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Statistical formulae of the energy distribution among a globular protein structure ensemble.

In prediction of a protein main-chain structure into which a query sequence of amino acids folds, one evaluates the relative stability of a candidate structure against reference structures. We developed a statistical theory for calculating the energy distribution over a main-chain structure ensemble, only with an amino acid composition given as a single argument. Then, we obtained a statistical formulae of the ensemble mean and ensemble variance V[E] of the reference structural energies, as explicit functions of the amino acid composition. The mean and the variance V[E] calculated from the formulae were well or roughly consistent with those resulting from a gapless threading simulation. We can use the formulae not only to perform the high-through-put screening of sequences in the inverse folding problem, but also to handle the problem analytically.

Animals↗

A stochastic model for determining the necessary staff level in a service industry.

Determining sufficient staff levels and providing quality, economical and efficient service is a problem that is difficult for some staffing managers to solve. The objectives in this paper are to derive a stochastic model for determining the necessary staff levels in various service environments such as hospitals, banks, or in manufacturing settings where the demand for a good staff is erratic. In order to assess the proper staff levels, an equation must be used which involves previous service demand hours that are considered as a distribution integrated within the statistical capability scale distribution. The most important property of this staffing model is that the results are independent of the mix of the jobs, the variation of the in-service time for jobs, and the stationary or nonstationary job arrival rate.

Humans↗

Source mechanisms for unit activity in isolated crayfish central nervous system.

As a tool for the identification of source mechanisms underlying the activity of single interneurons in the isolated crayfish abdominal cord, pulse trains from a sample of such neurons are statistically described (shape, mean, standard deviation, and serial correlation coefficient of interval distributions). These statistics were measured under four independent means of obtaining different average frequencies: (a) naturally occurring frequencies under standard conditions, (b) temperature control, (c) dc polarization, and (d) electrical stimulation of presynaptic fibers. 40 of 44 units studied had unimodal histograms, symmetrical when the mean interval was small and positively skewed with large means. Under standard conditions these units had SD = k (mean)(n), with n approximately 2. Fifteen single units were caused to fire at varied frequencies by cooling or dc stimulation. The resulting SD-vs.-mean plots for single units showed: (a)all points for a given unit fell approximately on a single line, regardless of whether temperature, dc, or neither was used to vary frequency, and (b) the average value of n (slope of log SD vs. log mean) for the fifteen units was 1.9 +/- 0.2. A paradox arises from interpretation of these data via gamma distributions. It is concluded that most of the spontaneous activity in the isolated abdominal cord may result from pacemaker activity within each cell and does not require a network of active units. Finally, the fact that the SD-mean relation was found not to depend measurably on temperature is interpreted as a useful restriction on models for neuronal noise processes.

Animals↗

Interpretation of relaxation time constants for amorphous pharmaceutical systems.

The molecular mobility of amorphous pharmaceutical materials is known to be a key factor in determining their stability, reactivity, and physicochemical properties. Usually such molecular mobility is quantified using relaxation time constants. Typically relaxation processes in amorphous systems are non-exponential and relaxation time constants are usually obtained from experimental data using a curve fitting procedure involving the empirical Kohlrausch-Williams-Watts (KWW) equation. In this article we explore the possible relationship between the KWW curve fitting parameters (tau(KWW), beta(KWW)) and common statistical measures of the average and the distribution (e.g., median, standard deviation) of the relaxation time values. This analysis is performed for several common statistical distributions (e.g., normal, lognormal, and Lorentzian), and the results are compared and analyzed in the context of pharmaceutical product stability predictions. The KWW function is able to describe relaxation processes stemming from several different statistical distribution functions. Under some circumstances the "average" relaxation time constant of the KWW equation (tau(KWW)) is significantly different from common statistical measures of the central value of a distribution (e.g., median). Simply knowing the relaxation time constants from the fit of the KWW equation is not sufficient to completely characterize and quantify the molecular mobility of amorphous pharmaceutical materials. An appreciation of the distribution of relaxation times and the resulting effects upon the KWW constants should be considered to be essential when working with amorphous pharmaceutical materials, especially when attempting to use relaxation time constants for predicting their physical or chemical stability.

Algorithms↗

The application of independent component analysis to the multi-channel surface electromyographic signals for separation of motor unit action potential trains: part I-measuring techniques.

The purpose of this study is to examine whether or not the application of independent component analysis (ICA) is useful for separation of motor unit action potential trains (MUAPTs) from the multi-channel surface EMG (sEMG) signals. In this study, the eight-channel sEMG signals were recorded from tibialis anterior muscles during isometric dorsi-flexions at 5%, 10%, 15% and 20% maximal voluntary contraction. Recording MUAP waveforms with little time delay mounted between the channels were obtained by vertical sEMG channel arrangements to muscle fibers. The independent components estimated by FastICA were compared with the sEMG signals and the principal components calculated by principal component analysis (PCA). From our results, it was shown that FastICA could separate groups of similar MUAP waveforms of the sEMG signals separated into each independent component while PCA could not sufficiently separate the groups into the principal components. A greater reduction of interferences between different MUAP waveforms was demonstrated by the use of FastICA. Therefore, it is suggested that FastICA could provide much better discrimination of the properties of MUAPTs for sEMG signal decomposition, i.e. waveforms, discharge intervals, etc., than not only PCA but also the original sEMG signals.

Action Potentials↗

Comparison of kinetic and end-point diffusion methods for quantitating human serum immunoglobulins.

Proficiency testing results were used to compare the kinetic and end-point versions of the single radial immunodiffusion method for quantitating human serum immunoglobulins. Statistical analysis of the results indicated that the results were not normally distributed but that the log normal distribution gives the best fit of any of the well-known frequency distributions. Consequently, statistical analysis of immunoglobulin results must be log transformed before parametric statistical tests can be appropriately applied. In general, there were no significant differences in level, precision, or interlaboratory comparability for these two methods. However, levels were different for participants using Hyland reagents, and better interlaboratory comparability was achieved by the end-point assay for immunoglobulin M. There were no significant differences in reported levels when compared by manufacturer within the same method.

Humans↗

Analysis of the distribution pattern of sister chromatid exchanges in mitotic chromosomes of human T-lymphocytes.

Band locations of 344 sister chromatid exchanges (SCE), observed in chromosome preparations of peripheral T-lymphocyte cultures, were identified using a sequential Q-banding-sister chromatid differentiation staining protocol. A comparison between expected Poisson, expected negative binomial distributions and observed SCE patterns, revealed that the negative binomial distribution provided a better fit to our SCE data. The aggregated pattern of SCE distribution indicated that some bands were more prone to undergo these events. Genetic markers assigned to those bands recording a significant number of exchanges seemed to correspond with the transcriptionally active genes. The results confirm that SCE are induced at the early S-phase of the cell cycle involving the early replicating genes in these events. Potential applications of cytogenetic techniques employed in the present study are proposed.

Chromosome Banding↗

Goodness-of-fit tests for GEE modeling with binary responses.

Analysis of data with repeated measures is often accomplished through the use of generalized estimating equations (GEE) methodology. Although methods exist for assessing the adequacy of the fitted models for uncorrelated data with likelihood methods, it is not appropriate to use these methods for models fitted with GEE methodology. We propose model-based and robust (empirically corrected) goodness-of-fit tests for GEE modeling with binary responses based on partitioning the space of covariates into distinct regions and forming score statistics that are asymptotically distributed as chi-square random variables with the appropriate degrees of freedom. The null distribution and the statistical power of the proposed goodness-of-fit tests were assessed using simulated data. The proposed goodness-of-fit tests are illustrated by two examples using data from clinical studies.

Antidepressive Agents↗

Analysis of speckle in ultrasound images using fractional order statistics and the homodyned k-distribution.

It is necessary to identify speckled regions in ultrasound images to control adaptive speckle suppression algorithms, for tissue characterisation, and to estimate the elevational separation of B-scans by speckle decorrelation. Previous authors have proposed classification techniques based on second order powers of the homodyned k-distribution, or lower order powers of the more limited k-distribution. In this paper we explore the speckle discrimination properties of statistics based on arbitrary powers of the ultrasound echo envelope signal using a combination of simulations and theoretical results from the homodyned k-distribution. We conclude that statistics based on powers less than one are surprisingly less effective than some higher powers. A simple discriminant function for speckle is evaluated quantitatively in simulation and qualitatively on sample B-scan images.

Algorithms↗

Statistics on continuous IBD data: exact distribution evaluation for a pair of full(half)-sibs and a pair of a (great-) grandchild with a (great-) grandparent.

BACKGROUND: Pairs of related individuals are widely used in linkage analysis. Most of the tests for linkage analysis are based on statistics associated with identity by descent (IBD) data. The current biotechnology provides data on very densely packed loci, and therefore, it may provide almost continuous IBD data for pairs of closely related individuals. Therefore, the distribution theory for statistics on continuous IBD data is of interest. In particular, distributional results which allow the evaluation of p-values for relevant tests are of importance. RESULTS: A technology is provided for numerical evaluation, with any given accuracy, of the cumulative probabilities of some statistics on continuous genome data for pairs of closely related individuals. In the case of a pair of full-sibs, the following statistics are considered: (i) the proportion of genome with 2 (at least 1) haplotypes shared identical-by-descent (IBD) on a chromosomal segment, (ii) the number of distinct pieces (subsegments) of a chromosomal segment, on each of which exactly 2 (at least 1) haplotypes are shared IBD. The natural counterparts of these statistics for the other relationships are also considered. Relevant Maple codes are provided for a rapid evaluation of the cumulative probabilities of such statistics. The genomic continuum model, with Haldane's model for the crossover process, is assumed. CONCLUSIONS: A technology, together with relevant software codes for its automated implementation, are provided for exact evaluation of the distributions of relevant statistics associated with continuous genome data on closely related individuals.

Chromosome Mapping↗

Effects of data manipulation and statistical methods on species sensitivity distributions.

Species sensitivity distribution (SSD) methodology currently is used in environmental risk assessment to determine the predicted no-effect concentration (PNEC) of a substance in cases where a sufficient number of chronic ecotoxicological tests have been carried out on the substance, covering, for the aquatic environment with which we are concerned, three taxonomic groups: algae, invertebrates, and vertebrates. In particular, SSD methodology enables calculation of a hazardous concentration that is assumed to protect 95% of species (HC5). This approach is based on the hypothesis that the species for which results of ecotoxicological tests are known are representative, in terms of sensitivity, of the totality of the species in the environment, which raises a number of questions, both theoretical and practical. In this study, we compared various methods of constructing a species sensitivity-weighted distribution (SSWD). Each method is characterized by a different way of taking into account intraspecies variation and proportions of taxonomic groups (vertebrates, invertebrates, and algae), as well as by the statistical method of calculation of the HC5 and its confidence interval. Those methods are tested on 15 substances by using chronic no-observed-effect concentration data available in the literature. The choice of data (intraspecies variation and proportions between taxonomic groups) was found to have more effect on the value of the HC5 than the statistical method used to construct the distribution. The weight of each taxonomic group is the most important parameter for the result of the SSWD and letting literature references decide which proportions of data are used to construct it is not satisfactory.

Analysis of Variance↗

A theoretical model for event statistics in microdosimetry. II: Nonuniform distribution of heavy ion tracks.

A microdosimetry model, described in Part I, applies to the case of a convex site immersed in a uniform distribution of heavy particle tracks, and assumes no restrictions in site geometry or the kind of randomness. In Part II, this model is extended to include nonuniform distributions of particle tracks. This situation is relevant to the study of microdosimetry, for example, in boron neutron capture, in irradiation experiments using heavy ion particle beams, where the sources of particle tracks are external to the cell, or in irradiation from internally incorporated particle-emitting radionuclides, such as environmental radon or occupational exposure to radioactive materials. The formalism developed permits the calculation of statistical properties, track length distributions, and microdosimetric spectra for convex sites where the "inner" and "outer" concentrations of sources may be different, or for tracks originating on the surface of a convex site. Expressions applicable to the case of surface-distributed sources of tracks are presented that may represent situations such as boron compounds bound to the membrane of a cellular nucleus in boron neutron capture. A series of Monte Carlo calculations and analytical solutions, illustrating the case of spherical site geometry, are presented and compared. Finally, microdosimetric spectra and specific energy averages are calculated for alpha and lithium particles originating from thermal neutron capture in 10B, showing their dependence on 10B localization (extra-site, uniform, intra-site, or surface-distributed).

Biophysical Phenomena↗

Investigation of granulocytopoietic kinetics by microdensitometric evaluation of primary granule naphthol-AS-D-chloroacetate esterase activity.

Using a scanning microscope photometer we determined quantitatively the enzymecytochemical reaction product for naphthol-AS-D-chloroacetate esterase in neutrophilic granulocytes and their precursors in man. Evaluation of neutrophilic cells from three healthy donors resulted in a logarithm-normal distribution. After subdivision of these cells in their morphologically defined maturational stages no statistically bimodal distribution was shown within the single cell groups. Myelocytes showed twice the amount of the polymorphonuclear neutrophil absorption values. The highest promyelocyte obsorptions were double the values of the myelocyte absorptions. The standard deviation of the absorbance obtained with promyelocytes (which encompass cells already producing granules up to cells reaching their maximal granule content) was significantly higher than the standard deviation of the myelocytes. As already known, primary granules are only synthesized at the promyelocyte stage and - according to the present knowledge - their chloracylesterase and peroxidase activities are not lost during further maturation. Consequently, our results indicate that only enzyme-rich, late promyelocytes undergo mitosis transforming into myelocytes. Correspondingly, their absorption value was halved. Since the absorbance from myelocytes to polymorphonuclears is again halved, myelocytes divide only once. Metamyelocyte absorptions in part correspond to that of myelocytes. This indicates that no distinction can be made between myelocytes with mitotic capacity and "true" if only the size and the nuclear shape are considered metamyelocytes which are not longer capable of undergoing mitosis.

Adult↗

Malignancy-associated changes in lactiferous duct epithelium.

OBJECTIVE: To determine whether cells from histologically normal appearing epithelium of the lactiferous duct from women with a remote ductal lesion in the breast provide any clues indicating the existence of such a lesion. STUDY DESIGN: Tissue sections cut to 4 microns and stained with hematoxylin and eosin were prepared from duct tissue of 20 women with breast lesions and of 20 women free of any such lesion who had undergone mammoplastic procedures or resection for benign reasons. One hundred nuclei were measured from each case. Measures of nuclear deviation from normal were computed, discriminant functions were derived, and multivariate significance tests were conducted. RESULTS: Nuclei from histologically normal appearing regions of lactiferous duct epithelium from women harboring distant lesions exhibited changes in the distribution pattern of their nuclear chromatin, indicating the presence of these lesions. The statistical significance of these changes was documented. The changes were clearly evident in all 20 subjects with lesions and were not observed in 19 of the 20 subjects without lesions. CONCLUSION: The results suggest that studies aimed at detecting malignancy-associated changes in cells collected by ductal lavage might lead to a minimally invasive screening procedure for breast lesions.

Adult↗