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Signal Transduction is mediated by protein complexes whose spatial- and temporal-distribution, composition and function within cells are often regulated by different post-translational modifications (PTM). As PTMs add or subtract a specific mass difference to a protein, mass spectrometry becomes very amenable for modification analysis. These modifications have conventionally been monitored by fragmenting the modified protein or peptide by collision induced dissociation (CID) within the mass spectrometer, and then screening for the characteristic neutral fragment or fragment ion (marker ion), which is particular to the modification in question. Unfortunately, there are two major issues with respect to the traditional mass spectrometric analysis of PTMs: (1) as there are over 300 known types of modifications, the characteristic fragmentation of only a fraction of these modifications has been studied and (2) the traditional mass spectrometric approaches can only monitor these modifications sequentially, and thus comprehensive modification analysis would be unfeasible considering the breadth of PTMs. The following work aims to address these issues by (1) analyzing PTMs that have never been characterized mass spectrometrically and (2) developing a multiplexed technique for comprehensive PTM monitoring by simultaneously screening for all known characteristic fragments. With respect to the first issue, the characteristic fragmentation of lipid modifications and HNO-induced modifications was investigated. The most prevalent indicator(s) of the modification within the mass spectra are as follows: fragmentation of N-terminal myristoylated peptides produced marker ions at 240 and 268 Th, fragmentation of cysteine farnesylated peptides produced a marker ion at 205 Th and a neutral fragment of 204 Da, and fragmentation of cysteine palmitoylated peptides produced a neutral fragment of 272 Th. For HNO-induced modifications, fragmentation of the sulfinamide- and sulfinic acid-modified peptides produced a neutral fragment of 65 Da and 66 Da, respectively. With respect to the second issue, a multiplexed technique for monitoring modifications that fragment as neutral losses, termed Multiple Neutral Loss Monitoring (MNM), has been developed, successfully validated, and then shown to be the most sensitive approach for PTM analysis. MNM, combined with a second multiplexed approach, targeted Multiple Precursor Ion Monitoring, has been used to provide a comprehensive PTM analysis.

Home modification practice for people with impairments of ability involves redesigning existing residential environments as distinct from the creation of a new dwelling. A redesigner alters existing structures, fittings and fixtures to better meet the occupant�s ability requirements. While research on case-based design reasoning and healthcare informatics are well documented, the reasoning and process of redesign and its integration with individual human functional abilities remains poorly understood. Developing a means of capturing redesign knowledge in the form of case documentation online provides a means for integrating and learning from individual case-based redesign episodes where assessment and interventions are naturally linked. A key aim of the research outlined in this thesis was to gain a better understanding of the redesign of spaces for individual human ability with the view to computational modelling. Consequently, the foundational knowledge underpinning the model development includes design, redesign, case-based building design and human functional ability. Case-based redesign as proposed within the thesis, is a method for capturing the redesign context, the residential environment, the modification and the transformational knowledge involved in the redesign. Computational simulation methods are traditionally field dependent. Consequently, part of the research undertaken within this thesis involved the development of a framework for analysing cases within an online case-studies library to validate redesign for individuals and a method of acquiring reuse information so as to be able to estimate the redesign needs of a given population based on either their environment or ability profile. As home modification for people with functional impairments was a novel application field, an explorative action-based methodological approach using computational modelling was needed to underpin a case-based reasoning method. The action-based method involved a process of articulating and examining existing knowledge, suggesting new case-based computational practices, and evaluating the results. This cyclic process led to an improvement cycle that included theory, computational tool development and practical application. The rapid explosion of protocols and online redesign communities that utilise Web technologies meant that a web-based prototype capable of acquiring cases directly from home modification practitioners online and in context was both desirable and achievable. The first online version in 1998-99, encoded home modification redesigns using static WebPages and hyperlinks. This motivated the full-scale more dynamic and robust HMMinfo casestudies prototype whose action-based development is detailed within this thesis. The home modification casestudies library results from the development and integration of a novel case-based redesign model in combination with a Human- Activity-Space computational ontology. These two models are then integrated into a relational database design to enable online case acquisition, browsing, case reuse and redesign learning. The application of the redesign ontology illustrates case reuse and learning, and presents some of the implementation issues and their resolution. Original contributions resulting from this work include: extending case-based design theory to encompass redesign and redesign models, distinguishing the importance of human ability in redesign and the development of the Human-Activity-Space ontology. Additionally all data models were combined and their associated inter-relationships evaluated within a prototype made available to redesign practitioners. v Reflective and practitioner based evaluation contributed enhanced understanding of redesign case contribution dynamics in an online environment. Feedback from redesign practitioners indicated that gaining informed consent to share cases from consumers of home modification and maintenance services, in combination with the additional time required to document a case online, and reticence to go public for fear of critical feedback, all contributed to a less than expected case library growth. This is despite considerable interest in the HMMinfo casestudies website as evidenced by web usage statistics. Additionally the redesign model described in this thesis has practical implications for all design practitioners and educators who seek to create new work by reinterpreting, reconstructing and redesigning spaces.

Thesis (Ph.D.)--Tennessee Technological University, 2006. / Bibliography: leaves 60-62.

Thesis (Ph.D.)--Tennessee Technological University, 2008. / Bibliography: leaves 277-298.

Thesis (M.S.)--University of North Texas, May, 2008. / Title from title page display. Includes bibliographical references.

Thesis (Ed.D.)--Teachers College, Columbia University. / Typescript; issued also on microfilm. Sponsor: Terri Astuto. Dissertation Committee: Francis Ianni. Bibliography: leaves 110-120.

Thesis (Ed. D.)--West Virginia University, 1999. / Title from document title page. Document formatted into pages; contains xv, 225 p. Vita. Includes abstract. Includes bibliographical references (p. 209-224).

Thesis--University of Florida. / Description based on print version record. Typescript. Vita. Includes bibliographical references (leaves [80]-86).

Thesis (Ph. D.)--University of Wales, Bangor, 2003. / Includes bibliographical references (leaves 203-222). Also available online (PDF file) by a subscription to the set or by purchasing the individual file.