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At least 253 records · Page 14Linked to original sources

PubMed1999

Selective assembly of cyclodextrins on poly(ethylene oxide)-poly(propylene oxide) block copolymers.

This paper presents a computational study on the formation of a molecular necklace formed by specific threading of cyclodextrins (CDs) on block copolymers. Structural as well as energetic principles for the selective complexation of alpha- and beta-cyclodextrin with poly(ethylene oxide)-poly(propylene oxide) block copolymers (PEO-PPO) are elucidated considering a diblock copolymer of equimolecular composition (PEO)4-(PPO)4 as guest. A non-statistical distribution of CDs, i.e. alpha-CDs primarily located on the PEO chain and beta-CDs on PPO blocks of the polymer, is based on a variety of structural features and energetic preferences considering both potential as well as solvation energies. This selectivity becomes already obvious considering 1:1 complexes between PEO and PPO monomers and the two CDs, but is increasingly evident when calculating higher order ensembles. Besides the host-guest interaction, docking between CDs themselves is an important, also non-statistical, prerequisite for the self-assembly of highly ordered tubes. The formation of intermolecular hydrogen bonds between adjacent CDs in a tubular aggregate gives an important contribution to the overall stability of the molecular necklace. The net effect, based on the preferential interaction between host and guest as well as between the host molecules themselves, results in the formation of a stable, highly ordered macromolecular, multicomponent aggregate.

Cyclodextrins↗

PubMed1981

Analysis of the spatial organization of the cell: a statistical method for revealing the non-random location of an organelle.

A method is proposed for testing the randomness of the location of an organelle within a given area of a cell section. The approach chosen is to analyse the distance between this organelle and a specific point considered as a point of reference. The method consists of converting this distance into the ratio of one given area to another and comparing the statistical distribution of the converted values to the uniform distribution. This method has the advantage of being valid in the absence of any restrictive assumptions concerning the heterogeneity in size and/or shape of the collection of sections sampled. Detailed examples are given to illustrate the practical use of the method, and its possible extensions are discussed.

Cell Nucleolus↗

PubMed1997

Advances in statistical methods to map quantitative trait loci in outbred populations.

Statistical methods to map quantitative trait loci (QTL) in outbred populations are reviewed, extensions and applications to human and plant genetic data are indicated, and areas for further research are identified. Simple and computationally inexpensive methods include (multiple) linear regression of phenotype on marker genotypes and regression of squared phenotypic differences among relative pairs on estimated proportions of identity-by-descent at a locus. These methods are less suited for genetic parameter estimation in outbred populations but allow the determination of test statistic distributions via simulation or data permutation; however, further inferences including confidence intervals of QTL location require the use of Monte Carlo or bootstrap sampling techniques. A method which is intermediate in computational requirements is residual maximum likelihood (REML) with a covariance matrix of random QTL effects conditional on information from multiple linked markers. Testing for the number of QTLs on a chromosome is difficult in a classical framework. The computationally most demanding methods are maximum likelihood and Bayesian analysis, which take account of the distribution of multilocus marker-QTL genotypes on a pedigree and permit investigators to fit different models of variation at the QTL. The Bayesian analysis includes the number of QTLs on a chromosome as an unknown.

Bayes Theorem↗

PubMed1995

The mutational demography of protein C deficiency.

The geographical distribution and prevalence of 256 single base-pair substitutions (105 of them being different) within the coding region of the human protein C (PROC) gene were correlated with their initial likelihoods of generation. A significant positive correlation was observed between these "mutational likelihoods" and the geographical dispersal of the PROC gene lesions within and between 16 different countries. This relationship could be attributed to the fact that, with few exceptions, high dispersal was only exhibited by CG-->TG and CG-->CA transitions, i.e. those substitutions that are known to arise de novo at the highest frequency. The statistical distribution of mutational likelihoods was as predicted on the basis of the PROC cDNA sequence alone, allowing however for the redundancy of the genetic code. These findings suggest (1) that genetic drift and lesion-specific selection have been of relatively minor importance in determining the mutational spectrum observed in the PROC gene and (2) that most multiple reports of particular substitutions in different geographical locations appear to reflect recurrent mutation rather than identity-by-descent.

Blood Coagulation Disorders↗

PubMed2000

Learning overcomplete representations.

In an overcomplete basis, the number of basis vectors is greater than the dimensionality of the input, and the representation of an input is not a unique combination of basis vectors. Overcomplete representations have been advocated because they have greater robustness in the presence of noise, can be sparser, and can have greater flexibility in matching structure in the data. Overcomplete codes have also been proposed as a model of some of the response properties of neurons in primary visual cortex. Previous work has focused on finding the best representation of a signal using a fixed overcomplete basis (or dictionary). We present an algorithm for learning an overcomplete basis by viewing it as probabilistic model of the observed data. We show that overcomplete bases can yield a better approximation of the underlying statistical distribution of the data and can thus lead to greater coding efficiency. This can be viewed as a generalization of the technique of independent component analysis and provides a method for Bayesian reconstruction of signals in the presence of noise and for blind source separation when there are more sources than mixtures.

Algorithms↗

PubMed1996

Using neural networks to model conditional multivariate densities.

Neural network outputs are interpreted as parameters of statistical distributions. This allows us to fit conditional distributions in which the parameters depend on the inputs to the network. We exploit this in modeling multivariate data, including the univariate case, in which there may be input-dependent (e.g., time-dependent) correlations between output components. This provides a novel way of modeling conditional correlation that extends existing techniques for determining input-dependent (local) error bars.

Economics↗

PubMed1991

Correlations between directional and orientational tuning of cells in cat striate cortex.

Simple (N = 284) and complex cells (N = 125) in the central projection area (0-5 degrees eccentricity) of the striate cortex of cats were stimulated with moving light bars and the responses to different directions of movement were recorded and plotted as polar-plots. Fourier analysis was applied to polar plots (SDO-analysis, Wörgötter and Eysel 1987; Wörgötter et al. 1990) to determine the general sensitivity (S) of the cells to visual stimulation, the directional (D) and orientational (O) tuning strength as well as preferred direction (PD) and preferred orientation (PO). Statistical distributions of the S, D and O parameters were determined for simple and complex cells of the cortical layers II-VI. Simple cells were more strongly tuned for direction and orientation than complex cells, whereas complex cells had a greater general sensitivity to visual stimulation. Directional tuning was significantly stronger in layer VI than in layer IV simple cells, otherwise no differences were detected between these two layers. We found that cells with large D and small O components are generally rare. The D and O components were plotted against each other to determine any possible correlation between the tuning strengths. The correlations were statistically significant for simple and complex cells but the correlation coefficients were very small (r less than 0.3). It is suggested that only a very weak coupling between directional and orientational tuning exists, preferentially in the deeper layer simple cells.

Animals↗

PubMed1986

A mathematical model of survival kinetics. I. Theoretical basis.

A mathematical model of mortality and survival kinetics is proposed based upon the two main aspects of survival data, namely, the rate of vitality reduction with age and its statistical distribution. Certain mathematical assumptions are made on the time-course of both vitality and its distribution. Then, these two aspects are integrated in a single model which can be used to describe survivorship, cumulative mortality or dying. The model is capable of fitting empirical curves even at very advanced ages, where the widely used Gompertz law fails. Examples are provided, derived from populations having rather different lifespans such as rotifers, flies, rats and horses. The model maintains one of the most interesting characteristics of Gompertz law, namely, the possibility to estimate the 'design constant for longevity' relating maximum lifespan to one of the parameters of the model. It also has the potential characteristics enabling it to be used to judge the statistical significance of the difference between two empirical survival curves.

Aging↗

PubMed1984

Simultaneous determination of trace elements in serum by energy-dispersive x-ray fluorescence spectrometry.

Energy-dispersive x-ray fluorescence is applied in the analysis of human serum to determine the concentrations of several elements simultaneously with minimal manipulation of the sample. The analytical procedure has been developed with standard sera, and standardization, detection limits, and reproducibility have been established. A 50-microL sample of diluted serum, to which an internal standard has been added, is deposited on a thin (4-microns thick) polypropylene film and analyzed by x-ray fluorescence. We report the statistical distributions of the concentrations of Fe, Cu, Zn, and Br obtained in the population (103 samples) studied, and report detection limits for the other 22 elements studied. The simplicity of the method, the high throughput, and the possibility of automating the measurements make this procedure suitable for screening large numbers of sera.

Bromine↗

PubMed1975

[Hereditary melanotic tumors of Drosophila. Determination of the tumorous transformation of larva hemocytes].

Two different phenomena contribute to the histogenesis of melanotic formations in tumoral strains of drosophila : an abnormal multiplication of certain blood cells and their encapsulation by normal hemocytes. The statistical distribution of melanotic tumors in populations of individuals submitted during precise periods of their life to the action of agents such as supraoptimal temperature or ionizing radiations, permits to suggest for the tumoral transformation of larval hemocytes in drosophila, the following mechanism : this transformation is caused by an event occuring in the cytoplasm and determined by the activity of a nuclear gene.

Animals↗

PubMed1998

Correlation of plasma clearance of 54 extensively metabolized drugs between humans and rats: mean allometric coefficient of 0.66.

PURPOSE: To evaluate the distribution of allometric exponents for relationship of total plasma clearance of 54 extensively metabolized drugs, with wide-ranging linear clearance values, between humans and rats, to provide a rationale for the observed data, and to discuss potential significance of the findings. METHODS: Human and rat plasma clearance values of 54 drugs with markedly different physicochemical properties were obtained from the literature. Standard allometric analysis was performed for each drug using both rat and human data. Unbound vs. total plasma clearances were obtained for 15 out of 54 drugs and their correlations between humans and rats were compared. RESULTS: The mean+/-SD of the allometric exponent for the 54 drugs studied is 0.660+/-0.190. The median clearance ratio based on unit body weight is 7.41 and the median exponent is 0.645. Excluding two outliers the correlation coefficient of plasma clearance between humans and rats was 0.745 (p < 0.0001). For the 15 drugs, use of unbound plasma clearance approach seems to significantly improve the correlation coefficient compared to total plasma clearance (0.940 vs. 0.841). CONCLUSIONS: The present study indicates that on average, humans and rats may eliminate extensively metabolized drugs at a rate similar to that expected from the allometric or body surface area relationship of basal metabolic rate between the two species. A simple statistical distribution hypothesis is used to rationalize the species difference in plasma drug clearance. Rat may serve as an useful animal model to predict (unbound) plasma clearance of drugs in humans.

Animals↗

PubMed1988

Distribution of embryos and 500-microM microspheres in the rabbit oviduct: controls for acute motion analysis during transport.

Distributions of embryos and 500-micron diameter microspheres were measured in the cleared oviducts of 32 rabbits at 8 intervals post coitus (pc) and normalized to percentage of isthmic length. By 18 h pc, 46% of the embryos had entered the isthmus and were denuded of the cumulus, while 55% of the microspheres had entered the isthmus. By 24 h pc, all embryos and microspheres were in the isthmus. At 72, 78, and 84 h pc, 6.5, 37, and 93% of embryos and 21, 73, and 95% of microspheres were in the cornu, respectively. The mean positions of embryos and microspheres progressed at approximately 1% of isthmic length per hour between 24 and 72 h pc. Throughout isthmic transport, embryos and microspheres in individual oviducts were tightly grouped and had similar statistical distributions. Although microspheres began to transfer into the uterine horns earlier than embryos, the data suggest that 500-micron microspheres can be used in studies to quantify discrete movements within the oviduct prior to 72 h pc. The data further suggest that opposing forces may be generated by contractile events that keep embryos grouped and possibly control their rate of progress through the oviduct.

Animals↗

PubMed1998

Understanding artificial neural networks and exploring their potential applications for the practicing urologist.

Artificial neural networks (ANNs) are complex mathematical models that are distantly based on the human neuronal structure. They are capable of modeling elaborate biologic systems without making assumptions based on statistical distributions. Preliminary work has been reported on their application in urology. The initial results have been promising, particularly as an additional tool in the detection of early prostate cancer using the ProstAsure Index, which has been the most extensively studied urologic ANN to date. We review the basic concepts behind ANNs and examine currently existing and potential future applications of this new dynamic technology both in urology and in general clinical medicine.

Clinical Medicine↗

PubMed1998

[Pressure-controlled mechanical ventilation: a simplified titration method of the extrinsic positive expiratory pressure].

OBJECTIVES: Extrinsic positive end-expiratory pressure (PEEPe) may improve gas distribution within the lungs, induce alveolar recruitment or, conversely, produce pulmonary overdistension, and modify the respiratory impedance. Under pressure-controlled mechanical ventilation (PCV) this phenomenon modifies the minute ventilation and the dynamic compliance of the respiratory system (Crs,dyn). This study was aimed to assess the incidence of a significant gain in Crs,dyn under the effect of PEEPe during PCV. STUDY DESIGN: Prospective, open, descriptive, case series study. PATIENTS: Surgical intensive care unit patients, under sedation, neuromuscular blockade and PCV because of severe hypoxaemia (ARDS or acute lung injury). METHODS: Four incremental levels of PEEPe (4 to 16 cmH2O) of 30 minute duration were applied. Crs,dyn, and PaO2/FIO2 were recorded at the end of each level of PEEPe. The resulting gain in Crs,dyn was calculated and considered as significant if it was greater than the upper limit of confidence (at 99.8%) of the statistical distribution of all the recorded gains. RESULTS: Thirty patients were included, median and extreme values (within brackets) of PaO2/FIO2 of 117 [53-230] and Crs,dyn without PEEPe of 29 [14.3-46.8] mL.cmH2O-1. Among the 120 recorded gains, a gain in Crs,dyn was found significant at least once in 15 tests of PEEPe out of 30. Within the two groups of patients, the increase in PaO2/FIO2 with incremental PEEPe was similar. The levels of PEEPe producing the greatest increase in Crs,dyn were not correlated with the increase in PaO2/FIO2. CONCLUSION: In 50% of the studied patients a significant gain in Crs,dyn was found, allowing a less traumatic PCV. These results suggest the clinical usefulness of this method of titration of PEEPe, which requires neither specific devices nor a disconnection of the patient.

Adult↗

PubMed1995

Adaptive control of drug dosage regimens using maximum a posteriori probability Bayesian fitting.

Optimal drug therapy can only be achieved if a drug is given in the right dosage regimen. Therefore the dosage regimen needs to be optimized, using the available information of the drug, the patient, and his disease. The optimization of drug therapy comprises two major steps: First, the clinician should define explicit therapeutic goals for each patient individually. Second, a strategy to achieve these goals with the greatest possible precision should be chosen. An overview of the optimization of drug therapy is presented, with special reference to maximum a posteriori probability (MAP) Bayesian fitting. Drug dosage optimization requires 1. measurement of a performance index related to the therapeutic goal, generally one or more plasma concentration measurements, 2. population pharmacokinetic parameters, including mean values, standard deviations, covariances and information on the statistical distribution, and 3. reliable software for adaptive control strategy and optimal dosage regimen calculation. The benefit of optimal drug therapy by adaptive control using MAP Bayesian fitting has been proven, resulting in improved patient outcome by improved efficacy of therapy and a reduction of adverse reactions, and in reduced costs, mainly due to a reduction of hospitalization. Newer strategies might replace the MAP Bayesian fitting procedure, if their advantage has been demonstrated convincingly, and if reliable and user-friendly software is available.

Bayes Theorem↗

PubMed1992

DNA damage caused by ionizing radiation.

A survey is given of continuous-time Markov chain models for ionizing radiation damage to the genome of mammalian cells. In such models, immediate damage induced by the radiation is regarded as a batch-Poisson arrival process of DNA double-strand breaks (DSBs). Enzymatic modification of the immediate damage is modeled as a Markov process similar to those described by the master equation of stochastic chemical kinetics. An illustrative example is the restitution/complete-exchange model. The model postulates that, after being induced by radiation, DSBs subsequently either undergo enzymatically mediated restitution (repair) or participate pairwise in chromosome exchanges. Some of the exchanges make irremediable lesions such as dicentric chromosome aberrations. One may have rapid irradiation followed by enzymatic DSB processing or have prolonged irradiation with both DSB arrival and enzymatic DSB processing continuing throughout the irradiation period. Methods for analyzing the Markov chains include using an approximate model for expected values, the discrete-time Markov chain embedded at transitions, partial differential equations for generating functions, normal perturbation theory, singular perturbation theory with scaling, numerical computations, and certain matrix methods that combine Perron-Frobenius theory with variational estimates. Applications to experimental results on expected values, variances, and statistical distributions of DNA lesions are briefly outlined. Continuous-time Markov chains are the most systematic of those radiation damage models that treat DSB-DSB interactions within the cell nucleus as homogeneous (e.g., ignore diffusion limitations). They contain virtually all other relevant homogeneous models and semiempirical summaries as special cases, limiting cases, or approximations. However, the Markov models do not seem to be well suited for studying spatial dependence of DSB interactions, which is known to be important in some situations.

Animals↗

PubMedDate not supplied

[Exposure levels of persons involved in cleaning-up after the Chernobyl AES accident and included in the Russian State Medical and Dosimetric Registry].

Theoretical and practical problems related to the dosimetric data verification for recovery workers at the Chernobyl NBB are considered. Approaches and conclusions presented in the paper of L.A. Ilyin at al, (1). By using probability theory it was clearly that the method of dose verification developed in the reviewed paper and based on delta-entropy of statistical distribution failed to be scientifically founded. It does not permit to prove the existence of non-random component in random sampling without additional assumptions. The main conclusion of the reviewed paper, that 60% of individual doses included in the all-russia state medical and dosimetric state registry (ARMDSR) differ from the real exposure doses, is analysed and quantitatively estimated for several group of recovery workers. Our results present evidence that ARMDSR data do not contain a considerable part of "distorted" values even if the above mentioned method to take as valid.

Humans↗

PubMed1987

Quantification and localization of galactose-specific binding sites in rat liver during postnatal development.

We investigated the number and distribution of galactose-specific binding sites in developing livers from suckling rats of various ages using Lac-BSA-Au5 (lactosylated bovine serum albumin adsorbed onto colloidal gold particles 5 nm in diameter) as electron-dense ligand, and performing transmission electron microscopy of the specimen. It has been reported that the number of galactose-specific binding sites increases rapidly during organ development post partum (p.p.) and this was ascribed to hepatocyte receptor increase only. We now have investigated in in situ and in vitro experiments whether the binding sites of identical sugar specificity but located on sinusoidal cells show the same increase in expression or are independently regulated. We therefore quantified the number of particles bound by isolated hepatocytes and liver macrophages and found a gradual increase of both binding activities with age, the binding levels of adult liver cells being reached at day 15 p.p. This was confirmed with experiments using in situ prefixed organs thus proving the validity of this finding also for the intact organ. In both sets of experiments--in vitro as well as in vivo--ligand was found binding statistically distributed as single particles on hepatocytes of all ages, whereas on liver macrophages the binding pattern changed during development. On liver macrophages from rats 15 days of age ligand binding occurs in the preclustered pattern described for macrophages from adult rat livers whereas liver macrophages of newborn rats express a different binding pattern: they bind the ligands mostly as single particles with only few and small microaggregates.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗