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PubMed1985

Interaction between short- and longer-wavelength cones in hue cancellation codes: nonlinearities of hue cancellation as a function of stimulus intensity.

Hue cancellation experiments were carried out to test the linear additivity of chromatic valences. There were two kinds of experiments: the measurements of the yellow-blue cancellation function and of the red-green one. The opponent-color equilibria were determined as a function of stimulus intensity for mixture lights of various spectral compositions. The results of the yellow-blue cancellation functions showed that the nonlinearity of the cancellation code strongly depended on the spectral compositions of stimuli: the nonlinearity became evident under conditions producing a relative increase in the long-wavelength-cone excitation, while it was reduced under conditions producing a relative increase in the middle-wavelength-cone excitation. This property could be well explained if we assume that the gain of the short-wavelength signal might be controlled by a difference signal between the long- and middle-wavelength cones. The results of the red-green cancellation functions showed that the cancellation function for a violet light was nonlinear under some specific conditions, while the cancellation function for a red light remained linear. The nonlinearity of the short-wavelength red response became more prominent under conditions producing a relative increase in the long-wavelength-cone excitation. It is suggested that the cone-interaction between the short- and longer-wavelength cones may be responsible for the nonlinearities of the yellow-blue and red-green hue cancellation codes.

Adaptation, Ocular↗

PubMed2003

The formation of spatial patterns in social insects: from simple behaviours to complex structures.

Many of the collective activities performed by social insects result in the formation of complex spatio-temporal patterns. Without centralized control, workers are able to work together and collectively tackle tasks far beyond the abilities of any one individual. The resulting patterns produced by a colony are not explicitly coded at the individual level, but rather emerge from nonlinear interactions between individuals or between individuals and their environment. We present a few selected examples to illustrate some of the basic mechanisms used by social insects, such as templates, stigmergy and self-organization. These mechanisms can be used in combination to organize pattern formation at the colony level.

Adaptation, Physiological↗

PubMed1998

Nonlinearity of radiation health effects.

The prime concern of radiation protection policy since 1959 has been to protect DNA from damage. In 1994 the United Nations Scientific Community on the Effects of Atomic Radiation focused on biosystem response to radiation with its report Adaptive Responses to Radiation of Cells and Organisms. The 1995 National Council on Radiation Protection and Measurements report Principles and Application of Collective Dose in Radiation Protection states that because no human data provides direct support for the linear nonthreshold hypothesis (LNT), confidence in LNT is based on the biophysical concept that the passage of a single charged particle could cause damage to DNA that would result in cancer. Several statistically significant epidemiologic studies contradict the validity of this concept by showing risk decrements, i.e., hormesis, of cancer mortality and mortality from all causes in populations exposed to low-dose radiation. Unrepaired low-dose radiation damage to DNA is negligible compared to metabolic damage. The DNA damage-control biosystem is physiologically operative on both metabolic and radiation damage and effected predominantly by free radicals. The DNA damage-control biosystem is suppressed by high dose and stimulated by low-dose radiation. The hormetic effect of low-dose radiation may be explained by its increase of biosystem efficiency. Improved DNA damage control reduces persistent mis- or unrepaired DNA damage i.e., the number of mutations that accumulate during a lifetime. This progressive accumulation of gene mutations in stem cells is associated with decreasing DNA damage control, aging, and malignancy. Recognition of the positive health effects produced by adaptive responses to low-dose radiation would result in a realistic assessment of the environmental risk of radiation.

Animals↗

PubMed1995

[Deterministic chaos in biology].

Higher physiological organisms are characterised by a complex interaction of multiple control systems. This interaction permits man to adapt those unexpected demands given by experimental changes. The idea of complexity results basically from the non linearity of dynamic systems that are correlated to each other through feedback cycles. These systems fluctuate in an apparent chaos. The improvidence and the non uniformity of biological systems are basic qualities that define the state of health. It is anyhow possible to discriminate in them a certain repeatability of interaction that succeeded each other; this repeatability makes the system fit for a fractal interpretation.

Biology↗

PubMed2005

Adaptation without parameter change: Dynamic gain control in motion detection.

Many sensory systems adapt their input-output relationship to changes in the statistics of the ambient stimulus. Such adaptive behavior has been measured in a motion detection sensitive neuron of the fly visual system, H1. The rapid adaptation of the velocity response gain has been interpreted as evidence of optimal matching of the H1 response to the dynamic range of the stimulus, thereby maximizing its information transmission. Here, we show that correlation-type motion detectors, which are commonly thought to underlie fly motion vision, intrinsically possess adaptive properties. Increasing the amplitude of the velocity fluctuations leads to a decrease of the effective gain and the time constant of the velocity response without any change in the parameters of these detectors. The seemingly complex property of this adaptation turns out to be a straightforward consequence of the multidimensionality of the stimulus and the nonlinear nature of the system.

Adaptation, Physiological↗

PubMed2005

Paradigm shifts in radiation biology: their impact on intervention for radiation-induced disease.

New mechanistic cell and molecular studies on the effects of very low doses of radiation have resulted in three major paradigm shifts. First, the observation of bystander effects demonstrated that non-hit cells may respond as well as cells in which energy is deposited. Second, it was thought that gene mutations and chromosome aberrations were the most important early changes that represented the initiation phase of radiation-induced cancer. Now genomic instability that leads to the loss of genetic control appears to play a major role in the development of cancer. Finally, recent studies have demonstrated that radiation-induced changes in gene expression can be demonstrated at very low radiation doses. These changes can result in alterations in response pathways, many of which appear to be involved in protective or adaptive responses. The demonstration that unique genes are up- and down-regulated depending on the radiation type, dose and dose rate suggests that different molecular mechanisms are involved in responses to high and low radiation doses. The ability to alter radiation response by physical and chemical treatments suggests that it may be possible to intervene in the progression of radiation-induced diseases. Such intervention may decrease the cancer risk from radiation exposure. This new research also demonstrates that many nonlinear biological processes have an impact on the induction of cancer and the shape of dose-response functions. Thus, for low-LET radiation delivered at low dose rates, the linear, no-threshold hypothesis is not well supported, but it is adequately conservative in protecting against low-dose radiation risks.

Adaptation, Physiological↗

PubMed2006

Network reorganization driven by temporal interdependence of its elements.

We employ an adaptive parameter control technique based on detection of phase/lag synchrony between the elements of the system to dynamically modify the structure of a network of nonidentical, coupled Rossler oscillators. Two processes are simulated: adaptation, under which the initially different properties of the units converge, and rewiring, in which clusters of interconnected elements are formed based on the temporal correlations. We show how those processes lead to different network structures and investigate their optimal characteristics from the point of view of resulting network properties.

Action Potentials↗

PubMed1994

A phase I and pharmacokinetic study of intravenous phenylacetate in patients with cancer.

Phenylacetate has recently been shown to suppress tumor growth and promote differentiation in experimental models. A phase I trial of phenylacetate was conducted in 17 patients with advanced solid tumors. Each patient received a single i.v. bolus dose followed by a 14-day continuous i.v. infusion of the drug. Twenty-one cycles of therapy were administered at four dose levels, achieved by increasing the rate of the continuous i.v. infusion. Phenylacetate displayed nonlinear pharmacokinetics [Km = 105.1 +/- 44.5 (SD) microgram/ml, Vmax = 24.1 +/- 5.2 mg/kg/h and Vd = 19.2 +/- 3.3 L]. There was also evidence for induction of drug clearance. Ninety-nine % of phenylacetate elimination was accounted for by conversion to phenylacetylglutamine, which was excreted in the urine. Continuous i.v. infusion rates resulting in serum phenylacetate concentrations exceeding Km often resulted in rapid drug accumulation and dose-limiting toxicity, which consisted of reversible central nervous system depression, preceded by emesis. Three of nine patients with metastatic, hormone-refractory prostate cancer maintained stable prostatic specific antigen levels for more than 2 months; another had less bone pain. One of six patients with glioblastoma multiforme, whose steroid dosage has remained unchanged for the duration of therapy, has sustained functional improvement for more than 9 months. The use of adaptive control with feedback for the dosing of each patient enabled us to safely maintain stable phenylacetate concentrations up to the range of 200-300 micrograms/ml, which resulted in clinical improvement in some patients with advanced disease.

Adult↗

PubMed2005

Investigations on the reaction pattern of photosystem II in leaves from Arabidopsis thaliana wild type plants and mutants with genetically modified lipid content.

The role of digalactosyldiacylglycerol (DGDG) for the functional competence of photosystem II (PS II) has been analyzed in leaves of Arabidopsis thaliana plants where the lipid composition was selectively modified by genetic mutations. Measurements with a newly developed laser flash fluorometer and data evaluation within the framework of an extended "3-quencher" model lead to the following results: (i) the normalized fluorescence transients F(t)/F(0) induced by an actinic laser flash in dark adapted leaves are virtually the same in wild type (WT) and mutants with diminished (about 50%) monogalactosyldiacylglycerol (MGDG) content (mgd1 mutant); (ii) significant changes of the F(t)/F(0) curves are observed in mutants with a severely reduced DGDG content; (iii) in mutants dgd1 and dgd1 dgd2-1 with DGDG contents of 1/15 of the control and below the detection limit, respectively, the probability of the dissipative recombination reaction between P680(+)(*) and Q(A)(-) increases by factors of about two and four, respectively; (iv) the acceptor side reactions are only slightly affected; (v) excitation with actinic laser flash energies above the saturation level of photosynthesis gives rise to elevated carotenoid triplet formation in mutants dgd1 and dgd1 dgd2-1; and (vi) the relationship between DGDG content and functional effect(s) on PS II is strikingly nonlinear. A small fraction of DGDG molecules of the total pool is inferred to be specifically bound to PS II as an essential constituent for its functional competence.

Arabidopsis↗

PubMed2005

Adaptive complete synchronization of two identical or different chaotic (hyperchaotic) systems with fully unknown parameters.

This paper studies the adaptive complete synchronization of chaotic and hyperchaotic systems with fully unknown parameters. In practical situations, some systems' parameters cannot be exactly known a priori, and the uncertainties often affect the stability of the process of synchronization of the chaotic oscillators. An adaptive scheme is proposed to compensate for the effects of parameters' uncertainty based on the structure of chaotic systems in this paper. Based on the Lyapunov stability theorem, an adaptive controller and a parameters update law can be designed for the synchronization of chaotic and hyperchaotic systems. The drive and response systems can be nonidentical, even with different order. Three illustrative examples are given to demonstrate the validity of this technique, and numerical simulations are also given to show the effectiveness of the proposed chaos synchronization method. In addition, this synchronization scheme is quite robust against the effect of noise.

Adaptation, Physiological↗

PubMed2002

Stabilizing and tracking unknown steady States of dynamical systems.

An adaptive dynamic state feedback controller for stabilizing and tracking unknown steady states of dynamical systems is proposed. We prove that the steady state can never be stabilized if the system and controller in sum have an odd number of real positive eigenvalues. For two-dimensional systems, this topological limitation states that only an unstable focus or node can be stabilized with a stable controller, and stabilization of a saddle requires the presence of an unstable degree of freedom in a feedback loop. The use of the controller to stabilize and track saddle points (as well as unstable foci) is demonstrated both numerically and experimentally with an electrochemical Ni dissolution system.

Feedback↗

PubMed1998

A model for geometric and mechanical adaptation of arteries to sustained hypertension.

This study aimed to model phenomenologically the dynamics of arterial wall remodeling under hypertensive conditions. Sustained hypertension was simulated by a step increase in blood pressure. The arterial wall was considered to be a thick-walled tube made of nonlinear elastic incompressible material. Remodeling rate equations were postulated for the evolution of the geometric dimensions of the hypertensive artery at the zero-stress state, as well as for one of the material constants in the constitutive equations. The driving stimuli for the geometric adaptation are the normalized deviations of wall stresses from their values under normotensive conditions. The geometric dimensions are modulated by the evolution of the deformed inner radius, which serves to restore the level of the flow-induced shear stresses at the arterial endothelium. Mechanical adaptation is driven by the difference between the area compliance under hypertensive and normotensive conditions. The predicted time course of the geometry and mechanical properties of arterial wall are in good qualitative agreement with published experimental findings. The model predicts that the geometric adaptation maintains the stress distribution in arterial wall to its control level, while the mechanical adaptation restores the normal arterial function under induced hypertension.

Adaptation, Physiological↗

PubMed2005

Direct thermal dose control of constrained focused ultrasound treatments: phantom and in vivo evaluation.

The first treatment control system that explicitly and automatically balances the efficacy and safety goals of noninvasive thermal therapies is described, and its performance is evaluated in phantoms and in vivo using ultrasound heating with a fixed, focused transducer. The treatment efficacy is quantified in terms of thermal dose delivered to the target. The developed feedback thermal dose controller has a cascade structure with the main nonlinear dose controller continuously generating the reference temperature trajectory for the secondary, constrained, model predictive temperature controller. The control system ensures thermal safety of the normal tissue by automatically complying with user-specified constraints on the maximum allowable normal tissue temperatures. To reflect hardware limitations and to prevent cavitation, constraints on the maximum transducer power can also be imposed. It is shown that the developed controller can be used to achieve the minimum-time delivery of the desired thermal dose to the target without violating safety constraints, which is a novel and clinically desirable feature. The developed controller is model based, and requires patient- and site-specific models for its operation. These models were obtained during pre-treatment identification experiments. In our implementation, predictive models, internally used by the automatic treatment controller, are dynamically updated each time new temperature measurements become available. The adaptability of internal models safeguards against adverse effects of modelling errors, and ensures robust performance of the control system in the presence of a priori unknown treatment disturbances. The successful validation with two experimental models of considerably different thermal and ultrasound properties suggests the applicability of the developed treatment control system to different anatomical sites.

Animals↗

PubMed2006

Optimal movement variability: a new theoretical perspective for neurologic physical therapy.

Variability is a natural and important feature of human movement. Using existing theoretical frameworks as a foundation, we propose a new model to explain movement variability as it relates to motor learning and health. We contend that mature motor skills and healthy states are associated with an optimal amount of movement variability. This variability also has form and is characterized by a chaotic structure. Less than optimal movement variability characterizes biological systems that are overly rigid and unchanging, whereas greater than optimal variability characterizes systems that are noisy and unstable. Both situations characterize systems that are less adaptable to perturbations, such as those associated with abnormal motor development or unhealthy states. From our perspective, the goal of neurologic physical therapy should be to foster the development of this optimal amount of movement variability by incorporating a rich repertoire of movement strategies. The development of such a repertoire can be enhanced by incorporating a multitude of experiences within the therapeutic milieu. Promoting complex variation in human movement allows either motor development or the recovery of function after injury not to be hard coded, but determined instead by the active engagement of the individual within their environment. Measurement tools derived from nonlinear dynamics that characterize the complexity of movement variability provide useful means of testing these propositions. To illustrate, we present 2 clinical case studies, one pediatric and one adult, where we applied our theoretical framework to measuring change in postural control.

Adolescent↗

PubMed2005

Statistical validation of mutual information calculations: comparison of alternative numerical algorithms.

Given two time series X and Y , their mutual information, I (X,Y) = I (Y,X) , is the average number of bits of X that can be predicted by measuring Y and vice versa. In the analysis of observational data, calculation of mutual information occurs in three contexts: identification of nonlinear correlation, determination of an optimal sampling interval, particularly when embedding data, and in the investigation of causal relationships with directed mutual information. In this contribution a minimum description length argument is used to determine the optimal number of elements to use when characterizing the distributions of X and Y . However, even when using partitions of the X and Y axis indicated by minimum description length, mutual information calculations performed with a uniform partition of the XY plane can give misleading results. This motivated the construction of an algorithm for calculating mutual information that uses an adaptive partition. This algorithm also incorporates an explicit test of the statistical independence of X and Y in a calculation that returns an assessment of the corresponding null hypothesis. The previously published Fraser-Swinney algorithm for calculating mutual information includes a sophisticated procedure for local adaptive control of the partitioning process. When the Fraser and Swinney algorithm and the algorithm constructed here are compared, they give very similar numerical results (less than 4% difference in a typical application). Detailed comparisons are possible when X and Y are correlated jointly Gaussian distributed because an analytic expression for I (X,Y) can be derived for that case. Based on these tests, three conclusions can be drawn. First, the algorithm constructed here has an advantage over the Fraser-Swinney algorithm in providing an explicit calculation of the probability of the null hypothesis that X and Y are independent. Second, the Fraser-Swinney algorithm is marginally the more accurate of the two algorithms when large data sets are used. With smaller data sets, however, the Fraser-Swinney algorithm reports structures that disappear when more data are available. Third, the algorithm constructed here requires about 0.5% of the computation time required by the Fraser-Swinney algorithm.

Journal Article↗

PubMed2000

Analysis of nonlinear volume-dependent respiratory system mechanics in pediatric patients.

OBJECTIVE: Analysis of dynamic respiratory system mechanics is generally based on a resistance-compliance model in which nonlinearities of the respiratory mechanics indices are not considered. The recently developed SLICE method analyzing consecutive volume slices of the tidal volume was used for determination of non-linear volume-dependent respiratory system mechanics. Volume-dependent compliance C(Slice) and resistance R(Slice) were compared with C(MLR) and R(MLR) obtained by standard multiple linear regression analysis (MLR). DESIGN: Prospective observational study. SETTING: Pediatric intensive care unit in a university hospital. PATIENTS: Fifteen pediatric patients, aged 24 days to 9.6 yrs, weighing 3-67.5 kg. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: With respect to their pulmonary status, the patients were grouped into three clinical groups: patients with no lung diseases, patients with restrictive lung diseases, and patients with obstructive lung diseases. All patients were mechanically ventilated via a cuffed endotracheal tube in the pressure-controlled mode. Flow and airway pressure were measured at the proximal end of the tube and tracheal pressure was continuously calculated. Respiratory mechanics were determined either with the SLICE method or, as reference, by using standard MLR. In most patients, the pressure-volume relationship was nonlinear, particularly in patients with restrictive and obstructive lung diseases. In the presence of considerable nonlinearity, the volume-dependent respiratory mechanics indices obtained by the SLICE method showed better agreement between recalculated and original pressure-volume loops compared with the MLR results. Furthermore, signs of overdistension of the patient's lung became obvious when using the SLICE method, whereas they were undetected by MLR. CONCLUSIONS: The SLICE method is well suited for the analysis of nonlinear volume-dependent respiratory system mechanics in pediatric patients. The SLICE method may be used as a first step toward an adaptation of ventilator settings with respect to the actual mechanical status of the patient's respiratory system, and, to prevent pulmonary overdistension.

Journal Article↗

PubMed2005

Subsarcolemmal and intermyofibrillar mitochondria play distinct roles in regulating skeletal muscle fatty acid metabolism.

Skeletal muscle contains two populations of mitochondria that appear to be differentially affected by disease and exercise training. It remains unclear how these mitochondrial subpopulations contribute to fiber type-related and/or training-induced changes in fatty acid oxidation and regulation of carnitine palmitoyltransferase-1beta (CPT1beta), the enzyme that controls mitochondrial fatty acid uptake in skeletal muscle. To this end, we found that fatty acid oxidation rates were 8.9-fold higher in subsarcolemmal mitochondria (SS) and 5.3-fold higher in intermyofibrillar mitochondria (IMF) that were isolated from red gastrocnemius (RG) compared with white gastrocnemius (WG) muscle, respectively. Malonyl-CoA (10 muM), a potent inhibitor of CPT1beta, completely abolished fatty acid oxidation in SS and IMF mitochondria from WG, whereas oxidation rates in the corresponding fractions from RG were inhibited only 89% and 60%, respectively. Endurance training also elicited mitochondrial adaptations that resulted in enhanced fatty acid oxidation capacity. Ten weeks of treadmill running differentially increased palmitate oxidation rates 100% and 46% in SS and IMF mitochondria, respectively. In SS mitochondria, elevated fatty acid oxidation rates were accompanied by a 48% increase in citrate synthase activity but no change in CPT1 activity. Nonlinear regression analyses of mitochondrial fatty acid oxidation rates in the presence of 0-100 muM malonyl-CoA indicated that IC(50) values were neither dependent on mitochondrial subpopulation nor affected by exercise training. However, in IMF mitochondria, training reduced the Hill coefficient (P < 0.05), suggesting altered CPT1beta kinetics. These results demonstrate that endurance exercise provokes subpopulation-specific changes in mitochondrial function that are characterized by enhanced fatty acid oxidation and modified CPT1beta-malonyl-CoA dynamics.

Animals↗

PubMed1993

The effect of position of immobilisation on resting length, resting stiffness, and weight of the soleus muscle of the rabbit.

The extent of immobilisation-induced adaptations of muscle length and muscle weight is known to be profoundly influenced by the position (or length) at which the muscle is immobilised. However, the effect of the full range of positions of immobilisation on subsequent adaptations of muscle length and weight has not yet been investigated. To examine further the effect of position of immobilisation, we used cast-immobilisation of the hind limbs of 23 rabbits, in various positions between full plantar flexion and full dorsiflexion. Six muscles from non-immobilised rabbits were used as the controls. After 10 days of immobilisation, the wet weight of the soleus muscle and the resting length and resting stiffness of the soleus muscle-tendon unit were determined. Immobilisation in a shortened position was associated with a significantly greater decrease in length and weight than was immobilisation in a lengthened position. In addition, immobilisation produced significant increases in the resting stiffness of muscle-tendon units, although there was no evidence of a position-dependent increase in stiffness. Muscle weight was influenced by the position of immobilisation in a nonlinear way. The data support the views that the pre-immobilisation resting length of the muscle represents a threshold length and that immobilisation at lengths longer than this retards immobilisation-induced atrophy.

Animals↗