Systems biology approach to study permeability of paracetamol and its solid dispersion

Physiological changes that take place at cellular level are usually reflective of their level of gene expression. Different formulation excipients have an impact on physiological behavior of the exposed cells and in turn affect transporter genes, enterocyte-mediated metabolism and toxicity biomarkers. The aim of this study was to prepare solid dispersion of paracetamol and evaluate genetic changes that occur in Caco-2 cell lines during the permeability of paracetamol alone and paracetamol solid dispersion formulations. Paracetamol-PEG 8000 solid dispersion was prepared by melt fusion method and the formulation was characterised using differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). Formulation of solid dispersion resulted in the conversion of crystalline drug into an amorphous form. Permeability studies showed that paracetamol absorption was higher from the solid dispersion formulation. DNA microarrays analysis was carried out in order to investigate the involvement of any efflux/uptake transporters in paracetamol or its solid dispersion permeability. Neither transporter carriers nor efflux proteins were found to be involved in the absorption of paracetamol or its PEG solid dispersion. Gene expression analysis established that paracetamol toxicity was potentially reduced upon formulation into solid dispersion when ATP binding cassette (ABC) and solute carrier transporter (SLC) genes were analyzed.

The development of hard real-time systems using a formal approach

Hard real-time systems are a class of computer control systems that must react to demands of their environment by providing `correct' and timely responses. Since these systems are increasingly being used in systems with safety implications, it is crucial that they are designed and developed to operate in a correct manner. This thesis is concerned with developing formal techniques that allow the specification, verification and design of hard real-time systems. Formal techniques for hard real-time systems must be capable of capturing the system's functional and performance requirements, and previous work has proposed a number of techniques which range from the mathematically intensive to those with some mathematical content. This thesis develops formal techniques that contain both an informal and a formal component because it is considered that the informality provides ease of understanding and the formality allows precise specification and verification. Specifically, the combination of Petri nets and temporal logic is considered for the specification and verification of hard real-time systems. Approaches that combine Petri nets and temporal logic by allowing a consistent translation between each formalism are examined. Previously, such techniques have been applied to the formal analysis of concurrent systems. This thesis adapts these techniques for use in the modelling, design and formal analysis of hard real-time systems. The techniques are applied to the problem of specifying a controller for a high-speed manufacturing system. It is shown that they can be used to prove liveness and safety properties, including qualitative aspects of system performance. The problem of verifying quantitative real-time properties is addressed by developing a further technique which combines the formalisms of timed Petri nets and real-time temporal logic. A unifying feature of these techniques is the common temporal description of the Petri net. A common problem with Petri net based techniques is the complexity problems associated with generating the reachability graph. This thesis addresses this problem by using concurrency sets to generate a partial reachability graph pertaining to a particular state. These sets also allows each state to be checked for the presence of inconsistencies and hazards. The problem of designing a controller for the high-speed manufacturing system is also considered. The approach adopted mvolves the use of a model-based controller: This type of controller uses the Petri net models developed, thus preservIng the properties already proven of the controller. It. also contains a model of the physical system which is synchronised to the real application to provide timely responses. The various way of forming the synchronization between these processes is considered and the resulting nets are analysed using concurrency sets.

Estimating parameters in stochastic systems:a variational Bayesian approach

This work is concerned with approximate inference in dynamical systems, from a variational Bayesian perspective. When modelling real world dynamical systems, stochastic differential equations appear as a natural choice, mainly because of their ability to model the noise of the system by adding a variation of some stochastic process to the deterministic dynamics. Hence, inference in such processes has drawn much attention. Here a new extended framework is derived that is based on a local polynomial approximation of a recently proposed variational Bayesian algorithm. The paper begins by showing that the new extension of this variational algorithm can be used for state estimation (smoothing) and converges to the original algorithm. However, the main focus is on estimating the (hyper-) parameters of these systems (i.e. drift parameters and diffusion coefficients). The new approach is validated on a range of different systems which vary in dimensionality and non-linearity. These are the Ornstein–Uhlenbeck process, the exact likelihood of which can be computed analytically, the univariate and highly non-linear, stochastic double well and the multivariate chaotic stochastic Lorenz ’63 (3D model). As a special case the algorithm is also applied to the 40 dimensional stochastic Lorenz ’96 system. In our investigation we compare this new approach with a variety of other well known methods, such as the hybrid Monte Carlo, dual unscented Kalman filter, full weak-constraint 4D-Var algorithm and analyse empirically their asymptotic behaviour as a function of observation density or length of time window increases. In particular we show that we are able to estimate parameters in both the drift (deterministic) and the diffusion (stochastic) part of the model evolution equations using our new methods.

An iterative-style approach to constructing intelligent tutoring systems in mathematics

Mathematics is highly structured and also underpins most of science and engineering. For this reason, it has proved a very suitable domain for Intelligent Tutoring System (ITS) research, with the result that probably more tutoring systems have been constructed for the domain than any other. However, the literature reveals that there still exists no consensus on a credible approach or approaches for the design of such systems, despite numerous documented efforts. Current approaches to the construction of ITSs leave much to be desired. Consequently, existing ITSs in the domain suffer from a considerable number of shortcomings which render them 'unintelligent'. The thesis examines some of the reasons why this is the case. Following a critical review of existing ITSs in the domain, and some pilot studies, an alternative approach to their construction is proposed (the 'iterative-style' approach); this supports an iterative style, and also improves on at least some of the shortcomings of existing approaches. The thesis also presents an ITS for fractions which has been developed using this approach, and which has been evaluated in various ways. It has, demonstrably, improved on many of the limitations of existing ITSs; furthermore, it has been shown to be largely 'intelligent', at least more so than current tutors for the domain. Perhaps more significantly, the tutor has also been evaluated against real students with, so far, very encouraging results. The thesis thus concludes that the novel iterative-style approach is a more credible approach to the construction of ITSs in mathematics than existing techniques.

Strategic information systems at the Colombian President's Office (1990-1992) : a managerial cybernetic approach

This research studies the issue of using strategic information technology for improving organisational effectiveness. It analyses different academic approaches explaining the nature of information systems and the need organisations feel of developing strategic information systems planning processes, to improve organisational effectiveness. It chooses Managerial Cybernetics as the theoretical foundation supporting development of a "Strategic Information Systems Planning" Framework, and uses it for supporting the analysis of a documented story about the process lived by the Colombian President's Office, in 1990-1992. It argues that by analysing the situation through this new analysis framework we may enlighten some previously unclear situations lived, and not yet properly explained through other approaches to strategic information systems planning. The documented history explains the organisational context and strategic postures of the Colombian President's Office and the Colombian Public Sector, at that time, as well as some of the strategic information systems defined and developed. In particular it analyses a system developed jointly by the President's Office and the National Planning Department, for measuring results of the main national development programmes. Then, it reviews these situations, in the light of the new framework and presents the main findings of the exercise. Finally, it analyses the whole research exercise, the perceived usefulness of the chosen frameworks and tools to enlighten the real situations analysed that were not clear enough, and some open research paths to follow for future researchers interested in the issue.

An approach to the development of expert systems within production planning and control

The thesis presents an account of an attempt to utilize expert systems within the domain of production planning and control. The use of expert systems was proposed due to the problematical nature of a particular function within British Steel Strip Products' Operations Department: the function of Order Allocation, allocating customer orders to a production week and site. Approaches to tackling problems within production planning and control are reviewed, as are the general capabilities of expert systems. The conclusions drawn are that the domain of production planning and control contains both `soft' and `hard' problems, and that while expert systems appear to be a useful technology for this domain, this usefulness has by no means yet been demonstrated. Also, it is argued that the main stream methodology for developing expert systems is unsuited for the domain. A problem-driven approach is developed and used to tackle the Order Allocation function. The resulting system, UAAMS, contained two expert components. One of these, the scheduling procedure was not fully implemented due to inadequate software. The second expert component, the product routing procedure, was untroubled by such difficulties, though it was unusable on its own; thus a second system was developed. This system, MICRO-X10, duplicated the function of X10, a complex database query routine used daily by Order Allocation. A prototype version of MICRO-X10 proved too slow to be useful but allowed implementation and maintenance issues to be analysed. In conclusion, the usefulness of the problem-driven approach to expert systems development within production planning and control is demonstrated but restrictions imposed by current expert system software are highlighted in that the abilities of such software to cope with `hard' scheduling constructs and also the slow processing speeds of such software can restrict the current usefulness of expert systems within production planning and control.

Resource allocation in decentralised computational systems:an evolutionary market-based approach

We present a novel market-based method, inspired by retail markets, for resource allocation in fully decentralised systems where agents are self-interested. Our market mechanism requires no coordinating node or complex negotiation. The stability of outcome allocations, those at equilibrium, is analysed and compared for three buyer behaviour models. In order to capture the interaction between self-interested agents, we propose the use of competitive coevolution. Our approach is both highly scalable and may be tuned to achieve specified outcome resource allocations. We demonstrate the behaviour of our approach in simulation, where evolutionary market agents act on behalf of service providing nodes to adaptively price their resources over time, in response to market conditions. We show that this leads the system to the predicted outcome resource allocation. Furthermore, the system remains stable in the presence of small changes in price, when buyers' decision functions degrade gracefully. © 2009 The Author(s).

Fokker-Planck equation approach to the description of soliton statistics in optical fiber transmission systems

We derive rigorously the Fokker-Planck equation that governs the statistics of soliton parameters in optical transmission lines in the presence of additive amplifier spontaneous emission. We demonstrate that these statistics are generally non-Gaussian. We present exact marginal probability-density functions for soliton parameters for some cases. A WKB approach is applied to describe the tails of the probability-density functions. © 2005 Optical Society of America.

An investigation of management accounting control systems in the palm oil industry:a sociomaterial approach to practice change

The primary aim of this research is to understand what constitutes management accounting and control (MACs) practice and how these control processes are implicated in the day to day work practices and operations of the organisation. It also examines the changes that happen in MACs practices over time as multiple actors within organisational settings interact with each other. I adopt a distinctive practice theory approach (i.e. sociomateriality) and the concept of imbrication in this research to show that MACs practices emerge from the entanglement between human/social agency and material/technological agency within an organisation. Changes in the pattern of MACs practices happens in imbrication processes which are produced as the two agencies entangle. The theoretical approach employed in this research offers an interesting and valuable lens which seeks to reveal the depth of these interactions and uncover the way in which the social and material imbricate. The theoretical framework helps to reveal how these constructions impact on and produce modifications of MACs practices. The exploration of the control practices at different hierarchical levels (i.e. from the operational to middle management and senior level management) using the concept of imbrication process also maps the dynamic flow of controls from operational to top management and vice versa in the organisation. The empirical data which is the focus of this research has been gathered from a case study of an organisation involved in a large vertically integrated palm oil industry company in Malaysia specifically the refinery sector. The palm oil industry is a significant industry in Malaysia as it contributed an average of 4.5% of Malaysian Gross Domestic Product, over the period 1990 -2010. The Malaysian palm oil industry also has a significant presence in global food oil supply where it contributed 26% of the total oils and fats global trade in 2010. The case organisation is a significant contributor to the Malaysian palm oil industry. The research access has provided an interesting opportunity to explore the interactions between different groups of people and material/technology in a relatively heavy process food industry setting. My research examines how these interactions shape and are shaped by control practices in a dynamic cycle of imbrications over both short and medium time periods.

An Ontology-based Approach to Student Skills in Multiagent e-Learning Systems

The main idea of our approach is that the domain ontology is not only the instrument of learning but an object of examining student skills. We propose for students to build the domain ontology of examine discipline and then compare it with etalon one. Analysis of student mistakes allows to propose them personalized recommendations and to improve the course materials in general. For knowledge interoperability we apply Semantic Web technologies. Application of agent-based technologies in e-learning provides the personification of students and tutors and saved all users from the routine operations.

Ontological Approach to Domain Knowledge Representation for Information Retrieval in Multiagent Systems

An ontological representation of buyer interests’ knowledge in process of e-commerce is proposed to use. It makes it more efficient to make a search of the most appropriate sellers via multiagent systems. An algorithm of a comparison of buyer ontology with one of e-shops (the taxonomies) and an e-commerce multiagent system are realised using ontology of information retrieval in distributed environment.