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PubMed1984

RECFIT: a microcomputer-based nonlinear regression curve-fitting package for the quantitative resolution of beta-adrenoceptor subtypes and estimation of nonspecific binding.

A dedicated nonlinear regression based curve-fitting packages has been developed for quantitative analysis of beta-adrenoceptor subtypes. A feature of this package is the provision to obtain initial parameter estimates using a conversational graphical technique where the user is prompted for parameter estimates, and the resulting curve is displayed over the data. Data are then fitted to a one- or two-binding site model with user-selected weighting and constraints on the parameters. A novel feature is the provision to estimate the nonspecific binding component in the assays as a parameter in the model. The printout for each model consists of the parameters and their standard deviations, estimates of the goodness of fit, an analysis of residuals, and a graph of the data points overlayed with the fitted curve. The nonlinear regression algorithm is based on that of Gauss-Newton. When unweighted, the values determined by RECFIT are essentially the same as those found using the BMDPAR programs on an ICL 2976 mainframe computer. The implementation is reasonably efficient; a typical run for a two-site fit, using nine data points and estimating nonspecific binding, took a total time of about 8 min, excluding data entry and derivation of initial estimates, 4 min for the fitting, 30 sec for graph generation, and 2-3 min for printing of the graph and data.

Binding Sites↗
PubMed1999

Endoscopic mucosal resection with a cap-fitted endoscope versus freehand gastric mucosectomy in an animal model.

BACKGROUND: Endoscopic mucosal resection with a cap-fitted endoscope appears to be as effective but easier to perform than freehand mucosectomy. However, experience with this technique has been limited to small case series and there is a lack of data from direct comparison trials. METHODS: Nine pigs were randomized to mucosectomy using a cap-fitted endoscope or the freehand technique. Five mucosal resections were performed at five different sites in the gastric body in each pig. Eight to ten milliliters of a saline, epinephrine, and methylene blue solution were injected to raise a bleb to simulate a mucosal lesion. Endoscopic mucosal resection with a cap-fitted endoscope was performed by suctioning the bleb into the cap device pre-looped with an oval snare; mucosectomy was performed electrosurgically. Freehand mucosectomy was performed by encircling and then resecting the bleb using an oval snare. The ease of procedure (1 = "very easy" to 5 = "unable to complete") was assessed after each resection. The animals were recovered, maintained, and then humanely sacrificed after 2 weeks. RESULTS: Five pigs underwent endoscopic mucosal resection with a cap-fitted endoscope and 4 underwent freehand mucosectomy. Eight animals survived for 2 weeks without complications and one animal from the freehand group died of massive hemorrhage within 48 hours of endoscopy. Both methods produced rounded resection specimens measuring 9 to 12 mm in diameter of the full thickness of the mucosa and the submucosa. Overall ease of resection was 1.84 +/- 0.52 for the cap-fitted group and 2.98 +/- 0.86 for the freehand group (p < 0.0001). All of the sites identified at autopsy were completely re-epithelialized, except for the five sites found in the pig that died prematurely. CONCLUSIONS: Endoscopic mucosal resection with a cap-fitted endoscope is as effective, safe, but easier to perform compared with freehand mucosectomy.

Animals↗
PubMed1987

On the difficulties of fitting the double Michaelis-Menten equation to kinetic data.

The double Michaelis-Menten equation describes the reaction kinetics of two independent, saturable uptake mechanisms. The use of this equation to describe drug uptake has been reported several times in the literature, and several methods have been published to fit the equation to data. So far, however, confidence intervals on the fitted kinetic parameters have not been provided. We present a grid-search method for fitting the double Michaelis-Menten equation to kinetic uptake data, and a Monte-Carlo procedure for estimating confidence intervals on the fitted parameters. We show that the fitting problem is extremely ill-conditioned, and that very accurate data are required before any confidence can be placed in the fitted parameters.

Algorithms↗
PubMed2003

Stress-relieving and porcelain firing cycle influence on marginal fit of commercially pure titanium and titanium-aluminum-vanadium copings.

OBJECTIVES: This study evaluated: (1) the marginal fit of copings fabricated from commercially pure titanium (cp Ti) and titanium-aluminum-vanadium alloy (Ti-6Al-4V) after each firing cycle for a recommended porcelain; and (2) the effectiveness of a stress-relieving treatment on the fit. The results were compared with copings made with Pd-Ag alloy submitted to the recommended porcelain firing protocol. METHODS: Bovine teeth were machined for metal-ceramic crowns and die casts were obtained for waxing patterns. The firing cycle of titanium porcelain was performed on cp Ti and Ti-6Al-4V copings obtained using the Rematitan System. A stress-relieving treatment (cp Ti treated and Ti-6Al-4V treated groups) was performed on original invested castings at the first porcelain firing temperature (800 degrees C). Fit (microm) was measured in the 'as cast' condition and after each porcelain firing cycle with a traveling microscope. The values were compared using the analysis of variance and Tukey's test (P<0.05), the Pd-Ag group was compared to titanium groups using Dunnett's test (P<0.05). RESULTS: The marginal fit values in the as-cast condition (initial) were 84.43 microm for Ti-6Al-4V not treated, 76.35 microm for Ti-6Al-4V treated, 86.09 microm for cp Ti not treated, 97.66 microm for cp Ti treated and 58.11 microm for Pd-Ag group. The Ti-6Al-4V, cp Ti, and Pd-Ag groups exhibit significant differences in marginal fit values when the as-cast condition (initial) was compared with those after the recommended porcelain firing protocol (by Tukey's test at 5% probability level). No significant differences were observed between stress-relieving treated and not treated groups.Significance. The firing cycles used for porcelain build-up may worsen the fit of titanium copings to values that suggest no inferences to the detriment of clinical applications.

Alloys↗
PubMed1990

Effect of press-fit femoral stems on strains in the femur. A photoelastic coating study.

A photoelastic coating method was used to study the strain patterns on the surface of the femur, before and after insertion of femoral stems. The anatomically shaped stems were press-fit without a collar, press-fit with a collar, and press-fit with proximal cementing to approximate a bone ingrowth situation. The strain patterns of the intact femurs were consistent with bending. The pattern changed considerably after stem insertion, probably due to the stiffening effect of the stems. Nevertheless, the collarless press-fit stem preserved 64% of the magnitude of the proximal medial strain. The collar restored the average to normal, but the surface strains varied because of the localized regions of contact between the collar and the bone. Proximal cementing gave results similar to those of the collarless press-fit. The press-fit stems often showed local patches of high strain, probably reflecting local endosteal contact points. Local high stresses at the level of the distal tip were seen in only a few instances.

Cadaver↗
PubMedDate not supplied

Evolutionary robots with on-line self-organization and behavioral fitness.

We address two issues in Evolutionary Robotics, namely the genetic encoding and the performance criterion, also known as the fitness function. For the first aspect, we suggest to encode mechanisms for parameter self-organization, instead of the parameters themselves as in conventional approaches. We argue that the suggested encoding generates systems that can solve more complex tasks and are more robust to unpredictable sources of change. We support our arguments with a set of experiments on evolutionary neural controllers for physical robots and compare them to conventional encoding. In addition, we show that when also the genetic encoding is left free to evolve, artificial evolution will select to exploit mechanisms of self-organization. For the second aspect, we shall discuss the role of the performance criterion, als known as fitness function, and suggest Fitness Space as a framework to conceive fitness functions in Evolutionary Robotics. Fitness Space can be used as a guide to design fitness functions as well as to compare different experiments in Evolutionary Robotics.

Evolution, Molecular↗
PubMed2002

The fitness of filamentous fungi.

Fitness is a common currency in comparative biology. Without data on fitness, hypotheses about the adaptive significance of phenotypes or basic mechanisms of evolution, for example natural selection, remain speculative. Experiments with fungi can address questions specific to fungi or questions with a broader significance. Fungi can challenge the generality of fundamental evolutionary principles, yet there are no standard measures of fungal fitness. We argue that focusing on a single aspect of a complex life cycle, or a single measure of fitness (e.g. the number of asexual spores) is appropriate. Choosing which aspect of fitness to measure can be facilitated by an understanding of how fitness measures are correlated. Choices can also be based on the ecology of a species, for example whether a fungus is semelparous and reproduces once, or iteroparous and reproduces multiple times.

Biological Evolution↗
PubMed2003

A measure of curve fitting error for noise filtering diffusion tensor MRI data.

A parameter, chi2p, based on the fitting error was introduced as a measure of reliability of DT-MRI data, and its properties were investigated in simulations and human brain data. Its comparison with the classic chi2 revealed its sensitivity to both the goodness of fit and the pixel signal-to-noise-ratio (SNR), unlike the classic chi2, which is sensitive only to the goodness of fit. The new parameter was thus able to separate effectively pixels with coherent signals (having small fitting error and/or high SNR) from those with random signals (having inconsistent fitting and/or low SNR). A practical advantage of chi2p over the classic chi2 was that chi2p is quantified directly from the data of each pixel, without requiring accurate estimation of data-dependent parameters (such as noise variance), which often makes application of the classic chi2 problematic. Analytical approximations of chi2p enabled an objective (data-independent) and automated calculation of a threshold value, used for internal scaling of the chi2p map. Apart from assessing data reliability on a pixel-by-pixel basis, chi2p was used to develop an objective and generic methodology for the exclusion of pixels with unreliable DT information by discarding pixels with chi2p values exceeding the threshold. Pixels corresponding to very low SNR, and poorly fitted cerebrospinal fluid and surrounding brain tissue, had increased chi2p values and were successfully excluded, providing DT anisotropy maps free from artifactual anisotropic appearance.

Adult↗
PubMed2002

Fitness of drug resistant HIV-1: methodology and clinical implications.

Recent studies of human immunodeficiency virus type 1 (HIV-1) fitness have examined the potential relationship with plasma viral load, drug resistance, and disease progression. For example, treatment of HIV-1 infected individuals with antiretroviral drugs may result in the selection and emergence of inhibitor-resistant variants with reduced replicative capacity. However, it is still unclear whether in vitro HIV-1 fitness has any direct relationship to in vivo disease progression or treatment success. A related question is which in vitro assay of viral fitness is the most appropriate for comparison with in vivo HIV-1 fitness. Characterization of the relative viral fitness of drug-resistant HIV-1 strains may lead to a better understanding of whether or not less fit viruses pose a clinical benefit to the patient.

Antiretroviral Therapy, Highly Active↗
PubMed1999

Fitness of wild-caught Drosophila melanogaster females: allozyme variants of GPDH, ADH, PGM, and EST.

We have collected several hundred Drosophila melanogaster flies (near Davis, California), isolated them individually, without anesthesia, at the collecting site, and estimated the fitness components of the wild-caught females under different environmental conditions. The fitness parameters measured are fecundity, oviposition rate, and productivity (egg-to-adult viability, development rate, and number of progeny). The environmental variables are two temperatures (22 degrees C and 28 degrees C) and two densities ('scant' and 'crowded'). After the fitness measurements are completed for each individual female, its genotype is determined at four loci encoding enzymes: GPDH and ADH, located on chromosome II; and PGM and EST-C, located on chromosome III. Density has a large significant effect on productivity; temperature has significant effects on fecundity, oviposition rate, and development rate. The experiments show that allozyme polymorphisms are associated with selection effects. Fitness differences between allozyme genotypes occur for all fitness components, except oviposition rate. But which genotype is superior depends on the environmental conditions; heterozygotes exhibit higher fitness than homozygotes in a number of cases, but inferior in others. A unique feature of the present experiments is that the experimental flies are wild-caught females rather than laboratory-bred individuals.

Alcohol Dehydrogenase↗
PubMed1998

The impact of ratee's disability on performance judgments and choice as partner: the role of disability-job fit stereotypes and interdependence of rewards.

An experiment assessed the impact of disability-job fit stereotypes and reward interdependence on personnel judgments about persons with disabilities. Students (N = 87) evaluated 3 confederates. The experiment varied disability of the target confederate (dyslexia vs. nondisabled), task, and dependence of rater rewards on partner performance. Two disability-task combinations represented stereotypical poor fit and good fit. Dependent variables were performance evaluations, performance expectations, and ranking of target as a partner. There was negative bias against the confederate with dyslexia in poor-fit conditions. In the interdependent reward condition, there was a negative main effect for disability, regardless of fit. No effects for disability were found on performance ratings or expectations. Results indicate the need to consider disability-job fit stereotypes and consequences to raters when assessing the impact of disability on personnel judgments.

Adult↗
PubMed2004

The effect of applicant influence tactics on recruiter perceptions of fit and hiring recommendations: a field study.

The present study examined the effect of applicant influence-tactic use on recruiter perceptions of fit. Two tactics, ingratiation and self-promotion, were expected to have positive effects on recruiter perceptions of fit and on recruiter hiring recommendations. In addition, the authors expected recruiter fit perceptions to mediate the relationship between applicant influence tactics and recruiter hiring recommendations. Results suggested that ingratiation had a positive effect on perceived fit and recruiter hiring recommendations (and indirectly, on receipt of a job offer). In addition, perceived fit mediated the relationship between ingratiation and hiring recommendations. The effects of self-promotion on fit and hiring recommendations were generally weak and nonsignificant. Implications and directions for future research are discussed.

Adult↗
PubMed2005

Global, local, and graphical person-fit analysis using person-response functions.

Person-fit statistics test whether the likelihood of a respondent's complete vector of item scores on a test is low given the hypothesized item response theory model. This binary information may be insufficient for diagnosing the cause of a misfitting item-score vector. The authors propose a comprehensive methodology for person-fit analysis in the context of nonparametric item response theory. The methodology (a) includes H. Van der Flier's (1982) global person-fit statistic U3 to make the binary decision about fit or misfit of a person's item-score vector, (b) uses kernel smoothing (J. O. Ramsay, 1991) to estimate the person-response function for the misfitting item-score vectors, and (c) evaluates unexpected trends in the person-response function using a new local person-fit statistic (W. H. M. Emons, 2003). An empirical data example shows how to use the methodology for practical person-fit analysis.

Humans↗
PubMed2006

Robustness-epistasis link shapes the fitness landscape of a randomly drifting protein.

The distribution of fitness effects of protein mutations is still unknown. Of particular interest is whether accumulating deleterious mutations interact, and how the resulting epistatic effects shape the protein's fitness landscape. Here we apply a model system in which bacterial fitness correlates with the enzymatic activity of TEM-1 beta-lactamase (antibiotic degradation). Subjecting TEM-1 to random mutational drift and purifying selection (to purge deleterious mutations) produced changes in its fitness landscape indicative of negative epistasis; that is, the combined deleterious effects of mutations were, on average, larger than expected from the multiplication of their individual effects. As observed in computational systems, negative epistasis was tightly associated with higher tolerance to mutations (robustness). Thus, under a low selection pressure, a large fraction of mutations was initially tolerated (high robustness), but as mutations accumulated, their fitness toll increased, resulting in the observed negative epistasis. These findings, supported by FoldX stability computations of the mutational effects, prompt a new model in which the mutational robustness (or neutrality) observed in proteins, and other biological systems, is due primarily to a stability margin, or threshold, that buffers the deleterious physico-chemical effects of mutations on fitness. Threshold robustness is inherently epistatic-once the stability threshold is exhausted, the deleterious effects of mutations become fully pronounced, thereby making proteins far less robust than generally assumed.

Epistasis, Genetic↗
PubMed1994

Fusion between Newcastle disease virus and erythrocyte ghosts using octadecyl Rhodamine B fluorescence assay produces dequenching curves that fit the sum of two exponentials.

The kinetics of fusion between Newcastle disease virus and erythrocyte ghosts has been investigated with the octadecyl Rhodamine B chloride assay [Hoekstra, De Boer, Klappe, and Wilschut (1984) Biochemistry 23, 5675-5681], and the data from the dequenching curves were fitted by non-linear regression to currently used kinetic models. We used direct computer-assisted fitting of the dequenching curves to the mathematical equations. Discrimination between models was performed by statistical analysis of different fits. The experimental data fit the exponential model previously published [Nir, Klappe, and Hoekstra (1986) Biochemistry 25, 2155-2161] but we describe for the first time that the best fit was achieved for the sum of two exponential terms: A1[1-exp(-k1t)]+A2[1-exp(-k2t)]. The first exponential term represents a fast reaction and the second a slow dequenching reaction. These findings reveal the existence of two independent, but simultaneous, processes during the fusion assay. In order to challenge the model and to understand the meaning of both equation, fusion experiments were carried out under different conditions well known to affect viral fusion (changes in pH, temperature and ghost concentration, and the presence of disulphide-reducing agents or inhibitors of viral neuraminidase activity), and the same computer fitting scheme was followed. The first exponential equation represents the viral protein-dependent fusion process itself, because it is affected by the assay conditions. The second exponential equation accounts for a nonspecific reaction, because it is completely independent of the assay conditions and hence of the viral proteins. An interpretation of this second process is discussed in terms of probe transfer between vesicles.

Animals↗
PubMedDate not supplied

Primary stability with tibial press-fit fixation of patellar ligament graft: An experimental study in ovine knees.

PURPOSE: To investigate the initial fixation strength and to assess the value of tibial press-fit fixation of the bone-tendon-bone graft in anterior cruciate ligament reconstruction. TYPE OF STUDY: Nonrandomized control trial. METHODS: For tibial press-fit fixation, the tibial bone block of the bone-tendon-bone graft is countersunk in a bony groove at the distal tunnel outlet and fixed over a bone bridge with 2 No. 6 Ethibond sutures. The bone cylinder harvested from the tibial tunnel using an oscillating hollow saw is plugged into the tibial tunnel parallel to the graft, thus providing for additional anchoring of the graft by tibial press-fit fixation. In a comparative experimental study in 46 ovine knees, this fixation method was assessed for its value in anterior cruciate ligament reconstruction. A tibial bone tunnel was placed in routine manner in each ovine tibia using a target drill unit and an oscillating hollow saw. The complete patellar ligament, proximally attached to the patella and distally to a cylindrical bone block (20 x 8.4 mm), served as graft. Tibial fixation in group A (n = 10) was done using a titanium interference screw (20 x 8 mm), in group B (n = 10) using a titanium staple, in group C (n = 12) using suture fixation over a bone bridge, and in group D (n = 14) using the press-fit fixation described above. In a materials testing machine, all specimens were subjected to continuously increasing load until failure at a velocity of 1 mm/second. Ultimate failure load, stiffness, stress-strain characteristics, and failure mode were evaluated. RESULTS: Ultimate load to failure was 572 N (range, 473 to 680 N) in group A, corresponding to a fixation stiffness of 17.68 N/mm. For group B, ultimate load to failure was 608.4 N (range, 511 to 727 N) and stiffness of 19.92 N/mm. Bone block dislocation was the failure mode in groups A and B. Group C with exclusive suture fixation showed an ultimate load to failure of 304.5 N (range, 120 to 327 N) and a stiffness of only 6.96 N/mm. The mode of failure was suture cutout caused by the bone block in 9 of the cases and untying of the suture knot in 3 cases. Group D with press-fit fixation showed a significantly higher primary stability of 758 N (range, 513 to 993 N) relative to group C, with a corresponding stiffness of 25.12 N/mm (P <.02). In this group, the mode of failure was ligamentous rupture from the bone block. Regarding mechanical properties, no significant differences were seen between groups A, B, and D. CONCLUSIONS: Tibial press-fit fixation allows for metal-free fixation with high primary stability. By refilling the bone tunnel, the ligament (with a rather small cross-sectional diameter compared with hamstrings) is safely fixed within the bone tunnel to prevent potential postoperative tunnel enlargement due to movement of the graft within the tunnel. Anchoring the graft at the entrance into the joint, it provides for reduced graft length and adequate elasticity and accomplishes the requirements of fixation at the correct anatomic insertion site.

Animals↗
PubMed2005

On fitting a gold embedded atom method potential using the force matching method.

We fit a new gold embedded atom method (EAM) potential using an improved force matching methodology which included fitting to high-temperature solid lattice constants and liquid densities. The new potential shows a good overall improvement in agreement to the experimental lattice constants, elastic constants, stacking fault energy, radial distribution function, and fcc/hcp/bcc lattice energy differences over previous potentials by Foiles, Baskes, and Daw (FBD) [Phys. Rev. B 33, 7983 (1986)] Johnson [Phys. Rev. B 37, 3924 (1988)], and the glue model potential by Ercolessi et al. [Philos. Mag. A 50, 213 (1988)]. Surface energy was improved slightly as compared to potentials by FBD and Johnson but as a result vacancy formation energy is slightly inferior as compared to the same potentials. The results obtained here for gold suggest for other metal species that further overall improvements in potentials may still be possible within the EAM framework with an improved fitting methodology. On the other hand, we also explore the limitations of the EAM framework by attempting a brute force fit to all properties exactly which was found to be unsuccessful. The main conflict in such a brute force fit was between the surface energy and the liquid lattice constant where both could not be fitted identically. By intentionally using a very large number of spline sections for the pair potential, electron-density function, and embedding energy function, we eliminated a lack of functional freedom as a possible cause of this conflict and hence can conclude that it must result from a fundamental limitation in the EAM framework.

Journal Article↗
PubMed2004

The distribution of fitness effects caused by single-nucleotide substitutions in an RNA virus.

Little is known about the mutational fitness effects associated with single-nucleotide substitutions on RNA viral genomes. Here, we used site-directed mutagenesis to create 91 single mutant clones of vesicular stomatitis virus derived from a common ancestral cDNA and performed competition experiments to measure the relative fitness of each mutant. The distribution of nonlethal deleterious effects was highly skewed and had a long, flat tail. As expected, fitness effects depended on whether mutations were chosen at random or reproduced previously described ones. The effect of random deleterious mutations was well described by a log-normal distribution, with -19% reduction of average fitness; the effects distribution of preobserved deleterious mutations was better explained by a beta model. The fit of both models was improved when combined with a uniform distribution. Up to 40% of random mutations were lethal. The proportion of beneficial mutations was unexpectedly high. Beneficial effects followed a gamma distribution, with expected fitness increases of 1% for random mutations and 5% for preobserved mutations.

Animals↗