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PubMed2004

An adaptive neuro-fuzzy method (ANFIS) for estimating single-trial movement-related potentials.

This study aims to recover transient, trial-varying evoked potentials (EPs), in particular the movement-related potentials (MRPs), embedded within the background cerebral activity at very low signal-to-noise ratios (SNRs). A new adaptive neuro-fuzzy technique will attempt to estimate movement-related potentials within multi-channel EEG recordings, enabling this method to completely adapt to each input sweep without system training procedures. We assume that one of the sensors is corrupted by noise deriving from other sensors via an unknown function that will be estimated. We will approach this problem by: (1) spatially decorrelating the sensors in the preprocessing phase, (2) choosing the most informative of the filtered channels that will permit the best MRP estimation (input-selection phase) and (3) training the neuro-fuzzy model to fit the noise over the chosen sensor and therefore estimating the buried MRP. We tested this framework with simulations to validate the analytical results before applying them to the real biological data. Whenever it is applied to biological data, this method improves the SNR by more than 12 dB, even to very low SNRs. The processing method proposed here is likely to complement other estimation techniques and can be useful to process, enhance and analyse single-trial MRPs.

Adult↗

PubMed2001

Entrapment by Cremophor EL decreases the absorption of paclitaxel from the gut.

BACKGROUND: Recent studies in mice and patients have shown that the low oral bioavailability of paclitaxel can be increased by coadministration of P-glycoprotein blockers. However, in patients an increase in the oral paclitaxel dose from 60 to 300 mg/m(2) does not result in proportionally higher plasma levels. We hypothesized that the surfactant Cremophor EL, present in the formulation of paclitaxel, may be responsible for this nonlinear absorption by entrapping paclitaxel within the intestinal lumen, probably by inclusion in micelles. METHODS: Paclitaxel was administered to mdr1ab P-glycoprotein knockout mice with either the conventional (controls) or a seven-fold higher amount of Cremophor EL (test group). Plasma, gastrointestinal tissues with their contents and faeces were collected and analysed by high-performance liquid chromatography to determine the levels of paclitaxel and Cremophor EL. The critical micellar concentrations of Cremophor EL in the contents of the small intestine were also established by an in vitro assay. RESULTS: Paclitaxel recoveries in the faeces of the control and test groups were 7.6% and 35.8%, respectively. The peak plasma level and plasma AUC were reduced in the test group by about 75% and 40%, respectively. Only in mice from the test group did substantial quantities of paclitaxel together with Cremophor EL reach the caecum, thus passing through the small intestine. The concentration of Cremophor EL in the distal part of the small intestine and the caecum was 15 times higher in the test group and well above the critical micellar concentration of Cremophor EL. CONCLUSIONS: These results show that Cremophor EL prevents efficient uptake of paclitaxel from the gut, probably by entrapment within micelles. Other formulations should be developed for oral therapy with paclitaxel.

Administration, Oral↗

PubMed1987

Trabecular bone remodeling around smooth and porous implants in an equine patellar model.

The objective of this investigation was to examine the stress-morphology relationships for trabecular bone around implants with different surface characteristics. Stainless steel spheres with either a polished surface or a sintered-bead porous coating were implanted unilaterally into equine patellae and maintained for a 6 month period. Stereological methods were used to quantify the trabecular bone morphology and finite element analyses were performed to predict the trabecular bone stresses. In general, the remodeling response around the smooth implants was greater than that around those porous implants that exhibited bone ingrowth. In accordance with these differences, the finite element models predicted greater changes in the stresses adjacent to the smooth implants due to the nonlinear boundary conditions. However, it did not appear that the trajectorial theory, in its simplest form, was applicable to the remodeling induced by the implants. A linear relationship between the change in bone areal density and the change in von Mises effective stress provides support for the hypothesis that the architecture of trabecular bone corresponds to an optimal structure. The results also demonstrated that, under certain circumstances, small changes in the stress state may result in large changes in the principal material orientation.

Animals↗

PubMed2005

Acute alteration of emotional behaviour in epileptic seizures is related to transient desynchrony in emotion-regulation networks.

OBJECTIVE: During focal epileptic seizures, patients may express intense agitation, screaming and facial expressions of rage, fear or anger. The precise anatomical origin of such intense ictal emotional behaviour is not fully understood and the mechanisms by which the epileptic discharges provoke these phenomena are unknown. In the present study, we analysed the neurophysiological mechanisms underlying ictal emotional behaviour in 3 patients with frontal lobe epilepsies undergoing intracerebral recordings for presurgical evaluation. METHODS: We analyzed the interactions between regions forming 'emotional networks', before and during behavioural alterations. Intracerebral recordings (SEEG method) of seizures from 3 patients presenting with frontal lobe seizures were analyzed. A nonlinear measure of SEEG signal interdependencies was used to evaluate the functional couplings occurring between brain structures. RESULTS: We found that these intense emotional alterations were associated with a decrease of synchrony between signals recorded from the neural networks known to be involved in emotional processing, and in particular a loss of synchrony between the orbito-frontal cortex and the amygdala. This disruption of functional connections could then result in the disruption of emotional regulation leading to the release of altered behaviour, as observed in epileptic patients during seizures. CONCLUSIONS: We propose that the occurrence of intense ictal emotional behaviour disturbance in frontal lobe seizures is related to a disruption of the normal mechanisms of emotional regulation SIGNIFICANCE: These results provide some insight into our understanding of the pathophysiological processes involved in human partial epilepsies as well as in the interpretation of clinical semiology.

Adult↗

PubMed2006

Sorption and desorption behaviors of diuron in soils amended with charcoal.

Charcoal derived from the partial combustion of vegetation is ubiquitous in soils and sediments and can potentially sequester organic contaminants. To examine the role of charcoal in the sorption and desorption behaviors of diuron pesticide in soil, synthetic charcoals were produced through carbonization of red gum (Eucalyptus spp.) wood chips at 450 and 850 degrees C (referred to as charcoals BC450 and BC850, respectively, in this paper). Pore size distribution analyses revealed that BC850 contained mainly micropores (pores approximately 0.49 nm mean width), whereas BC450 was essentially not a microporous material. Short-term equilibration (< 24 h) tests were conducted to measure sorption and desorption of diuron in a soil amended with various amounts of charcoals of both types. The sorption coefficients, isotherm nonlinearity, and apparent sorption-desorption hysteresis markedly increased with increasing content of charcoal in the soil, more prominently in the case of BC850, presumably due to the presence of micropores and its relatively higher specific surface area. The degree of apparent sorption-desorption hystersis (hysteresis index) showed a good correlation with the micropore volume of the charcoal-amended soils. This study indicates that the presence of small amounts of charcoal produced at high temperatures (e.g., interior of wood logs during a fire) in soil can have a marked effect on the release behavior of organic compounds. Mechanisms of this apparent hysteretic behavior need to be further investigated.

Adsorption↗

PubMed2005

Non-random nature of spontaneous mIPSCs in mouse auditory brainstem neurons revealed by recurrence quantification analysis.

A change in the spontaneous release of neurotransmitter is a useful indicator of processes occurring within presynaptic terminals. Linear techniques (e.g. Fourier transform) have been used to analyse spontaneous synaptic events in previous studies, but such methods are inappropriate if the timing pattern is complex. We have investigated spontaneous glycinergic miniature synaptic currents (mIPSCs) in principal cells of the medial nucleus of the trapezoid body. The random versus deterministic (or periodic) nature of mIPSCs was assessed using recurrence quantification analysis. Nonlinear methods were then used to quantify any detected determinism in spontaneous release, and to test for chaotic or fractal patterns. Modelling demonstrated that this procedure is much more sensitive in detecting periodicities than conventional techniques. mIPSCs were found to exhibit periodicities that were abolished by blockade of internal calcium stores with ryanodine, suggesting calcium oscillations in the presynaptic inhibitory terminals. Analysis indicated that mIPSC occurrences were chaotic in nature. Furthermore, periodicities were less evident in congenitally deaf mice than in normal mice, indicating that appropriate neural activity during development is necessary for the expression of deterministic chaos in mIPSC patterns. We suggest that chaotic oscillations of mIPSC occurrences play a physiological role in signal processing in the auditory brainstem.

Animals↗

PubMed2006

Relation of apical dendritic spikes to output decision in CA1 pyramidal cells during synchronous activation: a computational study.

Recent studies on the initiation and propagation of dendritic spikes have modified the classical view of postsynaptic integration. Earlier we reported that subthreshold currents and spikes recruited by synaptic currents play a critical role in defining outputs following synchronous activation. Experimental factors strongly condition these currents due to their nonlinear behaviour. Hence, we have performed a detailed parametric study in a CA1 pyramidal cell model to explore how different variables interact and initiate dendritic spiking, and how they influence cell output. The input pattern, the relative excitability of axon and dendrites, the presence/modulation of voltage-dependent channels, and inhibition were cross analysed. Subthreshold currents and spikes on synaptically excited branches fired spikes in other branches to jointly produce different modalities of apical shaft spiking with a variable impact on cell output. Synchronous activation initiated a varying number and temporal scatter of firing branches that produced in the apical shaft-soma axis nonpropagating spikes, pseudosaltatory or continuous forward conduction, or backpropagation. As few as 6-10 local spikes within a time window of 2 ms ensure cell output. However, the activation mode varied extremely when two or more variables were cross-analysed, becoming rather unpredictable when all the variables were considered. Spatially clustered inputs and upper modulation of dendritic Na(+) or Ca(2+) electrogenesis favour apical decision. In contrast, inhibition biased the output decision toward the axon and switched between dendritic firing modes. We propose that dendrites can discriminate input patterns and decide immediate cell output depending on the particular state of a variety of endogenous parameters.

Action Potentials↗

PubMed2006

Mechanical characterization of anisotropic planar biological soft tissues using large indentation: a computational feasibility study.

Traditionally, the complex mechanical behavior of planar soft biological tissues is characterized by (multi)axial tensile testing. While uniaxial tests do not provide sufficient information for a full characterization of the material anisotropy, biaxial tensile tests are difficult to perform and tethering effects limit the analyses to a small central portion of the test sample. In both cases, determination of local mechanical properties is not trivial. Local mechanical characterization may be performed by indentation testing. Conventional indentation tests, however, often assume linear elastic and isotropic material properties, and therefore these tests are of limited use in characterizing the nonlinear, anisotropic material behavior typical for planar soft biological tissues. In this study, a spherical indentation experiment assuming large deformations is proposed. A finite element model of the aortic valve leaflet demonstrates that combining force and deformation gradient data, one single indentation test provides sufficient information to characterize the local material behavior. Parameter estimation is used to fit the computational model to simulated experimental data. The aortic valve leaflet is chosen as a typical example. However, the proposed method is expected to apply for the mechanical characterization of planar soft biological materials in general.

Animals↗

PubMed2004

Stress, quality of life and physical activity in women with varying degrees of premenstrual symptomatology.

Premenstrual symptomatology, stress, quality of life (QOL) and exercise frequency, volume, and intensity were assessed in 114 females (18-33 years). Based on premenstrual symptoms (PMS), women were divided into high and low PMS groups and compared on stress, QOL and exercise variables. Results revealed women with high PMS had significantly more stress and poorer QOL than women with low PMS (p <.05 for both comparisons). Groups did not significantly differ on any of the exercise variables. Further analyses were performed to determine if exercise variables impacted PMS symptoms, stress and QOL reports in the high PMS group. While exercise volume and intensity did not impact any of the variables assessed, women with high PMS who reported exercising "sometimes" had more stress than women who reported exercising "often" or "never". This nonlinear relationship suggests that women with the worst symptoms may respond by exercising, while women who exercise often or never do not associate exercise with their symptoms.

Adaptation, Psychological↗

PubMed2002

Structural instability, multiple stable states, and hysteresis in periphyton driven by phosphorus enrichment in the Everglades.

Periphyton is a key component of the Everglades ecosystems. It is a major primary producer, providing food and habitat for a variety of organisms, contributing material to the surface soil, and regulating water chemistry. Periphyton is sensitive to the phosphorus (P) supply and P enrichment has caused dramatic changes in the native Everglades periphyton assemblages. Periphyton also affects P availability by removing P from the water column and depositing a refractory portion into sediment. A quantitative understanding of the response of periphyton assemblages to P supply and its effects on P cycling could provide critical supports to decision making in the conservation and restoration of the Everglades. We constructed a model to examine the interaction between periphyton and P dynamics. The model contains two differential equations: P uptake and periphyton growth are assumed to follow the Monod equation and are limited by a modified logistic equation. Equilibrium and stability analyses suggest that P loading is the driving force and determines the system behavior. The position and number of steady states and the stability also depend upon the rate of sloughing, through which periphyton deposits refractory P into sediment. Multiple equilibria may exist, with two stable equilibria separated by an unstable equilibrium. Due to nonlinear interplay of periphyton and P in this model, catastrophe and hysteresis are likely to occur.

Conservation of Natural Resources↗

PubMed1993

Sample-distance partial least squares: PLS optimized for many variables, with application to CoMFA.

Three-dimensional molecular modeling can provide an unlimited number m of structural properties. Comparative Molecular Field Analysis (CoMFA), for example, may calculate thousands of field values for each model structure. When m is large, partial least squares (PLS) is the statistical method of choice for fitting and predicting biological responses. Yet PLS is usually implemented in a property-based fashion which is optimal only for small m. We describe here a sample-based formulation of PLS which can be used to fit any single response (bioactivity). SAMPLS reduces all explanatory data to the pairwise 'distances' among n samples (molecules), or equivalently to an n-by-n covariance matrix C. This matrix, unmodified, can be used to fit all PLS components. Furthermore, SAMPLS will validate the model by modern resampling techniques, at a cost independent of m. We have implemented SAMPLS as a Fortran program and have reproduced conventional and cross-validated PLS analyses of data from two published studies. Full (leave-each-out) cross-validation of a typical CoMFA takes 0.2 CPU s. SAMPLS is thus ideally suited to structure-activity analysis based on CoMFA fields or bonded topology. The sample-distance formulation also relates PLS to methods like cluster analysis and nonlinear mapping, and shows how drastically PLS simplifies the information in CoMFA fields.

Computer Simulation↗

PubMed2000

Temperature dependent luminescence characteristics of Sm3+-doped silicate glass.

We report here on the optical characterisation of Sm3+ (5 wt%): SiO2 + Al2O3 + Li2O + Na2O + MgO glass from the measurements of optical absorption spectra (at 300 K), total luminescence spectra (10-300 K) and fluorescence lifetimes (10-300 K) of the prominent emission transitions of the Sm3+ ions. Besides its spectral properties, physical and nonlinearity characterising property parameters have also been computed to understand the optical dispersive power of this glass. By the application of Judd-Ofelt parameters (omega(lambda)) of the measured absorption spectrum, the radiative transition probability factors (A) and stimulated emission cross-section (sigma(p)E) of the observed fluorescent levels have been analysed. Both emission intensity and measured lifetimes of the prominent luminescent transition (4G(5/2) --> 6H(7/2)) concerning Sm3+-glass has been showing a descending trend with the rise in temperature with N2-laser (337.1 nm) as the source of excitation.

Glass↗

PubMed2005

Numerical and experimental study of critical roof collapse conditions in soft lithography.

One of the major issues during soft lithographic processes is that, if the pressing force on the stamp becomes too high, the stamp may erroneously come into contact with the substrate in zones where contact is not intended. This decreases the patterning accuracy and may lead to badly or nonperforming electronic devices and is therefore undesired. Design rules, available at an early stage in the design phase, are desired to speed-up the development of this technique. Ultimately, these rules should give an indication of the critical pressure that can safely be applied on the stamp thereby avoiding unwanted contact between the stamp and the substrate. To obtain these critical pressures, numerical analyses of the deformation behavior of two characteristic configurations in the microstructured surface pattern of the rubber stamp are performed. The deformation behavior of the rubber is modeled according to a Gaussian and a non-Gaussian approach, leading to a neo-Hookean and Arruda-Boyce constitutive model, respectively. Besides these material nonlinearities, geometrical nonlinearities are taken into account as well. The calculated pressure at which undesired contact takes place (the roof collapse pressure) is compared to experimentally obtained values for two particular types of structures, and the results are in agreement within the error margins of the experiments and those ensuing from the assumptions of the numerical simulations.

Journal Article↗

PubMed1990

Determination of a constitutive relation for passive myocardium: II. Parameter estimation.

In the first paper of this series, we proposed a new transversely isotropic pseudostrain-energy function W for describing the biomechanical behavior of excised noncontracting myocardium. The specific functional form of W was inferred directly from biaxial data to be a polynomial function of two coordinate invariant measures of the finite deformation and five material parameters. In this paper, best-fit values of the material parameters are determined from biaxial data using a nonlinear least-squares regression. These values of the parameters are shown to be well-determined, and the final constitutive relation is shown to have good predictive capabilities. Since the proposed constitutive relation describes much broader classes of in-vitro biaxial data than previously proposed relations, it may be better applicable to analyses of stress in the passive heart.

Animals↗

PubMed1991

Are spontaneous otoacoustic emissions generated by self-sustained cochlear oscillators?

Theoretical analyses supporting the assumption that spontaneous otoacoustic emissions (SOAEs) can be described as self-sustained oscillations (requiring a power source) are reviewed and extended. Spectral and statistical properties of spontaneous otoacoustic emissions are examined and shown to be consistent with this assumption. Several alternative models of spontaneous emissions (noise-driven saturating memoryless nonlinearity, noise-driven nonlinear-stiffness oscillator) are examined. Although some of these models are able to produce the types of statistical distributions of amplitude and displacement similar to those observed in the experimental data, this similarity is destroyed upon narrow-band filtering.

Animals↗

PubMed2005

Population pharmacokinetic studies in pediatrics: issues in design and analysis.

The current review addresses the following 3 frequently encountered challenges in the design and analysis of population pharmacokinetic studies in pediatrics: (1) body size adjustments during the development of pharmacostatistical models, (2) design and validation of limited sampling strategies, and (3) the integration of historical priors in data analysis and trial simulation. Size adjustments with empiric approaches based on body weight or body surface area have frequently proven as a pragmatic tool to overcome large size differences in a pediatric study population. Allometric size adjustments, however, provide a more mechanistic, physiologically based approach that, if used a priori, allows delineation of the effect of size from that of other covariates that show a high degree of collinearity. The frequent lack of dense data sets in pediatric clinical pharmacology because of ethical and logistic constraints in study design can be overcome with the application of D-optimality-based limited sampling schemes in combination with Bayesian and nonlinear mixed-effects modeling approaches. Empirically based dose selection and clinical trial designs for pediatric clinical pharmacology studies can be improved by applying clinical trial simulation techniques, especially if they integrate adult and pediatric in vitro and/or in vivo data as historic priors. Although integration of these concepts and techniques in population pharmacokinetic analyses is not only limited to pediatric research, their application allows researchers to overcome some major hurdles frequently encountered in pharmacokinetic studies in pediatrics and, thus, provides the basis for additional clinical pharmacology research in this previously insufficiently studied fraction of the general population.

Humans↗

PubMed1986

Physiological properties of the luteinizing hormone pulse signal: impact of intensive and extended venous sampling paradigms on its characterization in healthy men and women.

The pulsatile nature of the gonadotropin signal is a critical determinant of physiological activation of the gonadal axis. Nonetheless, major uncertainties exist regarding the exact patterns of LH secretion that constitute normal physiological profiles in man. To assess possible bases for the discrepancies in the literature, we sampled blood at 5-min intervals for 24 h in eight normal men and eight normal women in the early follicular phase of the menstrual cycle. The constituent 5-, 10-, 15-, and 20-min immunoactive LH series and the consituent 6-, 12-, or 24-h sampling durations provided ranges of sampling intensities and durations for analysis of significant LH pulses. A technique for minimizing the influence of false positive immunoassay errors on peak detection was used to aid in estimating apparent true positive LH pulse frequency. Nonlinear curve fitting of the relationship between sampling intensity and apparent true positive LH pulse frequency revealed a stable pulse frequency estimate at intensive rates of venous sampling, with values of 19.5 +/- 1.9 (+/- SEM) pulses/24 h (periodicity, 73.8 +/- 6.5 min/pulse) in men and 20.6 +/- 3.6 pulses/24 h (periodicity, 70.0 +/- 10 min/pulse) in women. Further analyses indicated that sampling every 3.1 and 2.0 min for 24 h would be required to capture 90% of the LH pulses in men and women, respectively. Moreover, even with a 5-min sampling rate, the statistical counting errors of the LH pulse frequency estimates varied markedly with sampling duration; for example, in men sampled in 6-, 12-, and 24-hr sessions, the values were, respectively, 49%, 35%, and 24% of the observed pulse frequencies. Similar variations were found in women. Counting errors were 30-50% higher for conventional 20-min sampling rates than for 5-min sampling intervals. Measured interpulse intervals varied widely from 10-330 min (median, 60 min; n = 131 LH pulses) in men and from 10-340 min (median, 65 min; n = 125 LH pulses) in women. In addition, absolute LH pulse amplitudes varied from 1-28 mIU/ml (median, 4.1 mIU/ml) in men and from 1-24 mIU/ml (median, 3.6 mIU/ml) in women. These estimates were associated with a median number of points identified within each pulse of 6.0 in men and 4.0 in women. In summary, the present exhaustive sampling studies demonstrate for the first time stable estimates of physiological LH pulsations in normal men and women, and document broad ranges of normal LH pulse amplitudes and interpulse intervals.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1994

Ultrasound nonlinearity parameter (B/A) in biological tissues.

The ultrasonic nonlinearity parameter B/A is determined using the finite amplitude distortion method. The generation of second harmonic as a result of propagation of ultrasonic wave through the media, were measured by the receiving transducer (4.0 MHz) placed coaxial with the same sized cylindrical transmitting transducer (2.0 MHz). The second harmonic component of the wave, were analysed and recorded. The values of B/A of liver, kidney, spleen and heart tissues turns out to be 7.48, 6.75, 9.89 and 6.45 respectively.

Animals↗