Information transfer in signaling pathways : a study using coupled simulated and experimental data

Background: The topology of signaling cascades has been studied in quite some detail. However, how information is processed exactly is still relatively unknown. Since quite diverse information has to be transported by one and the same signaling cascade (e.g. in case of different agonists), it is clear that the underlying mechanism is more complex than a simple binary switch which relies on the mere presence or absence of a particular species. Therefore, finding means to analyze the information transferred will help in deciphering how information is processed exactly in the cell. Using the information-theoretic measure transfer entropy, we studied the properties of information transfer in an example case, namely calcium signaling under different cellular conditions. Transfer entropy is an asymmetric and dynamic measure of the dependence of two (nonlinear) stochastic processes. We used calcium signaling since it is a well-studied example of complex cellular signaling. It has been suggested that specific information is encoded in the amplitude, frequency and waveform of the oscillatory Ca2+-signal. Results: We set up a computational framework to study information transfer, e.g. for calcium signaling at different levels of activation and different particle numbers in the system. We stochastically coupled simulated and experimentally measured calcium signals to simulated target proteins and used kernel density methods to estimate the transfer entropy from these bivariate time series. We found that, most of the time, the transfer entropy increases with increasing particle numbers. In systems with only few particles, faithful information transfer is hampered by random fluctuations. The transfer entropy also seems to be slightly correlated to the complexity (spiking, bursting or irregular oscillations) of the signal. Finally, we discuss a number of peculiarities of our approach in detail. Conclusion: This study presents the first application of transfer entropy to biochemical signaling pathways. We could quantify the information transferred from simulated/experimentally measured calcium signals to a target enzyme under different cellular conditions. Our approach, comprising stochastic coupling and using the information-theoretic measure transfer entropy, could also be a valuable tool for the analysis of other signaling pathways

Information transfer in signaling pathways : a study using coupled simulated and experimental data

Background: The topology of signaling cascades has been studied in quite some detail. However, how information is processed exactly is still relatively unknown. Since quite diverse information has to be transported by one and the same signaling cascade (e.g. in case of different agonists), it is clear that the underlying mechanism is more complex than a simple binary switch which relies on the mere presence or absence of a particular species. Therefore, finding means to analyze the information transferred will help in deciphering how information is processed exactly in the cell. Using the information-theoretic measure transfer entropy, we studied the properties of information transfer in an example case, namely calcium signaling under different cellular conditions. Transfer entropy is an asymmetric and dynamic measure of the dependence of two (nonlinear) stochastic processes. We used calcium signaling since it is a well-studied example of complex cellular signaling. It has been suggested that specific information is encoded in the amplitude, frequency and waveform of the oscillatory Ca2+-signal. Results: We set up a computational framework to study information transfer, e.g. for calcium signaling at different levels of activation and different particle numbers in the system. We stochastically coupled simulated and experimentally measured calcium signals to simulated target proteins and used kernel density methods to estimate the transfer entropy from these bivariate time series. We found that, most of the time, the transfer entropy increases with increasing particle numbers. In systems with only few particles, faithful information transfer is hampered by random fluctuations. The transfer entropy also seems to be slightly correlated to the complexity (spiking, bursting or irregular oscillations) of the signal. Finally, we discuss a number of peculiarities of our approach in detail. Conclusion: This study presents the first application of transfer entropy to biochemical signaling pathways. We could quantify the information transferred from simulated/experimentally measured calcium signals to a target enzyme under different cellular conditions. Our approach, comprising stochastic coupling and using the information-theoretic measure transfer entropy, could also be a valuable tool for the analysis of other signaling pathways

High-order noise filtering in nontrivial quantum logic gates

Treating the effects of a time-dependent classical dephasing environment during quantum logic operations poses a theoretical challenge, as the application of non-commuting control operations gives rise to both dephasing and depolarization errors that must be accounted for in order to understand total average error rates. We develop a treatment based on effective Hamiltonian theory that allows us to efficiently model the effect of classical noise on nontrivial single-bit quantum logic operations composed of arbitrary control sequences. We present a general method to calculate the ensemble-averaged entanglement fidelity to arbitrary order in terms of noise filter functions, and provide explicit expressions to fourth order in the noise strength. In the weak noise limit we derive explicit filter functions for a broad class of piecewise-constant control sequences, and use them to study the performance of dynamically corrected gates, yielding good agreement with brute-force numerics.Comment: Revised and expanded to include filter function terms beyond first order in the Magnus expansion. Related manuscripts available from http://www.physics.usyd.edu.au/~mbiercu

Palatini Variational Principle for NN-Dimensional Dilaton Gravity

We consider a Palatini variation on a general $N$-Dimensional second order, torsion-free dilaton gravity action and determine the resulting equations of motion. Consistency is checked by considering the restraint imposed due to invariance of the matter action under simple coordinate transformations, and the special case of N=2 is examined. We also examine a sub-class of theories whereby a Palatini variation dynamically coincides with that of the "ordinary" Hilbert variational principle; in particular we examine a generalized Brans-Dicke theory and the associated role of conformal transformations.Comment: 16 pages, LaTe

The orbits of subdwarf-B + main-sequence binaries. II. Three eccentric systems; BD+29 3070, BD +34 1543 and Feige 87

The predicted orbital-period distribution of the subdwarf-B (sdB) population is bi-modal with a peak at short ( 250 days) periods. Observationally, many short-period sdB systems are known, but the predicted long period peak is missing as orbits have only been determined for a few long-period systems. As these predictions are based on poorly understood binary-interaction processes, it is of prime importance to confront the predictions with reliable observational data. We therefore initiated a monitoring program to find and characterize long-period sdB stars. In this paper we aim to determine the orbital parameters of the three long-period sdB+MS binaries BD+29 3070, BD+34 1543 and Feige 87, to constrain their absolute dimensions and the physical parameters of the components. High-resolution spectroscopic time series were obtained with HERMES at the Mercator telescope on La Palma, and analyzed to determine the radial velocities of both the sdB and MS components. Photometry from the literature was used to construct the spectral-energy distribution (SED) of the binaries. Atmosphere models were used to fit these SEDs and to determine the surface gravities and temperatures of both components of all systems. Spectral analysis was used to check the results of the SEDs. An orbital period of 1283 +- 63 d, a mass ratio of q = 0.39 +- 0.04 and a significant non-zero eccentricity of e = 0.15 +- 0.01 were found for BD+29 3070. For BD+34 1543 we determined P = 972 +- 2 d, q = 0.57 +- 0.01 and again a clear non-zero eccentricity of e = 0.16 +- 0.01. Last, for Feige 87 we found P = 936 +- 2 d, q = 0.55 +- 0.01 and e = 0.11 +- 0.01. BD+29 3070, BD+34 1543 and Feige 87 are long period sdB + MS binaries on clearly eccentric orbits. These results are in conflict with the predictions of stable Roche-lobe overflow models.Comment: 15 pages, 6 figures, Accepted by A&

Transition from stochastic to deterministic behavior in calcium oscillations

Simulation and modeling is becoming more and more important when studying complex biochemical systems. Most often, ordinary differential equations are employed for this purpose. However, these are only applicable when the numbers of participating molecules in the biochemical systems are large enough to be treated as concentrations. For smaller systems, stochastic simulations on discrete particle basis are more accurate. Unfortunately, there are no general rules for determining which method should be employed for exactly which problem to get the most realistic result. Therefore, we study the transition from stochastic to deterministic behavior in a widely studied system, namely the signal transduction via calcium, especially calcium oscillations. We observe that the transition occurs within a range of particle numbers, which roughly corresponds to the number of receptors and channels in the cell, and depends heavily on the attractive properties of the phase space of the respective systems dynamics. We conclude that the attractive properties of a system, expressed, e.g., by the divergence of the system, are a good measure for determining which simulation algorithm is appropriate in terms of speed and realism

Multidimensional perfect fluid cosmology with stable compactified internal dimensions

Multidimensional cosmological models in the presence of a bare cosmological constant and a perfect fluid are investigated under dimensional reduction to 4-dimensional effective models. Stable compactification of the internal spaces is achieved for a special class of perfect fluids. The external space behaves in accordance with the standard Friedmann model. Necessary restrictions on the parameters of the models are found to ensure dynamical behavior of the external (our) universe in agreement with observations.Comment: 11 pages, Latex2e, uses IOP packages, submitted to Class.Quant.Gra