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Results for “nonlinear analyses”

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PubMed2006

Acoustic analyses of sustained and running voices from patients with laryngeal pathologies.

In this paper, we investigated the acoustic characteristics of sustained and running vowels from normal subjects and patients with laryngeal pathologies. Perturbation methods (including jitter and shimmer), signal-to-noise ratio (SNR), and nonlinear dynamic methods (such as correlation dimension and second-order entropy) were used to analyze sustained and running vowels. We found that the sustained vowels and running voices from normal subjects and patients with laryngeal pathologies had low-dimensional dynamic characteristics. For sustained vowels, the analyses of jitter, shimmer, correlation dimension, and second-order entropy revealed significant differences between normal and pathological voices. For running voices, jitter and shimmer did not statistically discriminate between normal and pathological voices, but a significant difference was found for SNR, correlation dimension, and second-order entropy. The results suggest that nonlinear dynamic analysis and traditional SNR analysis may be valuable for the analysis of sustained and running vowels; perturbation analysis may be applicable for the analysis of sustained vowels but should be applied with caution for running voice analysis.

Adult↗

PubMed2004

Finite element analysis of moment-rotation relationships for human cervical spine.

A comprehensive, geometrically accurate, nonlinear C0-C7 FE model of head and cervical spine based on the actual geometry of a human cadaver specimen was developed. The motions of each cervical vertebral level under pure moment loading of 1.0 Nm applied incrementally on the skull to simulate the movements of the head and cervical spine under flexion, tension, axial rotation and lateral bending with the inferior surface of the C7 vertebral body fully constrained were analysed. The predicted range of motion (ROM) for each motion segment were computed and compared with published experimental data. The model predicted the nonlinear moment-rotation relationship of human cervical spine. Under the same loading magnitude, the model predicted the largest rotation in extension, followed by flexion and axial rotation, and least ROM in lateral bending. The upper cervical spines are more flexible than the lower cervical levels. The motions of the two uppermost motion segments account for half (or even higher) of the whole cervical spine motion under rotational loadings. The differences in the ROMs among the lower cervical spines (C3-C7) were relatively small. The FE predicted segmental motions effectively reflect the behavior of human cervical spine and were in agreement with the experimental data. The C0-C7 FE model offers potentials for biomedical and injury studies.

Biomechanical Phenomena↗

PubMed1997

Computer classification of state in healthy preterm neonates.

Nineteen electroencephalographic (EEG) sleep measures describing four physiologic aspects of sleep behavior (i.e. sleep continuity, EEG spectra, body and eye movements, and autonomic measures) were derived from visual and computer analyses of 71 24-channel, 3-hour EEG sleep recordings on 52 healthy preterm neonates from 28-36.5 weeks postconceptional age (PCA). Forty-eight subjects were neurodevelopmentally normal up to 2 years of age. Four electrographic states that comprise tracé discontinu of the preterm neonate were defined in terms of increasing seconds of EEG quiescence per minute. A regression analysis was performed after transformations of nonlinear data sets representing the 19 EEG sleep measures, with the four sleep states as outcome variables. Postconceptional age was also included in these analyses as the 20th explanatory variable. Four measures best defined the EEG sleep states, explaining 75% of the variance: decreasing rapid eye movements per minute, decreasing numbers of spontaneous arousals per minute, increasing spectral theta energies, and decreasing facial movements per minute. Other cerebral and noncerebral measures, including total spectral EEG energies, spectral EEG energies in three bandwidths (i.e. delta, alpha, beta), cardiac and respiratory measures, and body movements, did not contribute as significantly to the prediction. Inclusion of PCA into the regression equation with the four EEG measures, selected by the analysis procedure, indicated that its contribution to state prediction was also small; the effect of PCA on state was found to be explained by the four EEG sleep measures.

Electroencephalography↗

PubMed1999

Finite strain elastodynamics of intracranial saccular aneurysms.

Various investigators suggest that intracranial saccular aneurysms are dynamically unstable, that they resonate in response to pulsatile blood flow. This hypothesis is based on linearized analyses or experiments on rubber "models", however, and there is a need for a more critical examination. Toward this end, we (a) derive a new nonlinear equation of motion for a pulsating spherical aneurysm that is surrounded by cerebral spinal fluid and whose behavior is described by a Fung-type pseudostrain-energy function that fits data on human lesions, and (b) use methods of nonlinear dynamics to examine the stability of such lesions against perturbations to both in vivo and in vitro conditions. The numerical results suggest that this sub-class of lesions is dynamically stable. Moreover, with the exception of transients associated with initial perturbations, inertial effects appear to be insignificant for fundamental forcing frequencies less than 10 Hz and hence for typical physiologic and laboratory conditions. We submit, therefore, that further study of the mechanics of saccular aneurysms should be focused on quasi-static stress analyses that investigate the roles of lesion geometry and material properties, including growth and remodeling.

Algorithms↗

PubMed2002

Model based analysis of the heart rate and blood pressure relationship.

The main intention of this contribution is to measure the coupling between bivariate time series using the dual sequence method to estimate the baroreflex as well as a nonlinear regression approach, namely the maximal correlation method, to get a better understanding of the underlying processes. The data we analyse are heart rate and blood pressure variability time series from 27 patients with dilated cardiomyopathy as well as from a control group of 27 age- and sex-matched healthy subjects. The results strongly indicate and confirm the mechanisms of respiratory sinus arrhythmia in heart rate. Revealing the coupling direction and the strength of coupling between heart rate and blood pressure via optimal transformations in addition to the baroreflex estimation seems to be a very promising approach.

Adult↗

PubMed2025

Distinct Behavioral Profiles and Neuronal Correlates of Heroin Vulnerability Versus Resiliency in a Multi-Symptomatic Model of Heroin Use Disorder in Rats.

OBJECTIVE: The behavioral and diagnostic heterogeneity within the opioid use disorder (OUD) diagnosis is not readily captured in current animal models, limiting the translational relevance of the mechanistic research that is conducted in experimental animals. The authors hypothesized that a nonlinear clustering of OUD-like behavioral traits would capture population heterogeneity and yield subpopulations of OUD vulnerable rats with distinct behavioral and neurocircuit profiles. METHODS: Over 900 male and female heterogeneous stock rats, a line capturing genetic and behavioral heterogeneity present in humans, were assessed for several measures of heroin use and rewarded and non-rewarded seeking behaviors. A nonlinear stochastic block model clustering analysis was used to assign rats to OUD vulnerable, intermediate, and resilient clusters. Additional behavioral tests and circuit analyses using c-fos protein activation were conducted on the vulnerable and resilient subpopulations. RESULTS: OUD vulnerable rats exhibited greater heroin taking and seeking behaviors relative to those in the intermediate and resilient clusters. Akin to human OUD diagnosis, further vulnerable rat subclustering revealed subpopulations with different combinations of behavioral traits, including sex differences. Lastly, heroin cue-induced neuronal patterns of circuit activation differed between resilient and vulnerable phenotypes. Behavioral sex differences were recapitulated in patterns of circuitry activation, including preferential engagement of extended amygdala stress circuitry in males and cortico-striatal drug cue-seeking circuitry in females. CONCLUSION: Using a nonlinear clustering approach in rats, the analysis captured behavioral diagnostic heterogeneity reflective of human OUD diagnosis. OUD vulnerability and resiliency were associated with distinct neuronal activation patterns, posing this approach as a translational tool in assessing neurobiological mechanisms underpinning OUD.

Animals↗

PubMed2001

The effect of a receptor layer on the measurement of rate constants.

Many cellular reactions involve a reactant in solution binding to or dissociating from a reactant attached to a surface. Most studies assume that the reactions occur on this surface, when in actuality the receptors usually lie in a thin layer on top of it. The effect of this layer is considered, particularly as it relates to the BIAcore measurement device, though the results are applicable to biological systems. A dimensionless parameter measuring the strength of the effect of the receptor layer is found. Asymptotic and singular perturbation techniques are used to analyse association and dissociation kinetics, though the effect of the receptor layer need not be small. Linear and nonlinear integral equations result from the analysis; explicit and asymptotic solutions are constructed for physically realizable cases. In addition, effective rate constants are derived that illustrate the combined effects of transport and the receptor layer on the measured rate constants. All these expressions provide a direct way to estimate rate constants from BIAcore binding data.

Cell Membrane↗

PubMed2001

ESS analysis of mechanistic models for territoriality: the value of scent marks in spatial resource partitioning.

In this paper elements of game theory are used to analyse a spatially explicit home range model for interacting wolf packs. The model consists of a system of nonlinear partial differential equations whose parameters reflect the movement behavior of individuals within each pack and whose solutions describe the patterns of space-use by each pack. By modifying the behavioral parameters, packs adjust their patterns of movement so as to maximize their reproductive output. This involves a tradeoff between maximizing prey intake and minimizing conflict with neighbors. Evolutionarily stable choices of the behavioral parameters yields territories that are immune to invasion by groups with alternate behaviors.

Animals↗

PubMed2005

Responses to subchronic inhalation of low concentrations of diesel exhaust and hardwood smoke measured in rat bronchoalveolar lavage fluid.

Air pollution exposure is associated with adverse health effects, but the causal components and mechanisms are unclear. We compared effects of daily exposure for 6 mo to diesel exhaust (DE) or hardwood smoke (HWS) at 4 concentrations between 30 and 1000 microg/(3) of total particulate matter, or filtered air, in male and female rats. Lung lavage fluid was assayed for toxicity indicators, cytokines, and glutathione. Statistical analyses included pairwise comparisons with control and exposure-related trends, modeled using techniques that facilitated evaluation of nonlinear exposure effects. Lactate dehydrogenase increased with exposure concentration in DE-exposed females, but in other groups, low exposure concentrations caused increases while higher concentrations had less effect. Total protein in the HWS-exposed males and females followed similar patterns. Alkaline phosphatase increased in DE-exposed females, but decreased in HWS-exposed males and females. Beta-Glucuronidase decreased in HWS- and DE-exposed males, but HWS-exposed females showed decreases at low exposure concentrations and weak increases at higher exposure concentrations. Macrophage inflammatory protein-2 decreased in HWS-exposed males and females and DE-exposed females. Tumor necrosis factor-alpha levels decreased in DE-exposed females and males, but HWS-exposed males showed small increases. DE did not affect total glutathione in either gender, but HWS decreased glutathione in females, while in males, increases at low exposure concentrations but not at higher exposure levels were observed. Thus, these two combustion emissions differentially affect lung responses, with gender affecting response patterns. Furthermore, effects may be nonmonotonic functions of exposure levels, with maximal responses in environmentally or occupationally relevant exposure ranges.

Air Pollutants↗

PubMed2000

In vitro kinetics of coumarin 3,4-epoxidation: application to species differences in toxicity and carcinogenicity.

Coumarin, a natural product and fragrance ingredient, is a well recognized rat liver toxicant, and dietary administration at toxic dosages increased the incidence of rat cholangiocarcinomas and parenchymal liver-cell tumors in a chronic bioassay. Hepatotoxicity in rats is site- and species-specific, and is thought to result from the formation of coumarin 3,4-epoxide and its rearrangement product, o-hydroxyphenylacetaldehyde (o-HPA). The goals of the current study were to describe the in vitro kinetics of the metabolic activation of coumarin, and determine whether species differences in susceptibility to liver injury correlate with coumarin bioactivation determined in vitro. Coumarin 3,4-epoxidation was quantified via the formation of o-HPA in pooled hepatic microsomes from female B6C3F1 mice, male F344 rats, and individual humans (n = 12 subjects), and the apparent kinetic constants for o-HPA production were calculated using nonlinear regression and fitting to either a one-enzyme or two-enzyme model. Eadie-Hofstee analyses indicated that o-HPA formation was biphasic in both rat and mouse liver. Although the apparent high affinity K:(m) in rat and mouse liver microsomes was 38.9 and 47.2 microM, respectively, the overall rate of o-HPA formation was far greater in mouse than in rat liver microsomes. Furthermore, the total clearance (CL(int)) of coumarin via o-HPA formation in mouse liver microsomes was 4-fold greater than in rat liver microsomes. Since mice are relatively resistant to hepatotoxicity, the data indicated that rates of o-HPA formation in rat and mouse liver microsomes were not directly predictive of liver toxicity in vivo, and further suggested that o-HPA detoxification played a role in modulating coumarin-mediated toxicity. The current studies also indicated that coumarin 3,4-epoxidation in human hepatic microsomes was minimal. In human liver microsomes (n = 12), the kinetics of o-HPA formation were best described by a single enzyme model, with the K(m) for o-HPA formation ranging from 1320-7420 microM. In the most active human sample, the intrinsic clearance of coumarin via the 3,4-epoxidation pathway was 1/9 and 1/38 that of the rat and mouse, respectively. The in vitro kinetics of o-HPA formation, and in particular, the large quantities of coumarin required for o-HPA production in human liver microsomes, strongly suggest that humans are unlikely to produce toxicologically relevant concentrations of this metabolite following low level coumarin exposures.

Acetaldehyde↗

PubMed2005

Recurrence time analysis, long-term correlations, and extreme events.

The recurrence times between extreme events have been the central point of statistical analyses in many different areas of science. Simultaneously, the Poincaré recurrence time has been extensively used to characterize nonlinear dynamical systems. We compare the main properties of these statistical methods pointing out their consequences for the recurrence analysis performed in time series. In particular, we analyze the dependence of the mean recurrence time and of the recurrence time statistics on the probability density function, on the interval whereto the recurrences are observed, and on the temporal correlations of time series. In the case of long-term correlations, we verify the validity of the stretched exponential distribution, which is uniquely defined by the exponent gamma, at the same time showing that it is restricted to the class of linear long-term correlated processes. Simple transformations are able to modify the correlations of time series leading to stretched exponentials recurrence time statistics with different gamma, which shows a lack of invariance under the change of observables.

Journal Article↗

PubMed1984

The determination of calcium-binding sites of human erythrocyte membranes.

Calcium binding to leaky erythrocyte plasma membranes was measured by three different procedures: Millipore filtration, equilibrium dialysis, and partition centrifugation. The curve derived from the binding equation, which best fit the means of the raw data, was used to estimate the association constants and capacities of the binding sites. A computer program (Gaushaus) which uses a nonlinear, least-squares regression protocol was also used to confirm these estimates. On the basis of these analyses we propose the presence of three classes of calcium-binding sites with the following apparent association constants and capacities: site 1, Ka = 3 X 10(4) M-1 and n = 30 nmol/mg protein; site 2, Ka = 3 X 10(3) M-1 and n = 200 nmol/mg protein; site 3, Ka = approximately 10(2) M-1 and n = approximately 200 nmol/mg protein. Calcium binding to erythrocyte membranes sealed in a high-salt solution showed the presence of site 3, but not site 2. The influence of phospholipids on the binding of calcium was evaluated by pretreating ghosts with phospholipase C (Clostridium welchii, EC 3.1.4.3). Treatment with this enzyme removed 80% of the total membrane phosphorus, predominantly from sphingomyelin, phosphatidylcholine, and phosphatidylethanolamine. By the method of partition centrifugation two classes of binding sites were identified by computer analysis. Their association constants and capacities are, respectively, 1.1 X 10(5) M-1 and 20 nmol/mg protein for site 1 and 4.4 X 10(3) M-1 and 200 nmol/mg protein for site 2. We speculate that calcium-binding site 1 is composed of acidic phospholipids, calcium-binding site 2 is composed of spectrin and actin, and calcium-binding site 3 is composed of sialic acid.

Binding Sites↗

PubMed2006

Pharmacokinetics of cetuximab after administration of escalating single dosing and weekly fixed dosing in patients with solid tumors.

PURPOSE: Previous studies of cetuximab pharmacokinetics did not fully characterize its elimination phase. The purpose of this trial was to evaluate the pharmacokinetics of cetuximab given as a single dose followed by weekly fixed repeated dosing in patients with solid tumors. EXPERIMENTAL DESIGN: Patients were randomly assigned to treatment with a single 2-hour infusion of cetuximab at doses of 50, 100, 250, 400, or 500 mg/m2 followed 3 weeks later by weekly 1-hour infusions of cetuximab at a fixed dose of 250 mg/m2. Extended pharmacokinetic sampling was collected through 504 hours after the first drug administration. Trough samples were obtained before each fixed weekly dose. Single and multidose pharmacokinetic variables were correlated with clinical outcomes. RESULTS: Forty patients were enrolled. Pharmacokinetic analysis confirmed previous reports of nonlinear pharmacokinetics for cetuximab. Modeling studies predicted a 90% saturation of clearance at a dose of 260 mg/m2. Analyses of weekly trough concentrations indicated a slight accumulation of drug concentrations following repeated weekly dosing. Correlative studies indicated a significant association between cetuximab clearance and both body surface area (P=0.002) and weight (P=0.002). The occurrence of rash was significantly associated with disease stability (P<0.002) but not with cetuximab pharmacokinetic variables. CONCLUSIONS: Pharmacokinetic results support using body surface area or weight in calculating individual cetuximab doses. A weekly dose of 250 mg/m2 is predicted to nearly fully saturate cetuximab clearance and, by inference, epidermal growth factor receptors. The association between rash and disease stability supports further prospective studies of this relationship.

Adult↗

PubMedDate not supplied

Predictive value of sperm hyperactivation measurements based on the dilution effect method in clinical in vitro fertilization.

Sperm hyperactivation motility characterized by wide oscillatory movements of the sperm head, nonlinear directions, and rapid motility with occasional star-shaped pattern of movement was measured during routine semen analyses prior to an in vitro fertilization procedure. The method consisted of diluting liquefied semen 1:20 with Ham's F-10 supplemented with processed human cord sera followed by incubation at 37 degrees C for 30 minutes. At the end of the incubation period, aliquots of semen samples were evaluated by phase contrast microscopy for sperm hyperactivation. The results indicated that (1) sperm samples exhibiting 15% or more hyperactive motility were associated with a significantly higher percent fertilization of oocytes during the IVF procedure; (2) sperm hyperactive motility was correlated to sperm fertilizability during IVF treatment cycles.

Female↗

PubMed2000

Dose-response analyses of the carcinogenic effects of trichloroethylene in experimental animals.

In lifetime bioassays, trichloroethylene (TCE, CAS No. 79-01-6) causes liver tumors in mice following gavage, liver and lung tumors in mice following inhalation, and kidney tumors in rats following gavage or inhalation. Recently developed pharmacokinetic models provide estimates of internal, target-organ doses of the TCE metabolites thought responsible for these tumor responses. Dose-response analyses following recently proposed methods for carcinogen risk assessment from the U.S. Environmental Protection Agency (U.S. EPA) are conducted on the animal tumor data using the pharmacokinetic dosimeters to derive a series of alternative projections of the potential carcinogenic potency of TCE in humans exposed to low environmental concentrations. Although mechanistic considerations suggest action of possibly nonlinear processes, dose-response shapes in the observable range of tumor incidence evince little sign of such patterns. Results depend on which of several alternative pharmacokinetic analyses are used to define target-organ doses. Human potency projections under the U.S. EPA linear method based on mouse liver tumors and internal dosimetry equal or somewhat exceed calculations based on administered dose, and projections based on mouse liver tumors exceed those from mouse lung or rat kidney tumors. Estimates of the carcinogenic potency of the two primary oxidative metabolites of TCE--trichloroacetic acid and dichloroacetic acid, which are mouse liver carcinogens in their own right--are also made, but it is not clear whether the carcinogenic potency of TCE can be quantitatively ascribed to metabolic generation of these metabolites.

Animals↗

PubMed2005

Generalizations of the Moran effect explaining spatial synchrony in population fluctuations.

The Moran effect for populations separated in space states that the autocorrelations in the population fluctuations equal the autocorrelation in environmental noise, assuming the same linear density regulation in all populations. Here we generalize the Moran effect to include also nonlinear density regulation with spatial heterogeneity in local population dynamics as well as in the effects of environmental covariates by deriving a simple expression for the correlation between the sizes of two populations, using diffusion approximation to the theta-logistic model. In general, spatial variation in parameters describing the dynamics reduces population synchrony. We also show that the contribution of a covariate to spatial synchrony depends strongly on spatial heterogeneity in the covariate or in its effect on local dynamics. These analyses show exactly how spatial environmental covariation can synchronize fluctuations of spatially segregated populations with no interchange of individuals even if the dynamics are nonlinear.

Demography↗

PubMed1997

A thermodynamic approach to the compromise between power and efficiency in muscle contraction.

An analysis of muscle contraction based on irreversible thermodynamics is presented in this work. From reported experimental results, it is shown that a muscle, as an energy converter, does not obey linear phenomenological relations. Some more suitable nonlinear phenomenological relations are found and discussed from an evolutionary point of view. In those relations a parameter alpha appears which is related to the nonlinearity of the equations. It is suggested that this parameter determines the compromise between the power output and the efficiency reached by the muscle. By analysing the energetics of some suitable performance regimes, we suggest that the fact that alpha values greater than 0.4 are not found in muscles of higher species, can be interpreted as an evolutionary necessity.

Animals↗

PubMedDate not supplied

Hybrid parametric-physiological glottal modelling with application to voice quality assessment.

A glottal model based on physical constraints is proposed. The model describes the vocal fold as a simple oscillator, i.e. a damped mass-spring system. The oscillator is coupled with a nonlinear block, accounting for fold interaction with the airflow. The nonlinear block is modelled as a regressor-based functional with weights to be identified, and a pitch-synchronous identification procedure is outlined. The model is used to analyse voiced sounds from normal and from pathological voices, and the application of the proposed analysis procedure to voice quality assessment is discussed.

Cluster Analysis↗