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Spectral estimation for characterization of acoustic aberration.

Spectral estimation based on acoustic backscatter from a motionless stochastic medium is described for characterization of aberration in ultrasonic imaging. The underlying assumptions for the estimation are: The correlation length of the medium is short compared to the length of the transmitted acoustic pulse, an isoplanatic region of sufficient size exists around the focal point, and the backscatter can be modeled as an ergodic stochastic process. The motivation for this work is ultrasonic imaging with aberration correction. Measurements were performed using a two-dimensional array system with 80 x 80 transducer elements and an element pitch of 0.6 mm. The f number for the measurements was 1.2 and the center frequency was 3.0 MHz with a 53% bandwidth. Relative phase of aberration was extracted from estimated cross spectra using a robust least-mean-square-error method based on an orthogonal expansion of the phase differences of neighboring wave forms as a function of frequency. Estimates of cross-spectrum phase from measurements of random scattering through a tissue-mimicking aberrator have confidence bands approximately +/- 5 degrees wide. Both phase and magnitude are in good agreement with a reference characterization obtained from a point scatterer.

Adipose Tissue↗

On using polynomial chaos for modeling uncertainty in acoustic propagation.

The use of polynomial chaos for incorporating environmental variability into propagation models is investigated in the context of a simplified one-dimensional model, which is relevant for acoustic propagation when the random sound speed is independent of depth. Environmental variability is described by a spectral representation of a stochastic process and the chaotic representation of the wave field then consists of an expansion in terms of orthogonal random polynomials. Issues concerning implementation of the relevant equations, the accuracy of the approximation, uniformity of the expansion over the propagation range, and the computational burden necessary to evaluate different field statistics are addressed. When the correlation length of the environmental fluctuations is small, low-order expansions work well, while for large correlation lengths the convergence of the expansion is highly range dependent and requires high-order approximants. These conclusions also apply in higher-dimensional propagation problems.

Journal Article↗

Maximum-likelihood procedures and the inattentive observer.

In most experimental situations, it is expected that observers will achieve perfect detection at extremely high signal levels. Technically, it is assumed that the asymptote of the psychometric function is unity. In many practical psychophysical tests, such as those involving children, patients, or nonhuman animals, the observers are occasionally inattentive. Using computer simulations, it was assumed that inattention can be modeled as a stationary stochastic process whose major effect is to produce a psychometric function having an asymptote less than unity. A maximum-likelihood procedure was used to estimate threshold, because it has been shown to provide reasonably stable threshold estimates using very few observations. Inattention increases the variability of the threshold estimate, as would be expected, because inattention reduces the slope of the psychometric function. The simulations also show that the maximum-likelihood procedure poorly estimates the amount of inattention, and can, thereby, produce a strong bias in the threshold estimates, overestimating or underestimating the true values under different circumstances. Inattention appears to affect the two-alternative forced-choice procedure more strongly than the yes-no (go/nogo) procedure.

Attention↗

On the nature of stopping an earlier intended voluntary action.

The ability to inhibit an earlier intended action in a stop-signal task is commonly assessed using the measures of latency and probability. The usual findings from stop-signal trials of lower response probabilities and shorter reaction latencies at reduced stop-signal delays were reported, as described in previous studies in terms of an independent race between stochastic processes. In addition, using the less common measure of amplitude, a continuum of reductions in surface EMG onsets was reported. Weakened motor discharges have yet to be explained in terms of a mechanism of inhibitory control. Using computer simulations of neural functioning, the properties of independence and non-independence were examined for their effects on motor pool output in terms of probability, latency, and EMG onsets. The data provided support to question the requirement of independent processes for a theory of inhibitory control.

Behavior Control↗

Endothelial progenitor cell therapy for atherosclerosis: the philosopher's stone for an aging population?

Much of the increased risk for atherosclerosis progression with age may be a result of age-related declines in the capacity of precursor cells to repair damage in the arterial endothelium. To estimate the impact of progenitor cell therapy for atherosclerosis on cardiovascular disease (CVD) mortality, life expectancy, and survival, as compared with the lifetime control of conventional risk factors, we modeled the health effects of bone marrow-derived endothelial progenitor cell therapy using data from the 1950 to 1996 follow-up of the Framingham Heart Study. To model cardiovascular disease mortality, we assumed that progenitor cell therapy was applied at age 30, with the effect assumed to be a 10-year delay in atherosclerosis progression. Age projections were constructed analytically using the stochastic process model for risk factor dynamics and mortality and microsimulation techniques. We considered three types of interventions: (i) keeping risk factors within selected limits to model current clinical recommendations; (ii) an age shift of 10 years to model the effects of progenitor cell therapy; and (iii) elimination of a competing risk (such as cancer). Our study suggests that progenitor cell therapy might increase life expectancy in the population as much as the complete elimination of cancer (in females, an additional 3.67 versus 3.37 years; in males, an additional 5.94 versus 2.86 years, respectively).

Adult↗

Edge effects and the extinction of populations inside protected areas

Theory predicts that small populations may be driven to extinction by random fluctuations in demography and loss of genetic diversity through drift. However, population size is a poor predictor of extinction in large carnivores inhabiting protected areas. Conflict with people on reserve borders is the major cause of mortality in such populations, so that border areas represent population sinks. The species most likely to disappear from small reserves are those that range widely-and are therefore most exposed to threats on reserve borders-irrespective of population size. Conservation efforts that combat only stochastic processes are therefore unlikely to avert extinction.

Journal Article↗

Diversity of Wolbachia endosymbionts in heteropteran bugs.

An extensive survey of Wolbachia endosymbionts in Japanese terrestrial heteropteran bugs was performed by PCR detection with universal primers for wsp and ftsZ genes of Wolbachia, cloning of the PCR products, restriction fragment length polymorphism analysis of infecting Wolbachia types, and molecular phylogenetic characterization of all the detected Wolbachia strains. Of 134 heteropteran species from 19 families examined, Wolbachia infection was detected in 47 species from 13 families. From the 47 species, 59 Wolbachia strains were identified. Of the 59 strains, 16 and 43 were assigned to A group and B group in the Wolbachia phylogeny, respectively. The 47 species of Wolbachia-infected bugs were classified into 8 species with A infection, 28 species with B infection, 2 species with AA infection, 3 species with AB infection, 5 species with BB infection, and 1 species with ABB infection. Molecular phylogenetic analysis showed little congruence between Wolbachia phylogeny and host systematics, suggesting frequent horizontal transfers of Wolbachia in the evolutionary course of the Heteroptera. The phylogenetic analysis also revealed several novel lineages of Wolbachia. Based on statistical analyses of the multiple infections, we propose a hypothetical view that, in the heteropteran bugs, interactions between coinfecting Wolbachia strains are generally not intense and that Wolbachia coinfections have been established through a stochastic process probably depending on occasional horizontal transfers.

Animals↗

Requirement of protein synthesis for the degradation of host mRNA in Friend erythroleukemia cells infected wtih herpes simplex virus type 1.

We describe experiments which demonstrate that shortly after infection of Friend erythroleukemia cells with herpes simplex virus (HSV), polyribosomes dissociate and cellular mRNA degrades. Analysis of infected cell extracts on sucrose density gradients demonstrates that the majority of the polyribosomes have dissociated to monoribosomes at 2 h postinfection. Physical measurements of infected-cell RNAs support this conclusion and demonstrate that the polyadenylated RNAs decrease in size. The degradation of mRNA is apparently a stochastic process as judged by the failure to detect a shift in the Crt1/2 when polyadenylated RNA extracted from infected cells at different times is hybridized to globin complementary DNA. In experiments designed to determine whether dissociation of polyribosomes is sufficient to cause degradation of globin mRNA, the amount of globin mRNA in uninfected cells did not change when cells were treated with NaF or pactamycin at concentrations sufficient to dissociate all polyribosomes. In cells infected with UV-irradiated virus polyribosomes dissociate but globin mRNA does not degrade, suggesting that it is possible to separate dissociation from degradation.

Animals↗

Genetic drift can dominate short-term human immunodeficiency virus type 1 nef quasispecies evolution in vivo.

The evolution of human immunodeficiency virus (HIV) type 1 nef quasispecies in a patient clonally infected with a contaminated batch of blood clotting factor IX was monitored. nef sequences were derived at 11, 25, and 41 months postinfection from infected peripheral blood mononuclear cells after molecular cloning of PCR-amplified proviral DNA. The phylogenetic relationships among a total of 41 informative sequences were established by split decomposition analysis and used as a basis to establish a substitution matrix and to score synonymous (s) and nonsynonymous (ns) substitutions. The number of observed in-phase stop codons within the nef sequences was comparable to that expected on a random basis. Similarly, the numbers of observed s and ns substitutions did not differ significantly from expected values. No codon position was preferentially mutated. The maximum sequence divergence increased in a linear manner, with approximately 4.4 nucleotide and approximately 3.2 amino acid changes per year. It appears that stochastic processes strongly influence short-term HIV nef quasispecies evolution in vivo.

Amino Acid Sequence↗

Structure and temporal dynamics of populations within wheat streak mosaic virus isolates.

Variation within the Type and Sidney 81 strains of wheat streak mosaic virus was assessed by single-strand conformation polymorphism (SSCP) analysis and confirmed by nucleotide sequencing. Limiting-dilution subisolates (LDSIs) of each strain were evaluated for polymorphism in the P1, P3, NIa, and CP cistrons. Different SSCP patterns among LDSIs of a strain were associated with single-nucleotide substitutions. Sidney 81 LDSI-S10 was used as founding inoculum to establish three lineages each in wheat, corn, and barley. The P1, HC-Pro, P3, CI, NIa, NIb, and CP cistrons of LDSI-S10 and each lineage at passages 1, 3, 6, and 9 were evaluated for polymorphism. By passage 9, each lineage differed in consensus sequence from LDSI-S10. The majority of substitutions occurred within NIa and CP, although at least one change occurred in each cistron except HC-Pro and P3. Most consensus sequence changes among lineages were independent, with substitutions accumulating over time. However, LDSI-S10 bore a variant nucleotide (G(6016)) in NIa that was restored to A(6016) in eight of nine lineages by passage 6. This near-global reversion is most easily explained by selection. Examination of nonconsensus variation revealed a pool of unique substitutions (singletons) that remained constant in frequency during passage, regardless of the host species examined. These results suggest that mutations arising by viral polymerase error are generated at a constant rate but that most newly generated mutants are sequestered in virions and do not serve as replication templates. Thus, a substantial fraction of variation generated is static and has yet to be tested for relative fitness. In contrast, nonsingleton variation increased upon passage, suggesting that some mutants do serve as replication templates and may become established in a population. Replicated mutants may or may not rise to prominence to become the consensus sequence in a lineage, with the fate of any particular mutant subject to selection and stochastic processes such as genetic drift and population growth factors.

Biological Evolution↗

Statistics of copolymer sequences obtained by polymeranalogous reactions of homopolymer globules.

For the first time the macrokinetics of polymeranalogous reaction in a homopolymer globule is considered theoretically. Using mathematical apparatus of the theory of markovian stochastic processes we examined the statistical characteristics of the chemical structure of the emerging copolymers. It is shown that when the reaction is kinetically-controlled the sequence distribution of monomeric units in copolymer chains follows Bernoullian statistics. In the opposite regime, when the reaction is diffusion-controlled it is proved that the resulting primary structure is described by the Levy flight distribution. Such copolymers with nonmarkovian character of the alteration of units in macromolecules can not be synthesized in the bulk or in concentrated solutions by means of standard synthetic polymerization procedures.

Journal Article↗

Mechanisms of polarized growth and organelle segregation in yeast.

Cell polarity, as reflected by polarized growth and organelle segregation during cell division in yeast, appears to follow a simple hierarchy. On the basis of physical cues from previous cell cycles or stochastic processes, yeast cells select a site for bud emergence that also defines the axis of cell division. Once polarity is established, rho protein-based signal pathways set up a polarized cytoskeleton by activating localized formins to nucleate and assemble polarized actin cables. These serve as tracks for the transport of secretory vesicles, the segregation of the trans Golgi network, the vacuole, peroxisomes, endoplasmic reticulum, mRNAs for cell fate determination, and microtubules that orient the nucleus in preparation for mitosis, all by myosin-Vs encoded by the MYO2 and MYO4 genes. Most of the proteins participating in these processes in yeast are conserved throughout the kingdoms of life, so the emerging models are likely to be generally applicable. Indeed, several parallels to cellular organization in animals are evident.

Actins↗

Evolution of Wheat streak mosaic virus: dynamics of population growth within plants may explain limited variation.

Like many other plant RNA viruses, Wheat streak mosaic virus (WSMV) sequence diversity within and among infected plants is low given the large number of virions produced. This may be explained by considering aspects of plant virus life history. Intracellular replication of RNA viruses is predominately linear, not exponential, which means that the rate at which mutations accumulate also is linear. Bottlenecks during systemic movement further limit diversity. Analysis of mixed infections with two WSMV isolates suggests that about four viral genomes participate in systemic invasion of each tiller. Low effective population size increases the role of stochastic processes on dynamics of plant virus population genetics and evolution. Despite low pair-wise diversity among isolates, the number of polymorphic sites within the U.S. population is about the same as between divergent strains or a sister species. Characteristics of polymorphism in the WSMV coat protein gene suggest that most variation appears neutral.

Biological Evolution↗

Mathematical modeling of vascular endothelial layer maintenance: the role of endothelial cell division, progenitor cell homing, and telomere shortening.

Maintenance of the endothelial cell (EC) layer of the vessel wall is essential for proper functioning of the vessel and prevention of vascular disorders. Replacement of damaged ECs could occur through division of surrounding ECs. Furthermore, EC progenitor cells (EPCs), derived from the bone marrow and circulating in the bloodstream, can differentiate into ECs. Therefore, these cells might also play a role in maintenance of the endothelial layer in the vascular system. The proliferative potential of both cell types is limited by shortening of telomeric DNA. Accelerated telomere shortening might lead to senescent vascular wall cells and eventually to the inability of the endothelium to maintain a continuous monolayer. The aim of this study was to describe the dynamics of EC damage and repair and telomere shortening by a mathematical model. In the model, ECs were integrated in a two-dimensional structure resembling the endothelium in a large artery. Telomere shortening was described as a stochastic process with oxidative damage as the main cause of attrition. Simulating the model illustrated that increased cellular turnover or elevated levels of oxidative stress could lead to critical telomere shortening and senescence at an age of 65 yr. The model predicted that under those conditions the EC layer could display defects, which could initiate severe vascular wall damage in reality. Furthermore, simulations showed that 5% progenitor cell homing/yr can significantly delay the EC layer defects. This stresses the potential importance of EPC number and function to the maintenance of vascular wall integrity during the human life span.

Arteriosclerosis↗

Effect of interbreath fluctuations on characterizing exercise gas exchange kinetics.

Breathing has inherent irregularities that produce breath-to-breath fluctuations ("noise") in pulmonary gas exchange. These impair the precision of characterizing nonsteady-state gas exchange kinetics during exercise. We quantified the effects of this noise on the confidence of estimating kinetic parameters of the underlying physiological responses and hence of model discrimination. Five subjects each performed eight transitions from 0 to 100 W on a cycle ergometer. Ventilation, CO2 output, and O2 uptake were computed breath by breath. The eight responses were interpolated uniformly, time aligned, and averaged for each subject; and the kinetic parameters of a first-order model (i.e., the time constant and time delay) were then estimated using three methods: linear least squares, nonlinear least squares, and maximum likelihood. The breath-by-breath noise approximated an uncorrelated Gaussian stochastic process, with a standard deviation that was largely independent of metabolic rate. An expression has therefore been derived for the number of square-wave repetitions required for a specified parameter confidence using methods b and c; method a being less appropriate for parameter estimation of noisy gas exchange kinetics.

Adult↗

DNA histogram interpretation based on statistical approaches.

Image cytometric DNA measurements provide data which are most often interpreted as equivalent to the chromosomal ploidy although the chromosomal and the DNA ploidy are not identical. The common link between them is the cell cycle. Therefore, if destined for DNA ploidy interpretations, the DNA cytometry should be performed on a population-oriented stochastic basis. Using stochastic sampling the data can be interpreted by applying the rules of stochastic processes. A set of statistical methods is given that enables a DNA histogram to be interpreted objectively and without human interaction. These statistics analyse the precision and accuracy of the entire measurement process. They give in error probabilities for accepting a measurement as reliable, for recognition of stemlines, stemline aneuploidy, and for evaluating so-called rare events. Nearly 300 image cytometric DNA measurements from breast cancers and rat liver imprints examples have been selected to demonstrate the efficiency of the statistics in each step of interpreting DNA histograms.

Aneuploidy↗

Spectral analysis of the EEG. Some fundamentals revisited and some open problems.

This tutorial was presented during the 1986 training course of the International Pharmaco-EEG Group (IPEG) in Santa Margherita Ligure, Italy. During recent years spectral analysis has been increasingly used in experimental EEG. However, to avoid misinterpretations of results, its limitations must still be carefully considered. The tutorial starts with revisiting the fundamentals of the technique, emphasizes the practical estimation of auto- and cross-spectra, discusses the assumptions underlying the spectral analysis of stochastic processes, and ends with a brief discussion concerning the postprocessing of spectral data.

Computers↗

Analysis of HLA haplotype segregation in the Schmiedeleut Hutterites of South Dakota.

HLA data from 1,085 South Dakotan Schmiedeleut Hutterites were examined for evidence of nonrandom transmission of haplotypes. The inheritance of haplotypes was viewed as a series of genetic contests between competing pairs of parental haplotypes using a maximum likelihood approach first put forward by Carlisle and Woodbury. Haplotype transmission probabilities were expressed in terms of weights, and the null hypothesis that the inheritance pattern was a random stochastic process, equivalent to the equality of the weights, was tested via the likelihood ratio. A total of 1,517 competitions was subjected to analysis, first globally using all data, and then for particular haplotypes of interest. Transmission of haplotype observed to compete with only a single other haplotype was also assessed using an exact procedure. No evidence of preferential transmission of HLA haplotypes was found. These results do not rule out transmission biases that may arise because of selection against homozygotes, mechanisms specifically affecting particular alleles or haplotypes not considered in the present study, or biases arising from maternal-fetal interactions.

Consanguinity↗