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At least 1,477 records · Page 82Linked to original sources
PubMed1992

Bayesian restoration of single-channel patch clamp recordings.

The technique of patch clamp recording makes possible the measurement of current flowing through a single ion channel in a cell membrane. Examination of such recordings suggests that the current is quantal in nature, alternating in a seemingly random manner between "on" and "off," but the recordings are corrupted by noise from a variety of sources. In this paper we propose and illustrate methods for restoring the underlying quantal signal from such noisy measurements. The methods use a Markov chain prior distribution for the underlying quantal process and base the restoration on the resulting posterior distribution.

Algorithms↗
PubMed2006

Pair approximations and the inclusion of indirect transmission: theory and application to between farm transmission of Salmonella.

The spatial-temporal dynamics of farm animal diseases depend both on disease specific processes and the underlying contact network between farms. Indirect transmission via free-living bacteria in the environment is an important transmission route and contributes significantly to the dynamics. The pair-wise model has been developed to include both direct transmission and indirect transmission via free stages. The model is compared with stochastic simulations of epidemics on contact networks. The network framework is applied to the investigation of the epidemiological dynamics of between-herd transmission of Salmonella spp. The main results help to explain differences in observed epidemiological patterns and to identify possible causes for different strains of Salmonella developing so much variation in their infection dynamics in UK dairy herds. Numerical results show that shorter infectious period, more persistent immune response and more rapid removal of faeces result in a lower prevalence of infection and a greater tendency for (damped) oscillation. A possible control strategy is consequently suggested. Furthermore, the effect of network structure on long-term dynamics is examined.

Animals↗
PubMed1996

Sources of uncertainty in estimating HIV infection rates by back-calculation: an application to Italian data.

The effects on back-calculated HIV diffusion estimates of the uncertainties in a number of factors that may potentially influence the estimation process are examined and compared. More specifically, the effect on HIV infection estimates of uncertainties in: (i) the sequence of periodical AIDS incidence cases; (ii) the estimation of the AIDS incubation period, including the influence of therapeutic treatment on the same; and (iii) the choice of a particular back-calculation method, including the stochastic uncertainty associated with each method, are examined. The choice of one particular back-calculation model over another, among three different methods considered, seems to be a minor component of the uncertainty, when compared to the uncertainty, due to all other sources. HIV incidence and prevalence in Italy for different risk categories are estimated.

Algorithms↗
PubMed2005

Patterns of spontaneous activity in single rat olfactory receptor neurons are different in normally breathing and tracheotomized animals.

Spontaneous firing of olfactory receptor neurons (ORNs) was recently shown to be required for the survival of ORNs and the maintenance of their appropriate synaptic connections with mitral cells in the olfactory bulb. ORN spontaneous activity has never been described or characterized quantitatively in mammals. To do so we have made extracellular single unit recordings from ORNs of freely breathing (FB) and tracheotomized (TT) rats. We show that the firing behavior of TT neurons was relatively simple: they tended to fire spikes at the same average frequency according to purely random (Poisson) or simple (Gamma or Weibull) statistical laws. A minority of them were bursting with relatively infrequent and short bursts. The activity of FB neurons was less simple: their firing rates were more diverse, some of them showed trends or were driven by breathing. Although more of them were regular, only a minority could be described by simple laws; the majority displayed random bursts with more spikes than the bursts of TT neurons. In both categories bursts and isolated spikes (outside bursts) occurred completely at random. The spontaneous activity of ORNs in rats resembles that of frogs, but is higher, which may be due to a difference in body temperature. These results suggest that, in addition to the intrinsic thermal noise, spontaneous activity is provoked in part by mechanical, thermal, or chemical (odorant molecules) effects of air movements due to respiration, this extrinsic part being naturally larger in FB neurons. It is suggested that spontaneous activity may be modulated by respiration. Because natural sampling of odors is synchronized with breathing, such modulation may prepare and keep olfactory bulb circuits tuned to process odor stimuli.

Action Potentials↗
PubMed1993

A diffusion model of a neuron and neural nets.

In the paper a diffusion model of a neuron is treated. A new, less restrictive than usually, condition of applicability of a diffusion model is presented. As a result the point-process-to-point-process model of a neuron is obtained, which produces an output signal of the same kind as the accepted input signals.

Action Potentials↗
PubMed1984

Redundancy reducing processes in single neurons.

Interaction mechanisms between excitatory and inhibitory impulse sequences operating on neurons play an important role for the processing of information by the nervous system. For instance, the convergence of excitatory and inhibitory influences on retinal ganglion cells to form their receptive fields has been taken as an example for the process of neuronal sharpening by lateral inhibition. In order to analyze quantitatively the functional behavior of such a system, Shannon's entropy method for multiple access channels has been applied to biological two-inputs-one-output systems using the theoretical model developed by Tsukada et al. (1979). Here we give an extension of this procedure from the point of view to reduce redundancy of information in the input signal space of single neurons and attempt to obtain a new interpretation for the information processing of the system. The concept for the redundancy reducing mechanism in single neurons is examined and discussed for the following two processes. The first process is concerned with a signal space formed by superposing two random sequences on the input of a neuron. In this process, we introduce a coding technique to encode the inhibitory sequence by using the timing of the excitatory sequence, which is closely related to an encoding technique of multiple access channels with a correlated source (Marko, 1966, 1970, 1973; Slepian and Wolf, 1973) and which is an invariant transformation in the input signal space without changing the information contents of the input. The second process is concerned with a procedure of reducing redundant signals in the signal space mentioned before.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2005

Time autocorrelation function analysis of master equation and its application to atomic clusters.

We derive the energy fluctuation Delta(2)E, and the time autocorrelation kappa(tau) and its Fourier transformation--the fluctuation spectra S(omega)--of the master-equation transition matrix. The contribution from each eigenmode of the transition matrix to these fluctuation quantities reveals the relevant importance of the individual mode in the relaxation processes. The time scales associated with these relaxation processes are determined by the corresponding eigenvalues. Unlike traditional time evolution analysis, the autocorrelation function and fluctuation spectra analysis does not involve an arbitrary initial population. It is also more suitable for analyzing the underlying dynamic, kinetic behavior near the equilibrium and the behavior of the long-time-scale rare events. We utilize our technique to analyze the solid-liquid phase coexistence of the 13-atom Morse cluster and the fcc-to-icosahedral structure transition of the 38-atom Lennard-Jones cluster. For the processes studied, the fluctuation spectra from the master equation simplify the analysis of the transition matrix, and the important relaxation modes are easily extracted.

Chemistry, Physical↗
PubMed2004

Calcium regulation of single ryanodine receptor channel gating analyzed using HMM/MCMC statistical methods.

Type-II ryanodine receptor channels (RYRs) play a fundamental role in intracellular Ca(2+) dynamics in heart. The processes of activation, inactivation, and regulation of these channels have been the subject of intensive research and the focus of recent debates. Typically, approaches to understand these processes involve statistical analysis of single RYRs, involving signal restoration, model estimation, and selection. These tasks are usually performed by following rather phenomenological criteria that turn models into self-fulfilling prophecies. Here, a thorough statistical treatment is applied by modeling single RYRs using aggregated hidden Markov models. Inferences are made using Bayesian statistics and stochastic search methods known as Markov chain Monte Carlo. These methods allow extension of the temporal resolution of the analysis far beyond the limits of previous approaches and provide a direct measure of the uncertainties associated with every estimation step, together with a direct assessment of why and where a particular model fails. Analyses of single RYRs at several Ca(2+) concentrations are made by considering 16 models, some of them previously reported in the literature. Results clearly show that single RYRs have Ca(2+)-dependent gating modes. Moreover, our results demonstrate that single RYRs responding to a sudden change in Ca(2+) display adaptation kinetics. Interestingly, best ranked models predict microscopic reversibility when monovalent cations are used as the main permeating species. Finally, the extended bandwidth revealed the existence of novel fast buzz-mode at low Ca(2+) concentrations.

Algorithms↗
PubMed2002

Optimization of feeding profile for a fed-batch bioreactor by an evolutionary algorithm.

The optimal feeding profile of a fed batch process was designed by means of an evolutionary algorithm. The algorithm chromosomes include the real-valued parameters of a profile function, defined by previous knowledge. Each chromosome is composed of the parameters that define the feeding profile: the feed rates, the singular arc parameters and the switching times between the profile states. The feed profile design was tested on a fed-batch process simulation. The accepted profiles were smooth and similar to those derived analytically in other studies. Two selection functions, roulette wheel and geometric ranking, were compared. In order to overcome the problem of model mismatches, a novel optimization scheme was carried out. During its operation the process was sampled, the model was updated and the optimization procedure was applied. The on-line optimization showed improvement in the objective function for relatively low sample times. Choosing the sampling frequencies depends on the process dynamics and the time required for the measurements and optimization. Further study on experiments of fed-batch process demonstrated the use of complex, non-differentiable model and produced improved process performances using the optimal feeding profile.

Algorithms↗
PubMed2006

The evolution of parasite manipulation of host dispersal.

We investigate the evolution of manipulation of host dispersal behaviour by parasites using spatially explicit individual-based simulations. We find that when dispersal is local, parasites always gain from increasing their hosts' dispersal rate, although the evolutionary outcome is determined by the costs-to-benefits ratio. However, when dispersal can be non-local, we show that parasites investing in an intermediate dispersal distance of their hosts are favoured even when the manipulation is not costly, due to the intrinsic spatial dynamics of the host-parasite interaction. Our analysis highlights the crucial importance of ecological spatial dynamics in evolutionary processes and reveals the theoretical possibility that parasites could manipulate their hosts' dispersal.

Adaptation, Physiological↗
PubMed1993

Effects on response time of factors selectively influencing processes in acyclic task networks with OR gates.

The mental processes involved in performing some tasks can be represented as directed arcs in an acyclic network. A path directed from the head of one arc to the tail of another indicates that the process represented by the first arc must be executed prior to the process represented by the second arc. If there is no directed path from one arc to another, the corresponding processes can be executed concurrently. Information about the arrangement of processes in an acyclic network can be found from the effects on response times of factors selectively influencing the processes. The methodology was developed earlier for critical path networks, in which a process begins execution when all its immediate predecessors have finished. This paper considers shortest path networks, in which a process begins execution as soon as any immediate predecessor is finished. Results analogous to those for critical path networks are reported. New results are presented enabling investigators to distinguish sequential and concurrent processes in both critical path and shortest path networks. This information is sufficient to construct an acyclic network representing the processes. Further, by examining the effects of selectively influencing processes, one can determine whether a task network is a critical path network or a shortest path network.

Animals↗
PubMed2004

A versatile petri net based architecture for modeling and simulation of complex biological processes.

The research on modeling and simulation of complex biological systems is getting more important in Systems Biology. In this respect, we have developed Hybrid Function Petri net (HFPN) that was newly developed from existing Petri net because of their intuitive graphical representation and their capabilities for mathematical analyses. However, in the process of modeling metabolic, gene regulatory or signal transduction pathways with the architecture, we have realized three extensions of HFPN, (i) an entity should be extended to contain more than one value, (ii) an entity should be extended to handle other primitive types, e.g. boolean, string, (iii) an entity should be extended to handle more advanced type called object that consists of variables and methods, are necessary for modeling biological systems with Petri net based architecture. To deal with it, we define a new enhanced Petri net called hybrid functional Petri net with extension (HFPNe). To demonstrate the effectiveness of the enhancements, we model and simulate with HFPNe four biological processes that are diffcult to represent with the previous architecture HFPN.

Algorithms↗
PubMedDate not supplied

[Behavioral activity in an uncertain environment (the methodological characteristics of an experimental study)].

A fundamental resemblance between processes of probabilitive training and conditional reflex forming exist wile using lowintensive signal stimulus and probabilitive way of confirmation. A base of intrinsic unity of these methodical variants is a complicated way of elicitation of bond between signal stimulus and confirmation, absence of one-way interpreted information about an environment presuming probabilitive estimate using. In this case informative interaction between an individual and subjectively accidental environment takes place or the same, a process of subjectively probabilitive training. Accordingly probabilitive training is a dinamic process of training under conditions of subjective uncertainty based probabilitive estimate application and feedback elements existence.

Animals↗
PubMed2002

Intrinsic and extrinsic contributions to stochasticity in gene expression.

Gene expression is a stochastic, or "noisy," process. This noise comes about in two ways. The inherent stochasticity of biochemical processes such as transcription and translation generates "intrinsic" noise. In addition, fluctuations in the amounts or states of other cellular components lead indirectly to variation in the expression of a particular gene and thus represent "extrinsic" noise. Here, we show how the total variation in the level of expression of a given gene can be decomposed into its intrinsic and extrinsic components. We demonstrate theoretically that simultaneous measurement of two identical genes per cell enables discrimination of these two types of noise. Analytic expressions for intrinsic noise are given for a model that involves all the major steps in transcription and translation. These expressions give the sensitivity to various parameters, quantify the deviation from Poisson statistics, and provide a way of fitting experiment. Transcription dominates the intrinsic noise when the average number of proteins made per mRNA transcript is greater than approximately 2. Below this number, translational effects also become important. Gene replication and cell division, included in the model, cause protein numbers to tend to a limit cycle. We calculate a general form for the extrinsic noise and illustrate it with the particular case of a single fluctuating extrinsic variable-a repressor protein, which acts on the gene of interest. All results are confirmed by stochastic simulation using plausible parameters for Escherichia coli.

Biophysical Phenomena↗
PubMed1999

Maintaining life and health by natural selection of protein molecules.

A concept for a life and health-preserving principle is presented, with reference to evolutionary, medical, and biochemical observations. Life comprises two basic phenomena: it unfolds over longer periods at the population level, and is sustained for the duration of individual life spans. The evolution of life within populations by means of natural selection of individuals is central to Darwin's theory of evolution. An important component of maintaining individual life is proposed here to be the natural selection of molecular components-the proteins, a process of preferred removal of denatured and old, synonymous with the selection of younger, functional molecules. The proteins of the cell are committed to fulfilling all the tasks programmed by the genome while continuously maintaining all appropriate cellular functions, including protecting the DNA. Physiological and environmental influences accelerate the breakdown of aged protein molecules, driving this renewal process so that the cell can maintain its protein stock at high-performance levels. The principle of selection makes the incredible dynamics of continual protein turnover, and hence not only the preservation of life, but the maintenance of health in individual beings, comprehensible. Arguments are presented to counter the hypothesis that protein breakdown is a stochastic, random process governed by first-order kinetics.

Animals↗
PubMed2001

Detection of mutual determinism between a pair of spike trains.

A method for detecting mutual deterministic dependence between a pair of spike trains is proposed. When it is assumed that a cell assembly, which is a subgroup of neurons processing a common task, is constituted as a dynamical system, then the mutual determinism between constituent neurons may be directly reflected in functional connectivity in the assembly. The deterministic dependence between two spike trains can be measured with statistical significance using a method of nonlinear prediction. Some examples of simulations are demonstrated in both deterministic and stochastic cases.

Action Potentials↗
PubMed1995

Poisson-process electrical stimulation: circuit and axonal responses.

This work describes a simple circuit which generated a highly Poisson-like sequence of pulses. Resistor noise was amplified in three series stages followed by rectification through a relatively large shunt resistance. This yielded a sequence of variable-amplitude transients, which were inverted, amplified with DC adjustment, and fed into a Schmitt trigger/multivibrator chip for pulse generation. The pulse generation frequency was modulated by the amplification of the rectified transients. The stochastic characteristics of the output pulse train were Poisson-like over a wide frequency range, as assessed using the intervent interval distribution and expectation density as steady-state and real-time estimators, respectively. In separate tests, the output pulse train was applied to forelimb cutaneous axons of the anesthetized cat; trains of elicited propagating action potentials were recorded extracellularly from individual G1 axons in the cuneate fasciculus. The stochastic properties of the action potential train differed from those of the stimulus, with longer deadtime, lower mean rate, and an early expectation density peak. These physiological responses to circuit output were similar to those elicited by other generators of Poisson-like stimulation.

Action Potentials↗
PubMed2004

[Epistemological views about vicious epigenetic circles due to aging].

Aging is not a disease. Age changes occur in every adult animal. They take place in all species. Yet, malignant tumours and neurodegenerative diseases grow with age. Nobody dies from aging. Death results from age-associated diseases. Muscular and digestive atrophies rise with age. But should it be said that digestive atrophy leads to malnutrition, or is it the contrary? Where is the chicken and where is the egg? We are enclosed in a vicious circle. A vicious circle is not a simple cycle. It is an irreversible phenomenon that happens when a system of objects is acting on itself. Vicious circles now reach the molecular level. This paper tries to show that the destruction of elastin and of fibronectin in connective tissues produces a self destruction effect. Von Neumann showed that a model of self reproduction with the help of reproductive automata could be imagined. We attempt now to show that nature has imagined a model to produce self destruction, trough degradation products of fibronectin and of elastin. This self destruction process is neither purely stochastic, nor genetically programmed. It is an epigenetical process. It is not present in the beginning, as an a priori instruction, it emerges. We try to give here a unusual specific philosophical definition of the word "emergence".

Aging↗