Improved parameter estimates in drug-protein binding studies by non-linear regression.
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Binding Sites↗
SEARCH · PubMed Health
Results for “parameter estimation”
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Anomalous parameter estimates in the one-compartment model with first-order absorption.
A difficulty sometimes encountered in least-squares fitting of a one-compartment model with first-order absorption is that estimated values (ka and ke) of the rate constants of absorption and elimination are almost identical, are highly correlated and have very large standard deviations. This anomaly is explained by the existence of a class of data sets for which least-squares estimates of the rate constants are complex quantities. Such data sets may arise either from an unfortunate combination of random (e.g. assay) errors in the concentration values if ka and ke are sufficiently similar in magnitude, or from delayed absorption.
Algorithms↗
Uncertainties associated with parameter estimation in atmospheric infrasound arrays.
This study describes a method for determining the statistical confidence in estimates of direction-of-arrival and trace velocity stemming from signals present in atmospheric infrasound data. It is assumed that the signal source is far enough removed from the infrasound sensor array that a plane-wave approximation holds, and that multipath and multiple source effects are not present. Propagation path and medium inhomogeneities are assumed not to be known at the time of signal detection, but the ensemble of time delays of signal arrivals between array sensor pairs is estimable and corrupted by uncorrelated Gaussian noise. The method results in a set of practical uncertainties that lend themselves to a geometric interpretation. Although quite general, this method is intended for use by analysts interpreting data from atmospheric acoustic arrays, or those interested in designing and deploying them. The method is applied to infrasound arrays typical of those deployed as a part of the International Monitoring System of the Comprehensive Nuclear-Test-Ban Treaty Organization.
Journal Article↗
Source parameter estimates of echolocation clicks from wild pygmy killer whales (Feresa attenuata).
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Animals↗
Identifying sites under positive selection with uncertain parameter estimates.
Codon-based substitution models are routinely used to measure selective pressures acting on protein-coding genes. To this effect, the nonsynonymous to synonymous rate ratio (dN/dS = omega) is estimated. The proportion of amino-acid sites potentially under positive selection, as indicated by omega > 1, is inferred by fitting a probability distribution where some sites are permitted to have omega > 1. These sites are then inferred by means of an empirical Bayes or by a Bayes empirical Bayes approach that, respectively, ignores or accounts for sampling errors in maximum-likelihood estimates of the distribution used to infer the proportion of sites with omega > 1. Here, we extend a previous full-Bayes approach to include models with high power and low false-positive rates when inferring sites under positive selection. We propose some heuristics to alleviate the computational burden, and show that (i) full Bayes can be superior to empirical Bayes when analyzing a small data set or small simulated data, (ii) full Bayes has only a small advantage over Bayes empirical Bayes with our small test data, and (iii) Bayesian methods appear relatively insensitive to mild misspecifications of the random process generating adaptive evolution in our simulations, but in practice can prove extremely sensitive to model specification. We suggest that the codon model used to detect amino acids under selection should be carefully selected, for instance using Akaike information criterion (AIC).
Amino Acids↗
Stability of parameter estimates derived from the power/time relationship.
The hyperbolic relationship between power output (P) and time to exhaustion (t) is described as t = W'/(P-theta PA). The purpose of this study was to determine the stability of estimations of estimates of theta PA and W', said to reflect maximal sustainable power and anaerobic capacity, respectively. Thirteen women and 13 men performed five bouts of cycling exercise to exhaustion. Individual theta PA and W' were calculated from the results of these five bouts (Trial 1). These procedures were repeated (Trial 2). For both sexes, Trial 2 estimates of theta PA were 5 to 6% higher than Trial 1 estimates, but they were highly correlated. Mean W' estimates were the same in Trials 1 and 2, with higher trial-to-trial correlations in the men than in the women.
Exercise Test↗
Use of ionic currents to identify and estimate parameters in models of channel blockade.
Models of ion channel blockade are frequently validated with observations of ionic currents resulting from electrical or chemical stimulation. Model parameters for some models (modulated receptor hypothesis) cannot be uniquely determined from ionic currents. The time course of ionic currents reflects the activation (fraction of available channels that conduct in the presence of excitation) and availability of channels (the ability of the protein to make a transition to a conducting conformation and where this conformation is not complexed with a drug). In the presence of a channel blocking agent, the voltage dependence of availability appears modified and has been interpreted as evidence that drug-complexed channels exhibit modified transition rates between channel protein conformations. Because blockade and availability both modify ionic currents, their individual contributions to macroscopic conductance cannot be resolved from ionic currents except when constant affinity binding to a bindable site is assumed. Experimental studies of nimodipine block of calcium channels and lidocaine block of sodium channels illustrate these concepts.
Animals↗
Model of brain serotonin metabolism. I. Structure determination-parameter estimation.
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Animals↗
Frequency response of the chest: modeling and parameter estimation.
The frequency response of the respiratory system was studied in the range from 3 to 70 Hz in 15 normal subjects by applying sinusoidal pressure variations around the chest and measuring gas flow at the mouth. The observed input-output relationships were systematically compared to those predicted on the basis of linear differential equations of increasing order. From 3 to 20 Hz the behavior of the system was best described by a 3rd-order equation, and from 3 to 50 Hz by a 4th-order one. A mechanistic model of the 4th order, featuring tissue compliance (Ct), resistance (Rt) and inertance (It), alveolar gas compressibility (Cg) and airway resistance (Raw), and inertance (Iaw) was developed. Using that model, the following mean values were found: Ct = 2.08-10(-2)1-hPa-1 (1 hPa congruent to 1 cm of water); Rt = 1.10-hPa-1(-1)-s; It = 0.21-10(-2)hPa-1(-1)-s2; Raw = 1.35-hPa-1(-1)-s; Iaw = 2.55-10(-2)hPa-1(-1)-s2. Additional experiments devised to validate the model were reasonably successful, suggesting that the physical meaning attributed to the coefficients was correct. The validity of the assumptions and the physiological meaning of the coefficients are discussed.
Airway Resistance↗
Biokinetic parameter estimation for degradation of 2,4,6-trinitrotoluene (TNT) with Pseudomonas putida KP-T201.
The purpose of this study is to determine the biodegradation kinetics of 2,4,6-trinitrotoluene (TNT) by a newly isolated microorganism. Hundreds of microorganisms were isolated from explosives-contaminated soil in Korea. Examination of culture tests revealed that a few species of microorganisms have good ability to degrade TNT. The most efficient one was selected and identified as Pseudomonas putida KP-T201. Biodegradation of TNT was tested in a batch reactor using a pure culture of P. putida KP-T201. The effect of different concentrations of TNT on the rate of bacterial biodegradation was investigated. The Haldane equation seems to be an adequate expression for the cell growth data, and the kinetic constants obtained were mu(m)=0.65 h(-1), K(S)=0.62 mgl(-1), and K(i)=115 mgl(-1). The dependence of the bacterial specific growth rate on the concentration of TNT could be explained as a conventional model of substrate inhibition.
Journal Article↗
Genetic, phenotypic, and environmental parameter estimates of calving difficulty, weight, and measures of pelvic size in beef heifers.
The heritabilities for and the genetic, phenotypic, and environmental correlations among calving difficulty scores (CDS) and measures of size of the pelvic inlet were estimated using 547 records of 2-yr-old heifers from three synthetic breed groups. Calving difficulty score was treated first as a trait of the dam and then as a trait of the calf and was analyzed on three scales: raw scores from 0 to 3 (0 = normal birth, 3 = most difficult delivery requiring a hard pull, veterinary assistance, or surgical intervention), Snell-transformed scores, and a binary (0, 1) scale. Estimates of heritability for CDS as a trait of the dam were similar to those when it was considered a trait of the calf. Heritability estimates for CDS on the raw and transformed scales were similar and moderate in magnitude (.36 +/- .15 to .47 +/- .18) but were higher than most reported estimates. However, on the binary scale the estimates were lower (.26 +/- .17, .28 +/- .14). Estimates of heritability for the horizontal and vertical pelvic diameters and the pelvic area were high, implying that pelvic size in heifers might be readily modified by selection. The genetic and phenotypic correlations between CDS as a dam trait and pelvic dimensions were low, whereas the correlations between CDS and dam weight at calving were moderate. As a calf trait, CDS was highly correlated genetically with calf birth weight, but the phenotypic correlations were moderate.
Analysis of Variance↗
Genetic parameter estimates of ultrasound-measured longissimus muscle area and 12th rib fat thickness in Brangus cattle.
Data from 2,101 Brangus calves born from 1986 to 1990 were analyzed with a REML procedure using a derivative-free algorithm in a mixed linear animal model to obtain variance component estimates of ultrasound-measured longissimus muscle area and fat thickness. Direct additive heritabilities (ha2) of .39 and .40 were obtained for age-constant weaning and yearling longissimus muscle area (WLMA and YLMA, respectively), with a genetic correlation (rg) of .66 between them. The rg of YLMA with birth weight (BWT), weaning weight (WWT), postweaning gain (PWG), yearling weight (YWT), frame score (FS), and scrotal circumference (SC) were .17, .29, .43, .38, .01, and .19, respectively. The ha2 of age-constant yearling 12th rib fat thickness (FAT) was .14, and cattle averaged .44 cm (SD = .19). Positive rg were obtained between FAT and WLMA (.19) and YLMA (.12). Negative rg of FAT with WWT, YWT, and SC were -.17, -.53, and -.33, respectively. Positive rg were obtained between FAT and BWT (.52), PWG (.44), and FS (.14). Maternal heritabilities (hm2) of WLMA, YLMA, and FAT were .01, .01, and .10, respectively. Weight-constant WLMA, YLMA, and FAT ha2 were .36, .39, and .11, respectively. Selection based on either age-constant YLMA or FAT could potentially result in 1.06 cm2 or .005 cm change per year, respectively, which would be slightly greater than change from selection based on weight-constant YLMA or FAT. Selection based on WLMA or YLMA should be effective, and changes in these traits, growth, and SC should be possible in tandem.(ABSTRACT TRUNCATED AT 250 WORDS)
Adipose Tissue↗
Genetic parameter estimates and expected progeny differences for mature size in Angus cattle.
Mature size records collected on Angus cows of 5 to 12 yr of age were used to estimate heritabilities, genetic correlations, and EPD for mature weight and mature height. A total of 256 sires were evaluated using mature size data collected on 2,732 daughters. Data were analyzed using REML procedures with a two-trait sire model to estimate sire and error variances for mature weight and height. Models with and without adjustment of weight for body condition score were investigated. The linear model for weight and height included fixed herd-year-month the records were taken, sire genetic group, random sire, and residual error. Using unadjusted mature weights, heritabilities were .48 +/- .10 for weight and .83 +/- .11 for height. When condition score adjustments were made, heritability estimates were .45 +/- .10 for weight and .83 +/- .11 for height. Genetic (phenotypic) correlations between weight and height were .78(.58) for adjusted data and .66(.54) with no adjustment. Spearman rank correlations between sire EPD for adjusted and unadjusted data were .94 for weight and .99 for height. Two-trait models of mature cow weight with immature weights (birth weight, 205-d weight, 365-d weight) were used to assess genetic relations among mature and immature cow weights. Genetic correlations between mature weight and immature weights were .57 with birth weight, .62 with 205-d weight, and .45 with 365-d weight.
Animals↗
Genetic parameter estimation of postweaning gain, feed intake, and feed efficiency for Hereford and Angus bulls fed two different diets.
Postweaning gain performance and individual feed intake on 271 Hereford and 263 Angus bulls were recorded during three 168-d test periods from 1984 to 1986. Each breed was composed of two lines and within each breed bulls were fed either a high-energy (HD) or a medium-energy (MD) diet. Energy intake was partitioned into energy for maintenance and growth based on predicted individual animal requirements. Estimates of heritability were obtained using Restricted Maximum Likelihood with an individual animal model including fixed effects of year, diet, and covariates of initial weight and backfat change by breed and with line effects for overall data. Bulls fed the HD grew faster and had higher metabolizable energy intake per day (MEI), residual feed consumption (RFC), and gross and net feed efficiency (FE and NFE) (P < .001) than those fed the MD. Estimates of heritability for Hereford and Angus bulls, respectively, were .46 and .16 for 200-d weaning weight (WWT), .16 and .43 for average daily gain (ADG), .19 and .31 for intake per day (MEI), .43 and .45 for yearling weight (YWT), .07 and .23 for RFC, .08 and .35 for FE, and .14 and .28 for NFE. Genetic and phenotypic correlations between MEI and ADG, MEI and YWT, ADG and YWT, ADG and FE, YWT and FE, and FE and NFE were moderately to highly positive for both breeds. Negative genetic and phenotypic correlations between NFE and ADG show partial correlations of FE with ADG after accounting for energy requirement for maintenance. Residual feed consumption was negatively associated with YWT, FE, and NFE, indicating a possible genetic improvement.
Animal Feed↗
Parameter estimates for direct, maternal, and grandmaternal genetic effects for birth weight and weaning weight in Hereford cattle.
Birth and weaning weights adjusted for age of dam from four lines of Hereford cattle were analyzed to determine the relationships among grandmaternal, maternal, and direct genetic effects. Three lines were selected for 1) weaning weight (WWL), 2) yearling weight (YWL), and 3) an index of yearling weight and muscle score (IXL). The fourth line was an unselected control line (CTL). Numbers of observations ranged from 1,699 (CTL) to 2,811 (WWL), and number of animals in the pedigree file ranged from 2,266 to 3,192. Two animal models were used to obtain estimates by REML using an average information method. Model 1 included random direct and maternal genetic, permanent maternal environmental, and residual environmental effects, and fixed sex x year effects. Model 2 additionally included random grandmaternal genetic and permanent grandmaternal environmental effects. For birth weight, Models 1 and 2 gave almost identical estimates for direct and maternal heritability, and for the fraction of variance that was due to maternal permanent environmental effects. Estimates for grandmaternal heritability could be obtained only for IXL (.03) and CTL (.01). For weaning weight, estimates for direct heritability were similar from both models. Estimates for maternal heritability from Model 1 were .18, .20, .13, and .20, and corresponding estimates from Model 2 were .34, .31, .13, and .34 for WWL, YWL, IXL, and CTL, respectively. For IXL, estimates for variances that were due to grandmaternal genetic and grandmaternal permanent environmental variances could not be obtained and were set to zero. Grandmaternal heritability estimates for WWL, YWL, and CTL were .05, .09, and .12. Estimates of correlations between direct and maternal genetic effects were -.13, -.44, -.11, and -.26 for WWL, YWL, IXL, and CTL. Estimates of correlations between direct and grandmaternal genetic effects were .21, .83, and .55, and those between maternal and grandmaternal genetic effects were -.99, -.84, and -.76 for WWL, YWL, and CTL, respectively. These results indicate that grandmaternal effects may be important for weaning weight and that maternal heritability may be underestimated if grandmaternal effects are not included in the model.
Animals↗
Genetic parameter estimates for serum insulin-like growth factor-I concentration and carcass traits in Angus beef cattle.
Divergent selection for serum insulin-like growth factor-I (IGF-I) concentration began at the Eastern Ohio Resource Development Center (EORDC) in 1989 using 100 spring-calving (50 high line and 50 low line) and 100 fall-calving (50 high line and 50 low line) purebred Angus cows. Following weaning, bull and heifer calves were fed in drylot for a 140-d postweaning period. At the conclusion of the postweaning test, bulls not selected for breeding were slaughtered and carcass data were collected at a commercial abbatoir. At the time of this analysis, IGF-I measurements were available for 1,283 bull and heifer calves, and carcass data were available for 452 bulls. A set of multiple-trait, derivative-free, restricted maximum likelihood (MTDFREML) computer programs were used for data analysis. Estimates of direct heritability for IGF-I concentration at d 28, 42, and 56 of the postweaning period, and for mean IGF-I concentration were .32, .59, .31, and .42, respectively. Direct heritabilities for carcass traits ranged from .27 to 1.0, .26 to 1.0, and .23 to 1.0 when the age-, fat-, and weight-constant end points, respectively, were used, with marbling score having the smallest heritability and longissimus muscle area having the highest heritability in each case. Maternal heritability and the proportion of phenotypic variance due to permanent environmental effect of dam generally were < or = .21 for IGF-I concentrations and for carcass traits other than longissimus muscle area. Additive genetic correlations of IGF-I concentrations with backfat thickness, longissimus muscle area, hot carcass weight, marbling score, quality grade, and yield grade averaged -.26, .19, -.04, -.53, -.45, and -.27, respectively, when carcass data were adjusted to an age-constant end point. Bulls with lower IGF-I concentrations had higher marbling scores and quality grades, but also had higher backfat thickness and yield grades regardless of the slaughter end point. Serum IGF-I concentration may be a useful selection criterion when efforts are directed toward improvement of marbling scores and quality grades of beef cattle.
Animals↗
Simulation study of teat score in first-parity Gelbvieh cows: parameter estimation.
Teat scores from 9,598 first-parity Gelbvieh cows were used to investigate the adequacy of grouping approaches to decrease score misclassifications or inconsistencies as well as to simplify the data collection process. The procedure was tested using simulated data and then validated using teat score records of Gelbvieh cattle. First-parity cows were considered to be 4 yr of age or younger at first calving, did not have multiple records within 280 d, and were at least 50% Gelbvieh. Producers scored cows within 24 h of parturition. Teat score, a subjective measure of teat size, ranged from 0 (very large) to 50 (very small). A linear mixed model that included herd-year, month of calving, and age at calving as systematic effects; regression on the percentage of Gelbvieh; and additive breeding values (BV) and residual as random effects was used to generate the data. Simulated data were analyzed using one of three scoring methods: all values (S50), 10 classes (S10), and five classes (S5). The 10 classes were formed by subdividing every five scores into a single class starting at score zero. Similarly, the five classes were formed by combining every 10 scores into one class. The average Pearson correlations, based on five replicates, between the true and estimated BV (systematic effects) were 0.36 (0.85), 0.35 (0.89), and 0.32 (0.87) using S50, S10, and S5, respectively. Average correlations between estimated BV (systematic effects) were 0.97 (0.95), 0.89 (0.92), and 0.92 (0.97) based on S50 and S10, S50 and S5, and S10 and S5, respectively. Field data were used to validate the simulation procedure. The field data were categorized into 10 classes (F10) and five classes (F5) as described for the simulated data. Pearson correlations between estimated BV (systematic effects) were 0.99 (0.93), 0.93 (0.88), and 0.93 (0.96), based on F50 with F10, F50 with F5, and F10 with F5, respectively. The extremely high correlations between predicted BV based on S50, S10, S5, F50, F10, with F5 suggest that a simplified score classification method could be adopted without compromising the expected genetic progress for the trait under consideration. Furthermore, the difference in corresponding Pearson correlations across the field and simulated data might suggest the presence of some inconsistencies or misclassifications of the actual scoring system.
Animals↗
Genetic parameter estimates for serum insulin-like growth factor-I concentration and ultrasound measurements of backfat thickness and longissimus muscle area in Angus beef cattle.
A divergent selection experiment for serum IGF-I concentration began at the Eastern Ohio Resource Development Center in 1989 using 100 spring-calving (50 high line and 50 low line) and 100 fall-calving (50 high line and 50 low line) purebred Angus cows. Following weaning, bull and heifer calves were fed in drylot for a 140-d period. Real-time ultrasound measurements of backfat thickness and longissimus muscle area were taken on d 56 and 140 of the postweaning test. Only ultrasound data from calves born from fall 1995 through spring 1999 were included in the analysis. At the time of this study, IGF-I measurements were available for 1,521 bull and heifer calves, and ultrasound data were available for 636 bull and heifer calves. Data were analyzed by multiple-trait, derivative-free, restricted maximum likelihood methods. Estimates of direct heritability for IGF-I concentration at d 28, 42, and 56 of the postweaning period, and for mean IGF-I concentration were 0.26 +/- 0.07, 0.32 +/- 0.08, 0.26 +/- 0.07, and 0.32 +/- 0.08, respectively. Direct heritabilities for ultrasound estimates of backfat thickness ranged from 0.17 +/- 0.11 to 0.28 +/- 0.12, whereas direct heritabilities for longissimus muscle area ranged from 0.20 +/- 0.10 to 0.36 +/- 0.12, depending on the time of measurement and the covariate used for adjustment (age vs. weight). Direct genetic correlations of IGF-I concentrations with backfat thickness at d 56 and 140 and with longissiumus muscle area at d 56 and 140 averaged 0.02, 0.20, -0.08, and 0.23, respectively, when age was used as the covariate for both IGF-I and ultrasound measurements. Corresponding genetic correlations when age was used as the covariate for IGF-I and weight was used as the covariate for ultrasound measurements were 0.05, -0.07, -0.22, and -0.04, respectively. Therefore, the positive associations of serum IGF-I concentration with backfat thickness and longissimus muscle area at d 140 seem to have been partially mediated by weight. Results of this study do not indicate strong associations of serum IGF-I concentration with fat thickness or muscling of bulls and heifers during the postweaning feedlot period.
Adipose Tissue↗