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PubMed1991

Organizational levels analysis: a key to understanding processes in natural systems.

Recent research conducted on a hypothetical four-parameter system generated by two stochastic processes has shown that errors of interpretation are likely to result when the relative importance of an underlying generating process is inferred from the analysis of an emergent pattern of a natural system. This paper presents an approach which substantially reduces that error for the hypothetical system, taken as an analog for a natural system. This approach is based on recognition of the organizational levels composing the system and utilizes observations on structure at a lower organizational level to resolve the properties of the generating processes at the lower level. The resulting knowledge of those underlying structures and the processes which created them are then used to determine the relative importance of those processes in affecting the emergent pattern of the system at a higher organizational level. It is concluded that in order to understand the role of a process in a natural system, measurements of system structure must be performed at a frequency which isolates the process from the other processes in the system.

Animals↗
PubMed2003

Species richness in agamid lizards: chance, body size, sexual selection or ecology?

Why does species richness vary so greatly across lineages? Traditionally, variation in species richness has been attributed to deterministic processes, although it is equally plausible that it may result from purely stochastic processes. We show that, based on the best available phylogenetic hypothesis, the pattern of cladogenesis among agamid lizards is not consistent with a random model, with some lineages having more species, and others fewer species, than expected by chance. We then use phylogenetic comparative methods to test six types of deterministic explanation for variation in species richness: body size, life history, sexual selection, ecological generalism, range size and latitude. Of eight variables we tested, only sexual size dimorphism and sexual dichromatism predicted species richness. Increases in species richness are associated with increases in sexual dichromatism but reductions in sexual size dimorphism. Consistent with recent comparative studies, we find no evidence that species richness is associated with small body size or high fecundity. Equally, we find no evidence that species richness covaries with ecological generalism, latitude or range size.

Adaptation, Physiological↗
PubMed1996

Maturation pathways for E. coli tRNA precursors: a random multienzyme process in vivo.

tRNA maturation consists of the specific removal of precursor sequences from both the 5' and 3' termini of an initial RNA transcript. How this is accomplished has heretofore not been ascertained in any system. Using Northern analysis of RNA isolated from a variety of RNase-deficient E. coli strains, we have identified the processing intermediates that accumulate in the absence of specific processing nucleases. From this information we have established the maturation pathways for 12 different E. coli tRNAs including the specific role of each of the relevant RNases in the process. The surprising conclusion from this work is that tRNA maturation is a stochastic process that lacks a defined order and that can proceed with a variety of alternative 3' processing nucleases.

Base Sequence↗
PubMed2002

Cellular coenzyme Q10 redox poise constitutes a major cell metabolic and gene regulatory system.

A hypothesis as to the nature of the ageing process is presented. Our studies lead us to emphasise that ageing is a stochastic process; it is individualistic, it is species specific, it is different for individuals within a species, it is organ and tissue specific as well as varying among individual cells of a tissue. Human ageing is a slow process which takes place over decades; it is a cellular process in a dynamic equilibrium of continuing damage and repair. Tissues are damage mosaics. We hypothesise that the characteristic of ageing post-mitotic tissues is the progressive, slow loss of cells; those cells which no longer adequately function are removed by an apoptotic or non-inflammatory necrotic process. A case is made for an encompassing role for coenzyme Q10 in the regulation of systemic disease, cellular metabolism and ageing.

Coenzymes↗
PubMed2006

Statistical mechanics of histories: a cluster Monte Carlo algorithm.

We present an efficient computational approach to sample the histories of nonlinear stochastic processes. This framework builds upon recent work on casting a d-dimensional stochastic dynamical system into a (d+1)-dimensional equilibrium system using the path-integral approach. We introduce a cluster algorithm that efficiently samples histories and discuss how to include measurements that are available into the estimate of the histories. This allows our approach to be applicable to the simulation of rare events and to optimal state and parameter estimation. We demonstrate the utility of this approach for Phi4 Langevin dynamics in two spatial dimensions where our algorithm improves sampling efficiency up to an order of magnitude.

Journal Article↗
PubMed2006

Efficient inefficiency: biochemical "junk" may represent molecular bridesmaids awaiting emergent function as a buffer against environmental fluctuation.

The biochemical function of many parts of the genome, transcriptome, proteome, and interactome remain largely unknown. We propose that portions of these fundamental building blocks of life have no current biochemical function per se. Rather, sections of these "omes" may contribute to an inventory of biochemical parts and circuits that participate in the development of emergent functions. Low fidelity deoxyribonucleic acid replication, transcription, translation, and post-translational modification all represent potential mechanisms to produce an inventory of parts. Stochastic processes that influence the conformations of ribonucleic acid molecules and proteins may also contribute to potential biochemical inventory. Some components of the biochemical inventory may enable future adaptations, some may produce disease, and some may remain useless. The function of many of these components await discovery, not by science, but by evolution. While carrying such purposeless biochemical units may appear to dilute fitness by exacting a thermodynamic cost, we argue that net fitness becomes enhanced when considering the value for potential future innovations. One can envision components that intermingle, interact, and act out mock pathways, but in most cases remain molecular bridesmaids. Given sufficiently low thermodynamic cost, such stochastic cycling may persist until a markedly advantageous or cataclysmically disadvantageous trait emerges. Maladaptive screening and utilization of inventory content can lead to disease phenotypes, a process buffered and regulated in part by the heat shock protein and stress response network. Whereas failure of the ubiquitin pathway to recycle misfolded proteins has become increasingly recognized as a source of disease, protein misfolding may itself represent one step in a process that maximizes functional innovation through increasing proteomic diversity. Fractal correlates of these processes occur at the organizational level of cells and organisms. That the abnormal accumulation of units induces local collapse may serve to limit the extension of damage to the greater system at large. The immune and cognitive systems that selectively sample and prune environmental content may serve as additional portals for innovation.

Adaptation, Physiological↗
PubMed1975

Control by Preynaptic Correlation: a mechanism affecting information transmission from Ia fibers to motoneurons.

1. In the unanesthetized spinal cord of the cat, simultaneous intracellular recordings were made from two motoneurons belonging to the gastronemius motor nucleus. 2. Supramaximal iterative stimulation of small branches of the gastrocnemius nerve produced monosynaptic EPSPs (Ia EPSPs) of varying amplitude superimposed on a fluctuating base line. 3. In most cases the variance of the motoneuron membrane potential was increased above base-line levels with a time course approximately matching the Ia EPSP. This suggests that Ia EPSP fluctuations are greater than can be accounted for by the base-line fluctuations alone. 4. For a given series of Ia EPSPs, the smaller responses in the series had about the same decay phase as the larger EPSPs, suggesting that most of the Ia EPSP fluctuations were not due to systematic changes in postsynaptic conductances produced by ongoing activity, but rather to a presynaptic mechanism. 5. Simultaneous recording from two motoneurons showed that base-line fluctuations were positively correlated. In most cases, however, there was an additional increased correlation above base-line levels resembling the time course of the Ia EPSPs, indicating positive correlation between EPSP fluctuations which is attributed to a presynaptic mechanism. 6. Conditioning volleys to group I muscle afferents or to low-threshold cutaneous afferents reduced the variance of the Ia EPSPs and also their correlation in motoneuron pairs, often without changing the mean Ia EPSPs. 7. It is concluded that, in the unanesthetized spinal cord, in addition to the random process which governs transmitter release intrinsic to a given synaptic terminal, there is another stochastic process affecting, in a correlated manner, transmitter release in large sets of Ia synaptic terminals. Most likely, the correlation in transmitter release is achieved by membrane potential fluctuations imposed on the Ia terminal arborizations by ongoing activity of the segmental mechanism mediating primary afferent depolarization. 8. The effects of such a correlating influence on cell firing behavior have been analyzed. The results suggest that this mechanism, referred to as control by presynaptic correlation, is able to modulate the information transmitted from Ia fibers to motoneurons.

Animals↗
PubMed1982

A deconvolution program for processing radiotracer dilution curves.

We present a computer program for deconvolution of noisy signals. The unknown signal is modelled as a stochastic process and the solution is given by the 'maximum a posteriori estimator'. This is computed by two algorithms: the first uses and the Kalman filter; the second the conjugate gradient technique which permits introduction of a positivity constraint. The program has proved to give accurate results in stimulation studies. It has been applied to the deconvolution analysis of radionuclide angiocardiography time-activity curves. This improves the reliability of the results in left-to-right cardiac shunt quantitation.

Angiocardiography↗
PubMed1996

Application of dimension estimation and surrogate data to the time evolution of EEG topographic variables.

Dimensional complexity (estimated correlation dimension) was measured for two topographic EEG time series: (a) the time evolution of global field power (GFP) and (b) the time evolution of sequential dissimilarity (SQD) for resting, eyes-closed and eyes-open data. Eyes-closed GFP and eyes-closed/open SQD all had an element of nonlinearity in their dynamics as evidenced by increased dimensional complexity associated with the phase-angle randomization, Gaussian surrogate-data procedure. However, none of the three gave any evidence of being deterministic chaotic processes. Eyes-open GFP dimensional complexity could not be distinguished from a linear-stochastic process.

Adult↗
PubMed1996

Measurement of airborne 218Po--a Bayesian approach.

The standard mathematical treatment of the buildup and decay of airborne radionuclides on a filter paper uses the solutions of the so-called Bateman equations adapted to the sampling process. These equations can be interpreted as differential equations for the expectation of an underlying stochastic process, which describes the random fluctuations in the accumulation and decay of the sampled radioactive atoms. The process for the buildup and decay of airborne 218Po can be characterized as an "immigration-death process" in the widely adopted, biologically based jargon. The probability distribution for the number of 218Po atoms, accumulated after sampling time t, is Poisson. We show that the distribution of the number of counts, registered by a detector with efficiency epsilon during a counting period T after the end of sampling, is also Poisson, with mean dependent on epsilon, t, T, the flowrate and N(o), the number of airborne 218Po atoms per unit volume. This Poisson distribution was used to construct the likelihood given the observed number of counts. After inversion with Bayes' Theorem we obtained the posterior density for N(o). This density characterizes the remaining uncertainty about the measured number of 218Po atoms per unit volume of air.

Air Pollution, Radioactive↗
PubMed2002

Universality class of nonequilibrium phase transitions with infinitely many absorbing states.

We consider systems whose steady states exhibit a nonequilibrium phase transition from an active state to one-among an infinite number-absorbing state, as some control parameter is varied across a threshold value. The pair contact process, stochastic fixed-energy sandpiles, activated random walks, and many other cellular automata or reaction-diffusion processes are covered by our analysis. We argue that the upper-critical dimension below which anomalous fluctuation driven scaling appears is d(c)=6, in contrast to a widespread belief. We provide the exponents governing the critical behavior close to or at the transition point to first order in an epsilon =6-d expansion.

Journal Article↗
PubMed1997

Iterated Prisoner's Dilemma: pay-off variance.

The iterated Prisoner's Dilemma (IPD) is usually analysed by evaluating arithmetic mean pay-offs in an ESS analysis. We consider several points that the standard argument does not address. Finite population size and finite numbers of matches in the IPD game lead us to consider both pay-off variance and the sampling process in the evolutionary game. We provide a general form for the pay-off variance of the Markov strategist in the IPD game, and present a general analysis of the initial invasion process of an "all defection strategist" (ALLD) into a "tit-for-tat" (TFT) strategist population by considering stochastic processes. Finite population size, strategic error an the variances of pay-offs alter the prediction concerning the initial invasion of ALLD compared with the standard Evolutionarily Stable Strategy (ESS) analysis. Even though TFT gets the larger arithmetic mean, the variance of its pay-off is also larger when the expected iterations of the game are sufficiently large. Therefore, the boundary of the parameter of the probability of game continuity, w, above which ALLD does not have advantage to invade into the TFT population, becomes a bit larger than predicted by the deterministic model.

Biological Evolution↗
PubMedDate not supplied

Reactive oxygen species as mediators of cellular senescence.

Aging has often been viewed as a random process arising from the accumulation of both genetic and epigenetic changes. Increasingly, the notion that aging is a stochastic process is being supplanted by the concept that maximum lifespan of an organism is tightly regulated. This knowledge has led to a growing overlap between classical signal transduction paradigms and the biology of aging. We review certain specific examples where these seemingly disparate disciplines intersect. In particular, we review the concept that intracellular reactive oxygen species function as signalling molecules and that oxidants play a central role as mediators of cellular senescence.

Animals↗
PubMed1999

Relation between the probability density and other properties of a stationary random process.

We consider the Pope-Ching differential equation [Phys. Fluids A 5, 1529 (1993)] connecting the probability density p(x)(x) of a stationary, homogeneous stochastic process x(t) and the conditional moments of its squared velocity and acceleration. We show that the solution of the Pope-Ching equation can be expressed as n(x) , where n(x) is the mean number of crossings of the x level per unit time and is the mean inverse velocity of crossing. This result shows that the probability density at x is fully determined by a one-point measurement of crossing velocities, and does not imply knowledge of the x(t) behavior outside of the infinitesimally narrow window near x.

Journal Article↗
PubMed2002

Internal quality control system for non-stationary, non-ergodic analytical processes based upon exponentially weighted estimation of process means and process standard deviation.

The analytical processes in clinical laboratories should be considered to be non-stationary, non-ergodic and probably non-stochastic processes. Both the process mean and the process standard deviation vary. The variation can be different at different levels of concentration. This behavior is shown in five examples of different analytical systems: alkaline phosphatase on the Hitachi 911 analyzer (Roche), vitamin B12 on the Access analyzer (Beckman), prothrombin time and activated partial thromboplastin time on the STA Compact analyzer (Roche) and PO2 on the ABL 520 analyzer (Radiometer). A model is proposed to assess the status of a process. An exponentially weighted moving average and standard deviation was used to estimate process mean and standard deviation. Process means were estimated overall and for each control level. The process standard deviation was estimated in terms of within-run standard deviation. Limits were defined in accordance with state of the art- or biological variance-derived cut-offs. The examples given are real, not simulated, data. Individual control sample results were normalized to a target value and target standard deviation. The normalized values were used in the exponentially weighted algorithm. The weighting factor was based on a process time constant, which was estimated from the period between two calibration or maintenance procedures. The proposed system was compared with Westgard rules. The Westgard rules perform well, despite the underlying presumption of ergodicity. This is mainly caused by the introduction of the starting rule of 12s, which proves essential to prevent a large number of rule violations. The probability of reporting a test result with an analytical error that exceeds the total allowable error was calculated for the proposed system as well as for the Westgard rules. The proposed method performed better. The proposed algorithm was implemented in a computer program running on computers to which the analyzers were linked on-line. Each result was evaluated on-line, and a limit violation was immediately reported. The system has performed satisfactorily in our laboratory for ten analyzers for over 1 year.

Biometry↗
PubMed2005

Active transport: a kinetic description based on thermodynamic grounds.

We show that active transport processes in biological systems can be understood through a local equilibrium description formulated at the mesoscale, the scale to describe stochastic process. This new approach uses the method established by nonequilibrium thermodynamics to account for the irreversible processes occurring at this scale and provides nonlinear kinetic equations for the rates in terms of the driving forces. The results show that the application domain of nonequilibrium thermodynamics method to biological systems goes beyond the linear domain. A model for transport of Ca2+ by the Ca2+-ATPases, nonlinear way. Our results unify thermodynamic and kinetic descriptions, thereby opening new perspectives in the study of different transport phenomena in biological systems.

Animals↗
PubMed2001

Fractional non-Brownian motion and trapping-time distributions of grains in rice piles.

Non-Gaussian height fluctuations occurring on the fueling time scale of a slowly driven rice pile match those observed in some turbulent/critical phenomena, forming an anticorrelated random fractal process with Hurst exponent H=0.2. Inspired by this observation, the concept of fractional Brownian motion (FBM) is extended to treat stochastic processes with skewed increments. Simulations of this process for antipersistent motion have first return time distribution deviating from the t(-2+H) law for FBM. The first return time distribution of this fractional non-Brownian motion describes and quantitatively determines the trapping-time distribution of grains in rice piles upon incorporating a continuous representation of the additional height fluctuations that occur on the time scale between fueling events.

Journal Article↗
PubMedDate not supplied

[Reliability of autoregulatory mechanisms of biosystems as affected by ionizing radiation].

Reliability of biosystems in processes of adaptation and homeostasis after whole-body irradiation of rats with different doses was determined in terms of the stochastic process theory developed for the autoregulatory systems with random parameters. Fluctuations in the rate of spontaneous chemiluminescence of blood serum and accumulation of lipid peroxidation products by erythrocyte membranes of rat blood were taken as the initial material. The analysis of fluctuations of peculiar parameters permitted to predict the adaptability of the system and to make timely corrections.

Animals↗