ALBERT

Notizen: Abstract The partial differential equation of the random walk problem with persistence of direction and external bias is derived. By persistence of direction or internal bias we mean that the probability a particle will travel in a given direction need not be the same for all directions, but depends solely upon the particle's previous direction of motion. The external bias arises from an anisotropy of the medium or an external force on the particle. The problem is treated by considering that the net displacement of a particle arises from two factors, namely, that neither the probability of the particle traveling in any direction after turning nor the distance the particle travels in a given direction need be the same for all directions. A modified Fokker-Planck equation is first obtained using the assumptions that the particles have a distribution of travel times and speeds and that the average time of travel between turns need not be zero. The fional equation incopporating the assumption of a persistence of direction and an external bias is then derived. Applications to the study of diffusion and to long-chain polymers are then made.

Notizen: Abstract The transmission of some information or behavior pattern is treated as a flow of “particles” which execute random motions over a population of individuals and which may multiply or disappear. Equations are derived for the number density of these “particles” and from this is calculated the number of individuals through which the “particles” have passed. The results are applied to a number of situations such as 1) uniform spatial distribution with multiplication factor decreasing with time because of loss of interest or confusion of the information, 2) multiplication factor constant but the rate of spreal decreasing with multiple hearings, 3) one-dimensional region with a small starting region with or without an absorbing barrier 4) two-dimensional region with absorbing barrier, 5) continous sources of information within a small region in one dimension, 6) uniform spatial distribution in which individuals do not respond to more than one hearing.

Notizen: Abstract A situation is considered in which a fluid containing a substance flows through a vessel at a constant rate, the substance being permeable to the vessel wall. In the region outside the vessel there is supposed to be rapid mixing in the direction perpendicular to the axis of the vessel but no mixing longitudinally. The solution for the spatial distribution at any time is given for the case of an arbitrary initial distribution along the vessel length in the absence of an input. The solution is also given for the case of a single impulsive input, the concentration being initially zero everywhere.

Notizen: Abstract Organisms orient themselves to a stimulus by two general methods. One method is by directed orientation (taxis); the other is by undirected locomotory reaction (kinesis). An equation, and the methods for finding the necessary parameters of this equation, is derived for the distribution of organisms within a container, with the following limitations: (1) the organisms have no accommodation, (2) they are always active, and (3) the stimulus changes slowly with position. Necessary modifications of the equation are then derived, so that the last two limitations may be eliminated. The equation cannot be solved excatly because of its complexity; hence an approximation method must be used. This method is discussed, an approximate solution is found, and a time constant for equilibrium to be established is derived. Applications tovarious experiments in the literature are then made with fairly satisfactory results. A new interpretation of the theory of klino-kinesis with accommodation is found upon application of the equations developed to experimental work. Further limitations and uses of these equations are then discussed.

Notizen: Abstract Certain parameters are defined which roughly characterize the internal structure of networks. A given network structure uniquely determines the values of the parameters, but the reverse is not true. The parameters therefore define certain classes of networks. One of the parameters, thedispersion D(S) gives an indication of the “compactness” of the internal structure. Addition theorems and inequalities are derived relating the dispersions of sub-systems to the dispersion of the complete structure.

Notizen: Abstract A mathematical theory is developed which permits the determination of certain parameters of an inhomogenous tissue, such as a nerve trunk without its epineurium. The parameters are the permeability coefficients for entrance into an exit of a substance from the nerve fibers, and the diffusion coefficient of the interstitial material. The experimental data required are the dimensions of the cross-section, the average diameter of the fibers, and the ratio of the cross-sectional are of the fibers to the total cross-section, as well as the time course of the decrease of the fraction of the substance left in the nerve trunk, when the trunk is immersed in a bathing solution containing none of it.

Notizen: Abstract A model based on enzyme localization is developed which gives rise to an apparent active transport of a metabolite into or out of cells. The model is applied to three simple situations, using Fick's equation and the Rashevsky approximation. It is shown that the apparent efficiency can be made as large as desired if, for constant reaction, the outer cell region is made sufficiently small, or, for autocatalytic reaction, if the metabolite concentration in the outer region is sufficiently small. The physical limitations imposed by this mechanism are developed for all three situations.

Notizen: Abstract A previously derived iteration formula for a random net was applied to some data on the spread of information through a population. It was found that if the axon density (the only free parameter in the formula) is determined by the first pair of experimental values, the predicted spread is much more rapid than the observed one. If the successive values of the “apparent axon density” are calculated from the successive experimental values, it is noticed that this quantity at first suffers a sharp drop from an initial high value to its lowest value and then gradually “recovers”. An attempt is made to account for this behavior of the apparent axon density in terms of the “assumption of transitivity”, based on a certain socio-structural bias, namely, that the likely contacts of two individuals who themselves have been in contact are expected to be strongly overlapping. The assumption of transitivity leads to a drop in the apparent axon density from an arbitrary initial value to the vicinity of unity (if the actual axon density is not too small). However, the “recovery” is not accounted for, and thus the predicted spread turns out to beslower than the observed.

Notizen: Abstract The assumption of transitivity treated in part I is modified in various ways to describe an information-diffusion process, in which a certain amount of randomness of contact does occur. In one model a parameter is introduced which is indicative of a tendency to go beyond one's immediate vicinity to spread the information as the vicinity becomes saturated with knowers. In another model the randomness appears in the assumption that new knowers are uniformly distributed among the knowers. Two of the equations thus derived, each with two free parameters are in good agreement with experimental results.

Notizen: Abstract It is suggested that a system of chemical substances, called morphogens, reacting together and diffusing through a tissue, is adequate to account for the main phenomena of morphogenesis. Such a system, although it may originally be quite homogeneous, may later develop a pattern or structure due to an instability of the homogeneous equilibrium, which is triggered off by random disturbances. Such reaction-diffusion systems are considered in some detail in the case of an isolated ring of cells, a mathematically convenient, though biologically unusual system. The investigation is chiefly concerned with the onset of instability. It is found that there are six essentially different forms which this may take. In the most interesting form stationary waves appear on the ring. It is suggested that this might account, for instance, for the tentacle patterns onHydra and for whorled leaves. A system of reactions and diffusion on a sphere is also considered. Such a system appears to account for gastrulation. Another reaction system in two dimensions gives rise to patterns reminiscent of dappling. It is also suggested that stationary waves in two dimensions could account for the phenomena of phyllotaxis. The purpose of this paper is to discuss a possible mechanism by which the genes of a zygote may determine the anatomical structure of the resulting organism. The theory does not make any new hypotheses; it merely suggests that certain well-known physical laws are sufficient to account for many of the facts. The full understanding of the paper requires a good knowledge of mathematics, some biology, and some elementary chemistry. Since readers cannot be expected to be experts in all of these subjects, a number of elementary facts are explained, which can be found in text-books, but whose omission would make the paper difficult reading.

Notizen: Abstract The classical metaphor of the genetic program written in the DNA nucleotidic sequences is reconsidered. Recent works on algorithmic complexity and logical properties of computer programs and data are used to question the explanatory value of that metaphor. Structural properties of strings are looked for which would be necessary to apply to DNA sequences if the metaphor is to be taken literally. The notion of sophistication is used to quantify meaningful complexity and to distinguish it from classical computational complexity. In this context, the distinction between program and data becomes relevant and an alternative metaphor of DNA as data to a parallel computing network embedded in the global geometrical and biochemical structure of the cell is discussed. An intermediate picture of an evolving network emerges as the most likely where the output of the cellular computing network can produce, at a different time scale, changes in the structure of the network itself by means of changes in the DNA activity patterns.

Notizen: Abstract When two strings of symbols are aligned it is important to know whether the observed number of matches is better than that expected between two independent sequences with the same frequency of symbols. When strings are of different lengths, nulls need to be inserted in order to align the sequences. One approach is to use simple approximations of sampling for replacement. We describe an algorithm for exactly determining the frequencies of given numbers of matches, sampling without replacement. This does not lead to a simple closed form expression. However we show examples where sampling with, or without, replacement give very similar results and the simple approach may be adequate for all but the smallest cases.

Notizen: Abstract Pairwise optimal alignments between three or more sequences are not necessarily consistent as a whole, but consistent and inconsistent residues are usually distributed in clusters. An efficient method has been developed for locating consistent regions when each pairwise alignment is given in the form of a “skeletal representation” (Bull. math. Biol. 52, 359–373). This method is further extended so that the combination of pairwise alignments that gives the greatest consistency is found when possibly many alignments are equally optimal for each pairwise comparison. A method for acceleration of simultaneous multiple sequence alignment is proposed in which consistent regions serve as “anchor points” limiting application of direct multi-way alignment to the rest of “inconsistent” regions.

Notizen: Abstract Sufficient conditions are given for the unlimited growth or otherwise in multitype population size dependent Galton-Watson processes. These conditions are given in terms of moments of offspring distributions and extend known conditions for processes with one type.

Notizen: Abstract The variability of the duration of the cell cycle is explained by the phenomenon of sensitive dependence upon initial conditions; as may occur in deterministic non-linear systems. Chaotic dynamics of a system is the result of this sensitive dependence. First a deterministic system is formulated that is equivalent to the Smith-Martin transition probability model of the cell cycle. Next the model is extended to a dynamic process that ranges over the cell generations. A deterministic non-linear relationship between the cycle time of the mother and daughter cell is established. It clarifies the variability of mother-daughter correlation for the different cell types. The model is fitted to two different cell cultures; it shows that the graph of the non-linear relation has the same shape for different cell types.

Notizen: Abstract Recently a mathematical model of the prevascular phases of tumor growth by diffusion has been investigated (S. A. Maggelakis and J. A. Adam,Math. Comput. Modeling, in press). In this paper we examine in detail the results and implications of that mathematical model, particularly in the light of recent experimental work carried out on multicellular spheroids. The overall growth characteristics are determined in the present model by four parameters:Q, γ, b, andδ, which depend on information about inhibitor production rates, oxygen consumption rates, volume loss and cell proliferation rates, and measures of the degree of non-uniformity of the various diffusion processes that take place. The integro-differential growth equation is solved for the outer spheroid radiusR 0(t) and three related inner radii subject to the solution of the governing time-independent diffusion equations (under conditions of diffusive equilibrium) and the appropriate boundary conditions. Hopefully, future experimental work will enable reasonable bounds to be placed on parameter values referred to in this model: meanwhile, specific experimentally-provided initial data can be used to predict subsequent growth characteristics ofin vitro multicellular spheroids. This will be one objective of future studies.

Notizen: Abstract Workers of the speciesLeptothorax acervorum show age-polyethism, they start their life as broodworkers and later on they become nestworkers and foragers. Nestworkers and foragers of this ant species are inactive for 72% and 15% of the total time respectively. The short bursts of activity within the nest do not occur randomly but are synchronized so that the whole nest population exhibits nonperiodic pulses of activity: the ants were seen to wake each other actively. In addition starvation experiments were done to assess whether ants react upon food availability. In appeared that during a longlasting period of starvation the proportion of active ants in the nest is at a higher approximately constant level.

Notizen: Abstract In the framework of the neural network theory effects similar to hypnotic displays are constructed. They are based on the associative paradigm involving non-linear interaction of excitatory and inhibitory channels with synaptic memory. The non-linearity of long-term memorizing processes may cause effects exhibited by blind spots, which are interpreted as the first stage of hypnosis. More complicated phenomena are discussed in terms of a two-layer network.

Notizen: Abstract Mutation is introduced into autocatalytic reaction networks. The differential equations obtained are neither of repliator-type nor can they be transformed straightway into a linear equation. Examples of low dimensional dynamical systems —n=2, 3 and 4 — are discussed and complete qualitative analysis is presented. Error thresholds known from simple replication-mutation kinetics with frequency independent replication rates occur here as well. Instead of cooperative transitions or higher order phase transitions the thresholds appear here as supercritical or subcritical bifurcations being analogous to first-order phase transitions.

Notizen: Abstract The non-linear behavior of a differential equations-based predator-prey model, incorporating a spatial refuge protecting a consant proportion of prey and with temperature-dependent parameters chosen appropriately for a mite interaction on fruit trees, is examined using the numerical bifurcation code AUTO 86. The most significant result of this analysis is the existence of a temperature interval in which increasing the amount of refuge dynamically destabilizes the system; and on part of this interval the interaction is less likely to persist in that predator and prey minimum population densities are lower than when no refuge is available. It is also shown that increasing the amount of refuge can lead to population outbreaks due to the presence of multiple stable states. The ecological implications of a refuge are discussed with respect to the biological control of mite pests.

Notizen: Abstract In many applications of control theory on plant growth models biomass maximization is postulated to avoid analytically unsolvable problems while fruit maximization is commonly considered to be a more realistic criterion. In a special case, we are able to compare these criteria. Iwasa and Roughgarden (1984,Theor. Pop. Biol. 25, 78–105) have investigated a certain class of plant growth models using a fruit maximization criterion. They proved that, in the vegetative growth period, the organs follow a certain path of balanced growth. We show that this path remains optimal when biomass maximization is postulated. This underlines the importance of the balanced growth path found by Iwasa and Roughgarden. Furthermore, our result suggests that in the vegetative growth period the biomass maximization criterion is a good approximation of fruit maximization. In another theoretical control investigation, Schultzeet al. (1983,Oecologia 58, 169–177) derived a different type of balanced growth path. We apply the theory of Iwasa and Roughgarden to an improved version of the model of Schulzeet al. This leads to a new description of balanced growth between root and shoot that reflects non-linearities in the water uptake process and constitutes an interesting hypothesis for further experimental testing.

Notizen: Abstract In this paper the effects of changing the ion concentration in and around a sample of soft tissue are investigated. The triphasic theory developed by Laiet al. (1990,Biomechanics of Diarthrodial Joints, Vol. 1, Berlin, Springer-Verlag) is reduced to two coupled partial differential equations involving fluid ion concentration and tissue solid deformation. These equations are given in general form for Cartesian, cylindrical and spherical geometries. After solving the two equations quantities such as fluid velocity, fluid pressure, chemical potentials and chemical expansion stress may be easily calculated. In the Cartesian geometry comparison is made with the experimental and theoretical work of Myerset al. (1984,ASME J. biomech. Engng,106, 151–158). This dealt with changing the ion concentration of a salt shower on a strip of bovine articular cartilage. Results were obtained in both free swelling and isometric tension states, using an empirical formula to acount for ion induced deformation. The present theory predicts lower ion concentrations inside the tissue than this earlier work. A spherical sample of tissue subjected to a change in salt bath ion concentration is also considered. Numerical results are obtained for both hypertonic and hypotonic bathing solutions. Of particular interest is the finding that tissue may contract internally before reaching a final swollen equilibrium state or swell internally before finally contracting. By considering the relative magnitude, and also variation throughout the time course of terms in the governing equations, an even simpler system is deduced. As well as being linear the concentration equation in the new system is uncoupled. Results obtained from the linear system compare well with those from the spherical section. Thus, biological swelling situations may be modelled by a simple system of equations with the possibility, of approximate analytic solutions in certain cases.

Notizen: Abstract Many models of immune networks have been proposed since the original work of Jerne [1974,Ann. Immun. (Inst. Pasteur) 125C, 373–389]. Recently, a limited class of models (Weisbuchet al., 1990,J. theor. Biol. 146, 483–499) have been shown to maintain immunological memory by idiotypic network interactions. We examine generalizations of these models when the networks are both large and highly connected to study their memory capacity, i.e. their ability to account for immunization to a large number of random antigens. Our calculations show that in these minimal models, random connectivities with continuously distributed affinities reduce the memory capacity to essentially nil.

Notizen: Abstract A kinetic model is proposed to delineate the factors that determine the coronary reactive hyperemic response (RHR) to transient ischemia. The model comprises of myocardial-interstitial (M) and vascular (V) compartments. Vasodilator metabolites (VM) are produced in the M compartment during the interval of coronary occlusion. The rate of VM production is dependent on the flow rate during the ischemic period, the ratio of excess flow above the control level (R) to the loss of flow during occlusion period (D), the amount of oxygen stored and the degree of vasodilation in the V compartment prior to occlusion. Following a complete release of occlusion, VM are transported from the M to V compartment and are washed out or degraded with time. The time course of RHR is determined by the coronary patency which is proportional to VM concentration in the V compartment. Based on a set of numerical constants, the model is tested by simulating RHR to the various occlusion manoeuvres: a pair of 10 sec occlusions separated by brief release, a 15 sec release followed by a second brief occlusion, a brief release of an occlusion followed by restriced inflow and a period of restricted inflow after occlusion. The simulated results fit the experimental R/D and RH durations data of canine hearts. Factors that determine the impairment of RH capacity in coronary stenosis are suggested in terms of the model scheme.

Notizen: Abstract In the present paper a kinetic study is made of the behaviour of a Michaelis-Menten enzyme-catalysed reaction in the presence of irreversible inhibitors rendered unstable in the medium by their reaction with the product of enzymatic catalysis. A general mechanism involving competitive, non-competitive, uncompetitive and mixed irreversible inhibition with one or two steps has been analysed. The differential equation that describes the kinetics of the reaction is non-linear and computer simulations of its dynamic behaviour are presented. The results obtained show that the systems studied here present kinetic co-operativity for a target enzyme that follows the simple Michaelis-Menten mechanism in its action on the substrate, except in the case of an uncompetitive-type inhibitor.

Notizen: Abstract The relative contributions of mitochondrial β-oxidation and peroxisomal β-oxidation and peroxisomal ω-oxidation to the oxidation of a given fatty acidin vivo can be quantitated by an isotopic method. The approach requires infusion of a fatty acid labelled on two specific carbon atoms (e.g. [1-14C] and [11-14C] palmitate) to an isotopic steady state, with subsequent isolation and degradation of an acetylated conjugate as a product of the liver cytosolic acetyl CoA pool and of ketone bodies as a product of the liver mitochondrial acetyl CoA pool.

Notizen: Abstract Pancreatic β-cells in intact islets of Langerhans perfused with various glucose concentrations exhibit periodic bursting electrical activity (BEA) consisting of active and silent phases. The fraction of the time spent in the active phase is called the plateau fraction and appears to be strongly correlated with the rate of release of insulin from islets as glucose concentration is varied. Here this correlation is quantified and a theoretical development is presented in detail. Experimental rates of insulin release are correlated with “effective” plateau fractions over a range of glucose concentrations. There are a number of different models for BEA in pancreatic β-cells and a method is developed here to quantify the dependence of a glucose dependent parameter on glucose concentration. As an example, the plateau fractions computed from the Sherman-Rinzel-Keizer model are matched with experimental plateau fractions to obtain a relationship between the model's glucose-dependent parameter, β, and glucose concentration. Knowledge of the relationships between β and glucose concentration and between experimental measurements of rates of insulin release and plateau fractions permits the determination of theoretical rates of insulin release from the model.

Notizen: Abstract When a suspension of bacterial cells of the speciesBacillus subtilis is placed in a chamber with its upper surface open to the atmosphere complex bioconvection patterns are observed. These arise because the cells: (1) are denser than water; and (2) usually swim upwards, so that the density of an initially uniform suspension becomes greater at the top than the bottom. When the vertical density gradient becomes large enough, an overturning instability occurs which ultimately evolves into the observed patterns. The reason that the cells swim upwards is that they are aerotactic, i.e. they swim up gradients of oxygen, and they consume oxygen. These properties are incorporated in conservation equations for the cell (N) and oxygen (C) concentrations, and these are solved in the pre-instability phase of development whenN andC depend only on the vertical coordinate and time. Numerical results are obtained for both shallow- and deep-layer chambers, which are intrinsically different and require different mathematical and numerical treatments. It is found that, for both shallow and deep chambers, a thin boundary layer, densely packed with cells, forms near the surface. Beneath this layer the suspension becomes severely depleted of cells. Furthermore, in the deep chamber cases, a discontinuity in the cell concentration arises between this cell-depleted region and a cell-rich region further below, where no significant oxygen concentration gradients develop before the oxygen is fully consumed. The results obtained from the model are in good qualitative agreement with the experimental observations.

Notizen: Abstract We describe a classification scheme for bursting oscillations which encompasses many of those found in the literature on bursting in excitable media. This is an extension of the scheme of Rinzel (inMathematical Topics in Population Biology, Springer, Berlin, 1987), put in the context of a sequence of horizontal cuts through a two-parameter bifurcation diagram. We use this to describe the phenomenological character of different types of bursting, addressing the issue of how well the bursting can be characterized given the limited amount of information often available in experimental settings.

Notizen: Abstract To ensure its sustained growth, a tumour may secrete chemical compounds which cause neighbouring capillaries to form sprouts which then migrate towards it, furnishing the tumour with an increased supply of nutrients. In this paper a mathematical model is presented which describes the migration of capillary sprouts in response to a chemoattractant field set up by a tumour-released angiogenic factor, sometimes termed a tumour angiogenesis factor (TAF). The resulting model admits travelling wave solutions which correspond either to successful neovascularization of the tumour or failure of the tumour to secure a vascular network, and which exhibit many of the characteristic features of angiogenesis. For example, the increasing speed of the vascular front, and the evolution of an increasingly developed vascular network behind the leading capillary tip front (the brush-border effect) are both discernible from the numerical simulations. Through the development and analysis of a simplified caricature model, valuable insight is gained into how the balance between chemotaxis, tip proliferation and tip death affects the tumour's ability to induce a vascular response from neighbouring blood vessels. In particular, it is possible to define the success of angiogenesis in terms of known parameters, thereby providing a potential framework for assessing the viability of tumour neovascularization in terms of measurable quantities.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Notizen: Abstract The impressed field, “Window Field” (WF), due to a half-wave action potential on a muscle fiber, has been calculated on the basis of potential theory. It has been shown that in spite of the small intensity of the field, its integrated action can transfer the energy needed to induce, contraction from the membrane to the interior of the fiber. The energy of polarization has been found to be sufficient to exceed the energy of, thermal agitation on that length of fiber, which can be identified as the length of a sarcomere. The changes of ion concentration, caused by the WF, if calculated on the assumption of the semipermeability of theZ membranes, was found to be equal to the changes necessary to induce contraction of actomyosinin vitro.

Notizen: Abstract Some general properties of the solution of the diffusion equation are deduced for the steady-state, spherically symmetric system. On the basis of these developments some results of N. Rashevsky (Bull. Math. Biophysics,11, 15, 1949) are discussed and the results of a previous investigation (Hearon,Bull. Math. Biophysics,12, 135, 1950b) are extended to more general conditions. In particular these extensions apply to the flow of a soluteagainst its concentration gradient, the nonzero gradient of an inert metabolite, and theaccumulation or exclusion of an inert metabolite in a metabolic system.

Notizen: Abstract The approximation method of N. Rashevsky is discussed and reviewed. It is shown that in addition to theexplicit assumptions and approximations there is involved the assumption that the rate of metabolism is the same at every point in the cell and that theaverage rate of metabolism is different from zero. An expression is given for the error in the approximate method when the rate of metabolism is any function of the concentration. It is also shown that a solution in theform of that obtained by the approximate method is not possible if the generalized laws of diffusion are assumed to apply.

Notizen: Abstract Rate equations for the enzymatic oxidation of succinic acid are derived on the assumption that when a single molecule of substrate combines with an enzyme molecule, it can do so with either one or two sites on the enzyme, and that oxidation occurs only in the second case. In addition it is assumed that the product of the reaction, fumaric acid, combines reversibly with the enzyme. With certain enzyme preparations the data fitted such an equation satisfactorily. In others the rate was that of a first-order reaction, but addition of cytochrome changed it to the former type. It was concluded that the transfer of hydrogen to oxygen was a first-order reaction and dominated the whole rate when enzyme preparations were used which had been washed relatively free of cytochrome. When the limiting factor was succino-dehydrogenase the rates followed the new equation. Criteria for recognizing noncompetitive inhibition are given, and inhibition by di-tertiary butyl peroxide was shown to be of this type.

Notizen: Abstract This paper deals with the following question: Which distributions of radiosensitivity in a population can lead to an exponential survival curve? The problem is solved exactly, with statistical fluctuations in dose fully accounted for. It is shown that only an exponential distribution of sensitivities can give rise to an exponential survival curve.

Notizen: Abstract An approximation method is introduced which enables a number of diffusion-type problems to be solved in an approximate but simple manner. Many cases require only the solution of a simple first-order differential equation. The method is applied to a number of cases in which the exact solutions are available. A comparison shows that the method is quite satisfactory in these cases. The method is applied to diffusion problems with rate of consumption proportional to concentration or to the square of the concentration. In the latter case, the result obtained is essentially the same as that found by H. G. Landau (1950) after elaborate calculations.

Notizen: Abstract It is shown that a slight modification of a model of excitatory phenomena in irritable tissues, which has been treated before, exhibits spontaneous oscillations. The frequency of these oscillations and the time-course of the potential across the model membrane have been determined, together with the dependence of some of their characteristics on some important parameters, particularly (Ca++).

Notizen: Abstract It is demonstrated that, if the variations of viscosity throughout a cell are considered, swelling stresses may produce elongation and division. To do this it is necessary to generalize Betti's theorem to cover systems containing viscosity gradients and such a generalization is presented. On the basis of two special assumptions it is shown that most of the results of the diffusion drag theory of cell division may be duplicated by the present theory.

Notizen: Abstract The theory of imitative behavior, developed previously, is applied to the case of two social groups which are separated spatially. If the information of each group as to the behavior of the other is complete, the case reduces to that of a single group. When any information is lacking at all, the two groups are independent. If we have two mutually exclusive behaviorsA andB, all four combinationsAA, AB, BA, andBB are possible. If the mutual information gradually increases from zero, then for a certain value of it, the group which is more informed about the behavior of the other will change to that behavior if it did not already exhibit it. If for constant information the size of the group increases, then above a certain threshold value, the larger group imposes its behavior on the smaller.

Notizen: Abstract Local regulation of blood flow as determined by capillary diameter and the number of open capillaries in a region is considered. The local changes in capillary diameter and in the number of open capillaries are assumed to be due to concentration changes of a diffusible, nonspecified metabolite. This metabolite is produced in the tissue and carried away by the blood stream. Using these assumptions and applying pertinent data on capillaries, deductions are made concerning: (a) the law of blood flow as a function of temperature and capillary radius for the hyperemia of high temperature, (b) high flow as it depends on metabolism during strenuous exercise of muscle, and (c) a first approximation to the time duration of occlusion hyperemia.

Notizen: Abstract The necessary and sufficient condition is given forn integers to be the score structure of a society with a dominance relation. A proof is also given for a theorem showing that there are members who dominate every other member either directly or indirectly through a single intermediate member.

Notizen: Abstract On the basis of a previous general formulation (Bull. Math. Biophysics,15, 21–29, 1953a) a discussion is given of the error in the approximation method of N. Rashevsky. This error, inherent in the method when the metabolic rate is different at each point in the cell, is discussed in detail and numerical values are presented for two particular cases: the rate proportional to the concentration and the rate a prescribed function of the spatial coordinates. It is shown that the formulation for the first case also applies to several other cases, that the error is negligible provided the rate is sufficiently small, and that the error is fairly sensitive to the cell size. If the rate depends upon the coordinatesalone a small rate is not sufficient to insure a negligible error. The relations between the exact method, the standard approximate method, an earlier approximate method (Physics,7 260, 1936), and a more recent refinement (Bull. Math. Biophysics,10, 201, 1948) of the standard method are discussed.

Notizen: Abstract It is shown on the basis of (1) conservation of mass, (2) positive concentrations, and (3) the principle of detail balancing that periodic reactions cannot occur in a closed system described bylinear differential equations. The matrix,A, of the rate equations must be such that |A|=0,a ij〉0 fori≠j,a ii〈0, andVAV −1=B, whereV is diagonal andB is symmetric. These properties ofA imply that the latent roots are real and non-positive and that neither catalysis nor inhibition can be described bylinear equations. It is further shown that periodic reactions cannot occur in anopen system for which the matrix associated with the chemical reactions has the above properties and in which thesimple law of diffusion is obeyed. The relation of these results to Onsager's reciprocal relations and to previous work on periodic and cyclic chemical reactions is discussed. The utility of certain of these results for the treatment of isotope kinetics is indicated.

Notizen: Abstract It is demonstrated that an explanation of the small radius effect or the so-called sigma phenomenon may be obtained by noting that one of the effects of the presence of suspended particles in a flowing fluid is to increase the velocity of flow near the wall over that existing in the absence of particles. This effect may be considered equivalent to relaxing the boundary conditions at the wall. An expression for the viscosity is compared with data and fit is found to be good.

Notizen: Abstract The solution for the spatial distribution of ions in a Donnan equilibrium has been given by J. H. Bartlett and R. A. Kromhout (1952). The present note gives an explicit solution for the case in which the length of the region containing the membrane is large; in biological situations this requires only that the length considered should be greater than a few hundred Ångstrom units. The Donnan equilibrium may be considered to be a special case of a situation in which forces other than electrical act upon the ions; in particular, it represents the case in which only one ion is acted upon and the energy difference on the two sides of the membrane is infinite. An expression is given for the difference in energy of theith in terms of the electrical potential and of the ion concentrations. As an illustration, the results are applied to nerve membrane potentials.

Notizen: Abstract A mechanism is described which accounts for the active transport of Na+ ions through a membrane. It is assumed that at one side of the membrane the ion combines with a carrier ion, the resulting carrier compound then diffuses through the membrane and decomposes at the other side of the membrane. The free diffusion of the ions is also taken into account. The time rate of accumulation of the ion in question at the latter side of the membrane is calculated in terms of the concentrations of the ion at both sides of the membrane.

Notizen: Abstract The recent extension of the approximation method is applied to enable us to arrive at the time course of the concentrations at both sides of a membrane. From the differential equations which govern these, the steady-state solution is obtained in terms of the parameters, which are determined by the thickness of the diffusion layers, the chemical composition and reactions, and the diffusion constant of the membrane.

Notizen: Abstract An equation is derived from the spread of a “state” by contact through a thoroughly mixed population, in which the probability of transmission depends both on the over-all duration of the process and on the time an individual has been in the “state.” Cases in which this probability is a function of only one or the other of the two “times” are worked out. It is shown that in the case of dependence on “private time” alone the asymptotic value of the fraction of the population effected is the same as that derived by the random net approach.

Notizen: Abstract The reflection of pressure waves in a fluid enclosed within a tube with an elastic wall is studied for the case of a localized change in diameter of the tube. The concept of impedance is introduced. The relation of the reflection characteristics of the parts of the tube at either side of the change is derived on the basis of the continuity of pressure and mass flow at the site of the change. This relations is used to derive the expression for the ratio of the pressure oscillations measured in front of, and behind, the constriction in terms of the constants of the system. As a result, a method is indicated to locate the coarctation from measurements of the pressures in front of, and behind it.

Notizen: Abstract The question is raised concerning the possible causes of abnormally small standard deviations found in counting samples in which particles are distributed at random (e.g., blood cells, fat globules in milk, etc.). The effect of discarding abnormal samples is discounted inasmuch as small standard deviations occur even when all samples are counted. An approximation method is used to calculate the effect of finite particle size, of known repulsive forces between particles and of convection currents. This calculation shows that neither finite size nor the known repulsive forces are sufficient to account for the observed abnormality of standard deviation, but that convection currents can possibly account for it. The possible presence of long-range repulsive forces cannot, however, be excluded.

Notizen: Abstract The effect of finite particle size on the standard deviation in sample counts is computed for the one-dimensional case. To a first order of approximation the correction is found to be identifical with that found by H. de Vries (1953) using a general approximation method.

Notizen: Abstract A critical examination of the “classical” theories of photoreception in view of more recent experimental findings yields the result that these theories do not possess the property to describe all the more significant phenomena of photoreception correctly, and to some extent suffer the lack of more general applicability. The basis for a new and presumably more general theory of photoreception based on dynamical aspects is laid out. Emphasis is put on the time course of afferent and efferent excitation in the photoreception model, consisting of a receptor element, an afferent and an efferent neuron of the one-factor Rashevsky-type, and an effector organ.

Notizen: Abstract A mathematical model for the development of human society, beginning with the earliest stages of urban cultures, is outlined. In the early stages of history, behavior was characterized largely by adherence to a number of beliefs and prejudices of diffeirent kinds, which were accepted on faith and not subject to critical rational analysis. Due to psychobiological variability a very small number of individuals spontaneously appear at all times who challenge the accepted beliefs and prejudices and do not follow the accepted patterns of social behavior. The effect of these individuals upon the rest of the society, especially upon the younger generation, depends on the facilities with which information spreads in society. In earliest societies, when modern methods of mass communication were unknown, the channels of communication were practically identical with the channels of economic transport. The latter in its turn depended on the nature of the roads, and especially on the presence of waterway, which facilitated transportation. The sizes of the earliest cities and the distances between them were largely determined by relative ease of transporation. Expressions are derived for the average size of the earliest cities and for the average distance between them. The calculated average populations of the earliest cities are of the order of 103; the distance of the order of 102 km. Both are in agreement with some archaeological findings. An expression for the time spaon required for the development from the earliest stages of urban cultures to the present time is derived and shown to depend on the specific shoreline of the country, that is, the length of the shorline divided by the area of the country. It is pointed out that western Europe's specific shoreline, including land bordering both seas and rivers, is ten times as large as the shoreline area of other parts of the world. It is shown that this greater specific shoreline may account quantitatively for the faster social and technological development of western Europe in the last few centuries. The calculated total span of time of development from earliest urban cultures to our days is found to be of the order of magnitude of ten thousand years. It is shown that the model accounts for the existence at the present time of primitive cultures. A number of suggestions is made in regard to other possible applications of mathematics to history.

Notizen: Abstract The assumptions latent in the derivation of the integral equation of Branson are rendered explicit and discussed. It is shown that the equation is valid only for systems in which the substance disappears according to a linear rate law.

Notizen: Abstract It is shown that the validity of Branson's integral description of metabolizing systems is subject to severe limitations. The validity is insured only in cases where the reaction is of first order, or quasi of first order. In all other cases Branson's equation has to be modified to insure general applicability. The consequences of a different definition of the metabolizing functionF have also been investigated. With the new definitionF describes the pure effect of metabolization. It is found that in this case the integral equation is only capable of describing first-order reactions. With a slight modification of the integral equation it is possible to describe metabolites “with age”, which do not have reactions of definite order, but which satisfy the superposition principle.

Notizen: Abstract A problem in probability is stated with included the problem of the distribution of bacterial mutants as a special case. This problem is solved exactly but since the resulting expressions are too complicated for practical use, various approximate expressions for the distribution are considered, especially for the bacterial mutation case.

Notizen: Abstract Simple reaction and discrimination reaction, under the influence of imitation, are considered for the situation in which the stimulus or the stimuli vary slowly with time. The result is analogous to hysteresis under certain conditions. The calculations are facilitated by the solution of $$x = \int_{ - \infty }^{a + \beta x} {g\left( \xi \right)d} \xi ,$$ g(ξ) being the normal error function. Values ofx(α, β) are given in a table.

Notizen: Abstract On the basis of simple physical considerations the blood flow in a branching circulatory system is studied. The case of two groups of parallel vessels is treated. The vessels of the same group are supposed to be identical. The resistance of each group is determined by the resistance of each vessel in the group and by the number of vessels in the group. From the dependence of the resistance of each vessel on its radius an expression is obtained for the blood flow through each group of vessels in terms of the numbers and sizes of the vessels in each group. The number of open vessels in an organ and the radius of each of those vessels are assumed to depend on the metabolic rate of that organ. The relations so obtained, together with the expression above, are applied to derive the blood flow through an organ as a function of the metabolic rate of that organ. It is indicated that the relations obtained might describe the shifting of blood from one organ to another if the activity of one of them changes. A way is pointed out to treat neural regulation of this phenomenon.

Notizen: Abstract A stochastic model of population growth is treated using the Bellman-Harris theory of agedependent stochastic branching processes. The probability distribution for the population size at any time and the expectation are obtained when it is assumed that there is probability (1−σ), 0≤σ〈1, of the organism dividing into two at the end of its lifetime, and probability σ that division will not take place.

Notizen: Abstract In a previous paper, in which a possible mathematical approach to history was outlined, it was shown that urbanization plays an important part in the propagation of new ideas. The rate of such propagation influences the rate of historical developments. The present paper deals in more detail with possible mechanisms of formation of earliest cities. Equations are derived which give the limiting size of such cities and their rate of growth. Of particular importance for the spread of new ideas is the spread of information. The latter largely depends on the fraction of individuals who travel between city and country. Expressions for this quantity are derived. An approach is outlined to the mathematical study of the earliest social classes, which may have been formed as a result of military, religious, or economic stratifications.

Notizen: Abstract The velocity of propagation of a disturbance wave in a liquid flowing in a distensible tube is computed. The mathematical model is more general than those used in previous analyses: the tube wall properties are realistic; the convective part of the axial inertia forces is taken into account; radial inertia forces of both the fluid and tube wall are present; viscous stresses are present. Four parameters influencing the velocity of propagation are obtained and discussed. Curves are plotted illustrating the effects of the parameters. Contrary to the results of previous analyses, viscous effects are shown to be appreciable in blood flow. It is also shown that radial inertia effects can be important in laboratory set-ups.

Notizen: Abstract A general theory of the drying of frozen tissue is developed and applied to the measurement of the drying rate of frozen guinea pig liver. It is shown that for a given temperature of the subliming ice crystals the mininum drying time of a piece of guinea pig liver is greater than the minimum sublimation time of a piece of ice of the same size and shape by a factor of the order of one thousand. This fact has many implications in the design of freeze-dry apparatus which will be developed in a following paper.

Notizen: Abstract The equations governing the time course of the exchange of substances between the blood in the capillaries and the extracellular space are solved for the case of substances which do not penetrate the cells. The equations given relate the time course of the exchange process to the various tissue and circulation parameters such as the specific capillary wall area, the pore area, the inter-capillary distance, the size of the extra-vascular, extra-cellular space, the diffusion coefficient in this space, and the velocity of blood in the capillaries. Some experimental work on capillary exchange is discussed in relation to the theory and estimates are made of the relative importance of the various tissue and circulation parameters in the exchange of substances in different tissues.

Notizen: Abstract Random clone mapping of genomic DNA is a subject of great interest in molecular biology.E. coli has just been mapped and work is progressing on some human chromosomes. In this paper we give estimates of the fraction of genomic DNA which is not clonable by partial digest with a restriction enzyme.