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.

Parallel implementation of stochastic simulation for large scale cellular processes

Experimental and theoretical studies have shown the importance of stochastic processes in genetic regulatory networks and cellular processes. Cellular networks and genetic circuits often involve small numbers of key proteins such as transcriptional factors and signaling proteins. In recent years stochastic models have been used successfully for studying noise in biological pathways, and stochastic modelling of biological systems has become a very important research field in computational biology. One of the challenge problems in this field is the reduction of the huge computing time in stochastic simulations. Based on the system of the mitogen-activated protein kinase cascade that is activated by epidermal growth factor, this work give a parallel implementation by using OpenMP and parallelism across the simulation. Special attention is paid to the independence of the generated random numbers in parallel computing, that is a key criterion for the success of stochastic simulations. Numerical results indicate that parallel computers can be used as an efficient tool for simulating the dynamics of large-scale genetic regulatory networks and cellular processes

Structure and dynamics of a gene network model incorporating small RNAs

As advances in molecular biology continue to reveal additional layers of complexity in gene regulation, computational models need to incorporate additional features to explore the implications of new theories and hypotheses. It has recently been suggested that eukaryotic organisms owe their phenotypic complexity and diversity to the exploitation of small RNAs as signalling molecules. Previous models of genetic systems are, for several reasons, inadequate to investigate this theory. In this study, we present an artificial genome model of genetic regulatory networks based upon previous work by Torsten Reil, and demonstrate how this model generates networks with biologically plausible structural and dynamic properties. We also extend the model to explore the implications of incorporating regulation by small RNA molecules in a gene network. We demonstrate how, using these signals, highly connected networks can display dynamics that are more stable than expected given their level of connectivity.

Dynamics of gene expression in an artificial genome

Complex systems techniques provide a powerful tool to study the emergent properties of networks of interacting genes. In this study we extract models of genetic regulatory networks from an artificial genome, represented by a sequence of nucleotides, and analyse how variations in the connectivity and degree of inhibition of the extracted networks affects the resulting classes of behaviours. For low connectivity systems were found to be very stable. Only with higher connectivity was a significant occurrence of chaos found. Most interestingly, the peak in occurrence of chaos occurs perched on the edge of a phase transition in the occurrence of attractors.

Controlling protein molecular dynamics:how to accelerate folding while preserving the native state

The dynamics of peptides and proteins generated by classical molecular dynamics (MD) is described by using a Markov model. The model is built by clustering the trajectory into conformational states and estimating transition probabilities between the states. Assuming that it is possible to influence the dynamics of the system by varying simulation parameters, we show how to use the Markov model to determine the parameter values that preserve the folded state of the protein and at the same time, reduce the folding time in the simulation. We investigate this by applying the method to two systems. The first system is an imaginary peptide described by given transition probabilities with a total folding time of 1 micros. We find that only small changes in the transition probabilities are needed to accelerate (or decelerate) the folding. This implies that folding times for slowly folding peptides and proteins calculated using MD cannot be meaningfully compared to experimental results. The second system is a four residue peptide valine-proline-alanine-leucine in water. We control the dynamics of the transitions by varying the temperature and the atom masses. The simulation results show that it is possible to find the combinations of parameter values that accelerate the dynamics and at the same time preserve the native state of the peptide. A method for accelerating larger systems without performing simulations for the whole folding process is outlined.

Computer simulation of liquid flow patterns on distillation trays

This thesis describes work carried out to improve the fundamental modelling of liquid flows on distillation trays. A mathematical model is presented based on the principles of computerised fluid dynamics. It models the liquid flow in the horizontal directions allowing for the effects of the vapour through the use of an increased liquid turbulence, modelled by an eddy viscosity, and a resistance to liquid flow caused by the vapour being accelerated horizontally by the liquid. The resultant equations are similar to the Navier-Stokes equations with the addition of a resistance term.A mass-transfer model is used to calculate liquid concentration profiles and tray efficiencies. A heat and mass transfer analogy is used to compare theoretical concentration profiles to experimental water-cooling data obtained from a 2.44 metre diameter air-water distillation simulation rig. The ratios of air to water flow rates are varied in order to simulate three pressures: vacuum, atmospheric pressure and moderate pressure.For simulated atmospheric and moderate pressure distillation, the fluid mechanical model constantly over-predicts tray efficiencies with an accuracy of between +1.7% and +11.3%. This compares to -1.8% to -10.9% for the stagnant regions model (Porter et al. 1972) and +12.8% to +34.7% for the plug flow plus back-mixing model (Gerster et al. 1958). The model fails to predict the flow patterns and tray efficiencies for vacuum simulation due to the change in the mechanism of liquid transport, from a liquid continuous layer to a spray as the liquid flow-rate is reduced. This spray is not taken into account in the development of the fluid mechanical model. A sensitivity analysis carried out has shown that the fluid mechanical model is relatively insensitive to the prediction of the average height of clear liquid, and a reduction in the resistance term results in a slight loss of tray efficiency. But these effects are not great. The model is quite sensitive to the prediction of the eddy viscosity term. Variations can produce up to a 15% decrease in tray efficiency. The fluid mechanical model has been incorporated into a column model so that statistical optimisation techniques can be employed to fit a theoretical column concentration profile to experimental data. Through the use of this work mass-transfer data can be obtained.

Investigating viscous fluid flow in an internal mixer using computational fluid dynamics

This thesis presents an effective methodology for the generation of a simulation which can be used to increase the understanding of viscous fluid processing equipment and aid in their development, design and optimisation. The Hampden RAPRA Torque Rheometer internal batch twin rotor mixer has been simulated with a view to establishing model accuracies, limitations, practicalities and uses. As this research progressed, via the analyses several 'snap-shot' analysis of several rotor configurations using the commercial code Polyflow, it was evident that the model was of some worth and its predictions are in good agreement with the validation experiments, however, several major restrictions were identified. These included poor element form, high man-hour requirements for the construction of each geometry and the absence of the transient term in these models. All, or at least some, of these limitations apply to the numerous attempts to model internal mixes by other researchers and it was clear that there was no generally accepted methodology to provide a practical three-dimensional model which has been adequately validated. This research, unlike others, presents a full complex three-dimensional, transient, non-isothermal, generalised non-Newtonian simulation with wall slip which overcomes these limitations using unmatched ridding and sliding mesh technology adapted from CFX codes. This method yields good element form and, since only one geometry has to be constructed to represent the entire rotor cycle, is extremely beneficial for detailed flow field analysis when used in conjunction with user defined programmes and automatic geometry parameterisation (AGP), and improves accuracy for investigating equipment design and operation conditions. Model validation has been identified as an area which has been neglected by other researchers in this field, especially for time dependent geometries, and has been rigorously pursued in terms of qualitative and quantitative velocity vector analysis of the isothermal, full fill mixing of generalised non-Newtonian fluids, as well as torque comparison, with a relatively high degree of success. This indicates that CFD models of this type can be accurate and perhaps have not been validated to this extent previously because of the inherent difficulties arising from most real processes.

The dynamics and control of a remotely piloted plan-symmetric helicopter

Prior to the development of a production standard control system for ML Aviation's plan-symmetric remotely piloted helicopter system, SPRITE, optimum solutions to technical requirements had yet to be found for some aspects of the work. This thesis describes an industrial project where solutions to real problems have been provided within strict timescale constraints. Use has been made of published material wherever appropriate, new solutions have been contributed where none existed previously. A lack of clearly defined user requirements from potential Remotely Piloted Air Vehicle (RPAV) system users is identified, A simulation package is defined to enable the RPAV designer to progress with air vehicle and control system design, development and evaluation studies and to assist the user to investigate his applications. The theoretical basis of this simulation package is developed including Co-axial Contra-rotating Twin Rotor (CCTR), six degrees of freedom motion, fuselage aerodynamics and sensor and control system models. A compatible system of equations is derived for modelling a miniature plan-symmetric helicopter. Rigorous searches revealed a lack of CCTR models, based on closed form expressions to obviate integration along the rotor blade, for stabilisation and navigation studies through simulation. An economic CCTR simulation model is developed and validated by comparison with published work and practical tests. Confusion in published work between attitude and Euler angles is clarified. The implementation of package is discussed. dynamic adjustment of assessment. the theory into a high integrity software Use is made of a novel technique basing the integration time step size on error Simulation output for control system stability verification, cross coupling of motion between control channels and air vehicle response to demands and horizontal wind gusts studies are presented. Contra-Rotating Twin Rotor Flight Control System Remotely Piloted Plan-Symmetric Helicopter Simulation Six Degrees of Freedom Motion ( i i)

Modelling manufacturing planning and control systems:the application of object-oriented principles and discrete-event simulation

Manufacturing planning and control systems are fundamental to the successful operations of a manufacturing organisation. 10 order to improve their business performance, significant investment is made by companies into planning and control systems; however, not all companies realise the benefits sought Many companies continue to suffer from high levels of inventory, shortages, obsolete parts, poor resource utilisation and poor delivery performance. This thesis argues that the fit between the planning and control system and the manufacturing organisation is a crucial element of success. The design of appropriate control systems is, therefore, important. The different approaches to the design of manufacturing planning and control systems are investigated. It is concluded that there is no provision within these design methodologies to properly assess the impact of a proposed design on the manufacturing facility. Consequently, an understanding of how a new (or modified) planning and control system will perform in the context of the complete manufacturing system is unlikely to be gained until after the system has been implemented and is running. There are many modelling techniques available, however discrete-event simulation is unique in its ability to model the complex dynamics inherent in manufacturing systems, of which the planning and control system is an integral component. The existing application of simulation to manufacturing control system issues is limited: although operational issues are addressed, application to the more fundamental design of control systems is rarely, if at all, considered. The lack of a suitable simulation-based modelling tool does not help matters. The requirements of a simulation tool capable of modelling a host of different planning and control systems is presented. It is argued that only through the application of object-oriented principles can these extensive requirements be achieved. This thesis reports on the development of an extensible class library called WBS/Control, which is based on object-oriented principles and discrete-event simulation. The functionality, both current and future, offered by WBS/Control means that different planning and control systems can be modelled: not only the more standard implementations but also hybrid systems and new designs. The flexibility implicit in the development of WBS/Control supports its application to design and operational issues. WBS/Control wholly integrates with an existing manufacturing simulator to provide a more complete modelling environment.