On parameter estimation in population models

We describe methods for estimating the parameters of Markovian population processes in continuous time, thus increasing their utility in modelling real biological systems. A general approach, applicable to any finite-state continuous-time Markovian model, is presented, and this is specialised to a computationally more efficient method applicable to a class of models called density-dependent Markov population processes. We illustrate the versatility of both approaches by estimating the parameters of the stochastic SIS logistic model from simulated data. This model is also fitted to data from a population of Bay checkerspot butterfly (Euphydryas editha bayensis), allowing us to assess the viability of this population. (c) 2006 Elsevier Inc. All rights reserved.

Accounting for management costs in sensitivity analyses of matrix population models

Traditional sensitivity and elasticity analyses of matrix population models have been used to p inform management decisions, but they ignore the economic costs of manipulating vital rates. For exam le, the growth rate of a population is often most sensitive to changes in adult survival rate, but this does not mean that increasing that rate is the best option for managing the population because it may be much more expensive than other options. To explore how managers should optimize their manipulation of vital rates, we incorporated the cost of changing those rates into matrix population models. We derived analytic expressions for locations in parameter space where managers should shift between management of fecundity and survival, for the balance between fecundity and survival management at those boundaries, and for the allocation of management resources to sustain that optimal balance. For simple matrices, the optimal budget allocation can often be expressed as simple functions of vital rates and the relative costs of changing them. We applied our method to management of the Helmeted Honeyeater (Lichenostomus melanops cassidix; an endangered Australian bird) and the koala (Phascolarctos cinereus) as examples. Our method showed that cost-efficient management of the Helmeted Honeyeater should focus on increasing fecundity via nest protection, whereas optimal koala management should focus on manipulating both fecundity and survival simultaneously, These findings are contrary to the cost-negligent recommendations of elasticity analysis, which would suggest focusing on managing survival in both cases. A further investigation of Helmeted Honeyeater management options, based on an individual-based model incorporating density dependence, spatial structure, and environmental stochasticity, confirmed that fecundity management was the most cost-effective strategy. Our results demonstrate that decisions that ignore economic factors will reduce management efficiency.

Stochastic modelling of the invasion process of nematodes in fly larvae

Stochastic models based on Markov birth processes are constructed to describe the process of invasion of a fly larva by entomopathogenic nematodes. Various forms for the birth (invasion) rates are proposed. These models are then fitted to data sets describing the observed numbers of nematodes that have invaded a fly larval after a fixed period of time. Non-linear birthrates are required to achieve good fits to these data, with their precise form leading to different patterns of invasion being identified for three populations of nematodes considered. One of these (Nemasys) showed the greatest propensity for invasion. This form of modelling may be useful more generally for analysing data that show variation which is different from that expected from a binomial distribution.

Robustness of mathematical models for biological systems

The robustness of mathematical models for biological systems is studied by sensitivity analysis and stochastic simulations. Using a neural network model with three genes as the test problem, we study robustness properties of synthesis and degradation processes. For single parameter robustness, sensitivity analysis techniques are applied for studying parameter variations and stochastic simulations are used for investigating the impact of external noise. Results of sensitivity analysis are consistent with those obtained by stochastic simulations. Stochastic models with external noise can be used for studying the robustness not only to external noise but also to parameter variations. For external noise we also use stochastic models to study the robustness of the function of each gene and that of the system.

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

Accelerated leap methods for simulating discrete stochastic chemical kinetics

Biologists are increasingly conscious of the critical role that noise plays in cellular functions such as genetic regulation, often in connection with fluctuations in small numbers of key regulatory molecules. This has inspired the development of models that capture this fundamentally discrete and stochastic nature of cellular biology - most notably the Gillespie stochastic simulation algorithm (SSA). The SSA simulates a temporally homogeneous, discrete-state, continuous-time Markov process, and of course the corresponding probabilities and numbers of each molecular species must all remain positive. While accurately serving this purpose, the SSA can be computationally inefficient due to very small time stepping so faster approximations such as the Poisson and Binomial τ-leap methods have been suggested. This work places these leap methods in the context of numerical methods for the solution of stochastic differential equations (SDEs) driven by Poisson noise. This allows analogues of Euler-Maruyuma, Milstein and even higher order methods to be developed through the Itô-Taylor expansions as well as similar derivative-free Runge-Kutta approaches. Numerical results demonstrate that these novel methods compare favourably with existing techniques for simulating biochemical reactions by more accurately capturing crucial properties such as the mean and variance than existing methods.

A novel approach to modelling and exploiting uncertainty in stochastic control systems

We consider an inversion-based neurocontroller for solving control problems of uncertain nonlinear systems. Classical approaches do not use uncertainty information in the neural network models. In this paper we show how we can exploit knowledge of this uncertainty to our advantage by developing a novel robust inverse control method. Simulations on a nonlinear uncertain second order system illustrate the approach.

Robust control of nonlinear stochastic systems by modelling conditional distributions of control signals

We introduce a novel inversion-based neuro-controller for solving control problems involving uncertain nonlinear systems that could also compensate for multi-valued systems. The approach uses recent developments in neural networks, especially in the context of modelling statistical distributions, which are applied to forward and inverse plant models. Provided that certain conditions are met, an estimate of the intrinsic uncertainty for the outputs of neural networks can be obtained using the statistical properties of networks. More generally, multicomponent distributions can be modelled by the mixture density network. In this work a novel robust inverse control approach is obtained based on importance sampling from these distributions. This importance sampling provides a structured and principled approach to constrain the complexity of the search space for the ideal control law. The performance of the new algorithm is illustrated through simulations with example systems.

On models for magnetic field line diffusion

In this contribution, certain aspects of the nonlinear dynamics of magnetic field lines are reviewed. First, the basic facts (known from literature) concerning the Hamiltonian structure are briefly summarized. The paper then concentrates on the following subjects: (i) Transition from the continuous description to discrete maps; (ii) Characteristics of incomplete chaos; (iii) Control of chaos. The presentation is concluded by some remarks on the motion of particles in stochastic magnetic fields.

Cost models for engineering services

This thesis describes the procedure and results from four years research undertaken through the IHD (Interdisciplinary Higher Degrees) Scheme at Aston University in Birmingham, sponsored by the SERC (Science and Engineering Research Council) and Monk Dunstone Associates, Chartered Quantity Surveyors. A stochastic networking technique VERT (Venture Evaluation and Review Technique) was used to model the pre-tender costs of public health, heating ventilating, air-conditioning, fire protection, lifts and electrical installations within office developments. The model enabled the quantity surveyor to analyse, manipulate and explore complex scenarios which previously had defied ready mathematical analysis. The process involved the examination of historical material costs, labour factors and design performance data. Components and installation types were defined and formatted. Data was updated and adjusted using mechanical and electrical pre-tender cost indices and location, selection of contractor, contract sum, height and site condition factors. Ranges of cost, time and performance data were represented by probability density functions and defined by constant, uniform, normal and beta distributions. These variables and a network of the interrelationships between services components provided the framework for analysis. The VERT program, in this particular study, relied upon Monte Carlo simulation to model the uncertainties associated with pre-tender estimates of all possible installations. The computer generated output in the form of relative and cumulative frequency distributions of current element and total services costs, critical path analyses and details of statistical parameters. From this data alternative design solutions were compared, the degree of risk associated with estimates was determined, heuristics were tested and redeveloped, and cost significant items were isolated for closer examination. The resultant models successfully combined cost, time and performance factors and provided the quantity surveyor with an appreciation of the cost ranges associated with the various engineering services design options.