Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

Sphingolipids and ceramides are essential components of cellular membranes and important signalling molecules. Because of a growing appreciation for their diverse biological roles, understanding of the biosynthesis and regulation of sphingolipids has recently become a key goal in drug discovery. Serine palmitoyltransferase (SPT) is a pyridoxal 5′-phosphate (PLP)-dependent enzyme that catalyses the condensation between L-serine and a long-chain acyl thioester such as palmitoyl-CoA (C16-CoA). This first step in sphingolipid biosynthesis is conserved in all organisms studied to date, from microbes to man. The fungal natural product myriocin is a potent inhibitor of SPT; however, the molecular details of inhibition are not fully understood. Myriocin contains a long alkyl chain and a polar head group thus it displays features of both SPT substrates. Therefore, the prevailing hypothesis is that inhibition of SPT occurs because myriocin acts as a mimic of a key transition state of the catalytic mechanism. Through a combination of UV-vis spectroscopy, mass spectrometry, x-ray crystallography and enzyme inhibition assays it has been possible to study the interaction between S. paucimobilis SPT and myriocin. I have shown that myriocin initially forms an inhibitory PLP:myriocin aldimine complex in the active site that displays a Ki of 967 nM. Interestingly, this complex is susceptible to unexpected, slow enzymatic degradation. The mechanism for myriocin breakdown has been elucidated as a retro-aldol type reaction, which results in cleavage of the C2-C3 bond producing a C18 aldehyde. This aldehyde is then capable of covalently modifying the active site lysine265, forming a second (suicide) inhibitory complex and rendering the enzyme catalytically inactive. Substitution of the active site lysine produced SPT K265A, an inactive enzyme that did not catalyse the breakdown of the PLP:myriocin complex. However, the determination of the crystal structure of the SPT K265A:PLP-myriocin complex revealed that the myriocin had undergone decarboxylation. Nevertheless, this SPT:PLP:decarboxymyriocin structure revealed details about myriocin’s mechanism of inhibition for the first time. The novel mechanism of myriocin degradation has implications on the structure activity relationship (SAR) and design of drugs targeted towards SPT, the role of feedback regulation by long chain aldehydes and further expands the range of reactions catalysed by this important enzyme. As well as inhibition studies the structure of bacterial SPT was also examined by preparing an N-terminally truncated S. paucimobilis SPT. This version, shortened by 21 amino acids, was ~5-fold slower than the wild-type enzyme and suggests that the N-terminus may play a role in catalysis. Additional work has been undertaken to study an unusual membrane-bound viral SPT, composed of two naturally fused open reading frames (SPT2-SPT1) with the proposed SPT2 domain at the N-terminus and the SPT1 domain at the C-terminus. To study soluble mimics of this interesting fusion I prepared a bacterial S. paucimobilis SPT fused wild-type and mutant construct and isolated a fused SPT2-SPT1 with what appears to be single PLPbinding site.

The Eastern box turtle (Terrapene carolina carolina) is one of the most common reptiles in North America, but is soon to be threatened due to increased urbanization, disease, and the pet and food trades. In order to assist resource managers in choosing suitable sites for relocation studies, more information on the winter ecology of this species is necessary. We examined the temperature tolerance, microhabitat and degree of philopatry to hibernacula for juvenile and adult E. box turtles for two consecutive winters in Charles City Co, VA. The turtles were tracked via radio telemetry to record point locations during the active and inactive seasons. iButton data loggers were attached to each turtle to record temperature throughout winter. Vegetation data were collected and analyzed to determine if there are microhabitat differences between adult and juvenile turtles, and between occupied and random plots. Philopatry to wintering hibernacula was determined by measurements in the field and using ArcGIS. Adults had significantly higher minimum temperatures than juveniles during the first winter (P=0.027), but not during the second winter (P=0.327). Shrub and canopy cover were marginally higher for random plots than for occupied turtle hibernacula plots (P=0.066 and P=0.092, respectively); however there were no significant differences for any of the vegetation variables between adults and juveniles. Some of the turtles demonstrated site fidelity of their hibernacula. The temperature data from this study suggests that juveniles may have poorer hibernacula selection and therefore lower minimum temperatures compared with adults, but this was not seen in our second season suggesting that juvenile turtles may learn to choose better hibernacula or to dig deeper. The difference in findings for the two winters could be attributed to illness by several of the turtles the first winter, by increased maturity in the juveniles the second winter or by the significant difference in ambient temperature for the two winters (P=0.0001). Juveniles do not differ from adults in microhabitat selection, therefore resource managers may not need to plan differently for juveniles and adults in relocation studies. We also conclude that both age groups of T. c. carolina exhibit site fidelity of hibernacula.

Provisional or unfinished images, forms and actions can sustain their status by continuing to change. This can resist programmed experience of their state, and shift their relationship as images within time. The sub-aesthetics of the unfinished and entropic can alter our understanding of where and how images are formed and located within time. My paintings each exist within their own emergent systems of time, structure and productive disorder. This thesis discusses these ideas in relation to DAY FOLDER and other work made during my MFA studies.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Large areas of the UK have witnessed intense industrialisation since the industrial revolution in the latter part of the 18th Century. Increased environmental awareness and pressure to redevelop brown field sites, have resulted in the majority of civil engineering projects undertaken within the UK encountering some form of contamination. In order to collect the vast amount of information required to assess a potentially contaminated site, a multi-stage site investigation (preliminary investigation, exploratory and detailed investigation) is usually undertaken. The information collected during the investigation allows the three components of the risk assessment process to be identified. These components are the source of contamination, possible pathways for the movement of contaminants and vulnerable targets on and off site. A prototype knowledge-based system (ATTIC Assessment Tool for The Investigation of Contaminated Land) has been developed to demonstrate that knowledge-based technology can be applied to the preliminary stage of the investigation of contaminated land. ATTIC assesses information collected during the preliminary stage of an investigation (past use, geological map, hydrological maps etc.) and assists with the risk assessment process, with the prediction of potential contaminants, hazards and risk to neighbouring areas. The system has been developed, using CLIPS software. It consists of four knowledgebases (source, pathway, target and health and safety knowledge-base), containing 1600 rules. The knowledge within the knowledge-bases was obtained from two main sources. The initial and main source was the technical literature. Obtaining knowledge from technical literature involved reviewing published material, extracting relevant information and converting information into rules suitable for the knowledge-base system. The second source of knowledge was domain experts via a knowledge elicitation exercise. The exercise took the form of a questionnaire relating to the rules and parameters within the system. A Visual Basics interface was also developed in conjunction with the knowledge-based system, in order to allow data entry to the system. The interface uses a series of forms relating to different components within the risk assessment process. On completion of compiling the prototype, the system was validated against a number of case studies. The system predicted the likely contaminants with a reasonable match to those observed, even though the input data for the case studies was limited. The assessment of risks to neighbouring target areas was generally in agreement with the case study reports, matching similar risk values and directions. In addition to the development of the prototype system, a database modelled on the Association of Geotechnical Specialists electronic format for the transfer of ground investigation data was also developed to store preliminary investigation information. The data structures were implemented using Microsoft Access relational database management system software. This allowed the database to be developed within a Microsoft Windows environment.

Master of Landscape Architecture / Department of Landscape Architecture/Regional and Community Planning / Blake Belanger / Resilience in social-ecological systems, defined by ecologist C.S. Holling (1973), is the persistence of systems after a disturbance. This theory of resilience is becoming increasingly important, especially in urban areas where human systems dominate. Therefore, creating resilient social-ecological systems is emerging as a focus for many landscape architects when designing urban landscapes. Researchers and practitioners have created frameworks and strategies for applying resilience theory, but designers are still lacking tangible methods they can use to implement design strategies to create resilient landscapes. This research presents a set of resilient design strategies, so landscape architects can have a tool to design generally resilient social-ecological systems in urban areas. In order to discover strategies which improve system resilience, I conducted a literature review and created a perceptual model of the social-ecological systems operating in the study site, Washington Square Park in Kansas City, Missouri. The perceptual model determined systems and system components I focused on in this research. These systems are soil, water, vegetation, fauna, and people. Strategies suggested by Jack Ahern (2011), Brian Walker and David Salt (2006), and Kevin Cunningham (2013) for creating resilience determined strategies which were applied to the system components in order to evaluate the park for resilience. The strategies suggested are modularity, redundancy, tight feedbacks, and ecosystem services. In addition, the system components and strategies were used to analyze case studies. I used strategies discovered in the case study analyses along with goals for the redesign of Washington Square Park, discovered by analyzing the site and previous park documents, to create the guidelines. I then used the guidelines to create a design proposal for the park. The current state of the system components in the park and the proposed state from the redesign were used to show the guidelines’ success in increasing the general resilience of Washington Square Park. These guidelines have potential to increase resilience in other urban civic spaces through a similar methodology I used for Washington Square Park. In addition, the guidelines have the potential to further research in applying resilience theory to the design of landscapes.

The topic of this thesis is search engine optimization (SEO). This term covers many activities, procedures and techniques. When using SEO you can improve your position in a search engine and narrow it to so called key words. The first part of the theoretical part acquaints readers with the basic facts, statistics and defines the basic terminology. The main objective of the second part is concentrated on the main elements which affect the successes of optimalization. The practical part is dealing with analysis of the optimalized e-shop including its competitors. The changes and recommendations of improvement and development of the e-shop were suggested on the basis of the analysis, the theoretical acquirements and the experience of the author. These changes are gradually implemented in the following part of the thesis. The impact on the attendance and placement in the search engines is reviewed after the realization of the suggested above.

Thesis advisor: Dale Herbeck / The established standard for incitement articulated in Brandenburg v. Ohio (1969) has developed into a staple of First Amendment law. The Brandenburg standard for incitement works in the real world, but questions have been raised about whether it can be extended into cyberspace. This thesis examines this question through an analysis of threatening web sites such as the Nuremberg Files, and accompanying jurisprudence. The ability of web sites to incite illegal action is undoubtedly compromised by the characteristics that differentiate them from the physical world—What is to be done when laws intended to encompass a much simpler form of expression lose their relevance? / Thesis (BA) — Boston College, 2010. / Submitted to: Boston College. College of Arts and Sciences. / Discipline: Communication Honors Program. / Discipline: Communication.

1: Por este livro passam outros. 1.1: Que são teses e dissertações senão livros? 1.2: O livro como um lugar, não um livro objeto, mas enquanto meio, programa. 2: Um corpo cujo contorno renega seu papel continente, sempre apontando sua razão de existir para além de seus limites. 3: Uma aproximação mimética, na medida em que se utiliza das possibilidades dispostas, categorias e ítens sobressalentes de um dispositivo opaco: a nota de rodapé, o registro fotográfico, a escrita formatada, a descrição como maneira, a pretensão de distância reflexiva, a objetividade anunciada em resumos. 4: O resgate suspeitoso de um mito de origem: a inserção da produção de arte no campo de erudição acadêmico sem que a primeira tivesse de se submeter ao segundo, (daí a noção de hóspede tomada de Duchamp, e como consequência sua dimensão fantasmática). 3. 1: Costurar tudo pela narrativa de um sujeito que a um só tempo analisa, olha e é visto, predicado. 5: Manipular os dados, e por isso, admitir a manipulação como método científico. Então afirmar tudo como num Tratado. 3.2: Foi dado um aviso: \"descrever muitas vezes nos desobriga de explicar\". Mas veio demasiado tarde: já se havia optado, como estratégia, pela distração. 5. 1: Propor a leitura, implicada em sua ficção, de uma linha de pesquisa e o que esta guarda de específico - quem sabe um manual, no sentido de que o livro pode-se ter em mãos. Mas nem vale fazer caso desta introdução. Resumo nenhum abre mão de sua pretensão de roteiro conciso que dispensa o que finge anunciar, o parodiar de mais uma Tese. / If the images give in to the association urge that gives them impulse, without the bond that condemns them to the shroud of ordinate thought. If writing renounces the imposed duty of servant to the ideas. If the footnotes leak through the page, allowing the book\'s layout to breath. If translation is confronted by treason, we assume this treason as creation and books cease to disguise as mere support for content: \"By this book elapse others. What are thesis and dissertations, but books?\" What would then be necessary to grant this Thesis, despite its uncommon format, any trace of respectability? In different languages, the political pretensions which are close to us sound like the resume of a fairy tale: \"In a far a way University, ranked first amidst those from Cruzeiro do Sul, there is a singular line of research, understood by us as a place among others...\" But it might come handy since we still defend fictional grounds as something proper of our condition. A matter of resistance to the appropriation faced by our writings to strange purposes -- although our purpose itself might be the strange one. To quote academics as writers, to quote Bataille`s Story of the Eye and, without notice, to grant the story a scientific status. To quote fiction itself and the wealthiest concepts in the most readable way, keeping its improper spelling: Concept. And thinking in a pragmatic way, how glamorous wouldn\'t be a well formulated monograph -- extended linearly and permeated with reflections proper to its medium -- named with an easily translatable title: Thesis as Site?