Stochastic computational modelling of complex drug delivery systems

As modern drug formulations become more advanced, pharmaceutical companies face the need for adequate tools to permit them to model complex requirements and to reduce unnecessary adsorption rates while increasing the dosage administered. The aim of the research presented here is the development and application of a general stochastic framework with agent-based elements for building drug dissolution models, with a particular focus on controlled release systems. The utilisation of three dimensional Cellular Automata and Monte Carlo methods, to describe structural compositions and the main physico-chemical mechanisms, is shown to have several key advantages: (i) the bottom up approach simplifies the definition of complex interactions between underlying phenomena such as diffusion,polymer degradation and hydration, and the dissolution media; (ii) permits straightforward extensibility for drug formulation variations in terms of supporting various geometries and exploring effects of polymer composition and layering; (iii) facilitates visualisation, affording insight on system structural evolution over time by capturing successive stages of dissolution. The framework has been used to build models simulating several distinct release scenarios from coated spheres covering single coated erosion and swelling dominated spheres as well as the influence of multiple heterogeneous coatings. High-performance computational optimisation enables precision simulations of the very thin coatings used and allows fast realisation of model state changes. Furthermore, theoretical analysis of the comparative impact of synchronous and asynchronous Cellular Automata and the suitability of their application to pharmaceutical systems is performed. Likely parameter distributions from noisy in vitro data are reconstructed using Inverse Monte Carlo methods and outcomes are reported

Why High-Performance Modelling and Simulation for Big Data Applications Matters

Modelling and Simulation (M&S) offer adequate abstractions to manage the complexity of analysing big data in scientific and engineering domains. Unfortunately, big data problems are often not easily amenable to efficient and effective use of High Performance Computing (HPC) facilities and technologies. Furthermore, M&S communities typically lack the detailed expertise required to exploit the full potential of HPC solutions while HPC specialists may not be fully aware of specific modelling and simulation requirements and applications. The COST Action IC1406 High-Performance Modelling and Simulation for Big Data Applications has created a strategic framework to foster interaction between M&S experts from various application domains on the one hand and HPC experts on the other hand to develop effective solutions for big data applications. One of the tangible outcomes of the COST Action is a collection of case studies from various computing domains. Each case study brought together both HPC and M&S experts, giving witness of the effective cross-pollination facilitated by the COST Action. In this introductory article we argue why joining forces between M&S and HPC communities is both timely in the big data era and crucial for success in many application domains. Moreover, we provide an overview on the state of the art in the various research areas concerned

Evolutionary approaches to robot path planning

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.The ultimate goal in robotics is to create machines which are more independent and rely less on humans to guide them in their operation. There are many sub-systems which may be present in such a robot, one of which is path planning — the ability to determine a sequence of positions or configurations between an initial and goal position within a particular obstacle cluttered workspace. Many classical path planning techniques have been developed, but these tend to have drawbacks such as their computational requirements; the suitability of the plans they produce for a particular application; or how well they are able to generalise to unseen problems. In recent years, evolutionary based problem solving techniques have seen a rise in popularity, possibly coinciding with the improvement in the computational power afforded researches by successful developments in hardware. These techniques adopt some of the features of natural evolution and mimic them in a computer. The increase in the number of publications in the areas of Genetic Algorithms (GA) and Genetic Programming (GP) demonstrate the success achieved when applying these techniques to ever more problem areas. This dissertation presents research conducted to determine whether there is a place for Evolutionary Approaches, and specifically GA and GP, in the development of future path planning techniques

Massivel y parallel declarative computational models

Current computer archictectures are parallel, with an increasing number of processors. Parallel programming is an error-prone task and declarative models such as those based on constraints relieve the programmer from some of its difficult aspects, because they abstract control away. In this work we study and develop techniques for declarative computational models based on constraints using GPI, aiming at large scale parallel execution. The main contributions of this work are: A GPI implementation of a scalable dynamic load balancing scheme based on work stealing, suitable for tree shaped computations and effective for systems with thousands of threads. A parallel constraint solver, MaCS, implemented to take advantage of the GPI programming model. Experimental evaluation shows very good scalability results on systems with hundreds of cores. A GPI parallel version of the Adaptive Search algorithm, including different variants. The study on different problems advances the understanding of scalability issues known to exist with large numbers of cores; ### SUMÁRIO: Actualmente as arquitecturas de computadores são paralelas, com um crescente número de processadores. A programação paralela é uma tarefa propensa a erros e modelos declarativos baseados em restrições aliviam o programador de aspectos difíceis dado que abstraem o controlo. Neste trabalho estudamos e desenvolvemos técnicas para modelos de computação declarativos baseados em restrições usando o GPI, uma ferramenta e modelo de programação recente. O Objectivo é a execução paralela em larga escala. As contribuições deste trabalho são as seguintes: a implementação de um esquema dinâmico para balanceamento da computação baseado no GPI. O esquema é adequado para computações em árvores e efectiva em sistemas compostos por milhares de unidades de computação. Uma abordagem à resolução paralela de restrições denominadas de MaCS, que tira partido do modelo de programação do GPI. A Avaliação experimental revelou boa escalabilidade num sistema com centenas de processadores. Uma versão paralela do algoritmo Adaptive Search baseada no GPI, que inclui diferentes variantes. O estudo de diversos problemas aumenta a compreensão de aspectos relacionados com a escalabilidade e presentes na execução deste tipo de algoritmos num grande número de processadores

Evolutionary approaches to optimisation in rough machining

This thesis concerns the use of Evolutionary Computation to optimise the sequence and selection of tools and machining parameters in rough milling applications. These processes are not automated in current Computer-Aided Manufacturing (CAM) software and this work, undertaken in collaboration with an industrial partner, aims to address this. Related research has mainly approached tool sequence optimisation using only a single tool type, and machining parameter optimisation of a single-tool sequence. In a real world industrial setting, tools with different geometrical profiles are commonly used in combination on rough machining tasks in order to produce components with complex sculptured surfaces. This work introduces a new representation scheme and search operators to support the use of the three most commonly used tool types: end mill, ball nose and toroidal. Using these operators, single-objective metaheuristic algorithms are shown to find near-optimal solutions, while surveying only a small number of tool sequences. For the first time, a multi-objective approach is taken to tool sequence optimisation. The process of ‘multi objectivisation’ is shown to offer two benefits: escaping local optima on deceptive multimodal search spaces and providing a selection of tool sequence alternatives to a machinist. The multi-objective approach is also used to produce a varied set of near-Pareto optimal solutions, offering different trade-offs between total machining time and total tooling costs, simultaneously optimising tool sequences and the cutting speeds of individual tools. A challenge for using computationally expensive CAM software, important for real world machining, is the time cost of evaluations. An asynchronous parallel evolutionary optimisation system is presented that can provide a significant speed up, even in the presence of heterogeneous evaluation times produced by variable length tool sequences. This system uses a distributed network of processors that could be easily and inexpensively implemented on existing commercial hardware, and accessible to even small workshops

Parallel Markov Chain Monte Carlo

The increasing availability of multi-core and multi-processor architectures provides new opportunities for improving the performance of many computer simulations. Markov Chain Monte Carlo (MCMC) simulations are widely used for approximate counting problems, Bayesian inference and as a means for estimating very highdimensional integrals. As such MCMC has found a wide variety of applications in fields including computational biology and physics,financial econometrics, machine learning and image processing. This thesis presents a number of new method for reducing the runtime of Markov Chain Monte Carlo simulations by using SMP machines and/or clusters. Two of the methods speculatively perform iterations in parallel, reducing the runtime of MCMC programs whilst producing statistically identical results to conventional sequential implementations. The other methods apply only to problem domains that can be presented as an image, and involve using various means of dividing the image into subimages that can be proceed with some degree of independence. Where possible the thesis includes a theoretical analysis of the reduction in runtime that may be achieved using our technique under perfect conditions, and in all cases the methods are tested and compared on selection of multi-core and multi-processor architectures. A framework is provided to allow easy construction of MCMC application that implement these parallelisation methods

Compilation Techniques for High-Performance Embedded Systems with Multiple Processors

Institute for Computing Systems ArchitectureDespite the progress made in developing more advanced compilers for embedded systems, programming of embedded high-performance computing systems based on Digital Signal Processors (DSPs) is still a highly skilled manual task. This is true for single-processor systems, and even more for embedded systems based on multiple DSPs. Compilers often fail to optimise existing DSP codes written in C due to the employed programming style. Parallelisation is hampered by the complex multiple address space memory architecture, which can be found in most commercial multi-DSP configurations. This thesis develops an integrated optimisation and parallelisation strategy that can deal with low-level C codes and produces optimised parallel code for a homogeneous multi-DSP architecture with distributed physical memory and multiple logical address spaces. In a first step, low-level programming idioms are identified and recovered. This enables the application of high-level code and data transformations well-known in the field of scientific computing. Iterative feedback-driven search for “good” transformation sequences is being investigated. A novel approach to parallelisation based on a unified data and loop transformation framework is presented and evaluated. Performance optimisation is achieved through exploitation of data locality on the one hand, and utilisation of DSP-specific architectural features such as Direct Memory Access (DMA) transfers on the other hand. The proposed methodology is evaluated against two benchmark suites (DSPstone & UTDSP) and four different high-performance DSPs, one of which is part of a commercial four processor multi-DSP board also used for evaluation. Experiments confirm the effectiveness of the program recovery techniques as enablers of high-level transformations and automatic parallelisation. Source-to-source transformations of DSP codes yield an average speedup of 2.21 across four different DSP architectures. The parallelisation scheme is – in conjunction with a set of locality optimisations – able to produce linear and even super-linear speedups on a number of relevant DSP kernels and applications