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J Timmer

Publications and source records attributed to J Timmer.

At least 73 records · Page 4Linked to original sources
PubMed1998

Numerical methods to determine calcium release flux from calcium transients in muscle cells.

Several methods are currently in use to estimate the rate of depolarization-induced calcium release in muscle cells from measured calcium transients. One approach first characterizes calcium removal of the cell. This is done by determining parameters of a reaction scheme from a fit to the decay of elevated calcium after the depolarizing stimulus. In a second step, the release rate during depolarization is estimated based on the fitted model. Using simulated calcium transients with known underlying release rates, we tested the fidelity of this analysis in determining the time course of calcium release under different conditions. The analysis reproduced in a satisfactory way the characteristics of the input release rate, even when the assumption that release had ended before the start of the fitting interval was severely violated. Equally good reconstructions of the release rate time course could be obtained when the model used for the analysis differed in structure from the one used for simulating the data. We tested the application of a new strategy (multiple shooting) for fitting parameters in nonlinear differential equation systems. This procedure rendered the analysis less sensitive to ill-chosen initial guesses of the parameters and to noise. A locally adaptive kernel estimator for calculating numerical derivatives allowed good reconstructions of the original release rate time course from noisy calcium transients when other methods failed.

Algorithms↗
PubMed1998

Evaluation of forced oscillation technique for early detection of airway obstruction in sleep apnea: a model study.

The forced oscillation technique (FOT) is a non-invasive method which may be suitable for assessing upper airway obstruction in obstructive sleep apnea/hypopnea syndrome (OSAS) patients. The aim of this study was to determine in vitro if FOT can provide an early detection index of total or partial upper airway occlusion. A respiratory system analog was developed which includes an upper airway analog that allows simulation of upper airway collapse (thus mimicking the situation in patients with OSAS). We simulated different degrees of upper airway obstructions ranging from 0 (unobstructed airways) to 1 (total occlusion). Furthermore, we imitated the collapsible upper airway wall by means of elastic membranes with ten different wall compliances ranging from 3.3 x 10(-4) to 1 1/mbar. For the two stiffest rubber membranes (Cwall = 0.01 and 3.3 x 10(-4) l/mbar) the absolute value of the impedance (¿Z¿) showed a marked increase for obstructions greater than 0.6. For the two membranes with the highest wall compliances (Cwall = 0.03 and 1 1/mbar) obstructions with an increase in ¿Z¿ could not be detected before the obstruction reached 0.8. For degrees of obstruction less than 0.6 the phase angle of collapsible membranes with low compliance (stiff airway wall) were about 1.5pi which significantly differed from phase angles of 1.77pi measured in membranes with high compliance (elastic airway wall); p < 0.01. We hypothesized that stiffness of upper airway walls corresponds with their muscle tone, i.e., stiff airway walls are related with high muscle tone and vice versa. Thus, a decrease in upper airway muscle activity would cause an increase of upper airway wall elasticity that enables upper airway collapse. As a consequence the phase angle phi could be expected to change from values characterizing stiff membranes to values characterizing more elastic membranes which could be used as early indicator for obstructive respiratory events. We have frequently observed such changes in morphology of phi(t) data obtained from patients with OSAS.

Airway Obstruction↗
PubMed1997

Saccadic reaction times: a statistical analysis of multimodal distributions.

The distributions of saccadic reaction times (SRT) often deviate from unimodal normal distributions. An excess-mass procedure was used to detect peaks in 963 data sets containing 90,927 reaction times from 170 subjects. About 55% showed one, 30% two, 12% three and 3% four peaks. According to their clustering along the reaction time scale the modes could be classified into express (90-120 msec), fast regular (135-170 msec) and slow regular (200-220 msec) modes. Among the unimodal distributions 29% had peaks in the range of the express mode and 46% had peaks in the range of the fast regular mode. Therefore, 87% of the data sets support the notion of saccadic reaction time distributions being the superposition of three modes. All experimental distributions were fitted by as many gamma distributions as determined by the excess-mass test. The significance of the multimodality for saccade generation processes is discussed.

Fixation, Ocular↗
PubMed1997

Modeling volatility using state space models.

In time series problems, noise can be divided into two categories: dynamic noise which drives the process, and observational noise which is added in the measurement process, but does not influence future values of the system. In this framework, we show that empirical volatilities (the squared relative returns of prices) exhibit a significant amount of observational noise. To model and predict their time evolution adequately, we estimate state space models that explicitly include observational noise. We obtain relaxation times for shocks in the logarithm of volatility ranging from three weeks (for foreign exchange) to three to five months (for stock indices). In most cases, a two-dimensional hidden state is required to yield residuals that are consistent with white noise. We compare these results with ordinary autoregressive models (without a hidden state) and find that autoregressive models underestimate the relaxation times by about two orders of magnitude since they do not distinguish between observational and dynamic noise. This new interpretation of the dynamics of volatility in terms of relaxators in a state space model carries over to stochastic volatility models and to GARCH models, and is useful for several problems in finance, including risk management and the pricing of derivative securities. Data sets used: Olsen & Associates high frequency DEM/USD foreign exchange rates (8 years). Nikkei 225 index (40 years). Dow Jones Industrial Average (25 years).

Artificial Intelligence↗
PubMed1997

Analysis of multichannel patch clamp recordings by hidden Markov models.

Conventional methods of analysis do not allow the kinetics of patch clamped ion channels to be completely determined if more than one channel is present in the patch. This hinders investigations on small ion channels as well as on channel cooperativity and the homogeneity of channel populations. We present a method to extract the rate constants and current amplitudes for each individual channel from multichannel patches by a one-step procedure. For this purpose, the current record is modeled by the superposed Markov processes of the opening and closing of each channel that is contaminated by noise (Hidden Markov Model). Channel parameters are obtained by maximum likelihood methods. Because the parameters can be calculated directly from the unfiltered record, the dwell time and missed event problems are widely diminished. Confidence bounds for the estimated parameters are given. Statistical tests to decide whether channels switch identically and/or independently are introduced. The application of the method is demonstrated with simulated data.

Biometry↗
PubMed1996

Increased sensitivity of the inositol-phospholipid system in neutrophils from patients with acute major depressive episodes.

Evidence from in vitro and in vivo studies suggests that the therapeutic and prophylactic effects of lithium in recurrent affective disorders are due to an attenuation of the inositol-phospholipid (IPL) second messenger system. An increased sensitivity of this signal transduction system might therefore constitute a risk factor for affective illness. The extent of the agonist-induced release of intracellular Ca2+ (Ca2+ response) can be used as an indicator of the sensitivity of the IPL system. Using this paradigm, we have measured the agonist-induced Ca2+ response in neutrophils of 17 unmedicated patients who were experiencing an acute major depressive episode. The neutrophils were stimulated by the chemotactic peptide formylmethionylleucylphenylalanine, which activates the IPL system in the cells. The sensitivity of the IPL system in these patients was significantly greater (dose-response curve shifted to the left) compared with its sensitivity in healthy age- and sex-matched control subjects. The results indicate that acute episodes of major depression are associated with an increased sensitivity of the IPL system.

Adult↗
PubMed1996

Clinical neurophysiology of tremor.

The neurophysiological analysis of tremor has a long tradition. These attempts were directed to understand the mechanisms underlying tremor, on the one hand, and to develop tools to better diagnose the different types of tremor, on the other. Meanwhile, reasonable criteria are available to distinguish between centrally and peripherally mediated tremors. However, no generally accepted means exist to differentiate the different forms of central tremors. Frequency is a useful classifier for cerebellar tremor, rubral tremor, and orthostatic tremor. Although the highest amplitudes are found in Parkinson's disease, this parameter does not well distinguish between the different tremors. Waveform analysis of tremor is a promising tool to separate between the different tremors. Polymyography is pathognomonic for some rare forms of tremor. New approaches to classify tremors are based on positron emission tomography scanning, analysis of ballistic movement, and reflex testing. The means to separate myoclonias from tremors include EEG/EMG correlation techniques, long-latency reflexes, and polymyography. Provided these techniques are applied in the setting of careful clinical analysis of tremor syndromes, they may prove to be helpful in clinical practice.

Cerebellum↗
PubMed1996

Both adenosine A1- and A2-receptors are required to stimulate microglial proliferation.

The neuromodulator adenosine is one of the major endogenous inhibitors of overactive excitatory neurotransmission. Adenosine receptors have been identified on neuronal but also on glial surfaces, indicating a role of glial cells in mediation of adenosine effects. Microglia, the immunocompetent cells of the brain, typically respond with proliferation, migration and production of inflammatory substances to viral or bacterial stimuli or to cell damage and degeneration. Since adenosine is released in large amounts in conditions of, for example, hypoxic or ischemic stress, it might be involved in the activation process of microglia. Proliferation of microglia was determined by incorporation of [3H]thymidine into microglial DNA after stimulation with adenosine A1- and A2-receptor agonists. N6-Cyclopentyl adenosine (CPA) and CGS-21680, a specific adenosine A2-receptor agonist had no effect on microglial proliferation. However, combinations of CPA and CGS-21680 as well as the mixed agonist, N6-ethyl-carboxamido adenosine (NECA) increased incorporation of radiolabel above controls. The effect of NECA was inhibited by the adenosine A1-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). From these results, it is concluded that proliferation of microglia can be increased only by simultaneous stimulation of both adenosine A1- and A2-receptors. Targeted interference with the activation of A1-adenosine receptors by specific drugs appears to be sufficient to reduce microglial activation. The findings may have implications for the treatment of neurodegenerative diseases in which microglial activation is supposed to play a causative role.

Adenosine↗
PubMed1996

Quantitative analysis of tremor time series.

Spectral analysis is applied to tremor time series in basic research and treatment monitoring. The estimation of the spectra from the data is usually done by averaging the squared modulus of the Fourier transform of segments of the data. We discuss drawbacks of this method and propose an alternative procedure to estimate the spectra adaptively based on the data. Thus, the method can be applied to all types of tremor. Applying the theory of spectral estimation, we propose a method to decide whether a spectrum exhibits multiple significant peaks and discuss different approaches to determine the amplitude of the tremor from the spectrum.

Electromyography↗
PubMed1995

Some considerations on estimating event-related brain signals.

Understanding the timing of mental acts is one of the prominent questions in information processing research. The analysis of event related potentials (ERP) with their high temporal resolution might make access to cognition related brain activity possible. We consider three major problems which make the application of ERPs questionable and then propose some solutions to these problems. The primary problem concerns the separation of the ERPs from the background EEG which is not related to the stimulus. The most common method used is averaging. We argue that this is not the most appropriate method and suggest an alternative for estimating the signal in single-trial recordings. Artifacts present a second problem. We will first review established methods of dealing with eye-movement artifacts and then propose an alternative. We will also report on current work on the parametrisation of single-trial signal estimates, which constitute the third problem considered.

Algorithms↗
PubMed1993

Characteristics of hand tremor time series.

Tremor is classified into physiological, essential, and parkinsonian tremor by means of clinical criteria. The aim of our work was to extract quantitative features from the measurements of the acceleration of human postural hand tremor. Different mathematical methods were adopted and modified in order to separate these three types of tremor. Best discrimination between physiological and pathological tremors has been achieved by methods distinguishing nonlinear from linear behavior. On the other hand, methods separating different forms of nonlinear behavior have been found to be superior in discriminating parkinsonian and essential tremor. By these methods physiological and pathological tremors can be separated with an error rate below 20% and essential and parkinsonian tremor with an error rate below 10%. This may help to classify tremor time series by objective mathematical criteria and may increase the understanding of the pathophysiological differences underlying these kinds of tremor.

Cybernetics↗
PubMed1993

Cytokine production during sleep and wakefulness and its relationship to cortisol in healthy humans.

A growing body of evidence indicates that cytokines, especially interleukin-1 beta, are involved in the regulation of sleep and wakefulness. The aim of the present pilot study was to investigate the relationship between interleukin-1 beta (IL-1 beta) and gamma-interferon (gamma-IFN) production and the regulation of sleep and wakefulness. Four healthy male volunteers were investigated. After one adaptation night, beginning at 8 a.m. in the morning, the EEG was recorded by means of a mobile long-term EEG and blood samples were drawn every 45 min for the analysis of IL-1 beta, gamma-IFN and cortisol for 24 h. For the analysis of cytokines whole blood cultures were established. After 48 h of incubation in the presence of endotoxin Salmonella typhimurium, IL-1 beta and gamma-IFN levels were measured in the culture supernatants using specific immunodetection assays. Methods of stochastic time series analysis were adopted to evaluate the biochemical data. Our results show the capability of cultured blood cells to produce cytokines upon endotoxin challenge to be at a maximum around the time of sleep onset and during the first hours of sleep, declining during the night to a minimum level in the morning hours. The opposite was observed for cortisol. The analysis of autocorrelation functions gives evidence of a 24-hour rhythm of cortisol and cytokines. The results indicate that the cytokines IL-1 beta and gamma-IFN may play a role in sleep regulation.

Adult↗
PubMed1992

Analyzing the dynamics of hand tremor time series.

We investigate physiological, essential and parkinsonian hand tremor measured by the acceleration of the stretched hand. Methods from the theory of dynamical systems and from stochastics are used. It turns out that the physiological tremor can be described as a linear stochastic process, and that the parkinsonian tremor is nonlinear and deterministic, even chaotic. The essential tremor adopts a middle position, it is nonlinear and stochastic.

Hand↗