Oscillatory regulation of Hes1: Discrete stochastic delay modelling and simulation

Discrete stochastic simulations are a powerful tool for understanding the dynamics of chemical kinetics when there are small-to-moderate numbers of certain molecular species. In this paper we introduce delays into the stochastic simulation algorithm, thus mimicking delays associated with transcription and translation. We then show that this process may well explain more faithfully than continuous deterministic models the observed sustained oscillations in expression levels of hes1 mRNA and Hes1 protein.

Computational approaches for modelling intrinsic noise and delays in genetic regulatory networks

This chapter focuses on the interactions and roles between delays and intrinsic noise effects within cellular pathways and regulatory networks. We address these aspects by focusing on genetic regulatory networks that share a common network motif, namely the negative feedback loop, leading to oscillatory gene expression and protein levels. In this context, we discuss computational simulation algorithms for addressing the interplay of delays and noise within the signaling pathways based on biological data. We address implementational issues associated with efficiency and robustness. In a molecular biology setting we present two case studies of temporal models for the Hes1 gene (Monk, 2003; Hirata et al., 2002), known to act as a molecular clock, and the Her1/Her7 regulatory system controlling the periodic somite segmentation in vertebrate embryos (Giudicelli and Lewis, 2004; Horikawa et al., 2006).

Stochastic simulation for spatial modelling of dynamic process in a living cell

One of the fundamental motivations underlying computational cell biology is to gain insight into the complicated dynamical processes taking place, for example, on the plasma membrane or in the cytosol of a cell. These processes are often so complicated that purely temporal mathematical models cannot adequately capture the complex chemical kinetics and transport processes of, for example, proteins or vesicles. On the other hand, spatial models such as Monte Carlo approaches can have very large computational overheads. This chapter gives an overview of the state of the art in the development of stochastic simulation techniques for the spatial modelling of dynamic processes in a living cell.

Microwave curing of non-traditional polymer materials used in manufacture of injection moulds

Microwave heating technology is a cost-effective alternative way for heating and curing of used in polymer processing of various alternate materials. The work presented in this paper addresses the attempts made by the authors to study the glass transition temperature and curing of materials such as casting resins R2512, R2515 and laminating resin GPR 2516 in combination with two hardeners ADH 2403 and ADH 2409. The magnetron microwave generator used in this research is operating at a frequency of 2.45 GHz with a hollow rectangular waveguide. During this investigation it has been noted that microwave heated mould materials resulted with higher glass transition temperatures and better microstructure. It also noted that Microwave curing resulted in a shorter curing time to reach the maximum percentage cure. From this study it can be concluded that microwave technology can be efficiently and effectively used to cure new generation alternate polymer materials for manufacture of injection moulds in a rapid and efficient manner. Microwave curing resulted in a shorter curing time to reach the maximum percentage cure.

Modeling intrinsic noise and delays in chemical kinetics of coupled autoregulated oscillating cells

Delays are an important feature in temporal models of genetic regulation due to slow biochemical processes, such as transcription and translation. In this paper, we show how to model intrinsic noise effects in a delayed setting by either using a delay stochastic simulation algorithm (DSSA) or, for larger and more complex systems, a generalized Binomial τ-leap method (Bτ-DSSA). As a particular application, we apply these ideas to modeling somite segmentation in zebra fish across a number of cells in which two linked oscillatory genes (her1 and her7) are synchronized via Notch signaling between the cells.

Evolving noisy oscillatory dynamics in genetic regulatory networks

We introduce a genetic programming (GP) approach for evolving genetic networks that demonstrate desired dynamics when simulated as a discrete stochastic process. Our representation of genetic networks is based on a biochemical reaction model including key elements such as transcription, translation and post-translational modifications. The stochastic, reaction-based GP system is similar but not identical with algorithmic chemistries. We evolved genetic networks with noisy oscillatory dynamics. The results show the practicality of evolving particular dynamics in gene regulatory networks when modelled with intrinsic noise.

Evolving genetic regulatory networks performing as stochastic switches

Recent studies have shown that small genetic regulatory networks (GRNs) can be evolved in silico displaying certain dynamics in the underlying mathematical model. It is expected that evolutionary approaches can help to gain a better understanding of biological design principles and assist in the engineering of genetic networks. To take the stochastic nature of GRNs into account, our evolutionary approach models GRNs as biochemical reaction networks based on simple enzyme kinetics and simulates them by using Gillespie’s stochastic simulation algorithm (SSA). We have already demonstrated the relevance of considering intrinsic stochasticity by evolving GRNs that show oscillatory dynamics in the SSA but not in the ODE regime. Here, we present and discuss first results in the evolution of GRNs performing as stochastic switches.

Arterial travel time estimation : revisiting the classical procedure

Travel time is an important network performance measure and it quantifies congestion in a manner easily understood by all transport users. In urban networks, travel time estimation is challenging due to number of reasons such as, fluctuations in traffic flow due to traffic signals, significant flow to/from mid link sinks/sources, etc. The classical analytical procedure utilizes cumulative plots at upstream and downstream locations for estimating travel time between the two locations. In this paper, we discuss about the issues and challenges with classical analytical procedure such as its vulnerability to non conservation of flow between the two locations. The complexity with respect to exit movement specific travel time is discussed. Recently, we have developed a methodology utilising classical procedure to estimate average travel time and its statistic on urban links (Bhaskar, Chung et al. 2010). Where, detector, signal and probe vehicle data is fused. In this paper we extend the methodology for route travel time estimation and test its performance using simulation. The originality is defining cumulative plots for each exit turning movement utilising historical database which is self updated after each estimation. The performance is also compared with a method solely based on probe (Probe-only). The performance of the proposed methodology has been found insensitive to different route flow, with average accuracy of more than 94% given a probe per estimation interval which is more than 5% increment in accuracy with respect to Probe-only method.

Analysis for the use of cumulative plots for travel time estimation on signalized network

This paper provides fundamental understanding for the use of cumulative plots for travel time estimation on signalized urban networks. Analytical modeling is performed to generate cumulative plots based on the availability of data: a) Case-D, for detector data only; b) Case-DS, for detector data and signal timings; and c) Case-DSS, for detector data, signal timings and saturation flow rate. The empirical study and sensitivity analysis based on simulation experiments have observed the consistency in performance for Case-DS and Case-DSS, whereas, for Case-D the performance is inconsistent. Case-D is sensitive to detection interval and signal timings within the interval. When detection interval is integral multiple of signal cycle then it has low accuracy and low reliability. Whereas, for detection interval around 1.5 times signal cycle both accuracy and reliability are high.

Considering weather in simulation traffic

The impact of weather on traffic and its behavior is not well studied in literature primarily due to lack of integrated traffic and weather data. Weather can significant effect the traffic and traffic management measures developed for fine weather might not be optimal for adverse weather. Simulation is an efficient tool for analyzing traffic management measures even before their actual implementation. Therefore, in order to develop and test traffic management measures for adverse weather condition we need to first analyze the effect of weather on fundamental traffic parameters and thereafter, calibrate the simulation model parameters in order to simulate the traffic under adverse weather conditions. In this paper we first, analyses the impact of weather on motorway traffic flow and drivers’ behaviour with traffic data from Swiss motorways and weather data from MeteoSuisse. Thereafter, we develop methodology to calibrate a microscopic simulation model with the aim to utilize the simulation model for simulating traffic under adverse weather conditions. Here, study is performed using AIMSUN, a microscopic traffic simulator.

Evolution of traffic management measures on road traffic noise

Road traffic noise affects the quality of life in the areas adjoining the road. The effect of traffic noise on people is wide ranging and may include sleep disturbance and negative impact on work efficiency. To address the problem of traffic noise, it is necessary to estimate the noise level. For this, a number of noise estimation models have been developed which can estimate noise at the receptor points, based on simple configuration of buildings. However, for a real world situation we have multiple buildings forming built-up area. In such a situation, it is almost impossible to consider multiple diffractions and reflections in sound propagation from the source to the receptor point. An engineering solution to such a real world problem is needed to estimate noise levels in built-up area.

Benefits and issues of urban network travel time prediction

This paper presents the benefits and issues related to travel time prediction on urban network. Travel time information quantifies congestion and is perhaps the most important network performance measure. Travel time prediction has been an active area of research for the last five decades. The activities related to ITS have increased the attention of researchers for better and accurate real-time prediction of travel time. Majority of the literature on travel time prediction is applicable to freeways where, under non-incident conditions, traffic flow is not affected by external factors such as traffic control signals and opposing traffic flows. On urban environment the problem is more complicated due to conflicting areas (intersections), mid-link sources and sinks etc. and needs to be addressed.

Additive manufacturing of tissues and organs

Additive manufacturing techniques offer the potential to fabricate organized tissue constructs to repair or replace damaged or diseased human tissues and organs. Using these techniques, spatial variations of cells along multiple axes with high geometric complexity in combination with different biomaterials can be generated. The level of control offered by these computer-controlled technologies to design and fabricate tissues will accelerate our understanding of the governing factors of tissue formation and function. Moreover, it will provide a valuable tool to study the effect of anatomy on graft performance. In this review, we discuss the rationale for engineering tissues and organs by combining computer-aided design with additive manufacturing technologies that encompass the simultaneous deposition of cells and materials. Current strategies are presented, particularly with respect to limitations due to the lack of suitable polymers, and requirements to move the current concepts to practical application.