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At least 379 records · Page 21Linked to original sources

Lumped parameter estimation for the embryonic chick vascular system: a time-domain approach using MLAB.

We have evaluated several lumped parameter analog models for the early chick embryonic vascular system that may be used to infer loading characteristics of the developing heart. We measured dorsal aortic pressure and flow simultaneously with a servo-null pressure system and a pulsed Doppler velocimeter. Four different analog circuit models were chosen for comparisons. We formulated the time-domain differential equations specifying the relations between pressure and flow in the models, and then estimated the lumped parameters that produced the best fit. The MLAB mathematical modeling software was used for solving differential equations, and for minimizing the difference between model-predicted values and experimental data. The traditional three-element Windkessel model with an added inductance term was most often the best-fitting model. This is compatible with the previous study using a frequency-domain approach. The procedures developed for the current study are adaptable for the study of a variety of nonlinear models, and distributed parameter models for mammalian cardiovascular development with mechanically, pharmacologically, or genetically altered conditions.

Analog-Digital Conversion↗

Simulation and parameter estimation study of a simple neuronal model of rhythm generation: role of NMDA and non-NMDA receptors.

Simple neural network models of the Xenopus embryo swimming CPG, based on the one originally developed by Roberts and Tunstall (1990), were used to investigate the role of the voltage-dependent N-methyl-D-aspartate (NMDA) receptor channels, in conjunction with faster non-NMDA components of synaptic excitation, in rhythm generation. The voltage-dependent NMDA current "follows" the membrane potential, leading to a postinhibitory rebound that is more efficient than one without voltage dependency and allows neurons to fire more than one action potential per cycle. Furthermore, the model demonstrated limited rhythmic activity in the absence of synaptic inhibition, supporting the hypothesis that the NMDA channels provide a basic mechanism for rhythmicity. However, the rhythmic properties induced by the NMDA current were observed only when there was moderate activation of the non-NMDA synaptic channels, suggesting a modulatory role for this component. The simulations also show that the voltage dependency of the NMDA conductance, as well as the fast non-NMDA current, stabilizes the alternation pattern versus synchrony. To verify that these effects and their implications on the mechanism of swimming and transition to other types of activity take place in the real preparation, constraints on parameter values have to be specified. A method to estimate synaptic parameters was tested with generated data. It is shown that a global analysis, based on multiple iterations of the optimization process (Foster et al., 1993), gives a better understanding of the parameter subspace describing network activity than a standard fit with a sensitivity analysis for an individual solution.

Animals↗

Influence of body segments' parameters estimation models on inverse dynamics solutions during gait.

The purpose of the present study was to examine the influence of anthropometric data on joint kinetics during gait. We particularly focused on the sensitivity of inverse dynamics solutions to the use of models for body segment parameters (BSP) estimation. Six often used estimation models were selected to provide BSP values for the three segments of the lower limb. Kinematics and dynamics were sampled from seven subjects performing barefoot gait at three different speeds. Joint kinetics were estimated with the bottom-up method using BSP values derived from each estimation model as anthropometric inputs. The BSP estimates were highly sensitive to the model used with deviations ranging from at least 9.73% up to 60%. Maximal variations of peak values for the hip joint flexion/extension moment during the swing phase were 20.11%. Hence, our findings suggest that the influence of BSP cannot be neglected. Observed deviations are especially due to the effect of varying simultaneously the mass, moments of inertia and the center of mass location values, according to the underlying relationship of interdependency linking each component. Considering both the differences found in joint kinetics and the level of accuracy of BSP models, evidence is provided that using multiple regression BSP estimation functions derived from Zatsiorsky and Seluyanov should be recommended to assess joint kinetics.

Adult↗

Kinetic parameters estimation for ascorbic acid degradation in fruit nectar using the Partial Equivalent Isothermal Exposures (PEIE) method under non-isothermal continuous heating conditions.

With the purpose of testing the Paired Equivalent Isothermal Exposures (PEIE) method to determine reaction kinetic parameters under non-isothermal conditions, continuous pasteurizations were carried out with a tropical fruit nectar [25% cupuaçu (Theobroma grandiflorum) pulp and 15% sugar] to estimate the ascorbic acid thermal degradation kinetic parameters. Fifteen continuous thermal exposures were studied, with seven being cycled. The experimental ascorbic acid thermal degradation kinetic parameters were estimated by the PEIE method (E(a) = 73 +/- 9 kJ/mol, k(8)(0)( degrees )(C) = 0.017 +/- 0.001 min(-)(1)). These values compared very well to the previously determined values for the same product under isothermal conditions (E(a) = 73 +/- 7 kJ/mol, k(8)(0)( degrees )(C) = 0.020 +/- 0.001 min(-)(1)). The predicted extents of reaction presented a good fit to the experimental data, although the cycled thermal treatments presented some deviation. In addition to being easier and faster than the Isothermal method, the PEIE method can be a more reliable method to estimate first-order reaction kinetic parameters when continuous heating is considered.

Ascorbic Acid↗

Phenotypic and genetic parameter estimates for racing traits of Arabian horses in Turkey.

The racing records for Arabian horses used in the study were obtained from the Turkish Jockey Club. The traits used in the study were racing time, best racing time, rank, annual earnings, earnings per start, log annual earnings and log earnings per start. Genetic parameters were estimated by the restricted maximum likelihood (REML) procedure using the DFREML program. The effects of age, sex and origin of horse were significant for each trait. The effect of year was significant on time and earning traits, but not rank. The effect of month on time traits was also significant. Heritability estimates of the entire data set were 0.280, 0.281, 0.069, 0.139, 0.174, 0.152 and 0.171 for racing time, best racing time, rank, annual earnings, earnings per start, log annual earnings and log earnings per start respectively. Estimates of repeatability varied from 0.349 to 0.500 for racing time, from 0.430 to 0.524 for best racing time and from 0.129 to 0.171 for rank depending on the data set used in the analyses. Best racing time was the most appropriate trait for selection in this study, as this might lead to genetic improvement than other traits.

Age Factors↗

Parameter estimation of human nerve C-fibers using matched filtering and multiple hypothesis tracking.

We describe how multiple-target tracking may be used to estimate conduction velocity changes and recovery constants of human nerve C-fibers. These parameters discriminate different types of C-fibers and pursuing this may promote new insights into differential properties of nerve fiber membranes. Action potentials (APs) were recorded from C-fibers in the peroneal nerve of awake human subjects. The APs were detected by a matched filter constituting a maximum-likelihood constant false-alarm rate detector. Using the multiple-hypothesis tracking method and Kalman filtering, the detected APs (targets) in each trace (scan) were associated to individual nerve fibers (tracks) by their typical conduction latencies in response to electrical stimulation. The measurements were one-dimensional (range only) and the APs were spaced in time with intersecting trajectories. In general, the AP amplitude of each C-fiber differed for different fibers. Amplitude estimation was therefore incorporated into the tracking algorithm to improve the performance. The target trajectory was modeled as an exponential decay with three unknowns. These parameters were estimated iteratively by applying the simplex method on the parameters that enter nonlinearly and the least squares method on the parameters that enter linearly.

Action Potentials↗

Parameter estimation in stochastic biochemical reactions.

Gene regulatory, signal transduction and metabolic networks are major areas of interest in the newly emerging field of systems biology. In living cells, stochastic dynamics play an important role; however, the kinetic parameters of biochemical reactions necessary for modelling these processes are often not accessible directly through experiments. The problem of estimating stochastic reaction constants from molecule count data measured, with error, at discrete time points is considered. For modelling the system, a hidden Markov process is used, where the hidden states are the true molecule counts, and the transitions between those states correspond to reaction events following collisions of molecules. Two different algorithms are proposed for estimating the unknown model parameters. The first is an approximate maximum likelihood method that gives good estimates of the reaction parameters in systems with few possible reactions in each sampling interval. The second algorithm, treating the data as exact measurements, approximates the number of reactions in each sampling interval by solving a simple linear equation. Maximising the likelihood based on these approximations can provide good results, even in complex reaction systems.

Algorithms↗

A model of intestinal iron absorption and plasma iron kinetics: optimal parameter estimates for normal dogs.

A multicompartment model describing the physiological processes of intestinal iron absorption has been developed. The model accounts for uptake by the intestinal mucosa of iron in the lumen, followed by either iron incorporation into a mucosal storage pool (presumably ferritin) or direct iron transfer to the plasma. To enable analysis of iron absorption from noninvasive measurements, plasma iron kinetics were also analyzed. The model was validated in studies of three beagle dogs given oral 59Fe-citrate and intravenous 55Fe-transferrin simultaneously. Model parameters were estimated from the best (least-squares) fit of the model outputs to the tracer iron activity in venous blood samples and in the whole body. The parameter values show that both incorporation of iron into the mucosal storage pool and transfer of iron from the mucosa to the plasma occur at rates approximately 100 times greater than mucosal uptake of iron from the gut lumen. Further, release of iron from mucosal storage, while measurable, occurs at a slow rate. The study demonstrates the practicality of this noninvasive approach for the simultaneous study of iron absorption and plasma iron kinetics.

Animals↗

Hemodynamic parameter estimation from ocular fluorescein angiograms.

BACKGROUND: A method is proposed for parameterizing choroidal blood flow from fluorescein angiograms. METHODS: After digitizing and aligning the angiographic sequence, the intensity build-up curves of fluorescence are analysed per pixel (approx. 10 microns in fundo). Two models are compared. A one-compartment model predicts an exponential build-up curve, from which the following parameters are estimated: maximum fluorescence, dye appearance time and local perfusion rate (reciprocal of the time constant of the exponential). To account for the contribution of the systemic circulation to the shape of the build-up curve, a two-compartment model is used which predicts a bi-exponential curve. RESULTS: Introduction of the second (systemic) compartment resulted in a significant improvement of fit in 37 of 48 patients studied. The rate constants of the systemic compartment found were mainly in the range of 0.30-1.00 s-1. CONCLUSION: For the individual patient, the local perfusion rates may vary strongly, with lower perfusion rates possibly being of prognostic value for ocular diseases such as glaucoma or diabetic retinopathy.

Blood Flow Velocity↗

Practical application of dynamic temperature profiles to estimate the parameters of the square root model.

Optimal experimental design for parameter estimation (OED/PE) is a promising method to improve parameter estimation accuracy and minimise experimental effort in the field of predictive microbiology. In this paper, the OED/PE methodology was applied on two practical examples: the growth of Bacillus cereus and Enterobacter cloacae in liquid whole egg product. Both strains were recovered from samples of a commercial product. The goal of the modelling exercise was to quantify the influence of temperature on bacterial growth. The Baranyi-model for bacterial growth combined with the Ratkowsky square root model to describe temperature dependence was used. Using this model, a temperature step profile was calculated based on the optimal D-criterion. The model was then fitted against the experimental bacterial growth curve measured under the dynamic temperature conditions. This process was repeated until the parameters could be estimated with sufficient accuracy, apparent by the model prediction errors. For B. cereus, prior information could be extracted from the literature, allowing calculating a dynamic temperature profile directly. Two-step profiles were sufficient to obtain a good estimation for the model parameters. No prior information could be found for E. cloacae. Therefore, a limited series of static experiments had to be conducted to obtain usable prior model parameters estimates. Only one dynamic experiment was then needed to achieve a good estimation.

Bacillus cereus↗

Parameter estimation for a mathematical model of the cell cycle in frog eggs.

Parameter values for a kinetic model of the nuclear replication-division cycle in frog eggs are estimated by fitting solutions of the kinetic equations (nonlinear ordinary differential equations) to a suite of experimental observations. A set of optimal parameter values is found by minimizing an objective function defined as the orthogonal distance between the data and the model. The differential equations are solved by LSODAR and the objective function is minimized by ODRPACK. The optimal parameter values are close to the "guesstimates" of the modelers who first studied this problem. These tools are sufficiently general to attack more complicated problems, where guesstimation is impractical or unreliable.

Animals↗

Modelling and parameter estimation of the enzymatic synthesis of oligosaccharides by beta-galactosidase from bacillus circulans

The aim of this research is to develop a model to describe oligosaccharide synthesis and simultaneously lactose hydrolysis. Model A (engineering approach) and model B (biochemical approach) were used to describe the data obtained in batch experiments with beta-galactosidase from Bacillus circulans at various initial lactose concentrations (from 0.19 to 0.59 mol.kg(-1)). A procedure was developed to fit the model parameters and to select the most suitable model. The procedure can also be used for other kinetically controlled reactions. Each experiment was considered as an independent estimation of the model parameters, and consequently, model parameters were fitted to each experiment separately. Estimation of the parameters per experiment preserved the time dependence of the measurements and yielded independent sets of parameters. The next step was to study by ordinary regression methods whether parameters were constant under the altering conditions examined. Throughout all experiments, the parameters of model B did not show a trend upon the initial lactose concentration when inhibition was included. Therefore model B, a galactosyl-enzyme complex-based model, was chosen to describe the oligosaccharide synthesis, and one parameter set was determined for various initial lactose concentrations. Copyright 1999 John Wiley & Sons, Inc.

Journal Article↗

HPLC-analysis and preliminary pharmacokinetic parameter estimations of chloroquine.

An HPLC method for the separate determination of chloroquine and its major metabolites has been developed. Separation was on an octadecyl RP column. Fluorimetric detection followed after on-line post-column buffering of the mobile phase to pH = 9.25. The method is highly selective for the compounds of interest with a detection limit down to 1 ng/ml. Preliminary data on the pharmacokinetics of chloroquine are reported, as obtained with this method. Kinetic parameters were estimated with the aid of the non-linear regression computer programme NON-LIN.

Chloroquine↗

Logistic curve fitting and parameter estimation using nonlinear noniterative least-squares regression analysis.

A microcomputer program has been developed for the fitting of the logistic curve to biological, medical, and other experimental data. In addition to supplying estimates for all of the logistic curve parameters, the program provides the fitted result for each input datum thus allowing for the immediate assessment of the logistic curve and detection of possible outliers.

Biometry↗

Equilibrium expert: an add-in to Microsoft Excel for multiple binding equilibrium simulations and parameter estimations.

An add-in to Microsoft Excel was developed to simulate multiple binding equilibriums. A partition function, readily written even when the equilibrium is complex, describes the experimental system. It involves the concentrations of the different free molecular species and of the different complexes present in the experiment. As a result, the software is not restricted to a series of predefined experimental setups but can handle a large variety of problems involving up to nine independent molecular species. Binding parameters are estimated by nonlinear least-square fitting of experimental measurements as supplied by the user. The fitting process allows user-defined weighting of the experimental data. The flexibility of the software and the way it may be used to describe common experimental situations and to deal with usual problems such as tracer reactivity or nonspecific binding is demonstrated by a few examples. The software is available free of charge upon request.

Algorithms↗

Parameter estimation in a three-compartment model for blood alcohol curves.

Models of alcohol input and absorption are crucial to the description and understanding of the effects of alcohol in the human body. In this paper, the pharmacokinetics of alcohol after oral administration are described by a three-compartment model with a supposed concentration-dependent absorption and elimination. The absorption of alcohol from the small intestine into the blood is represented by a first-order rate constant ka. To describe the delay in peak concentration of alcohol the gastric emptying rate is represented as a first-order parameter with a feedback control depending on the amount of alcohol remaining in the stomach. The alcohol ingestion can then be represented as a bolus input. The elimination process is described by a model similar to the Michaelis-Menten model for enzyme kinetics. Parameters are estimated by means of an iterative algorithm minimizing a non-linear function. A good fit of the model was obtained for blood alcohol curves from six men and six women who each had received an alcohol dose of 28.5 g on three consecutive days. It is concluded that the model can be recommended to describe adequately the absorption and elimination of alcohol.

Adult↗

Predicting the radiation control probability of heterogeneous tumour ensembles: data analysis and parameter estimation using a closed-form expression.

A closed-form formula describing the tumour control probability (tcp) of a heterogeneous collection of tumours has been obtained by analytically averaging the homogeneous double-exponential tcp formula over inter-tumour distributions of clonogen radiosensitivity, density and repopulation rate, tumour volume and dose. The formula can be straightforwardly and relatively quickly fitted to clinical data, yielding radiobiological parameter values for use in tcp modelling. The formula was fitted to published tcp data which catalogued tumour control records grouped by dose and tumour volume, and treatment duration. Fitted parameter values, confidence intervals and goodness-of-fit statistics were determined. The sets of parameter values obtained are unique only to within a scaling factor. The formula provides non-rejectable fits to data which grouped tcp by dose and volume when radiosensitivity parameters take values close to laboratory estimates, the fitted volume dependence parameter, however, taking rather high values. Good fits are obtainable with the intuitively reasonable volume parameter value of one, but with radiosensitivity values around one-third of their laboratory estimates. Non-rejectable fits to data which grouped tcp by dose and treatment duration may be obtained with radiosensitivity and repopulation rate parameters lying close to laboratory estimates.

Breast Neoplasms↗

On the covariance between parameter estimates in models of twin data.

We study the covariance between estimates of additive genetic variance and either dominance genetic variance or common environmental variance in likelihood-based twin analyses. The central tools used in these investigations are the asymptotic covariances of variance component estimates, which we present for several commonly used twin models. We first illustrate the use of the asymptotic covariance terms for determining the optimal ratio of monozygotic to dizygotic group sample sizes for a twin study. We then focus attention on the asymptotic correlations between estimates of additive genetic variance, and either dominance genetic variance or common environmental variance, and their use in understanding when parameters are efficiently estimable from twin data. The results of this investigation are confirmed by simulation studies, and highlight inherent limitations of the twin model, in the sense that having only twin data limits the ability to detect individual variance components. Finally, remarks on possible alternative statistical methods are given, and results are presented to illustrate the improvements in efficiency that are possible with additional family data. In particular, the results provide insight into the limitations of inference from twin data.

Analysis of Variance↗