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At least 433 records · Page 24Linked to original sources

PubMed2003

Conformational flexibility of the group B meningococcal polysaccharide in solution.

To elucidate the role of secondary structure in the immune response against alpha(2-->8)-linked polysialic acid, the capsular polysaccharide of Group B meningococci, we have investigated its solution dynamics by using specific models of molecular motion and hydrodynamic modeling to interpret experimental NMR data. (13)C-[(1)H] NMR relaxation times and steady-state NOE enhancements were measured for two aqueous solutions of alpha(2-->8)-linked sialic acid polysaccharides. Each contained a unique distribution of polysaccharide chain lengths, with average lengths estimated at 40 or 400 residues. Models for rigid molecule tumbling, including two based on helical conformations proposed for the polysaccharide,(31) could not explain the NMR measurements. In general for these helices, the correlation times for their overall tumbling that best account for the NMR data correspond to polysaccharide chains between 9 and 18 residues in length, far short of the average lengths estimated for either solution. The effects of internal motions incorporated into these helices was modeled with an effective correlation time representing helix tumbling as well as internal motion. This modeling demonstrated that even with extreme amounts of internal motion, "flexible helices" of 25 residues or more still could not produce the NMR measurements. All data are consistent with internal and segmental motions dominating the nuclear magnetic relaxation of the polysaccharide and not molecular tumbling. Statistical distributions of correlation times have been found specifically for the pyranose rings, linkage groups, and methoxy groups that can account for the measured relaxation times and NOE enhancements. The distributions suggest that considerable flexibility attends the polysaccharide in solution, and the ranges of motional frequencies for the linkage groups and pyranose rings are comparable. We conclude that the Group B meningococcal polysaccharide is a random coil chain in solution, and therefore, does not have antigenic epitopes dependent upon a rigid, ordered conformation.

Bacterial Capsules↗

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↗

PubMed2006

Impact of correlation between pesticide parameters on estimates of environmental exposure.

Monte Carlo techniques are increasingly used in pesticide exposure modelling to evaluate the uncertainty in predictions arising from uncertainty in input parameters and to estimate the confidence that should be assigned to modelling results. The approach typically involves running a deterministic model repeatedly for a large number of input values sampled from statistical distributions. A key decision in setting up a probabilistic analysis is whether there is correlation between any of the inputs to the analysis. Pesticide properties are often the most sensitive in exposure assessment. Analysis of the literature demonstrated that there are examples of both positive and negative correlation between the sorption and degradation behaviour of a pesticide, but that general trends are not apparent at present. The inclusion of even weak correlation between sorption and degradation was found to greatly influence a probabilistic analysis of leaching through soil. Correlation will reduce the predicted extent of leaching for pesticides, and it is recommended to set the correlation to zero unless the experimental data support an alternative assumption (i.e. where the correlation is statistically significant (P <or= 0.05) and experimental artefacts can be excluded).

Environmental Exposure↗

PubMed2004

Exploratory data analysis of the multilevel anthropogenic copper cycle.

A comprehensive multilevel contemporary cycle for stocks and flows of copper is analyzed by the tools of exploratory data analysis (EDA). The analysis is performed at three discrete spatial levels--country (56 countries or country groups that comprise essentially all anthropogenic stocks and flows of copper), eight world regions, and the planet as a whole. Among the most interesting results are the following: (1) EDA is employable and valuable for use in the analysis of material flows, especially those across multiple spatial levels; (2) All distributions of country-level stock and flow data are highly skewed, a few countries having large magnitudes, many having small magnitudes; (3) Rates of fabrication of copper-containing products for the countries are poorly correlated with rates of extraction, reflecting the fact that many countries that extract copper do not fabricate products from copper to any significant degree and vice versa; (4) Virtually all countries are adding copper to stock (in pipe, wire, etc.); These rates of addition are highly correlated with rates of copper entering use in all regions and are higher in regions under vigorous development; (5) With weak confidence, the rate of copper landfilling by regions is about one-half the rate of copper discarded; (6) The statistical distributions of both country-level and regional-level copper cycle parameters have successively lower standard deviations at later life stages; and (7) Copper flow distributions at different life stages tend to reflect those of lower spatial level extreme values, but Asia's and Europe's regional patterns are much more reflective of country-level distributions as a whole.

Asia↗

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↗

PubMed2003

Rank order metrics for quantifying the association of sequence features with gene regulation.

MOTIVATION: Genome sequences and transcriptome analyses allow the correlation between gene regulation and DNA sequence features to be studied at the whole-genome level. To quantify these correlations, metrics are needed that can be applied to any sequence feature, regardless of its statistical distribution. It is also desirable for the metric values to be determined objectively, that is, without the use of subjective threshold values. RESULTS: We compare two metrics for quantifying the correlation of DNA sequence features with gene regulation. Each of the metrics is calculated from a rank-ordering of genes based on the value of the sequence feature of interest. The first metric is the area under the curve for a receiver operator characteristic plot (ROC AUC), a common way of summarizing the tradeoff between sensitivity and specificity for different values of a prediction criterion. We call the second metric the mean normalized conditional probability (MNCP). The MNCP can be thought of as the predictive value of the sequence feature averaged over all regulated genes. The statistical significance (P-value) of each metric can be estimated from simulations. Importantly, the P-value of the MNCP metric is less dramatically affected by the presence of false positives among the set of co-regulated genes than is the ROC AUC. This is especially useful in analyzing gene sets identified by DNA microarray analysis because such data cannot distinguish direct regulation by transcription factor binding from indirect regulation. We demonstrate that these two metrics, taken together, are useful tools for defining the binding site representation and regulatory control regions that best explain the difference between genes that are regulated by a given transcription factor and those that are not. Applications to other gene features are also described. AVAILABILITY: A Python program for calculating the ROC AUC and MNCP metric values given input rank orders is available from ftp://ftp.bs.jhmi.edu/users/nclarke/MNCP/

Algorithms↗

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↗

PubMed2005

Asymmetric distribution of cooperativity in the binding cascade of normal human hemoglobin. 2. Stepwise cooperative free energy.

Stepwise cooperative free energies and intermediate Hill coefficients are used to assess the presence of noncooperative sequences in the database of binding free energies previously obtained for the eight partially ligated intermediates of human hemoglobin, encompassing a variety of hemesite analog substitutions. This analysis is prompted by the observed noncooperative binding of two ligands to hemoglobins that are partially substituted with Zn2+-heme, an analog of deoxy Fe2+-heme (Holt et al. (2005) Biochemistry 44, XXXXX). The results show that noncooperative binding sequences are observed in all hemesite analog studied to date. The noncooperative binding observed in (alpha2Znbeta2FeO2) and (alpha2FeO2beta2Zn) is therefore not a Zn-specific substitution artifact. One of several binding sequences from singly to triply ligated hemoglobin is also observed to occur with little or no positive cooperativity. These results demonstrate the variability possible among different ligation pathways in a highly cooperative multi-subunit system such as hemoglobin. As a direct consequence of this variability, differences among ligation pathways are not always detectable using cooperativity functions based on statistical distributions, such as the Hill coefficient n(H). The limitations of Hill coefficient analysis in evaluating cooperativity in intermediates of complex systems is contrasted with the utility of the stepwise binding parameters.

Energy Transfer↗

PubMed2005

Thermodynamic functions of liquid water calculated from the temperature evolution of the vibration spectrum contour.

Configurational contributions of hydrogen bonds to thermodynamic properties of water (internal energy, entropy, and heat capacity) are calculated on the basis of statistical distributions of frequencies of the OH vibrations of liquid water, calculated earlier from the experimental Raman spectra in frameworks of the fluctuation theory of hydrogen bonding. Distributions of the energy of hydrogen bonds are determined. It is shown by comparison with computer experiments that previously established dependence of energy on frequency, E(nu), must be considered in this formalism as the effective energy of hydrogen bonding averaged over those configurations of hydrogen bridge O-H...O which lead to the given frequency nu in the vibrational spectrum. Contribution of van der Waals interactions not affecting the frequency shift to heat capacity is evaluated.

Entropy↗

PubMed2004

Bayesian mixture model based clustering of replicated microarray data.

MOTIVATION: Identifying patterns of co-expression in microarray data by cluster analysis has been a productive approach to uncovering molecular mechanisms underlying biological processes under investigation. Using experimental replicates can generally improve the precision of the cluster analysis by reducing the experimental variability of measurements. In such situations, Bayesian mixtures allow for an efficient use of information by precisely modeling between-replicates variability. RESULTS: We developed different variants of Bayesian mixture based clustering procedures for clustering gene expression data with experimental replicates. In this approach, the statistical distribution of microarray data is described by a Bayesian mixture model. Clusters of co-expressed genes are created from the posterior distribution of clusterings, which is estimated by a Gibbs sampler. We define infinite and finite Bayesian mixture models with different between-replicates variance structures and investigate their utility by analyzing synthetic and the real-world datasets. Results of our analyses demonstrate that (1) improvements in precision achieved by performing only two experimental replicates can be dramatic when the between-replicates variability is high, (2) precise modeling of intra-gene variability is important for accurate identification of co-expressed genes and (3) the infinite mixture model with the 'elliptical' between-replicates variance structure performed overall better than any other method tested. We also introduce a heuristic modification to the Gibbs sampler based on the 'reverse annealing' principle. This modification effectively overcomes the tendency of the Gibbs sampler to converge to different modes of the posterior distribution when started from different initial positions. Finally, we demonstrate that the Bayesian infinite mixture model with 'elliptical' variance structure is capable of identifying the underlying structure of the data without knowing the 'correct' number of clusters. AVAILABILITY: The MS Windows based program named Gaussian Infinite Mixture Modeling (GIMM) implementing the Gibbs sampler and corresponding C++ code are available at http://homepages.uc.edu/~medvedm/GIMM.htm SUPPLEMENTAL INFORMATION: http://expression.microslu.washington.edu/expression/kayee/medvedovic2003/medvedovic_bioinf2003.html

Algorithms↗

PubMed1992

Stochastic population forecasts and their uses.

"The properties and uses of stochastic forecasts are discussed here. For linear stochastic projections, we show how the computation of forecast moments and the statistical distribution of forecasts depend on the multiplicative and autoregressive structure of the dynamics. Both scalar and vector projection methods are discussed, and their similarities are explored. Next we discuss the uses of stochastic forecasts, arguing that it is important to relate forecasts to the specific decision-making criteria of particular forecast users. The example of [the U.S. system of] Social Security is used to show how a dynamic programming approach may be used to explore alternative decisions in a probabilistic context."

Americas↗

PubMed2004

Measuring synchronization in neuronal networks for biosensor applications.

Cultures of neurons can be grown on microelectrode arrays (MEAs), so that their spike and burst activity can be monitored. These activity patterns are quite sensitive to changes in the environment, such as chemical exposure, and hence the cultures can be used as biosensors. One key issue in analyzing the data from neuronal networks is how to quantify the level of synchronization among different units, which represent different neurons in the network. In this paper, we propose a synchronization metric, based on the statistical distribution of unit-to-unit correlation coefficients. We show that this synchronization metric changes significantly when the networks are exposed to bicuculline, strychnine, or 2,3-dioxo-6-nitro-l,2,3,4-tetrahydrobenzoquinoxaline-7-sulphonamide (NBQX). For that reason, this metric can be used to characterize pharmacologically induced changes in a network, either for research or for biosensor applications.

Action Potentials↗

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↗

PubMed2005

A random polymer model of the statistical significance of structure alignment.

A theory for assessing the statistical significance of structure alignment is developed using a random or Gaussian chain model. In this model, we consider the statistical distribution of the root mean square distance (rmsd) of the alignment between two random chains of equal length and common center of mass (referred to as Case 1). We demonstrate that the rmsd2 is distributed as a sum of independent Gamma variables. Analytic results on the mean and variance of the rmsd2 are presented. Since rmsd is strongly dependent on the length, we define the dimensionless quantity, reduced rmsd, as the rmsd divided by the radius of gyration. We find that the reduced rmsd can be accurately approximated by an extreme value distribution (EVD) that is independent of chain length and of bond length. The parameters of the EVD can be calculated from the mean and the variance of the rmsd2. We also consider the case of two chains with a common center of mass that are then rotated to minimize the rmsd (Case 2). In this case, the distribution of reduced rmsd can again be accurately approximated by an EVD, which is independent of the chain length and expected bond length. This distribution is used to calculate the p-value for a given reduced rmsd. Performing an analogous comparison for proteins, we find that approximately M(nu) and nu = 0.28 and 0.32 for Case 1 and Case 2, respectively, where M is the chain length. This result for Case 2 exactly matches with previous scaling results and suggests that rmsd/M(nu)is an appropriate metric for protein structure alignment and will be independent of chain length. We also find that the new score roughly follows the EVD.

Computer Simulation↗

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↗

PubMed2006

Effect of anchoring groups on single-molecule conductance: comparative study of thiol-, amine-, and carboxylic-acid-terminated molecules.

We studied the effect of anchoring groups on the conductance of single molecules using alkanes terminated with dithiol, diamine, and dicarboxylic-acid groups as a model system. We created a large number of molecular junctions mechanically and analyzed the statistical distributions of the conductance values of the molecular junctions. Multiple sets of conductance values were found in each case. The I-V characteristics, temperature independence, and exponential decay of the conductance with the molecular length all indicate tunneling as the conduction mechanism for these molecules. The prefactor of the exponential decay function, which reflects the contact resistance, is highly sensitive to the anchoring group, and the decay constant is weakly dependent on the anchoring group. These observations are attributed to different electronic couplings between the molecules and the electrodes and alignments of the molecular energy levels relative to the Fermi energy level of the electrodes introduced by different anchoring groups. For diamine and dicarboxylic-acid groups, the conductance values are sensitive to pH due to protonation and deprotonation of the anchoring groups. Further insight into the binding strengths of these anchoring groups to gold electrodes is obtained by statistically analyzing the stretching length of molecular junctions.

Journal Article↗