44 research outputs found
Parametric, nonparametric and parametric modelling of a chaotic circuit time series
The determination of a differential equation underlying a measured time
series is a frequently arising task in nonlinear time series analysis. In the
validation of a proposed model one often faces the dilemma that it is hard to
decide whether possible discrepancies between the time series and model output
are caused by an inappropriate model or by bad estimates of parameters in a
correct type of model, or both. We propose a combination of parametric
modelling based on Bock's multiple shooting algorithm and nonparametric
modelling based on optimal transformations as a strategy to test proposed
models and if rejected suggest and test new ones. We exemplify this strategy on
an experimental time series from a chaotic circuit where we obtain an extremely
accurate reconstruction of the observed attractor.Comment: 19 pages, 8 Fig
A mathematical model for breath gas analysis of volatile organic compounds with special emphasis on acetone
Recommended standardized procedures for determining exhaled lower respiratory
nitric oxide and nasal nitric oxide have been developed by task forces of the
European Respiratory Society and the American Thoracic Society. These
recommendations have paved the way for the measurement of nitric oxide to
become a diagnostic tool for specific clinical applications. It would be
desirable to develop similar guidelines for the sampling of other trace gases
in exhaled breath, especially volatile organic compounds (VOCs) which reflect
ongoing metabolism. The concentrations of water-soluble, blood-borne substances
in exhaled breath are influenced by: (i) breathing patterns affecting gas
exchange in the conducting airways; (ii) the concentrations in the
tracheo-bronchial lining fluid; (iii) the alveolar and systemic concentrations
of the compound. The classical Farhi equation takes only the alveolar
concentrations into account. Real-time measurements of acetone in end-tidal
breath under an ergometer challenge show characteristics which cannot be
explained within the Farhi setting. Here we develop a compartment model that
reliably captures these profiles and is capable of relating breath to the
systemic concentrations of acetone. By comparison with experimental data it is
inferred that the major part of variability in breath acetone concentrations
(e.g., in response to moderate exercise or altered breathing patterns) can be
attributed to airway gas exchange, with minimal changes of the underlying blood
and tissue concentrations. Moreover, it is deduced that measured end-tidal
breath concentrations of acetone determined during resting conditions and free
breathing will be rather poor indicators for endogenous levels. Particularly,
the current formulation includes the classical Farhi and the Scheid series
inhomogeneity model as special limiting cases.Comment: 38 page
Hybrid optimization method with general switching strategy for parameter estimation
This article is available from: http://www.biomedcentral.com/1752-0509/2/26[Background] Modeling and simulation of cellular signaling and metabolic pathways as networks of
biochemical reactions yields sets of non-linear ordinary differential equations. These models usually
depend on several parameters and initial conditions. If these parameters are unknown, results from
simulation studies can be misleading. Such a scenario can be avoided by fitting the model to
experimental data before analyzing the system. This involves parameter estimation which is usually
performed by minimizing a cost function which quantifies the difference between model predictions
and measurements. Mathematically, this is formulated as a non-linear optimization problem which
often results to be multi-modal (non-convex), rendering local optimization methods detrimental.[Results] In this work we propose a new hybrid global method, based on the combination of an
evolutionary search strategy with a local multiple-shooting approach, which offers a reliable and
efficient alternative for the solution of large scale parameter estimation problems.[Conclusion] The presented new hybrid strategy offers two main advantages over previous
approaches: First, it is equipped with a switching strategy which allows the systematic
determination of the transition from the local to global search. This avoids computationally
expensive tests in advance. Second, using multiple-shooting as the local search procedure reduces
the multi-modality of the non-linear optimization problem significantly. Because multiple-shooting
avoids possible spurious solutions in the vicinity of the global optimum it often outperforms the
frequently used initial value approach (single-shooting). Thereby, the use of multiple-shooting yields
an enhanced robustness of the hybrid approach.This work was supported by the European Community as part of the FP6
COSBICS Project (STREP FP6-512060), the German Federal Ministry of
Education and Research, BMBF-project FRISYS (grant 0313921) and Xunta
de Galicia (PGIDIT05PXIC40201PM).Peer reviewe
Rho-kinase-dependent F-actin rearrangement is involved in the inhibition of PI3-kinase/Akt during ischemia–reperfusion-induced endothelial cell apoptosis
Activation of cytoskeleton regulator Rho-kinase during ischemia–reperfusion (I/R) plays a major role in I/R injury and apoptosis. Since Rho-kinase is a negative regulator of the pro-survival phosphatidylinositol 3-kinase (PI3-kinase)/Akt pathway, we hypothesized that inhibition of Rho-kinase can prevent I/R-induced endothelial cell apoptosis by maintaining PI3-kinase/Akt activity and that protective effects of Rho-kinase inhibition are facilitated by prevention of F-actin rearrangement. Human umbilical vein endothelial cells were subjected to 1 h of simulated ischemia and 1 or 24 h of simulated reperfusion after treatment with Rho-kinase inhibitor Y-27632, PI3-kinase inhibitor wortmannin, F-actin depolymerizers cytochalasinD and latrunculinA and F-actin stabilizer jasplakinolide. Intracellular ATP levels decreased following I/R. Y-27632 treatment reduced I/R-induced apoptosis by 31% (P < 0.01) and maintained Akt activity. Both effects were blocked by co-treatment with wortmannin. Y-27632 treatment prevented the formation of F-actin bundles during I/R. Similar results were observed with cytochalasinD treatment. In contrast, latrunculinA and jasplakinolide treatment did not prevent the formation of F-actin bundles during I/R and had no effect on I/R-induced apoptosis. Apoptosis and Akt activity were inversely correlated (R2 = 0.68, P < 0.05). In conclusion, prevention of F-actin rearrangement by Rho-kinase inhibition or by cytochalasinD treatment attenuated I/R-induced endothelial cell apoptosis by maintaining PI3-kinase and Akt activity
A Combined Approach for the Identification of Continuous Nonlinear Systems
The identification of a nonlinear continuous output-only system from a time series is considered for the case that the functional form of the model is not known beforehand. To estimate both functions and parameters, a combination of nonparametric modeling based on nonlinear regression and parametric modeling based on a multiple shooting algorithm is proposed. This strategy to determine nonlinear differential equations is exemplified on experimental data from a chaotic circuit where an accurate reconstruction of the observed attractor is obtained
Identification of rate constants and non-observable absorption spectra in nonlinear biochemical reaction dynamics
On analyzing data of biochemical reaction dynamics monitored by time-resolved spectroscopy, one faces the problem that the concentration time courses of the involved components are not directly observed, but the superposition of their absorption spectra. Furthermore the single spectra are often unknown, because the corresponding reagents cannot be isolated. We propose a method based on Bock's multiple shooting algorithm to estimate the rate constants and individual spectra simultaneously. Applying this procedure to a biochemical reaction we identify the specific rate constants characterizing the reaction dynamics as well as the nonobservable absorption spectra. The results lead to a better understanding of the kinetics of a novel modification reaction which was used as trapping reaction in disulfide bond mediated protein folding reactions