ALBERT

Notizen: Abstract Equations were derived showing the relationship between the membrane potential and the quantities which influence it under steady state conditions. Essentially, the membrane potential is caused by the valence and concentration of the non-permeating ions. The permeating ions can modify the membrane potential by altering the relative concentration of the non-permeating ions with respect to the concentration of the permeating ions. For muscle, the sodium cations act as the non-permeating ions in the extracellular environment by the maintenance of some type of active metabolic process and large anions act as the non-permeating ions in the intracellular environment. Both of these non-permeating ions contribute about equally to the maintenance of the resting membrane potential. When the active metabolic process for sodium extrusion breaks down or when acids are added, the membrane potential should decrease. Water should enter the cell when the sodium metabolic process is diminished; water should leave the cell when acids are added. When acid is added, it is expected that the cations potassium and sodium will leave the cell with little or no shift of the chloride ions.

Notizen: Abstract A purely information-theoretical approach to the problem of self-replication of elementary living units implies that pure chance is the determining factor in the formation of the first living unit. The probability of such a spontaneous formation can be calculated from the minimum amount of information which an organism must possess in order to replicate itself. An estimation of this amount of information is made here by two different methods. First by a “paper and pencil experiment” which indicates the minimum amount of information needed on a printed page in order that with given tools the page could be reproduced. Second—by an analytical consideration of some hypothetical molecular mechanisms. A general method for handling such problems is suggested. On the basis of estimated information contents it is shown that under most favorable conditions the probability of a spontaneous generation by pure chance during the lifetime of the earth is vanishingly small. It is concluded that dynamic factors, which may reduce tremendously the information content, must play a role in the genesis of life on earth.

Notizen: Abstract The binding energy of a very long molecular chain, composed of different classes of molecules, depends in general on the order of the molecules. It is shown that under very general conditions there exists for a givenbrutto chemical composition of a chain, a class of chains which is characterized by a total binding energy which is equal to the total binding energy of any other prescribed chain of different composition within the limits of unsharpness of the energy level. This establishes a criterion formapping of a class of configurations of long chain molecules on another class. To the extent that a mapping constitutes a generalized code those results contribute to the theory of molecular codes. Applying to our results the results of a previous paper (1959,Bull. Math. Biophysics,21, 309–326), we arrive at the conclusion that the self-replication of a living molecule may be the property not of a particular structure but of classes of structures.

Notizen: Abstract Making some plausible assumptions about the over-all mechanism of food catching and consumption by fishes and evaluating in the light of those assumptions some available experimental data, it is possible to calculate from those data the variation of several important factors with the concentration of food. The factors considered are: total rate of metabolism, total diurnal energy expenditure in the process of feeding, average number of hours per day during which the fish feeds, average length of path traveled by a fish per day, and the so-called “energetic coefficient of growth.” A possible relation with the work of N. Rashevsky (Bull. Math. Biophysics,20, 299–308, 1959) is discussed.

Notizen: Abstract The theory of measurement of flow and volume by indicator dilution techniques is given in conditions of time-variable flow rates. It is shown that the usual Hamilton (1932,Am. J. Physiol.,99, 534–551) methods can be misleading if the flow changes at a rate of close to that of the transport function.

Notizen: Abstract Freese’s Hypothesis states that a single specific alteration in the sequence of nucleotides of an information-bearing DNA molecule results in a specific mutational effect. Within the framework of the DNA-protein coding problem developed elsewhere, and assuming the quasi-ergodicity of the general coding process, it is shown that Freese’s Hypothesis allows us to derive expressions for the length of the smallest mutable DNA molecule and to obtain a bound for the maximal number of allelic molecules of fixed length. To illustrate these ideas, calculations are carried out on appropriate data from bacternophage and man, and the results are shown to differ by a factor of 10 (modulo the rather crude approximations used). It is further shown that, if ρ(N) and ϱ(N) are respectively the number of information-bearing words of lengthN in a given code and the number of words of lengthN, then the number lim ρ(N)/ϱ(N) depends sensitively on the parameter ∈ which specifiesN→∞ the given code. The implications of this result for the spontaneous aggregation of a sufficient number of information-bearing words to characterize an organism are discussed.

Notizen: Abstract As a “base line” of memorization performance, the behavior of a “perfect learner” is considered. He is characterized by a perfect memory and by the ability to choose the best search procedure in problems where the correct response from a given repertoire is to be found to each of several stimuli under the condition of “right” and “wroing” promptings by the experimenter. Expected learning curves are derived for the case of disjoint response repertoires associated with the stimuli under cyclic and random presentation of the stimuli and for the case of a single response repertoire (a one-to-one matching problem) under cyclic presentation.

Notizen: Abstract Detailed equations are given for the computation of aortic distensibility in the intact living human patient from measurements of systolic and diastolic arterial pressures, heart rate and cardiac output. From these equations, the aortic characteristics of a large series of normal men of different ages were computed. Comparing these results with measurements on excised aortas, a more pronounced trend toward increasing aortic stiffness with increasing age is evident in living than in dead aortas. Nor-epinephrine and exercise apparently cause the living aortas to constrict but to become more distensible. The same change occurs after 30 minutes of high spinal anesthesia. The ganglionic blocking agents hexamethonium, pentamethonium, and tetraethylammonium usually cause the living aorta to become stiffer, presumably due to dilatation. The aortas of patients with pulmonary disease usually react in different fashion to exercise or tetraethylammonium. The increased aortic distensibility that occurs with the hypertension induced by nor-epinephrine or exercise acts as a compensatory mechanism by decreasing systolic pressure.

Notizen: Abstract Dimensional analysis is discussed from the viewpoint of its basic group properties and shown to be an algebraic Abelian group that is useful for analysis of physical measurements. The application of the method to various types of equations and the formulation of previously unclassified dimensions are discussed. Functional dimensional analysis is applied to the problems of cell size and biomass proliferation; future applications are also noted. A number of dimensionless terms have been formulated for cellular physiochemical phenomena. They apparently represent the first systematic study of biological dimensionless numbers recorded in the literature. A dimensionless proliferation law is suggested. A brief analysis of the physical dimensionality associated with information measures is carried out. Entropy and “information” are shown to be completely different in their dimensional meaning; other informational measures of possible interest in biology are proposed. The dimensional coding and computor analysis of biomathematical equations is suggested.

Notizen: Abstract Expenditure of energy under several simultaneous forms (mechanical, chemical, etc.) is associated with all muscular activity. The energy is directly related to what is commonly called exertion or effort. This paper defines “muscular effort” quantitatively in terms of some of the elements of the dynamics of the human (and animal) body. It postulates that in all likelihood the individual will, consciously or otherwise, determine his motion (or his posture, if at rest) in such a manner as to reduce his total muscular effort to a minimum consistent with imposed conditions, or “constraints”. The principle, formulated in mathematical terms, is sufficient to ascribe to the moments at all body joints—a matter generally of free choice on the part of the individual—their most likely magnitudes. It therefore renders the equations of human (and animal) motion determinate within this context. The paper also describes briefly an iteration method for the solution of these equations, once they have been made determinate. A simple illustrative application of the principle is included.

Notizen: Abstract It is pointed out that two fundamentally different views of primary genetic processes occur in the literature which are frequently confused. The first is a true communication-theoretic view, which regards the genetic apparatus as containing a real information-source and a transducer which converts that information to useful form. The second view is generally expressed as a template scheme based on the Watson-Crick model; it is shown that in this model there is actually no such thing as genetic information in a communication-theoretic sense. Both views are then discussed on the basis of microphysical principles developed in previous work of the author (Bull. Math. Biophysics,22, 227–255, 1960) in an attempt to find which approach is in closer accord with the biological facts. It is shown that, if the communication-theoretic view is correct, then the information-bearing object must act as a “catalyst,” but it is pointed out that the type of catalysis involved must be of a fundamentally different nature than that occurring in familiar enzyme-catalyzed reactions. On the basis of general considerations of irreversible changes in microphysical measuring systems, it is shown that any type of template must suffer a gradual and irreversible denaturation, which seems to make it unlikely that a template could play a primary role in fundamental genetic processes.

Notizen: Abstract The theory developed in previous papers and based on distribution curves of definite form is generalized to any form of unimodel distributions. The time course of the change from one behavior to another is discussed and a general theorem about the time course is established.

Notizen: Résumé Nous appliquons le modèle de neurone introduit dans un article antérieur à l’étude d’une microstructure isotrope. La stabilité de cette microstructure implique l’existence d’une régulation d’activité que le principe de construction adéquate permet de définir entièrement. Nous aboutissons à une conception stratifiée du cerveau. Un réseau de neurones spécialisés exercerait, grâce à certains médiateurs chimiques, une action diffuse qui modulerait les propriétés du réseau localisé classique. Les lois de Pavlov peuvent être retrouvées à partir des propriétés de la microstructure et de celles de la régulation. La microstructure isotrope peut également fonctionner comme analyseur. Un certain nombre de temps caractéristiques apparaissent alors, qui semblent jouer un grand rôle en psychologie.

Notizen: Abstract In the arteries, blood flow and blood pressure are pulsatile in nature (Roston, 1962a; Roston 1962b). The patterns of blood movement and mural distension in the arteries are important because they may be associated with life-threatening degenerative changes in the arterial walls. As the vascular channels narrow, the pulsation decreases. At the level of the capillaries, almost no pulsation exists (Best and Taylor, 1961). The tissues are affected by the direct flow in the capillaries and not by the pulsation in the arteries. Thus, such quantities as pulse pressure, systolic pressure, and diastolic pressure which characterize blood movement in the arteries are not important as far as the tissues are concerned. Rather, the average pressure and flow in the capillaries are the quantities significant for tissue blood flow. The present study analyzes the local blood circulation in a typical tissue. Logical extension of this analysis results in insights into the physiological behavior of the circulation which integrate a considerable body of experimental data.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Notizen: Abstract 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.

Notizen: 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.

Notizen: 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.

Notizen: 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.

Notizen: 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.

Notizen: 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.

Notizen: 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.

Notizen: 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.

Notizen: 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.

Notizen: 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.

Notizen: 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.

Notizen: 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).

Notizen: 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.

Notizen: 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.

Notizen: 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.

Notizen: 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.

Notizen: 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.

Notizen: 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).

Notizen: 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.

Notizen: 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.

Notizen: 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.

Notizen: Abstract A dynamical model of the left ventricle as a thick-walled cylinder contracting radially is used to derive the P-V (pressure-volume) relation in the left ventricular cavity during contraction. It is shown how the mathematical results derived could apply to experimental results.

Notizen: Abstract We give conditions for local and global stability of discrete one-dimensional population models. We give a new test for local stability when the derivative is −1. We give several sufficient conditions for global stability. We use these conditions to show that local and global stability coincide for the usual models from the literature and even for slightly more complicated models. We give population models, which are in some sense the simplest models, for which local and global stability do not coincide.

Notizen: Abstract We consider efficient methods for computing a difference metric between two sequences of symbols, where the cost of an operation to insert or delete a block of symbols is a concave function of the block's length. Alternatively, sequences can be optimally aligned when gap penalties are a concave function of the gap length. Two algorithms based on the ‘candidate list paradigm’ first used by Waterman (1984) are presented. The first computes significantly more parsimonious candidate lists than Waterman's method. The second method refines the first to the point of guaranteeingO(N 2 lgN) worst-case time complexity, and under certain conditionsO(N 2). Experimental data show how various properties of the comparison problem affect the methods' relative performance. A number of extensions are discussed, among them a technique for constructing optimal alignments inO(N) space in expectation. This variation gives a practical method for comparing long amino sequences on a small computer.

Notizen: Abstract It is well documented, in the biological literature, that many species throughout the animal kingdom exhibit Gompertzian or Weibull-like population level total survival distributions. Many researchers have long assumed, believed, or otherwise postulated that an individual organism, in such a population, survived according to an exponential survival distribution. Using well-known results from reliability theory, it is shown that if every individual in the population has an exponentially distributed lifespan, then a Gompertzian or Weibull-like group/population level dynamics (or any other dynamics with a strictly increasing mortality rate for some interval) is not possible. This implies that, for species with a population level Gompertzian or Weibull (with the mortality rate strictly increasing) survival curve, some or all of the individual organisms must have non-exponentially distributed lifespans.

Notizen: Abstract In flow cytometric measurement of cell DNA distribution one of the major problems is accounting for the effect of fragmentation in the staining process. This work considers a recent probabilistic model that has been proposed for the fragmentation process and species under which conditions it is possible to uniquely identify the DNA distributions of the original population using flow cytometric data. Attention is given both to the normal and to the polyploid case.

Notizen: Abstract The nonlinear behavior of a particular Kolmogorov-type exploitation differential equation system assembled by May (1973,Stability and Complexity in Model Ecosystems, Princeton University Press) from predator and prey components developed by Leslie (1948,Biometrica 35, 213–245) and Holling (1973,Mem. Entomol. Soc. Can. 45, 1–60), respectively, is re-examined by means of the numerical bifurcation code AUTO 86 with model parameters chosen appropriately for a temperature dependent mite interaction on fruit trees. The most significant result of this analysis is that, in addition to the temperature ranges over which the single community equilibrium point of the system iseither globally stableor gives rise to a globally stable limit cycle, there can also exist a range wherein multiple stable states occur. These stable states consist of a focus (spiral point) and a limit cycle, separated from each other in the phase plane by an unstable limit cycle. The ecological implications of such metastability, hysteresis and threshold behavior for the occurrence of outbreaks, the persistence of oscillations, the resiliency of the system and the biological control of mite populations are discussed. It is further suggested that a model of this sort which possesses a single community equilibrium point may be more useful for representing outbreak phenomena, especially in the presence of oscillations, than the non-Kolmogorov predator-prey systems possessing three community equilibrium points, two of which are stable and the other a saddle point, traditionally employed for this purpose.

Notizen: Abstract This note is concerned with a simple mathematical model of how a population of bacterial spores decrease with time when subjected to a uniform temperature. The model assumes that there is a Boltzman distribution of energy among water or other molecules surrounding the assumed single lethal target in a spore; it assumes that repair is not possible; and that only molecules with energies above a critical level cause inactivation. The model provides new insight concerning the ‘kill-rate’ of spores during ultra heat treatment.

Notizen: Abstract We present a new symmetric model of the idiotypic immune network. The model specifies clones of B-lymphocytes and incorporates: (1) influx and decay of cells; (2) symmetric stimulatory and inhibitory idiotypic interactions; (3) an explicit affinity parameter (matrix); (4) external (i.e. non-idiotypic) antigens. Suppression is the dominant interaction, i.e. strong idiotypic interactions are always suppressive. This precludes reciprocal stimulation of large clones and thus infinite proliferation. Idiotypic interactions first evoke proliferation, this enlarges the clones, and may in turn evoke suppression. We investigate the effect of idiotypic interactions on normal proliferative immune responses to antigens (e.g. viruses). A 2-D, i.e. two clone, network has a maximum of three stable equilibria: the virgin state and two asymmetric immune states. The immune states only exist if the affinity of the idiotypic interaction is high enough. Stimulation with antigen leads to a switch from the virgin state to the corresponding immune state. The network therefore remembers antigens, i.e. it accounts for immunity/memory by switching beteen multiple stable states. 3-D systems have, depending on the affinities, 9 qualitatively different states. Most of these also account for memory by state switching. Our idiotypic network however fails to account for the control of proliferation, e.g. suppression of excessive proliferation. In symmetric networks, the proliferating clones suppress their anti-idiotypic suppressors long before the latter can suppress the former. The absence of proliferation control violates the general assumption that idiotypic interactions play an important role in immune regulation. We therefore test the robustness of these results by abandoning our assumption that proliferation occurs before suppression. We thus define an “escape from suppression” model, i.e. in the “virgin” state idiotypic interactions are now suppressive. This system erratically accounts for memory and never for suppression. We conclude that our “absence of suppression from idiotypic interactions” does not hinge upon our “proliferation before suppression” assumption.

Notizen: Abstract Analytical bounding functions for diffusion problems with Michaelis-Menten kinetics were recently presented by Anderson and Arthurs, 1985 (Bull. math. Biol. 47, 145–153). Their methods, successful to some extent for a small range of parameters, has the disadvantage of providing a weak upper bound. The optimal approach for the use of one-line bounding kinetics is presented. The use of two-line bounding kinetics is also shown, in order to give, sufficient accuracy in those cases where the one-line approach does not provide satisfactory results. The bounding functions provide excellent upper and lower bounds on the true solution for the entire range of kinetic and transport parameters.

Notizen: Abstract Thresholds for survival and extinction are important for assessing the risk of mortality in systems exposed to exogeneous stress. For generic, rudimentary population models and the classical resource-consumer models of Leslie and Gallopin, we demonstrate the existence of a survival threshold for situations where demographic parameters are fluctuating, generally, in a nonperiodic manner. The fluctuations are assumed, to be generated by exogenous, anthropogenic stresses such as toxic chemical exposures. In general, the survival threshold is determined by a relationship between mean stress measure in organisms to the ratio of the population intrinsic growth rate and stress response rate.

Notizen: Abstract A stochastic analog to a deterministic model describing subpopulation emergence in heterogeneous tumors is developed. The resulting system is described by the Fokker-Planck or forward Kolmogorov equation. A finite element approach for the numerical solution to this equation is described. Four biological and clinical scenarios are simulated (emergence of heterogeneity, exclusion of a subpopulation, and induction of drug resistance in both pure and heterogeneous tumors). The results of the simulations show that the stochastic model describes the same basic dynamics as its deterministic counterpart via a convective component, but that for each simulation a distribution of tumor sizes and mixes can also be derived from a diffusive component in the model. These distributions yield estimates for subpopulation extinction probabilities. The biological and clinical relevance of these results are discussed.

Notizen: 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.

Notizen: 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.

Notizen: 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.