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PubMed1993

Thymocyte development in major histocompatibility complex-deficient mice: evidence for stochastic commitment to the CD4 and CD8 lineages.

The mechanism resulting in commitment of precursor cells in the thymus to either the CD4 or CD8 lineage remains poorly understood. In principle, this may reflect a stochastic process or may reflect instructional signals from host major histocompatibility complex (MHC) molecules. We have examined the role of MHC products in subset commitment by using mice deficient in class I or class II MHC products. Normal numbers of committed CD4 intermediates (CD4+ CD8lo) develop in the thymus in the absence of class II molecules. Similarly, CD8 transitional cells (CD4loCD8+) are present in the thymus of mice lacking class I products. These findings suggest that commitment of CD4+8+ precursor cells to either lineage is a stochastic process that does not depend on instructive signals from MHC molecules (i.e., expression of alternative differentiative options by uncommitted precursor cells is independent of this environmental signal). These studies also suggest that an interaction between the T-cell antigen receptor (TCR) and MHC molecules that is independent of CD4/CD8 coreceptor engagement enhances stochastic coreceptor downregulation substantially and leads to upregulation of TCR expression as a prelude to selective events that require joint coreceptor/TCR engagement. We suggest that this initial interaction molds the TCR repertoire of stochastically generated T-cell subsets toward recognition of self-MHC products.

Animals↗
PubMed1983

Statistical analysis of ongoing activity of neurones in the substantia gelatinosa and in lamina III of cat spinal cord.

Intracellular recordings from substantia gelatinosa (s.g.) neurones in chloralose-anaesthetized cats and in decerebrate preparations revealed the existence of ongoing synaptic activity. 59% of s.g. neurones showed ongoing spiking activity at rates of more than one per second. The ongoing activity of twenty s.g. neurones was subjected to statistical analysis. Stationarity was established for the activity of each neurone, the interspike interval (i.s.i.) distributions were bell-shaped, and no evidence of dependency of the length of an interval on the one preceding it was found. The mechanism of spike generation in these neurones is therefore an example of a renewal stochastic process. The pattern of ongoing discharge of twelve neurones recorded in lamina III was markedly different, and generated in each case a unimodal asymmetric i.s.i. histogram with a sharp rise to mode after a short dead time and a slow decay. The activity was stationary only in the long term, and there was strong evidence of dependency of intervals. The spike generating mechanism was therefore an example of a non-renewal stochastic process. The different patterns of activity are discussed in relation to differences in cutaneous input, and it is suggested that the pattern of activity in the s.g. neurones is the result of convergence on the neurones of a large number of small independent excitatory influences, whereas that of the neurones in lamina III is the result of excitation by powerful synchronous synaptic inputs. It is re-emphasized that statistical analysis of neural impulse sequences is a valuable technique in investigation of the function of a neurone within its network.

Anesthesia, General↗
PubMed2024

Seasonal hydrological dynamics affected the diversity and assembly process of the antibiotic resistome in a canal network.

The significant threat of antibiotic resistance genes (ARGs) to aquatic environments health has been widely acknowledged. To date, several studies have focused on the distribution and diversity of ARGs in a single river while their profiles in complex river networks are largely known. Here, the spatiotemporal dynamics of ARG profiles in a canal network were examined using high-throughput quantitative PCR, and the underlying assembly processes and its main environmental influencing factors were elucidated using multiple statistical analyses. The results demonstrated significant seasonal dynamics with greater richness and relative abundance of ARGs observed during the dry season compared to the wet season. ARG profiles exhibited a pronounced distance-decay pattern in the dry season, whereas no such pattern was evident in the wet season. Null model analysis indicated that deterministic processes, in contrast to stochastic processes, had a significant impact on shaping the ARG profiles. Furthermore, it was found that Firmicutes and pH emerged as the foremost factors influencing these profiles. This study enhanced our comprehension of the variations in ARG profiles within canal networks, which may contribute to the design of efficient management approaches aimed at restraining the propagation of ARGs.

Seasons↗
PubMed1989

An illness-death process with time-dependent covariates.

A general model for the illness-death stochastic process with covariates has been developed for the analysis of survival data. This model incorporates important baseline and time-dependent covariates in order to make an appropriate adjustment for the transition and survival probabilities. The follow-up period is subdivided into small intervals and a constant hazard is assumed for each interval. An approximation formula is derived to estimate the transition parameters when the exact transition time is unknown. The method developed is illustrated with data from a study on the prevention of the recurrence of a myocardial infarction and subsequent mortality, the Beta-Blocker Heart Attack Trial (BHAT). This method provides an analytical approach with which the effectiveness of the treatment can be compared between the placebo and propranolol treatment groups with respect to fatal and nonfatal events simultaneously.

Biometry↗
PubMed1978

Compartment model approach to the estimation of tumor incidence and growth: investigation of a model of cancer latency.

Consideration is made of the problems involved in determining the effects of a chronic disease process, such as stomach cancer, on the observed mortality of the U.S. population. Specifically, since the time of initiation of tumor growth is unknown and the tumor becomes clinically manifest only after reaching considerable size, the early rate and pattern of tumor growth is unobserved. As a possible solution to the analysis of such problems, it is proposed to use stochastic compartment modelling techniques which deal with the problems of estimating the transition probabilities of a partially observed stochastic process. Implementation of the stochastic compartment techniques in this case depends on the selection of certain mathematical expressions from theories of carcinogenesis, epidemiologic studies and animal studies which allow the calculation of transition probabilities to unobserved states by making them explicit functions of time or age. Though the selection of the specific functions might be subject to debate, the general strategy of explicitly selecting such functions, and thereby exposing them for review in terms of biologic reasonableness and consistency with the data, seems to be a valid and useful methodology. Furthermore, various ways of viewing the model results (say from its internal behavior, e.g., from implied distributions of waiting times in various disease states) yield different insights into the various factors in carcinogenesis. The model, with parameters representing tumor incidence, time to tumor death given onset, genetic susceptibility to tumor growth and the effects of competing forces of mortality, is fitted to data on deaths due to stomach cancer for male U.S. residents age 25 and over in 1969. Two basic forms of the model, one with a waiting time distribution for occupants of the latent state and another with a single latency time, achieved excellent fits to the data. Examination of parameter estimates and compartment waiting time distributions are consistent with theoretical expectations and intuition. It is concluded that such strategies, involving the integration of clinical, experimental and vital statistics data into a comprehensive model of population carcinogenesis, are potentially powerful tools for investigation of the temporal dimensions of disease development in a human population.

Adult↗
PubMed1991

Segmentation of speckle images based on level-crossing statistics.

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

Image Processing, Computer-Assisted↗
PubMed1991

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

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

Adult↗
PubMed1992

Analyzing the dynamics of hand tremor time series.

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

Hand↗
PubMed1978

Mechanism of antigen-induced antibody biosynthesis from antibody precursors, the heavy and light immunoglobulin chains.

The immediate precursors of antibody molecules, the heavy (H) and light (L) peptide chains of the immunoglobulins, combine with each other by means of disulfide bonds formed by dehydrogenation of their cysteine residues. In the absence of an antigen this process yields the heterogeneous mixture of normal immunoglobulins. Antigens or their processed derivatives (Ag) interfere with this stochastic process by noncovalent combination with complementarily fitting H chains. The (Ag.H)(n) complexes thus formed, owing to the loss of rotational and translational freedom, combine preferentially with those L chains whose V(L) regions have some affinity for the determinants of the antigen molecule. Subsequent release of Ag from the (Ag.H.L)(n) complexes yields free antigen and antibody molecules. Each of the released Ag molecules can be used repeatedly for the same reaction cycle and thus can induce the biosynthesis of a large number of antibody molecules. Any macromolecule, natural or synthetic, that has at least a few polar groups and that can penetrate to the nascent H and L chains can thus act as an antigen. Whereas the structure of the H and L chains is genetically determined and transmitted through the germ line, the process induced by the antigen is a phenotypic phenomenon. The antigen acts in this process as a stereospecific cofactor or regulator of the thiol-disulfide transhydrogenation of the combining H and L chains of immunoglobulins.

Antibody Formation↗
PubMed1978

Eye movements of African chameleons: spontaneous saccade timing.

Despite asynchrony, saccades of left and right eyes of African chameleons had similar timing statistics. Prominent qualitative aspects of these statistics did not change if one or both eyes were masked. Evidently, an internal stochastic process regulated chameleon saccade generation.

Animals↗
PubMed1983

Movements of the luminal contents in two different regions of the caput epididymidis of the rat in vitro.

Transport of the epididymal contents was studied in vitro by filming, for 1-2.5 h, the movements of tiny, stained oil droplets injected through a micropipette into two regions of the lumen of the caput epididymidis: the most proximal part, with the widest outer diameter (region I), and the neighbouring, narrowest portion (region II). The movements of the oil droplets were pendular. Displacement, caused by a contraction of the wall spreading in either direction, was followed by a shorter, usually passive reflux leading to a small net displacement, delta l. The distance of transport during 5 min periods varied between 0.09 and 16.79 mm (median 1.0 mm) in region I and 0.05 and 3.62 mm (median 0.42 mm) in region II. Transport divided into periods when little or no net transport took place (slow transport) and periods when the transport was effective (fast transport). Although the periods of fast transport were infrequent, their significance in transport towards the ductus deferens was high. During 5 min sampling periods of fast transport, the pendular movements were longer in both regions: delta l was longer in region I and the probability of delta l being in the direction of transport was higher than during slow transport in both regions. The mean probability of delta l being in the direction of the ductus deferens was 0.63 in region I and 0.57 in region II. Higher frequency of pendular movements, longer delta l values and higher probability of delta l being towards the ductus deferens in region I than II suggest that the transport speed is higher in region I than II. Transport consisting of short steps occurring with variable probabilities in both directions is a stochastic process.

Animals↗
PubMed1989

The propagation of uncertainty in human mortality processes operating in stochastic environments.

This paper presents a model describing how the uncertainty due to influential exogenous processes combines with stochasticity intrinsic to physiological aging processes and propagates through time to generate uncertainty about the future physiological state of the population. Variance expressions are derived for (a) the future values of the physiological variables under the assumption that external factors evolve under a linear stochastic diffusion process, and (b) the cohort survival functions and cohort life expectancies which reflect the uncertainty in the future values of the physiological variables. The model implies that a major component of uncertainty in forecasts of the physiological characteristics of a closed cohort is due to differential rates of survival associated with different realizations of the external process. This suggests that the limits to forecasting may be different in physiological systems subject to systematic mortality than in physical systems such as weather where the concepts of closed cohorts and of mortality selection have no simple analog.

Aging↗
PubMed1994

Selection against deleterious mutations and the maintenance of biparental sex.

The mutational deterministic hypothesis postulates an advantage to sexual over asexual reproduction when mutation rates are on the order of 1.0 per genome per generation, provided that selection takes the form of a synergistic epistasis. While the efficacy of this mechanism has been investigated for infinite populations, its ability to protect sex in finite populations exhibiting stochastic dynamics remains untested. Stochastic processes have the potential to undermine protection for sex in two ways: (1) asexual lineages derived from sexual ancestors may, by chance, be founded by individuals bearing fewer than the equilibrium mean number of mutations, and (2) once established, such lineages will undergo random perturbations in the rates at which they grow and accumulate mutations. In the present study, I show using computer simulation that sexual populations of as many as 10,000 individuals are susceptible to invasion by asexual lineages for mutation rates higher than predicted under the mutational deterministic hypothesis. My simulations differ from previous investigations in that they model the progress of asexual lineages into sexual populations as both stochastic and deterministic processes for various mutation rates, selection regimes, and population sizes. It is suggested that ecological factors, such as parasitism or release from competition, could interact with selection against deleterious mutations to protect sex. To provide the sole explanation for sex, however, may require that selection against deleterious mutations be accompanied by mutation rates on the order of 2.0 per genome per generation.

Animals↗
PubMed1990

Non-stationary analysis of electromyographic activity prior to a ballistic voluntary contraction.

The electromyogram (EMG) in a ballistic voluntary action of muscle after a slight sustained contraction shows a short period of decrease or disappearance of the activity prior to the onset of phasic discharge. The EMG of elbow extensor (triceps brachii) prior to phasic discharge was analyzed as a non-stationary stochastic process. The distribution of the EMG amplitude began to change from 100 ms before the phasic discharge. The statistical test showed that the EMG activity became non-Gaussian from 30 to 50 ms before the phasic discharge. The standard deviation of the EMG showed a decreasing tendency from 80 to 100 ms prior to the phasic discharge. The statistical evidence for the EMG depression was also confirmed in fourth and sixth order coefficients of the orthogonal expansion of the probability density function. These results suggested that the EMG process profoundly changed its statistical characteristics just before the phasic discharge.

Action Potentials↗
PubMed1980

Intraclonal variation in proliferative potential of human diploid fibroblasts: stochastic mechanism for cellular aging.

At several points during the growth of a clone of human embryonic lung fibroblasts in vitro, 100 to 200 cells were removed at random and the proliferative potential of each cell was determined. At each sample point, a wide variation in remaining population doubling ability was observed among the individual cells and the distributions of doubling potentials were distinctly bimodal. Furthermore, the two cells arising from a single mitosis differed in their ability to proliferate by as many as eight population doublings (256-fold in the number of cells produced). The results suggest that a stochastic process is responsible for determining the limited proliferative potential of human embryonic lung fibroblasts.

Cell Division↗