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PubMed2000

Estimation of population profiles of two strains of the fly Megaselia scalaris (Diptera: Phoridae) by bootstrap simulation.

Based on experimental population profiles of strains of the fly Megaselia scalaris (Phoridae), the minimal number of sample profiles was determined that should be repeated by bootstrap simulation process in order to obtain a confident estimation of the mean population profile and present estimations of the standard error as a precise measure of the simulations made. The original data are from experimental populations founded with SR and R4 strains, with three replicates, which were kept for 33 weeks by serial transfer technique in a constant temperature room (25 +/- 1.0 degrees C). The variable used was population size and the model adopted for each profile was a stationary stochastic process. By these simulations, the three experimental population profiles were enlarged so as to determine minimum sample size. After sample size was determined, bootstrap simulations were made in order to calculate confidence intervals and to compare the mean population profiles of these two strains. The results show that with a minimum sample size of 50, stabilization of means begins.

Animals↗
PubMed1990

Analysis of stomach cancer incidence by histologic subtypes based on a mathematical model of multistage cancer induction and exponential growth.

A mathematical model incorporating the processes of both cancer induction and subsequent tumor growth has been developed. The model was applied to incidence data of stomach classified into histologic subtypes: papillary adenocarcinoma (PAP), well and moderately differentiated tubular adenocarcinomas (WEL and MOD), poorly differentiated adenocarcinoma (POR), mucinous adenocarcinoma (MUC) and signet-ring cell carcinoma (SIG). The multistage theory was assumed for cancer induction as in the Armitage-Doll model. For the period of growth, exponential growth was assumed and clinical surfacing was formulated as a stochastic process related to tumor diameter. The number of stages in cancer induction and the tumor growth rate were simultaneously estimated for each histologic subtype using the maximum likelihood procedure. The present model showed better fits than the Armitage-Doll model in most histologic subtypes except WEL, PAP, WEL and MOD, which are characterized as differentiated subtypes with less mucous production, showed different features from POR, MUC and SIG: 1) the number of stages was estimated to be larger, 2) the differences in incidence rates between males and females were more marked, and 3) males tended to have larger growth rates in PAP and MOD, while in POR, MUC and SIG, females had larger values. The present study showed that an analysis by histologic subtypes is of importance in stomach cancer and that the period of tumor growth should not be ignored when formulating a model of the natural history of stomach cancer.

Adenocarcinoma↗
PubMed2003

Developmental noise, ageing and cancer.

Development is a very robust but far from perfect process, subjected to random variation due to the combined factors that constitute the so-called developmental noise. The effects of early developmental noise may have long-term consequences resulting from slight differences in the make-up and organisation of the former developing system. Here we present evidence suggesting that cancer is not an acquired but an intrinsic process resulting from random factors acting during early development, thus leading to a mixture of susceptibility types that may develop cancer sooner or later, depending on the combination of the environment acting upon such different susceptibility types. We discuss evidence suggesting that some supposedly tumour-suppressor functions, such as those associated with the p53 protein, actually evolved as buffering functions against the early effects of developmental noise that might compromise the stability of embryonic cells and hence of development. Ageing is a stochastic process characterised by progressive failure of somatic maintenance and repair. We put forth the notion that progressive loss of the morphological coherence of the organism (morphological disorder) is a form of ageing, and that morphological disorder is the common theme of most types of cancer. Thus, we suggest that the exhaustion of both developmental constraints and buffering developmental mechanisms link ageing and cancer. Moreover, we propose that cancer may represent one of the most radical forms of ageing, because it generally satisfies the criteria of senescence: intrinsicality, progressiveness and deleteriousness.

Aged↗
PubMed2003

The origin, emergence and evolutionary genetics of dengue virus.

Dengue is one of the most important emerging viruses, posing a threat to one-third of the global human population. Herein we show how the comparative analysis of gene sequence data has shed light on the origin and spread of dengue virus, as well as on the evolutionary processes that structure its genetic diversity. This reveals that dengue virus has a relatively recent evolutionary history, with the four serotypes originating approximately 1000 years ago and only establishing endemic transmission in humans in the last few hundred years. However, its place of origin remains uncertain as does the extent of genetic and phenotypic diversity present in the sylvatic (primate) transmission cycle. Although there is some evidence that viral strains differ in key phenotypic features such as virulence, and for positive selection at immunologically important sites, it seems likely that stochastic processes also play a major role in shaping viral genetic diversity, with lineage extinction a common occurrence. A more complete understanding of the evolution and epidemiology of dengue virus, particularly with respect to the aetiology of severe disease, will require large-scale prospective studies and the comparative analysis of complete genome sequences.

Animals↗
PubMed2006

Analysing grouping of nucleotides in DNA sequences using lumped processes constructed from Markov chains.

The most commonly used models for analysing local dependencies in DNA sequences are (high-order) Markov chains. Incorporating knowledge relative to the possible grouping of the nucleotides enables to define dedicated sub-classes of Markov chains. The problem of formulating lumpability hypotheses for a Markov chain is therefore addressed. In the classical approach to lumpability, this problem can be formulated as the determination of an appropriate state space (smaller than the original state space) such that the lumped chain defined on this state space retains the Markov property. We propose a different perspective on lumpability where the state space is fixed and the partitioning of this state space is represented by a one-to-many probabilistic function within a two-level stochastic process. Three nested classes of lumped processes can be defined in this way as sub-classes of first-order Markov chains. These lumped processes enable parsimonious reparameterizations of Markov chains that help to reveal relevant partitions of the state space. Characterizations of the lumped processes on the original transition probability matrix are derived. Different model selection methods relying either on hypothesis testing or on penalized log-likelihood criteria are presented as well as extensions to lumped processes constructed from high-order Markov chains. The relevance of the proposed approach to lumpability is illustrated by the analysis of DNA sequences. In particular, the use of lumped processes enables to highlight differences between intronic sequences and gene untranslated region sequences.

3' Untranslated Regions↗
PubMed1995

An image processing procedure for the assessment of normality curves of motility of human granulocytes in micropore filters.

With the conventional methods used in current practice, the results of human granulocyte motility assays are expressed by a numerical value that defines the leading front of cells into micropore filters. The authors have developed a fast procedure which allows the complete curve of polymorphonuclear leukocyte (PMN) migration to be obtained, from the initial plane of a filter to the maximum propagation depth. In this way, more information is given than that expressed by a single parameter. The paper describes the procedure used to determine the normality curves both for random and stimulated migration, according to a simple model which defines the PMN propagation in micropore filters. A normality band that defines variations due to the stochastic process is also reported.

Cell Movement↗
PubMed2006

Texture synthesis: textons revisited.

This paper introduces a technique for synthesizing natural textures, with emphasis on quasiperiodic and structural textures. Textures are assumed to be composed of three components, namely illumination, structure, and stochastic. The contribution of this work is that, in contrast to previous techniques, it proposes a joint approach for handling the texture's global illumination, irregular structure, and stochastic component which may be correlated to the other two components. Furthermore, the proposed technique does not produce verbatim copies in the synthesized texture. More specifically, a top-down approach is used for extraction of texture elements (textons) in which, in contrast to previous texton-based approaches, no assumptions regarding perfect periodicity are made. The structure itself can be modeled as a stochastic process. Consequently, textons are allowed to have irregular and nonidentical shapes. In the synthesis stage, a new nonregular textural structure is designed from the original one that defines the place holders for textons. We call such place holders empty textons (e-textons). The e-textons are filled in by a representative texton. Since e-textons do not have identical shapes, a texton shape-matching procedure is required. After adding the illumination to the structural component, a strictly localized version of a block sampling technique is applied to add the stochastic component. The block sampling technique combined with the addition of the illumination component provides a significant improvement in the appearance of synthesized textures. Results show that the proposed method is successful in synthesizing structural textures visually indistinguishable to the original. Moreover, the method is successful in synthesizing a variety of stochastic textures.

Algorithms↗
PubMed1990

The biology of cancer metastasis.

The formation of a metastasis entails a complex sequence of events with the end result dependent on the interaction of malignant cells with host factors. Intrinsic properties of the metastatic tumor cells, including production of proteolytic enzymes, cell surface properties, adhesiveness, and the ability to grow in a distant organ environment, act in concert to influence the tumor cells' interactions with host cells in forming metastases. Life-threatening metastases are formed only by those tumor cells that have survived all steps in a process that has been shown in many experimental studies to be a highly selective event. The results of studies on the distribution of radiolabelled mouse melanoma cells injected into syngeneic mice support the concept that the fate of tumor cells released into the bloodstream is determined by sequential and selective events, and introduces a third regulatory factor. Cells endowed with metastatic properties, isolated by cloning a heterogeneous tumor or selected from a metastasis, have a higher probability of forming metastases than cells not so endowed, yet this probability is not 100%. Metastasis should thus be considered as a selective, sequential and stochastic process. Interruption of the process at any stage will prevent the formation of metastatic disease. Hence, a better understanding of the metastatic process will provide the basis for rational approaches for the prevention or destruction of this most fatal aspect of cancer.

Animals↗
PubMed1984

Analysis of cell movement.

The methods of statistical physics have been applied to the analysis of cell movement. Human leukocytes (granulocytes) were observed using time-lapse photography. The center of gravity of a cell, variations of cell shape, and cell orientation were investigated. This analytical description leads to a better understanding of cell movement. Stationary motion of a cell is described by the anisotropy of the cell shape. The cell displacement can be characterized by three different types of movement: The persistent mode where the cell moves away from an arbitrary chosen origin with its track velocity. The diffusion mode where the cells become dispersed in space by a random walk process. The drift mode where the cell moves with a drift velocity, v parallel, in a concentration gradient of chemoattractant molecules. The chemokinetic response is described by the diffusion constant D (= 240 microns2/min) and the track velocity vc (= 30 microns/min). The chemotactic response is described by the degree of orientation P1 (= 0.8), which is identical with the McCutcheon index and the chemotropism index. Cell movement can be described by elementary moving states, and the life time of such a moving state is 0.5 min. The survival probability of the moving state is determined by an internal program. It is not described by a stochastic process. The angular change in moving direction is also programmed, as the square root of the mean square angular change is +/- 50 degrees. The plus and minus direction are equally probable in a chemokinetic response. However, in a chemotactic assay the plus and minus directions are not equally probably. We found that the information transfer from the chemotactic gradient to the migrating cell is 1 bit per change in moving direction. A disturbance in this information transfer leads to an order-disorder transition. Furthermore, we found that the migrating cell exhibits a directional memory of 75 s.

Biophysical Phenomena↗
PubMedDate not supplied

RAPD variation and population genetic structure of Physalaemus cuvieri (Anura: Leptodactylidae) in Central Brazil.

Studies about the organization of the genetic variability and population structure in natural populations are used either to understand microevolutionary processes or the effects of isolation by human-inducted landscape modifications. In this paper, we analyzed patterns of genetic population structure using 126 RAPD loci scored for 214 individuals of Physalaemus cuvieri, sampled from 18 local populations. Around 97% of these loci were polymorphic. The among-population variation component (Phi(ST)) obtained by AMOVA was equal to 0.101 and theta B obtained using a Bayesian approach for dominant markers was 0.103. Genetic divergence, analyzed by Mantel spatial correlogram, revealed only a short-distance significant correlation between genetic and geographic distances. This is expected if low levels of population differentiation, due to high abundance buffering the effect of stochastic processes, are combined with low spatially restricted gene flow. Although this may be consistent with the current knowledge of species' biology, the spatial distribution of local populations observed in this study also suggest that, at least in part, recent human occupation and habitat fragmentation may also explain part of the interpopulational component of the genetic variation.

Animals↗
PubMed2004

Automatic generation of lymphocyte heterogeneity: Division-dependent changes in the expression of CD27, CCR7 and CD45 by activated human naive CD4+ T cells are independently regulated.

Lymphocyte differentiation is a complex process regulated by the integration of signals received through a variety of cell surface receptors that results in populations of differentiated cells that have acquired novel characteristics and effector functions. Differentiation of T and B lymphocytes into effector cells, such as cytokine-secreting CD4+ T cells, cytotoxic CD8+ T cells and Ig-secreting B cells, as well as alterations in cell surface phenotype, have been reported to be associated with cell division. Nevertheless, the genesis of heterogeneity in effector cell type is unknown. A strictly deterministic view holds that heterogeneity arises from distinct signalling histories for each functionally or phenotypically different cell type. In contrast, a probabilistic interpretation proposes that internal stochastic regulation of gene expression gives rise to lymphocytes of mixed phenotypes. To help distinguish between these explanations, we examined the expression of CD27, CCR7, CD45RA and CD45RO by human naive CD4+ T cells in the context of the division history of the lymphocyte. Our results show that each marker independently changes with progressive divisions, strongly supporting the proposal that phenotypic heterogeneity in lymphocytes can arise as the result of independent stochastic processes controlling the expression of individual molecules.

Antibodies, Monoclonal↗
PubMed2005

Genetic and stochastic influences on the interaction of human immunodeficiency virus type 1 and cytotoxic T lymphocytes in identical twins.

Human immunodeficiency virus type 1 (HIV-1) evolves in vivo under selective pressure from CD8+ T-lymphocyte (CTL) responses, which are in turn determined by host and viral genetic factors, such as restricting major histocompatibility complex molecules and the available viral epitope sequences. However, CTL are derived stochastically through the random gene rearrangements to produce T-cell receptors (TCR), and the relative impact of genetic versus stochastic processes on CTL targeting of HIV and immune-driven viral evolution is unclear. Here we evaluate identical twins infected with HIV-1 as neonates from a common blood transfusion, with subsequently similar environmental exposures, thereby allowing controlled comparisons of CTL targeting and viral evolution. Seventeen years after infection, their CTL targeting of HIV-1 was remarkably similar. In contrast, their overall TCR profiles were highly dissimilar, and a dominant epitope was recognized by distinctly different TCR in each twin. Furthermore, their viral epitopes had diverged, and there was ongoing viral phylogenetic divergence between the twins between 12 and 17 years after infection. These results indicate that while CTL targeting is predominately genetically determined, stochastic influences render the interaction of HIV-1 and host immunity, and therefore viral escape and CTL efficacy, unpredictable.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Further studies of a model for azimuthal encoding: lateral superior olive neuron response curves and developmental processes.

A number of investigators have published measurements of the outputs of single neurons from the lateral superior olive (LSO) of the cat for a variety of auditory signals. The response curves show a very wide range of shapes and thresholds. In this paper, the single neuron response curves predicted by a previously published model for the encoding of azimuthal location by the LSO to the experimental curves are compared. The predicted curves are in good qualitative agreement with the experiments and, in addition, the model provides an explanation of the seemingly paradoxical drop in output as interaural intensity difference (IID) is held fixed and absolute intensities are raised. The particular shape of the response curve depends on the location of the LSO neuron examined. In the model, two possible developmental programs to form the adult pattern of connections from the anteroventral cochlear nucleus and the medial nucleus of the trapezoid body onto the LSO are also examined. In the first, connections are made by a forward stochastic process in which there is a limit on the numbers of synapses formed on each LSO cell. In the second, there is no such limit, but in later developmental stages pruning of synapses occurs which reduces their number to the limit. Both schemes give similar adult connectional patterns. The LSO response curves generated by the model are similar to those observed in LSO neurons of the developing gerbil by Sanes and Rubel [J. Neurosci. 8, 682-700 (1988)]. Thus the model mechanism not only encodes azimuthal location by activity across the population of neurons, but is also consistent with single unit neurophysiological measurements of LSO output in both developing and adult animals.

Animals↗
PubMed1997

Simulation of protein evolution: evidence for a non-linear aminoacidic substitution rate.

Protein evolution is characterized by several processes. In the theory of neutral evolution the rate of mutation is considered a linear process in which the amount of aminoacidic substitutions in proteins is constant in time. A simulation approach has been developed by using a model of amino-acidic substitution. The frequency of spontaneous mutations has been assumed to be equal to about 10(-9)/base/year. The aim of the present work is to show that starting from a constant mutation rate (nucleotide substitutions) the corresponding process of aminoacidic substitutions becomes non-linear if some criteria of mutation selection are introduced. The basic criteria used are the physical-chemical characteristics of aminoacids, the same criteria that have made it possible to classify aminoacids. Different classifications based on differences in such criteria give different results, indicating that the degenerate nature of the genetic code determines a non-linear behaviour of protein evolution. Simulations have been performed on short protein subsequences of five aminoacids. A further analysis has been made to verify, on the basis of the code structure and of accepted selection criteria, the mechanisms of aminoacidic substitutions and the existence of preferential paths. We have concluded that aminoacidic substitution is not a simple stochastic process, but that complex Markov's chains are involved. The consequences are important, although generally ignored.

Amino Acid Substitution↗
PubMed1990

Reducing bias in estimates of the richards growth function shape parameter.

A process error model developed by White and Brisbin (1980) is used frequently for estimation of the parameters of the Richards sigmoid growth function. The Richards function includes a parameter, m, that describes the shape of familiar three-parameter functions, such as the monomolecular (m = 0), von Bertalanffy (m = 2/3), Gompertz (m----1) and logistic m = 2), as well as other sigmoid functions. We show that this model systematically underestimates the shape parameter, m. In calibration runs and simulations, bias decreased with increased frequency of sampling during the period of rapid growth and with smaller values of true m. Relative bias was insensitive to the magnitude of m. A simple correction reduced the bias to negligible values for both deterministic and stochastic process error models. Biases in estimated asymptote, A, and growing time, T, were small for a variety of sampling intervals and shape parameters.

Animals↗
PubMed2001

Possibility between earthquake and explosion seismogram differentiation by discrete stochastic non-Markov processes and local Hurst exponent analysis.

The basic scientific point of this paper is to draw the attention of researchers to new possibilities of differentiation of similar signals having different nature. One example of such kinds of signals is presented by seismograms containing recordings of earthquakes (EQ's) and technogenic explosions (TE's). EQ's are among the most dramatic phenomena in nature. We propose here a discrete stochastic model for possible solution of a problem of strong EQ forecasting and differentiation of TE's from the weak EQ's. Theoretical analysis is performed by two independent methods: by using statistical theory of discrete non-Markov stochastic processes [Phys. Rev. E 62, 6178 (2000)] and the local Hurst exponent. The following Earth states have been considered among them: before (Ib) and during (I) strong EQ, during weak EQ (II) and during TE (III), and in a calm state of Earth's core (IV). The estimation of states I, II, and III has been made on the particular examples of Turkey (1999) EQ's, state IV has been taken as an example of Earth's state before underground TE. Time recordings of seismic signals of the first four dynamic orthogonal collective variables, six various planes of phase portrait of four-dimensional phase space of orthogonal variables and the local Hurst exponent have been calculated for the dynamic analysis of states of systems I-IV. The analysis of statistical properties of seismic time series I-IV has been realized with the help of a set of discrete time-dependent functions (time correlation function and first three memory functions), their power spectra, and the first three points in the statistical spectrum of non-Markovity parameters. In all systems studied we have found a bizarre combination of the following spectral characteristics: the fractal frequency spectra adjustable by phenomena of usual and restricted self-organized criticality, spectra of white and color noises and unusual alternation of Markov and non-Markov effects of long-range memory, detected earlier [J. Phys. A 27, 5363 (1994)] only for hydrodynamic systems. Our research demonstrates that discrete non-Markov stochastic processes and long-range memory effects play a crucial role in the behavior of seismic systems I-IV. The approaches, permitting us to obtain an algorithm of strong EQ forecasting and to differentiate TE's from weak EQ's, have been developed.

Journal Article↗
PubMed2006

A cross-national study of transitions in deficit counts in two birth cohorts: implications for modeling ageing.

Generally, health does not improve with age, and many physical and physiological functions are known to decline. These changes do not occur uniformly, however; for many reasons, some people experience significant improvement in their health over non-trivial time intervals. Earlier, we showed that 5-year transitions in health status in elderly people (age 65+ years) can be modeled as a stochastic process, using a modified Poisson distribution with four readily interpretable parameters. The original description was based on follow-up of a single cross-sectional study, thus mixing age and cohort effects. Here, we again used a multistate Markov chain to model 5-year deficit accumulation in relation to frailty in both a Swedish birth cohort (aged 70 years at inception) and, from the original cross-sectional study, a Canadian birth cohort, aged 69-71. In both datasets, we found again that a modified Poisson describes the transition in health status with high precision. The parameters of the model though different, are close to each other, even though the cohorts are from different countries, were assembled 20 years apart, and counted different deficits. The model suggests that all health transitions, including health improvement, worsening, and death, can be summarized in a unified stochastic model with a few interpretable parameters.

Aged↗
PubMed1981

Does quantitative tRNA adaptation to codon content in mRNA optimize the ribosomal translation efficiency? Proposal for a translation system model.

Neither a dynamic nor an energetic approach of the translation process has taken into account that intracellular levels of iso-tRNA species are adapted or adjusted to the codon frequency of mRNA being decoded (Bombyx mori silk gland, rabbit reticulocyte). A critical study of available experimental data suggests that the average elongation rate of a protein is maximized in the presence of an adapted tRNA population, usually an homologous tRNA. In addition, the amount of synthesized protein parallels that of corresponding mRNA. Other evidences--including in vitro and in vivo elongation assays with fibroin mRNA--show that individual elongation rates are not uniform. Pauses occur at certain sites of the mRNA chain. The relative lifetime of these pauses depends on the tRNA pool used. Finally, it appears that translation accuracy also depends on the balanced tRNA population. We propose to explain these different effects by using a codon-anticodon recognition model, called "trial and error system" based on a stochastic processing of the ribosome. Accordingly, various acylated tRNA species which surround a ribosome randomly encounter the receptor A site. Every trapped tRNA species is tested for a proper pairing with the codon to be recognized at the level of a comparator or discriminator function. If the pairing is correct, transpeptidation becomes irreversible. If not, the aminoacyl-tRNA is rejected and another randomly trapped tRNA is processed in turn. Mathematical analysis of this model shows that the mean number of trials used for translating the whole sequence of a mRNA is minimized when the proportion of different iso-tRNA species is correlated with the square root of codon frequency. Quantitations of reticulocyte tRNA support such a parabolic relation. Our translation system model brings some light into the role of tRNA adaptation for optimizing translation efficiency, i.e. maximizing both speed and accuracy. Some consequences of the model are discussed.

Codon↗