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Decreased 5-HT2 but not 5-HT1 receptor binding in cortex of rat after chronic administration of dothiepin. Application of the Woolf plot to analysis of binding parameters.

Prolonged administration of the antidepressant drug, dothiepin hydrochloride (30 mg/kg orally twice daily for 24 days), resulted in a significant decrease in the population of serotonin2 (5-HT2) binding sites in the frontal cortex of rats whereas serotonin1 (5-HT1) binding sites remained unaltered. No significant differences in affinity constants for either ligand-binding site interaction were observed. Analyses of the binding parameters was performed using linear transformation methods of the specific binding isotherms according to Scatchard (1949) [Ann. N.Y. Acad. Sci. 51: 660-672] or Woolf (see Haldane, 1957: Nature 179: 832). The resulting parameter estimates generated in each analysis were compared. Although both methods demonstrated the decreased Bmax for 5-HT2 binding sites with no change in 5-HT1 sites after prolonged administration of dothiepin, Woolf analyses gave reliably better estimates of the binding parameters as judged by examination of the respective correlation coefficients for best fit linear regression lines.

Animals↗

Transport of Escherichia coli bacteria through laboratory columns of glacial-outwash sediments: estimating model parameter values based on sediment characteristics.

Bacterial transport through cores of intact, glacial-outwash aquifer sediment was investigated with the overall goal of better understanding bacterial transport and developing a predictive capability based on the sediment characteristics. Variability was great among the cores. Normalized maximum bacterial-effluent concentrations ranged from 5.4x10(-7) to 0.36 and effluent recovery ranged from 2.9x10(-4) to 59%. Bacterial breakthrough was generally rapid with a sharp peak occurring nearly twice as early as the bromide peak. Bacterial breakthrough exhibited a long tail of relatively constant concentration averaging three orders of magnitude less than the peak concentration for up to 32 pore volumes. The tails were consistent with non-equilibrium detachment, corroborated by the results of flow interruption experiments. Bacterial breakthrough was accurately simulated with a transport model incorporating advection, dispersion and first-order non-equilibrium attachment/detachment. Relationships among bacterial transport and sediment characteristics were explored with multiple regression analyses. These analyses indicated that for these cores and experimental conditions, easily-measurable sediment characteristics--median grain size, degree of sorting, organic-matter content and hydraulic conductivity--accounted for 66%, 61% and 89% of the core-to-core variability in the bacterial effective porosity, dispersivity and attachment-rate coefficient, respectively. In addition, the bacterial effective porosity, median grain size and organic-matter content accounted for 76% of the inter-core variability in the detachment-rate coefficient. The resulting regression equations allow prediction of bacterial transport based on sediment characteristics and are a possible alternative to using colloid-filtration theory. Colloid-filtration theory, used without the benefit of running bacterial transport experiments, did not as accurately replicate the observed variability in the attachment-rate coefficient.

Bromides↗

Experimental evaluation of adaptive three-tank level control.

Liquid level control through regulation of mass flow rates is an important application in various areas of the power industry. Very often a PID controller is used for these applications. This paper compares a nonconventional PID controller and three different types of adaptive controller, a direct model reference adaptive controller (MRAC), an indirect MRAC with Lyapunov estimation, and an indirect MRAC with recursive least-squares (RLS) updating estimation, for liquid level control. By implementing all four controllers on a three-tank system, the performances of each are compared. All controllers track a sinusoidal input very well and overall exhibit somewhat varying performance. The direct MRAC and the indirect MRAC with RLS estimation give the best performance. With Lyapunov estimation and RLS estimation, all the system parameter estimates converge to the reference model values. However, RLS estimation has a much faster convergence. It is concluded that adaptive liquid level control is an improvement over traditional liquid level control when precise level control in three coupled tanks is desired.

Journal Article↗

A statistical analysis of NMR spectrometer noise.

Estimation of NMR spectral parameters, using e.g. maximum likelihood methods, is commonly based on the assumption of white complex Gaussian noise in the signal obtained by quadrature detection. Here we present a statistical analysis with the purpose of discussing and testing the validity of this fundamental assumption. Theoretical expressions are derived for the correlation structure of the noise under various conditions, showing that in general the noise in the sampled signal is not strictly white, even if the thermal noise in the receiver steps prior to digitisation can be characterised as white Gaussian noise. It is shown that the noise correlation properties depend on the ratio between the sampling frequency and the filter cut-off frequency, as well as the filter characteristics. The theoretical analysis identifies conditions that are expected to yield non-white noise in the sampled signal. Extensive statistical characterisation of experimental noise confirms the theoretical predictions. The statistical methods outlined here are also useful for residual analysis in connection with validation of the model and the parameter estimates.

Magnetic Resonance Spectroscopy↗

Comparison of non-linear temperature-dependent development rate models applied to in vitro growth of entomopathogenic fungi.

Five non-linear models with three to five parameters, built to quantify the effect of temperature on insect development and microbial growth, were tested to describe the influence of temperature on in vitro-measured growth rates of entomopathogenic hyphomycetes. Data from two isolates of each of the four fungal species, Paecilomyces fumosoroseus, Beauveria bassiana, Metarhizium anisopliae, Metarhizium flavoviride, were used to assess the features of each model. Criteria for model evaluation included the statistical quality of parameters estimates, the goodness of fit to data, as well as the ability to provide estimates of several key parameters: the upper and lower development thresholds, the thermal optimum and the maximal growth rate at thermal optimum. The second model proposed by Brière et al. (1999) was found to be the best, and Ratkowsky's model (1983) also exhibited good features.

Hot Temperature↗

Transport and kinetic processes underlying biomolecular interactions in the BIACORE optical biosensor.

The transport and kinetic processes describing biomolecular interactions in the BIACORE optical biosensor have been studied with the help of a mathematical model. In comparison to previous models, the model presented here couples, for the first time, transport phenomena in the flow channel with hindered diffusive transport and reactions inside the hydrogel. Simulated experiments based on this model, and two simpler models extant in the literature, are used to identify cases under which the detailed model is essential for accurate prediction of kinetic parameters. It is shown that this model can substantially improve the accuracy of kinetic parameter estimation when transport limitations in the flow channel and/or the hydrogel significantly influence the observed instrument response curves. The model can extend the range of the instrument's applicability to higher concentrations of immobilized species within the hydrogel. It can also be used for accurate design of experiments with the purpose of minimizing errors in the estimation of the kinetic parameters.

Antibodies↗

Phosphorus saturation potential: a parameter for estimating the longevity of constructed wetland systems.

Phosphorus (P) adsorption capacities of materials derived from batch experiments can vary by several orders of magnitude depending on the method used, leading to potential misinterpretation of the P retention capacity on a long-term basis and unrealistic estimations of constructed wetland systems (CWS) longevity. The objective of this study was to determine if the P saturation of the material in a column could be used for this purpose with an improved accuracy. A 278-d column experiment with a synthetic P solution was conducted to investigate the long-term P retention capacity of electric arc furnace (EAF) steel slag up to its P saturation point. EAF slag showed a high affinity for P, reaching a saturation value of 1.35 g of P kg(-1). Investigations of the regeneration of the P adsorbing capacity by this material showed that, after 4 weeks of water desaturated resting, EAF steel slag was able to increase its initial P adsorptive capacity to 2.35 g of P kg(-1). A sequential P fractionation experiment was performed to quantify the proportion of P bound to mineral compounds in EAF. From the most loosely bound to the most strongly bound P fraction, P was associated with resin extractable (14%), Fe extractable (0.5 M Na2CO3, 47%), Al extractable (0.1 M NaOH, 1%), Ca extractable (1 M HCl, 12%), and Ca in a stable residual pool (concentrated hot HCl, 26.5%). X-ray fluorescence analyses of EAF steel slag chemical composition revealed that the continuous application of a P solution resulted in 75% and 59% increases in K2O and P2O5 respectively; Al2O3 and FeO increased by 8%, while the portion of CaO remained unchanged. The investigated properties (P retention potential, regeneration of P adsorption, P fractionation) provide useful data about the suitability of slag material as a media for long-term P removal and should enable an improved prediction of the longevity of full-scale CWS.

Adsorption↗

An application of population kinetics analysis to estimate pharmacokinetic parameters of sodium tungstate after multiple-dose during preclinical studies in rats.

The purpose of this study was to use a population approach in the preclinical development program of sodium tungstate in the rat in order i) to compute individual pharmacokinetic parameters of this compound after repeated oral administrations, until the 4-week toxicology study, using an empirical Bayes methodology; and ii) to study the influence of the administered dose, of the gender and of the duration of treatment on the pharmacokinetic parameters. Four studies were used representing a mixture of single intravenous administration and multiple oral administrations. The treatment duration ranged from 7 to 28 days. Intravenous dose was 9 mg/kg; three different oral doses were tested, 50, 100 and 200 mg/kg/day. Plasma concentration profiles versus time were compatible with a two-compartment model. A significant gender effect was found on bioavailability. The duration of treatment and the administered dose did not significantly explain part of the interindividual variability of pharmacokinetic parameters. The absorption of tungsten was rapid (1-3 hr). Total plasma clearance and elimination half-life averaged 2.8 ml/min/kg and 3.04 hr in males, and 3 ml/min/kg and 2.74 hr in females. The bioavailability was on an average 70%; being significantly higher in females than in males (0.78 versus 0.61). This compartmental approach should be considered as complementary to the usual non-compartmental approach used for analysis of preclinical data and should be a valuable tool to characterise the pharacokinetic/pharmacodynamic behaviour of a drug.

Administration, Oral↗

Comparing the unaided visual exam to lateral cinefluorography in estimating several parameters of velopharyngeal function.

Retrospectively, the medical records of patients with known velopharyngeal insufficiency (VPI) were reviewed for comments based on an unaided visual examination regarding their velopharyngeal function. These comments were compared to objective findings obtained from the cinefluorographic evaluations performed on each of the patients. A total of 68 recorded comments (47 patients) were identified and fell into four broad categories: (1) velar length, (2) depth of the nasopharynx, (3) velopharyngeal closure, and (4) velar mobility. The results revealed an agreement level of 60% between judgements made from visual examinations and cinefluorographic evaluations. This relatively poor agreement suggests that management decisions concerning VPI must include some method of objectively assessing velopharyngeal form and function during connected speech.

Cineradiography↗

Theoretical basis for genetic linkage analysis in autotetraploid species.

Linkage analysis in autotetraploid species has been an historical challenge in quantitative genetics theory and is a stumbling block that urgently needs to be removed in the rapidly emerging genome research on this species, such as cultivated potato. This article presents theory of a full model of tetrasomic linkage and develops a statistical framework for the linkage analysis. The model considers both double reduction and recombination, the most essential features of tetrasomic inheritance with linked loci, whereas the statistical method takes appropriate account of the major complexities in analyzing both dominant and codominant molecular marker data during map reconstruction in tetraploid species. These complexities include the problems arising from multiple dosage of allelic inheritance, the null allele, allelic segregation distortion, mixed bivalent and quadrivalent pairing in meiosis, and incomplete information of marker phenotype data. The theoretical analysis established the relationship between the coefficients of double reduction at linked loci, which is essential in the present tetrasomic linkage analysis and in assessing the impact of double reduction on the evolution of tetraploid populations. The statistical method, based on the combination of theoretical analysis and a computer-based algorithm, provided analytical tools for predicting the maximum-likelihood estimates of the model parameters. A simulation study showed the feasibility of a practical implementation of the method, detailed the procedure of the analysis, validated the power and reliability in the parameter estimation, and compared the present method with those proposed in the current literature.

Computer Simulation↗

Modelling of migration from multi-layers and functional barriers: estimation of parameters.

Functional barriers form parts of multi-layer packaging materials, which are deemed to protect the food from migration of a broad range of contaminants, e.g. those associated with reused packaging. Often, neither the presence nor the identity of the contaminants is known, so that safety assessment of the materials has to rely on predictive tools. Several complementary freeware described here allow one to model diffusion in multi-layer films. These tools require the input of parameters that are not easy to determine or predict. Previous work has focused on the prediction of diffusion coefficients at storage temperatures of packaging in contact with food. However, many other kinetic and thermodynamic parameters are needed to describe transport properties during the processing of a material at high temperature and during its shelf-life. All parameters needed for the calculations are discussed. In order to propose default values, the approach consists of (1) reviewing the available literature data, (2) running experiments on polypropylene, polyethylene and poly(ethylene vinyl alcohol) in typical conditions (separately diffusion during processing and migration) and (3) simulating numerical sets for typical situations. Several freeware are proposed to simulate migration from multi-layers and functional barriers using the default parameters.

Computer Simulation↗