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  • 1
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    Bulletin of mathematical biology 33 (1971), S. 49-54 
    ISSN: 1522-9602
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Mathematics
    Notes: Abstract In the theory of organismic sets (Bull. Math. Biophysics,31, 159–198, 1969) we considered organisms as sets endowed with certain “activities,” the latter’s resulting in a set of “products.” Those products may be of a material nature, like a hormone secreted by a cell, or of a non-material nature, like a feeling or an attitude. In the present paper aggressiveness and submissiveness are considered as such non-material products of the activities of the brain cells. A general description of aggressiveness and submissiveness is given in terms of organismic sets. Cycles in “peck order” are thus naturally explained.
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  • 2
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    Bulletin of mathematical biology 33 (1971), S. 55-66 
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    Notes: Abstract In line with previous studies on organismic sets, the division of all organismic sets intogeneral autotrophic and heterotrophic is introduced. The first produce their food themselves from some external source of energy, which in general may be an energy of any kind. The others use other organismic sets as the source of their food and energy. On earth we know only one kind of generalgeneral autotrophic organismic sets, namely, the autotrophic plants which use solar radiation as their source of energy and for production of their own food. It is shown why autotrophic animals do not exist on earth except as microorganisms like, e.g.,Euglena. A rigorous proof of the previously derived theorem that in an organismic set of ordern〉1 no element can be completely specialized is given. It requires the introduction of new postulates. Finally, in considering the organic world as a whole, the notion of organismic sets ofmixed order is introduced.
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  • 3
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    Bulletin of mathematical biology 33 (1971), S. 67-81 
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    Notes: Abstract It appears to be axiomatic that termolecular and higher order reactions occur relatively rarely. The basis for this judgment seems to lie in the supposition that successful 3-Body collisions of 3 interactive species of molecules cannot occur frequently enought to account for chemical or biochemical transformation. In order to provide a more complete mathematical framework than now exists for examining this hypothesis the probability of effective termolecular “δ-collisions” as a function of time is derived. This amounts to adding to the class of reactions for which stochastic models are now available the termolecular reaction. In common with the unimolecular and bimolecular cases this process is seen to satisfy the criterion of consistency-in-the-mean with respect to deterministic formulations. It is planned next to use the termolecular process and the lower order processes in computer-assistedin numero experimental studies aimed at comparing alternative mechanisms of reaction.
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  • 4
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    Bulletin of mathematical biology 33 (1971), S. 83-96 
    ISSN: 1522-9602
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    Notes: Abstract Small sample properties of the maximum likelihood estimator for the rate constant of a stochastic first order reaction are investigated. The approximate bias and variance of the maximum likelihood estimator are derived and tabulated. If observations of the system are made at timesiτ,i=1, 2, ...,N; τ〉0, the observational spacing τ which minimizes the approximate variance of the maximum likelihood estimator is found. The non-applicability of large sample theory to confidence interval derivation is demonstrated by examination of the relative likelihood. Bartlett’s method is employed to derive approximate confidence limits, and is illustrated by using simulated kinetic runs.
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  • 5
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    Bulletin of mathematical biology 33 (1971), S. 339-354 
    ISSN: 1522-9602
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    Topics: Biology , Mathematics
    Notes: Abstract The representation of biological systems by means of organismic supercategories, developed in previous papers (Bull. Math. Biophysics,30, 625–636;31, 59–71;32, 539–561), is further discussed. The different approaches to relational biology, developed by Rashevsky, Rosen and by Băianu and Marinescu, are compared with Qualitative Dynamics of Systems which was initiated by Henri Poincaré (1881). On the basis of this comparison some concrete result concerning dynamics of genetic system, development, fertilization, regeneration, analogies, and oncogenesis are derived.
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  • 6
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    Bulletin of mathematical biology 33 (1971), S. 303-319 
    ISSN: 1522-9602
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    Notes: Abstract Some years ago (Rosen 1958a, b; 1959) we described a class of metaphorical, relational paradigms for cellular activity which we termed (M, R)-systems. A sizable amount of subsequent work, to be itemized below, has been devoted to an exploration of some of the properties of these systems. The main purpose of the present paper is to put this class of paradigms into a general system-theoretic perspective, with a particular view to appraising the relation between the type of system description embodied in the (M, R)-system and other kinds of physical and mathematical descriptions of cellular systems. Thus, the principal aim is to establish the relationships and connections between the global relational formalism embodied in the (M, R)-systems and the empirical descriptions which still represent the bulk of our biological knowledge.
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  • 7
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    Bulletin of mathematical biology 33 (1971), S. 321-338 
    ISSN: 1522-9602
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    Topics: Biology , Mathematics
    Notes: Abstract After giving a brief review of the theory of organismic sets (Bull. Math. Biophysics,29, 139–152, 1967;31, 159–198, 1969), in which the concept of relational forces, introduced earlier (Bull. Math. Biophysics,28, 283–308, 1966a) plays a fundamental role, the author discusses examples of possible different structures produced by relational forces. For biological organisms the different structures found theoretically are in general agreement with observation. For societies, which are also organismic sets as discussed in the above references, the structures can be described only in an abstract space, the nature of which is discussed. Different isomorphisms between anatomical structures, as described in ordinary Euclidean space, and the sociological structures described in an abstract space are noted, as should be expected from the theory of organismic sets.
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  • 8
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    Notes: Abstract Current psychological research into the inference (diagnostic) process is briefly reviewed, using as a vehicle an investigation of the prediction of the probability of success of hypothetical applicants to a graduate program in biology. Brunswik’s lens model and multiple regression analysis are used, as is a Bayesian approach. Four judges’ (biologists’) predictions are analyzed. Some general conclusions about inference, drawn from the current data in psychology, are presented.
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  • 9
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    Bulletin of mathematical biology 33 (1971), S. 451-462 
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    Notes: Abstract A mathematical model has been developed to simulate the glucose-insulin interaction following a glucose load such as occurs in an IVGTT. This model differs from earlier models in that the insulin response to glucose loading is a recurring all or none threshold response. The model has been simulated on a digital computer using the digital analog simulation language CSMP.
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  • 10
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    Bulletin of mathematical biology 33 (1971), S. 463-479 
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    Notes: Abstract The composite nature of bone dictates the use of a model for bone which is transversely isotropic. We solve the associated sets of partial differential equations governing the dynamic elastic behavoor of a two-layered cylindrical-shaped bone. The solution is analyzed for long, short, and intermediate length waves. The special case of compact bone is treated for long and short wave lengths and a numerical example is worked out to determine the wave speeds (for short wave lengths) given a set of elastic constants, determined by ultrasonic methods, and the bone density, wave frequency, and radius.
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  • 11
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    Bulletin of mathematical biology 33 (1971), S. 481-481 
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  • 12
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    Bulletin of mathematical biology 46 (1984), S. 967-969 
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    Notes: Abstract It is observed that a dynamical continuity equation for biomass distribution yields the asymptotic steady-state exponential dependencen=A exp( $$ - m/\bar m$$ ) exhibited by certain fishery data, wherem is the biomass of an individual,n is the number of individuals per unit biomass interval, andA, $$\bar m$$ are positive constants. This dynamical approach to biomass distribution is an alternative to the global maximization principle proposed recently by Lurié and Wagensberg.
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  • 13
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    Bulletin of mathematical biology 46 (1984), S. 971-972 
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  • 14
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    Bulletin of mathematical biology 46 (1984), S. 973-974 
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  • 15
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    Bulletin of mathematical biology 49 (1987), S. 321-327 
    ISSN: 1522-9602
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    Notes: Abstract The entropy budget of a white-tailed deer (50kg) on a maintenance diet and a full-feed diet in a standing posture in an open field under clear nocturnal skies with an air temperature of −20°C is investigated based on the energetics given by Moen. Entropy inflow into a white-tailed deer due to infra-red radiation and entropy outflows from a deer due to infra-red radiation, convection, evaporation of water and conduction to ingested food are calculated. Also the entropy production due to metabolic heat production is estimated. Net entropy flow into a deer from its environment becomes negative. On the assumption that a white-tailed deer is in a steady state in entropy, the total entropy production in a deer on a maintenance diet becomes +0.46 J/sec/K. Positiveness of the entropy production shows that the Second Law of Thermodynamics certainly holds in a white-tailed deer. The entropy production per effective radiating surface area of a deer on a maintenance diet is 0.32×10−4 J/cm2/sec/K. On the other hand, the entropy production in a deer on a full-feed diet is 0.59 J/sec/K and that per effective surface area is 0.41×10−4 J/cm2/sec/K. Uptake of 1 g of food produces 22 J/K of entropy within the body of a white-tailed deer. Comparison is made with the results for entropy production in a lizard and in plant leaves.
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  • 16
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    Bulletin of mathematical biology 49 (1987), S. 507-517 
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  • 17
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    Bulletin of mathematical biology 49 (1987), S. I 
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  • 18
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    Bulletin of mathematical biology 49 (1987), S. 531-538 
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    Notes: Abstract Biological adaptability has been proved to be analysable by means of the Maximum Entropy Formalism (MAXENT) in some cases of non-interacting systems. This formalism is extended to the biomass statistical structures of populations exhibiting internal interactions (i.e. predatorprey effects).
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  • 19
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    Notes: Abstract The temporal behaviours of the nonlinear substructure of a self-organized compartmental model of calcium metabolism were investigated. The order-two autocatalytic process included in this simple two-dimensional model is compared to some secondary nucleation mechanisms which should take place at the extracellular fluid-bone interface. The model gives rise to complex dynamic behaviours, and multistability properties, involving up to two stable periodic regimes (birhythmicity), were established in different topological configurations. The bifurcations occurring on the boundaries between regions of different qualitative behaviour have been determined. These properties are discussed in relation to the dynamical behaviour of other two-variable models, especially those including the same nonlinearity.
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  • 20
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    Bulletin of mathematical biology 49 (1987), S. 615-627 
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    Notes: Abstract A linearized oscillation theorem due to Kulenović, Ladas and Meimaridou (1987,Quart. appl. Math. XLV, 155–164) and an extension of it are applied to obtain the oscillation of solutions of several equations which have appeared in population dynamics. They include the logistic equation with several delays, Nicholson's blowflies model as described by Gurney, Blythe and Nisbet (1980,Nature, Lond. 287, 17–21) and the Lasota-Wazewska model of the red blood cell supply in an animal. We also developed a linearized oscillation result for difference equations and applied it to several equations taken from the biological literature.
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  • 21
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    Bulletin of mathematical biology 49 (1987), S. I 
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  • 22
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    Notes: Abstract A theoretical approach to the explanation of the structural design of metabolic pathway is presented. It is based on the hypothesis that due to natural selection during evolution the cellular metabolism of present-day organisms may be characterized by optimal properties. Two cardinal terms enter the theory: (i) the efficiency of a metabolic pathway and (ii) the evolutionary effort for the change of the kinetic parameters of enzymes by mutations of the corresponding genes. For both quantities simple mathematical expressions are proposed. While the efficiency is related to the reaction rates of the enzymes constituting the metabolic pathway, the evolutionary effort is considered to be a monotonically increasing function of the parameter values. By maximizing the efficiency under the constraint of a fixed evolutionary effort the theory allows the calculation of the optimal parameter distribution as the outcome of evolution processes. The methods developed are applied to the following systems: (a) linear reaction sequences with very low affinities of the enzymes towards substrates, (b) linear sequences consisting of saturable enzymatic reactions, (c) branched metabolic pathways consisting of segments of linear chains and (d) glycolysis of erythrocytes. The conclusion is derived that the optimal distribution of kinetic constants depends strongly on the equilibrium constants of the reactions as well as on the total osmolarity of the metabolic intermediates. Without osmotic constraints the evolutionary effort is mainly spent on the enzymes at the beginning of the chain. Using Michaelis-Menten equations the optimal state is characterized by a decrease of the maximal activities of the enzymes towards the end of the chain. These results are modified if osmotic constraints are taken into account. At the investigation of branched pathways the following results were obtained: firstly, if a certain end product may be synthesized along different pathways those which are thermodynamically more unfavourable (e.g. characterized by a small change of free energy) are eliminated in the course of evolution; secondly, if a branched pathway leads to several important end products those reaction segments which are thermodynamically unfavourable are characterized by a higher evolutionary effort. The application of the theory to a realistic model of glycolysis of erythrocytes leads to a correct description of various functionally important properties of the system, such as the ratio between fluxes through different branches and the ATP/ADP ratio, whereas the theory cannot predict the strong separation of time constants observed in the real glycolytic system. It is concluded that the improvement of the predictive power of the theory necessitates the use of more complex functionals for the efficiency which take into account not only the fluxes but also other system properties such as the stability of the pathway or homoeostatic effects.
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  • 23
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    Bulletin of mathematical biology 46 (1984), S. 11-17 
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    Notes: Abstract Linear birth and death processes are used to derive simple expressions for sequential extinction times and gene fixation probabilities in asexual populations.
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    Bulletin of mathematical biology 46 (1984), S. 1-10 
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    Notes: Abstract We are here concerned with the functionf which assigns to each pointP of an object the numberf(P) which is the shortest distance fromP to the border. This function appears in various guises in diverse biological studies. The functionf(P) is itself a measure of shape—or more precisely, an infinite set of measures, one for each point (and hence, in view of its geometric definition, usually in a form inconvenient for use). Thus in this paper we sought a reasonable representative of this infinite set of measures, namely themean of the numbersf(P) asP ranges over all points of the entity. Computability studies are developed for various classes of shapes. For example, (1) the mean for a lamina bounded by a polygon circumscribable about a circle of radiusr isr/3; (2) the mean for a domain bounded by a polyhedron circumscribable about a sphere of radiusr isr/4. The transition from pointwise to piecewisef(P), especially in the non-convex case, requires working with inequalities.
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    Bulletin of mathematical biology 46 (1984), S. 19-40 
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    Notes: Abstract A mathematical model for traveling bands of motile and chemotactic bacteria in the presence of cell growth and death is examined. It is found that asymptotic traveling wave solutions exist in the absence of chemotaxis, due to the balance of growth, death and random motility. Thus random motility confers the ecological advantage of population propagation through migration into nutrient-rich regions. The presence of chemotaxis amplifies this advantage by moving more cells into higher nutrient concentration regions, resulting in larger and faster bands. Therefore there seem to be two types of traveling bands that can be attained by chemotactic bacteria in the presence of growth and death: (1) these growth/death/motility bands; and (2) pure chemotactic ‘Keller-Segel'-type bands. Comparison to experimental observations by Chapman in 1973 indicate that the latter seem to be formed. The relationship between these two types of solution is at present uncertain. The growth/death/motility bands may have relevance on longer time or distance scales characteristic of microbial ecological systems.
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    Bulletin of mathematical biology 46 (1984), S. 115-125 
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    Notes: Abstract Based on the principle of minimum power, a mathematical model of the pathological functional state of the oxygen transport system is presented. The model is used to determine the optimal functional parameters of the oxygen transport system in hyperthyroidism, anemia and hypertension. Theoretical results are compared with clinical data.
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    Bulletin of mathematical biology 46 (1984), S. 139-153 
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    Notes: Abstract A modified SIRS model is developed as a framework for the study of epizootiological dynamics in an insect-pathogen system. Linearized stability analysis reveals that the system with one immune and one susceptible host class can exhibit stable, periodic or unstable behavior depending on model parameters. In general, high pathogenicity, short pathogen propagule lifespan and high host reproductive rate are stabilizing influences. Pathogen transmissibility and propagule production/host do not influence local stability. The effect of seasonal host reproduction is studied because most insect hosts are seasonal in temperate climates. The basic stability dependence on model parameters holds except as modified by the length of the reproduction interval. The results of this study are compared with the recent work of Anderson and May.
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    Bulletin of mathematical biology 46 (1984), S. 175-184 
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    Notes: Abstract The random predator-prey type interactions of the population species in a random varying environment have been investigated. The Fokker-Planck equation for the transition probability, corresponding to the stochastic differential equations established from Lotka-Volterra equations by the introduction of randomness and variability, has been integrated in the form of a path integral. The transition probabilities for extinction or survival of one or several species have been approximately evaluated and investigated.
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    Bulletin of mathematical biology 46 (1984), S. 155-174 
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    Notes: Abstract If two microbial populations compete for a single resource in a homogeneous environment with time invariant inputs they cannot coexist indefinitely if the resource competed for is not renewed by biological activity within the system. Mathematical studies have shown that in a predator-prey system, where the resource (prey) is self-renewing, the two competitors (predators) can coexist in a limit cycle. This suggests that if the resource competed for is renewed by biological activity within the system coexistence can occur in any microbial system provided that it exhibits the same features as, but without being, a predator-prey one. A food chain involving commensalism, competition and amensalism is presented here. Two subcases are considered. It is only when maintenance effects are taken into account that coexistence, in limit cycles, can occur for this system. Limit cycle solutions for the system are demonstrated with the help of computer simulations. Some necessary conditions for coexistence are presented, as are some speculations regarding the possible physical explanations of the results.
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    Bulletin of mathematical biology 46 (1984), S. 127-137 
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    Notes: Abstract The branching structure of the mammalian arterial tree has been known to be close to that of an optimal conduit system of the minimum work model characterized as the branch system of constant wall shear rate. The physiological mechanism producing such construction was considered to be based on the local response of arterial caliber induced by the wall shear stress (shear rate × blood viscosity) and thereby maintaining this stress constant, which was previously observed at the canine common carotid artery shunted to the external jugular vein. The stress levels at various parts of the arterial system estimated from available data fell within ±50% of the mean (15 dyn/cm2), which was consistent with the value predicted from the model. Theoretical analyses on the cost function of the model indicated that the suspected variation of shear rate levels in the arterial tree due to the anomalous changes in blood viscosity which might bring about 3- to 4-fold differences between the minimum and maximum shear rates would cause less than 10% increase in the total energy cost. It was concluded that a local adaptive response to wall shear stress is the mechanism which effectively optimizes the design of the arterial tree.
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    Bulletin of mathematical biology 46 (1984), S. 185-185 
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    Bulletin of mathematical biology 46 (1984), S. 187-203 
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    Notes: Abstract The structure of the genetic code is related to a Gray code, which is a plausible theoretical model for an amino acid code. The proposed model implies that the most important factor in shaping the code was the effects of mistakes in translation, not effects of mutations. Another possible implication is that the preservation of stiffness and flexibility at appropriate places in a protein chain is as important in protein structure as the appropriate placement of hydrophilic (external) and hydrophobic (internal) residues. Other results are a simple conceptualization of the relationships among the 20 amino acids and their relations to their codons. The detailed relationships are summarized in the following ‘similarity alphabet’: ala, thr, gly, pro, ser; asp, asn, glu, gln, lys; his, arg, trp, tyr, phe; leu, met, ile, val, cys; (ATGPS DNEQK HRWYF LMIVC in the one-letter code). This alphabet falls into four groups of amino acids: small, external, large, internal. The approximate relation of the groups to their codons is expressed as: the first base of a codon controls size—a purine means a small amino acid, a pyrimidine means large; the middle base controls cloisterednes—purine means external, pyrimidine means internal. These relationships express the minimum change principle upon which the code appears to be founded.
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    Bulletin of mathematical biology 46 (1984), S. 269-282 
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    Notes: Abstract A theoretical study of the Brusselator model with non-uniform distribution of component A and a concentration-dependent diffusion coefficient has been performed. Numerical simulation reveals that a variable diffusion coefficient alters the bifurcation pattern and the stability properties of the steady-state as well as periodic solutions. A simple approximate method, based on one-point collocation, has been proposed to analyze the bifurcation phenomena for the case of fixed boundary conditions and low system size.
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    Bulletin of mathematical biology 46 (1984), S. 283-294 
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    Notes: Abstract In this paper the effects of the occurrence of cut trees in the topological analysis of branching patterns have been studied. It is assumed that branches are removed at random from the trees. We prove that, for both the segmental and terminal growth models, the probability distributions of the cut trees are identical to those of complete trees.
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    Bulletin of mathematical biology 46 (1984), S. 247-268 
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    Notes: Abstract The goal of this work is an examination of capillary exchange models as mathematical operators. The concentration function relations for the Krogh cylinder of a single capillary, basic to many organ models, are studied via the theory of operators on the Lebesgue normed spacesL p[0,∞], (1〈-p〈-∞). A discussion is included of theL p -normsvis-à-vis the coefficient of variation currently used in finding capillary parameters and evaluating parameter searches. The capillary model determines two operators on the space of locally integrable functions: O K (relating extravascular concentration to intravascular) and K a, k (relating intravascular concentration to input), wherek is the ratio of permeabilitysurface area (PS) to extravascular volume, and α is the ratio of PS to flow. These operators are shown to induce contractive (‖O K ‖ p 〈-1, ‖K a, k ‖ p 〈-1), isotone, linear operators onL p . The uniform convergence relation $$K_{a,k} = \mathop {\lim _{(p)} }\limits_{N \to \infty } \left( {\sum\limits_{n = 0}^N {P_n (a)O_k^n } } \right)$$ (as operators onL p) is derived, whereP n (a) is the Poisson probabilitye −a a n /n!. For the important special cases ofp=∞, 1, 2 the norms are found (‖Ok‖=‖Ka,k‖p=1). Consideration is also given to the norms and operators when the functions involved are limited to a finite interval of time.
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    Bulletin of mathematical biology 46 (1984), S. 295-326 
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    Notes: Abstract One particular kind of structure offers possible explanations, for long-term memory, efficient consolidation of stored information from the environment, clustering of data strings and multimodal functioning. It is a possible model for pieces of neural structure and its use offers a uniform method for both studying and constructing an extensive class of mechanisms.
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    Bulletin of mathematical biology 46 (1984), S. 327-332 
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    Notes: Abstract Levenshtein dissimilarity measures are used to compare sequences in application areas including coding theory, computer science and macromolecular biology. In general, they measure sequence dissimilarity by the length of a shortest weighted sequence of insertions, deletions and substitutions required, to transform one sequence into another. Those Levenshtein dissimilarity measures based on insertions and deletions are analyzed by a model involving valuations on a partially ordered set. The model reveals structural relationships among poset, valuation and dissimilarity measure. As a consequence, certain Levenshtein dissimilarity measures are shown to be metrics characterized by betweenness properties and computable in terms of well-known measures of sequence similarity.
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    Bulletin of mathematical biology 46 (1984), S. 337-337 
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    Bulletin of mathematical biology 46 (1984), S. 333-336 
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    Notes: Abstract It is pointed out that the methane flux measured experimentally for certain ponds and swamps is quantitatively consistent with a commensal dependence of Methanobacteria on O2-chemotactic motile aerobic bacteria. The Methano species is thereby shielded from oxygen and provided with carbon dioxide for the anaerobic production of methane.
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    Bulletin of mathematical biology 46 (1984), S. 357-370 
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    Notes: Abstract A sufficient condition is given for stochastic boundedness persistence of a top predator in generalized Lotka-Volterra-type stochastic food web models in arbitrary bounded regions of state space. The main result indicates that persistence in the corresponding deterministic system is preserved in the stochastic system if the intensities of the random fluctuations are not too large.
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    Bulletin of mathematical biology 46 (1984), S. 371-377 
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    Notes: Abstract One of Bobisud's models for the evolution of cannibalism is reanalyzed by applying the method of finding evolutionarily stable strategies (or ESS's). It is demonstrated that ‘no cannibalism’ never will be an ESS if the initial rate of cannibalism is too large. It is further demonstrated that individual selection may even result in the evolution of cannibalism during food abundance. Some empirical case studies are briefly discussed in relation to this model.
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    Bulletin of mathematical biology 46 (1984), S. 379-387 
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    Notes: Abstract A computer algorithm is presented which equiprobably generates any member of the set of all directed trees withk labeled terminal nodes and unlabeled interior nodes. The algorithm requires roughlyk 2 /2 storage locations. The one-time initialization requiresO(k 2 ) time, while generating each tree requiresO(k) time.
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    Bulletin of mathematical biology 46 (1984), S. 515-527 
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    Notes: Abstract The comparison of several sequences is central to many problems of molecular biology. Finding consensus patterns that define genetic control regions or that determine structural or functional themes are examples of these problems. Previously proposed methods, such as dynamic programming, are not adequate for solving problems of realistic size. This paper gives a new and practical solution for finding unknown patterns that occur imperfectly above a preset frequency. Algorithms for finding the patterns are given as well as estimates of statistical significance.
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    Bulletin of mathematical biology 46 (1984), S. 501-514 
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    Notes: Abstract A new development is introduced here in the use of dynamic programming in finding pattern similarities in genetic sequences, as was first done by Needleman and Wunsch (1969). A condition of pattern similarity is defined and an algorithm is given which scans any set of similarities and screens out those which fail to meet the condition. When the set to be scanned contains every pair of segments, one from each of two given sequences of lengthsm andn (i.e. every possible location for a pattern similarity), then it completes the scan in a number of computational steps proportional tom·n, leaving those pairs of segments which satisfy the similarity condition. The algorithm is based on the concept of match density, as suggested by Goad and Kanehisa (1982).
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    Bulletin of mathematical biology 46 (1984), S. 529-543 
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    Notes: Abstract This paper concerns sequences of letters in which certain “distinguished” words are of interest. Such sequences arise as data in numerous fields including genetics and neuroscience. A probability distribution is given for the number of occurrences of a chosen word in a randomized sequence of letters. Such words are considered “favored” if they occur more than expected at random. Favored words have been discovered in nerve impulse trains and may reflect a neural coding scheme.
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    Bulletin of mathematical biology 46 (1984), S. 545-552 
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    Notes: Abstract As the volume of protein sequence data grows, rapid methods for searching the protein sequence database become of primary importance. Rigorous comparison of sequences is obtained with the well-known dynamic programming algorithms. However, these algorithms are not rapid enough to use for routinely searching the entire database. In this paper we discuss some methods that can be used for rapid searches.
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    Bulletin of mathematical biology 46 (1984), S. 553-566 
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    Notes: Abstract We give algorithms for computing the extent of similarity between two or three sequences of letters. The similarity measures we consider include a penalty for inserting gaps within the sequence in order to enhance similarity. The magnitude of the penalty for gaps is assumed to be independent of their size in order to accommodate certain biological applications. Our algorithm for three sequence comparisons, which is based on solving a system of recursive equations, improves upon the efficiency of existing methods. Although the system of recursive equations utilized by the algorithm is quite complicated as it stands, it has none the less been simplified by appeal to combinatorial considerations.
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    Bulletin of mathematical biology 46 (1984), S. 567-577 
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    Notes: Abstract Well-known dynamic programming algorithms exist for comparing two finite sequences inO(N 2) time and storage, whereN is the common sequence length. Extensions to the comparison ofM finite sequences requireO((2N) M) time and storage, making such algorithms difficult even forM=3. A simple generalization of the sequences makes it possible to obtain some results about the geometry of sequence alignments. These ideas suggest heuristic approaches to problems of comparing several sequences. IfM sequences are known to be related by a binary tree, they can be aligned inO(MN 2) time andO(N 2+NM) storage.
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    Bulletin of mathematical biology 46 (1984), S. 661-672 
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    Notes: Abstract Protein sequences of the Dayhoff databank of 1984 have been analyzed to evaluate the occurrences of the 400 dipeptides and 8000 tripeptides. Expected values and standard deviations for the di- and tripeptides were determined by Monte Carlo and binomial approximation. A condensed format containing this information, labeled a uniqueness diagram, is presented and made available in the form of a microfiche.
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    Bulletin of mathematical biology 46 (1984), S. 827-844 
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    Notes: Abstract In two-state sliding filament models of muscle contraction a partial differential equation must be solved to find the cross-bridge distribution functionn(x, t). In this paper the analytical form of this function is obtained by integration along the characteristic line and special cases are presented in which the explicit expression forn(x, t) can be completely determined. These analytical solutions provide a direct mathematical connection between the microscopic contraction parameters contained in the kinetic theories and macroscopic muscle dynamics and are thus used to investigate what parameters influence the transient contractile tension in typical experimental conditions. The results of this investigation are consistent with relevant aspects of muscle physiology.
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    Bulletin of mathematical biology 46 (1984), S. 845-857 
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    Notes: Abstract Experiments on random binary, ternary, etc. (P=2, 3,…, 10) switching nets are reported. Behavioral cycle lengths are examined as functions of output variety,P, input connectance,K, and net size,N. Overall, output variety appears an influential, well-behaved net property. Strong, but well-behaved interactions appear among net variables. In high connectance nets, median cycle length grows approx. asP N/2. Other factors constant, one-connected nets show the shortest cycles, and connectance effects appear to converge asymptotically aroundN. Data for cycle length as a function of net size suggest a concavity not compatible with the Kauffman “square root law” (Kauffman, 1969). Evidence of a positive relationship between cycle length and run-in length is found in two-input nets; weaker evidence is obtained that in higher connectance nets this relationship becomes negative in sign. The “modular complexity” ofP〉2 nets is examined briefly.
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    Bulletin of mathematical biology 46 (1984), S. 869-877 
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    Notes: Abstract The influence of topographical situation on the spread of infection is studied. The investigation is based on a multigroup model. The population under consideration is thought to be divided into subpopulations living in regions that are separated from each other by natural barriers (mountains). Infection is carried from one region to another by migrating infectives. Migration is possible only along the river system so that the structure of the epidemiological network is that of a symmetric tree. The results allow comparison of the velocity of propagation of the epidemic for different geographical situations and allow quantification of the “channel-effect”, according to which mountainous regions are channels rather than barriers to the spread of an epidemic.
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    Bulletin of mathematical biology 49 (1987), S. i 
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    Bulletin of mathematical biology 49 (1987), S. iv 
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    Bulletin of mathematical biology 49 (1987), S. 75-91 
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    Notes: Abstract Bayesian image processing formalisms which incorporatea priori information about valued-uncorrelated and valued-correlated (patterned) source distributions are introduced and the corresponding iterative algorithms are derived using the EM technique. Striking improvement in image processing is demonstrated when applying these algorithms to Poisson and Gaussian randomized data in one-dimensional cases.
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    Bulletin of mathematical biology 33 (1971), S. 97-115 
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    Notes: Abstract A stochastic model is developed for an enzyme reaction in an open linear system. The proposed model assumes that the open system maintains the concentration of substrate and inhibitor at constant levels and that the product molecules are removed from the system by a first order reaction. Stochastic models for several enzyme reactions occurring in this open system are shown to correspond to special cases of theGI/M/∞ queue. Takács’ (1958) results for this queueing system are used to obtain the stochastic properties of the enzyme systems. A specific model we studied assumed completely competitive inhibition in an open system. The stationary distribution for the number of product molecules in the system is obtained. The enzyme reaction which incorporated the “intermediate chain hypothesis” can also be investigated by the queueing theory approach. It is shown that for this open system, if the model which incorporated the intermediate chain hypothesis has the same deterministic properties as the Michaelis-Menten model, then the latter has greater stochastic variation than the former.
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    Bulletin of mathematical biology 33 (1971), S. 153-153 
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    Bulletin of mathematical biology 33 (1971), S. 117-128 
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    Notes: Abstract The existing methods to solve the problems of pulsatile flow in the cardiovascular system are based on either linear axisymmetric equations or non-linear one-dimensional equations. The solutions thus obtained give only a mediocre comparison with measurements. In this paper, a non-linear axisymmetric theory is proposed. The starting point of the present theory is a third degree polynomial representation of the velocity profile. Integral methods are then applied to obtain the governing equations. To ascertain the accuracy of the theory proposed above, the calculations for a simple case involving pulsatile flow in a long rigid tube were performed. The results are: (a) the average velocities compare very well with exact solutions and (b) the velocity profiles for a given frequency agree very well with exact solutions for flow in small tubes, but tend to differ as tube size is increased.
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    Bulletin of mathematical biology 33 (1971), S. 129-151 
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    Notes: Résumé Le but de ce travail est la mise en évidence d’éventuels “patterns” temporels privilégiés de potentiels d’action neuronaux masqués par la superposition d’une activité aléatoire. Dans la première partie, on propose un modèle susceptible de rendre compte de cette activité aléatoire. Dans la seconde, on expose une méthode d’extraction des patterns privilégiés, compatible avec les paramètres du modèle neuronal proposé. Son algorithme fait notamment intervenir l’estimation de la fonction d’expectation. Cette méthode peut, en fait, ment intervenir l’estimation de la fonction d’expectation. Cette méthode peut, en fait, être appliquée à l’étude de séries temporelles d’événements dans des domaines très divers.
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    Bulletin of mathematical biology 33 (1971), S. 155-156 
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    Bulletin of mathematical biology 33 (1971), S. 355-372 
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    Notes: Abstract An effort is made to begin widening the scope of kinetics by merging the concepts and point of view of molecular set theory with the stochastic approach to kinetics, beginning with the simplest unimolecular molecular set transformation. In this spirit the new concept ofmolecular set variable is introduced as the basic unit of kinetics as opposed to simply the traditionalconcentration (or cardinality) unit, connoting that the composition as well as the size of a molecular set are significant dynamic features of a system. The changes in state (or “value”) of the molecular set variable are characterized by a Markovian stochastic process and the relationship between this process and the corresponding unimolecular process for the concentration variable introduced earlier is discussed. The possible role of molecular set theory in terms of the underlying biomathematical structure of relational biology is also considered.
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    Bulletin of mathematical biology 33 (1971), S. 387-401 
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    Notes: Abstract The problem of the forms of plants and models of branching are discussed using experimental data on the mistletoe. The number of branches by division, the distribution of divisions with regard to the number of branches per division and to the level of division, the geometrical characters of branches according to the level of division and the host, the stability of model are studied. One gives an interpretation of the model of branching as a model of growth.
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    Bulletin of mathematical biology 33 (1971), S. 373-386 
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    Notes: Abstract A quantum model for the general enzymic reaction,E+S ⇌ ES → P, is presented, starting with the assumptions that any chemical substanceS, which may be a substrate for a particularE (S)-enzyme is a microphysical system and any enzymeE-molecule, capable of interacting with anS-substrate is a “measuring system” which will “measure” one or more of theS-observables. According to the above assumptions a stochastic model of the reaction is constructed and a computer simulation of the steady state performed. The results thus obtained predicted fluctuations in the enzymic reaction rate, function of the substrate “perturbation”. On an experimental basis it is demonstrated that the irradiation of an enzymic substrate with low energies results in the inducement of a dose-dependent oscillatory behavior in the corresponding enzymic reaction rate. In the reaction type, the oscillations thus induced in theE-activity by the corresponding substrates are out-of-phase, realizing a biochemical discriminating net. Likewise, in an $$S_1 \xleftarrow{{E_1 }}S\xrightarrow{{E_2 }}S_2$$ reaction type, the oscillations induced by the irradiatedS-substrate in the activities of the respective enzyme, realize a biochemical switching net.
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    Bulletin of mathematical biology 49 (1987), S. iii 
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    Bulletin of mathematical biology 49 (1987), S. 1-11 
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    Notes: Abstract A stochastic model for the population regulated by logistic growth and spreading in a given region of two-or three-dimensional space has been introduced. For many-species population the interactions among the species have also been icorporated in this model. From the random variables that describe stochastic processes of a Wiener type the space-dependent random population densities have been formed and shown to satisfy the Langevin equations. The Fokker-Planck equation corresponding to these Langevin equations has been approximately solved for the transition probability of the population spreading and it has been found that such approximate expressions of the transition probability depend on the solutions of the deterministic equations of the diffusion model with logistic growth and interactions. Also, the stationary or equilibrium solutions of the Fokker-Planck equation together with the special discussion on the pattern of single-species population spreading have been made.
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    Bulletin of mathematical biology 49 (1987), S. 13-50 
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    Notes: Abstract The notion of an evolutive hierarchical system proposed in this paper is a mathematical model for systems, like organisms, with more or less complex objects. This model, based on category theory, retains the following characteristics of natural systems: they have an internal organization consisting of components with interrelations; they maintain their organization in time though their components are changing; their components are divided into several levels corresponding to the increasing complexity of their own organization, and the system may be studied at any of these levels (e.g. molecular, cellular...). The state of the system at a given instant is modeled by a category whose objects are its components, the state transition by a functor, a complex object by the (direct) limit of a pattern of linked objects (which describes its internal organization). The properties of limits in a category make it possible to ‘measure’ the emergence of properties for a complex object with respect to its components, and to reduce the study of a hierarchical system to that of its components of the lowest degree and their links. Categorical constructions describe the formation of a hierarchical evolutive system stepwise, by means of the operations: absorption of external objects, destruction of some components, formation of new complex objects.
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    Bulletin of mathematical biology 49 (1987), S. 93-123 
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    Notes: Abstract An algorithmic formulation is presented for the inference procedure concerning lineage models. The problem is to find lineage rules from observed sequences of tree structures under the assumption that no interactions take place in the course of development and that sufficiently frequent observations are available at equal time intervals. The underlying structural pattern is taken to be a OL system, and the goal is to find propagating and deterministic OL schemes with minimal properties satifsying certain biological reliance criteria. Upper bounds have been found for the complexity of the inference algorithms.
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    Bulletin of mathematical biology 49 (1987), S. 125-131 
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    Notes: Abstract A statistical theory of non-equilibrium fluctuation in Volterra-Lotka systems has been presented on the basis of the technique of statistical linearization of non-linear coupled stochastic differential equations.
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    Bulletin of mathematical biology 49 (1987), S. 135-152 
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    Notes: Abstract Under certain basic assumptions the branching pattern of dendrites can be modeled as a Galton-Watson process in varying environment. Using results from graph theory we compute the probability distributions, expectations and variances for biologically significant variables such as the number of (intermediate and terminal) branches, the maximum number of orders, etc., together with the limit behavior of these quantities. Furthermore, the probability measure induced by the Galton-Watson process on the set of all trees is calculated. The measure assigns to any set of branching patterns the probability that it is realized by a certain process, which is completely described through the bifurcation probabilities.
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    Bulletin of mathematical biology 49 (1987), S. 187-216 
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    Notes: Abstract Theoretical models for DNA repair mechanisms are constructed. Reliability studies considering the living cell as a repairable system are done. The DNA repair process is discussed along with applications and comparison with available experimental data.
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    Bulletin of mathematical biology 49 (1987), S. 153-169 
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    Notes: Abstract A mathematical model has been developed to simulatein vivo transmural accumulation of an intravenously injected tracer in the aortic wall of experimental animals. Parameters have been included to represent the following processes that affect tracer distribution: permeation of the blood-tissue interface, diffusion through the layers of the artery wall,convective solute drag through the same, and degradation. Of particular interest for thein vivo situation situation is the inclusion of boundary conditions that account for the variation in the plasma concentration of injected tracer as a function of time. Two analytical solutions are presented. The first describes a system in which two boundaries must be delineated; it pertains if the tracer is allowed to circulate until it enters the avascular media of the artery wall both across its luminal boundary and from the capillaries in its outer layer. The second applies to shorter duration experiments in which entry across only the luminal boundary is considered. A limiting case of the solution for short circulation times is presented, compared with a previously published solution, and examined for its potential utility in parameter estimation. Because of its treatment of time-dependent boundary conditions, the model has unique application toin vivo experiments related to macromolecular transport in atherosclerosis that may otherwise elude proper interpretation.
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    Bulletin of mathematical biology 49 (1987), S. 233-252 
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    Notes: Abstract Several current reaction-diffusion mechanisms have been proposed as models for morphogenesis in the Turing (1952,Phil. Trans. R. Soc. Lond. B 237, 37–72) sense. We introduce and exploit a quantity, we have termed heterogeneity, which allows us to elaborate the differences between the various models with regard to spatial pattern formation. It is shown that this quantity provides a concise view for the comparison of theoretical models with experimental observations. Two model mechanisms are treated explicitly both for linear and for biased diffusion.
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    Bulletin of mathematical biology 49 (1987), S. 351-361 
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    Notes: Abstract The optimum number of total capillaries in the whole human body was estimated from the analysis of the efficiency for oxygen (O2) transport in the vascular-tissue system. We used a tissue model composed of uniform spheres in which O2 diffuses from the capillary located at the centre of each sphere towards the surrounding tissue consuming O2 at a constant rate. The tissue mass supplied by a single capillary was estimated as the area of positive O2 concentration under a given condition of capillary flow and O2 consumption rate. Total tissue mass was determined as the function of the capillary numbern and the total blood flow. On the other hand, the energy cost required to maintain the vascular system withn terminals was assessed by using the minimum volume model (Kamiya and Togawa,Bull. math. Biophys. 34, 431–438, 1972). The efficiency of the entire vascular-tissue system was evaluated by calculating the ratio of total tissue mass/cost function. The result of the calculation using physiological data of cardiac output and O2 consumption for an average human adult during a heavy exercise revealed the maximum efficiency occurring at the capillary number 3.7×1010 which coincided well with its normal range of physiological estimates (3.2×1010–4.2×1010). We concluded that the entire vascular-tissue system is constructed so as to attain the highest efficiency in O2 transport at its maximum activity.
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    Bulletin of mathematical biology 49 (1987), S. 379-394 
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    Notes: Abstract A kinetic model involving synthesis of proinsulin in the rough endoplasmic reticulum, maturation through the Golgi apparatus and granules, with conversion to insulin, is proposed to account for data on the amount of insulin and of proinsulin both secreted during various time intervals and remaining in islets. Introducing three compartments for granules makes it possible to account for the measurement of both hot (pulse labeled with tritiated leucine) and cold proinsulin and insulin over a period of 21/2 hr under constant glucose. Data from islets from animals pretreated with tolbutamide are also presented and modeled. The model is then expanded so that it can be successfully applied to available data on the effects of a period of glucose deprivation on secretion of both hot and cold hormone. Parameters have essentially the same values, where they overlap, as were obtained (Landahl and Grodsky, 1982Bull. math. Biol. 44, 399–410) from insulin secretion by perfused rat pancreas stimulated by a variety of temporal patterns of glucose concentration.
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    Bulletin of mathematical biology 49 (1987), S. 413-429 
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    Notes: Abstract Two models of binary tree growth are examined in terms of the Strahler order branching ratio (Rb) and the types of vertex produced during growth, and their inter-relationship. The sequential growth model is that described by Van Pelt and Verwer (1985,Bull. math. Biol. 47, 323–336) in which random growth occurs according to attributed probabilities on terminal or internal segments, one branch at a time. This model generates values ofRb≥3. The synchronous growth model is new and permits more than one segment to branch at a time, again randomly with attributed probabilities. This model generates values ofRb≥2 and in particular, when only terminal branching is permitted, gives 2≤Rb〈3. Such a model might explain the branching in the human bronchial tree, in which 2.5≤Rb≤2.8. Our synchronous model is an alternative to the centrifugal-order-dependent sequential model of Van Pelt and Verwer.
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    Bulletin of mathematical biology 49 (1987), S. 449-460 
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    Notes: Abstract From an energy budget of a deciduous plant leaf in moderate conditions, entropy fluxes into or out of the leaf due to solar radiation, infrared radiation, evaporation of water and heat conduction are calculated. Net entropy flow into the leaf is negative. On the assumption that the entropy in the leaf is in a steady state, the entropy production in the typical deciduous leaf in moderate conditions [the solar energy absorbed by both sides of the leaf isE solar=0.0602 (J cm−2 s−1)] becomesS prod=1.8×10−4 (J cm−2 s−1 K−1). The positiveness of the entropy production shows that the Second Law of Thermodynamics certainly holds in the plant leaf. Entropy productions in other conditions are also calculated. The entropy production in the leafS prod becomes a linear function of the solar energy absorbed by the leafE solar:S prod≈-(29.5E solar)×10−4. A theorem is presented: the entropy production in plant leaves oscillates during the period of one day, paralleling the daily solar energy absorbed by leaves.
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    Bulletin of mathematical biology 49 (1987), S. 461-467 
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    Notes: Abstract Molecular biologists strive to infer evolutionary relationships from quantitative macromolecular comparisons obtained by immunological, DNA hybridization, electrophoretic or amino acid sequencing techniques. The problem is to find unrooted phylogenies that best approximate a given dissimilarity matrix according to a goodness-of-fit measure, for example the least-squares-fit criterion or Farris'sf statistic. Computational costs of known algorithms guaranteeing optimal solutions to these problems increase exponentially with problem size; practical computational considerations limit the algorithms to analyzing small problems. It is established here that problems of phylogenetic inference based on the least-squares-fit criterion and thef statistic are NP-complete and thus are so difficult computationally that efficient optimal algorithms are unlikely to exist for them.
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    Bulletin of mathematical biology 33 (1971), S. 403-412 
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    Notes: Abstract This paper is the second of a pair dealing with some mathematical properties of metabolic steady state. An investigator wishing to compute the rate of appearance and/or disappearance of a metabolite in steady state within an intact biological system will usually appeal to a method involving radioactive tracers. It is shown that while the investigator’s choice of the mode of tracer administration (constant infusion or single injection) is largely arbitrary, the mathematical interpretation of the results may depend upon the presence or absence of gradients in certain of the variables of the system. The latter will be the case if the system is sampled at a point within the distribution space of the metabolite which is not a source point but is otherwise arbitrary. In order to deduce a formula which gives the required rate, he must have knowledge of the gradient of concentration of the traced substance, and sometimes of the gradient of specific activity.
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    Bulletin of mathematical biology 33 (1971), S. 413-424 
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    Notes: Abstract Making a medical diagnosis consists of correlating knownpatterns of disease with the various classes of clinical data elicited from the history, physical examination, and batteries of tests relative to the diagnostic dynamics symbolized by atree branching into the various possible diagnostic decisions. In this paper a relational mathematical model of the reasoning aspects of the conventional medical diagnostic process is suggested as a way of extracting a general, formal concept of medical diagnosis. Computer implementation of the model is discussed briefly.
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    Bulletin of mathematical biology 33 (1971), S. 425-437 
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    Notes: Abstract Biomedical data in the form of series of observations made on a single process at regular intervals constitute a discrete time series and are eligible for time series methods of analysis. The models yielded by this analysis provide the framework within which exponential smoothing methods may operate on the data to provide recurrent forecasts of future states of the process. Because the forecasts may be made on an individual basis and are sensitive to the past behavior of the individual process, the methods are presented as being potentially of great utility in the management of chronic and progressive illnesses. When incorporated into automated testing and diagnostic systems, the forecasting method will provide the capability of making prognoses for large numbers of individuals, quickly, routinely and reproducibly.
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    Bulletin of mathematical biology 49 (1987), S. I 
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    Bulletin of mathematical biology 49 (1987), S. 279-287 
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    Notes: Abstract In order to understand the abnormal flow conditions of blood in a locally constricted blood vessel, the analytical results are obtained for the oscillatory flow of blood which behaves as a Newtonian fluid. It is here assumed that the surface roughness is cosine-shaped and the maximum height of the roughness is very small compared with the radius of the unconstricted tube. Numerical solutions are presented for the instantaneous flow rate, resistive impedance, wall shear stress and phase lag.
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    Bulletin of mathematical biology 49 (1987), S. 289-305 
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    Notes: Abstract In order to better understand the effect of initial stress in blood flow in arteries, a theoretical analysis of wave propagation in an initially inflated and axially stretched cylindrical thick shell is investigated. For simplicity in the mathematical analysis, the blood is assumed to be an incompressible inviscid fluid while the arterial wall is taken to be an isotropic, homogeneous and incompressible elastic material. Employing the theory of small deformations superimposed on a large initial field the governing differential equations of perturbed solid motions are obtained in cylindrical polar coordinates. Considering the difficulty in obtaining a closed form solution for the field equations, an approximate power series method is utilized. The dispersion relations for the most general case of this approximation and for the thin tube case are thoroughly discussed. The speeds of waves propagating in an unstressed tube are obtained as a special case of our general treatment. It is observed that the speeds of both waves increase with increasing inner pressure and axial stretch.
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    Bulletin of mathematical biology 46 (1984), S. 81-102 
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    Notes: Abstract The temperature regulation in homothermic animals is an example of a negative feedback system. It shows sudden changes of parameter values, and therefore suggests the use of catastrophe theory for its description. This paper reports on work done on the human temperature regulation mechanism to shows that the five-dimensional dual butterfly catastrophe model is sufficient for its description. Nearly all experiments reported in the literature overlook the dynamic multiparametric nature of the process. Use of catastrophe theory, on the other hand, shows that one cannot find a model with fewer than five parameters for such a system. From work by Benzinger and Kitzinger, the exact shape of part of the corresponding bifurcation set is determined.
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    Bulletin of mathematical biology 46 (1984), S. 103-114 
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    Notes: Abstract This paper is an analytical study on the pulse wave velocities in the aorta. In conformity to a physiologic state of loading, the distensibility of the vessel wall has been accounted for. The wall material is treated by using the theory of large elastic deformations. The orthotropicity of wall tissues and the effect of the surrounding tissues have been incorporated in the analysis which is based on the use of the strain energy function suggested by Vaishnavet al. Numerical values of the wave velocities of the canine middle descending thoracic aorta are computed by using the derived analytical expressions.
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    Bulletin of mathematical biology 46 (1984), S. 41-80 
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    Notes: Abstract The theory of a symmetrical 3-barrier, 4-site, single-filing ionic channel is developed. The model goes beyond earlier models by including additional sites, as well as barriers which need not be symmetrical in the applied field, and contains the earlier models as special cases. It is itself a special case of the most general 4-site model, which has 5 barriers. By considering the barriers at the mouth and middle of the channel to be sufficiently larger than the barriers separating the sites in each channel half, these barriers can be neglected; thus this case reduces to a 3-barrier model where the sites in each channel half can then be assumed to be in equilibrium with each other. The alternative 3-barrier, 4-site case, where the barrier between the sites is considered to be larger than that at the mouth of the channel, is considered elsewhere. Pure cation permeation is considered and only single-salt properties of the system are analyzed, namely occupancy, conductance, flux ratio exponent and current-voltage relation. The concentration dependences of these properties are computed and interrelated and, where possible, also given in analytical form. The mathematical relations are obtained for a channel which is symmetrical around its middle, which is the appropriate assumption for the gramicidin channel. However, the barriers themselves are allowed to be asymmetric with respect to the potential dependence, which has been found to be essential for gramicidin. Mathematically, a straight-forward matrix formulation is used; but a general theoretical method is presented for reducing a complex model (with more than 2 sites) to a simpler cases when equilibrium exists across one or several barriers, as is often the cases. This method is a prototype which makes analytical solutions of complex barrier models possible in many cases.
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    Bulletin of mathematical biology 46 (1984), S. 219-227 
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    Notes: Abstract A chain-like arrangement of four urns (a catenary system) into which different color balls (white, corresponding to radio atoms, and black, corresponding to stable atoms) are being transferred is used to simulate the transport of atoms down the GI tract of man and animals. Into the first urn (stomach) are placedw o white balls andr black balls while in the 2nd (small intestines) and 3rd (large intestines) urn, onlyr blacks are put in, with no whites. A sample of sizer is transferred from the 1st, 2nd and 3rd urns to the 2nd, 3rd and 4th (infinite universe) urns. From the random variable difference equations the first and second moments for the distribution of the number of radio atoms present in each urn are obtained. The variance of the contents of radioatoms in the excretion urn is
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    Bulletin of mathematical biology 46 (1984), S. 229-234 
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    Notes: Abstract A power series solution is presented which describes the steady-state concentration profiles for substrate and product molecules in immobilized enzyme systems. Diffusional effects and product inhibition are incorporated into this model. The kinetic consequences of diffusion limitation and product inhibition for immobilized enzymes are discussed and are compared to kinetic behavior characteristic of other types of effects, such as substrate inhibition and substrate activation.
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    Bulletin of mathematical biology 46 (1984), S. 205-217 
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    Notes: Abstract The use of spheroids as a tumor model has become commonplace since it was discovered that many cell lines can form spheroids when grown on a surface to which the cells cannot attach. This culture system complicates experiments which depend on oxygen supply because the oxygen concentration in the vicinity of a stationary spheroid has not been well defined. We present in this paper solutions to the oxygen diffusion equation for simple geometries: a spheroid in an infinite stationary medium and in a finite spherical stationary medium. Comparison of these solutions provides an estimate of the oxygen supply to a spheroid in a Petri dish. We show that typical spheroids can be expected to cause a substantial depletion of the oxygen in the nearby medium. Any disturbance of the medium or the spheroids will temporarily increase the oxygen supply. We provide a method for estimating the rate of return to equilibrium in the finite cases. These results indicate that the oxygen supply to stationary spheroids can be altered temporarily by small movements or changes in temperature which cause convection currents, or permanently by changes in the depth of the medium.
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    Bulletin of mathematical biology 46 (1984), S. 235-246 
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    Notes: Abstract Alternative sufficient conditions are derived that guarantee the stability of spatially heterogenous steady-state distributions of motile aerobic bacterial populations attracted chemotactically by oxygen, motile anaerobic populations repelled by oxygen, and the oxygen concentration itself through a stationary aqueous medium. In particular, it follows from the latter criteria that the heterogeneous steady-state distributions for cylindrical regions with arbitrary cross-sections, uniform depth and mixed Dirichlet-Neumann boundary conditions on the oxygen concentration (appropriate to certain still-water bodies in nature) are stable with respect to arbitrary perturbations in the bacteria cell and the oxygen distributions.
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    Bulletin of mathematical biology 46 (1984), S. 339-355 
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    Notes: Abstract Closed positive feedback loops of catalytic reactions between macromolecules, or hypercycles, provide a kinetic mechanism whereby each Species serves to catalyze selfreproduction of its successor in the loop. Hypercycles of five members or more evolve into limit cycles characteristic of a biochemical clock. Computer study of the coupled non-linear differential equations which describe these systems shows that the periodT n of then-species limit cycle is given byT n=nτn, where τn is an elemental repeat period reflecting translational time invariance. Analytic solutions of the equations are developed so that the time evolution of elementaryn-hypercycles can be traced in dynamical detail. It is shown that the magnitude of τn is, to good approximation, a linear function ofn. For a givenn, τn is a very sensitive function of the relative concentration a given member of the loop has at the time its predecessor dominates the state of the hypercycle. These concentrations decrease with increasingn. Aroundn=15 they become so small that elementary hypercycles become unstable against disruptive concentration fluctuations. Species concentrations for more realistic hypercycles tend not to be as small, so that the present estimate of a maximum number of components is a lower bound.
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    Bulletin of mathematical biology 46 (1984), S. 399-406 
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    Notes: Abstract The technique of the probability generating function is used to derive the stochastic differential equations for a nonlinear model based on Eigen and Schuster's theory of biomolecular selection and evolution. The stabilities of various steady states are analyzed by using the linear stability approximation. The instability of a small starting population is investigated numerically. The minimum starting populations required for steady-state survival are then estimated for a wide range of parameters.
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    Bulletin of mathematical biology 46 (1984), S. 389-398 
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    Notes: Abstract Some morphological features of the human bronchial tree were simulated by computergenerated trees. The trees were ordered by the methods of Horsfield and Strahler. Delta, the difference between the Horsfield orders of the two branches at a bifurcation, was determined by pseudorandom numbers generated according to a distribution of probabilities defined on input. By trial and error a distribution was found which resulted in trees being generated with average Strahler order branching ratios of 2.82, similar to a real bronchial tree. Branching angles and length ratio could also be defined on input. By varying these input parameters it was found that the form of the tree was quite sensitive to them, and that by a suitable choice the intrasegmental part of the bronchial tree could be simulated. It is concluded that branching ratio, length ratio, mean branching angles and distribution of delta are controlled within tight limits in the bronchial tree, and this may support the concept of optimal design.
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    Bulletin of mathematical biology 46 (1984), S. 407-422 
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    Notes: Abstract In this paper perturbation methods are used for the mathematical analysis of coupled relaxation oscillators. This study covers entrainment by an external periodic stimulus as well as mutual entrainment of coupled oscillators with different limit cycles. The oscillators are of a type one meets in the modeling of biological oscillators by chemical reactions and electronic circuits. Special attention is given to entrainment different from 1∶1. The results relate to phenomena occurring in physiological experiments, such as the periodic stimulation of neural and cardiac cells, and in the non-regular functioning of organs and organisms, such as the AV-block in the heart.
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    Bulletin of mathematical biology 46 (1984), S. 423-446 
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    Notes: Abstract A new, more realistic model of the action of ionizing radiation on mammalian cells growingin vitro is presented. Although this model requires a large number of parameters, these are linked to biologically observable quantities rather than being abstract sensitivities, as had previously been the case. Three different stochastic processes are required: {X(t);t ∈ [0, τ]}, representing damage alterations during irradiation; {(X(t), S(t));t ∈ [τ, τ+T D]}, representing changes in both damageX(t) and cell cycle positionS(t) during the post-irradiation cell cycle; and {N x(t);t ∈ [0,T G]}, representing the subsequent colony growth process conditioned on the value ofX(τ+T D). The assumptions used to define these processes extend a previous model of short term DNA damage formation and repair (Nelson S. J. 1982,Radiat. Res. 92, 120–145) to include the influence of cell cycle progression on damage in the irradiated cell and the effect of permanent inherited damage on the daughter cells' colony growth pattern. Expressions corresponding to commonly measured radiation effects are derived from the model and compared with predictions from previous models. It is found that these previous models oversimplified the mechanism of radiation action because they did not adequately represent repair during irradiation, the influence of radiation-induced cycle delays and damage inheritance by any daughter cells. Suggestions are then made for ways in which the new model can be used to test the importance of these effects.
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    Bulletin of mathematical biology 46 (1984), S. 461-465 
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    Bulletin of mathematical biology 46 (1984), S. 467-472 
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    Bulletin of mathematical biology 46 (1984), S. 447-460 
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    Notes: Abstract A stochastic approach is utilized to develop a model equation capable of describing the time course of germination in a sample of bacterial spores. The time required by a spore to complete the change characteristic of germination consists of an initial interval of no change followed immediately by the duration of the change itself. The experimental basis of the proposed model is the observation that each of these time intervals is distributed over a range of values in a spore sample. Mixed continuous and discrete probabilities are employed in arriving at an average single-spore germination curve which, to a different scale, describes the sample in time.
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    Bulletin of mathematical biology 46 (1984), S. 473-500 
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    Notes: Abstract Mathematical methods for comparison of nucleic acid sequences are reviewed. There are two major methods of sequence comparison: dynamic programming and a method referred to here as the regions method. The problem types discussed are comparison of two sequences, location of long matching segments, efficient database searches and comparison of several sequences.
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    Bulletin of mathematical biology 46 (1984), S. 579-590 
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    Notes: Abstract An algorithm for nucleic acid and protein sequence alignment is presented. It is a non-metric local similarity minimal-difference algorithm and in the current implementation, assembles the matching regions found into a pseudo-global format. Its strengths are its speed of execution and the especially convenient presentation of its output. The algorithm is intended for use in sequence melding and local (small-region) similarity searching. It is not designed to replace a metric Needleman-Wunsch-Sellers-type similarity algorithm. The program is written in FORTRAN and is designed to be easily transportable to a variety of computer systems.
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