Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Stochastic Processes”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 703 records · Page 39Linked to original sources
PubMed1997

Genetic evidence of widespread dispersal in a parthenogenetic freshwater ostracod.

We used an hierarchical analysis of allozyme variation to investigate for the freshwater ostracod Candonocypris novaezelandiae the relative contributions of sexual and asexual reproduction to recruitment into 42 local populations and to infer patterns of gene flow within and among four geographical regions (watersheds) in south-eastern Australia. Allele frequency variation among local populations was marked (mean F(ST)=0.228) but showed no regional differentiation. The allele frequency differences among local populations probably reflect the effects of stochastic processes, such as founder events, as well as variation in the success, and hence abundance, of particular clonal genotypes within water-bodies. Indeed, local populations were highly clonal, containing only females and displaying relatively low levels of genotypic diversity. Nevertheless, the distribution of genotypes within and among regions was surprising. The bulk of sampled individuals (88 per cent) were represented by just six common genotypes that were shared extensively among local populations and were geographically widespread. Individual samples contained a mean of 4.05, and up to 10, distinct four-locus genotypes and overall we detected a total of 26 electrophoretically distinct genotypes. In combination, our results suggest that either the south-eastern Australian populations of C. novaezelandiae arose through a recent colonization event (perhaps associated with an expansion of agricultural practices) or there is sufficient continuing gene flow between regions to prevent differentiation. However, the exact contributions of sexual and asexual reproduction to dispersal in this ostracod remain unclear.

Journal Article↗
PubMed2003

The random-coil 'C' fragment of the dihydropyridine receptor II-III loop can activate or inhibit native skeletal ryanodine receptors.

The actions of peptide C, corresponding to (724)Glu-Pro(760) of the II-III loop of the skeletal dihydropyridine receptor, on ryanodine receptor (RyR) channels incorporated into lipid bilayers with the native sarcoplasmic reticulum membrane show that the peptide is a high-affinity activator of native skeletal RyRs at cytoplasmic concentrations of 100 nM-10 microM. In addition, we found that peptide C inhibits RyRs in a voltage-independent manner when added for longer times or at higher concentrations (up to 150 microM). Peptide C had a random-coil structure indicating that it briefly assumes a variety of structures, some of which might activate and others which might inhibit RyRs. The results suggest that RyR activation and inhibition by peptide C arise from independent stochastic processes. A rate constant of 7.5 x 10(5) s(-1).M(-1) was obtained for activation and a lower estimate for the rate constant for inhibition of 5.9 x 10(3) s(-1).M(-1). The combined actions of peptide C and peptide A (II-III loop sequence (671)Thr-Leu(690)) showed that peptide C prevented activation but not blockage of RyRs by peptide A. We suggest that the effects of peptide C indicate functional interactions between a part of the dihydropyridine receptor and the RyR. These interactions could reflect either dynamic changes that occur during excitation-contraction coupling or interactions between the proteins at rest.

Adenosine Triphosphate↗
PubMed1996

Kinetics of colony formation by BFU-E grown under different culture conditions in vitro.

Colony formation by erythroid burst-forming units (BFU-E) involves a variable number of cell divisions before individual 'subcolonies' begin to appear. Consequently the numbers of subcolonies vary amongst individual bursts. If this observation is interpreted as a reflection of a stochastic process, the number of subcolonies in each individual burst represents the number of divisions by the BFU-E prior to commitment to terminal differentiation. This provides a means for quantitating the probability of erythroid differentiation (pD) and the probability of renewal (1 - pD). In order to determine whether these kinetics of burst formation can be influenced by exogenous factors we used three commercially available media designed for the growth of BFU-E. We found that subcolony numbers per burst ranged from one to 64 and that the cumulative distributions of subcolonies per burst followed a logarithmic curve (r > 0.90). Differences were observed in the distribution of subcolonies per burst when BFU-E were grown in different media (P=0.03; Kruskall-Wallis test). The probability of immediate terminal differentiation (i.e. committment to form a subcolony) was 0.25 for two of the media and 0.7 for the third. The corresponding renewal probabilities were O.75 and O.3. These data indicate that the proliferation kinetics of BFU-E are susceptible to regulation by exogenous factors.

Cell Culture Techniques↗
PubMed1997

Nonlinear deterministic analysis of tissue texture: a stereological study on mastopathic and mammary cancer tissue using chaos theory.

Signals from some dynamical systems look like stochastic processes although their latent mechanism is deterministic. When such systems show sensitive dependence on small changes of initial conditions, they are denoted as deterministic chaos. Motivated by recent advances in statistical inference methods for chaotic systems and by the concept of spatial chaos, we present a deterministic approach to the study of epithelial tissue texture. Methods for estimation of the autocorrelation function, for evaluation of the power spectrum, for attractor reconstruction, for estimation of the Lyapunov exponent and of the correlation dimension, and for the generation of surrogate data sets are outlined. In our biological example, these methods are applied to 20 cases of mastopathy as compared to 20 cases of mammary cancer. The input signals for the analysis were estimates of epithelial fraction measured at low magnification within 5100 equally spaced line segments per case perpendicular to an arbitrarily directed axis. The results suggest the existence of a low-dimensional deterministic attractor in mastopathic tissue texture, which is replaced by coloured noise in the majority of mammary carcinomas. Biological mechanisms for this finding and scale effects are discussed, and some methodological aspects and possible extensions of our approach are outlined.

Breast Neoplasms↗
PubMed2002

Contrasting patterns of divergence in quantitative traits and neutral DNA markers: analysis of clinal variation.

Clinal variation in quantitative traits is often attributed to the effects of spatially varying selection. However, identical patterns can be produced by the interplay between purely stochastic processes (i.e. drift in combination with spatially restricted gene flow). One means of distinguishing between adaptive and nonadaptive causes of geographical variation is to compare relative levels of between-population divergence in quantitative traits and neutral DNA markers. Such comparisons can be used to test whether levels of trait divergence attributable to additive genetic effects (as measured by QST) exceed null expectations based on the level of divergence at neutral marker loci (as measured by FST). The purpose of this study was to use an approach based on 'QST vs. FST' contrasts to test for evidence of diversifying selection on body size of an Indian fruit bat, Cynopterus sphinx (Chiroptera: Pteropodidae). Specifically, relative levels of between-population divergence in body size and microsatellite DNA markers were compared to assess whether the observed pattern of clinal size variation could be explained by a neutral model of isolation by distance. QST for body size was calculated using unbiased estimators of within- and between-population variance of principal component scores. The association between body size variation and geographical/environmental distance was tested using pairwise and partial matrix correspondence tests (MCTs). Independent variables (representing causal hypotheses) were constructed as between-locality distance matrices. The effects of neutral genetic divergence were assessed by including a matrix of pairwise FST as an independent variable. Partial MCTs revealed highly significant associations between phenotypic divergence (QST) and both geographical and environmental distance, even when the effects of neutral genetic divergence (FST) were partialled out. Results of the tests confirmed that migration-drift equilibrium is not a sufficient explanation for the latitudinal pattern of clinal size variation in C. sphinx. The geographical patterning of pairwise QST is most likely attributable to spatially varying selection and/or the direct influence of latitudinally ordered environmental effects.

Animals↗
PubMed2003

Nuclear markers, mitochondrial DNA and male secondary sexual traits variation in a newt hybrid zone (Triturus vulgaris x T. montandoni).

The smooth and the Montandon's newts (Triturus vulgaris and T. montandoni) are genetically similar sister species with highly divergent male secondary sexual traits involved in complex courtship behaviour. Their parapatric ranges overlap at moderate elevations in the Carpathian Mountains where they hybridize readily. Here we present a detailed study of genetic and morphological variation in populations from the area of sympatry. Analysis of variation at seven nuclear markers, mtDNA and male sexual secondary traits was complemented with an ecological survey of breeding sites characteristics. Extensive hybridization was revealed with back-cross individuals similar to either parental species predominating among hybrids. The hybrid zone exhibited a mosaic pattern: the genetic composition of the populations was correlated only weakly with their geographical position. No association with habitat type was found. Departures from Hardy-Weinberg proportions, significant linkage disequilibria and bimodal distribution of genotypes suggest strongly that assortative mating is an important factor shaping the genetic composition of hybrid populations. The pattern of cytonuclear disequilibria did not indicate much asymmetry in interspecific matings. Changes in the frequency of nuclear markers were highly concordant, whereas mtDNA showed much wider bidirectional introgression with 14% excess of T. montandoni haplotype. We argue that the mosaic structure of the newt hybrid zone results mainly from stochastic processes related to extinction and recolonization. Microgeographical differences in mtDNA introgression are explained by historical range shifts. Since morphologically intermediate males were underrepresented when compared to hybrid males identified by genetic markers, sexual selection acting against the morphological intermediates is implied. We discuss the implications of these findings in the context of reinforcement of prezygotic isolation in newts.

Animals↗
PubMed2001

A fractional diffusion equation for a marker in porous media.

To study the properties of the flow of a marker through an irregular packed bed, porosity is described by stochastic processes with exponentially decaying correlation functions. We show that the ensemble average concentration of the marker satisfies a fractional diffusion equation. (c) 2001 American Institute of Physics.

Journal Article↗
PubMed2004

Diagrammatic kinetic theory for a lattice model of a liquid. I. Theory.

We present a diagrammatic formalism for the time correlation functions of density fluctuations for an excluded volume lattice gas on a simple d-dimensional hypercubic lattice. We consider a multicomponent system in which particles of different species can have different transition rates. Our theoretical approach uses a Hilbert space formalism for the time dependent dynamical variables of a stochastic process that satisfies the detailed balance condition. We construct a Liouville matrix consistent with the dynamics of the model to calculate both the equation of motion for multipoint densities in configuration space and the interactions in the diagrammatic theory. A Boley basis of fluctuation vectors for the Hilbert space is used to develop two formally exact diagrammatic series for the time correlation functions. These theoretical techniques are generalizations of methods previously used for spin systems and atomic liquids, and they are generalizable to more complex lattice models of liquids such as a lattice gas with attractive interactions or polymer models. We use our formalism to construct approximate kinetic theories for the van Hove correlation and self-correlation function. The most simple approximation is the mean field approximation, which is exact for the van Hove correlation function of a one component system but an approximation for the self-correlation function. We use our first diagrammatic series to derive a two site multiple scattering approximation that gives a simple analytic expression for the spatial Fourier transform of the self-correlation function. We employ our second diagrammatic series to derive a simple mode coupling type approximation that provides a system of equations that can be solved for the self-correlation function.

Journal Article↗
PubMed2005

Inhomogeneous multiscale dynamics in harmonic lattices.

We use projection operators to address the coarse-grained multiscale problem in harmonic systems. Stochastic equations of motion for the coarse-grained variables, with an inhomogeneous level of coarse graining in both time and space, are presented. In contrast to previous approaches that typically start with thermodynamic averages, the key element of our approach is the use of a projection matrix chosen both for its physical appeal in analogy to mechanical stability theory and for its algebraic properties. We show that thermodynamic equilibrium can be recovered and obtain the fluctuation dissipation theorem a posteriori. All system-specific information can be computed from a series of feasible molecular dynamics simulations. We recover previous results in the literature and show how this approach can be used to extend the quasicontinuum approach and comment on implications for dissipative particle dynamics type of methods. Contrary to what is assumed in the latter models, the stochastic process of all coarse-grained variables is not necessarily Markovian, even though the variables are slow. Our approach is applicable to any system in which the coarse-grained regions are linear. As an example, we apply it to the dynamics of a single mesoscopic particle in the infinite one-dimensional harmonic chain.

Journal Article↗
PubMed2005

From diffusion to anomalous diffusion: a century after Einstein's Brownian motion.

Einstein's explanation of Brownian motion provided one of the cornerstones which underlie the modern approaches to stochastic processes. His approach is based on a random walk picture and is valid for Markovian processes lacking long-term memory. The coarse-grained behavior of such processes is described by the diffusion equation. However, many natural processes do not possess the Markovian property and exhibit anomalous diffusion. We consider here the case of subdiffusive processes, which correspond to continuous-time random walks in which the waiting time for a step is given by a probability distribution with a diverging mean value. Such a process can be considered as a process subordinated to normal diffusion under operational time which depends on this pathological waiting-time distribution. We derive two different but equivalent forms of kinetic equations, which reduce to known fractional diffusion or Fokker-Planck equations for waiting-time distributions following a power law. For waiting time distributions which are not pure power laws one or the other form of the kinetic equation is advantageous, depending on whether the process slows down or accelerates in the course of time.

Journal Article↗
PubMed2006

Three-dimensional-IR spectroscopy: beyond the two-point frequency fluctuation correlation function.

Three-dimensional-IR spectroscopy is proposed as a new spectroscopic technique that is sensitive to three-point frequency fluctuation correlation functions. This will be important when the statistics of the underlying stochastic process is non-Gaussian, and hence when the system does not follow the linear response hypothesis. Furthermore, a very general classification of nonlinear spectroscopy in terms of higher order frequency fluctuation correlation functions is introduced, according to which certain moments of a multidimensional spectrum are related to certain frequency fluctuation correlation functions. The classification is rigorous in the so-called inhomogeneous limit, but remains valid approximately also when motional narrowing becomes important. The work also puts a recent paper [J. Bredenbeck et al., Phys. Rev. Lett. 95, 083201 (2005)] onto solid theoretical grounds, where we have shown for the first time that fifth-order spectroscopy--in this case transient two-dimensional spectroscopy--is indeed sensitive to the three-point frequency fluctuation correlation function.

Journal Article↗
PubMed2006

Approximate first passage time distribution for barrier crossing in a double well under fractional Gaussian noise.

The distribution of waiting times, f(t), between successive turnovers in the catalytic action of single molecules of the enzyme beta-galactosidase has recently been determined in closed form by Chaudhury and Cherayil [J. Chem. Phys. 125, 024904 (2006)] using a one-dimensional generalized Langevin equation (GLE) formalism in combination with Kramers' flux-over-population approach to barrier crossing dynamics. The present paper provides an alternative derivation of f(t) that eschews this approach, which is strictly applicable only under conditions of local equilibrium. In this alternative derivation, a double well potential is incorporated into the GLE, along with a colored noise term representing protein conformational fluctuations, and the resulting equation transformed approximately to a Smoluchowski-type equation. f(t) is identified with the first passage time distribution for a particle to reach the barrier top starting from an equilibrium distribution of initial points, and is determined from the solution of the above equation using local boundary conditions. The use of such boundary conditions is necessitated by the absence of definite information about the precise nature of the boundary conditions applicable to stochastic processes governed by non-Markovian dynamics. f(t) calculated in this way is found to have the same analytic structure as the distribution calculated by the flux-over-population method.

Journal Article↗
PubMed2005

Metastatic properties and genomic amplification of the tyrosine kinase gene ACK1.

Metastasis of primary tumors leads to a very poor prognosis for patients suffering from cancer. Although it is well established that not every tumor will eventually metastasize, it is less clear whether primary tumors acquire genetic alterations in a stochastic process at a late stage, which make them invasive, or whether genetic alterations acquired early in the process of tumor development drive primary tumor growth and determine whether this tumor is going to be metastatic. To address this issue, we tested genes identified in a large-scale comparative genomic hybridization analysis of primary tumor for their ability to confer metastatic properties on a cancer cell. We identified amplification of the ACK1 gene in primary tumors, which correlates with poor prognosis. We further show that overexpression of Ack1 in cancer cell lines can increase the invasive phenotype of these cells both in vitro and in vivo and leads to increased mortality in a mouse model of metastasis. Biochemical studies show that Ack1 is involved in extracellular matrix-induced integrin signaling, ultimately activating signaling processes like the activation of the small GTPase Rac. Taken together, this study supports a theory from Bernards and Weinberg [Bernards, R. & Weinberg, R. A. (2002) Nature 418, 823], which postulates that the tendency to metastasize is largely predetermined.

Animals↗
PubMed2002

Survival without recovery after mass extinctions.

Because many survivors of mass extinctions do not participate in postrecovery diversifications, and therefore fall into a pattern that can be termed "Dead Clade Walking" (DCW), the effects of mass extinctions extend beyond the losses observed during the event itself. Analyses at two taxonomic levels provide a first-order test of the prevalence of DCWs by using simple and very conservative operational criteria. For four of the Big Five mass extinctions of the Phanerozoic, the marine genera that survived the extinction suffered approximately 10-20% attrition in the immediately following geologic stage that was significantly greater than the losses sustained in preextinction stages. The stages immediately following the three Paleozoic mass extinctions also account for 17% of all order-level losses in marine invertebrates over that interval, which is, again, significantly greater than that seen for the other stratigraphic stages (no orders are lost immediately after the end-Triassic or end-Cretaceous mass extinctions). DCWs are not evenly distributed among four regional molluscan time-series following the end-Cretaceous extinction, demonstrating the importance of spatial patterns in recovery dynamics. Although biotic interactions have been invoked to explain the differential postextinction success of clades, such hypotheses must be tested against alternatives that include stochastic processes in low-diversity lineages-which is evidently not a general explanation for the ordinal DCW patterns, because postextinction fates are not related to the size of extinction bottlenecks in Paleozoic orders-and ongoing physical environmental changes.

Animals↗
PubMed2000

Aging mechanisms.

Aging (senescence) has long been a difficult issue to be experimentally analyzed because of stochastic processes, which contrast with the programmed events during early development. However, we have recently started to learn the molecular mechanisms that control aging. Studies of the mutant mouse, klotho, showing premature aging, raise a possibility that mammals have an "anti-aging hormone." A decrease of cell proliferation ability caused by the telomeres is also tightly linked to senescence. Frontier experimental studies of aging at the molecular level are leading to fascinating hypotheses that aging is the price we had to pay for the evolution of the sexual reproduction system that produces a variety of genetic information and complex body structures.

Aging↗
PubMed2003

Autonomous T cell trafficking examined in vivo with intravital two-photon microscopy.

The recirculation of T cells between the blood and secondary lymphoid organs requires that T cells are motile and sensitive to tissue-specific signals. T cell motility has been studied in vitro, but the migratory behavior of individual T cells in vivo has remained enigmatic. Here, using intravital two-photon laser microscopy, we imaged the locomotion and trafficking of naive CD4(+) T cells in the inguinal lymph nodes of anesthetized mice. Intravital recordings deep within the lymph node showed T cells flowing rapidly in the microvasculature and captured individual homing events. Within the diffuse cortex, T cells displayed robust motility with an average velocity of approximately 11 microm x min(-1). T cells cycled between states of low and high motility roughly every 2 min, achieving peak velocities >25 microm x min(-1). An analysis of T cell migration in 3D space revealed a default trafficking program analogous to a random walk. Our results show that naive T cells do not migrate collectively, as they might under the direction of pervasive chemokine gradients. Instead, they appear to migrate as autonomous agents, each cell taking an independent trafficking path. Our results call into question the role of chemokine gradients for basal T cell trafficking within T cell areas and suggest that antigen detection may result from a stochastic process through which a random walk facilitates contact with antigen-presenting dendritic cells.

Adoptive Transfer↗
PubMed1979

Fixation of a deleterious allele at one of two "duplicate" loci by mutation pressure and random drift.

We consider a diploid population and assume two gene loci with two alleles each, A and a at one locus and B and b at the second locus. Mutation from wild-type alleles A and B to deleterious alleles a and b occurs with mutation rates va and vb, respectively. We assume that alleles are completely recessive and that only the double recessive genotype aabb shows a deleterious effect with relative fitness 1-epsilon. Then, it can be shown that if va greater than vb mutant a becomes fixed in the population by mutation pressure and a mutation-selection balance is ultimately attained with respect to the B/b locus alone. The main aim of this paper is to investigate the situation in which va = vb exactly. In this case a neutral equilibrium is attained and either locus can drift to fixation for the mutant allele. Diffusion models are developed to treat the stochastic process involved whereby the deleterious mutant eventually becomes fixed in one of the two duplicated loci by random sampling drift in finite populations. In particular, the equation for the average time until fixation of mutant a or b is derived, and this is solved numerically for some combinations of parameters 4Nev and 4Ne epsilon, where v is the mutation rate (va = vb = v) and Ne is the effective size of the population. Monte Carlo experiments have been performed (using a device termed "pseudo sampling variable") to supplement the numerical analysis.

Alleles↗
PubMed1990

Transfer of secretory proteins from the endoplasmic reticulum to the Golgi apparatus: discrimination between homologous and heterologous transfer in intact heterokaryons.

To examine aspects of the transfer of secretory proteins from the endoplasmic reticulum to the Golgi apparatus in situ, heterokaryons were formed between Hep G2 human hepatoma cells and WI-38 human fibroblasts. The cells were appropriately treated with cycloheximide before fusion, which emptied them of their respective secretory proteins, serum albumin for the Hep G2 cells and procollagen I for the WI-38 cells. After fusion was complete, the cycloheximide was washed out, protein synthesis was resumed, and the rates of reappearance of serum albumin and procollagen I in the two separated Golgi apparatuses within each heterokaryon were followed by immunofluorescence microscopy. Serum albumin was found to always reappear first in the Golgi apparatus contributed by the Hep G2 half of the heterokaryon, and procollagen I in the Golgi apparatus of the WI-38 half. These results suggest that the endoplasmic reticulum-to-Golgi apparatus transfer in situ is not simply a stochastic process but is either spatially restricted or exhibits cell-type specificity or both.

Carcinoma, Hepatocellular↗