Some dynamical systems are characterized by more than one time-scale, e.g. two well separated time-scales are typical for quasiperiodic systems. The aim of this paper is to show how singular perturbation methods based on the slow-fast decomposition can serve for an enhanced parameter estimation when the slowly changing features are rigorously treated. Although the ultimate goal is to reduce the standard error for the estimated parameters, here we test two methods for numerical approximations of...
The common goal of systems pharmacology, i.e. systems biology applied to the field of pharmacology, is to rely less on trial and error in designing an input-output systems, e.g. therapeutic schedules. In this paper we present, on the paradigmatic example of a regulatory network of drug-induced enzyme production, the further development of the study published by Duintjer Tebbens . (2019) in the Applications of Mathematics. Here, the key feature is that the nonlinear model in form of an ODE system...
FRAP (Fluorescence Recovery After Photobleaching) is a measurement technique for determination of the mobility of fluorescent molecules (presumably due to the diffusion process) within the living cells. While the experimental setup and protocol are usually fixed, the method used for the model parameter estimation, i.e. the data processing step, is not well established. In order to enhance the quantitative analysis of experimental (noisy) FRAP data, we firstly formulate the inverse problem of model...
The design of an experiment, e.g., the setting of initial conditions, strongly influences the accuracy of the process of determining model parameters from data. The key concept relies on the analysis of the sensitivity of the measured output with respect to the model parameters. Based on this approach we optimize an experimental design factor, the initial condition for an inverse problem of a model parameter estimation. Our approach, although case independent, is illustrated at the FRAP (Fluorescence...
We present the method for determination of phycobilisomes diffusivity (diffusion coefficient ) on thylakoid membrane
from fluorescence recovery after photobleaching (FRAP) experiments. This was usually done by analytical models consisting mainly of a simple curve fitting procedure. However, analytical models need some unrealistic conditions to be supposed. Our method, based on finite difference approximation of the
process governed by the Fickian diffusion equation and on the minimization of an...
The well-known bottleneck of systems pharmacology, i. e., systems biology applied to pharmacology, refers to the model parameters determination from experimentally measured datasets. This paper represents the development of our earlier studies devoted to inverse (ill-posed) problems of model parameters identification. The key feature of this research is the introduction of control (or periodic forcing by an input signal being a drug intake) of the nonlinear model of drug-induced enzyme production...
We develop and test a relatively simple enhancement of the classical model reduction method applied to a class of chemical networks with mass conservation properties. Both the methods, being (i) the standard quasi-steady-state approximation method, and (ii) the novel so-called delayed quasi-steady-state approximation method, firstly proposed by Vejchodský (2014), are extensively presented. Both theoretical and numerical issues related to the setting of delays are discussed. Namely, for one slightly...
A pharmacodynamic model introduced earlier in the literature for in silico prediction of rifampicin-induced CYP3A4 enzyme production is described and some aspects of the involved curve-fitting based parameter estimation are discussed. Validation with our own laboratory data shows that the quality of the fit is particularly sensitive with respect to an unknown parameter representing the concentration of the nuclear receptor PXR (pregnane X receptor). A detailed analysis of the influence of that parameter...
A mathematical model of the microalgal growth under various light regimes is required for the optimization of design parameters and operating conditions in a photobioreactor. As its modelling framework, bilinear system with single input is chosen in this paper. The earlier theoretical results on bilinear systems are adapted and applied to the special class of the so-called intermittent controls which are characterized by rapid switching of light and dark cycles. Based on such approach, the following...
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