Stochastic chemical kinetics and the quasi-steady-state assumption : application to the stochastic simulation algorithm and chemical master equation

Recently the application of the quasi-steady-state approximation (QSSA) to the stochastic simulation algorithm (SSA) was suggested for the purpose of speeding up stochastic simulations of chemical systems that involve both relatively fast and slow chemical reactions [Rao and Arkin, J. Chem. Phys. 118, 4999 (2003)] and further work has led to the nested and slow-scale SSA. Improved numerical efficiency is obtained by respecting the vastly different time scales characterizing the system and then by advancing only the slow reactions exactly, based on a suitable approximation to the fast reactions. We considerably extend these works by applying the QSSA to numerical methods for the direct solution of the chemical master equation (CME) and, in particular, to the finite state projection algorithm [Munsky and Khammash, J. Chem. Phys. 124, 044104 (2006)], in conjunction with Krylov methods. In addition, we point out some important connections to the literature on the (deterministic) total QSSA (tQSSA) and place the stochastic analogue of the QSSA within the more general framework of aggregation of Markov processes. We demonstrate the new methods on four examples: Michaelis–Menten enzyme kinetics, double phosphorylation, the Goldbeter–Koshland switch, and the mitogen activated protein kinase cascade. Overall, we report dramatic improvements by applying the tQSSA to the CME solver.

A Krylov-based finite state projection algorithm for solving the chemical master equation arising in the discrete modelling of biological systems

Biochemical reactions underlying genetic regulation are often modelled as a continuous-time, discrete-state, Markov process, and the evolution of the associated probability density is described by the so-called chemical master equation (CME). However the CME is typically difficult to solve, since the state-space involved can be very large or even countably infinite. Recently a finite state projection method (FSP) that truncates the state-space was suggested and shown to be effective in an example of a model of the Pap-pili epigenetic switch. However in this example, both the model and the final time at which the solution was computed, were relatively small. Presented here is a Krylov FSP algorithm based on a combination of state-space truncation and inexact matrix-vector product routines. This allows larger-scale models to be studied and solutions for larger final times to be computed in a realistic execution time. Additionally the new method computes the solution at intermediate times at virtually no extra cost, since it is derived from Krylov-type methods for computing matrix exponentials. For the purpose of comparison the new algorithm is applied to the model of the Pap-pili epigenetic switch, where the original FSP was first demonstrated. Also the method is applied to a more sophisticated model of regulated transcription. Numerical results indicate that the new approach is significantly faster and extendable to larger biological models.

Peer state assessment of TxDOT maintenance program and practices : workshop and road rally findings

In an effort to evaluate and improve their practices to ensure the future excellence of the Texas highway system, the Texas Department of Transportation (TxDOT) sought a forum in which experts from other state departments of transportation could share their expertise. Thus, the Peer State Review of TxDOT Maintenance Practices project was organized and conducted for TxDOT by the Center for Transportation Research (CTR) at The University of Texas at Austin. The goal of the project was to conduct a workshop at CTR and in the Austin District that would educate the visiting peers on TxDOT’s maintenance practices and invite their feedback. CTR and TxDOT arranged the participation of the following directors of maintenance: Steve Takigawa, CA; Roy Rissky, KS; Eric Pitts, GA; Jim Carney, MO; Jennifer Brandenburg, NC; and David Bierschbach, WA. One of the means used to capture the peer reviewers’ opinions was a carefully designed booklet of 15 questions. The peers provided TxDOT with written responses to these questions, and the oral comments made during the workshop were also captured. This information was then compiled and summarized in the following report. An examination of the peers’ comments suggests that TxDOT should use a more holistic, statewide approach to funding and planning rather than funding and planning for each district separately. Additionally, the peers stressed the importance of allocating funds based on the actual conditions of the roadways instead of on inventory. The visiting directors of maintenance also recommended continuing and proliferating programs that enhance communication, such as peer review workshops.

Preventing injuries on a state-wide basis : researchers and parliamentary committees are partners in turning injury prevention and safety research into practice and policy

Context: Parliamentary committees established in Westminster parliaments, such as Queensland, provide a cross-party structure that enables them to recommend policy and legislative changes that may otherwise be difficult for one party to recommend. The overall parliamentary committee process tends to be more cooperative and less adversarial than the main chamber of parliament and, as a result, this process permits parliamentary committees to make recommendations more on the available research evidence and less on political or party considerations. Objectives: This paper considers the contributions that parliamentary committees in Queensland have made in the past in the areas of road safety, drug use as well as organ and tissue donation. The paper also discusses the importance of researchers actively engaging with parliamentary committees to ensure the best evidence based policy outcomes. Key messages: In the past, parliamentary committees have successfully facilitated important safety changes with many committee recommendations based on research results. In order to maximise the benefits of the parliamentary committee process it is essential that researchers inform committees about their work and become key stakeholders in the inquiry process. Researchers can keep committees informed by making submissions to their inquiries, responding to requests for information and appearing as witnesses at public hearings. Researchers should emphasise the key findings and implications of their research as well as considering the jurisdictional implications and political consequences. It is important that researchers understand the differences between lobbying and providing informed recommendations when interacting with committees. Discussion and conclusions: Parliamentary committees in Queensland have successfully assisted in the introduction of evidence based policy and legislation. In order to present best practice recommendations, committees rely on the evidence presented to them including the results of researchers. Actively engaging with parliamentary committees will help researchers to turn their results into practice with a corresponding decrease in injuries and fatalities. Developing an understanding of parliamentary committees, and the typical inquiry process used by these committees, will help researchers to present their research results in a manner that will encourage the adoption of their ideas by parliamentary committees, the presentation of these results as recommendations within the report and the subsequent enactment of the committee’s recommendations by the government.

State of the art and future challenges for information literacy research

This short paper focuses on strategic issues and important research questions.

Volatile properties of particles emitted by compressed natural gas and diesel buses during steady state and transient driving modes

Volatile properties of particle emissions from four compressed natural gas (CNG) and four diesel buses were investigated under steady state and transient driving modes on a chassis dynamometer. The exhaust was diluted utilising a full-flow continuous volume sampling system and passed through a thermodenuder at controlled temperature. Particle number concentration and size distribution were measured with a condensation particle counter and a scanning mobility particle sizer, respectively. We show that, while almost all the particles emitted by the CNG buses were in the nanoparticle size range, at least 85% and 98% were removed at 100ºC and 250ºC, respectively. Closer analysis of the volatility of particles emitted during transient cycles showed that volatilisation began at around 40°C with the majority occurring by 80°C. Particles produced during hard acceleration from rest exhibited lower volatility than that produced during other times of the cycle. Based on our results and the observation of ash deposits on the walls of the tailpipes, we suggest that these non-volatile particles were composed mostly of ash from lubricating oil. Heating the diesel bus emissions to 100ºC removed ultrafine particle numbers by 69% to 82% when a nucleation mode was present and just 18% when it was not.

State convergence and the effectiveness of time-memory-data tradeoffs

Various time-memory tradeoffs attacks for stream ciphers have been proposed over the years. However, the claimed success of these attacks assumes the initialisation process of the stream cipher is one-to-one. Some stream cipher proposals do not have a one-to-one initialisation process. In this paper, we examine the impact of this on the success of time-memory-data tradeoff attacks. Under the circumstances, some attacks are more successful than previously claimed while others are less. The conditions for both cases are established.