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Fine structure analysis of temporal patterns in the light response of cells in the lateral geniculate nucleus of cat.

This study focuses on the analysis of temporal patterns in the spike train of cells in the lateral geniculate nucleus (LGN) of cat. Two-hundred eighty-three units have been recorded extracellularly in anesthetized animals during visual stimulation with flashing spot stimuli of different size. We used a novel method of temporally local computed interval distributions (intervalogram; Funke & Wörgötter, 1995) to visualize the statistical distribution of interspike intervals during different phases of the visual response. Multimodal interval distributions were observed mainly in X- and Y-ON cells, reflecting the tendency of these cells to fire with preferred intervals during the sustained light response. The shortest preferred interval is called the fundamental interval and the longer ones (higher-order intervals) are, in general, multiples thereof. During increasing surround inhibition a redistribution of the intervals towards the higher orders was observed. We regarded the different in the interval distributions as different components of possible temporal spike sequences and performed a pattern search up to the level of five subsequent intervals. While it is obvious, that the dominant peak is most strongly represented in any interval sequence, we also show that a significant overrepresentation of short sequences of similar intervals exists. The repetition rate is rather small (4-5 intervals) and, therefore, no long-lasting oscillatory pattern was observed in the autocorrelograms. Power spectral analysis of the peristimulus-time histograms, however, revealed that the sequential firing pattern is strongly stimulus locked at least for the majority of sweeps in the records. The mean firing rate of an LGN cell decreases with increasing stimulus size as well as with decreasing contrast. Therefore, the mean rate cannot be used to distinguish between these situations. While in the whole network this tradeoff can be resolved by the combined activity of multiple cells, our findings additionally suggest that contrast and size can be distinguished already at the single-cell level using different temporal patterns.

Animals↗

Voltage-clamp analysis of posttetanic potentiation of the mossy fiber to CA3 synapse in hippocampus.

1. Short-term changes in synaptic efficacy were studied at the mossy fiber (MF) to CA3 (MF-CA3) synapse in the in vitro hippocampus. Monosynaptic excitatory postsynaptic currents (EPSCs) were recorded before and during posttetanic potentiation (PTP) with the use of intracellular recording and single-electrode voltage-clamp (SEVC) techniques. 2. Repetitive stimulation (100 Hz for 1 s) of the MF synaptic inputs to CA3 pyramidal cells resulted in PTP averaging 170 +/- 19% (SE, n = 42) over control and decaying with a time constant (tau p) of 59.7 +/- 5 s(n = 23). Reproducible episodes of PTP could be recorded if low stimulus intensities were used. Also, after MF tetanization, a faster component, termed augmentation, preceded PTP but could not be accurately resolved within the experimental protocol; only estimates of this component are included. 3. Biophysical parameters of the EPSC that were monitored before and during PTP included synaptic conductance (G), synaptic reversal potential (Erev), decay time constant (tau EPSC), and input resistance of the postsynaptic cell. During PTP the EPSC synaptic conductance increased from 9.8 to 32.7 nS (P less than 0.02, n = 6), whereas there was no statistical change in Erev (-6.0 compared with -6.7 mV, n = 6), tau EPSC (4.3 compared with 4.5 ms, n = 9), or postsynaptic input resistance (59 compared with 63 M omega, n = 12). 4. A presynaptic contribution to PTP was studied directly by observing changes in transmitter release during PTP. Presynaptic mechanisms were assessed by determining the ratio of evoked synaptic excitatory postsynaptic potentials (EPSPs) over the total number of stimuli (EPSP-to-stimuli ratio). The ratio of EPSP to stimuli changed from 0.64 to 0.90 (P less than 0.01, n = 7) during PTP. A reduction in the number of synaptic failures can only be explained by a presynaptic mechanism. No assumptions concerning the statistical distribution of transmitter release were necessary because no statistical parameters were determined. 5. Changes in postsynaptic cell properties do not appear to contribute to PTP studied under the present experimental conditions. Direct stimulation of the postsynaptic neuron via the intracellular recording electrode (20-100 Hz/1 s) failed to produce potentiation of the EPSC; in fact, a slight depression was observed at 50 and 100 Hz direct stimulation. Likewise, the postsynaptic input resistance and synaptic Erev did not change during PTP. 6. The specific N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonovaleric acid (APV, 20 microM) had no effect on either the magnitude or duration of PTP.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

DNA in situ sensitivity to denaturation as a marker of human breast tumors.

DNA content and in situ sensitivity to denaturation were analyzed by flow cytometry of individual cell nuclei isolated from 40 breast carcinomas, nine fibroadenomas, and 14 samples of normal breast tissue. The extent of DNA denaturation induced by acid was expressed as alpha t, which represents the fraction of DNA staining metachromatically red with the fluorochrome acridine orange. In all cases of normal breast tissue DNA was very sensitive to denaturation and the frequency distribution of alpha t values was unimodal with over 90% of cells having alpha t above 0.6. All fibroadenomas were diploid; four had unimodal alpha t as in normal tissue and five had a bimodal distribution with an additional peak below 0.6. Twenty-seven adenocarcinomas (67%) had a DNA index above 1.0; of these 24 had bimodal alpha t distributions. Among 13 diploid carcinomas 10 had bimodal alpha t distributions. Statistically significant differences were observed in alpha t distributions of normal versus tumor breast tissue (P less than 0.005). In normal tissue and in all tumors a predominant proportion of cells with S and G2 + M DNA content were characterized by DNA resistant to denaturation (alpha t below 0.6). Of interest, the diploid cells from aneuploid tumors which may represent reactive host cells often displayed bimodal distributions of alpha t. These results may be interpreted in light of earlier studies demonstrating increased resistance of DNA to denaturation in diffuse chromatin of proliferating and/or transcriptionally active cells, and greater sensitivity to denaturation of DNA in condensed chromatin of quiescent cells. Thus, the presence of the second peaks representing cells with low alpha t values in breast tumors may indicate a high proportion of proliferating cells, whereas high alpha t populations may represent quiescent and differentiating (condensed chromatin) or dying (pycnotic nuclei) cells. It is likely that the low alpha t diploid cells detected in aneuploid tumors may represent the reactive (transcriptionally active and/or proliferating) infiltrating host cells (i.e., lymphocytes, monocytes) whose presence may also be of prognostic value. The data suggest that a DNA denaturability assay may be useful to characterize tumor and infiltrating host cell populations.

Acridine Orange↗

Extracorporeal irradiation of blood: dosimetry corrected for shortened erythrocyte lifespans.

The amount of radiation delivered to erythrocytes during extracorporeal irradiation of blood (ECIB) has been described using Poisson distribution statistics. The Poisson expression for erythrocyte radiation dose distribution was simplified by considering the slight dilution of blood with fluid that is initially in the extracorporeal tubing. An algorithm was devised that allows curtailed lifespans of irradiated erythrocytes to be taken into account in a short computer program of radiation dosimetry for ECIB. Radiation doses to erythrocytes with and without lifespan corrections are compared.

Blood Cells↗

The developmental basis for germline mosaicism in mouse and Drosophila melanogaster.

Data involving germline mosaics in Drosophila melanogaster and mouse are reconciled with developmental observations. Mutations that become fixed in the early embryo before separation of soma from the germline may, by the sampling process of development, continue as part of germline and/or differentiate into any somatic tissue. The cuticle of adult D. melanogaster, because of segmental development, can be used to estimate the proportion of mutant nuclei in the early embryo, but most somatic tissues and the germlines of both species continue from samples too small to be representative of the early embryo. Because of the small sample of cells/nuclei that remain in the germline after separation of soma in both species, mosaic germlines have percentages of mutant cells that vary widely, with a mean of 50% and an unusual platykurtic, flat-topped distribution. While the sampling process leads to similar statistical results for both species, their patterns of development are very different. In D. melanogaster the first differentiation is the separation of soma from germline with the germline continuing from a sample of only two to four nuclei, whereas the adult cuticle is a representative sample of cleavage nuclei. The presence of mosaicism in D. melanogaster germline is independent of mosaicism in the eye, head, and thorax. This independence was used to determine that mutations can occur at any of the early embryonic cell divisions and still average 50% mutant germ cells when the germline is mosaic; however, the later the mutation occurs, the higher the proportion of completely nonmutant germlines. In contrast to D. melanogaster, the first differentiation in the mouse does not separate soma from germline but produces the inner cell mass that is representative of the cleavage nuclei. Following formation of the primitive streak, the primordial germ cells develop at the base of the allantois and among a clonally related sample of cells, providing the same statistical distribution in the mouse germlines as in D. melanogaster. The proportion of mutations that are fixed during early embryonic development is greatly underestimated. For example, a DNA lesion in a postmeiotic gamete that becomes fixed as a dominant mutation during early embryonic development of the F1 may produce an individual completely mutant in the germ line and relevant somatic tissue or, alternatively, the F1 germline may be completely mutant but with no relevant somatic tissues for detecting the mutation until the F2. In both cases the mutation would be classified as complete in the F1 and F2, respectively, and not recognized as embryonic in origin. Because germ cells differentiate later in mammalian development, there are more opportunities for correlation between germline and soma in the mammal than Drosophila. However, because the germ cells and any somatic tissue, like blood, are derived from small samples, there may be many individuals that test negative in blood but have germlines that are either mosaic or entirely mutant.

Animals↗

The "random-coil" state of proteins: comparison of database statistics and molecular simulations.

This study presents a comparison of two models of the random-coil state, one based on statistical distributions from the structural database and the other based on molecular dynamics simulations. The database model relies on the assumption that the random- or statistical-coil state of a particular residue can be described by its conformational distribution in a sufficiently diverse subset of protein structures. The molecular dynamics model is based on distributions from molecular simulations carried out on "dipeptide" models (single residues with N-terminal acetyl and C-terminal N'-methyl amide blocking groups). A comparison of the two models for the residues Ala, Asn, Asp, Gly, and Val indicates that the database distributions are greatly influenced by long-range interactions and dominated by specific recognizable elements of protein structure. In contrast, the limited structural scope of the dipeptide models presents the extreme case of a peptide under the influence of only short-range interactions. The models were evaluated by a comparison of scalar coupling constants calculated from the conformational distributions and compared with experimentally values determined for unstructured peptides. Although the models gave different distributions, there was similar agreement with experiment. This comparison emphasizes the differences and limitations in each model and highlights the difficulty in presenting an accurate picture of the random-coil state. Proteins 1999;36:407- 418.

Computer Simulation↗

The acoustic properties of granular materials with pore size distribution close to log-normal.

The majority of realistic porous materials are composed of pores of which the shape is variable and the size of the pores normally obeys a distinctive statistical distribution. Although the variation of pore shape is less important, the statistical parameters of pore size distribution can have a considerable effect on the acoustic properties of porous media. This paper discusses the application of a simple model for the prediction of the acoustic properties of porous granular media with some assumed pore geometry and pore size distribution close to log-normal. The model is based on the rational (Padé) approximation approach [K. V. Horoshenkov, K. Attenborough, and S. N. Chandler-Wilde, J. Acoust. Soc. Am. 104, 1198-1209 (1998)] which has been developed for some simple pore geometries. It is shown that the experimentally determined pore size distribution for a representative range of granular materials is often close to log-normal. This assumption enables accurate predictions of the acoustic performance of these materials using the presented model. The water suction method is proposed to determine the parameters of the log-normal distribution, which are the mean pore size, (phi) and its standard deviation, sigma. This method is nonacoustic, modelless and well-adapted to acoustic materials and, unlike the BET method [S. Brunauer, P. H. Emmett, and E. Teller, J. Am. Chem. Soc. 60, 309-319 (1938)], is easy to reproduce in any basic acoustic laboratory requiring no expensive parts or chemicals. The proposed Padé approximation is based entirely on four measurable nonacoustic parameters, the porosity, omega, flow resistivity, Rb, tortuosity, q2 and the standard deviation of the pore size, sigma. The method is successfully tested on a representative selection of consolidated and nonconsolidated porous granular materials.

Journal Article↗

Lognormal distribution in physical work capacity in young healthy males.

This paper evaluates the statistical distribution of physical work capacity (Vo2 max) in young healthy males. For this purpose, the normally of Vo2 max data, collected on two random samples consisting of 123 and 120 young healthy male volunteers was tested. It is concluded that physical work capacity follows lognormal distribution and the quality of fit has been found to be good as tested by chi2 test.

Disability Evaluation↗

Distribution among sample test results when testing shelled corn lots for fumonisin.

The statistical distribution known as the compound gamma function was studied for suitability in describing the distribution of sample test results associated with testing lots of shelled corn for fumonisin. Thirty-two 1.1 kg test samples were taken from each of 16 contaminated lots of shelled corn. An observed distribution consisted of 32 sample fumonisin test results for each lot. The mean fumonisin concentration, c, and the variance, s2, among the 32 sample fumonisin test results along with the parameters for the compound gamma function were determined for each of the 16 observed distributions. The 16 observed distributions of sample fumonisin test results were compared with the compound gamma function using the Power Divergence test. The null hypothesis that the observed distribution could have resulted from sampling a family of compound gamma distributions was not rejected at the 5% significance level for 15 of the 16 lots studied. Parameters of the compound gamma distribution were calculated from the 32-fumonisin sample test results using the method of moments. Using regression analysis, equations were developed that related the parameters of the compound gamma distribution to fumonisin concentration and the variance associated with a fumonisin test procedure. An operating characteristic curve was developed for a fumonisin sampling plan to demonstrate the use of the compound gamma function.

Carboxylic Acids↗

Discrimination of speed distributions: sensitivity to statistical properties.

Two experiments examining the ability of human observers to detect differences in the statistical properties underlying velocity distributions were conducted. A four-alternative forced-choice methodology, using four simultaneous velocity distributions, was used in both experiments. In the first experiment the value of one statistical moment (mean, variance, skewness, or kurtosis) was manipulated while the others were held constant. The subjects task was to determine which of four velocity distributions contained the dissimilar value. In the second experiment only the latter three moments were examined. A similar procedure was used, however feedback was given after each trial to maximize observer performance. The results from both experiments indicate that human observers can reliably detect differences in both mean and variance information underlying velocity distributions. The results of this research has important implications for image segmentation and the detection of heading from optic flow.

Discrimination, Psychological↗

Quantifying uncertainty in geoacoustic inversion. II. Application to broadband, shallow-water data.

This paper applies the new method of fast Gibbs sampling (FGS) to estimate the uncertainties of seabed geoacoustic parameters in a broadband, shallow-water acoustic survey, with the goal of interpreting the survey results and validating the method for experimental data. FGS applies a Bayesian approach to geoacoustic inversion based on sampling the posterior probability density to estimate marginal probability distributions and parameter covariances. This requires knowledge of the statistical distribution of the data errors, including both measurement and theory errors, which is generally not available. Invoking the simplifying assumption of independent, identically distributed Gaussian errors allows a maximum-likelihood estimate of the data variance and leads to a practical inversion algorithm. However, it is necessary to validate these assumptions, i.e., to verify that the parameter uncertainties obtained represent meaningful estimates. To this end, FGS is applied to a geoacoustic experiment carried out at a site off the west coast of Italy where previous acoustic and geophysical studies have been performed. The parameter uncertainties estimated via FGS are validated by comparison with: (i) the variability in the results of inverting multiple independent data sets collected during the experiment; (ii) the results of FGS inversion of synthetic test cases designed to simulate the experiment and data errors; and (iii) the available geophysical ground truth. Comparisons are carried out for a number of different source bandwidths, ranges, and levels of prior information, and indicate that FGS provides reliable and stable uncertainty estimates for the geoacoustic inverse problem.

Acoustics↗

Accelerated test models for system strength based on Birnbaum-Saunders distributions.

Recent research in cumulative damage models for strengths of systems has yielded various statistical distributions that incorporate a system size variable and follow a generalized Birnbaum-Saunders form. These models can be unified as a three-parameter Birnbaum-Saunders-type family of distributions, where the third parameter arises from the size variable through the cumulative damage approach. In this paper, the generalized three-parameter Birnbaum-Saunders distribution is characterized, and examples of cumulative damage models for system strength that fit this form are given. Also, estimation and asymptotic theory are developed for the generalized distribution, and illustrations are presented for experimental strength data for carbon composite materials.

Carbon Compounds, Inorganic↗

[Rheology and spinning of alkaline solutions of sunflower seed globulin and casein].

The specific demand of sodium hydroxide is determined for the dissolution of sunflower seed globulin, casein and a mixture of them to equal parts. In low protein-containing solutions it depends for sunflower seed globulin very much on the sodium chloride concentration. From sunflower seed globulin, casein and a mixture of them to equal parts are prepared with sodium hydroxide high protein-containing alkaline solutions. Sunflower seed globulin forms temporally a gel phase. After this phase the solution of sunflower seed globulin shows like casein and a mixture of sunflower seed globulin/casein (I:I) pseudoplastic flow. The flow curves of the pseudoplastic solutions are described mathematically with the OSWALDian power statement. By alkaline solutions of casein and sunflower seed globulin/casein (I:I) the flow exponent n is distributed statistically about 0.9, by solutions of sunflower seed globulin a distribution exists about the mean values n = 0.85 and n = 0.50. lg k depends in all protein solutions on the concentration of protein, sodium chloride, sodium hydroxide and on the temperature and time. For all protein solutions exists a linear relation between the logarithm of viscosity and the reciprocal temperature for lg k and I/T, which is derived normally for NEWTONian flow behaviour. In a suitable scope of spinning for all protein solutions are carried out complete factorial experiment, which guide to regression equations of lg k; in the case of sunflower seed globulin are calculated also a regression equation of the flow exponent n. Going out from the parameters of the spinning process the properties of the spun sunflower seed globulin/casein (I:I) fibers are described.

Caseins↗

Cluster size diversity, percolation, and complex systems.

Diversity of cluster size has been used as a measurement of complexity in several systems that generate a statistical distribution of clusters. Using Monte Carlo simulations, we present a statistical analysis of the cluster size diversity and the number of clusters generated on randomly occupied lattices for the Euclidean dimensions 1 to 6. A tuning effect for diversity of cluster size and critical probabilities associated with the maximum diversity and the maximum number of clusters are reported. The probability of maximum diversity is related to the percolation threshold and several scaling relations between the variables measured are reported. The statistics of cluster size diversity has important consequences in the statistical description of the Universe as a complex system.

Journal Article↗

Selective growth and distribution of crystalline enantiomers in hydrogels.

The crystallization of sodium chlorate (NaClO3) is a classic example of spontaneous chirality, since it is achiral in solution but adopts a chiral form in the solid state. While crystal growth of NaClO3 from pure aqueous solutions yields a 50:50 statistical distribution of d- and l-crystals, large enantiomeric excesses of either d- and l-crystals can be achieved by crystal growth in agarose gel, a naturally occurring chiral polysaccharide. The influence of gel density (0.1-0.75 wt %), temperature, and the diffusion of cosolvents on crystal distribution was discerned from statistical data obtained from 752 gel-mediated crystallization experiments yielding 12,384 individual crystals. These studies demonstrate that the magnitude and direction of the bias can be selectively engineered toward either d- or l-forms by changing the gelation conditions. Aqueous agarose gels infused with 48 wt % NaClO3 at 6 degrees C, favored the growth of d-NaClO3 crystals, with ee's reaching 22% at the highest gel concentrations. Crystal growth under methanol diffusion favored deposition of the opposite enantiomorph, l-NaClO3. The bias in the crystal distribution is enhanced at higher temperatures. Aqueous gels at 24 degrees C infused with methanol cosolvent favored l-NaClO3, with ee's reaching 53%. The changing magnitude and direction of the enantiomorph bias can be ascribed to differences in the agarose conformation and intermolecular interactions between the gel and crystal surfaces that inhibit the formation of the two enantiomers to different extents.

Chlorates↗

[Evaluation of the clinical effectiveness of paradentosis therapy (author's transl)].

The x2 test of goodness of fit was used to assess the correlation between empirically determined distributions of a number of characteristics used in parodontology and the model of normal distribution. There was found a more or less pronounced asymmetry in the statistical distributions of some clinical and biochemical tests. It is recommended to use 10g X or square root of x in order to achieve approximation to the normal distribution. Inaccuracies in interpretation of clinical data due to neglect of variations from normal distribution are pointed out.

Diagnostic Errors↗

Simulations of protein folding and unfolding.

The 'new view' of protein folding is based on a statistical analysis of the landscape for protein folding. This perspective leads to the investigation of the statistical distributions of protein conformations as the folding protein approaches the native state from unfolded states. Molecular dynamics simulations of both the thermodynamics of protein folding and the kinetics of unfolding are beginning to explore the statistical nature of these distributions. They also provide connections between the theory of protein folding landscapes and the experimental observations of the properties of key ensembles of the conformations populated as folding progresses.

Models, Chemical↗

In vitro dissolution profile comparison--statistics and analysis of the similarity factor, f2.

PURPOSE: To describe the properties of the similarity factor (f2) as a measure for assessing the similarity of two dissolution profiles. Discuss the statistical properties of the estimate based on sample means. METHODS: The f2 metrics and the decision rule is evaluated using examples of dissolution profiles. The confidence interval is calculated using bootstrapping method. The bias of the estimate using sample mean dissolution is evaluated. RESULTS: 1. f2 values were found to be sensitive to number of sample points, after the dissolution plateau has been reached. 2. The statistical evaluation of f2 could be made using 90% confidence interval approach. 3. The statistical distribution of f2 metrics could be simulated using 'Bootstrap' method. A relatively robust distribution could be obtained after more than 500 'Bootstraps'. 4. A statistical 'bias correction' was found to reduce the bias. CONCLUSIONS: The similarity factor f2 is a simple measure for the comparison of two dissolution profiles. But the commonly used similarity factor estimate f2 is a biased and conservative estimate of f2. The bootstrap approach is a useful tool to simulate the confidence interval.

Chemistry, Pharmaceutical↗