Synthesizing attractors of Hindmarsh-Rose neuronal systems

In this paper a periodic parameter switching scheme is applied to the Hindmarsh-Rose neuronal system to synthesize certain attractors. Results show numerically, via computer graphic simulations, that the obtained synthesized attractor belongs to the class of all admissible attractors for the Hindmarsh-Rose neuronal system and matches the averaged attractor obtained with the control parameter replaced with the averaged switched parameter values. This feature allows us to imagine that living beings are able to maintain vital behavior while the control parameter switches so that their dynamical behavior is suitable for the given environment.Comment: published in Nonlinear Dynamic

Antiferromagnetic interlayer exchange coupling across an amorphous metallic spacer layer

By means of magneto-optical Kerr effect we observe for the first time antiferromagnetic coupling between ferromagnetic layers across an amorphous metallic spacer layer. Biquadratic coupling occurs at the transition from a ferromagnetically to an antiferromagnetically coupled region. Scanning tunneling microscopy images of all involved layers are used to extract thickness fluctuations and to verify the amorphous state of the spacer. The observed antiferromagnetic coupling behavior is explained by RKKY interaction taking into account the amorphous structure of the spacer material.Comment: Typset using RevTex, 4 pages with 4 figures (.eps

Global parameter identification of stochastic reaction networks from single trajectories

We consider the problem of inferring the unknown parameters of a stochastic biochemical network model from a single measured time-course of the concentration of some of the involved species. Such measurements are available, e.g., from live-cell fluorescence microscopy in image-based systems biology. In addition, fluctuation time-courses from, e.g., fluorescence correlation spectroscopy provide additional information about the system dynamics that can be used to more robustly infer parameters than when considering only mean concentrations. Estimating model parameters from a single experimental trajectory enables single-cell measurements and quantification of cell--cell variability. We propose a novel combination of an adaptive Monte Carlo sampler, called Gaussian Adaptation, and efficient exact stochastic simulation algorithms that allows parameter identification from single stochastic trajectories. We benchmark the proposed method on a linear and a non-linear reaction network at steady state and during transient phases. In addition, we demonstrate that the present method also provides an ellipsoidal volume estimate of the viable part of parameter space and is able to estimate the physical volume of the compartment in which the observed reactions take place.Comment: Article in print as a book chapter in Springer's "Advances in Systems Biology

Bayesian inference of biochemical kinetic parameters using the linear noise approximation

Background Fluorescent and luminescent gene reporters allow us to dynamically quantify changes in molecular species concentration over time on the single cell level. The mathematical modeling of their interaction through multivariate dynamical models requires the deveopment of effective statistical methods to calibrate such models against available data. Given the prevalence of stochasticity and noise in biochemical systems inference for stochastic models is of special interest. In this paper we present a simple and computationally efficient algorithm for the estimation of biochemical kinetic parameters from gene reporter data. Results We use the linear noise approximation to model biochemical reactions through a stochastic dynamic model which essentially approximates a diffusion model by an ordinary differential equation model with an appropriately defined noise process. An explicit formula for the likelihood function can be derived allowing for computationally efficient parameter estimation. The proposed algorithm is embedded in a Bayesian framework and inference is performed using Markov chain Monte Carlo. Conclusion The major advantage of the method is that in contrast to the more established diffusion approximation based methods the computationally costly methods of data augmentation are not necessary. Our approach also allows for unobserved variables and measurement error. The application of the method to both simulated and experimental data shows that the proposed methodology provides a useful alternative to diffusion approximation based methods

Global parameter estimation methods for stochastic biochemical systems

<p>Abstract</p> <p>Background</p> <p>The importance of stochasticity in cellular processes having low number of molecules has resulted in the development of stochastic models such as chemical master equation. As in other modelling frameworks, the accompanying rate constants are important for the end-applications like analyzing system properties (e.g. robustness) or predicting the effects of genetic perturbations. Prior knowledge of kinetic constants is usually limited and the model identification routine typically includes parameter estimation from experimental data. Although the subject of parameter estimation is well-established for deterministic models, it is not yet routine for the chemical master equation. In addition, recent advances in measurement technology have made the quantification of genetic substrates possible to single molecular levels. Thus, the purpose of this work is to develop practical and effective methods for estimating kinetic model parameters in the chemical master equation and other stochastic models from single cell and cell population experimental data.</p> <p>Results</p> <p>Three parameter estimation methods are proposed based on the maximum likelihood and density function distance, including probability and cumulative density functions. Since stochastic models such as chemical master equations are typically solved using a Monte Carlo approach in which only a finite number of Monte Carlo realizations are computationally practical, specific considerations are given to account for the effect of finite sampling in the histogram binning of the state density functions. Applications to three practical case studies showed that while maximum likelihood method can effectively handle low replicate measurements, the density function distance methods, particularly the cumulative density function distance estimation, are more robust in estimating the parameters with consistently higher accuracy, even for systems showing multimodality.</p> <p>Conclusions</p> <p>The parameter estimation methodologies described in this work have provided an effective and practical approach in the estimation of kinetic parameters of stochastic systems from either sparse or dense cell population data. Nevertheless, similar to kinetic parameter estimation in other modelling frameworks, not all parameters can be estimated accurately, which is a common problem arising from the lack of complete parameter identifiability from the available data.</p

Optimization in computational systems biology

Optimization aims to make a system or design as effective or functional as possible. Mathematical optimization methods are widely used in engineering, economics and science. This commentary is focused on applications of mathematical optimization in computational systems biology. Examples are given where optimization methods are used for topics ranging from model building and optimal experimental design to metabolic engineering and synthetic biology. Finally, several perspectives for future research are outlined

Unlimited Subrogation: Improving Medical Malpractice Liability by Allowing Insurers to Take Charge

This article proposes unlimited insurance subrogation (UIS) to improve the insurance and deterrence results of medical malpractice liability. Unlimited insurance subrogation enables patients to assign their entire potential medical malpractice claims to their first-party insurers without limitation as to the amount the insurers pay out in benefits or recover in tort damages. Unlimited insurance subrogation should improve insurance outcomes by converting suboptimal tort insurance into more optimal first-party insurance. Establishing first-party insurers as plaintiffs to confront liability insurers on the defense side should improve deterrence through more effective prosecution of meritorious claims and by harnessing the insurers' incentives for cooperation to reduce meritless and unnecessary litigation. In addition, UIS should encourage further reforms by contract between the first-party and liability insurers who would take charge of the system. This article shows that loss of patient cooperation, insurer gaming, and other possible problems with UIS are unlikely to arise or are readily solvable. (c) 2007 by The University of Chicago. All rights reserved..