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PubMedDate not supplied

A signal analysis approach to rat sleep scoring instrumentation.

Automated rat sleep analysis focuses on the statistically regular waveforms of the EEG, such as theta and delta rhythms. Such stochastic processes can be quantified in several manners. Time domain statistics such as auto- and cross-correlations produce outputs that are difficult to use and are best performed in software. Frequency domain statistics like spectral density accurately quantify the sleep state by power-frequency distributions but also require sophisticated computer processing. Continuous frequency analysis, using pass-band filtering, accurately measures signal power in an on-line fashion and employs relatively inexpensive hardware to estimate power by integrating the square of the signal. This method differs substantively from other previously reported systems which rely on signal amplitude analysis. Comparison of this system with a human scorer indicates high degrees of validity and reproducibility.

Animals↗
PubMed1980

Mathematical modelling of reaction latency: the structure of the models and its motivation.

The basic structural assumptions concerning the dynamic models of the reaction latency are presented. The linear dynamic stochastic model of the reaction latency is considered as a special case of dynamic model. The biological motivation for using these models are outlined. These models express the reaction latency as a first access time of the random threshold of a certain stochastic process. This approach was used in modelling the reaction latency in escape and avoidance experiments (the results will be presented in subsequent papers).

Animals↗
PubMed1995

The extended transentropy function as a useful quantifier of human motion variability.

A new concept is presented for quantifying the variability of iterated human motions and other recurrent biological phenomena. The concept is based on the idea of interpreting the variations occurring in repeatedly executed stereotyped motions as particular realizations of a regular stochastic process with superimposed but infrequently occurring chaotic excursions. Under these premises, the extended transentropy of such a process turns out to be a dimensionless and appropriate quantifier of motion variability. Extended transentropy functions can be used to monitor variability changes during motion execution. The practical applicability and usefulness of the new method is demonstrated by means of an example from gymnastics (the kip on the horizontal bar). Major areas of future applications are expected to be gait analysis, all sports movements, and the objective evaluation of the success rates of certain medical treatment procedures for specific movement disorders.

Gymnastics↗
PubMed1994

Prevalence of multidrug resistance related to activation of the mdr1 gene in human sarcoma mutants derived by single-step doxorubicin selection.

Fluctuation analysis experiments were performed in the human sarcoma cell line MES-SA to assess whether selection or induction mechanisms determine resistance to doxorubicin (DOX), mutation rates, and the nature of the surviving clones. Thirteen flasks were seeded with 2000 cells/flask and grown to confluent populations of approximately 3.3 x 10(6) cells. After reseeding in 96-well plates, each population was treated with 40 nM DOX for 2 weeks. Surviving colonies were scored and harvested. Clones were propagated and analyzed for drug resistance phenotype. Expression of the mdr1, mrp, and topoisomerase II alpha and II beta genes was analyzed by reverse transcription-polymerase chain reaction. Accumulation of the P-glycoprotein substrate rhodamine-123 was measured by flow cytometry, with and without the cyclosporin D analogue SDZ PSC 833. Cellular glutathione levels were measured by flow cytometry, and M(r) 110,000 vesicular protein (p110) expression was detected by immunohistochemistry. Analysis of variance supported the hypothesis of spontaneous mutations rather than induction conferring DOX resistance. At this stringent level (5-6 log cell killing) of drug exposure, the mutation rate was estimated at 1.8 x 10(-6) per cell generation. All 30 propagated clones demonstrated cross-resistance to vinblastine, etoposide, and paclitaxel (Taxol), but not to cisplatin or bleomycin. Increased mRNA levels of mdr1 were observed in all 27 clones tested, including at least 1 from each of the 13 populations. No alterations were found in expression or level of topoisomerase II alpha or II beta, mrp, glutathione, and p110. Expression of P-glycoprotein was confirmed by flow cytometry using the monoclonal antibody UIC2. In almost all tested clones, decreased intracellular rhodamine-123 accumulation was modulated by 2 microM SDZ PSC 833, and the vinblastine resistance in all examined clones was completely reversed by SDZ PSC 833 and verapamil. Our study demonstrates that survival of cells exposed to DOX in a single step occurs as a result of a stochastic process consistent with mutational events. Activation of the mdr1 gene is the predominant mechanism selected by DOX in these resistant clones.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

A sequence similarity search algorithm based on a probabilistic interpretation of an alignment scoring system.

We present a probabilistic interpretation of local sequence alignment methods where the alignment scoring system (ASS) plays the role of a stochastic process defining a probability distribution over all sequence pairs. An explicit algorithms is given to compute the probability of two sequences given and ASS. Based on this definition, a modified version of the Smith-Waterman local similarity search algorithm has been devised, which assesses sequence relationships by log likelihood ratios. When tested on classical examples such as globins or G-protein-coupled receptors, the new method proved to be up to an order of magnitude more sensitive than the native Smith-Waterman algorithm.

Algorithms↗
PubMed1996

Changepoint statistics for assessing a treatment-covariate interaction.

We formulate a stochastic process approach, related to that of Miller and Siegmund (1982, Biometrics 38, 1001-1016), for comparing two treatments in the setting where a covariate might affect the difference between the treatments. We illustrate the approach with data from a recent clinical trial examining whether pretreating subjects scheduled for major elective surgery with erythropoietin reduces their subsequent requirement for blood transfusion. The approach is valuable in identifying a changepoint in baseline hemoglobin level below which subjects appear to be more responsive to the infusion of erythropoietin.

Analysis of Variance↗
PubMed1996

Genetic variation in the population of Ibiza (Spain): genetic structure, geography, and language.

A sample of 203 individuals from Ibiza (Balearic Islands, Spain) were tested for blood group and serum protein genetic variation and compared with other circum-Mediterranean populations. Allele frequencies were calculated for the following blood group and serum systems: ABO, Rh, MNSs, P, Lewis, Duffy, Kell, ORM, GC, TF, PI, and HP. The allele frequencies from Ibiza were compared with those from other Balearic Islands (Majorca and Minorca) and with related European and North African groups using an assortment of analytical methods (genetic distances, R matrix analysis, and Mantel tests). R matrix analysis revealed that Ibiza is genetically different from the other Balearic populations and, because of gene flow from Spain, clusters with European groups. The level of genetic microdifferentiation of the Mediterranean populations, measured by RST (average of the R matrix diagonal elements, rii), is 0.028. An examination of the relationship between genetic, geographic, and linguistic distances by Mantel tests revealed that genetic distances are significantly correlated with linguistic distances, whereas the genetic distances are not significantly correlated with geographic distances. The plot of mean per locus heterozygosity versus the genetic distance from the centroid of distribution revealed that all three Balearic Islands have experienced considerable gene flow but that Ibiza has been most affected by the action of stochastic processes.

Blood Group Antigens↗
PubMed1979

Some invariant properties of IgE-mediated basophil activation and desensitization.

We investigate certain general properties of antigen induced degranulation of sensitized basophils by analyzing two types of experiments: Experiments in which we expose basophils to two antigens sequentially and then determine the fraction of histamine released; and experiments in which we obtain time-dependent release and desensitization curves. To analyze the latter type of experiments we introduce a new way to plot release and desensitization data that depends on the nature of the interactions of histamine-containing units (histamine quanta) with themselves or the cells degranulation apparatus, but not on any specific properties of the antigen. From our analysis we conclude that: 1) A fraction of histamine within a population of basophils is nonreleasable by antigenic stimulation. 2) When a basophil degranulates the initial release of histamine appears to inhibit subsequent release. 3) The rate of histamine release is proportional to the amount of releasable histamine remaining in the cells when the amount remaining is small, as expected if release of histamine granules is a stochastic process. 4) There is no dependence of desensitization on the extracellular calcium concentration.

Antigens↗
PubMed1997

Algorithmic complexity of growth hormone release in humans.

Most hormones are secreted in an pulsatile rather than in a constant manner. This temporal pattern of pulsatile hormone release plays an important role in the regulation of cellular function and structure. In healthy humans growth hormone (GH) secretion is characterized by distinct pulses whereas patients bearing a GH producing tumor accompanied with excessive secretion (acromegaly) exhibit a highly irregular pattern of GH release. It has been hypothesized that this highly disorderly pattern of GH release in acromegaly arises from random events in the GH-producing tumor under decreased normal control of GH secretion. Using a context-free grammar complexity measure (algorithmic complexity) in conjunction with random surrogate data sets we demonstrate that the temporal pattern of GH release in acromegaly is not significantly different from a variety of stochastic processes. In contrast, normal subjects clearly exhibit deterministic structure in their temporal patterns of GH secretion. Our results support the hypothesis that GH release in acromegaly is due to random events in the GH-producing tumorous cells which might become independent from hypothalamic regulation.

Acromegaly↗
PubMed1986

A stochastic description of evolutionary processes in underoccupied systems.

A stochastic description for underoccupied systems (large networks with small overall particle number) is given and represented by graphs. Evolutionary processes on this network are considered, especially the mutation process between components (hopping from one component to another) and the selection process.

Biological Evolution↗
PubMedDate not supplied

Toward a stochastic formulation of microbial growth in relation to bioreactor performances: case study of an E. coli fed-batch process.

A stochastic microbial growth model has been elaborated in the case of the culture of E. coli in fed-batch and scale-down reactors. This model is based on the stochastic determination of the generation time of the microbial cells. The determination of generation time is determined by choosing the appropriate value on a log-normal distribution. The appropriateness of such distribution is discussed and growth curves are obtained that show good agreement compared with the experimental results. The mean and the standard deviation of the log-normal distribution can be considered to be constant during the batch phase of the culture, but they vary when the fed-batch mode is started. It has been shown that the parameters related to the log-normal distribution are submitted to an exponential evolution. The aim of this study is to explore the bioreactor hydrodynamic effect on microbial growth. Thus, in a second time, the stochastic growth model has been reinforced by data coming from a previous stochastic bioreactor mixing model (1). The connection of these hydrodynamic data with the actual stochastic growth model has allowed us to explain the scale-down effect associated with the glucose concentration fluctuations. It is important to point out that the scale-down effect is induced differently according to the feeding strategy involved in the fed-batch experiments.

Bioreactors↗
PubMed1999

Hypothesis: genes which function in a stochastic lineage commitment process are subject to monoallelic expression.

The collection of genes which are now known to be monoallelically expressed in mammals is a diverse set. In the case of the genes which encode transducing receptors, such as immunoglobulins or odoront receptors, monoallelic expression ensures that cell activity is related to encountering a unique ligand. However, some monoallelically expressed genes do not encode receptors, and in these cases the physiological purpose of monoallelic expression is uncertain. Even more puzzling are the cases of imprinted genes, where only the maternal or only the paternal allele is expressed. In this article we consider the hypothesis that some of these cases of monoallelic expression reflect the unusual instances in development in which lineage commitment results from a selective rather than an instructive mechanism. These mechanisms are distinguished by their reliance on either external signals (instructive) or internal, cell autonomous events (selective) to cause the changes in gene expression which correspond to lineage commitment. While the instructive mechanism predicts that lineage commitment genes will be expressed or silenced biallelically, the selective mechanism predicts that commitment genes will be subject to monoallelic expression. Specifically, for the cases in which lineage commitment results from activating gene expression, the selective mechanism predicts that commitment genes will be monoallelically expressed following commitment, such as observed recently for some cytokine and transcription factor genes. For the cases in which extinction of gene expression causes commitment, the selective mechanism predicts that the commitment genes will be monoallelically expressed prior to commitment, as for X-linked and imprinted genes.

Alleles↗
PubMed1986

Stochastic response of human blood platelets to stimulation of shape changes and secretion.

Stopped-flow turbidimetric data indicate that platelets stimulated with low levels of thrombin undergo a shape transformation from disc to "sphere" to smaller spiny sphere that is indistinguishable from the shape change induced by ADP through different membrane receptor sites and a dissimilar receptor trigger mechanism. Under conditions where neither secretion nor aggregation occur, the extinction coefficients for total scattering by each of the three platelet forms are independent of the stimulus applied, and both reaction mechanisms can be described as stochastic (Poisson) processes in which the rate constant for the formation of the transient species is equal to the rate constant for its disappearance. This observation is independent of the shape assignment, and as the concentration of thrombin is increased and various storage organelles secrete increasing amounts of their contents into the external medium, the stochastic pattern persists. Progressively larger decreases in the extinction coefficients of the intermediate and final platelet forms, over and above those that reflect shape alterations alone, accompany or parallel the reaction induced by the higher thrombin concentrations. The excess turbidity decrease observed when full secretion occurs can be wholly accounted for by a decrease in platelet volume equal in magnitude to the fraction of the total platelet volume occupied by alpha granules. Platelet activation, as reported by the whole body light scattering of either shape changes alone or shape changes plus parallel (but not necessarily also stochastic) alpha granule secretion, thus manifests itself as a random series of transient events conceivably with its origins in the superposition of a set of more elementary stochastic processes that could include microtubule depolymerization, actin polymerization, and possibly diffusion. Although the real nature of the control mechanism remains obscure, certain properties of pooled stochastic processes suggest that a reciprocal connection between microtubule fragmentation and the assembly of actin-containing pseudopodal structures and contractile elements--processes that may exhibit reciprocal requirements for calcium--might provide a hypothetical basis for a rate-limiting step.

Adenosine Diphosphate↗
PubMed1987

Normalized auto- and cross-covariance functions for neuronal spike train analysis.

The normalized auto- and cross-covariance functions of discrete-time stochastic point process, used for quantitatively analyzing neuronal spike trains, were derived from the corresponding functions of general stochastic process using Kronecker delta functions. The auto-correlation and cross-correlation properties can be described as numerical differences on a monotonic scale ranging from -1 -1 to +1. A segmental integration method and a significance test for the normalized cross-covariance function estimate are suggested. Examples from real spike trains are illustrated, and Monte Carlo methods are used for controls and for testing the algorithms and computer programs.

Action Potentials↗
PubMed1997

Reconstructing potential energy functions from simulated force-induced unbinding processes.

One-dimensional stochastic models demonstrate that molecular dynamics simulations of a few nanoseconds can be used to reconstruct the essential features of the binding potential of macromolecules. This can be accomplished by inducing the unbinding with the help of external forces applied to the molecules, and discounting the irreversible work performed on the system by these forces. The fluctuation-dissipation theorem sets a fundamental limit on the precision with which the binding potential can be reconstructed by this method. The uncertainty in the resulting potential is linearly proportional to the irreversible component of work performed on the system during the simulation. These results provide an a priori estimate of the energy barriers observable in molecular dynamics simulations.

Binding Sites↗
PubMed2001

The epileptic process as nonlinear deterministic dynamics in a stochastic environment: an evaluation on mesial temporal lobe epilepsy.

The theory of deterministic chaos addresses simple deterministic dynamics in which nonlinearity gives rise to complex temporal behavior. Although biological neuronal networks such as the brain are highly complicated, a number of studies provide growing evidence that nonlinear time series analysis of brain electrical activity in patients with epilepsy is capable of providing potentially useful diagnostic information. In the present study, this analysis framework was extended by introducing a new measure xi, designed to discriminate between nonlinear deterministic and linear stochastic dynamics. For the evaluation of its discriminative power, xi was extracted from intracranial multi-channel EEGs recorded during the interictal state in 25 patients with unilateral mesial temporal lobe epilepsy. Strong indications of nonlinear determinism were found in recordings from within the epileptogenic zone, while EEG signals from other sites mainly resembled linear stochastic dynamics. In all investigated cases, this differentiation allowed to retrospectively determine the side of the epileptogenic zone in full agreement with results of the presurgical workup.

Adolescent↗
PubMed2006

Understanding intracellular transport processes pertinent to synthetic gene delivery via stochastic simulations and sensitivity analyses.

A major challenge in synthetic gene delivery is to quantitatively predict the optimal design of polymer-based gene carriers (polyplexes). Here, we report a consistent, integrated, and fundamentally grounded computational methodology to address this challenge. This is achieved by accurately representing the spatio-temporal dynamics of intracellular structures and by describing the interactions between gene carriers and cellular components at a discrete, nanoscale level. This enables the applications of systems tools such as optimization and sensitivity analysis to search for the best combination of systems parameters. We validate the approach using DNA delivery by polyethylenimine as an example. We show that the cell topology (e.g., size, circularity, and dimensionality) strongly influences the spatiotemporal distribution of gene carriers, and consequently, their optimal intracellular pathways. The model shows that there exists an upper limit on polyplexes' intracellular delivery efficiency due to their inability to protect DNA until nuclear entry. The model predicts that even for optimally designed polyethylenimine vectors, only approximately 1% of total DNA is delivered to the nucleus. Based on comparison with gene delivery by viruses, the model suggests possible strategies to significantly improve transfection efficiencies of synthetic gene vectors.

Biological Transport, Active↗
PubMed1986

The role of fluctuations of red blood cell LPO products in transition processes.

The stochastic reliability model of biosystem in transition processes (adaptation of rats to new ecological conditions) and in pathogenesis of trauma is discussed. The role of fluctuations of LPO products in transition processes is illustrated on autoregulation mechanisms of red blood cell membranes in rats. The first adaptation phase is characterized by an increased MDA concentration dispersion--the swing of biosystem. The second phase is characterized by decreased fluctuations and increased reliability. The degree of the "swing" plays an important role under extreme conditions of pathogenesis of trauma.

Adaptation, Physiological↗