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PubMed1998

Overestimation of base-rate differences in complex perceptual categories.

The optimality of multidimensional perceptual categorization performance was examined for several base-rate ratios, for both integral and separable dimension stimuli, and for complex category structures. In all cases, the optimal decision bound was highly nonlinear. Observers completed several experimental sessions, and all analyses were performed at the single-observer level using a series of nested models derived from decision-bound theory (Maddox, 1995; Maddox & Ashby, 1993). In every condition, all observers were found to be sensitive to the base-rate manipulations, but the majority of observers appeared to overestimate the base-rate difference. These findings converge with those for cases in which the optimal decision bound was linear (Maddox, 1995) and suggest that base-rates are learned in a similar fashion regardless of the complexity of the optimal decision bound. Possible explanations for the consistent overestimate of the base-rate difference are discussed. Several continuous-valued analogues of Kruschke's (1996) theory of base-rate learning with discrete-valued stimuli were tested. These models found some support, but in all cases were outperformed by a version of decision-bound theory that assumed accurate knowledge of the category structure and an overestimate of the base-rate difference.

Humans↗

PubMed1992

Determination of sensitivity to metocurine in exercised horses.

On the basis of results in dogs, conditioning exercise may increase sensitivity to nondepolarizing muscle relaxants. Five Thoroughbreds were exercised/conditioned 3 times weekly on a treadmill for 8 months. Increasing maximal rate of O2 consumption verified that the horses were responding to exercise conditioning. Six nonexercised Thoroughbreds served as the control group. Studies were done with horses under general anesthesia by use of halothane during partial paralysis by a brief constant-rate infusion with the muscle relaxant, metocurine iodide. Quantification of degree of paralysis of the hoof twitch (eg, digital extensor) occurred with simultaneous quantification of blood values of metocurine. Pharmacokinetic and pharmacodynamic analyses of the data were done by a nonlinear regression program, using the Hill equation. There were no differences in findings between exercised and nonexercised horses. The mean blood concentration for the 50% paralyzing dose of metocurine was 0.44 +/- 0.11 (SD) microgram/ml in exercised horses, and 0.58 +/- 0.22 microgram/ml in nonexercised horses. Despite evidence for a response to conditioning, a significant change in the sensitivity of the neuromuscular junction to metocurine was not found.

Animals↗

PubMed1987

Ultradian rhythmometry by adaptive line enhancer.

Widrow's adaptive line enhancer (ALE) was applied to human rectal temperatures at 12-min intervals for 9 days. Changes along the scale of 9 days in circadian pattern suggested the occurrence of infradian variation, resolved by analyses of the entire series by linear-nonlinear rhythmometry. Once the original signal is filtered to extract the circadian component, ultradian components appear. A wide peak with a period of about 100 min, seen each day, may reflect a consistent ultradian component. Other peaks at lower ultradian frequencies (around a period of approximately 8 hr) are unsteady and may correspond to harmonics of the partially extracted circadian oscillation. Ultradian components with periods of approximately 131 and approximately 68 min were also suggested independently by population-mean cosinor summarizing data collected over a total of 158 days. Results show the ability of ALE to detect and reconstruct periodic components in noise and to track their changes in frequency, notably when other methods are also used to assess separately the components and the corresponding uncertainties involved.

Biometry↗

PubMed2004

Second harmonic generation of shear waves in crystals.

Nonlinear self-interaction of shear waves in electro-elastic crystals is investigated based on the rotationally invariant state function. Theoretical analyses are conducted for cubic, hexagonal, and trigonal crystals. The calculations show that nonlinear self-interaction of shear waves has some characteristics distinctly different from that of longitudinal waves. First, the process of self-interaction to generate its own second harmonic wave is permitted only in some special wave propagation directions for a shear wave. Second, the geometrical nonlinearity originated from finite strain does not contribute to the second harmonic generation (SHG) of shear waves. Therefore, unlike the case of longitudinal wave, the second-order elastic constants do not involve in the nonlinear parameter of the second harmonic generation of shear waves. Third, unlike the nonlinearity parameter of the longitudinal waves, the nonlinear parameter of the shear wave exhibits strong anisotropy, which is directly related to the symmetry of the crystal. In the calculations, the electromechanical coupling nonlinearity is considered for the 6 mm and 3 m symmetry crystals. Complement to the SHG of longitudinal waves already in use, the SHG of shear waves provides more measurements for the determination of third-order elastic constants of solids. The method is applied to a Z-cut lithium niobate (LiNbO3) crystal, and its third-order elastic constant c444 is determined.

Journal Article↗

PubMed2006

Nonlinear dynamics as an essential tool for non-destructive characterization of soft nanostructures using tapping-mode atomic force microscopy.

Tapping-mode atomic force microscopy provides a means for successful and non-intrusive characterization of soft physical and biological structures at the nanoscale. Its full potential can only be realized, provided that the response of the oscillating probe tip to the strongly nonlinear, near-field force interactions with the structure and the intermittency of contact can be accurately modelled, analysed, controlled and interpreted. To this end, this paper reviews some experimental observations of fundamentally nonlinear behaviour of the tip dynamics. It discusses the nonlinear phenomenology that explains their presence in the tapping-mode operation of the atomic force microscope. Particular emphasis is placed on the coexistence of different steady-state responses and their origin in transitions across regions of rapidly varying force characteristics. The heuristics of a recently developed method for treating such transitions are presented and insights into its implications are drawn from related micro- and nanoscale applications.

Journal Article↗

PubMed2006

A penetration-based finite element method for hyperelastic 3D biphasic tissues in contact. Part II: finite element simulations.

The penetration method allows for the efficient finite element simulation of contact between soft hydrated biphasic tissues in diarthrodial joints. Efficiency of the method is achieved by separating the intrinsically nonlinear contact problem into a pair of linked biphasic finite element analyses, in which an approximate, spatially and temporally varying contact traction is applied to each of the contacting tissues. In Part I of this study, we extended the penetration method to contact involving nonlinear biphasic tissue layers, and demonstrated how to derive the approximate contact traction boundary conditions. The traction derivation involves time and space dependent natural boundary conditions, and requires special numerical treatment. This paper (Part II) describes how we obtain an efficient nonlinear finite element procedure to solve for the biphasic response of the individual contacting layers. In particular, alternate linearization of the nonlinear weak form, as well as both velocity-pressure, v-p, and displacement-pressure, u-p, mixed formulations are considered. We conclude that the u-p approach, with linearization of both the material law and the deformation gradients, performs best for the problem at hand. The nonlinear biphasic contact solution will be demonstrated for the motion of the glenohumeral joint of the human shoulder joint.

Anisotropy↗

PubMed2001

Striatal contributions to category learning: quantitative modeling of simple linear and complex nonlinear rule learning in patients with Parkinson's disease.

The contribution of the striatum to category learning was examined by having patients with Parkinson's disease (PD) and matched controls solve categorization problems in which the optimal rule was linear or nonlinear using the perceptual categorization task. Traditional accuracy-based analyses, as well as quantitative model-based analyses were performed. Unlike accuracy-based analyses, the model-based analyses allow one to quantify and separate the effects of categorization rule learning from variability in the trial-by-trial application of the participant's rule. When the categorization rule was linear, PD patients showed no accuracy, categorization rule learning, or rule application variability deficits. Categorization accuracy for the PD patients was associated with their performance on a test believed to be sensitive to frontal lobe functioning. In contrast, when the categorization rule was nonlinear, the PD patients showed accuracy, categorization rule learning, and rule application variability deficits. Furthermore, categorization accuracy was not associated with performance on the test of frontal lobe functioning. Implications for neuropsychological theories of categorization learning are discussed.

Aged↗

PubMed2006

A search for thresholds and other nonlinearities in the relationship between hexavalent chromium and lung cancer.

The exposure-response relationship for airborne hexavalent chromium exposure and lung cancer mortality is well described by a linear relative rate model. However, categorical analyses have been interpreted to suggest the presence of a threshold. This study investigates nonlinear features of the exposure response in a cohort of 2,357 chemical workers with 122 lung cancer deaths. In Poisson regression, a simple model representing a two-step carcinogenesis process was evaluated. In a one-stage context, fractional polynomials were investigated. Cumulative exposure dose metrics were examined corresponding to cumulative exposure thresholds, exposure intensity (concentration) thresholds, dose-rate effects, and declining burden of accumulated effect on future risk. A simple two-stage model of carcinogenesis provided no improvement in fit. The best-fitting one-stage models used simple cumulative exposure with no threshold for exposure intensity and had sufficient power to rule out thresholds as large as 30 microg/m3 CrO3 (16 microg/m3 as Cr+6) (one-sided 95% confidence limit, likelihood ratio test). Slightly better-fitting models were observed with cumulative exposure thresholds of 0.03 and 0.5 mg-yr/m3 (as CrO3) with and without an exposure-race interaction term, respectively. With the best model, cumulative exposure thresholds as large as 0.4 mg-yr/m3 CrO3 were excluded (two-sided upper 95% confidence limit, likelihood ratio test). A small departure from dose-rate linearity was observed, corresponding to (intensity)0.8 but was not statistically significant. Models in which risk-inducing damage burdens declined over time, based on half-lives ranging from 0.1 to 40 years, fit less well than assuming a constant burden. A half-life of 8 years or less was excluded (one-sided 95% confidence limit). Examination of nonlinear features of the hexavalent chromium-lung cancer exposure response in a population used in a recent risk assessment supports using the traditional (lagged) cumulative exposure paradigm: no intensity (concentration) threshold, linearity in intensity, and constant increment in risk following exposure.

Air Pollutants, Occupational↗

PubMed1999

Analysis of nonlinear hepatic clearance of a cyclopentapeptide, BQ-123, with the multiple indicator dilution method using the dispersion model.

PURPOSE: To bridge in vitro, in situ and in vivo kinetic analyses of the hepatic clearance of a cyclopentapeptide, BQ-123, by using dispersion models that assume nonlinear pharmacokinetics. METHODS: Rat livers were perfused by the multiple indicator dilution method with doses of BQ-123 ranging from 1-1000 microg. The outflow dilution curves were fitted to a two-compartment dispersion model that was solved numerically by the finite difference method. Further, in vivo plasma concentrations of BQ-123 after bolus injection were analyzed with a hybrid physiological model that incorporates the hepatic dispersion model. RESULTS: The calculated Michaelis-Menten constants (Km = 12.0 microM, Vmax = 321 pmol/min/10(6) cells, P(dif) = 1.2 microl/min/10(6) cells) were comparable to those obtained previously from the in vitro isolated hepatocyte experiment (Km = 9.5 microM, Vmax = 517 pmol/min/l0(6) cells, P(dif) = 1.1 microl/min/10(6) cells). The plasma concentrations of BQ-123 at doses of 1-25 mg/kg were explained well by the hybrid physiological model. CONCLUSIONS: These results suggest that carrier-mediated transport on the sinusoidal membrane was responsible for the in vivo hepatic elimination of BQ-123.

Animals↗

PubMed2003

Chaos and schizophrenia: does the method fit the madness?

Over the past 30 years, investigators have used nonlinear and so-called chaos theory-based techniques to examine a wide range of phenomena ranging from electroencephalogram and cardiac rate and rhythm analyses to stock market and weather predictions. Psychiatric neuroscientists are now beginning to apply nonlinear methods to mental disorders such as schizophrenia. These applications are relevant from the level of complex genetic architecture and calcium channel dynamics to the symptomatic, behavioral, and functional outcome of schizophrenia. The key point of this surge of interest is distinguishing complex, nonlinear but lawfully mediated systems from truly random systems. The application of these methods to studies in schizophrenia has yielded findings that are consistent with the general hypothesis that an altered sequential or temporal architecture is a key feature of this disorder. Specifically, we propose that the temporal architecture of schizophrenia is characterized by bursts of complex, nonlinear phenomena alternating with truly random events. Analyzing these patterns of molecular (e.g., calcium channel activity) to molar (e.g., symptom level) phenomena via nonlinear systems methods can provide new approaches to understanding complex temporal and sequential shifts in neural substrate activity, pathophysiology, and the course and treatment and outcome of schizophrenia.

Calcium Channels↗

PubMed2001

Progression of heterogeneous breast tumors.

Two possible pathways of breast tumor progression were investigated by searching for values of transition rates that could reproduce the clinically observed co-occurrence frequencies of grades of ductal carcinoma in situ and grades of invasive ductal carcinoma in heterogeneous tumors. Two different pathways were analysed, a linear pathway with seven parameters, and a nonlinear pathway with three parameters. In each pathway ductal carcinoma in situ (DCIS) is a progenitor of invasive carcinoma (IDC). In the linear pathway breast tumor progression is along increasing grades: DCIS 1-DCIS 2-DCIS 3-IDC 1-IDC 2-IDC 3. In the nonlinear pathway progression of DCIS and progression of IDC can proceed in parallel steps, and in addition, with transitions from each grade of DCIS to a corresponding grade of IDC. The biological pathways were interpreted mathematically as compartment models with transition rates between stages in an explicit series of coupled differential equations. Two methods were used to search for transition rates that could reproduce the observed co-occurrence frequencies, a limited empirical search and an extensive genetic algorithmic search. Neither search method, with either pathway, could find a combination of transition rates that would reproduce the set of observed co-occurrence frequencies. We conclude that neither the linear pathway, nor the nonlinear pathway considered here, is an adequate description of progression in heterogeneous breast tumors. This quantitative investigation lends support to previous evidence from histopathology and molecular biology that the grades of DCIS and IDC seen together in heterogeneous breast tumors may not be obligate steps in tumor progression.

Breast Neoplasms↗

PubMed2000

Density-dependent vital rates and their population dynamic consequences.

We explore a set of simple, nonlinear, two-stage models that allow us to compare the effects of density dependence on population dynamics among different kinds of life cycles. We characterize the behavior of these models in terms of their equilibria, bifurcations. and nonlinear dynamics, for a wide range of parameters. Our analyses lead to several generalizations about the effects of life history and density dependence on population dynamics. Among these are: (1) iteroparous life histories are more likely to be stable than semelparous life histories; (2) an increase in juvenile survivorship tends to be stabilizing; (3) density-dependent adult survival cannot control population growth when reproductive output is high: (4) density-dependent reproduction is more likely to cause chaotic dynamics than density dependence in other vital rates; and (5) changes in development rate have only small effects on bifurcation patterns.

Animals↗

PubMed2006

Correlating material properties with tissue composition in enzymatically digested bovine annulus fibrosus and nucleus pulposus tissue.

Aging and degeneration of the intervertebral disk are accompanied by decreases in water and proteoglycan contents, and structural alterations. The aim of this study was to determine the impact of compositional changes on the material properties of intervertebral disk tissues. Confined compression stress-relaxation experiments were applied to bovine caudal annulus fibrosus and nucleus pulposus tissue specimens that were separated into three experimental groups: in situ, free-swelling control (PBS), and digestion (chondroitinase-ABC). Measurements of glycosaminoglycan (GAG) and water content, as well as nonlinear finite deformation biphasic theory and multiple linear regression analyses were performed. The compressive modulus HA0 and permeability k0 of in situ specimens were 0.37+/-0.06 MPa and 0.49+/-0.08x10(-15) m4 N-1 s-1 for nucleus, and 0.74+/-0.13 MPa and 0.42+/-0.05x10(-15) m4 N-1 s-1 for annulus, respectively. There was a larger effect of swelling and digestion on the material properties and biochemical composition of nucleus pulposus than for annulus fibrosus. Alterations in proteoglycan and water content affected the compressive modulus and permeability, although the permeability was somewhat more strongly affected by water content than by proteoglycan content. Correlation coefficients r<or=0.75 for the multiple regression indicated water and GAG content can moderately predict material properties, however other compositional and structural factors must be considered.

Animals↗

PubMed2000

Viscoelastic properties of the human temporomandibular joint disc in patients with internal derangement.

PURPOSE: This study investigated the viscoelastic properties of human temporomandibular joint (TMJ) discs in patients with severe internal derangement (ID). PATIENTS AND METHODS: TMJ discs obtained from 5 patients with severe TMJ internal derangement were analyzed. Normal discs derived from 2 fresh cadavers and 4 patients without ID served as the controls. The viscoelastic responses of the discs to tensile forces were evaluated by means of stress-strain analyses. RESULTS: The discs in both groups exhibited a nonlinear stress-strain relationship that was represented by a power function of the strain. However, after stress relaxation, the ID discs were likely to exhibit a linear stress-strain relationship. The instantaneous elastic moduli were almost the same in both discs, but the relaxed elastic modulus of the ID discs was significantly greater than that of the controls in lower strain range of less than 2%. CONCLUSIONS: ID discs are more rigid than normal discs. These findings suggest that the changes in viscoelastic property of the discs in patients with ID are somewhat different from those that occur with aging.

Adult↗

PubMed1998

Quantification of muscarinic cholinergic receptors with [11C]NMPB and positron emission tomography: method development and differentiation of tracer delivery from receptor binding.

Quantification of human brain muscarinic cholinergic receptors was investigated with the use of [11C]N-methyl-4-piperidyl benzylate (NMPB) and positron emission tomography (PET). Whole-brain uptake of NMPB at 90 to 110 minutes after intravenous injection was approximately 10% of the administered dose. The initial cerebral distribution of NMPB corresponded to the pattern of cerebral perfusion; however, at progressively longer postinjection intervals, regional distinctions consistent with muscarinic receptor binding were evident: activity at 90 to 110 minutes postinjection was highest in the striatum and cerebral cortex, intermediate in the thalamus and pons, and lowest in the cerebellum. After the development of a chromatographic system for isolation of authentic [11C]NMPB in plasma, tracer kinetic modeling was used to estimate receptor binding from the cerebral and arterial plasma tracer time-courses. Ligand transport rate and receptor-binding estimates were obtained with the use of compartmental models and analytical methods of varying complexity, including a two-parameter pixel-by-pixel-weighted integral approach and regional least-squares curve-fitting analyses employing both two- and three-compartment model configurations. In test-retest experiments, precision of the methods and their abilities to distinguish altered ligand delivery from binding in occipital cortex during an audiovisual presentation were evaluated. Visual stimulation increased the occipital blood-to-brain NMPB transport rate by 25% to 46% in estimates arising from the various approaches. Weighted integral analyses resulted in lowest apparent transport changes and in a concomitant trend toward apparent binding increases during visual activation. The regional least-squares procedures were superior to the pixel-by-pixel method in isolating the effects of altered tracer delivery from receptor-binding estimates, indicating larger transport effects and unaltered binding. Precision was best (less than 10% test-retest differences) for the weighted integral analyses and was somewhat lower in the least-squares analyses (10-25% differences). The authors conclude that pixel-by-pixel-weighted integral analyses of NMPB distribution introduce transport biases into receptor-binding estimates. Similar confounding effects also are predicted in noncompartmental analyses of delayed radiotracer distribution. The use of regional nonlinear least-squares fitting to two- and three-compartment models, although more labor intensive, provides accurate distinction of receptor-binding estimates from tracer delivery with acceptable precision in both intra- and intersubject comparisons.

Adult↗

PubMed2002

Relationships among severity and duration of clinical mastitis and sire transmitting abilities for somatic cell score, udder type traits, productive life, and protein yield.

The objective of this study was to determine the relationships among severity and duration of clinical mastitis during first and second lactation and sire transmitting abilities for somatic cell score, udder type traits, productive life, and protein yield. Recording of clinical episodes began at first parturition for 1704 Holstein cows (in six Pennsylvania herds and one Nebraska herd) and continued into second lactation for 1055 of these cows. A total of 456 cows (sired by 168 bulls) had at least one clinical episode during first lactation, and 230 cows (sired by 100 bulls) had at least one clinical episode during second lactation. A severity code from 1 (normal milk) to 5 (acute systemic mastitis) was assigned daily (for up to 30 d after detection) to all quarters that had clinical mastitis. Only the severity codes for the first clinical episode to occur during first and second lactation are considered here. The initial and maximum severity codes, as well as the natural logarithms of both the sum of severity codes that were above normal (> 1) and the total days severity codes were above normal were regressed on herd (a classification variable), age at first calving, days in milk at clinical detection, and sire transmitting abilities taken one at a time. Linear and nonlinear effects were estimated for sire transmitting abilities. Separate analyses were conducted on dependent variables that considered severity and duration of clinical mastitis from: all organisms, coagulase-negative staphylococci, coliform species, streptococci other than Streptococcus agalactiae, and the most common environmental organisms (coliform species and streptococci other than Streptococcus agalactiae). Daughters of sires that transmit the lowest somatic cell score had the least severe and shortest clinical episodes from environmental organisms during first lactation. Selection for lower somatic cell score may reduce the severity and duration of clinical episodes from environmental organisms during first lactation.

Animals↗

PubMed1999

The effect of diameter ratio between vascular substitute and blood vessel on anastomosis.

It is necessary to maintain mechanical compatibility between a blood vessel and a vascular substitute to promote encapsulation around the anastomosed part. From this point of view, using linear elastic theory, we had previously performed stress analyses at the part anastomosed by tissue adhesion, in order to propose some methods of preventing stress concentration at this junction. In this study, based on the previous analyses, we have attempted to develop a concept that can be applied under the conditions of operation. That is, the initial diameter of a vascular substitute with high rigidity is chosen larger than that of a blood vessel. This will reduce the stress concentration around the anastomosed part, on average, during expansion of the blood vessel. We analysed the optimum diameter ratio between the vascular substitute and the blood vessel which causes the least stress concentration, on average, during this process, using linear elastic theory. Furthermore, numerical analyses of blood vessel deformation were performed using various nonlinear stress-strain laws. These results were compared to the analytical solution based on linear elastic theory.

Anastomosis, Surgical↗

PubMed1975

Developmental change in the apparent kinetic properties of drug-oxidizing enzymes in the human liver.

When analyzing the effect of substrate concentration on the reaction rate of aminopyrine N-demethylation, aniline p-hydroxylation, and 3,4-benzpyrene hydroxylation by human fetal and adult liver samples we found that Lineweaver-Burk and Eadie-Hofstee analyses yielded mostly linear lines with fetal liver, but nonlinear lines with adult livermthis may be taken to indicate that a qualitative change in drug-oxidizing enzymes of the human liver occurs during ontogenetic development, of the human liver occurs during ontogenetic development, possibly so that during the fetal period liver contains one ana during the adult period two enzymes metabolizing aminopyrine, anilinw, and 3,4-benzpyrene.

Adult↗