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Laser surface modification involves rapid melting and solidification is an elegant technique used for locally tailoring the surface morphology of alumina in order to enhance its abrasive characteristics. COMSOL Multiphysics® based heat transfer modeling and experimental approaches were designed and used in this study for single and multiple laser tracks to achieve densely-packed multi-facet grains via temperature history, cooling rate, solidification, scanning electron micrographs, and wear rate. Multi-facet grains were produced at the center of laser track with primary dendrites extending toward the edge of single laser track. The multiple laser tracks study indicates the grain/dendrite size increases as the laser energy density increases resulting in multiplying the abrasive edges which in turn enhance the abrasive qualities.

Post-translational modifications (PTMs), which biochemically modify proteins to generate diversity and control functionality, are important in the field of chemical biology research. However, typical bioconjugation methods involving nucleophilic addition of cysteine and lysine residues are limited by their lack of site-specificity. In this thesis, we have demonstrated the site-selective chemical modification of a variety of proteins through protein halogenation and subsequent pallado-biology strategies. The "Tag-and-Modify" approach, developed previously in our group and involving the creation of a protein tag for further manipulation, is a useful tool for site-selective chemical modification. Here, we envisioned extending its utility to a novel concept of [¹⁸F]-radiolabelling of proteins involving direct electrophilic fluorination, thus forming a C-F bond at a specific modification site and leading to the generation of protein species applicable for in vivo [¹⁸F]-PET imaging and diagnosis. We also explored several alternative methods for the installation of C-Br/C-I bonds onto a protein of interest. Our first attempts involved the biosynthetic incorporation of a synthetic bromotryptophan into the protein, however these processes were unsuccessful. As a workaround, we found IPy₂BF₄, an iodinating agent, to be very effective as a direct method for the site-specific installation of C-I bonds on tyrosine/histidine residues of proteins. We subsequently demonstrated novel and efficient palladium-catalysed cross-couplings of the resultant iodinated tyrosine/histidine moieties, leading to the creation of new C-C bonds. This approach was compatible with a wide range of functionally diverse boronic acids, using a water-soluble and phosphine-ligand-free Pd-complex catalyst under fully aqueous conditions. Our novel, successful method for C-C bond formation onto proteins is potentially applicable to the initial investigation of challenging in vivo Pd cross-coupling of thyroglobulin, based on our achievement of protein labelling under ex vivo conditions. In summary, we are able to create new chemical tools for the site-selective/site-specific chemical modification of proteins, enabling their use as biological probes.

Digitized by Kansas Correctional Industries

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.

La sumoylation représente, après l’ubiquitination, l’exemple le plus étudié de modification post-traductionnelle impliquant la liaison d’une protéine à une autre. Cependant, alors que l’ubiquitination est impliquée principalement dans la dégradation des protéines par le protéasome, la sumoylation semble réguler les propriétés biochimiques de ses substrats (localisation cellulaire, interaction protéique, activité, …). Pour venir lier une protéine appelée Sumo (Small Ubiquitin-like Modifier) sur un substrat, la sumoylation emprunte une voie enzymatique analogue à celle de l’ubiquitination mais utilise des enzymes différentes. A ce jour, bien que plusieurs centaines de substrats de la sumoylation aient été identifiés, seules 5 structures de protéines sumoylées ont été résolues. Elles ne sont vraisemblablement pas représentatives de l’ensemble des substrats de la sumoylation et mon travail de thèse vise à élargir les connaissances structurales sur la sumoylation pour permettre de dégager des concepts généraux. Les études sur la sumoylation se heurtent généralement à la difficulté d’obtenir les substrats sumoylés. Ce projet a donc nécessité, au niveau technique, la mise au point d’un système de sumoylation in vivo en bactérie permettant de modifier des quantités importantes de protéines et de les purifier efficacement. Des analyses bioinformatiques nous ont permis d’identifier des substrats de la sumoylation propices à une étude structurale de leur forme sumoylée. Au terme de ces analyses, nous avons retenu 3 protéines : DJ-1, PPARγ et IκBα. Bien que la complexité du sujet nous ait ensuite amené à écarter DJ-1 et PPARγ, nous sommes parvenus à purifier la forme sumoylée d’IκBα. Ce résultat nous a permis d’entreprendre une campagne de cristallogenèse d’IκBα complexé au facteur de transcription NF-κB. L’obtention d’IκBα sumoylé permettra également d’aborder des études fonctionnelles pour améliorer la compréhension du rôle de la sumoylation de ce substrat. Nos analyses bioinformatiques ont également révélé que dans plus de 60% des cas, les sites de sumoylation des substrats se trouvent dans des zones prédites intrinsèquement désordonnées. L’importance du désordre dans le processus de sumoylation était jusqu’alors largement sous-estimée. A titre d’exemple, nous avons étudié par diffusion des rayons X aux petits angles la structure du domaine transactivateur du facteur de transcription ERM sous forme non modifiée et sous forme sumoylée. Cette étude indique que la sumoylation d’ERM n’induit pas le repliement de ce domaine transactivateur. De même, il apparait peu probable, au vu de la flexibilité de cette région, que la sumoylation empêche des interactions avec certains partenaires cellulaires. Dans ce contexte, la sumoylation semble servir de plateforme de recrutement de partenaires, reconnaissant de manière spécifique le Sumo. Ce mécanisme pourrait se généraliser à l’ensemble des sites de sumoylation prédits dans des zones intrinsèquement désordonnées. Le système de sumoylation que nous avons développé permet de produire des protéines sumoylées pures en grande quantité et pourra également servir à identifier des protéines reconnaissant spécifiquement les substrats modifiés. Tous ces éléments devraient permettre de progresser dans la compréhension de cette modification post-traductionnelle impliquée dans de nombreux processus cellulaires fondamentaux.

The intent of this work is to improve the machining speed of an existing 3 axis CNC wood working lathe. This lathe is unique in that it is a modi ed manual lathe that is capable of machining complex sculptured surfaces. The current machining is too slow for the lathe to be considered useful in an industrial setting. To improve the machining speed of the lathe, several modi cations are made to the mechanical, electrical and software aspects of the system. It was found that the x-axis of the system, the axis that controls the depth of cut of the tool, is the limiting axis. A servo motor is used to replace the existing stepper motor, providing the x-axis with more torque and faster response times, which should improve the performance of the system. To control the servo motor, a 1st-order linear transfer function model is selected and identi ed. Then, an adaptive sliding mode controller is applied to make the x-axis a robust and accurate positioning system. A new trajectory generator is implemented to create a smooth motion for all three axes of the lathe. This trajectory uses a 5th-order polynomial to describe the position curve of the feed pro le, giving the system continuous jerk motion. This type of pro le is much easier for motors to follow, as discontinuous motion will always result in errors. These modi cations to the lathe system are then evaluated experimentally using a test case. Three test pieces are designed to represent three of the common shapes that are typically machined on the wood turning lathe. These test cases indicated a minimum reduction in machining time of 52:91% over the previous lathe system. An algorithm is also developed that attempts to sacri ce work piece model geometry to achieve speed gains. The algorithm is used when a certain feedrate is desired for a model, but machining at that speed will cause toolpath following errors, leaving surface defects in the work piece. The algorithm will attempt to solve this problem by sacri cing model geometry. A simulation tool is used to detect where surface defects will occur during machining and a then the work piece model is modi ed in the corresponding area. This will create a smoother part, which allows each axis of the system to follow the new toolpath more easily, as the dynamic requirements are reduced. The potential of this algorithm is demonstrated in an experimental test case. A test piece is created that has features of varying di culty to machine. When the algorithm is run, Matlab/Simulink is used simulate the output of the lathe and locate the areas in the part geometry that will cause defects. Once located, the geometry features are smoothed in SolidWorks using the fi llet feature. The algorithm produces a work piece with smoothed geometry that can be machined at a feedrate approximately 42:8% faster than before. Although it is only the first implementation of the algorithm, the experimental results con rm the potential of the method. Machining speed gains are successfully achieved through the sacrifice of model geometry.