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PubMed1995

Interactions between food components and drugs. Part 3. Interactions between pectin and propranolol.

Bioavailability of drugs can be affected distinctly by interactions with food components. Effects of structural parameters of the soluble dietary fiber pectin on lipid-membrane transport of propranolol (1) was investigated in vitro using a two-compartment model with a dodecanol-collodium membrane at pH 7.2 and 37 degrees C. Starting from practically fully esterified citrus pectin two series of defined and in their structural parameters gradually varied pectins were prepared. In presence of pectins with a blockwise distribution of free COOH-groups the portion of permeated 1 is significantly diminished with a decreasing degree of esterification (DE). On the other hand, only in the smallest DE pectins having statistically distributed free COOH-groups seemed to affect the transport rate of 1. The viscosity of the tested pectins possessed no significant influence on the passage of 1.

Biological Availability↗
PubMed1996

Quantitative anatomy, synaptic connectivity and physiology of amacrine cells with glucagon-like immunoreactivity in the turtle retina.

Although a wide variety of neuropeptides have been localized in vertebrate retinas, many questions remain about the function of these peptides and the amacrine cells that contain them. This is because many of these peptidergic amacrine cells have been studied using only immunocylochemical techniques. To address this limitation, the present study used a combination of quantitative anatomy, biochemistry and electrophysiology to examine amacrine cells in the turtle retina that contain the neuropeptide glucagon. In the turtle retina, there is a small population of 2500 glucagonergic amacrine cells, which probably represents < 1% of the total number of amacrine cells. Circular distribution statistics indicated that many of these tristratified amacrine cells had asymmetric dendritic arborizations that were radially oriented toward the retinal periphery. The cells were found to have similar dendritic coverage factors, to be distributed in a non-random arrangement in all regions of the retina, and to peak in density in the visual streak region. Electron microscopic studies indicated that glucagonergic amacrine cells made synaptic contacts primarily with other amacrine cells, and small numbers of bipolar cells. The synaptic inputs and outputs were balanced in the inner strata of the inner plexiform layer, and were biased toward synaptic outputs in the outer strata of the inner plexiform layer. These contacts involved small unlabelled synaptic vesicles, and not the large labelled dense core vesicles also found in these neurons. The biochemical studies indicated that glucagon could be released from the retina in a calcium dependent manner by high potassium stimulation. The electrophysiology found no color opponency, and the glucagonergic amacrine cells gave sustained hyperpolarizing responses to small stimulation spots and had antagonistic surrounds. The results of these studies suggest that there are significant regional specializations of glucagonergic amacrine cells, and that they may provide OFF-modulation in interactions between the ON-and OFF-centre visual pathways in the turtle retina.

Animals↗
PubMed2006

Inbreeding reduces power-law scaling in the distribution of fluctuating asymmetry: an explanation of the basis of developmental instability.

The study of fluctuating asymmetry has been controversial because of conflicting results found in much of the primary literature. It has been suggested that the source of this conflict is the fact that the basis of fluctuating asymmetry is poorly understood and that, as a consequence, methodology of fluctuating asymmetry studies may be flawed. A new model for the phenomenological basis of fluctuating asymmetry, that variation in fluctuating asymmetry is in large part due to the random exponential growth of cell populations (geometric Brownian motion) that are terminated randomly around a genetically programmed development time, is presented here. If termination of development has a genetic component, then scaling effects and kurtosis in the distribution of fluctuating asymmetry should increase with genetic redundancy of the population. This model prediction was tested by comparing the distribution of multivariate size and shape fluctuating asymmetry in large samples collected from both wild populations and four moderately inbred lines of Drosophila simulans. It was found that while wild populations were best described by a lognormal distribution with power-law scaled tails, the inbred lines derived from the wild stock were dramatically normalized (half-normal) in three of four cases. As predicted, the scaling exponent of the upper tail of the distribution of fluctuating asymmetry increased with inbreeding while the kurtosis and mean fluctuating asymmetry decreased with inbreeding. The model suggests an additional explanation of leptokurtosis in fluctuating asymmetry. Kurtosis and scaling of the statistical distribution of fluctuating asymmetry in a population is related directly to genetic differences between individuals and these differences affect their ability to buffer the process of development against random perturbations.

Animals↗
PubMed2000

Fluctuation-response relations for multitime correlations

We show that time-correlation functions of arbitrary order for any random variable in a statistical dynamical system can be calculated as higher-order response functions of the mean history of the variable. The response is to a "control term" added as a modification to the master equation for statistical distributions. The proof of the relations is based upon a variational characterization of the generating functional of the time correlations. The same fluctuation-response relations are preserved within moment closures for the statistical dynamical system, when these are constructed via the variational Rayleigh-Ritz procedure. For the two-time correlations of the moment variables themselves, the fluctuation-response relation is equivalent to an "Onsager regression hypothesis" for the small fluctuations. For correlations of higher order, there is a further effect in addition to such linear propagation of fluctuations present instantaneously: the dynamical generation of correlations by nonlinear interaction of fluctuations. In general, we discuss some physical and mathematical aspects of the Ansatze required for an accurate calculation of the time correlations. We also comment briefly upon the computational use of these relations, which is well suited for automatic differentiation tools. An example will be given of a simple closure for turbulent energy decay, which illustrates the numerical application of the relations.

Journal Article↗
PubMed1980

Influence of analytical quality on the diagnostic power of a single S-CK B test in patients with suspected acute myocardial infarction.

We have compared tow theoretical methods for assessing the effects of changing analytical quality of a clinical chemical test. The test considered was S-creatine kinase B subunit activity, used as the only diagnostic criterion for acute myocardial infarction. The two methods applied were based on (i) graphical analysis, and (ii) computer simulation. The results comprise the effects of changing analytical imprecision and bias on the weighted sum of misclassified cases on basis of the test results. The two methods yield comparable results at high analytical imprecision, but due to differences in assumptions about the error distribution of test results the difference increases with increased analytical imprecision. The graphical analysis is easily performed but is restricted in possible applications. The computer simulation is not a generally available methodology, but allows for mixing of different types of statistical distributions, which is not the case in conventional variance analysis.

Chemistry Techniques, Analytical↗
PubMed1993

Improvement of separation efficiency and concentrate purity of the Fresenius cell separator AS 104: results of a multicenter study. Haemapheresis Scientific Workshop Group of DGTI.

The aim of this multicenter study, initiated by the Haemapheresis Scientific Workshop Group of the DGTI was to evaluate separation protocols for the cell separator AS 104, marketed by Fresenius, using modified software and parameters which were believed to allow a more effective platelet collection with a significantly lower leukocyte contamination of the concentrates. Plateletpheresis data from 950 runs in ten hemapheresis centers, using virtually the same equipment, identical pheresis protocols, and cell counting methods were registered and statistically analyzed for each center and machine-related differences. Additionally, the counting methods of the centers were controlled by bi-weekly external cell count trials, and the plateletpheresis data were corrected using the results of these cell count trials, to obtain a comparison of the two versions of the protocol independent of the center effect. For protocol (or software version) 4.1, 610 runs were registered. The results of cell countings (chamber) are (given as means+/-standard deviations) 3.452x10 11+/-1.009x10 11 for the platelet yield (or thrombocyte yield), 9x10 6+/-23x10 8 for leukocyte contamination, and 17x10 6+/-70x10 6 for the erythrocyte contamination, and 53%+/-13.5% for the extraction efficiency, respectively. For software version 4.4 with 340 runs, the results are 3.642x10 11+/-0.974x10 11 for the platelet yield, 15x10 6+/-74x10 8 for leukocyte contamination, 20x10 6+/-44x10 6 for erythrocyte contamination, and 59%+/-12.4% for the extraction efficiency, respectively. For the leukocyte and erythrocyte contaminations, the means and standard deviations must be interpreted carefully since the statistical distribution showed a considerable skewing of the data. From the automatic counts, marginally smaller means were found. The data were corrected by the values from the ring study; and for these mathematically corrected data, statistical tests showed a significant improvement in the extraction efficiency from software version 4.1 to 4.4. At the same time, the leukocyte contamination was significantly lower with version 4.4.

Blood Component Removal↗
PubMed1987

Nasal resistance to airflow (its measurement, reproducibility and normal parameters).

A method of rhinomanometry is described for use in clinical research work. The statistical distribution of nasal resistance values is studied in a sample of 59 normal individuals. The variation of nasal resistance within two individuals is studied over a period of 7 hours. The choice of appropriate statistical tests to be used when comparing nasal resistance values is discussed. The reproducibility of nasal resistance measurements is assessed in 47 normal individuals. The results were used to define a normal range of values for total nasal resistance to airflow.

Adolescent↗
PubMed1990

Changes in the distribution of ventricular ectopic beats in long-term electrocardiograms.

Only simple methods have been used to assess antiarrhythmic and proarrhythmic effects when comparing baseline and on-therapy Holter recordings taken from the same patient. The paper suggests a new method for definition of these effects based upon comparisons of statistical distributions of ectopic beats. The method is based on multiple random sampling of the recordings and on application of the Smirnov test to compare the samplings. The results of these multiple comparisons are subsequently evaluated using the chi-squared test. An analysis is reported of Holter recordings made on seven patients suffering from ventricular arrhythmia but with anatomically normal heart. In each patient, one baseline recording and one recording on each of three different drugs were made. The results show that the definition of proarrhythmic effects can be partly addressed in a precise mathematical way. The method can also detect a significant change in the character of arrhythmia which can neither be classified as antiarrhythmic nor as proarrhythmic.

Arrhythmias, Cardiac↗
PubMed2006

Markov model of haploid random mating with given distribution of population size.

An exact Markov chain model is formulated and computed for random mating in a haploid gamete pool. There are two versions of the gamete, and there is a finite number of diploid monoecious organisms. The founder population is given, and the subsequent generations allow a prescribed statistical distribution over different population sizes. The non-homogeneous Markov chain works on the haploid gamete level provided the probability of self-fertilization is 1/n, where n is the number of diploid individuals. Standard deviations of gamete frequencies and fixation probabilities are calculated. Effective population sizes for different population size distributions are estimated, including periodic bottlenecks.

Genetics, Population↗
PubMed1964

WATER PERMEABILITY OF THE FETAL ERYTHROCYTE.

The rate constant for the diffusion of tritiated water across the fetal erythrocyte membrane has been measured as 0.056 +/- SD 0.013 msec.(-1) The equivalent pore radius calculated by the method of Paganelli and Solomon for the fetal erythrocyte is 3.9 A. The effect of a normal distribution of channel sizes within the erythrocyte membrane is discussed and the theoretical effect of variation of the distribution on the diffusion to bulk flow ratio is evaluated. Since membrane channels of 4 A characterize a variety of membranes, it is suggested that permeability differences may be associated with slight variations in the statistical distribution of the channel sizes within the membrane. The limits of +/-0.5 A standard deviation that qualitative experiments place on the expected variability of channel size will not account for the lower rate of water diffusion in the fetal cell.

Diffusion↗
PubMed2002

The influence of fabrication errors on the stopband magnitude responses of SAW devices.

This article is devoted to the analysis of the influence of manufacturing errors on the magnitude responses of surface acoustic wave (SAW) devices. Analytical analysis of these random errors provides statistical distributions of the relevant responses and their parameters. It allows significant reduction in the modeling computations compared to the Monte Carlo method, and it provides possibilities for further analytical analysis. After the application of the statistical analysis to different potential structures of SAW devices, it is possible to choose the least sensitive one during the design process without the need of costly trials. Experimental analysis confirmed the existence of some of the features predicted both theoretically and by modeling. The experimental procedure for the evaluation of the fabrication error variances is described. The application of these results to the design process of the SAW devices allows simplification of the requirements for the manufacturing equipment and/or improvement of the devices' parameters, especially stopband suppression.

Journal Article↗
PubMed2000

Probing magnetic properties of the reduced [2Fe-2S] cluster of the ferredoxin from Arthrospira platensis by 1H ENDOR spectroscopy.

The 1H electron nuclear double resonance (ENDOR) spectra in frozen solutions of the reduced [2Fe-2S] cluster in ferredoxin from Arthrospira (Spirulina) platensis have been measured at low temperatures (5-20 K) and simulated using orientational selection methods. The analysis confirmed the existence of a single paramagnetic species with iron valence states II and III connected uniquely to the cluster irons. The experimental ENDOR spectra were fitted to a model including the spin distribution on the centre, the orientation of the g-matrix, and the isotropic and anisotropic hyperfine couplings of the nearest protons in the crystallographically determined structure. In order to partially simulate ENDOR line shapes, a statistical distribution of the corresponding torsion angles between the Fe(III) centre and one of the beta-CH2 protons was introduced. From the analysis, four of the larger hyperfine couplings found were assigned to the cysteine beta-protons near the Fe(III) ion of the cluster, with isotropic hyperfine couplings ranging from 1.6 to 4.1 MHz. The spin distribution on the two iron ions was estimated to be +1.85 for the Fe(III) ion and -0.9 for the Fe(II) ion. The Fe(III) ion was identified as being coordinated to the cysteine ligands Cys49 and Cys79, confirming previous NMR results. The direction of the g-tensor with respect to the cluster was deduced. The g1-g2 plane is parallel to the planes through each iron and its adjacent cysteine sulfurs; the g2-g3 plane is nearly perpendicular to the latter planes and deviates by 25 degrees from the FeSSFe plane. The g1 direction is dominated by the bonding geometry of Fe(II) and does not align with the Fe(II)-Fe(III) vector.

Cyanobacteria↗
PubMed1994

The effect of early surgical intervention on mortality and cost-effectiveness in burn care, 1978-91.

A 14-year (1978-91) single centre analysis was performed involving 3561 patients. Several variables thought to influence burn outcome were included in the analysis, as was length of stay, interval between surgical interventions on each patient, and cost of care. Mortality rate declined by over 2 per cent (from 9.8 per cent during the first 7 years to 7.3 per cent in the second 7 years, P < 0.001). Multiple regression showed that percentage burn, presence of inhalation injury, and age had a significant effect on mortality. These variables, as well as the DRG distribution, were statistically evenly distributed over the 14-year study. There was a statistically significant decrease in length of stay (23 days in 1979 to 14.2 days in 1990), which significantly correlated with a decrease in interval between surgical interventions (14.76 days in 1979 to 6.12 days in 1990). The average annual increase of hospital charges for burn care grew at 9.6 per cent annually, higher than the consumer price index during the same time (5.8 per cent) but substantially lower than the hospital market as a whole (10.8 per cent). Mortality rate of major burns has decreased significantly in this study, while burn severity indices remained constant. Increase in cost of care was substantially lower than that of general hospital care. This apparent cost efficiency is driven by a decreased length of stay closely correlated with aggressive surgical intervention for closure of the burn wound.

Adult↗
PubMed1997

Experimental and modeling study of Na+ current heterogeneity in rat nodose neurons and its impact on neuronal discharge.

This paper is a combined experimental and modeling study of two fundamental questions surrounding the functional characteristics of Na+ currents in nodose sensory neurons. First, when distinctly different classes of Na+ currents are expressed in the same neuron, is there a significant difference in the intrinsic biological variability associated with the voltage- and time-dependent properties of these currents? Second, in what manner can such variability in functional properties impact the discharge characteristics of these neurons? Here, we recorded the whole cell Na+ currents in acutely dissociated rat nodose sensory neurons using the patch-clamp technique. Two general populations of neurons were observed. A-type neurons (n = 20) expressed a single rapidly inactivating tetrodotoxin-sensitive (TTX-S) Na+ current. C-type neurons (n = 87) coexpressed this TTX-S current along with a slowly inactivating TTX-resistant (TTX-R) Na+ current. The TTX-S currents in both cell types had submillisecond rates of activation at room temperature with thresholds near -50 mV. The TTX-R current exhibited about the same rates of activation but required potentials 20-30 mV more depolarized to reach threshold. Over the same clamp voltages the rates of inactivation for the TTX-R current were three to nine times slower than those for the TTX-S current. However, the TTX-R current recovered from complete inactivation at a rate 10-20 times faster than the TTX-S current (10 ms as compared with 100-200 ms). Across the population of neurons studied the TTX-S data formed a relatively tight statistical distribution, exhibiting low standard deviations across all measured voltage- and time-dependent properties. In contrast, the same pooled measurements on the TTX-R data exhibited standard deviations that were 3-10 times larger. The statistical profiles of the voltage- and time-dependent properties of these currents then were used as a physiological guide to adjust the relevant parameters of a mathematical model of nodose sensory neurons previously developed by our group (). Here, we show how the relative expression of TTX-S and TTX-R Na+ currents and the differences in their apparent biological variability can shape the regenerative discharge characteristics and action potential waveshapes of sensory neurons. We propose that the spectrum of variability robust reactivation characteristics of the TTX-R current are important determinants in establishing the heterogeneous stimulus-response characteristics often observed across the general population of C-type sensory neurons.

Action Potentials↗
PubMed2003

Which kind of data (normally distributed, standardized, transformed) for a realistic factor analysis?

Taking into account that the problem of the best pretreatment of data for factor analysis has not yet arrived at generally accepted solutions, it has been tried to estimate, by an empiric procedure, the goodness of the results of repeated factor analyses with different pretreatments, conditions and statistical distribution of variables. Sets of multivariate data for river waters have been constructed firstly, after fixing the number and nature of the latent factors corresponding to the sources of pollution. A series of R-mode factor analyses has then been performed on these data, using various pretreatments (autoscaling, logarithmic transformation and their combinations), various factor rotations (rigid and oblique) and methods of computation of significant factors (40 data processing on the whole). Factor analyses have also been performed on real data of the Po river in the Piedmont region. Comparisons between the results obtained by factor analysis and the actual situation of the systems investigated have made it possible to draw some conclusions on how to proceed in order to obtain realistic results with this chemometric technique.

Factor Analysis, Statistical↗
PubMed2001

The unreliable change of reliable change indices.

The classic method for assessment of reliable change, in 1991 re-introduced as Jacobson's RC, can be characterized as a confidence interval method. In recent years, several RC indices have been proposed using Kelley's (1947) (Kelley, T. L. (1947). Fundamentals of statistics. Cambridge: Harvard University Press) formula for estimating true change. In these proposals, interval estimation and confidence intervals are mixed up, which leads to unjustified probability statements. When Kelley's estimate is correctly expanded into a normal distributed statistic, the classic approach reveals itself as a large sample approximation of a properly constructed RCI based on Kelley's formula. Researchers should continue using the classic approach for the determination of reliable change.

Confidence Intervals↗
PubMed1984

GalNAc/Gal-specific rat liver lectins: their role in cellular recognition.

By investigating the presence and distribution of GalNAc/Gal-specific receptors on liver cells in vitro and in vivo, we provided evidence that the hepatocyte is not the only liver cell expressing receptor activity but that receptors of similar specificity are found on liver macrophages and also on endothelial cells. The receptor distribution in the plasma membrane is strinkingly different between the three cell types, as judged from the binding pattern of colloidal gold particles coated with asialofetuin or lactosylated serum albumin. Binding to hepatocytes occurs as single particles statistically distributed, binding to liver macrophages in a clustered arrangement all over the cell membrane and binding to endothelial cells also in a clustered arrangement but restricted to coated pits only. The different receptor distribution results in different binding and uptake abilities. Whereas hepatocytes bind and take up molecules and small particles (5 nm) only, the clustered receptor arrangement of endothelial cells and macrophages enables them to effectively bind and ingest larger particles. Ligands larger than 35 nm can be taken up by the macrophages only. The different receptor arrangement results also in different capacities of cell contact formation. Although in vitro liver macrophages and hepatocytes can both bind desialylated cells the macrophage needs much less galactosyl groups exposed on erythrocytes to establish stable contacts than the hepatocyte. The contacts formed by hepatocytes stay reversible for 30 min at 37 degrees C, whereas the contacts formed by the liver macrophages become irreversible after 10 min at 37 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2005

Surface-anchoring properties related to the distribution of polyimide chains in a twisted nematic liquid-crystal cell.

On the basis of a general Rapini and Papoular equation and the unified surface-anchoring energy, surface-anchoring strength is newly defined theoretically as a function of the azimuthal deviation angle of the surface liquid-crystal directors and the statistical distribution of polyimide chains in a typical twisted nematic liquid-crystal cell. Then these are determined experimentally by the surface second-harmonic generation method, which is nonlinear optics, and the optical phase retardation method. We assume that the anisotropy distribution of polyimide chains induced by the rubbing strength is dominated by a Gaussian distribution around the rubbing direction.

Journal Article↗