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PubMed1995

Active mutation in self-reproducing networks of machines and tapes.

Self-reproduction via description is discussed in a network model of machines and description tapes. Tapes consist of bit strings, which encode the machines' function A tape is replicated when it is read by adequate machines. Generally, a machine rewrites a tape without doing correct replication. The variation in a reproduced tape is taken as mutation. Because this mutation is caused by a machine's program, we call it active mutation. Which machine is translated from a given tape is dependent on what kind of a machine reads the tape. External noise is introduced in a machine's reading process to make errors. A new reaction pathway is induced by external noise via a machine's error action. We find that the induced pathways will be mimicked deterministically in an emerging core structure. This core structure will remain stable after turning off external noise. Low external noise develops a core structure of a minimal self-replicative loop. When external noise is elevated, a more complex network evolves. Machines containing a complex core network, which has been bred in high external noise, will actively rewrite tapes rather than just replicate them. Self-replication not as an individual but as a network now becomes important.

Biological Evolution↗
PubMed2000

Stochastic modelling of environmental variation for biological populations.

We examine stochastic effects, in particular environmental variability, in population models of biological systems. Some simple models of environmental stochasticity are suggested, and we demonstrate a number of analytic approximations and simulation-based approaches that can usefully be applied to them. Initially, these techniques, including moment-closure approximations and local linearization, are explored in the context of a simple and relatively tractable process. Our presentation seeks to introduce these techniques to a broad-based audience of applied modellers. Therefore, as a test case, we study a natural stochastic formulation of a non-linear deterministic model for nematode infections in ruminants, proposed by Roberts and Grenfell (1991). This system is particularly suitable for our purposes, since it captures the essence of more complicated formulations of parasite demography and herd immunity found in the literature. We explore two modes of behaviour. In the endemic regime the stochastic dynamic fluctuates widely around the non-zero fixed points of the deterministic model. Enhancement of these fluctuations in the presence of environmental stochasticity can lead to extinction events. Using a simple model of environmental fluctuations we show that the magnitude of this system response reflects not only the variance of environmental noise, but also its autocorrelation structure. In the managed regime host-replacement is modelled via periodic perturbation of the population variables. In the absence of environmental variation stochastic effects are negligible, and we examine the system response to a realistic environmental perturbation based on the effect of micro-climatic fluctuations on the contact rate. The resultant stochastic effects and the relevance of analytic approximations based on simple models of environmental stochasticity are discussed.

Animals↗
PubMed1998

Nonlinear feedforward networks with stochastic outputs: infomax implies redundancy reduction.

We prove that maximization of mutual information between the output and the input of a feedforward neural network leads to full redundancy reduction under the following sufficient conditions: (i) the input signal is a (possibly nonlinear) invertible mixture of independent components; (ii) there is no input noise; (iii) the activity of each output neuron is a (possibly) stochastic variable with a probability distribution depending on the stimulus through a deterministic function of the inputs (where both the probability distributions and the functions can be different from neuron to neuron); (iv) optimization of the mutual information is performed over all these deterministic functions. This result extends that obtained by Nadal and Parga (1994) who considered the case of deterministic outputs.

Feedback↗
PubMed1998

Stability analysis of the FitzHugh-Nagumo differential equations driven by impulses: applied to the electrical firing of magnocellular neurons.

A stability analysis is carried out for a mathematical model which describes the electrical firing of a single vasopressin neuron. The model used in a FitzHugh-Nagumo-type system which is driven by impulses. The analysis is based on recent developments in the stability theory of impulsive differential equations. Conditions are derived under which the system of differential equations is stable at two of its equilibrium points. Biologically this bistability represents the cell alternating between periods of electrical activity and silence. The conditions for stability are specified in terms of the amplitude and frequency of the impulses perturbing the system. Both stochastic and deterministic impulses are considered.

Action Potentials↗
PubMed1985

Decision making under uncertainty: a comparison of simple scalability, fixed-sample, and sequential-sampling models.

The purpose of this article is to investigate the learning and memory processes involved in decision making under uncertainty. In two different experiments, subjects were given a choice between a certain alternative that produced a single known payoff and an uncertain alternative that produced a normal distribution of payoffs. Initially this distribution was unknown, and in the first experiment it was learned through feedback from past decisions, whereas in the second experiment it was learned by observing sample outcomes. In the first experiment, a response deadline was used to limit the amount of time available for making a decision. In the second experiment, an observation cost was used to limit the number of samples that could be purchased. The mean and variance of the uncertain alternative and the value of the certain alternative were factorially manipulated to study their joint effects on choice probability, choice response time (Experiment 1), and number of observations purchased (Experiment 2). Algebraic-deterministic theories developed for decision making with simple gambles fail to explain the present results. Two new models are developed and tested--fixed- and sequential-sampling models--that attempt to describe the learning and memory processes involved in decision making under uncertainty.

Adult↗
PubMed1977

A mechanistic model of the aerobic growth of Saccharomyces cerevisiae.

A two-stage deterministic model of the growth of Saccharomyces cerevisiae is presented. The cell cycle of this organism was used to suggest the basic model structure. The model represents the preparatory processes of substrate uptake and conversion separately from replication and division. The regulation of the fraction of the culture devoted to each of these broad areas of metabolism, and the overall growth rate, is related to the nature and availability of the energy substrate. The simulation of respiration and glycolysis is achieved by including two alternative energy producing pathways. The regulation of these pathways is described in terms of the postulated primary regulation of the proportion of the culture required for substrate uptake and conversion, and the overall kinetic constants for each pathway. This regulation is dictated primarily by the growth rate rather than the nature or concentration of the energy substrate. The model successfully describes both batch and continuous growth of S. cerevisiae under conditons of glucose limitation and oxygen excess. A preliminary assessment indicates that adjustment of the relevant parameters will allow the model to describe the growth of S. cerevisiae on other sugars and under oxygen limitation. Similarly the model could be expected to describe the growth characteristics of other yeast species.

Aerobiosis↗
PubMed2000

Can varying concepts of susceptibility in risk assessment affect particulate matter standards?

The Clean Air Act mandates that sensitive subpopulations be considered in setting standards to protect the public's health. The purposes of this paper are to point out different conceptualizations of susceptibility, examine how it is approached in risk-related processes, and recommend ways it may be more explicitly framed for risk assessment and management purposes. We studied the traditional risk assessment paradigm, the U.S. Environmental Protection Agency (EPA) guidelines and revised PM standard, discussions from recent interdisciplinary meetings, and peer-reviewed literature. Areas of controversy include what factors intrinsic and extrinsic to the host should be incorporated in susceptibility, what health endpoints are of concern, whether susceptibility is deterministic or stochastic, and whether it should be defined on an individual or population scale. Recent discussions about susceptibility applied to PM indicate that it needs to be more clearly defined and evaluated for scientific and policy purposes. We conclude that varying concepts of susceptibility can affect risk-related processes such as PM standard setting. We recommend that susceptibility be clearly defined in the problem statement of risk assessments and be addressed in a specific subsection of risk characterization, integrating all susceptibility findings from the prior three steps in the risk assessment paradigm.

Air Pollution↗
PubMed2001

Using a continuous time hidden Markov process, with covariates, to model bed occupancy of people aged over 65 years.

Previously, the application of a continuous time hidden Markov model with discrete states was used to model geriatric inpatient behaviour. This was itself built on research using a discrete deterministic model to represent the flow of geriatric patients around departments of geriatric medicine. This paper uses the continuous time hidden Markov models and includes the effect of covariates, age and sex, in the model. Fitting the models we can visually see that the two compartment models provides estimates that are much closer to those observed in the data. The addition of covariates provides us with evidence of a difference in length of stay between men and women. However, even significant alterations to the mean age of patients in the model does not effect the length of stay.

Age Factors↗
PubMed1996

Deterministic pressure dissociation and unfolding of triose phosphate isomerase: persistent heterogeneity of a protein dimer.

Subunit dissociation and unfolding of dimeric rabbit muscle triose phosphate isomerase (TIM) induced by hydrostatic pressure were investigated. Changes in fluorescence emission of TIM (both intrinsic and of covalently attached probes) indicated that pressure ranging from 1 bar to 3.5 kbar promoted subunit dissociation and unfolding. Instrinsic fluorescence changes upon unfolding by pressure included a 27 nm red-shift of the emission, a decrease in fluorescence anisotropy from 0.14 to about 0.01, and a 1.5-fold increase in fluorescence quantum yield, similar to that observed in the presence of guanidine hydrochloride. Kinetics of pressure-induced fluorescence changes were slow (t 1/2 approximately 15 min) and little dependent on pressure. In order to selectively monitor subunit dissociation, fluorescence resonance energy transfer (FRET) measurements were carried out with TIM that was separately labeled with 5-((((2-iodoacetyl)-amino)ethyl)amino)naphthalene-1-sulfonic acid (1,5-IAEDANS) or fluorescein-5-isothiocyanate (FITC). FRET measurements indicated that subunit dissociation and unfolding took place concomitantly, both under equilibrium conditions and in kinetic experiments in which dissociation/unfolding was triggered by a sudden increase in pressure. Release of pressure caused monomer refolding and dimerization. Contrary to what would be expected for a process involving subunit dissociation, pressure effects on TIM were not dependent on protein concentration. Experiments involving a series of pressure jumps demonstrated persistent heterogeneity in sensitivity toward pressure in the ensemble of TIM dimers. This kind of deterministic behavior is similar to that exhibited by higher order protein aggregates and indicates that not all individual dimers are energetically identical in solution. The heterogeneity of native TIM revealed by sensitivity to pressure could not be detected by traditional means of protein separation, such as polyacrylamide gel electrophoresis (under both native and denaturing conditions) and size exclusion gel chromatography. This suggests that energetic heterogeneity originates from conformational heterogeneity of the protein. The possible biological relevance of the deterministic character of stability of TIM is discussed.

Animals↗
PubMed1997

Time-frequency plane Wiener filtering of the high-resolution ECG: background and time-frequency representations.

This paper introduces the concept of a posteriori Wiener filtering (APWF), performed in the time-frequency plane. The objective is to improve the signal-to-noise ratio (SNR) of the ensemble-averaged high-resolution electrocardiogram (HRECG). APWF was developed to address the problem of a limited ensemble size for estimating ensemble-averaged evoked potentials. For the HRECG, we identify the major challenge as adapting the time-frequency structure of the filter to that of low-level cardiac signals. Technical limitations and the characteristics of HRECG signals make time-frequency analysis of the ensemble average problematic. Normal and abnormal signal components are difficult to distinguish due to low time-frequency energy concentration and limited spectrotemporal resolution. However, considering the entire ensemble of repetitive ECG records, signal and noise components are separable in the time-frequency plane. This forms the basis of the new time-frequency plane Wiener (TFPW) filter, applicable to any ensemble averaging problem involving repetitive deterministic signals mixed with uncorrelated noise.

Electrocardiography↗
PubMed2000

Stochastic boundary conditions in the deterministic Nagel-Schreckenberg traffic model.

We consider open systems where cars move according to the deterministic Nagel-Schreckenberg rules [K. Nagel and M. Schreckenberg, J. Phys. I 2, 2221 (1992)] and with maximum velocity v(max)>1, which is an extension of the asymmetric exclusion process (ASEP). It turns out that the behavior of the system is dominated by two features: (a) the competition between the left and the right boundary, (b) the development of so-called "buffers" due to the hindrance that an injected car feels from the front car at the beginning of the system. As a consequence, there is a first-order phase transition between the free flow and the congested phase accompanied by the collapse of the buffers, and the phase diagram essentially differs from that for v(max)=1 (ASEP).

Journal Article↗
PubMed2001

Diffusion of particles bouncing on a one-dimensional periodically corrugated floor.

We report on a class of spatially extended mechanical systems sustaining a transport process of diffusive type. These systems consist of a point particle subject to a constant vertical acceleration and bouncing on a one-dimensional periodically corrugated floor. We show that the deterministic dynamics of these systems is chaotic with small elliptic islands for many parameter values. The motion of particles perturbed by a small noise has a horizontal diffusion that is normal. In such a case, we show that the diffusion coefficient oscillates periodically as the energy of particles increases. In the absence of noise, there still exists an effective numerical value for the diffusion coefficient and this value has an irregular dependence on energy.

Journal Article↗
PubMed1990

[The EEG and thinking].

The on-going EEG contains information on thinking strategies during cognitive and creative tasks and during listening to music. This was demonstrated by a method taking use of the fact that both the amount of local current production and the degree of electric coupling of brain regions is characteristically changed by mental tasks. In groups of volunteers the significant changes of absolute power and coherence caused by different mental tasks are computed and entered into schematic brain maps (EEG probability maps). The results indicate the existence of general brain strategies even in mental activities as specific as those referred to above. Moreover, several relationships between EEG, psychological test scores, degree of special education and intelligence were found. Studies with extreme value validation according to intelligence and creativity test scores yielded significant differences between the groups of the best and the poorest performers during a creative task in the EEG. The EEG thus can be conceived of as deterministic chaos with different degrees of organization according to its information content. In this context, the question arises as to a possible function of the EEG for the optimization of thinking processes.

Cognition↗
PubMed1991

Dynamic population epidemic models.

Most multipopulation epidemic models are of the contact distribution type, in which the locations of successive contacts are chosen independently from appropriate contact distributions. This paper is concerned with an alternative class of models, termed dynamic population epidemic models, in which infectives move among the populations and can infect only within their current population. Both the stochastic and deterministic versions of such models are considered. Their threshold behavior is analyzed in some depth, as are their final outcomes. Velocities of spread of infection are considered when the populations have a spatial structure. A criterion for finding the equivalent contact distribution epidemic for any given dynamic population epidemic is provided, enabling comparisons to be made for the velocities and final outcomes displayed by the two classes of models. The relationship between deterministic and stochastic epidemic models is also discussed briefly.

Disease Outbreaks↗
PubMed1999

Insufficient evidence: the problems of evidence-based nursing.

Evidence-based medicine was first proposed in the early 1990s as a means of integrating clinical expertise with the best evidence from research. It has recently gained a foothold in nursing, where despite calls for a broad and nursing-oriented definition of what should count as evidence, it appears to be propounding the randomized controlled trial (RCT) as the gold standard. This paper challenges the wisdom of basing nursing practice on the findings of large-scale statistical research studies, and offers a number of logical objections to the underpinning philosophy of evidence-based nursing and the randomized controlled trial. It concludes by arguing for a rethinking of what should count as evidence, and suggests a quasi-legal model based on reflection rather than research, in which evidence is employed to understand and justify practice after the event rather than being used deterministically to plan practice in advance.

Clinical Competence↗
PubMed1990

Receptor-mediated cell attachment and detachment kinetics. I. Probabilistic model and analysis.

The kinetics of receptor-mediated cell adhesion to a ligand-coated surface play a key role in many physiological and biotechnology-related processes. We present a probabilistic model of receptor-ligand bond formation between a cell and surface to describe the probability of adhesion in a fluid shear field. Our model extends the deterministic model of Hammer and Lauffenburger (Hammer, D.A., and D.A. Lauffenburger. 1987. Biophys. J. 52:475-487) to a probabilistic framework, in which we calculate the probability that a certain number of bonds between a cell and surface exists at any given time. The probabilistic framework is used to account for deviations from ideal, deterministic behavior, inherent in chemical reactions involving relatively small numbers of reacting molecules. Two situations are investigated: first, cell attachment in the absence of fluid stress; and, second, cell detachment in the presence of fluid stress. In the attachment case, we examine the expected variance in bond formation as a function of attachment time; this also provides an initial condition for the detachment case. Focusing then on detachment, we predict transient behavior as a function of key system parameters, such as the distractive fluid force, the receptor-ligand bond affinity and rate constants, and the receptor and ligand densities. We compare the predictions of the probabilistic model with those of a deterministic model, and show how a deterministic approach can yield some inaccurate results; e.g., it cannot account for temporally continuous cell attach mentor detachment, it can underestimate the time needed for cell attachment, it can overestimate the time required for cell detachment for a given level of force, and it can overestimate the force necessary for cell detachment.

Biophysical Phenomena↗
PubMed2000

Hitchhiking under positive Darwinian selection.

Positive selection can be inferred from its effect on linked neutral variation. In the restrictive case when there is no recombination, all linked variation is removed. If recombination is present but rare, both deterministic and stochastic models of positive selection show that linked variation hitchhikes to either low or high frequencies. While the frequency distribution of variation can be influenced by a number of evolutionary processes, an excess of derived variants at high frequency is a unique pattern produced by hitchhiking (derived refers to the nonancestral state as determined from an outgroup). We adopt a statistic, H, to measure an excess of high compared to intermediate frequency variants. Only a few high-frequency variants are needed to detect hitchhiking since not many are expected under neutrality. This is of particular utility in regions of low recombination where there is not much variation and in regions of normal or high recombination, where the hitchhiking effect can be limited to a small (<1 kb) region. Application of the H test to published surveys of Drosophila variation reveals an excess of high frequency variants that are likely to have been influenced by positive selection.

Animals↗