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Infant sensitivity to distributional information can affect phonetic discrimination.

For nearly two decades it has been known that infants' perception of speech sounds is affected by native language input during the first year of life. However, definitive evidence of a mechanism to explain these developmental changes in speech perception has remained elusive. The present study provides the first evidence for such a mechanism, showing that the statistical distribution of phonetic variation in the speech signal influences whether 6- and 8-month-old infants discriminate a pair of speech sounds. We familiarized infants with speech sounds from a phonetic continuum, exhibiting either a bimodal or unimodal frequency distribution. During the test phase, only infants in the bimodal condition discriminated tokens from the endpoints of the continuum. These results demonstrate that infants are sensitive to the statistical distribution of speech sounds in the input language, and that this sensitivity influences speech perception.

Attention↗

Applications and statistics for multiple high-scoring segments in molecular sequences.

Score-based measures of molecular-sequence features provide versatile aids for the study of proteins and DNA. They are used by many sequence data base search programs, as well as for identifying distinctive properties of single sequences. For any such measure, it is important to know what can be expected to occur purely by chance. The statistical distribution of high-scoring segments has been described elsewhere. However, molecular sequences will frequently yield several high-scoring segments for which some combined assessment is in order. This paper describes the statistical distribution for the sum of the scores of multiple high-scoring segments and illustrates its application to the identification of possible transmembrane segments and the evaluation of sequence similarity.

Amino Acid Sequence↗

Comparison between the phi distribution of the amino acids in the protein database and NMR data indicates that amino acids have various phi propensities in the random coil conformation.

It has been indicated that amino acids have various intrinsic phi and psi propensities, as demonstrated from the comparison between experimental secondary structure propensities and their relative statistical distribution in the protein database for the appropriate region of the Ramachandran plot. However, this does not eliminate the possibility that these experimental propensities are the result of context effects due to the secondary structure environment of the mutated position. To demonstrate that there are at least real intrinsic phi propensities, independent of context effects, we have used two different nuclear magnetic resonance parameters related to the phi dihedral angle (J3 alpha HN coupling constants and the chemical shift of the C alpha H proton), determined in random-coil tetra- and pentapeptides, and/or in proteins. Comparison of the experimentally determined values for these parameters with the theoretical ones determined from the analysis by different empirical and theoretical equations of the phi dihedral angle statistical distribution of the amino acids in the protein database, supports the idea that each amino acid has, at least, different phi intrinsic propensities. Consideration of all conformations, or only coil conformations, in the protein database produces similar results. The reasonable correlation between these experimental and theoretical data and the hydrogen-exchange data in random-coil peptides suggests that maximisation of hydrophobic surface-buried and hydrogen-bond formation with the solvent could be responsible for these different random-coil conformational preferences. Analysis of the intrinsic propensities for beta-strand, alpha-helix and polyproline II dihedral angles of the 20 amino acids in coil conformations, indicates that the side-chain of the amino acids is mainly determining the relative preferences for the phi angle.

Amino Acids↗

Exposure to agricultural treatment residues: some simple statistical considerations based on monitoring data for ethoxyquin on apples.

The data examined here concern ethoxyquin levels, mainly measured in apple samples from the retail market. In this study about three hundred measurements, carried out on apples in Northern-Central Italy and recently published, are examined, with the purpose of defining the main characteristics of value statistical distribution and variability and to optimize sampling criteria. The analysis did not indicate the presence of significantly high levels or consequently significantly high risks; nevertheless, it pointed out some important aspects in data collection and evaluation. First, it appeared that the statistical distribution of data is typically nonsymmetrical, non-Gaussian, and characterized by a tail extending toward the high values. The logarithmic transformation of data appeared useful in order to obtain a Gaussian distribution. As a rule, the data variability appeared to be high. The frequency and distribution of values above the analytical threshold resulted in significant change, both in time and in space. The percentage of positive values (above the analytical threshold) appeared to vary up to a factor of 2-3, as analogously did their geometric mean.(ABSTRACT TRUNCATED AT 250 WORDS)

Environmental Monitoring↗

Information tools for exploratory data analysis in population pharmacokinetics.

For a group of individuals, population pharmacokinetic studies describe the interindividual variability through a statistical distribution. These studies conducted during the drug development serve as a useful marker of the safety of the drug, provide information that might be decisive for future experiments and, in a clinical context, help establish guidelines for optimal use in each patient. As complementary tools to the existing statistical and graphical techniques for population pharmacokinetic data analysis, indexes derived from information theory were used to select the most appropriate modelfor the statistical distribution, to detect atypical individuals, and to screen influential covariates. The rationale for using these indexes is shown using simulated and real data.

Humans↗

Artificial neural nets: dependence of the EEG amplitude's probability distribution on statistical parameters.

The statistical laws governing the output of a population of unitary generators are not explicit with regard to the effect of population size and properties of the individual generators on the summed activity. Experimental work was therefore undertaken with artificial nerve nets, the activity of which simulates with a high degree of realism individual nerve cells and the electroencephalogram. It was found that the summed activity is not affected by the statistical properties of single generators even in nets of only 200-1000 elements. On the other hand, the output of the net is highly sensitive to the level of connectivity between individual generators. When connectivity is low, the summed output is distributed in normal (Gaussian) fashion. The output of the net becomes less and less Gaussian with increase in coupling between the generators.

Animals↗

Quantification of biological variability.

Pharmacokinetic models are usually developed to describe the kinetic behaviour of the chemical compounds in an average human body. There are however many situations were the effects of variations in a given pharmacokinetic parameter would be of interest. For example, in biological monitoring, the variability of biological data is a critical parameter when relating air and biological measures of an individual exposure. This paper reviews two possible approaches for the simulation of such variability in occupational pharmacokinetics. In the first, a simple one-compartment model is used together with statistical distributions for the intake and elimination of the compounds involved. Based on realistic distributions, this simple model is applied to the comparison of biological and air monitoring to estimate workers' exposure. The second involves a seven-compartment physiologically based pharmacokinetic model, which includes provision of the means to input satistical distributions for some of the parameters: exposures, physical workload, body height, body weight, liver function and renal function. It makes it possible to predict the pharmacokinetic response of groups of workers, who differ in their exposures and in their physiological parameters. Realistic statistical distributions are then used to describe biological monitoring variability. The advantages and disadvantages of both the simple pharmacokinetic model and the physiological model are discussed in the context of predicting and understanding variability in occupational situations. Other potential developments are also considered.

Environmental Monitoring↗

Human choriogonadotropin (hCG): comparisons between determinations of intact hCG, free hCG beta-subunit, and "total" hCG + beta in serum during the first half of high-risk pregnancy.

We have studied the concentrations of intact human choriogonadotropin (hCG) and the free hCG beta-subunit in blood samples from singleton pregnancies at risk for habitual or threatened abortion. The samples were obtained weekly between the 6th and 12th weeks and in the 14th and 16th weeks of gestational age. The concentrations of intact hCG, of the free hCG beta-subunit, and of "total" hCG (i.e., intact hCG and the free hCG beta-subunit: hCG + beta) were measured in serum by specific immunoassays. The distributional statistics (the 5th, 50th, and 95th percentiles) of "total" hCG + beta and of intact hCG showed very similar patterns, whereas the response curves for the free hCG beta-subunit showed very much lower serum concentrations. From these data we also estimated distributional statistics of the percent molar ratios of free hCG beta-subunit to intact hCG. We conclude that (a) the relatively small proportion of free hCG beta-subunit in serum during the first half of singleton pregnancy is far too low to interfere with the applied "total" hCG assay, as compared with the serum values obtained for intact hCG, and (b) the percent molar ratios of free hCG beta-subunit to intact hCG, or to "total" hCG + beta, never exceeded 1.0% throughout the period of pregnancy studied.

Abortion, Threatened↗

Incubation period of Creutzfeldt-Jakob disease in human growth hormone recipients in France.

OBJECTIVE: To estimate the statistical distribution of the incubation period of Creutzfeldt-Jakob disease (CJD) in human growth hormone (hGH) recipients in France. BACKGROUND: Published papers suggest that the median incubation period of hGH-related CJD is approximately 15 years, but there are as yet no statistical data that support this assertion. METHODS: Of the 1,361 hGH recipients who were included in this study, 55 had developed CJD at the time of the study. Individual data on hGH treatment history were available. Different mathematical models were used to estimate the statistical distribution of the incubation period. One main feature of the models was to take into account the occurrence of future CJD cases. RESULTS: Models showed that the mean incubation period was 9 to 10 years, and the 95th percentile of the distribution was 15 to 16 years. Data and models indicated that the incubation period was significantly shorter in homozygotes at codon 129 of the prion protein gene than in heterozygotes. CONCLUSIONS: The short mean incubation period of CJD in French hGH recipients may be due to high infectivity in hormone lots. Estimates of the 95th percentile indicate that the number of hGH-related CJD cases may continue to increase in the coming years.

Creutzfeldt-Jakob Syndrome↗

CD and 1H-n.m.r. studies on the side-chain conformation of tyrosine derivatives and tyrosine residues in di- and tripeptides.

Tyrosine, tyrosine peptides and derivatives, in total 11 species, were selected as models for the study of optical properties (1Lb band of phenolic group) and side-chain arrangement (rotamers around C alpha-C beta bond) of tyrosine as a function of chemical structure and pH effects. Circular dichroism spectra between 240 and 320 nm and n.m.r. spectra were recorded for the different ionization states. Results are discussed in terms of charge effects from N- and C-terminal groups and local conformation influence on 1Lb band of the phenolic chromophore and on distribution of rotamer populations in side-chain of tyrosine. Fractions of rotamer populations were estimated from alpha-beta proton-proton coupling constants and, in the cases of tyrosine and N-acetyl-tyrosine, from 15N-beta nitrogen-proton coupling constants, which allow the stereospecific assignment of the beta and beta' protons. The rotamer populations of tyrosine, averaged from all the data of the samples In solution, were then compared with their statistical distribution in th solid state. Interestingly, agreement is excellent when we refer to crystal of tyrosine, tyrosine derivatives or small peptides (31 samples) and poor in the case of proteins. This leads to a discussion on both the validity of using statistical distributions of rotamers in proteins as reference for rotamer preferences inside small peptides in solution and the choice of the appropriate Jg and Jt values in Pachler's approach. The possible existence of a correlation between ellipticity and rotamer populations for such samples is examined.

Circular Dichroism↗

[Distribution pattern, statistical analysis and correlation of selenium levels in swine selenium-indicating organs].

There is a potential risk of excessive selenium levels in organs of swine, resulting in toxicity and residues in pork, or selenium deficit. Therefore, random selenium mean values in "selenium-indicating" organs of pigs selected from suspicious populations were compared with mean and limiting values (reference or normal values) recorded from animals with intact metabolism. Prerequisites required for such comparative assessment included the availability of estimated variance values and knowledge of the presence of abscence of agreement between normal distribution and empirical frequency distribution for the population concerned. Knowledge must be available also on the informative value of measured selenium data in blood plasma and their relevance to the general selenium situation in the organism and muscle at large. These were some of the problems studied by determining selenium levels in the liver, kidneys, blood plasma, and M. longissimus dorsi. Organic selenium concentrations were found to be distributed with right axis deviation but almost normal. The parameters established were typical of the majority of data known from literature. Those date, however, are quite variable, so that the need for independently prepared reference values cannot be abandoned. Correlation analysis showed reciprocal relationships between selenium levels in blooc plasma, liver, and muscles but much less correlation between these, on the one hand, and selenium in kidneys, on the other. The correlations between blood plasma and muscle selenium were close enough to take blood plasma values recorded from the living animal as reference from which to draw conclusions as to the muscular selenium state.

Animals↗

Sleep and purposive behavior: inverse deviations from randomness of neuronal firing patterns in the feline thalamus. A new form of homeostasis?

In behaving cats trained to press a bar for small aliquots of milk reward, single neuronal firing patterns were monitored from the nucleus reticularis (NR) thalami during bar bressing (BP), subsequent quiet wakefulness with EEG spindles (S- QW ), grooming behavior (GR) and slow-wave sleep (SWS). The temporal patterns in the neuronal spike trains were analyzed using a non-parametric method based on relative relations between sequential spike intervals. The deviations of pattern occurrences from the random model were quantified. During BP, specific patterns occurred much more often while others occurred much less often than predicted by the random model. Patterns that were dominant during BP, were selectively suppressed or virtually eliminated during S- QW , GR and SWS, despite the increased firing rate; and, vice versa, patterns that were suppressed below chance level during BP, became dominant during S- QW , GR and SWS. The magnitudes of these inversions of the statistical distribution of patterns were not random but graded and positively correlated, thus indicating that they were homeostatically controlled. Since the inversions were already evident shortly after the satiated ceased bar pressing, they may be related to the 'need' for sleep. On the basis of the known mechanisms of pattern generation and changes in receptors for putative transmitters, it was postulated that the inversions of pattern distribution are related to the recuperative function of SWS, i.e. resensitization of receptors that had been desensitized during the animal's stereotypic BP performance. The NR and other neuronal ensembles seem to constitute an oscillatory system with two modes of reciprocal connectivities : one is supporting wakefulness and emission of specific firing patterns, and the other is incompatible with wakefulness and instead is associated with inversion of statistical distribution of firing patterns and recuperative function of SWS.

Animals↗

Mechanisms of CML hyporesponsiveness in long-term renal allograft recipients.

Long-term, HLA disparate, renal allograft recipients were assessed by a dose-dependent CML (cell-mediated lympholysis) assay for evidence of donor-specific CML hyporesponsiveness. The frequency of cytolytic T-cell (CTL) precursors capable of responding to donor alloantigen was also examined by a limiting-dilution assay and application of Poisson distribution statistics. Four recipients were found to have depressed CML responses against donor class I HLA antigens (mean 2-5% specific lysis), whereas significant responses against third party targets were noted (15-60% specific lysis). These data are consistent with an antigen-specific defect in the recipient CTL effector mechanism. To determine whether or not this may be due to a deletion of anti-donor alloreactive cells, a sensitive limiting-dilution assay was developed in conjunction with Poisson distribution statistics to obtain the frequency of both anti-donor and anti-third party CTLp present in recipient PBLs. A simultaneous reduction in the number of alloreactive clones and the presence of an active suppressor population were defined, suggesting that several mechanisms may operate concurrently in long-term renal allograft recipients with well-functioning grafts.

Cytotoxicity, Immunologic↗

Determination of fluid and gel domain sizes in two-component, two-phase lipid bilayers. An electron spin resonance spin label study.

The average sizes of fluid and gel domains in the two-component, two-phase system formed from mixtures of dimyristoyl phosphatidylcholine and distearoyl phosphatidylcholine were determined from an analysis of the electron spin resonance spectral lineshapes of a dimyristoyl phosphatidylcholine-nitroxide spin label as a function of spin label concentration. The ratio, R, of the intensities measured at two magnetic field strengths was found to be diagnostic of a statistical distribution of spin labels in disconnected domains. R is defined as V'/2Vpp, where Vpp is the maximum intensity and V' is the intensity at a position in the wings of a first derivative electron spin resonance line that is a constant multiple of the peak-to-peak linewidth. The intensity ratio for Gaussian or Voigt lineshapes is less than or equal to the value for a Lorentzian lineshape. The intensity ratio was found to be greater than the value for a Lorentzian line when spectra from disconnected domains containing a statistical distribution of spin labels undergoing spin-spin interactions were summed. The intensity ratio, R, calculated by spectral simulations as a function of the average number of labels per domain, N, was found to increase to a maximum with increasing N and then to decrease. The dependence on spin label concentration of the experimentally measured intensity ratios paralleled this predicted behavior. A method is presented to calculate the average number of lipids per fluid or gel domain based on a knowledge of R, and of the distribution of the spin label between the fluid and gel phases determined from the phase diagram. The results demonstrate that the number of lipids per domain increases linearly from a fixed number of nucleation sites, as the fraction of the phase that is disconnected increases. At any given mole fraction of the particular phase, the gel domains are bigger than the fluid domains because they have a lower nucleation density. The results also suggest that the disconnected domains are, in most cases, nonrandomly distributed in the plane of the bilayer.

Dimyristoylphosphatidylcholine↗

On the correct determination of reference values for serum antibodies against pigeon serum antigen using a group of healthy blood donors.

An enzymatic immunoassay was developed in order to evaluate the statistical distribution of IgG serum antibodies against pooled pigeon sera antigen in 102 healthy blood donors (HBD). A non-normal distribution was obtained as demonstrated by abnormal values of skewness (2.02) and kurtosis (6.50). A cut-off point (0.120) was determined from the mean plus 2 standard deviations of the optical density values obtained in the HBD group. This value was able to segregate 94% of subjects. However, when calculation of the mean less 2 SD was performed to delimit 95% of the samples, an aberrant negative value was obtained. In contrast, when the nonparametric method of percentile calculation was applied, an optical density value of 0.130 discriminated 97.5% of samples. In addition, the interval between p97.5 and p2.5 delimited 95% of samples. We conclude that when reference values and cut-off point are determined from an enzymatic immunoassay, careful analysis of the statistical distribution of reference values is necessary in order to avoid the inappropriate application of parametric procedures as demonstrated in this study for antibodies against pigeon serum antigens.

Adult↗

Generation, description and storage of dendritic morphology data.

It is generally assumed that the variability of neuronal morphology has an important effect on both the connectivity and the activity of the nervous system, but this effect has not been thoroughly investigated. Neuroanatomical archives represent a crucial tool to explore structure-function relationships in the brain. We are developing computational tools to describe, generate, store and render large sets of three-dimensional neuronal structures in a format that is compact, quantitative, accurate and readily accessible to the neuroscientist. Single-cell neuroanatomy can be characterized quantitatively at several levels. In computer-aided neuronal tracing files, a dendritic tree is described as a series of cylinders, each represented by diameter, spatial coordinates and the connectivity to other cylinders in the tree. This 'Cartesian' description constitutes a completely accurate mapping of dendritic morphology but it bears little intuitive information for the neuroscientist. In contrast, a classical neuroanatomical analysis characterizes neuronal dendrites on the basis of the statistical distributions of morphological parameters, e.g. maximum branching order or bifurcation asymmetry. This description is intuitively more accessible, but it only yields information on the collective anatomy of a group of dendrites, i.e. it is not complete enough to provide a precise 'blueprint' of the original data. We are adopting a third, intermediate level of description, which consists of the algorithmic generation of neuronal structures within a certain morphological class based on a set of 'fundamental', measured parameters. This description is as intuitive as a classical neuroanatomical analysis (parameters have an intuitive interpretation), and as complete as a Cartesian file (the algorithms generate and display complete neurons). The advantages of the algorithmic description of neuronal structure are immense. If an algorithm can measure the values of a handful of parameters from an experimental database and generate virtual neurons whose anatomy is statistically indistinguishable from that of their real counterparts, a great deal of data compression and amplification can be achieved. Data compression results from the quantitative and complete description of thousands of neurons with a handful of statistical distributions of parameters. Data amplification is possible because, from a set of experimental neurons, many more virtual analogues can be generated. This approach could allow one, in principle, to create and store a neuroanatomical database containing data for an entire human brain in a personal computer. We are using two programs, L-NEURON and ARBORVITAE, to investigate systematically the potential of several different algorithms for the generation of virtual neurons. Using these programs, we have generated anatomically plausible virtual neurons for several morphological classes, including guinea pig cerebellar Purkinje cells and cat spinal cord motor neurons. These virtual neurons are stored in an online electronic archive of dendritic morphology. This process highlights the potential and the limitations of the 'computational neuroanatomy' strategy for neuroscience databases.

Algorithms↗

Body mass index reference values (mean and SD) for Swedish children.

UNLABELLED: Body mass index (BMI) is an important indicator of nutritional status. Many studies have been done to present BMI reference values in centile values rather than mean and SD values since its statistical distribution is positively skewed. Both height and weight growth charts are usually available in terms of mean and 1, 2 and 3 SD around the means; it would be of clinical value to produce BMI reference charts in a similar way. The aim of this work was to derive the mean and +/- 1, 2 and 3 SD BMI reference ranges as a supplement to the BMI centile reference values published previously for the same group of Swedish children. The method was based on an age-dependent Box transformation, and the beta-value was given as a third-degree polynomial function over the paediatric age. The BMI reference values can be given from mathematical functions in addition to values for specific ages. CONCLUSION: The BMI reference values and charts derived as described effectively reflect the nature of the variant age-dependent positive skewed statistical distribution of BMI values in the population, and can serve as a valid supplementary tool in the evaluation of growth and nutrition during paediatric years.

Adolescent↗

Analysis of strain-induced EPR-line shapes and anisotropic spin-lattice relaxation in a [2Fe-2S] ferredoxin.

The electron paramagnetic resonance spectrum of the [2Fe-2S]1+(2+;1+) cluster in spinach-leaf ferredoxin has been measured at four microwave frequencies from 1 to 35 GHz. Using a modified g-strain formula, the asymmetrical spectrum has been simulated in detail without the assumption of signal multiplicity. In all but the lowest frequency bands the line width is dominated by an extremely anisotropic g-shift distribution, caused by a statistical distribution in dislocation strains. The crossover point of domination by unresolved proton splittings is around 2 GHz. The angle-dependent elasticity of the cluster can be related to an anisotropy in the spin-lattice relaxation rate. Intensity behaviour under continuous saturation, at temperatures in the two-phonon region, is in qualitative agreement with elementary theory. On the basis of these results it is argued that biochemists should be aware of the questionable nature of some ad hoc assumptions commonly made to interpret EPR of metalloproteins. Specifically, a physically meaningful determination of the number and stoicheiometry of distinguishable compounds, represented in a complex spectrum, may well require more advanced theoretical tools than the frequently employed deconvolution in symmetrical Gaussians with associated unique relaxation times.

Electron Spin Resonance Spectroscopy↗