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PubMed2005

Changes in frontal plane dynamics and the loading response phase of the gait cycle are characteristic of severe knee osteoarthritis application of a multidimensional analysis technique.

BACKGROUND: Osteoarthritis of the knee is related to many correlated mechanical factors that can be measured with gait analysis. Gait analysis results in large data sets. The analysis of these data is difficult due to the correlated, multidimensional nature of the measures. METHODS: A multidimensional model that uses two multivariate statistical techniques, principal component analysis and discriminant analysis, was used to discriminate between the gait patterns of the normal subject group and the osteoarthritis subject group. Nine time varying gait measures and eight discrete measures were included in the analysis. All interrelationships between and within the measures were retained in the analysis. FINDINGS: The multidimensional analysis technique successfully separated the gait patterns of normal and knee osteoarthritis subjects with a misclassification error rate of <6%. The most discriminatory feature described a static and dynamic alignment factor. The second most discriminatory feature described a gait pattern change during the loading response phase of the gait cycle. INTERPRETATION: The interrelationships between gait measures and between the time instants of the gait cycle can provide insight into the mechanical mechanisms of pathologies such as knee osteoarthritis. These results suggest that changes in frontal plane loading and alignment and the loading response phase of the gait cycle are characteristic of severe knee osteoarthritis gait patterns. Subsequent investigations earlier in the disease process may suggest the importance of these factors to the progression of knee osteoarthritis.

Adaptation, Physiological↗
PubMed1999

Biological regulation of receptor-hormone complex concentrations in relation to dose-response assessments for endocrine-active compounds.

Some endocrine-active compounds (EACs) act as agonists or antagonists of specific hormones and may interfere with cellular control processes that regulate gene transcription. Many mechanisms controlling gene expression are universal to organisms ranging from unicellular bacteria to more complex plants and animals. One mechanism, coordinated control of batteries of gene products, is critical in adaptation of bacteria to new environments and for development and tissue differentiation in multi-cellular organisms. To coordinately activate sets of genes, all living organisms have devised molecular modules to permit transitions, or switching, between different functional states over a small range of hormone concentration, and other modules to stabilize the new state through homeostatic interactions. Both switching and homeostasis are regulated by controlling concentrations of hormone-receptor complexes. Molecular control processes for switching and homeostasis are inherently nonlinear and often utilize autoregulatory feedback loops. Among the biological processes contributing to switching phenomena are receptor autoinduction, induction of enzymes for ligand synthesis, mRNA stabilization/activation, and receptor polymerization. This paper discusses a variety of molecular switches found in animal species, devises simple quantitative models illustrating roles of specific molecular interactions in creating switching modules, and outlines the impact of these switching processes and other feedback loops for risk assessments with EACs. Quantitative simulation modeling of these switching mechanisms made it apparent that highly nonlinear dose-response curves for hormones and EACs readily arise from interactions of several linear processes acting in concert on a common control point. These nonlinear mechanisms involve amplification of response, rather than multimeric molecular interactions as in conventional Hill relationships.

Animals↗
PubMed2005

Defective control and adaptation of reflex eye movements in mutant mice deficient in either the glutamate receptor delta2 subunit or Purkinje cells.

The ionotropic glutamate receptor delta2 subunit (GluRdelta2) is selectively expressed in cerebellar Purkinje cells and is implicated in long-term depression, synaptic formation and elimination. To study the effect of GluRdelta2 deficiency on motor control, we measured the vestibulo-ocular reflex (VOR) and optokinetic response (OKR) induced by sinusoidal rotation of the animal and/or the surrounding screen in two GluRdelta2 mutant mice: a GluRdelta2 knockout mouse (delta2-/-) and a lurcher mouse with a point mutation in the GluRdelta2 gene resulting in loss of all Purkinje cells. delta2-/- showed significantly higher VOR gain in the dark (VORD) than in the wild-type. In delta2-/-, the VOR gain in light was lower than that in the dark. The phase of OKR lagged more in delta2-/- than in lurcher and wild-type mice. Both mutant mice failed to change the VORD or OKR gain adaptively in response to sustained vestibular and/or visual stimulation. Basal properties of VOR and OKR changed little by lesion of the flocculus, but they changed substantially by lesion of the inferior olivary nuclei (IO). The abnormal VOR gain and OKR phase delay were clearly reduced in delta2-/- by the latter lesion. Our results indicate that failures in the GluRdelta2-dependent synaptic regulation affect motor performance more severely than loss of cerebellar cortical outputs. This study suggests that the anomalies in delta2-/- are dependent on inputs from IO and that GluRdelta2 deficiency changed properties of not only the cerebellar cortex but also the brainstem neuronal pathways controlling reflex eye movements during development.

Adaptation, Physiological↗
PubMed1988

Strength reductions from metastatic cortical defects in long bones.

The purpose of this investigation was to measure the reduction in bone strength resulting from drill holes in diaphyseal bone and to compare this with finite element and theoretical predictions for stresses in a tubular structure. Fifty-two pairs of canine femora were tested to failure in four-point bending. One bone of each pair was used as the control; the other femora had holes of variable size drilled in the lateral cortex. At a ratio of drill hole diameter to bone diameter of 0.2, the bone retained only 62% of its expected strength. A linear regression between the area fraction (the ratio of the cross-sectional area of the drilled specimen to the control specimen) and the percentage of expected strength yielded a strong positive correlation (R2 = 0.79). The average cross-sectional properties were used as the basis for linear orthotropic and nonlinear elastic-plastic finite element models of idealized geometry. The linear models proved insufficient for prediction of failure loads. The nonlinear models, which accounted for both material plasticity and the stress concentration effects of the defect, yielded good correspondence with the experimental data. While the influence of irregular borders and adaptive remodeling of the bone adjacent to the defect requires further investigation, our results suggest the possibility of prediction of fracture risk based on geometric properties of metastatic lesions. Prophylactic fixation remains a matter of clinical judgement based on the functional demands and expected strength of the affected bones.

Animals↗
PubMed1992

Loss of 'complexity' and aging. Potential applications of fractals and chaos theory to senescence.

The concept of "complexity," derived from the field of nonlinear dynamics, can be adapted to measure the output of physiologic processes that generate highly variable fluctuations resembling "chaos." We review data suggesting that physiologic aging is associated with a generalized loss of such complexity in the dynamics of healthy organ system function and hypothesize that such loss of complexity leads to an impaired ability to adapt to physiologic stress. This hypothesis is supported by observations showing an age-related loss of complex variability in multiple physiologic processes including cardiovascular control, pulsatile hormone release, and electroencephalographic potentials. If further research supports this hypothesis, measures of complexity based on chaos theory and the related geometric concept of fractals may provide new ways to monitor senescence and test the efficacy of specific interventions to modify the age-related decline in adaptive capacity.

Aging↗
PubMed1986

The Glenn A. Fry award lecture: adaptive regulation of accommodative vergence and vergence accommodation.

The tonic resting level of accommodation, measured with an objective infrared optometer in an open-loop state (pinhole pupil or empty field), was increased by more than 1.75 D from baseline measures of resting focus after adapting monocularly for 1 min to a 2 D minus lens. The accommodative aftereffect disappeared in darkness, but returned when a visible stimulus reappeared in the open-loop state. Stimulation of disparity vergence with 10 delta, while accommodation was in an open-loop state, also increased the resting focus of accommodation. Similarly, the tonic resting level of vergence became more esophoric after adapting for less than 1 min to base-out prism or to a minus lens presented while the vergence loop was opened. The effects of tonic accommodation on accommodative vergence and the effects of tonic vergence on vergence accommodation were investigated with the temporal frequency responses of the AC/A and CA/C ratios to sinusoidal variations in blur (2 D) and disparity (10 delta), respectively. Accommodative vergence was unresponsive to low temporal frequency sinusoidal variations in blur (less than 0.1 Hz). Similarly, vergence accommodation was unresponsive to low temporal frequency sinusoidal variations in disparity. However, accommodative vergence and vergence accommodation were responsive to higher temporal frequency stimuli (up to 0.5 Hz). When negative feedback to the stimulated system (accommodation or vergence) was cancelled electronically, the low temporal frequency response increased for the AC/A and CA/C ratios, respectively. There was also a nonlinear increase of both AC/A and CA/C ratios as stimulus amplitude increased. It is hypothesized that the nonlinearity resulted from limitations of adaptation to small stimuli. An inverse complementary relation is suggested between the amplitude of the AC/A ratio and adaptable tonic accommodation, and between the amplitude of the CA/C ratio and adaptable tonic vergence. This model predicts that in this complementary relation, adaptable tonic elements would sustain motor responses of accommodation and vergence that were initiated by phasic elements and cross-link interactions. It also predicts that the AC/A and CA/C ratios would decrease in time as dynamic control shifted from the phasic to the adaptable tonic control mechanisms of accommodation and vergence, respectively.

Accommodation, Ocular↗
PubMed1986

A two-stage nonlinear cochlear model possesses automatic gain control.

A model of the cochlea is explored using as stimuli two simultaneously presented sinusoids of equal amplitude. The model consists of two stages: a linear bandpass filter, followed by a reservoir-type representation of the hair-cell/nerve-fiber complex. Fast Fourier transforms of the model's output were computed. While the amplitudes of the individual response components were strongly nonlinear functions of intensity, the ratio of the magnitudes of the response components at the frequencies of the two stimulating sinusoids was found to be nearly equal, over a wide intensity range, to the ratio of the amplitudes which those stimulating sinusoids possessed at the output of the filter. Thus the reservoir stage exerts "automatic gain control".

Adaptation, Physiological↗
PubMed1979

Pattern generation in the lobster (Panulirus) stomatogastric ganglion. I. Pyloric neuron kinetics and synaptic interactions.

There are a number of perspectives gained from a quantitative analysis of the pyloric system which may be applicable to other simple pattern generators: 1. The system is organized around a dominant, endogenously-bursting neuron group, and its properties are tailored to that dominance. In particular, synaptic strengths and firing frequencies of that group appear just sufficient to suppress postsynaptic "follower" cells if the latter are not too highly excited. 2. Repetitive firing properties of follower neurons are such as to facilitate their switch-like mode of activity. This includes pacemaker response nonlinearities, rebound properties, and "burstiness" properties. 3. Proper sequencing of follower cells may be controlled by particular synaptic strengths and time-courses, feedback on the oscillator cells, and functional cellular properties of follower neurons (e.g., rebound; see also next paper). All such properties interact and must be tuned to each other for proper patterns to result.

Adaptation, Physiological↗
PubMed2004

Physiological complexity, aging, and the path to frailty.

Healthy physiological processes require the complex interaction of multiple control systems operating over multiple time scales. The output of these processes (for example, heart rate, blood pressure, hormonal rhythms, or postural sway) demonstrates complex variability that can be quantified using the concept of fractals, derived from the field of nonlinear dynamics. Complex physiological dynamics enable an organism to rapidly respond to the internal and external perturbations of everyday life. Aging and disease are associated with a loss of complexity in the dynamics of many physiological systems. This loss of complexity may reduce the ability to adapt to stress and lead to the syndrome of frailty.

Aged↗
PubMed1997

Continuous cultivation start-up control--an experimental investigation.

A control strategy to avoid development of synchronous growth in carbohydrate limited Saccharomyces cerevisiae cultivations is proposed and experimentally investigated. The basic idea is to control the metabolic flux through the pathways by manipulating the substrate feed rate to keep the ethanol concentration at a low level. An adaptive and a fixed parameter controller were investigated experimentally. Both controllers were initialized at the target conditions for the continuous cultivation, where the uncontrolled process is known to be marginally stable. The latter fact renders it unfeasible to attempt open loop operation at the critical dilution rate. The adaptive controller turned out to be superior to the fixed parameter controller. The superiority of the adaptive controller is ascribed to its ability to identify the process under varying cell activity. The obtained experimental results demonstrate that the desired operating point is reproducibly obtainable. However, after prolonged operation under different types of disturbances the yeast seemed to adapt towards an increased respiratory activity for the same low level of ethanol in the medium.

Algorithms↗
PubMed1999

Nonlinear alteration of transient vergence dynamics after sustained convergence.

BACKGROUND: Adaptation models of the horizontal disparity vergence system assume a nonadaptable transient component. They also predict identical postadaptation dynamics during convergence and divergence movements. METHOD: To test the adaptation property of the transient component, a set of experiments were performed in which closed-loop vergence dynamics measured before and after sustained convergence were compared, primarily by comparing the peak vergence velocity, occurrence time of peak vergence velocity, and steady-state vergence posture. Vergence dynamics after durations of 30, 60, and 90 s of sustained convergence were compared with those after a control duration of 5 s. RESULTS: The peak divergence velocity was reduced by about 25% within 30 s of sustained vergence. However, the peak convergence velocity was unchanged for all the exposure durations. Additionally, for all durations, the peak divergence velocity was significantly higher than peak convergence velocity. In contrast to peak velocities, the occurrence time of peak convergence and divergence velocity did not differ significantly and remained unchanged for all durations. CONCLUSIONS: The transient component is adaptable. Furthermore, the adaptation is direction dependent and affects divergence and convergence dynamics differently, thereby suggesting involvement of separate pathways for convergence and divergence in the vergence sensorimotor control.

Accommodation, Ocular↗
PubMed2004

Grid powered nonlinear image registration with locally adaptive regularization.

Multi-subject non-rigid registration algorithms using dense deformation fields often encounter cases where the transformation to be estimated has a large spatial variability. In these cases, linear stationary regularization methods are not sufficient. In this paper, we present an algorithm that uses a priori information about the nature of imaged objects in order to adapt the regularization of the deformations. We also present a robustness improvement that gives higher weight to those points in images that contain more information. Finally, a fast parallel implementation using networked personal computers is presented. In order to improve the usability of the parallel software by a clinical user, we have implemented it as a grid service that can be controlled by a graphics workstation embedded in the clinical environment. Results on inter-subject pairs of images show that our method can take into account the large variability of most brain structures. The registration time for images of size 256 x 256 x 124 is 5 min on 15 standard PCs. A comparison of our non-stationary visco-elastic smoothing versus solely elastic or fluid regularizations shows that our algorithm converges faster towards a more optimal solution in terms of accuracy and transformation regularity.

Algorithms↗
PubMedDate not supplied

A modification and validation of two urine ethanol procedures for use with the Monarch 2000 Chemistry System.

A modification of two commercially available enzymatic ethanol urine assays for use with the Monarch 2000 Chemistry System (Instrumentation Laboratory) is described. Both the Syva EMIT st Urine Ethyl Alcohol Assay and the Sigma Diagnostics Alcohol in Urine Assay, which utilize the reduction of nicotinamide adenine dinucleotide (NAD) to NADH associated with the oxidation of ethanol in the presence of alcohol dehydrogenase (ADH), were adapted to spectrophotometrically determine ethanol concentration. Precision was evaluated over a 3-day period. Within-day (n = 9) and total (n = 27) coefficients of variation (CV) were less than 7% for the controls greater than or equal to 200 mg/L (20 mg/dL). Enzymatic assay results utilizing the Monarch procedure were compared to a gas chromatographic (GC) reference method (n = 100 samples). Regression analysis of assay data with each reagent compared to the reference method resulted in correlation coefficients r = 0.972 (Syva) and 0.948 (Sigma). Both methods exhibited nonlinear results and therefore quantitative applications cannot be made. No false positive or negative results were encountered with either reagent, indicating that the assay is acceptable as a positive/negative screen for urine ethanol for a threshold less than or equal to 20 mg/dL.

Chromatography, Gas↗
PubMed2004

Hybrid internal model control and proportional control of chaotic dynamical systems.

A new chaos control method is proposed to take advantage of chaos or avoid it. The hybrid Internal Model Control and Proportional Control learning scheme are introduced. In order to gain the desired robust performance and ensure the system's stability, Adaptive Momentum Algorithms are also developed. Through properly designing the neural network plant model and neural network controller, the chaotic dynamical systems are controlled while the parameters of the BP neural network are modified. Taking the Lorenz chaotic system as example, the results show that chaotic dynamical systems can be stabilized at the desired orbits by this control strategy.

Algorithms↗
PubMed1990

The neural site of binocular rivalry relative to the analysis of motion in the human visual system.

Neural processing is disrupted during suppression phases of binocular rivalry, as evidenced by the temporary invisibility of an otherwise complex, high-contrast visual stimulus. This paper investigates the locus of this disruption relative to the processing of information about image motion. In one experiment, observers tracked binocular rivalry between a stationary textured field and a plaid composed of 2 drifting cosine gratings, with the angle between components varied to produce different pattern speeds. (Plaid speed is given by the ratio of the component speed to the cosine of the angle between the 2 directions of motion.) Predominance of the moving plaid increased with pattern speed, even though the speed of the individual components remained constant. Control measures verified that this influence of plaid speed was not attributable to specific component orientations. Information about coherent motion influences the rivalry process, implying that the site of coherent motion analysis, presumably the middle temporal area (MT), received input during dominance phases of rivalry. A second experiment investigated the effect of suppression on the processing of complex, nonlinear motion. Observers tracked rivalry phases for a rotating spiral, then indicated the duration of the subsequently perceived spiral aftereffect (SAE) for both rivalry and nonrivalry conditions. The SAE was reduced when adaptation occurred under the rivalry condition, with aftereffect duration proportional to the total duration of spiral visibility during adaptation. Earlier work places rivalry after the site of the linear motion aftereffect, and the present results show that rivalry suppression occurs prior to the site of spiral motion processing.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Ocular↗
PubMed2000

Adaptation to the edge of chaos in the self-adjusting logistic map.

Self-adjusting, or adaptive, systems have gathered much recent interest. We present a model for self-adjusting systems which treats the control parameters of the system as slowly varying, rather than constant. The dynamics of these parameters is governed by a low-pass filtered feedback from the dynamical variables of the system. We apply this model to the logistic map and examine the behavior of the control parameter. We find that the parameter leaves the chaotic regime. We observe a high probability of finding the parameter at the boundary between periodicity and chaos. We therefore find that this system exhibits adaptation to the edge of chaos.

Adaptation, Biological↗
PubMed1991

Dynamics of adaptation for vision with a stabilized image.

The addition of a uniform increment of light to a high-contrast image that has been stabilized on the retina reveals marked perceptual nonlinearities. When the increment is small, the pattern appears in its original phase (OP), large increments produce an apparent phase reversal (APR), and intermediate increments may yield an apparently blank field or an oscillation of the apparent phase. In the present series of studies the threshold values used to produce a stable OP and APR were determined as a function of adaptation time before the application of the increment. The stabilized target had a luminance profile consisting of the difference of two Gaussians. A model of detection incorporating a multiplicative gain controlled by a filtered version of the stimulus was used to account for the occurrence of the OP and the APR and the transitory phenomena following the uniform increment. It is argued that the midpoint of the transition zone between the OP and APR, corresponding to blanking, enables us to estimate the shape of the step response function of the gain filter independently of the subsequent detection processes.

Adaptation, Ocular↗
PubMed2005

The effect of stimulus duty cycle and "off" duration on BOLD response linearity.

An ongoing question in functional MRI is precisely how measured signal changes relate to neuronal activity. While this question has been probed using animal models and electrophysiologic measures of neuronal activity, it has also been probed by examining, in humans, the spatial location, magnitude, and temporal dynamics of signal changes to well understood stimuli. With regard to dynamics, several earlier studies have revealed a larger than expected response to brief stimuli, hypothesized to result from nonlinearities in either the hemodynamics or the neuronal activity. In this study, we investigate the linearity of the increase in blood oxygenation level dependent (BOLD) contrast as a function of stimulus duty cycle, as well as the linearity of the decrease in BOLD as a function stimulus "off" duration. These findings not only shed further light on the mechanisms behind BOLD contrast but also give practical information as to what to keep in mind when performing and interpreting event related fMRI experiments. These experiments demonstrated: a) the BOLD signal decrease, on stimulus cessation, was smaller than predicted by a linear system--opposite to what has been reported in the literature associated with a signal increase, and b) the deconvolved event-related BOLD signal is highly dependent on duty cycle (the fraction of time activated vs. non-activated), Several potential mechanisms explaining these dynamics are discussed and modeled. We find that the experimental results are most consistent with a nonlinear neuronal response, but do not rule out significant effects of nonlinear hemodynamic factors, in particular the nonlinear relationship between oxygen extraction fraction and blood flow.

Adaptation, Physiological↗