Probability distributed time delays: integrating spatial effects into temporal models

Background In order to provide insights into the complex biochemical processes inside a cell, modelling approaches must find a balance between achieving an adequate representation of the physical phenomena and keeping the associated computational cost within reasonable limits. This issue is particularly stressed when spatial inhomogeneities have a significant effect on system's behaviour. In such cases, a spatially-resolved stochastic method can better portray the biological reality, but the corresponding computer simulations can in turn be prohibitively expensive. Results We present a method that incorporates spatial information by means of tailored, probability distributed time-delays. These distributions can be directly obtained by single in silico or a suitable set of in vitro experiments and are subsequently fed into a delay stochastic simulation algorithm (DSSA), achieving a good compromise between computational costs and a much more accurate representation of spatial processes such as molecular diffusion and translocation between cell compartments. Additionally, we present a novel alternative approach based on delay differential equations (DDE) that can be used in scenarios of high molecular concentrations and low noise propagation. Conclusions Our proposed methodologies accurately capture and incorporate certain spatial processes into temporal stochastic and deterministic simulations, increasing their accuracy at low computational costs. This is of particular importance given that time spans of cellular processes are generally larger (possibly by several orders of magnitude) than those achievable by current spatially-resolved stochastic simulators. Hence, our methodology allows users to explore cellular scenarios under the effects of diffusion and stochasticity in time spans that were, until now, simply unfeasible. Our methodologies are supported by theoretical considerations on the different modelling regimes, i.e. spatial vs. delay-temporal, as indicated by the corresponding Master Equations and presented elsewhere.

Collective dynamics and control of a 3-D small-world network with time delays

The paper presents a detailed analysis on the collective dynamics and delayed state feedback control of a three-dimensional delayed small-world network. The trivial equilibrium of the model is first investigated, showing that the uncontrolled model exhibits complicated unbounded behavior. Then three control strategies, namely a position feedback control, a velocity feedback control, and a hybrid control combined velocity with acceleration feedback, are then introduced to stabilize this unstable system. It is shown in these three control schemes that only the hybrid control can easily stabilize the 3-D network system. And with properly chosen delay and gain in the delayed feedback path, the hybrid controlled model may have stable equilibrium, or periodic solutions resulting from the Hopf bifurcation, or complex stranger attractor from the period-doubling bifurcation. Moreover, the direction of Hopf bifurcation and stability of the bifurcation periodic solutions are analyzed. The results are further extended to any "d" dimensional network. It shows that to stabilize a "d" dimensional delayed small-world network, at least a "d – 1" order completed differential feedback is needed. This work provides a constructive suggestion for the high dimensional delayed systems.

The oculomotor system: (1) Vertical-horizontal interaction and signal recognition, (2) Time delays and power spectra

In the first section of this thesis, two-dimensional properties of the human eye movement control system were studied. The vertical - horizontal interaction was investigated by using a two-dimensional target motion consisting of a sinusoid in one of the directions vertical or horizontal, and low-pass filtered Gaussian random motion of variable bandwidth (and hence information content) in the orthogonal direction. It was found that the random motion reduced the efficiency of the sinusoidal tracking. However, the sinusoidal tracking was only slightly dependent on the bandwidth of the random motion. Thus the system should be thought of as consisting of two independent channels with a small amount of mutual cross-talk.

These target motions were then rotated to discover whether or not the system is capable of recognizing the two-component nature of the target motion. That is, the sinusoid was presented along an oblique line (neither vertical nor horizontal) with the random motion orthogonal to it. The system did not simply track the vertical and horizontal components of motion, but rotated its frame of reference so that its two tracking channels coincided with the directions of the two target motion components. This recognition occurred even when the two orthogonal motions were both random, but with different bandwidths.

In the second section, time delays, prediction and power spectra were examined. Time delays were calculated in response to various periodic signals, various bandwidths of narrow-band Gaussian random motions and sinusoids. It was demonstrated that prediction occurred only when the target motion was periodic, and only if the harmonic content was such that the signal was sufficiently narrow-band. It appears as if general periodic motions are split into predictive and non-predictive components.

For unpredictable motions, the relationship between the time delay and the average speed of the retinal image was linear. Based on this I proposed a model explaining the time delays for both random and periodic motions. My experiments did not prove that the system is sampled data, or that it is continuous. However, the model can be interpreted as representative of a sample data system whose sample interval is a function of the target motion.

It was shown that increasing the bandwidth of the low-pass filtered Gaussian random motion resulted in an increase of the eye movement bandwidth. Some properties of the eyeball-muscle dynamics and the extraocular muscle "active state tension" were derived.

Retinal adaptation of visual processing time delays.

A significant proportion of the processing delays within the visual system are luminance dependent. Thus placing an attenuating filter over one eye causes a temporal delay between the eyes and thus an illusion of motion in depth for objects moving in the fronto-parallel plane, known as the Pulfrich effect. We have used this effect to study adaptation to such an interocular delay in two normal subjects wearing 75% attenuating neutral density filters over one eye. In two separate experimental periods both subjects showed about 60% adaptation over 9 days. Reciprocal effects were seen on removal of the filters. To isolate the site of adaptation we also measured the subjects' flicker fusion frequencies (FFFs) and contrast sensitivity functions (CSFs). Both subjects showed significant adaptation in their FFFs. An attempt to model the Pulfrich and FFF adaptation curves with a change in a single parameter in Kelly's [(1971) Journal of the Optical Society of America, 71, 537-546] retinal model was only partially successful. Although we have demonstrated adaptation in normal subjects to induced time delays in the visual system we postulate that this may at least partly represent retinal adaptation to the change in mean luminance.

A novel scheme for human-friendly and time-delays robust neuropredictive teleoperation

A novel Neuropredictive Teleoperation (NPT) Scheme is presented. The design results from two key ideas: the exploitation of the measured or estimated neural input to the human arm or its electromyograph (EMG) as the system input and the employment of a predictor of the arm movement, based on this neural signal and an arm model, to compensate for time delays in the system. Although a multitude of such models, as well as measuring devices for the neural signals and the EMG, have been proposed, current telemanipulator research has only been considering highly simplified arm models. In the present design, the bilateral constraint that the master and slave are simultaneously compliant to each other's state (equal positions and forces) is abandoned, thus obtaining a simple to analyzesuccession of only locally controlled modules, and a robustness to time delays of up to 500 ms. The proposed designs were inspired by well established physiological evidence that the brain, rather than controlling the movement on-line, programs the arm with an action plan of a complete movement, which is then executed largely in open loop, regulated only by local reflex loops. As a model of the human arm the well-established Stark model is employed, whose mathematical representation is modified to make it suitable for an engineering application. The proposed scheme is however valid for any arm model. BIBO-stability and passivity results for a variety of local control laws are reported. Simulation results and comparisons with traditional designs also highlight the advantages of the proposed design.

Improvement on delay dependent absolute stability of Lurie control systems with multiple time delays

Absolute stability of Lurie control systems with multiple time-delays is studied in this paper. By using extended Lyapunov functionals, we avoid the use of the stability assumption on the main operator and derive improved stability criteria, which are strictly less conservative than the criteria in [2,3].

Partial state estimation for linear systems with output and input time delays.

This paper deals with the problem of partial state observer design for linear systems that are subject to time delays in the measured output as well as the control input. By choosing a set of appropriate augmented Lyapunov-Krasovskii functionals with a triple-integral term and using the information of both the delayed output and input, a novel approach to design a minimal-order observer is proposed to guarantee that the observer error is ε-convergent with an exponential rate. Existence conditions of such an observer are derived in terms of matrix inequalities for the cases with time delays in both the output and input and with output delay only. Constructive design algorithms are introduced. Numerical examples are provided to illustrate the design procedure, practicality and effectiveness of the proposed observer.

A reduced model clarifies the role of feedback loops and time delays in the Drosophila circadian oscillator.

Although several detailed models of molecular processes essential for circadian oscillations have been developed, their complexity makes intuitive understanding of the oscillation mechanism difficult. The goal of the present study was to reduce a previously developed, detailed model to a minimal representation of the transcriptional regulation essential for circadian rhythmicity in Drosophila. The reduced model contains only two differential equations, each with time delays. A negative feedback loop is included, in which PER protein represses per transcription by binding the dCLOCK transcription factor. A positive feedback loop is also included, in which dCLOCK indirectly enhances its own formation. The model simulated circadian oscillations, light entrainment, and a phase-response curve with qualitative similarities to experiment. Time delays were found to be essential for simulation of circadian oscillations with this model. To examine the robustness of the simplified model to fluctuations in molecule numbers, a stochastic variant was constructed. Robust circadian oscillations and entrainment to light pulses were simulated with fewer than 80 molecules of each gene product present on average. Circadian oscillations persisted when the positive feedback loop was removed. Moreover, elimination of positive feedback did not decrease the robustness of oscillations to stochastic fluctuations or to variations in parameter values. Such reduced models can aid understanding of the oscillation mechanisms in Drosophila and in other organisms in which feedback regulation of transcription may play an important role.

Improvement of the processes around the radiology workplace : avoidance of time delays

Radiologists have been confronted with multiple new challenges in recent years. While there has been a steady increase in the number of radiological examinations and imaging material per examination, examination protocols have become more complex and highly time-consuming whereas case-based remuneration is on the decline. The identification of inefficient components in examination processes and reporting is therefore essential. Where and why do time delays occur? How can they be avoided? The following article provides a brief overview and is designed to stimulate discussion.

Time Delays on the Identification of the Need for CPR for Limited English Proficient 9-1-1 Callers

Thesis (Master's)--University of Washington, 2016-08

Partial state estimation of LTI systems with multiple constant time-delays

Functional observer design for Multi-Input Multi-Output (MIMO) Linear Time-Invariant (LTI) systems with multiple mixed time delays in the states of the system is addressed. Two structures for the design of a minimum-order observer are considered: 1 - delay-dependent, and 2 - internal-delay independent. The parameters of the delay-dependent observer are designed using the Lyapunov Krasovskii approach. The delay-dependent exponential stability of the observer for a specified convergence rate and delay values is guaranteed upon the feasibility of a set of Linear Matrix Inequalities (LMIs) together with a rank condition. Using the descriptor transformation, a modified Jensen's inequality, and improved Park's inequality, the results can be less conservative than the available functional observer design methods that address LTI systems with single state delay. Furthermore, the necessary and sufficient conditions of the asymptotic stability of the internal-delay independent observer are obtained, which are shown to be independent of delay. Two illustrative numerical examples and simulation studies confirm the validity and highlight the performance of the proposed theoretical achievements.

Robust observer design for a class of one-sided Lipschitz systems subject to time delays and disturbances in both plants and outputs

In this paper, we consider the problem of designing state observers for a class of one-sided Lipschitz time-delay systems subject to disturbances. Not only the plants but also the outputs of the systems are subject to time delays and disturbances. The one-sided Lipschitz and quadraticallyinner-bounded conditions, which are more general than the traditional Lipschitz condition, are utilized to cover a broader class of nonlinearities. Based on the Lyapunov-Krasovskii approach, a robust observer design is proposed where synthesis condition is derived in terms of linear matrixinequality (LMI). A numerical example is given to show the effectiveness of the obtained results.