Evaluation of stochastic effects on biomolecular networks using the generalised Nyquist stability criterion

Abstract—Stochastic differential equations are now commonly used to model biomolecular networks in systems biology, and much recent research has been devoted to the development of methods to analyse their stability properties. Stability analysis of such systems may be performed using the Laplace transform, which requires the calculation of the exponential matrix involving time symbolically. However, the calculation of the symbolic exponential matrix is not feasible for problems of even moderate size, as the required computation time increases exponentially with the matrix order. To address this issue, we present a novel method for approximating the Laplace transform which does not require the exponential matrix to be calculated explicitly. The calculation time associated with the proposed method does not increase exponentially with the size of the system, and the approximation error is shown to be of the same order as existing methods. Using this approximation method, we show how a straightforward application of the generalized Nyquist stability criterion provides necessary and sufficient conditions for the stability of stochastic biomolecular networks. The usefulness and computational efficiency of the proposed method is illustrated through its application to the problem of analysing a model for limit-cycle oscillations in cAMP during aggregation of Dictyostelium cells

Robustness analysis of magnetic torquer controlled spacecraft attitude dynamics

This paper describes a systematic approach to the robustness analysis of linear periodically time-varying (LPTV) systems. The method uses the technique known as Lifting to transform the original time-varying uncertain system into linear fractional transformation (LFT) form. The stability and performance robustness of the system to structured parametric uncertainty can then be analysed non-conservatively using the structured singular value μ. The method is applied to analyse the stability robustness of an attitude control law for a spacecraft controlled by magnetic torquer bars, whose linearised dynamics can naturally be written in linear periodically time-varying form. The proposed method allows maximum allowable levels of uncertainty, as well as worst-case uncertainty combinations to be computed. The destabilising effect of these uncertain parameter combinations is verified in time-domain simulations

Validation of a model of regulation in the tryptophan operon against multiple experiment data using global optimisation

This paper is concerned with validating a mathematical model of regulation in the tryptophan operon using global optimization. Although a number of models for this biochemical network are proposed, in many cases only qualitative agreement between the model output and experimental data was demonstrated, since very little information is currently available to guide the selection of parameter values for the models. This paper presents a model validating method using both multiple experimental data and global optimization

Least-squares methods for identifying biochemical regulatory networks from noisy measurements

<b>Background</b>: We consider the problem of identifying the dynamic interactions in biochemical networks from noisy experimental data. Typically, approaches for solving this problem make use of an estimation algorithm such as the well-known linear Least-Squares (LS) estimation technique. We demonstrate that when time-series measurements are corrupted by white noise and/or drift noise, more accurate and reliable identification of network interactions can be achieved by employing an estimation algorithm known as Constrained Total Least Squares (CTLS). The Total Least Squares (TLS) technique is a generalised least squares method to solve an overdetermined set of equations whose coefficients are noisy. The CTLS is a natural extension of TLS to the case where the noise components of the coefficients are correlated, as is usually the case with time-series measurements of concentrations and expression profiles in gene networks. <b>Results</b>: The superior performance of the CTLS method in identifying network interactions is demonstrated on three examples: a genetic network containing four genes, a network describing p53 activity and <i>mdm2</i> messenger RNA interactions, and a recently proposed kinetic model for interleukin (IL)-6 and (IL)-12b messenger RNA expression as a function of ATF3 and NF-κB promoter binding. For the first example, the CTLS significantly reduces the errors in the estimation of the Jacobian for the gene network. For the second, the CTLS reduces the errors from the measurements that are corrupted by white noise and the effect of neglected kinetics. For the third, it allows the correct identification, from noisy data, of the negative regulation of (IL)-6 and (IL)-12b by ATF3. <b>Conclusion</b>: The significant improvements in performance demonstrated by the CTLS method under the wide range of conditions tested here, including different levels and types of measurement noise and different numbers of data points, suggests that its application will enable more accurate and reliable identification and modelling of biochemical networks

RISE: a fast-readout imager for exoplanet transit timing

By the precise timing of the low amplitude (0.005 - 0.02 magnitude) transits of exoplanets around their parent star it should be possible to infer the presence of other planetary bodies in the system down to Earth-like masses. We describe the design and construction of RISE, a fast-readout frame transfer camera for the Liverpool Telescope designed to carry out this experiment. The results of our commissioning tests are described as well as the data reduction procedure necessary. We present light curves of two objects, showing that the desired timing and photometric accuracy can be obtained providing that autoguiding is used to keep the target on the same detector pixel for the entire (typically 4 hour) observing run.Comment: Published in PROC SPIE, vol 7014, 70416

A geometrical formulation of the μ-lower bound problem

A new problem formulation for the structured singular value μ in the case of purely real (possibly repeated) uncertainties is presented. The approach is based on a geometrical interpretation of the singularity constraint arising in the μ lower bound problem. An interesting feature of this problem formulation is that the resulting parametric search space is independent of the number of times any parameter is repeated in the structured uncertainty matrix. A corresponding lower bound algorithm combining randomisation and optimisation methods is developed, and some probabilistic performance guarantees are derived. The potential usefulness of the proposed approach is demonstrated on two high-order real μ analysis problems from the aerospace and systems biology literature

Point-light biological motion perception activates human premotor cortex

Motion cues can be surprisingly powerful in defining objects and events. Specifically, a handful of point-lights attached to the joints of a human actor will evoke a vivid percept of action when the body is in motion. The perception of point-light biological motion activates posterior cortical areas of the brain. On the other hand, observation of others' actions is known to also evoke activity in motor and premotor areas in frontal cortex. In the present study, we investigated whether point-light biological motion animations would lead to activity in frontal cortex as well. We performed a human functional magnetic resonance imaging study on a high-field-strength magnet and used a number of methods to increase signal, as well as cortical surface-based analysis methods. Areas that responded selectively to point-light biological motion were found in lateral and inferior temporal cortex and in inferior frontal cortex. The robust responses we observed in frontal areas indicate that these stimuli can also recruit action observation networks, although they are very simplified and characterize actions by motion cues alone. The finding that even point-light animations evoke activity in frontal regions suggests that the motor system of the observer may be recruited to "fill in" these simplified displays

An electron Talbot interferometer

The Talbot effect, in which a wave imprinted with transverse periodicity reconstructs itself at regular intervals, is a diffraction phenomenon that occurs in many physical systems. Here we present the first observation of the Talbot effect for electron de Broglie waves behind a nanofabricated transmission grating. This was thought to be difficult because of Coulomb interactions between electrons and nanostructure gratings, yet we were able to map out the entire near-field interference pattern, the "Talbot carpet", behind a grating. We did this using a Talbot interferometer, in which Talbot interference fringes from one grating are moire'-filtered by a 2nd grating. This arrangement has served for optical, X-ray, and atom interferometry, but never before for electrons. Talbot interferometers are particularly sensitive to distortions of the incident wavefronts, and to illustrate this we used our Talbot interferometer to measure the wavefront curvature of a weakly focused electron beam. Here we report how this wavefront curvature demagnified the Talbot revivals, and we discuss applications for electron Talbot interferometers.Comment: 5 pages, 5 figures, updated version with abstrac

Development of planar pixel modules for the ATLAS high luminosity LHC tracker upgrade

The high-luminosity LHC will present significant challenges for tracking systems. ATLAS is preparing to upgrade the entire tracking system, which will include a significantly larger pixel detector. This paper reports on the development of large area planar detectors for the outer pixel layers and the pixel endcaps. Large area sensors have been fabricated and mounted onto 4 FE-I4 readout ASICs, the so-called quad-modules, and their performance evaluated in the laboratory and testbeam. Results from characterisation of sensors prior to assembly, experience with module assembly, including bump-bonding and results from laboratory and testbeam studies are presented

Strong Shift Equivalence of C∗C^*-correspondences

We define a notion of strong shift equivalence for $C^*$-correspondences and show that strong shift equivalent $C^*$-correspondences have strongly Morita equivalent Cuntz-Pimsner algebras. Our analysis extends the fact that strong shift equivalent square matrices with non-negative integer entries give stably isomorphic Cuntz-Krieger algebras.Comment: 26 pages. Final version to appear in Israel Journal of Mathematic