Tuberculosis is a disease that kills more people every year than any other infectious disease and is caused by the human pathogen, Mycobacterium tuberculosis (Mtb). This disease can be treated by a standard six month course of four antimicrobial drugs that have been in use since the 1960s. However, the rise of multi-drug resistant and extensively drug-resistant strains of TB has complicated the efforts to eradicate the disease. Therefore, there is a critical need for the development of new anti-TB drugs with a novel mechanism of action that can speed up treatment duration and help avoid resistance. The discovery of twenty genes encoding cytochrome P450 enzymes in the Mtb H37Rv genome sequence has pointed to the significance of these enzymes in the physiology and pathogenicity of this bacterium. Consequently, the characterisation of these Mtb P450 enzymes may define their physiological roles of which can be a novel anti-tubercular drug target. To date, the characterisations of selected Mtb P450 enzymes have highlighted their diverse and unexpected roles in the metabolism of cholesterol and lipids and the production of secondary metabolites. Biochemical and biophysical studies of these enzymes provided knowledge of their active site properties that may be exploited for drug discovery. Therefore, with the prospect of defining novel functions and identifying novel drug targets, characterisations of the remaining orphan Mtb P450s is of interest. M. tuberculosis CYP141A1 and CYP143A1 are orphan enzymes with unknown physiological function in Mtb which is characterised in this study through use of various spectroscopic and biophysical techniques. Interestingly, CYP141A1 can be expressed in form of which 54 amino acids (Del54CYP141A1) are deleted from the N-terminus. Although Del54CYP141A1 still retain spectroscopic characteristics, this form of P450 cannot be crystallized. Optimisation of full-length CYP141A1 buffer composition resulted to the formation of reproducible crystals and determination of CYP141A1 structure. Spectroscopic and structural characterisations presented in this thesis revealed many characteristics of CYP141A1 and CYP143A1 are comparable to previous Mtb P450s reported to date. CYP141A1 and CYP143A1 active site consist of b-type heme iron ligated by cysteine residue and a water molecule at its proximal and distal face, respectively. Both enzymes bind tightly to azole antifungal drugs highlighting their potential as a drug target. In addition, fragment-based screening applied to CYP141A1 and CYP143A1 provided the starting point for the development of potent, isoform-specific inhibitors for both orphan Mtb P450 enzymes. The first crystal structure of CYP141A1 and identification of new fragment binders of CYP141A1 and CYP143A1 are presented in this thesis. Overall, this research remains significant in providing new knowledge on the spectroscopic and structural properties of the M. tuberculosis P450s CYP141A1 and CYP143A1.

The thesis Mapping the Self-Portrait: Navigating Identity and Autobiography in Visual Art is a practical project. It explores the relationship between autobiography and self- portraiture, and how these notions of the self can be represented in visual art. The exhibition 360 Potential Truisms forms the major component in this thesis, and is accompanied by a written exegesis. This exegesis explores notions of the self-portrait and autobiography in relation to identity, with focus on a post-structural approach to fragmentation and movement. Artworks have been developed to reflect a shift towards an idea of the fragmented self, involving drawing, photography, and text to allow a constantly changing interpretation of self-portraiture.

PhD / The aims of this study were to test the efficacy of immunoglobulin and its Fab and Fc fragment in the treatment of experimental autoimmune neuritis (EAN) in Lewis rats, to investigate which portion of immunoglobulin is operative in the effect of IVIg, and to clarify the possible mechanisms by which immunoglobulin exerts its action in the treatment of rats EAN. EAN was induced by immunization with whole bovine peripheral nerve myelin. The immunized rats were randomized into groups, assessed clinically, electrophysiologically, and histologically, and intravenously injected with normal saline, albumin, human IVIg preparation, purified Fab or Fc fragments. The treatment efficacy was compared between normal saline and albumin groups, albumin and IVIg groups, albumin and Fab groups, albumin and Fc groups, Fab and Fc groups, Fab and IVIg groups, and Fc and IVIg groups. Methods of myelin isolation, antibody purification, and Western blot techniques were also applied. The results revealed that treatment with Fc fragment and IVIg at the onset of signs of disease effectively prevented further progression of disease, shortened disease duration, and facilitating recovery from illness as shown in clinical, electrophysiological and histological parameters. In the study which the efficacy of albumin and IVIg was compared, 5 out of 17 rats (29%) in the albumin group and 12 out of 17 (71%) in the IVIg group completely recovered from the clinical disease by day 30. The animals receiving IVIg treatment exhibited lower clinical scores, less prolongation of S wave latencies, better maintained S wave amplitudes, less reduction of distal motor NCVs, better maintained distal and proximal CMAP amplitudes, and lower histological grades. In the study which the efficacy of albumin, Fab fragment, Fc fragment, and IVIg was compared, 0 out of 8 (0%) in the albumin group, 1 out of 8 (13%) in the Fab group, 4 out of 8 (50%) in the Fc group, and 6 out of 9 (67%) rats in the IgG group completely recovered from the clinical disease by day 30. The animals receiving Fc fragment and IVIg treatment exhibited lower clinical scores, less prominent weight loss, less prolongation of S wave latencies, better maintained S wave amplitudes, less reduction of distal motor NCVs, better maintained distal and proximal CMAP amplitudes, and lower histological grades.

<p>In vitro-test för upptäckt och behandling av tumör eller mikrometastaser har de senaste 30 åren gjort stora framsteg tack vare immunokemi och nya framgångsrika cellodlings- tekniker som bättre reproducerar celltillväxt i tre dimensioner (3D) och det omgivande stromat (multicellulär tumörsfäroidodling). TS1-218 scFv (single chain variable fragment) är en monoklonal antikropp som har affinitet till ett protein tillhörande cytoskelettet (cytokeratin). Av TS1-218 har skapats olika varianter (en dimer TS1-218₂ och en mutant HE1-Q) med syftet att öka affinitet och retentionstid på platsen för dess verkan. I det här projektet försökte vi att testa och jämföra egenskaper hos alla 3 joderade antikropparna genom att inkubera odlade Hela Hep 2 tumörcellssfäroider med dessa antikroppar. Alla tre antikroppsvarianter visade god förmåga att penetrera sfäroider och att binda deras epitop i cytokeratin 8. Försöken visade att det fanns affinitetsskillnader mellan TS1-218 monomer, dimer och mutant vilket visade sig som olika inbindningsförmåga till sfäroiderna.</p>

For the past few years, with the rapid advance of VLSI and multimedia technology, the applications of three-dimensional (3D) graphic applications have been widely and rapidly spread into various areas, and not longer limited into specific technical areas performed by high-end workstations. In near future, the 3D graphic engine will become an indispensable part of most multimedia systems including the entertainment television sets, the personal electronic appliances etc. A general 3D graphics engine can be divided into the geometry subsystem and the raster sub- system. The main contribution of this thesis is to design an efficient fragment pipeline process. It also helps the development of the vertex processor, and the integration of geometry and raster subsystem. In the design of the per-fragment processor, since it contains vary processing stages, such as fog blending, visible test, and alpha blending. This thesis analyzes the dependence relationship between these stages to allow several stages to run in parallel to reduce the overall pipeline latency and adjust the processing order of these stages to avoid unnecessary texturing access. This thesis also proposes two memory buffer access mechanisms suitable for the tile-based 3D graphic rendering engine to reduce the overall system memory bandwidth. The first method is to include some additional control flags for each tile such that the frequent buffer clear operations can be integrated with the normal rendering processes to avoid the additional memory clear access. The second approach is to identify the non-modified pixels in each tile by building the dirty table to reduce the number of updated pixels. The experimental results show that the proposed methods can cause more than 50% reduction of memory access. The proposed design has been realized using 0.18um technology. The gate count of the vertex processor without special functions and per-fragment processor is 201k and 118k, respectively.

The study of tropical forest fragmentation addresses the difficult issues of diminishing forest area and concurrent biodiversity losses. In recent years much of the deforestation of the tropics has been challenged with policy changes and conservation efforts. The Firestone Center for Restoration Ecology, located in Costa Rica, is an area of relatively conserved and restored forest fragments that has proven resilient. This study focuses on a Geographic Information Systems (GIS) analysis, used to assess the level of forest fragmentation in the area. Fragmentation is the process by which continuous forest is diminished into smaller, geographically isolated portions of forest. It was determined that the area is relatively unfragmented, as compared to it’s status in 1972. Though anthropogenic stresses continue, fragmentation of primary forest is limited and the majority of forested area is in large, semi-continuous blocks made up of a mixture of primary and secondary forest, which likely allows for a preservation of biodiversity in the region. Further on-site studies are necessary to fully evaluate the level of anthropogenic stress on the region. However, compared to many tropical areas, Costa Rica is conserving forest and ecological diversity.

Le présent mémoire traite de l'interrelation (l'intéraction ou la relation) entre récit de soi et temps social, observable à travers le cinéma contemporain. Les individus créent un récit de soi, une narration cohérente de leur vie, pour lui donner un sens, pour la structurer. Les dernières décennies ont vu apparaître un processus de fragmentation du temps social. La question centrale de ce mémoire est de savoir comment les individus prennent en compte cette fragmentation dans leur récit de soi. Nous partons d'une hypothèse: les individus ressentent la fragmentation du temps social, soit pour s'y adapter, soit pour se conformer à elle. Nous avons choisi d'étudier le récit de soi de certains personnages de films contemporains. Nous pensons que le cinéma peut être un révélateur social, qu'il peut nous parler des configurations sociales en cours. Nous avons entrepris l'analyse de cinq films contemporains pour extraire les structures narratives qui les soutiennent, ainsi que les récits de soi des personnages. Nous avons observé, en premier lieu, que les individus ressentent la fragmentation du temps social et qu'ils mettent en oeuvre différentes stratégies pour s'adapter ou résister, la principale étant une valorisation du temps présent et des nouvelles logiques narratives éloignées de celles du récit typique de la modernité. ______________________________________________________________________________ MOTS-CLÉS DE L’AUTEUR : Récit de soi, Temps social fragmenté, Cinéma, Identité narrative, Dias de futbol, Wonderland, 101 Reykjavik, Les poupées russes, La moitié gauche du frigo.

In vitro-test för upptäckt och behandling av tumör eller mikrometastaser har de senaste 30 åren gjort stora framsteg tack vare immunokemi och nya framgångsrika cellodlings- tekniker som bättre reproducerar celltillväxt i tre dimensioner (3D) och det omgivande stromat (multicellulär tumörsfäroidodling). TS1-218 scFv (single chain variable fragment) är en monoklonal antikropp som har affinitet till ett protein tillhörande cytoskelettet (cytokeratin). Av TS1-218 har skapats olika varianter (en dimer TS1-2182 och en mutant HE1-Q) med syftet att öka affinitet och retentionstid på platsen för dess verkan. I det här projektet försökte vi att testa och jämföra egenskaper hos alla 3 joderade antikropparna genom att inkubera odlade Hela Hep 2 tumörcellssfäroider med dessa antikroppar. Alla tre antikroppsvarianter visade god förmåga att penetrera sfäroider och att binda deras epitop i cytokeratin 8. Försöken visade att det fanns affinitetsskillnader mellan TS1-218 monomer, dimer och mutant vilket visade sig som olika inbindningsförmåga till sfäroiderna.

With a   growing human population, cities keep growing worldwide altering ecosystem   and thereby affecting the species living in these areas. Most studies of   urbanization and its effect on ecosystem have been conducted in the western   world and little is known about its effect in the neotropical part of the   world. I examined effects of fragment size, vegetation structure and   connectivity of urban green areas on bird species richness, mean abundance,   diversity and biomass in La Paz, Bolivia. Additionally, the effects of   different disturbance variables on bird community were evaluated. In total,   36 bird species were found in 24 fragment of varying size, connectivity and   level of disturbance. Bird species richness decreased with increasing   disturbance while connectivity and fragment size did not contribute   significantly to explain the variation in species richness at count point scale (p&gt;0.005, multiple linear regression). At fragment   scale, however, species richness increased with fragment sizes,   which has been shown in other studies from neotrophical regions. Variation in   abundance, diversity or biomass could not be explained by connectivity,   fragment size or disturbance.     Furthermore, coverage of construction had a negative effect on species   richness while coverage of bushes and coverage of herbs were negatively   related to biomass and diversity, respectively. The composition of bird   species differed with size and disturbance of the fragments, so that more   omnivorous and granivorous species such as Zonotrichia capensis, Turdus chiguanco and Zenaida auriculata, were present in areas highly affected by human activities. Larger fragments,   less affected by human presence held a larger proportion of insectivorous   species.

In order to increase the data-path utilization of the programmable graphics processor units (GPU) which often stall by waiting for the execution results of those long-latency instructions, multi-thread technique is very often used in the design of GPU. This thesis proposes a multi-thread single unified core GPU design which owns several key features. First, its processor core can execute not only the vertex and fragment shading programs, but also the software rasteriation module which is mostly implemented by a individual hardware module in other GPU designs. Next, the thread-switching policy in our design is based on the non-preempt blocked scheduling. Normally, whether an instruction will be stalled cannot be detected until it enters the instruction-decode stage. In order to achieve zero-penalty thread switching, a single assistant bit will be padded to each instruction in a thread to tell if the next instruction in the same thread will be stalled or not. This mechanism can help achieve a speed-up of 1.4 in some benchmarks used in this thesis. The register file used in GPU processor is usually equipped with up to four access ports, such that it will occupy a significant portion of the entire GPU especially for muti-thread designs where the register set has to be duplicated by several copies. The implementation cost of the register file can be reduced by decreasing its access port number to two based on the proposed multi-bank approach in this thesis. Our experimental results show that this approach can help reduce the overall gate count by 26.12%. Finally, the rest of fixed-pipeline fragment operation is realized by an iterative time-sharing architecture in order to further save the silicon area. The overall gate count of the proposed GPU is 600K.