A comparative study of three different chloride currents in rat sympathetic neurones

Cl- ions are the most abundant anion in cells. Cl- conducting channels have been proposed to be involved in several cellular processes. These include the modulation of electrical excitability and synaptic inhibition, the regulation of intracellular pH and the regulation of cell volume. In this thesis three types of Cl- channels in rat superior cervical ganglion neurones have been investigated. These are a Ca2+ and protein kinase C-dependent Cl- current (ICl(m)), a hyperpolarization-activated Cl- current (ICL(HP)) and a swelling-activated Cl- current (Icl(swell))- These three currents differ in several properties including biophysical characteristics, sensitivity to pharmacological agents, anion permeability, Ca2+-dependence and involvement of second messenger pathways. Icl(m) is induced synergistically by Ca2+ and diacylglycerol. Consequently it can be activated by the actions of the excitatory neurotransmitter, acetylcholine, which causes a rise in intracellular Ca2+ via the activation of Ca2+ -permeable nicotinic ionotropic receptors, and generates diacylglycerol by stimulating muscarinic receptors. The hyperpolarization-activated Cl- current, (ICL(HP)), shows strong voltage- and time-dependence, is Ca2+-independent and is sensitive to block by the divalent cations, Cd2+ and Zn2+. Icl(swell) is activated in response to hypotonicity-induced cell swelling. The movement of Cl- ions out of the cell is accompanied by water which thus leads to a reversal of cell swelling (Regulatory Volume Decrease mechanism). I have shown that Icl(swell) is different to previously identified Cl- currents in these cells but shares several properties with swelling-activated Cl- currents in other cell types. To conclude, I have studied three types of neuronal Cl- currents which are distinct from one another. Icl(m) and ICL(HP) may have a physiological role in the regulation of electrical excitability, and Icl(swell) in the response of cells to osmolarity changes under both physiological and pathological conditions

Design guidance using simulation-based Bayesian Belief Networks

In our work, the task of complex computer-based system design optimization involves exploration of a number of possible candidate designs matching the optimisation criteria. However, the process by which the possible candidate designs are generated and rated is fundamental to an optimal outcome. It is dependent upon the set of system characteristics deemed relevant by the designer given the systems requirements. We propose a method which is aimed at providing the designer with guidance based upon description of the possible causal relationships between various system characteristics and qualities. This guidance information is obtained by employing principles of multiparadigm simulation to generate a set of data which is then processed by an algorithm to generate a Bayesian Belief Network representation of causalities present in the source system. Furthermore, we address the issues and tools associated with application of the proposed method by presenting a detailed simulation and network generation effort undertaken as part of a significant industrial case study. © 2008 IEEE

Critique of network management systems and their practicality

Networks have become an integral part of the computing landscape, forming a global interconnection of a staggering number of heterogeneous systems and services. Current research focuses on policy based management and autonomous systems and involves the utilisation of very different languages and technologies in concert. This paper examines four current proposals for autonomous network management and analyses them using architectural modelling, against a measure of practicality, as expressed by scalability, reliability and maintainability. © 2010 IEEE

A systems engineering approach to product modularity

Product modularity has been successfully adopted in a number of specific industries, such as computer technology and software development where it provides a number of advantages over monolithic product architectures. This paper presents initial findings from research at a range of companies within the UK where modularity is being applied or considered to address increasing product complexity and the growing need for the symbiosis of mechanical, electrical, electronic, optical, and software technologies in a wider range of manufactured products to meet discerning market requirements. The research identifies a need to address the current application of modularity within industry at three levels; a systems engineering based framework; a methodology for product modularisation; and the underlying process of modular product development. Concluding remarks highlight the issues drawn from the research and opportunities for addressing these issues