalignments because, unlike Needleman-Wunsch and Sellers similarities, this measure is nonlinear. A new pattern recognition algorithm is described for finding all locally optimal subalignments of two nucleotide sequences. The DD algorithm can uses(l, c) or any other reasonable similarity function to assess the relative interest of subalignments. The DD algorithm searches only the diagonal graph, which lacks insertions and deletions. This search strategy greatly decreases the computation time and does not require an arbitrary choice of gap cost. The paths of the resulting DD graph usually draw attention to likely locations for insertions and deletions. A heuristic formula is derived for estimating significance levels fors(l, c) in the context of the lengths of the two aligned sequences. The DD algorithm has been used to find interesting subalignments between the nucleotide sequences for human and murine interleukin 2.
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    Bulletin of mathematical biology 44 (1982), S. 1-15 
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    Notes: Abstract A theorem is proved, concerning expected values of a multitype branching process in a varying environment. The consequence of the theorem is that the branching process can be treated (in the sense of expected values) as a dynamical system with control terms. This is of importance in situations where the process serves as an abstract model of the dynamics of malignant cells for use in chemotherapy. A simple example of this kind is given.
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    Bulletin of mathematical biology 44 (1982), S. 29-42 
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    Notes: Abstract A method is developed for a full nonlinear evaluation of all velocities and stresses represented in the Navier-Stokes equations and in the general stress tensor. The information required is essentially that for solution of linearized forms. The solution is analytical except for the calculation of the axial velocity, which requires computer assistance to step through time and space. The treatment of the problem, although directed towards solutions involving fluid flow in elastic vessels, is also adaptable to solid deformations (strain vs rate of strain) where the general stress tensor applies. A special case for the distorting ellipse is presented as well as a limited, spatially analytic, solution.
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    Bulletin of mathematical biology 44 (1982), S. 43-56 
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    Notes: Abstract The stability characteristics and dynamical behavior of a system of mutually excitatory neurons in close spatial proximity are investigated with a mathematical model. The model predicts the existence of uniform, intermediate levels of activity other than those of no activity and maximal activity. The model also, yeilds a good explanation of data obtained from periglomerular neurons in the olfactory bulb of the cat.
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    Bulletin of mathematical biology 44 (1982), S. 75-86 
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    Notes: Abstract A multicompartmental model in which particles enter the system from the environment and reproduce according to a Markov branching process has been considered. Explicit expressions have been obtained for the mean vector and the correlation structure for the numbers of particles in different compartments in different time points of the system. Growth rates of the mean vector and some special cases of the system are also discussed.
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    Bulletin of mathematical biology 44 (1982), S. 57-74 
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    Notes: Abstract The study of bi-directionally coupled oscillators is relevant in biological modelling of such systems as gastro-intestinal electrical activity, cardiac pacemarkers, cardiovascular and respiratory interactions and circadian rhythms. Interconnecting pathways in biological systems often exhibit pure time-delay characteristics. In this paper the multiple-mode limit-cycle behaviour of such systems is analysed using the method of harmonic blance. It is shown that the coupling time delay radically affects the number, frequency and amplitudes of entrained limit-cycles.
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    Bulletin of mathematical biology 44 (1982), S. 87-102 
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    Notes: Abstract The effect of keeping all the parameters constant, except the diffusion coefficients, in a pair of reaction-diffusion equations is studied. It is shown that the stability of the constant solution and the bifurcation points can be easily established by constructing a simple stability diagram. The possible qualitatively different diagrams are enumerated.
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    Bulletin of mathematical biology 44 (1982), S. 103-117 
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    Notes: Abstract We have numerically examined more than one million Large Complex Systems (LCS) of interacting variables (interpretable as interacting populations) governed by Generalized Lotka-Volterra Equations (GLV), with self-regulation term. The scope was to have some insight on the stability-complexity relationship. We considered systems of prey-predator type, and we gave appropriate rules for constructing the model systems, rules that specify the behaviour of model systems in order to put them near the biological reality. The results show, among other things, a strict correlation between the stability and the prey-predator ratio (which, in our model, uniquely determines the connectedness of the system).
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    Bulletin of mathematical biology 44 (1982), S. 149-150 
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    Bulletin of mathematical biology 44 (1982), S. 119-134 
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    Notes: Abstract The rate-controlling process in the oxygenation of red blood cells is investigated using a Roughton-like model for oxygen diffusion and reaction with hemoglobin. The mathematical equations describing the model are solved using two independent techniques, numerical inversions of the Laplace transform of the equations and numerical solutions via an implicit-explicit finite difference form of the equations. The model is used to re-examine previous theoretical models that incorporate either a red cell membrane that is resistive to oxygen diffusion or an unstirred layer of water surrounding the cell. Although both models have been postulated to be equivalent, the results of the computer simulations demonstrate significant differences between the two models in the rate of oxygenation of the red cells, depending upon the values chosen for the diffusion coefficient for O2 in the membrane and the thickness of the water layer. The difference is apparently due to differences in the induction and transient periods of the water layer model relative to the membrane model.
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    Bulletin of mathematical biology 44 (1982), S. 537-547 
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    Notes: Abstract We examine certain mathematical structures presented in Part I. The most important of these are the energy structures determined by the couple (ω×E, ψ) the space of causality defined by ψ-1(0) and the notion of collapsibility, i.e., the descent of a species from a higher to a lower equilibrium configuration as a result of energy loss.
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    Bulletin of mathematical biology 44 (1982), S. 557-570 
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    Notes: Abstract This paper discusses a general stochastic model for a two-compartment reversible system with non-homogeneous Poisson inputs, arbitrary residence times at each of the compartments and time-dependent transition probabilities. The probability distributions of the number of particles in each compartment and in the system are obtained together with the number of particles which depart from the system. In addition, various covariance functions with a time lag are obtained. Some of the above obtained results are deduced for time-independent arrivals, exponential residence times and time-independent transition probabilities. Fluctuations of the particles present in the system are also analysed. Similar analysis is provided for the model into which some particles are initially introduced at the system. Some possible applications are discussed at the end.
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    Bulletin of mathematical biology 44 (1982), S. 571-578 
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    Notes: Abstract The general multispecies prey-predator system with Gompertz's antisymmetric interactions is nonlinearly stable in the absence of dispersion and continues to remain stable with dispersion under both homogeneous reservoir and zero flux boundary conditions in a region containing the equilibrium state. It is proved that a general multispecies food-web model without antisymmetric interactions is stable in the absence of dispersion and remains stable with dispersion in the above-mentioned region.
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    Bulletin of mathematical biology 44 (1982), S. 593-593 
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    Bulletin of mathematical biology 44 (1982), S. 579-585 
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    Notes: Abstract We introduce a graphical approach in the study of the qualitative behavior ofm species predator-prey systems. We prove that tree graphs imply global stability for Volterra models and local stability for general models; furthermore, we derive sufficient conditions so that loop graphs imply stability and boundedness of the solutions.
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    Bulletin of mathematical biology 44 (1982), S. 594-595 
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    Bulletin of mathematical biology 44 (1982), S. 731-739 
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    Notes: Abstract A system of integro-differential equations is derived to describe epizootics of a fungal pathogen in an insect population. Because of piecewise continuous behavior under some parametric conditions, it is concluded that standard phase orbits can be misleading. Using a different analytic approach yields a simple system of finite difference equations. Both the continuous and discrete versions are compared to classical forms. The continuous version differs from a classical one in possessing a second derivative dependent on population density. The discrete version differs in maintaining positive, non-zero populations of both infectives and susceptibles in finite time.
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    Bulletin of mathematical biology 44 (1982), S. 741-748 
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    Notes: Abstract This note is an attempt to demonstrate that hypothalamic pulsatile GnRH secretion is not the result of a short-term, negative steroid hormone feedback. Clarification of this point is of importance for further modelling the control of gonads.
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    Bulletin of mathematical biology 44 (1982), S. 749-760 
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    Notes: Abstract A modern theory of the calculus of variations is used to form necessary and sufficient conditions for the existence of a Lagrangian representation of a system of first-order ordinary differential equations. There exists a theorem to the effect that when a system of ordinary differential equations is variationally self-adjoint, the fulfillment of such conditions is guaranteed. In addition, self-adjointness, allows establishement of an algorithm by which a Lagrangian for the system may be explicitly constructed. Examples in mathematical biology are given to illustrate the use of the stated theorem.
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    Bulletin of mathematical biology 44 (1982), S. 793-808 
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    Notes: Abstract Engineering optimal control theory is applied to equations describing insulin and glucose interactions. The nature of the optimal controller is established. It is shown how the results can be utilized in a closed loop feedback control system.
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    Bulletin of mathematical biology 44 (1982), S. 777-791 
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    Notes: Abstract An attempt is made to compare the conditions for the general error-optimality of linear systems developed by Kalman with the conditions for feasibility of linear models of neuromuscular and physiological control systems. Models of three actual physiological systems are tested for both the above criteria. Theoretical analysis presented here shows that there are no simple relationships between the two sets of conditions. Analysis carried out on the physiological systems models suggests the need for a general set of conditions for other optimality criteria, such as time and energy minimization, similar to Kalman's condition for error minimization.
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    Bulletin of mathematical biology 44 (1982), S. 851-877 
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    Notes: Abstract Following arteriolar occlusion, tissue oxygen concentration decreases and anoxic tissue eventually develops. Although anoxia first appears in the region most distal to the capillary at the venous end, it eventually spreads throughout the entire region of supply. In this paper the changing oxygen concentration, from the time of occlusion until the tissue is entirely anoxic, is examined mathematically. The equations governing oxygen transport to tissue are solved by iterating a nonlinear integral equation. This solution is valid until anoxia first appears. After anoxia develops it is necessary to solve a moving boundary problem. This is done using the method of matched asymptotic expansions, and accurate solutions are obtained for a wide range of physiological conditions.
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    Bulletin of mathematical biology 44 (1982), S. 899-900 
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    Bulletin of mathematical biology 48 (1986), S. 633-660 
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    Notes: Abstract Nonlinear similarity functions are often better than linear functions at distinguishing interesting subalignments from those due to chance. Nonlinear similarity functions useful for comparing biological sequences are developed. Several new algorithms are presented for finding locally optimal subalignments of two sequences. Unlike previous algorithms, they may use any reasonable similarity function as a selection criterion. Among these algorithms are VV-1, which finds all and only the locally optimal subalignments of two sequences, and CC-1, which finds all and only the weakly locally optimal subalignments of two sequences. The VV-1 algorithm is slow and interesting only for theoretical reasons. In contrast, the CC-1 algorithm has average time complexityO(MN) when used to find only very good subalignments.
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    Bulletin of mathematical biology 48 (1986), S. 701-703 
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    Bulletin of mathematical biology 48 (1986), S. 681-699 
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    Notes: Abstract A resource-based competition model of two consumer species and one resource species is formulated in the form of a Lotka-Volterra system. The competition involves both exploitation and interference. By a method of asymptotic estimates, sufficient conditions are derived for the three species system to converge ast→∞ to an equilibrium point with all three species present; a generalization of the result forn≥2 and single resource species is indicated. The strong form of equilibrium perisistence of the three species consumer-resource system is achieved by the ability of each of the consumer species to exploit the resource and interfere with others in such a way which will avoid exclusion by the other.
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    Circuits, systems and signal processing 5 (1986), S. 3-36 
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    Notes: Abstract This paper is a brief historical review of linear singular systems, followed by a survey of results on their solution and properties. The frequency domain and time domain approaches are discussed together to sketch an overall picture of the current status of the theory.
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    Circuits, systems and signal processing 1 (1982), S. 93-104 
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    Notes: Abstract A stochastic approximation problem for polynomic operators is formulated. The performance of polynomic operators of various degrees is compared. The effect of causality constraints is also examined.
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    Circuits, systems and signal processing 1 (1982), S. 137-169 
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    Notes: Abstract A recently developed algebraic approach to the feedback system design problem is reviewed via the derivation of the theory in the single-variate case. This allows the simple algebraic nature of the theory to be brought to the fore while simultaneously minimizing the complexities of the presentation. Rather than simply giving a single solution to the prescribed design problem we endeavor to give a complete parameterization of the set of compensators which meet specifications. Although this might at first seem to complicate our theory it, in fact, opens the way for a sequential approach to the design problem in which one parameterizes the subset of those compensators which meet the second specification...etc. Specific problems investigated include feedback system stabilization, the tracking and disturbance rejection problem, robust design, transfer function design, pole placement, simultaneous stabilization, and stable stabilization.
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    Circuits, systems and signal processing 1 (1982), S. 267-268 
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    Circuits, systems and signal processing 1 (1982), S. 433-445 
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    Notes: Abstract We describe a recently developed framework for exploring the structure of linear time-invariant models of large systems, and for constructing interpretable or physically-based, reduced-order models that reproduce selected modes of the original systems to a desired accuracy. Application of this framework to constructing lumped approximations for interconnections of lumped and distributed systems is briefly explored.
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    Bulletin of mathematical biology 42 (1980), S. 147-160 
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    Notes: Abstract A theory of noise fluctuations is developed which is applicable to systems of any size in which unimolecular or bimolecular reactions are occurring. The main difference between small and large reacting systems is that in the former the probability of finding a particle in a particular state does not obey a Gaussian distribution, but satisfies a distribution which reflects the mechanism of the chemical reaction. This difference is reflected in the main result of the theory: an autocorrelation function that is expressible as a sum of exponentials, the amplitudes of which are explicit functions of the moments of the distribution. Thus, by using small systems, the autocorrelation function,in principle, allows the elucidation of reaction mechanisms. Numerical simulations indicate that for reacting systems having ten or fewer particles, the deviation of the autocorrelation function from a single exponential should be easily detectable, and that estimates of the first four moments of the distribution should be possible. Accurate inference of the distribution, however, will require further mathematical and experimental advances.
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    Bulletin of mathematical biology 42 (1980), S. 161-172 
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    Notes: Abstract The recent mathematical formalization of the concepts of matter and extrinsical energy, which are used for the relational representation of biological systems, is employed in the analysis of the important experimental discoveries of Comorosanet al. related to low energy electromagnetic irradiations on enzyme substrates. By means of the present analysis one of the properties inherent to the experimental phenomena is more precisely exposed, and theoretical developments corresponding to “energetical evolutions” in a biological system (Leguizamón, 1976) may now have an experimental basis. Important limitations are introduced for the validity of the commutativity and associativity of cartesian product of sets, when they represent matter and its linked extrinsical energy. In connection with this last aspect, new important knowledge is obtained for the relational mathematical representation of biological systems.
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    Bulletin of mathematical biology 42 (1980), S. 397-429 
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    Notes: Abstract The structure of solutions to a simple spatially dependent population model involving growth and death is investigated. Two forms of motility of the population are considered: (1) random motion only modeled by a Fickian law, and (2) a directed component of motion (chemotaxis), included in addition to the random motion. Under certain growth conditions a traveling wave of constant speed is approached. This speed can be increased by the addition of the chemotaxis with a corresponding increase in the asymptotic population. Development of initial conditions into a wave is illustrated numerically.
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    Bulletin of mathematical biology 42 (1980), S. 365-396 
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    Notes: Abstract This paper describes mechanisms of intracellular and intercellular adaptation that are due to spatial or temporal factors. The spatial mechanisms support self-regulating pattern formation that is capable of directing self-organization in a large class of systems, including examples of directed intercellular growth, transmitter production, and intracellular conductance changes. A balance between intracellular flows and counterflows causes adaptation. This balance can be shifted by environmental inputs. The decrease in Ca2+-modulated outward K+ conductance in certain molluscan nerve cells is a likely example. Examples wherein Ca2+ acts as a second messenger that shunts receptor sensitivity can also be discussed from this perspective. The systems differ in basic ways from recent diffusion models. Chemical transducers driven by membrane-bound intracellular signals can establish long-range intercellular interactions that compensate for variable intercellular distances and are invariant under developmental size changes; diffusional signals do not. The intracellular adaptational mechanisms are formally analogous to intercellular mechanisms that include cellular properties which are omitted in recent reaction-diffusion models of pattern formation. The cellular models use these properties to compute size-invariant properties despite wide variations in their intercellular signals. Mechanisms of temporal adaptation can be derived from the simplest laws of chemical transduction by using a correspondence principle. These mechanisms lead to such properties of intercellular signals as transient overshoot, antagonistic rebound, and an inverted U in sensitivity as intracellular signals or adaptation levels shift. Such effects are implicated in studies of behavioral, reinforcement, motor control, and cognitive coding.
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    Bulletin of mathematical biology 42 (1980), S. 447-459 
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    Notes: Abstract Large radiation doses to the lung can cause early death from cardiopulmonary insufficiency resulting from radiation pneumonitis and pulmonary fibrosis. A model for early death following inhalation of insoluble radioactive particles is propose. The model is based on three assumptions: (1) early death results from damage to a cluster of cells from a large number of cell clusters at risk, (2) the dose that causes early death depends on how the radiation is delivered in time and (3) the cell clusters at risk to damage are equally sensitive ro radiation. Results from asymptotic theory of extreme values, along with biophysical considerations, suggest that the cumultive distribution function for the absorbed radiation dose to the production of pulmonary injury sufficient to cause early death is best estimated by the third asymptotic distribution without a threshold. This distribution function is identical to the Weibull cumulative distribution function. Data for Beagle dogs after inhaling relatively insoluble forms of alpha- or beta-gamma-emitting particles are shown to support the Weibull model.
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    Bulletin of mathematical biology 42 (1980), S. 461-480 
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    Notes: Abstract Models of the human respiratory tract were developed based on detailed morphometric measurements of a silicone rubber cast of the human tracheobronchial airways. Emphasis was placed on the “Typical Path Lung Model” which used one typical pathway to represent a portion of the lung, such as a lobe, or to represent the whole lung. The models contain geometrical parameters, including airway segment diameters, lengths, branching angles and angles of inclination to gravity, which are needed for estimating inhaled particle deposition. Aerosol depositions for various breathing patterns and particle sizes were calculated using these lung models and the modified Findeisen-Landahl computational scheme. The results agree reasonably well with recent experimental data. Regional deposition, including lobar deposition fractions, are also calculated and compared with results based on the ICRP lung deposition model.
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    Bulletin of mathematical biology 42 (1980), S. 481-488 
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    Notes: Abstract The completely symmetrical system is defined as having identical transfer coefficients between pairs of compartments and the same loss coefficient for each compartment. The eigenvalues and eigenvector are explicitly found along with the inverses of the system matrix and the matrix of eigenvectors. Many properties, special instances of more general theorems, can be seen at once from the explicit analytic solution of the initial value, washout and washin problems. The system serves as a known case for testing estimation procedures, algorithms for solutions of linear systems, eigenvalue-eigenvector and inversion routines and is of considerable tutorial value.
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    Bulletin of mathematical biology 42 (1980), S. 431-446 
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    Notes: Abstract The mathematical structures underlying the theories of organismic sets, (M, R)-systems and molecular sets are shown to be transformed naturally within the theory of categories and functors. Their natural transformations allow the comparison of distinct entities, as well as the modelling of dynamics in “organismic” structures.
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    Bulletin of mathematical biology 42 (1980), S. 489-505 
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    Notes: Abstract To explain the sodium conductance change using Wei's dipole model (Wei, 1969), we may expect that during depolarization the dipole's population difference, ΔN, is first reduced and then returns more slowly to its resting value. This paper shows that the experimental results of gating currents support this idea. Such time course of ΔN, however, is not a usual relaxation process. To account for the unusual behavior of ΔN, we propose two additional assumptions: (1) there exists a special coupling system (probably the intramolecular vibrations) whose coupling strength with the dipoles is much stronger than with the thermal bath (intermolecular vibrations), and (2) there also exist “traps” for the dipole's excitation energy so that this energy is transformed into other energy forms at a rate increasing with the increase of depolarization. Experiments suggest that the traps are proteins located at the inner membrane surface.
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    Bulletin of mathematical biology 42 (1980), S. 507-528 
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    Notes: Abstract Current research into the dynamics of iterative ecological and biological models has lead to a number of theorems concerning the existence of various types of iterative dynamical behavior. In particular, much study has been done on the dynamical behavior of the “simplest dynamical system”f b(x)=bx(1−x), which is just the canonical discrete form of logistic growth equations found in ecology, sociobiology, and population biology. In this paper, we make use of some of the techniques and concepts of topological dynamics to construct a number of generalized conjugacy theorems. These theorems are then used to demonstrate that the mappingf b has a number of conjugacy classes in which the dynamics of the iterates is equivalent to within a change of variables. The concepts of fitness and survival in logistic equations are then shown to be independent, if we follow certain intuitive definitions for these concepts. This conclusion follows from a comparison of the conjugacy classes of the functionf b and the extinction sets off b.
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    Notes: Abstract For chemical reactions not at equilibrium but proceeding in the forward direction in the steady state, a result found by a method first introduced by H. G. Britton (1963, 1965) is generalized to prove that if $${{\vec J} \mathord{\left/ {\vphantom {{\vec J} {\overset{\lower0.5em\hbox{$\smash{\scriptscriptstyle\leftarrow}$}}{J} }}} \right. \kern-\nulldelimiterspace} {\overset{\lower0.5em\hbox{$\smash{\scriptscriptstyle\leftarrow}$}}{J} }}$$ is the unidirectional flux ratio, $${{\vec J} \mathord{\left/ {\vphantom {{\vec J} {\overset{\lower0.5em\hbox{$\smash{\scriptscriptstyle\leftarrow}$}}{J} }}} \right. \kern-\nulldelimiterspace} {\overset{\lower0.5em\hbox{$\smash{\scriptscriptstyle\leftarrow}$}}{J} }}$$ exp (−ΔG/RT). The conditions under which the equality or inequality applies are discussed. If the unidirectional fluxes are not in the steady state, the unidirectional flux ratio is time invariant in certain specific situations. One such important case is for chemical reaction systems with an ordered sequence of reactions. For systems with more than one pathway, $${{\vec J} \mathord{\left/ {\vphantom {{\vec J} {\overset{\lower0.5em\hbox{$\smash{\scriptscriptstyle\leftarrow}$}}{J} }}} \right. \kern-\nulldelimiterspace} {\overset{\lower0.5em\hbox{$\smash{\scriptscriptstyle\leftarrow}$}}{J} }}$$ is not constant except for special cases. These results also apply to diffusional and active transport systems.
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    Bulletin of mathematical biology 42 (1980), S. 599-600 
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    Bulletin of mathematical biology 42 (1980), S. 539-549 
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    Bulletin of mathematical biology 42 (1980), S. 551-597 
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    Notes: Abstract The nonlinear second-order difference equationx n+1=axn(1-xn−1), where 0≦x nX≦1 anda ≧1, is examined from varying points of view, analytical, numerical and geometrical. An analytic expression is obtained for an invariant attracting curveC ∞ (a) in phase space, which becomes the central object of study. This basic curve, which replaces the simple parabolic shape typical of many analogous first-order models, may have a complicated geometrical structure. As the parametera increases,C ∞(a) undergoes transformations characterized by the dynamical descriptions: stable node→stable focus→stable limit cycle →chaotic attractor. Although the limited characterization ofchaos by the appearance of nonperiodic solutions and solutions of arbitrarily large period is relied upon, this appears to be only a simplified approximation of the real behavior of solutions. Trajectories (x n, xn+1),n=0,1,…, are calculated using the related nonlinear planar mapT a(x,y)=(y,ay(1−x)), and regions of persistence and escape are described for characteristic values ofa. The study of persistence, of even more fundamental interest than the associated problems of periodicity and stability, receives special attention. We introduce a geometrical model, similar in many respects to that for the well-known analoguex n+1=axn(1−x n), but having several new and important features. It appears that as the parametera increases in the chaotic regime there are infinitely many intermittent bursts of increase in the probability that any initial point (x 0, x1) will persist in the unit square under successive iterations of the mappingT a, an unexpected property that should be of interest for applications. A discussion of the applicability of these results to population dynamics theory is given, and it is suggested that such equations might find useful application to problems in developmental biology as well.
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    Bulletin of mathematical biology 42 (1980), S. 627-645 
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    Notes: Abstract Based on the principle of minimum power, a mathematical model of the functional state of the oxygen transport system is presented. The optimization model minimizes the power expenditure of the heart, bone marrow, lung and other tissues. The model is used to determine the functional parameters of the oxygen transport system in man under both normal and varying barometric pressures. Theoretical results are compared with experimental data.
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    Bulletin of mathematical biology 42 (1980), S. 601-625 
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    Notes: Abstract A quantitative model of ion binding and molecular interactions in the lipid bilayer membrane is proposed and found to be useful in examining the factors underlying such membrane characteristics as shape, sidedness, stability and vesicle size at various cation concentrations. The lipid membrane behaves as a bilayer couple whose preferential radius of curvature depends on the expansion or contraction of one monolayer relative to the other. It is proposed that molecular packing may be altered by electrostatic repulsion of adjacent like-charged phospholipid headgroups, or by bringing two headgroups closer together by divalent cation crossbridging. The surface concentrations of each type of cation-phospholipid complex can be described by simple binding equilibria and the Gouy-Chapman-Stern formulation for the surface potential in a diffuse double layer. The asymmetric distribution of acidic phospholipids in most biological membranes can account for the differential effects of identical ionic environments on either side of the bilayer. The fraction of vesicle material which tends to have a right-side-out orientation may be approximated by a normal distribution about the mean curvature. The theory generates vesicle sidedness distributions that, when fitted to experimental results from human erythrocyte membranes, provide an alternative method of estimating intrinsic cationphospholipid dissociation constants and other molecular parameters of the bilayer. The results also corroborate earlier suggestions that the Gouy-Chapman theory tends to overestimate free counter-ion concentrations at the surface under large surface potentials.
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    Bulletin of mathematical biology 42 (1980), S. 681-689 
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    Notes: Abstract The “yellow strips” on the cuticle of the Oriental Hornet (Vespa orientalis, Hymenoptera, Vespinae), present photoelectric properties. A mathematical model for the relative changes in resistance as a photoconductive process conforms to the general model for a semiconductor with traps.
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    Bulletin of mathematical biology 42 (1980), S. 701-718 
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    Notes: Abstract Damped nonlinear oscillations in biological and biochemical systems are investigated by the extended Krylov-Bogoliubov-Mitropolskii (KBM) method. A review on the extension made by Popov to the KBM method is given and also further improvements are presented. Applications are made to models of oscillating chemical reactions (Lefever and Nicolis, 1971), FitzHugh (1961) equations, and population dynamics (Gatto and Rinaldi, 1977). Comparison to damped oscillating physical and engineering systems is made.
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    Bulletin of mathematical biology 42 (1980), S. 719-728 
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    Notes: Abstract The conditions that will allow the lumping together of several age classes in the Leslie model are investigated. We show that if the lumping is to be valid for all population distributions, then the parameters of the model must be periodic. Lumping is valid when the population is in equilibrium, but equilibrium should be tested before the model is lumped.
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    Bulletin of mathematical biology 42 (1980), S. 647-679 
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    Notes: Abstract Catastrophe theory is a mathematical theory which, allied with a new and controversial methodology, has claimed wide application, particularly in the biological and the social sciences. These claims have recently been heatedly opposed. This article describes the debate and assesses the merits of the different arguments advanced.
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    Bulletin of mathematical biology 42 (1980), S. 765-795 
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    Notes: Abstract Estimates of capillary tracer permeability calculated using multiple indicator data depend upon the particular model adopted to describe blood tissue exchange. The model proposed by Crone (1963) is appropriate when some of the injected tracer diffuses into the tissue but does not return appreciably to the bloodstream before data collection is terminated. Under these conditions extraction of tracer by the tissue depends on a single dimensionless parameter, αcap, defined as the ratio of capillary permeability surface area to water flow. The effects of finite red cell tracer permeability on the Crone model estimate of capillary permeability are examined in the present study. The results indicate that even when back diffusion from the extravascular space is negligible, significant errors in the Crone model estimate can be expected when capillary permeability is relatively high and the ratio of red cell to capillary permeability is less than unity. However, when an aliquot of blood is equilibrated with tracer prior to injection and the dimensionless capillary permeability is relatively low (i.e. αcap ≦ 0.25 for a haematocrit≦50%), the whole blood Crone model estimate of αcap will be within 10% of the actual value, irrespective of red cell permeability. Red cell-plasma exchange for commonly used tracer-organ combinations should not significantly affect Crone estimates of capillary permeability under normal physiological conditions, but may be important in low flow situations.
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    Bulletin of mathematical biology 42 (1980), S. 807-828 
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    Notes: Abstract Assuming truncated ellipsoidal geometry for the right and left ventricles, a model is developed for the myocardium enabling biventricular mechanical behavior to be studied. Employing pressure-volume data taken from normal dog hearts and from hearts in which the pulmonary artery has been banded over periods of 2–40 weeks, it is shown that: (a) right ventricular wall stresses are higher than left ventricular stresses; (b) right ventricular wall stress increases initially to a maximum after 3–4 weeks followed by a decline to normal and even subnormal levels, attaining a minimum value at 32–33 weeks; (c) left ventricular stresses behave in a similar manner, attaining their maximum and minimum levels after 7–8 weeks and 32–33 weeks respectively. These results suggest that surgical or medical therapy in patients with hypertrophied ventricles might be more appropriate during the period of wall stress reduction.
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    Bulletin of mathematical biology 42 (1980), S. 837-845 
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    Notes: Abstract In this paper we describe a mathematical model of the oscillations of the diaphragm which limits the vitreous body from the anterior segment of the human eye after the lens has been removed in a cataract operation. We study the motion of this diaphragm driven by movements of the eye. Firstly, a mathematical statement of the problem is given and then we solve the problem exactly for a given class of eye movements. From the analysis we deduce that significant oscillations of the membrane are driven by saccades and that it is the angular acceleration of the eye which causes these types of oscillations. A numerical example is given.
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    Bulletin of mathematical biology 42 (1980), S. 871-887 
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    Notes: Abstract The Lotka-Volterra system of prey-predator equations is considered with a special type of continuous time delay. In the case of equal diffusion coefficients Hopf’s bifurcation technique is used to show the existence of travelling wave train solutions for the prey-predator system.
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    Bulletin of mathematical biology 42 (1980), S. 861-870 
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    Notes: Abstract A mathematical model of prothrombin activation is being proposed which includes the feedback mechanism of thrombin and the alteration of factor V by thrombin. This model is in good agreement with experimental data for the dependence of the rate of thrombin formation on the concentrations of factors V and X a . In particular, it correctly predicts the existence and location of a maximum in both of these cases.
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    Bulletin of mathematical biology 42 (1980), S. 847-859 
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    Notes: Abstract A new model of the upper tracheobronchial tree is proposed to account for the three-dimensional nature of the airway system. In addition to the tube length, the tube diameter, and the branching angle, the model includes information on the orientation angle of each tube relative to its parent tube. The orientation angle, defined as the angle between two successive bifurcations, is useful for calculating the gravitational inclination of each tube. The information on orientation angle is further used to construct a binary coding system for identifying individual tubes in the airway tree. The proposed model is asymmetrical, but the same principles can be readily used to construct a symmetrical one.
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    Bulletin of mathematical biology 42 (1980), S. 889-897 
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    Notes: Abstract In any control system for which the number of independent controls is smaller than the number of degrees of freedom to be controlled, our choice of control in any state is restricted to a submanifold of smaller dimension than the tangent space. This simple fact has a number of important consequences for questions of biological import; we consider its implications for adaptation, for senescent phenomena and for the determination of tertiary structures of polypeptides through control of certain average properties. We also formulate the Pontryagin Maximum Principle of Optimal control theory in such a way as to inquire whether specific biodynamic systems can be regarded as optimal with respect to rate of accumulation of particular quantities of the system. We find that if this is possible, the quantity in question must play the role of a clock.
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    Bulletin of mathematical biology 42 (1980), S. 899-900 
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    Bulletin of mathematical biology 48 (1986), S. 59-75 
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    Notes: Abstract An understanding of the comparative statics of biological communities is important both as a means of explaining the long-term effects of changes in environmental conditions, and as a framework for viewing community time trajectories. A general formulation of community dynamics is presented here which, given full information about a particular community's dynamic behavior, describes the impact of a change in environmental conditions on the community steady state. However, since such full information is often lacking in studies of biological communities, various approaches to partial information analysis of comparative statics are presented and compared, including a generalized protocol for isocline analysis. The suggested isocline protocol is shown to be a useful tool for both full and partial information analyses, as well as for both general and partial equilibrium studies.
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    Bulletin of mathematical biology 48 (1986), S. 77-86 
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    Notes: Abstract Fujita's diagrams in phyllotaxis, showing the frequencies of divergence angles as a function of these angles for low phyllotactic patterns such as (2, 1) and (3, 2), which are approximately normal curves centered at the limitdivergence angle of 137.51°, are shown to be puzzling when compared to results and observations in the field. An analysis of these diagrams is proposed, in the context of Fujita's methodology, of data from other sources, of a mathematical theorem on lattices, and of the contact pressure theory of phyllotaxis.
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    Bulletin of mathematical biology 48 (1986), S. 87-95 
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    Notes: Abstract It is shown that a representative Fisher-Wright model withn(≥3) diallelic loci admits a necessary condition for existence of a time-independent steady-state probability distribution. This necessary condition states that a global integral depending on the phenotype fitness functions of natural selection must be larger than a certain quantity depending on the parameters associated with genetic drift.
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    Bulletin of mathematical biology 48 (1986), S. 149-166 
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    Notes: Abstract Equations for the time-dependent concentrations of all species involved in the general mechanism of human plasminogen activation proposed by Wohlet al. (J. biol. Chem. 255, 2005–2013, 1980) have been derived. These equations are valid for the whole course of the reaction: for both the transient phase and the steady state. In addition, we compare our results with the ones obtained by the above-mentioned authors for the steady state assuming rapid equilibrium conditions. Finally, we propose a method for the determination of all velocity constants.
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    Bulletin of mathematical biology 48 (1986), S. 189-195 
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    Notes: Abstract A special class of interval graphs is defined and characterized, and an algorithm is given for their construction. These graphs are motivated by an important representation of DNA called restriction maps by molecular biologists. Circular restriction maps are easily included.
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    Bulletin of mathematical biology 48 (1986), S. 253-278 
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    Notes: Abstract Over the past 25 years stepwise improvement in the cure of disseminated cancers has been good, fair or very poor depending on the particular cancer one is discussing. “Cancer chemotherapy provides variably effective treatment for the majority of forms of human cancer and curative treatment for some 12 categories.” We have been slow to gain and learn how to apply quantitative information on the biologic phenomena that underlie the responsiveness, or lack of responsiveness, of many different cancers to single drugs and combinations of drugs delivered in different ways. I am of the opinion that continuing development and integration of rational biomathematical models based on principles already identified, and testing them for compatibility with much already available experimental and clinical data, will lead to models that will help in planning more effective treatment regimens for cancers now classified as moderately refractory or very refractory to chemotherapy. Some of the critical variables are considered briefly. My advice, for what it is worth, is “try to be sure that the biologic concepts that you use in modeling are almost as good as the arithmetic.”
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    Bulletin of mathematical biology 48 (1986), S. 309-322 
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    Notes: Abstract A discussion of the bases of physiological pharmacokinetics is followed by a brief review of the fundamental mass balance equations of the models. Some examples are outlined, together with a listing of published reviews which give many more references and detailed examples. Finally, some thoughts on future research directions are presented.
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    Bulletin of mathematical biology 48 (1986), S. 323-336 
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    Notes: Abstract The use of stochastic simulation languages in cell kinetics research is discussed. Two special purpose simulation languages; CELLSIM and CELLGROW are described and example problems are presented.
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    Bulletin of mathematical biology 48 (1986), S. 293-307 
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    Notes: Abstract Mathematical models predicting tissue doses of chemical toxicants can be either highly complex or simple, depending upon the end results needed. As an example of a highly complex mathematical model, the Miller Model of the distribution of reactive gases in human and animal lungs is described. The Miller Model accounts for the convection, the radial and axial diffusion, and the chemical reactions of gases as an inhaled breath passes down the airways. The geometry and physiology of human and animal lungs are used to calculate the convection and diffusion likely in each generation or bifurcating series of airways commencing with the trachea and extending 24 generations in humans. The chemical reactivity of ozone, an air pollutant, is accounted for by simulating second-order chemical reactions with the fluid lining materials of the lung and tissue biological molecules. The flux of ozone into three compartments (pulmonary tissue, overlying liquid layer and capillary blood) in each generation of the lung is calculated to provide molecular doses of ozone reaching each region of the lung. These results of calculated molecular dose are then used to construct dose-response curves for a variety of biological endpoints. A much simpler model is also described which recognizes the saturable or Michaelis-Menten type of kinetics controlling the removal of nickelous ion (nickel) from the lung. This model is used to calculate the chronic lung burden of the human lung for occupational, environmental and cigarette smoking exposure scenarios. In both the complex Miller Model and the simpler nickel lung burden model, the results can be used to calculate molecular doses at the potential site of action of these environmental chemicals and to unify a wide variety of studies. The predictions made are more likely to be valid since multiple investigators using a variety of animal species have participated in generation of the primary data. As a methodology, mathematical modeling based on physiological, physicochemical and anatomical principles provides a means of eliminating non-scientific considerations from the important process of regulating and recognizing toxic or cancer causing chemicals in the human environment.
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    Bulletin of mathematical biology 48 (1986), S. 337-351 
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    Notes: Abstract This paper presents a brief review of applications of kinetic simulation of multi-enzyme networks to the study of antimetabolite drugs used as anticancer agents. Kinetic models consist of systems of nonlinear differential equations that describe changes in concentrations of cellular metabolites with respect to time. Such models have been used to predict the effect of changes in activity of enzymes, or changes in enzyme kinetic parameters, on sensitivity to inhibition. Kinetic simulation has provided insight into several aspects of the biochemical pharmacology of antimetabolites, including drug sensitivity and resistance, and drug-drug interactions. Two specific studies are described in detail. The first concerns the importance of the ratio of competing enzymes in determining the selectivity of inhibitors of one of the competing enzymes, studied by a simple model. The second case study examines the effect of alternative biosynthetic pathways, thede novo and salvage pathways of pyrimidine nucleotide biosynthesis, on the selectivity of antipyrimidine drugs, as studied by a detailed model of 27 reactions of pyrimidine metabolism.
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    Bulletin of mathematical biology 48 (1986), S. 381-404 
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    Notes: Abstract General (deterministic) ordinary differential equations for the representation of cancer growth are presented when the growth is perturbed due to the action of a chemotherapeutic agent. The Verhulst-Pearl equation is introduced as a particular example of a growth equation applicable to human tumors. An optimal control problem with general performance criterion and state equation is formulated and shown to possess a novel feedback control relationship. This relationship is used in two continuous drug delivery problems involving the Verhulst-Pearl equation.
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    Bulletin of mathematical biology 48 (1986), S. 353-380 
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    Notes: Abstract Complex networks of biological processes are analogous to electrical circuits. For each step in a biological or electrical network, flow is dependent on the driving force and the conductivity of the step. The relationship between biological flows and their driving forces can therefore be expressed as relationships between analogous currents and voltages. The time dependence of approach to equilibrium or a steady state is determined by the rates of depletion of material in various compartments. Electrical capacitance is therefore analogous to compartment volume. Once these generalized concepts of flow, force and capacitance are recognized, it becomes clear that computer programs designed for analysis of electrical circuits may be used for simulation of biological networks. A set of simple mathematical descriptions of the individual steps and a diagram showing how the steps are arranged with respect to each other are all that is necessary to perform a simulation; there is no need for computer programming skills or differential equations. The use of SPICE2 for simulation of the cellular and plasma pharmacokinetics of cytosine arabinoside (araC) is described as an example. A network model is developed which considers cellular pharmacokinetics (membrane transport, intracellular phosphorylation and dephosphorylation), and plasma pharmacokinetics following infusions of araC.
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    Bulletin of mathematical biology 48 (1986), S. 405-415 
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    Notes: Abstract Developments in computer hardware and software are making significant improvements in the availability of simulation for biomedical researchers. This paper reviews past and present techniques for digital computer simulation and looks at improvements likely in the near future. In the area of hardware, personal computers are making computing and simulation more widely available and at the same time, supercomputers and special-purpose numerical processors are making it possible to solve larger problems. Software developments for simulation are reducing the time, effort and special skills required to produce a simulation program. A new hierarchical linker is proposed to make it easy to synthesize a global model by combining existing submodels. In the more distant future, computer models may be constructed graphically and with the assistance of intelligent programs capable of analysis and information retrieval.
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    Bulletin of mathematical biology 48 (1986), S. 417-426 
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    Notes: Abstract Modeling is a ubiquitous and often misunderstood enterprise in which data from diverse disciplines are analyzed by techniques from other diverse disciplines in an attempt to confirm or falsify a set of hypotheses about the real world. Guidelines are offered for designing models to match the goals of modeling biological systems. Techniques for the construction and interpretation of models are discussed. The requirements for credibility of models are detailed, and tests are suggested for their validation.
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    Bulletin of mathematical biology 48 (1986), S. 453-453 
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    Bulletin of mathematical biology 48 (1986), S. 443-452 
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    Notes: Abstract Presentations and discussions at the symposium illustrate some general issues in biomedical modeling for cancer research. Given the motivations for modeling and assumptions concerning who should be involved in the modeling process, one can identify some basic needs to be met in supports to modelers. These concern both the models themselves and ways of presenting them to users. In conclusion, some thoughts are offered on economic and educational issues that may affect the infusion of modeling into biomedical research.
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    Bulletin of mathematical biology 48 (1986), S. I 
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    Bulletin of mathematical biology 44 (1982), S. 17-28 
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    Notes: Abstract The concept of natural selection is examined, which is one of basic principles for the Darwinian interpretation of evolution. In this model selection is defined as a solution of the deterministic Eigen equation. Next, the random effect is introduced through the mutation term. However, the probability of finding the solution expressing the selection is shown to be smallest. The validity of the model and its applicability to polynucleotide replication are discussed.
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