This project utilized synthesis and in vitro assays to generate antagonist SARs at various nAChR subtypes. Alkylation of the pyridino nitrogen of the nicotine molecule afforded subtype specific antagonists at a42* nAChR subtypes and nAChR subtypes that mediate nicotine-evoked dopamine release. Using this data, a series of mono-azaaromatic quaternary salts were produced and evaluated in binding and functional assays for a42* and a7* nAChR subtypes and nAChR subtypes that mediate nicotine-evoked dopamine release. Additionally, bis-azaaromatic quaternary salts were synthesized and evaluated in the same assays. Two potent lead compounds were identified. N-n-dodecylnicotinium iodide (NDDNI) was found to be very potent at both a42* nAChR subtypes and nAChR subtypes that mediate nicotine-evoked dopamine release. And the most promising candidate was N-N-bisdodecylpicolinium dibromide (bDDPiB), which was selective for the nAChR subtypes that mediate nicotine-evoked dopamine release (IC50 = 9 nM). Additionally, using the data from the SARs, predictive computer models were generated to assist in future compound assessment without in vitro assays. Three self-organizing map (SOMs) models were generated from three different sets of compounds. The groups consisted of the mono-substituted compounds, the bissubstituted compounds, and both sets combined. The models were able to successfully "bin" the test set of compounds after developing a model from a similar set of training compounds. Additionally, using genetic functional activity (GFA) algorithms an evolutionary approach to generating predictive model equations was applied to the compounds. Three separate equations were generated in order to form a predictive method for evaluating affinities at the a4b2* receptor subtype. In addition to the modeling and SAR work of the quaternary ammonium compounds, novel synthetic methods were also employed to develop enantiomerically pure nicotine analogs. Efficient enantioselective syntheses of (S)- and R-(+)-nornicotine, (S)-and R-(+)-anabasine, and (S)-and R-(+)-anatabine have been developed, affording isomers in high enantiomeric excess.

Graduation date: 1997

University of Technology, Sydney. Faculty of Business. / The need for more dynamic views on international joint ventures' control research has recently become a growing concern. Changes in the complexity of relationships between organisations and their environments have led to an increase in control problems and to a need to investigate a suitable framework of management control. The concept of self-organising systems that has emerged with the science of complexity produces some useful and interesting new ways to examine the behaviour of complex systems. Therefore, extending the recent development in self-organising systems into international joint ventures' control research is an opportunity to explore new insights into the development of joint ventures. This study takes an integrative approach by focusing on the integration of management control and self-organising properties of international joint ventures. The purpose of this study is to investigate the roles of management control systems in affecting international joint ventures' performance, from the perspective of alliance complexity constraints. A model of management control in international joint ventures as self-organising systems, representing a complexity-control-outcomes framework, is developed and tested empirically using the partial least square (FLS) approach, a distinctive structural equation modeling (SEM) based technique. The primary results of this study show that formal control mechanisms and control extent have significant direct effects on management automony and the international joint ventures' performance. Management autonomy as an intervening endogenous construct has a significant direct effect on the international joint ventures performance. Significant direct effects of organisational complexity on the formal control mechanisms and control extent are found, and a significant indirect effect of organisational complexity on the management autonomy is found. The overall results suggest a sound link between the complexity-control framework with the control-outcome framework, and the achievement of fit between these two frameworks is important for superior international joint ventures' performance.

Thesis (Ph.D.) - Carleton University, 2005. / Includes bibliographical references (p. 127-139). Also available in electronic format on the Internet.

Thesis (Ph.D.)--University of Wyoming, 2008. / Title from PDF title page (viewed on Apr. 2, 2010). Includes bibliographical references (p. 135-139).

Thesis (Ph. D.)--University of Florida, 2004. / Title from title page of source document. Document formatted into pages; contains 130 pages. Includes vita. Includes bibliographical references.

Thesis (Ph. D.)--University of Texas at Austin, 2003. / Vita. Includes bibliographical references. Available also from UMI Company.

Thesis (M. S.)--Materials Science and Engineering, Georgia Institute of Technology, 2009. / Committee Chair: Milam, Valeria; Committee Member: Boyan, Barbara; Committee Member: Li, Mo; Committee Member: McDevitt, Todd; Committee Member: Sandhage, Ken.

Thesis (Ph. D.)--UCLA, 2009. / Vita. Includes bibliographical references (leaves 289-313).

Thesis (Ph.D.) - University of Queensland, 2006. / Includes bibliography.