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[The relationship between genetic and stochastic damage during the process of cell and bodily aging].

The paper deals with the conception formulated by the author concerning the dual nature of the ageing process determined by genetic and random factors which manifest their action at the molecular, cellular and organism level. The review is given of the author's own studies in the ratio of programmed and stochastic mechanisms of ageing in different organisms and cells in the tissue culture. A conclusion is made that genetic factors are the leading ones in determining the main mechanisms of ageing.

Aging↗

Anomalous power law distribution of total lifetimes of branching processes: application to earthquake aftershock sequences.

We consider a general stochastic branching process, which is relevant to earthquakes, and study the distributions of global lifetimes of the branching processes. In the earthquake context, this amounts to the distribution of the total durations of aftershock sequences including aftershocks of arbitrary generation number. Our results extend previous results on the distribution of the total number of offspring (direct and indirect aftershocks in seismicity) and of the total number of generations before extinction. We consider a branching model of triggered seismicity, the epidemic-type aftershock sequence model, which assumes that each earthquake can trigger other earthquakes ("aftershocks"). An aftershock sequence results in this model from the cascade of aftershocks of each past earthquake. Due to the large fluctuations of the number of aftershocks triggered directly by any earthquake ("productivity" or "fertility"), there is a large variability of the total number of aftershocks from one sequence to another, for the same mainshock magnitude. We study the regime where the distribution of fertilities mu is characterized by a power law approximately 1/ mu(1+gamma) and the bare Omori law for the memory of previous triggering mothers decays slowly as approximately 1/ t(1+theta;) , with 0<theta;<1 relevant for earthquakes. Using the tool of generating probability functions and a quasistatic approximation which is shown to be exact asymptotically for large durations, we show that the density distribution of total aftershock lifetimes scales as approximately 1/ t(1+theta;/gamma) when the average branching ratio is critical (n=1) . The coefficient 1<gamma=b/alpha<2 quantifies the interplay between the exponent b approximately 1 of the Gutenberg-Richter magnitude distribution approximately 10(-bm) and the increase approximately 10(alpham) of the number of aftershocks with mainshock magnitude m (productivity), with 0.5<alpha<1 . The renormalization of the bare Omori decay law approximately 1/ t(1+theta;) into approximately 1/ t(1+theta;/gamma) stems from the nonlinear amplification due to the heavy-tailed distribution of fertilities and the critical nature of the branching cascade process. In the subcritical case n<1 , the crossover from approximately 1/ t(1+theta;/gamma) at early times to approximately 1/ t(1+theta;) at longer times is described. More generally, our results apply to any stochastic branching process with a power-law distribution of offspring per parent and a long memory.

Journal Article↗

Cortical activation, signal-to-noise ratio and stochastic resonance during information processing in man.

OBJECTIVES: The goal of this study was to determine the relation between EEG, event-related potentials and information processing as measured by an acoustical choice reaction time task. In particular, we wanted to find out to what extent reaction-time performance is related to the pre-stimulus EEG activity (frequency domain) and the magnitude of signal power as well as noise power (stimulus-uncorrelated activity) after the tones (time domain). MATERIALS AND METHODS: For parametrization, EEG-activity was factorized across pre-defined frequency bands and 19 electrode positions, applying spectral power and coherence analysis. Signal power was estimated by calculating the mean power of the evoked single sweeps. Noise power was computed by subtracting the latter minus the power of the average evoked potential. We investigated 254 healthy subjects who had to perform an acoustical choice reaction task during running EEG. RESULTS: In the frequency domain, it was found that high frontally pronounced delta-power in the pre-stimulus EEG correlates with fast reaction-time performance, which was regarded as the expression of a readiness potential in the frequency domain, reflecting increased cortical activation. In the time domain, fast reaction times were found to be correlated with the amplitude of the event-related potential N100 as well as with the signal power and signal-to-noise ratio of the evoked activity. This result pointed to the frequently described relation between evoked signals and information processing. In accordance with the theory of stochastic resonance, we also found a positive correlation between the magnitude of noise power after the stimulus and reaction-time performance. Besides, noise power was found to be positively correlated with pre-stimulus cortical activation (mainly in the delta and alphal frequency band), whereas no relation was found between pre-stimulus EEG and the signal power of the event-related activity, except for a weak relation to the alpha2 power. CONCLUSION: Our findings support the notion that information processing is not only dependent on signal strength but also on a certain amount of basic noise, reflecting the overall energy state of the brain.

Adolescent↗

Environmental stress mediates groundwater microbial community assembly.

Community assembly describes how different ecological processes shape microbial community composition and structure. How environmental factors impact community assembly remains elusive. Here we sampled microbial communities and >200 biogeochemical variables in groundwater at the Oak Ridge Field Research Center, a former nuclear waste disposal site, and developed a theoretical framework to conceptualize the relationships between community assembly processes and environmental stresses. We found that stochastic assembly processes were critical (>60% on average) in shaping community structure, but their relative importance decreased as stress increased. Dispersal limitation and 'drift' related to random birth and death had negative correlations with stresses, whereas the selection processes leading to dissimilar communities increased with stresses, primarily related to pH, cobalt and molybdenum. Assembly mechanisms also varied greatly among different phylogenetic groups. Our findings highlight the importance of microbial dispersal limitation and environmental heterogeneity in ecosystem restoration and management.

Phylogeny↗

Regularities and irregularities in the cell cycle of the fission yeast, Schizosaccharomyces pombe (a review).

In an exponentially growing wild-type fission yeast culture a size control mechanism ensures that mitosis is executed only if the cells have reached a critical size. However, there is some scattering both in cell length at birth (BL) and in cycle time (CT). By computational simulations we show here that this scattering cannot be explained solely by asymmetric cell division, therefore we assume that nuclear division is a stochastic, asymmetric process as well. We introduce an appropriate stochastic variable into a mathematical model and prove that this assumption is suitable to describe the CT vs. BL graph in a wild-type fission yeast population. In a double mutant of fission yeast (namely wee1-50 cdc25 delta) this CT vs. BL plot is even more curious: cycle time splits into three different values resulting in three clusters in this coordinate system. We show here that it is possible to describe these quantized cycles by choosing the appropriate values of the key parameters of mitotic entry and exit and even more the clustered behavior may be simulated by applying a further stochastic parameter.

Cell Cycle↗

Renewal-process approximation of a stochastic threshold model for electrical neural stimulation.

In a recent set of modeling studies we have developed a stochastic threshold model of auditory nerve response to single biphasic electrical pulses (Bruce et al., 1999c) and moderate rate (less than 800 pulses per second) pulse trains (Bruce et al., 1999a). In this article we derive an analytical approximation for the single-pulse model, which is then extended to describe the pulse-train model in the case of evenly timed, uniform pulses. This renewal-process description provides an accurate and computationally efficient model of electrical stimulation of single auditory nerve fibers by a cochlear implant that may be extended to other forms of electrical neural stimulation.

Action Potentials↗

Statistical evidence for a random commitment of pluripotent cephalic neural crest cells.

The neural crest (NC) of vertebrate embryos yields cell types belonging to the neural, melanocytic and mesectodermal lineages. To test the possibility that the precursors of these lineages segregate from pluripotent cells by a process involving stochastic determinants, we have analyzed with statistical methods the associations between six differentiated cell types in 201 clones obtained in vitro from migrating cephalic NC cells. Our analysis suggests that neuronal, adrenergic and Schwann cells are not randomly associated, whereas these neural cell types differentiate in the clones independently of both melanocytes and cartilage. These results raise the possibility that pluripotent NC progenitors give rise to the precursors of the major NC-derived lineages (neural, melanocytic and mesectodermal) by a process involving stochastic restrictions of their developmental potentialities.

Animals↗

Stochastic models for aggregation processes.

Three models are presented, which describe the aggregation of objects into groups and the distributions of groups sizes and group numbers within habitats. The processes regarded are pure accumulation processes which involve only formation and invasion of groups. Invasion represents the special case of fusion when only single objects - and not groups - join a group of certain size. The basic model is derived by a single parameter, the formation probability q, which represents the probability of an object to form a new group. A novel, discrete and finite distribution that results for the group sizes is deduced from this aggregation process and it is shown that it converges to a geometric distribution if the number of objects tends to infinity. Two extensions of this model, which both converge to the Waring distribution, are added: the model can be extended either with a beta distributed formation probability or with the assumption that the invasion probability depends on the group size. Relationships between the limiting distributions involved are discussed.

Animals↗

Gaussian process approach to spiking neurons for inhomogeneous Poisson inputs.

This article presents a new theoretical framework to consider the dynamics of a stochastic spiking neuron model with general membrane response to input spike. We assume that the input spikes obey an inhomogeneous Poisson process. The stochastic process of the membrane potential then becomes a gaussian process. When a general type of the membrane response is assumed, the stochastic process becomes a Markov-gaussian process. We present a calculation method for the membrane potential density and the firing probability density. Our new formulation is the extension of the existing formulation based on diffusion approximation. Although the single Markov assumption of the diffusion approximation simplifies the stochastic process analysis, the calculation is inaccurate when the stochastic process involves a multiple Markov property. We find that the variation of the shape of the membrane response, which has often been ignored in existing stochastic process studies, significantly affects the firing probability. Our approach can consider the reset effect, which has been difficult to deal with by analysis based on the first passage time density.

Action Potentials↗

Two variants of the first Nåsell-Hirsch model.

Two models are propounded on the general setting of the first Nåsell-Hirsch model for helminthic infections. They differ from it in the two processes of transmission of the infection, which are treated dissymmetrically. In each model only one of these processes will be deterministic, instead of both as in the Nåsell-Hirsch case, the other process being kept fully stochastic. These new models lead to results that show a general agreement with those of Nåsell and Hirsch but also some interesting differences.

Animals↗

Noise resistance in the spindle assembly checkpoint.

Genetically identical cells vary in the amount of expressed proteins even when growing under the same conditions. It is not yet clear how cellular information processing copes with such stochastic fluctuations in protein levels. Here we examine the capacity of the spindle assembly checkpoint to buffer temporal fluctuations in the expression of Cdc20, a critical checkpoint target whose activity is inhibited to prevent premature cell cycle progression. Using mathematical modeling, we demonstrate that the checkpoint can buffer significant fluctuations in Cdc20 production rate. Critical to this buffering capacity is the use of sequestering-based mechanism for inhibiting Cdc20, as apposed to inhibition by enhancing protein degradation. We propose that the design of biological networks is limited by the need to overcome noise in gene expression.

Cdc20 Proteins↗

Noisy signal amplification in ultrasensitive signal transduction.

Because intracellular processes are inherently noisy, stochastic reactions process noisy signals in cellular signal transduction. One essential feature of biological signal transduction systems is the amplification of small changes in input signals. However, small random changes in the input signals could also be amplified, and the transduction reaction can also generate noise. Here, we show theoretically how the abrupt response of ultrasensitive signal-transduction reactions results in the generation of large inherent noise and the high amplification of input noise. The inherently generated noise propagates with amplification through intracellular molecular network. We discuss how the contribution of such transmitted noise can be shown experimentally. Our results imply that the switch-like behavior of signal transduction could be limited by noise; however, high amplification reaction could be advantageous to generate large noise, which would be essential to maintain behavioral variability.

Gene Expression↗

Estimating risks in declining populations with poor data.

Census data on endangered species are often sparse, error-ridden, and confined to only a segment of the population. Estimating trends and extinction risks using this type of data presents numerous difficulties. In particular, the estimate of the variation in year-to-year transitions in population size (the "process error" caused by stochasticity in survivorship and fecundities) is confounded by the addition of high sampling error variation. In addition, the year-to-year variability in the segment of the population that is sampled may be quite different from the population variability that one is trying to estimate. The combined effect of severe sampling error and age- or stage-specific counts leads to severe biases in estimates of population-level parameters. I present an estimation method that circumvents the problem of age- or stage-specific counts and is markedly robust to severe sampling error. This method allows the estimation of environmental variation and population trends for extinction-risk analyses using corrupted census counts--a common type of data for endangered species that has hitherto been relatively unusable for these analyses.

Aging↗

Fluctuation theorems and the nonequilibrium thermodynamics of molecular motors.

The fluctuation theorems for the currents and the dissipated work are considered for molecular motors which are driven out of equilibrium by chemical reactions. Because of the molecular fluctuations, these nonequilibrium processes are described by stochastic models based on a master equation. Analytical expressions are derived for the fluctuation theorems, allowing us to obtain predictions on the work dissipated in the motor as well as on its rotation near and far from thermodynamic equilibrium. We show that the fluctuation theorems provide a method to determine the affinity or thermodynamic force driving the motor. This affinity is given in terms of the free enthalpy of the chemical reactions. The theorems are applied to the F1 rotary motor which turns out to be a stiff system typically functioning in the nonlinear regime of nonequilibrium thermodynamics. We show that this nonlinearity confers a robustness to the functioning of the molecular motor.

Computer Simulation↗

A stochastic population projection system based on general age-dependent branching processes.

"Algorithms for a stochastic population process, based on assumptions underlying general age-dependent branching processes in discrete time with time inhomogeneous laws of evolution, are developed through the use of a new representation of basic random functions involving birth cohorts and random sums of random variables. New algorithms provide a capability for computing the mean age structure of the process as well as variances and covariances, measuring variation about means. Four exploratory population projections, testing the implications of the algorithms for the case of time-homogeneous laws of evolution, are presented. Formulas extending mean and variance functions for unit population projections...are also presented. These formulas show that, in population processes with non-random laws of evolution, stochastic fluctuations about the mean function are negligible when initial population size is large. Further extensions of these formulas to the case of randomized laws of evolution suggest that stochastic fluctuations about the mean function can be significant even for large initial populations."

Age Factors↗

On the optimal control of behaviour: a stochastic perspective.

Evolution is a closed stochastic optimisation process driven by the interaction between behaviour and environment towards local maxima in fitness. It is inferred that nervous systems are selected to provide optimal control of behaviour (the 'assumption of optimality'), such that for some behaviours, the expectation of future hazards to survival are minimised. This is illustrated by goal-directed saccades in which minimising total flight-time of primary and secondary movements provides a better fit to observations than simply minimising the error of the primary movement. This optimisation is extended to intra-movement trajectories, where low-bandwidth (smooth) velocity profiles provide a more satisfactory description of observations than simple bang-bang control. Since minimum-time behaviours cannot be controlled by error feedback, it is concluded that the cerebellum must be executing a real-time unreferenced optimisation process. This requires explorative as well as exploitative behaviour. Stochastic gradient descent is discussed as a possible means by which the cerebellum may optimise behaviour.

Behavior↗

Stochastic resonance in geomagnetic polarity reversals.

Among noise-induced cooperative phenomena a peculiar relevance is played by stochastic resonance. In this paper we offer evidence that geomagnetic polarity reversals may be due to a stochastic resonance process. In detail, analyzing the distribution function P(tau) of polarity residence times (chrons), we found the evidence of a stochastic synchronization process, i.e., a series of peaks in the P(tau) at T(n) approximately (2n+1)T(Omega)/2 with n=0,1,...,j and T(omega) approximately 0.1 Myr. This result is discussed in connection with both the typical time scale of Earth's orbit eccentricity variation and the recent results on the typical time scale of climatic long-term variation.

Climate↗