http://hdl.handle.net/2374.OX/2981 2013-06-18T07:55:01Z http://hdl.handle.net/2374.OX/107938 Substance P Receptor Activation and Desensitization as Monitored By M Current Inhibition Meadows, Rena Marie Substance P (SP) is a neuropeptide that plays a variety of roles in the human body, including inflammation, nociception, and smooth muscle regulation. In the central and peripheral nervous systems, SP indirectly acts as an excitatory neurotransmitter by inhibiting the M-current, (IM), a time- and voltage-dependent outward potassium current. Activation of IM produces an outward (hyperpolarizing) current which acts to resist neuronal depolarization and action potential production. By inhibiting IM, SP has the ability to modulate neuronal excitability. Since activation of the SP receptor results in IM inhibition, IM amplitude was utilized in the present study as an indirect measure for SP receptor activation and desensitization. Whole-cell voltage-clamp recordings were used to monitor IM in acutely isolated bullfrog sympathetic ganglia neurons. The cell was voltage-clamped at a holding potential of -30 mV, where IM is largely activated. Steps to -60 mV deactivated IM, producing a slow, exponential decrease in current amplitude, followed by an exponential increase in current (reactivation) upon stepping back to -30 mV. Single exponential curve fits were utilized to measure IM amplitude during the reactivation phase. SP application (1 μM) initially produced a rapid and significant inhibition in IM amplitude. However, with continuous SP application, IM amplitude significantly recovered, returning to the control amplitude. This desensitization, defined as a decrease in responsiveness following prolonged or repeated exposure to an agonist, suggests a similar desensitizing loss of functioning by the SP receptor during SP application. The findings presented here support previous studies showing that SP application initially produces inhibition of IM, but continued drug application results in desensitization and loss of IM inhibition. 2009-04-10T08:16:37Z http://hdl.handle.net/2374.OX/107937 Synthesis and Reactions of bis(2,2,2-Trifluoroethyl)-β-Ketophosphonates White, Kevin Michael The research contained herein is focused on a previously unreported synthesis of bis(2,2,2-trifluoroethoxy)-β-ketophosphonates via the hydration of the corresponding bis(2,2,2-trifluoroethoxy) alkynylphosphonates. The first step was to prepare all starting materials, namely the bis(2,2,2-trifluoroethyl) alkynylphosphonates from the corresponding commercially available terminal alkynes and bis(2,2,2-trifluoethoxy) phosphorochloridate. The hydration of the bis(2,2,2-trifluoroethoxy) alkynylphosphonates to yield the desired products was accomplished using mercury sulfate and 10% sulfuric acid. 2,2,2-Trifluoethanol was used as the solvent. The use of these β-keto phosphonates in the Horner-Wadsworth-Emmons reaction was also examined. 2009-04-10T08:16:25Z http://hdl.handle.net/2374.OX/107936 Visualizing Epistemic Structures of Interrogative Domain Models Hughes, Tracey D. In this paper, we explore the concept of epistemic visualization in interrogative domains. Epistemic visualization is the process and result of developing visual models that capture the structure, content, justification and acquisition of knowledge obtained by a software agent in a knowledge-based system. The knowledge is the foundation in which the agent can respond to queries against a corpus containing questions and answers. The visualizations are therefore used to examine the quality of the software agent's knowledge. The visual models will include justification and commitment artifacts as well as knowledge acquisition flow. The visualization will demarcate the a priori and posteriori knowledge. The knowledge of the software agent is stored in epistemic structures which are knowledge representation schemes that supports the basic concepts of knowledge as defined by the tripartite analysis of knowledge. Epistemic visualization is used to analyze the quality of the knowledge of a software agent in an interrogative domain. For our purpose, interrogative domains are hearings, trials, interrogations, personality test or any document source in which the primary content is questions and answers pairs. In this paper, we introduce the Epistemic Structure Es that captures the agent's knowledge and the visualization of that epistemic structure using common visualization techniques. 2009-04-10T08:16:13Z http://hdl.handle.net/2374.OX/107935 Towards the Synthesis of N-Acetyl-2-amino-2-deoxy-D-mannopyranose uronic acid (D-ManNAcA) and Derivatives Cox, Glen Adam The following details attempts at a stereoselective synthesis of deoxygenated D-mannose uronic acid derivatives from D-glucurono-6,3-lactone. These derivatives will be tested as potential inhibitors of enzymes used by Staphylococcus aureus to form its polysaccharide microcapsule, which functions as a protective barrier against destruction by the host. Two serotypes (types 5 and 8) comprise the majority of S. aureus bacteria and also the most virulent strains of this bacterium. The goal of this research project is to synthesize glycomimetics of D-ManNAcA that may act as potential inhibitors of the enzymes such as UDP-GlcNAc 2-epimerase. Since infections caused by S. aureus are an increasing threat in hospitals and the general community, it is of considerable interest within the biological community to find new treatments to combat these drug-resistant bacteria. 2009-04-10T08:16:00Z