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PubMed2006

Cellular redox regulation and prooxidant signaling systems: a new perspective on the free radical theory of aging.

The overarching role of coenzyme Q(10) in gene regulation, bioenergy formation, cellular redox poise regulation, and hydrogen peroxide formation is presented. Coenzyme Q(10) has a central role acting as a prooxidant in the generation of H(2)O(2). Contrary to the dogma that superoxide and H(2)O(2) formation are highly deleterious to cell survival this premise is rejected. Data are discussed that continuous superoxide and hydrogen peroxide formation are essential for normal cell function and that they play a major role in subcellular redox state modulation. It is the prooxidant activity of the so-called antioxidants that may be responsible for previously claimed benefits for high doses of oxido-reduction nutritional supplements such as alpha lipoic acid and coenzyme Q(10). Oxygen-free radical formation is essential for the biological function and is not a direct causation of the mammalian aging process; aging is a multisystem stochastic process.

Aging↗
PubMed2004

A mathematical analysis of the generation and termination of calcium sparks.

Calcium sparks are local regenerative releases of Ca(2+) from a cluster of ryanodine receptors on the sarcoplasmic reticulum. During excitation-contraction coupling in cardiac cells, Ca(2+) sparks are triggered by Ca(2+) entering the cell via the T-tubules (Ca(2+)-induced Ca(2+) release). However under conditions of calcium overload, Ca(2+) sparks can be triggered spontaneously. The exact process by which Ca(2+) sparks terminate is still an open question, although both deterministic and stochastic processes are likely to be important. In this article, asymptotic methods are used to analyze a single Ca(2+) spark model, which includes both deterministic and stochastic biophysical mechanisms. The analysis calculates both spark frequencies and spark duration distributions, and shows under what circumstances stochastic transitions are important. Additionally, a model of the coupling of the release channels via the FK-binding protein is analyzed.

Animals↗
PubMed1998

Stochastic epidemics: the expected duration of the endemic period in higher dimensional models.

A method is presented to approximate the long-term stochastic dynamics of an epidemic modelled by state variables denoting the various classes of the population such as in SIR and SEIR model. The modelling includes epidemics in populations at different locations with migration between these populations. A logistic stochastic process for the total infectious population is formulated; it fits the long-term stochastic behaviour of the total infectious population in the full model. A good approximation is obtained if only the dynamics near the equilibria is fit.

Citrus↗
PubMed1991

Segmentation of speckle images based on level-crossing statistics.

When imaging is performed by using a coherent signal, the result is frequently a realization of the stochastic process known as speckle. The information sought from this process is often the mean value of its envelope or intensity at each point in the image plane. When only a single realization of the process is available, ergodicity is required within a sufficiently large region for accurate estimation of the mean. The identification of these regions is the segmentation problem that is addressed. The approach presented clips the speckle image at a constant threshold level and analyzes the resulting bilevel image based on the level-crossing statistics of the speckle process. An analysis of the level-crossing process leads to a decision rule for identifying or segmenting distinct regions of the image based on the sizes of the fades and the excursions in the clipped speckle. The measurement of these sizes is accomplished by using the morphological transformations of opening and closing. This new approach has been applied to computer-generated speckle images and may prove useful in laser, ultrasound, and radar imaging, in which speckle phenomena are manifest.

Image Processing, Computer-Assisted↗
PubMed1998

Modeling stochastic gene expression: implications for haploinsufficiency.

There is increasing recognition that stochastic processes regulate highly predictable patterns of gene expression in developing organisms, but the implications of stochastic gene expression for understanding haploinsufficiency remain largely unexplored. We have used simulations of stochastic gene expression to illustrate that gene copy number and expression deactivation rates are important variables in achieving predictable outcomes. In gene expression systems with non-zero expression deactivation rates, diploid systems had a higher probability of uninterrupted gene expression than haploid systems and were more successful at maintaining gene product above a very low threshold. Systems with relatively rapid expression deactivation rates (unstable gene expression) had more predictable responses to a gradient of inducer than systems with slow or zero expression deactivation rates (stable gene expression), and diploid systems were more predictable than haploid, with or without dosage compensation. We suggest that null mutations of a single allele in a diploid organism could decrease the probability of gene expression and present the hypothesis that some haploinsufficiency syndromes might result from an increased susceptibility to stochastic delays of gene initiation or interruptions of gene expression.

Computer Simulation↗
PubMedDate not supplied

An electricity price model with consideration to load and gas price effects.

Some characteristics of the electricity load and prices are studied, and the relationship between electricity prices and gas (fuel) prices is analyzed in this paper. Because electricity prices are strongly dependent on load and gas prices, the authors constructed a model for electricity prices based on the effects of these two factors; and used the Geometric Mean Reversion Brownian Motion (GMRBM) model to describe the electricity load process, and a Geometric Brownian Motion(GBM) model to describe the gas prices; deduced the price stochastic process model based on the above load model and gas price model. This paper also presents methods for parameters estimation, and proposes some methods to solve the model.

Computer Simulation↗
PubMed1996

[The first exploration of the properties and laws of mutation plastids transmitting with cell division].

Suppose there are m plastids in an initial cell, in which i plastids are mutated. In the this paper we discuss the probability that m mutated plastids are distributed in a cell simultaneously during in the process of mutant plastids dividing and randomly distributing with cell division. Let x(t) = 1 denote the stochastic event that a cell contains only mutant plastids in t-th division and x(t) = 0 denote the opposite event. We may find some properties of the stochastic process ¿x(t), t epsilon T¿ demonstrating that the process is a Markov chain. Finally we can obtain the matrixes of transition probability between homogeneous heterogeneous plastids, this reveals some laws of mutant plastids transmitting with cell division.

Cell Division↗
PubMed1991

Comparing functional (PET) images: the assessment of significant change.

Statistical parametric maps (SPMs) are potentially powerful ways of localizing differences in regional cerebral activity. This potential is limited by uncertainties in assessing the significance of these maps. In this report, we describe an approach that may partially resolve this issue. A distinction is made between using SPMs as images of change significance and using them to identify foci of significant change. In the first case, the SPM can be reported nonselectively as a single mathematical object with its omnibus significance. Alternatively, the SPM constitutes a large number of repeated measures over the brain. To reject the null hypothesis, that no change has occurred at a specific location, a threshold adjustment must be made that accounts for the large number of comparisons made. This adjustment is shown to depend on the SPM's smoothness. Smoothness can be determined empirically and be used to calculate a threshold required to identify significant foci. The approach models the SPM as a stationary stochastic process. The theory and applications are illustrated using uniform phantom images and data from a verbal fluency activation study of four normal subjects.

Adult↗
PubMed2002

Hsp90 as a capacitor of phenotypic variation.

Heat-shock protein 90 (Hsp90) chaperones the maturation of many regulatory proteins and, in the fruitfly Drosophila melanogaster, buffers genetic variation in morphogenetic pathways. Levels and patterns of genetic variation differ greatly between obligatorily outbreeding species such as fruitflies and self-fertilizing species such as the plant Arabidopsis thaliana. Also, plant development is more plastic, being coupled to environmental cues. Here we report that, in Arabidopsis accessions and recombinant inbred lines, reducing Hsp90 function produces an array of morphological phenotypes, which are dependent on underlying genetic variation. The strength and breadth of Hsp90's effects on the buffering and release of genetic variation suggests it may have an impact on evolutionary processes. We also show that Hsp90 influences morphogenetic responses to environmental cues and buffers normal development from destabilizing effects of stochastic processes. Manipulating Hsp90's buffering capacity offers a tool for harnessing cryptic genetic variation and for elucidating the interplay between genotypes, environments and stochastic events in the determination of phenotype.

Arabidopsis↗
PubMed2001

Waiting times to appearance and dominance of advantageous mutants: estimation based on the likelihood.

The germinal center reaction (GCR) of vertebrate immunity provides a remarkable example of evolutionary succession, in which an advantageous phenotype arises as a spontaneous mutation from the parental type and eventually displaces the parental type altogether. In the case of the immune response to the hapten (4-hydroxy-3-nitrophenyl)acetyl (NP), as with several other designed immunogens, the process is dominated by a single key mutation, which greatly simplifies the modeling of and analysis of data. We developed a two-stage model of this process in which the primary stage represents the appearance and establishment of the mutant population as a stochastic process while the second stage represents the growth and dominance of the clone as a deterministic process, conditional on its time of establishment from stage one. We applied this model to the analysis of population samples from several germinal center (GC) reactions and used maximum-likelihood methods to estimate the waiting times to arrival and to dominance of the mutant clone. We determined the sampling properties of the maximum-likelihood estimates using Monte Carlo methods and compared them to their asymptotic distributions. The methods we present here are well-suited for use in the analysis of other systems, such as tumor growth and the experimental evolution of bacteria.

Animals↗
PubMed2006

In silico simulations suggest that Th-cell development is regulated by both selective and instructive mechanisms.

Th-cell differentiation is highly influenced by the local cytokine environment. Although cytokines such as IL-12 and IL-4 are known to polarize the Th-cell response towards Th1 or Th2, respectively, it is not known whether these cytokines instruct the developmental fate of uncommitted Th cells or select cells that have already been committed through a stochastic process. We present an individual based model that accommodates both stochastic and deterministic processes to simulate the dynamic behaviour of selective versus instructive Th-cell development. The predictions made by each model show distinct behaviours, which are compared with experimental observations. The simulations show that the instructive model generates an exclusive Th1 or Th2 response in the absence of an external cytokine source, whereas the selective model favours coexistence of the phenotypes. A hybrid model, including both instructive and selective development, shows behaviour similar to either the selective or the instructive model dependent on the strength of activation. The hybrid model shows the closest qualitative agreement with a number of well-established experimental observations. The predictions by each model suggest that neither pure selective nor instructive Th development is likely to be functional as exclusive mechanisms in Th1/Th2 development.

Animals↗
PubMed2003

Predicting the dynamic postural control response from quiet-stance behavior in elderly adults.

Human postural sway, as measured by fluctuations of the center of pressure (COP) under the feet of a quietly standing individual, can be characterized as a stochastic process. The fluctuation-dissipation theorem (FDT) provides a linear relationship between the fluctuations of a quasi-static, stochastic system to the same system's relaxation to equilibrium following a perturbation. We applied a similar linear relationship, based on the FDT, to the human postural control system to explore whether anterior-posterior (AP) fluctuations of the COP during quiet stance can be used to predict the AP response of the postural control system to a weak posteriorly directed mechanical perturbation (tug or pull at the waist). We tested 10 healthy elderly (mean age of 69yr) and 10 healthy young (mean age of 25yr) adult subjects. We found that this linear relationship was applicable to the postural control system of all 10 young and eight of the 10 elderly adult subjects. These results suggest that it is possible to predict an individual's dynamic response to a mild perturbation using quiet-stance data, regardless of age. The existence of this FDT-based linear relationship with respect to the human postural control system suggests that, for a given individual, the postural control system may use the same control mechanisms during quiet stance and mild-perturbation conditions, regardless of age.

Adult↗
PubMed2005

Power-law correlated processes with asymmetric distributions.

Motivated by the fact that many physical systems display (i) power-law correlations together with (ii) an asymmetry in the probability distribution, we propose a stochastic process that can model both properties. The process depends on only two parameters, where one controls the scaling exponent of the power-law correlations, and the other controls the degree of asymmetry in the distributions leaving the correlations unaffected. We apply the process to air humidity data and find that the statistical properties of the process are in a good agreement with those observed in the data.

Algorithms↗
PubMed1996

Marker processes in survival analysis.

In the development of many diseases there are often associated variables which continuously measure the progress of an individual towards the final expression of the disease (failure). Such variables are stochastic processes, here called marker processes, and, at a given point in time, they may provide information about the current hazard and subsequently on the remaining time to failure. Here we consider a simple additive model for the relationship between the hazard function at time t and the history of the marker process up until time t. We develop some basic calculations based on this model. Interest is focused on statistical applications for markers related to estimation of the survival distribution of time to failure, including (i) the use of markers as surrogate responses for failure with censored data, and (ii) the use of markers as predictors of the time elapsed since onset of a survival process in prevalent individuals. Particular attention is directed to potential gains in efficiency incurred by using marker process information.

Biomarkers↗
PubMed2002

Can we tell how a community was constructed? A comparison of five evenness indices for their ability to identify theoretical models of community construction.

Evenness indices provide a simple measure of community structure. It might therefore be possible to use them to identify the process by which a community has been assembled. To test whether this is practicable, we constructed simulated community samples using five stochastic models of community construction, proposed by Tokeshi. We then examined the ability of five evenness indices to identify the model under which the community samples were produced. Each model produced samples with a range of evenness values, but mean evenness differed between the models. The dominance decay (DD) model produced community samples with the greatest evenness, followed by MacArthur fraction (MF). Evenness was lowest under the dominance pre-emption (DP) model. The differences between models were quite consistent across indices and consistent between 5-species and 15-species communities. Samples produced under the DD and MF models varied least in evenness between 5-species and 15-species samples, and those produced under the random assortment (RA) model varied most, irrespective of the evenness index used. Evenness varied considerably between replicate samples, as expected with stochastic processes. In 5-species communities, the greatest robustness in evenness across replicates was seen using indices O or E'. In 15-species communities, O and E(Q) were the most robust. The index best able to identify the model which had generated the sample differed between models and with species richness. If the model of interest is not known in advance, the best index for identifying the generating model is E(var) for communities of more than 10 species for RF, RA and DP models and O for other communities. The number of samples required in a data set before it could be effectively identified was, for example, more than 30 for 5-species samples produced under the random fraction (RF) model, and 3 for 15-species RF samples. In contrast, a 5-species DD data set could be effectively identified when it contained 15 or more samples. We conclude that evenness can be used to identify the process by which the community has been constructed, out of the five models considered here. The best evenness index for doing this varies with the species richness and the evenness of the community but we can suggest the use of O without knowing the model because its the more stable one against species richness and the more robust and unbiased against simulated samples and it encompass a good discriminating power between the models in most of the cases studied.

Abstracting and Indexing↗
PubMed1997

Stochastic events underlie Ca2+ signalling in neutrophils.

In order to probe the events which couple receptor occupancy to elevation of cytosolic free Ca2+ fast laser scanning of fluo3-loaded neutrophils was used to determine the timing of the initial phase of the Ca2+ response. This approach demonstrated that there was a measurable delay between the addition of stimulus and the onset of the cytosolic free Ca2+ signal which varied from cell to cell variable from 75 ms to greater than 1.5 s. The distribution of lag times was similar to that expected if the delay resulted from a series of obligatory stochastic processes. From the Poisson equation, a probability density function for the delays was generated which depended on n, the number of stochastic events in the series, and lambda, the stochastic rate for the events. The best fit between the data and theory was found to be for six stochastic steps in the series occurring with a stochastic rate similar to that expected for diffusion of known small molecular weight signalling molecules within the cell. We, therefore, propose that the delays in onset of the Ca2+ response in neutrophils were the result of sequence of diffusion steps, each with sufficiently small numbers of intracellular messenger molecules to generate stochastic behaviour.

Calcium↗
PubMed1992

Analyzing the dynamics of hand tremor time series.

We investigate physiological, essential and parkinsonian hand tremor measured by the acceleration of the stretched hand. Methods from the theory of dynamical systems and from stochastics are used. It turns out that the physiological tremor can be described as a linear stochastic process, and that the parkinsonian tremor is nonlinear and deterministic, even chaotic. The essential tremor adopts a middle position, it is nonlinear and stochastic.

Hand↗
PubMed1998

Autocorrelation function and power spectrum of two-state random processes used in neurite guidance.

During development neurons extend and retract cytoskeletal structures, chiefly microtubules and filopodia, to process informational cues from the extracellular environment and thereby guide growth cone migration toward an appropriate synaptic partner. This cytoskeleton-based exploration is achieved by stochastic switching, with microtubules and filopodia alternating between growing and shortening phases apparently at random. If stabilizing signals are not detected during the growth phase, then the structures switch to a shortening state, from which they can again return to a growth phase, and so forth. A useful means of characterizing these stochastic processes in a model-independent way is by autocorrelation and spectral analysis. Previously, we compared experiment to theory by performing Monte Carlo simulations and computing the autocorrelation function and power spectrum from the simulated dynamics, an approach that is computationally intensive and requires recalculation whenever model parameters are changed. Here we present analytical expressions for the autocorrelation function and power spectrum, which compactly characterize microtubule and filopodial dynamics based on the stochastic, two-state model. The model assumes that the phase times are of variable duration and gamma-distributed, consistent with experimental evidence for microtubules assembled in vitro from purified tubulin. The analytical expressions permit the precise quantitative characterization of changes in microtubule and filopodial searching behavior corresponding to changes in the shape of the gamma distribution.

Animals↗