Resistance to antimicrobials is an increasing problem in the world of today, and develops faster than man can counter. It is therefore of importance to study metabolic pathways in order to develop new antibiotics, but also to understand how resistance spreads and stabilizes in microbial populations. The commensal flora could be an important factor in the spread of antimicrobial resistance, as drugs aimed at other targets also hit the harmless commensal bacteria. If stable resistance develops in such a population, it could seriously impair a later treatment with the same drug. After a treatment with the macrolide clarithromycin, resistance to this antibiotic increased markedly in the untargeted throat flora, and resistance levels did not recede until at least one year later. Another example of stable resistance can also be seen in sulfonamide resistant Streptococcus pyogenes. Sequence determinations of the dihydropteroate synthase (dhps) gene conferring this resistance revealed a mosaic organisation implying that the it had been brought there by horizontal transfer. Molecular characterization of this gene showed that the sulfonamide resistance was due to mutations of structurally important amino acids in position 65 and 213. The folate synthesis pathway has potential for being exploited further as a drug target. One possible new drug target is hydroxymethyl-dihydropterin pyrophosphokinase (hppk). In the malaria parasite Plasmodium falciparum this enzyme is part of a polyfunctional entity, also encoding dhps. The HPPK part can be separated from DHPS, but that the opposite is not possible. The PfHPPK has two insertions: one also present in other plasmodia, and one apparently unique to P. falciparum. Both are crucial for enzyme activity. To further characterize HPPK, we developed a spectrophotometric activity assay and a method to measure substrate channelling of hydroxymethyl-dihydropterin diphosphate.

No description available.

Thesis (Ph.D.)--The Union Institute, 1997. / Includes bibliographical references (leaves 400-415).

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The four pillars of material science and engineering namely structure, processing, properties and performance form the so-called material paradigm. At the heart of the material paradigm is materials characterization, which is used to measure and identify the relationships. Materials Characterization typically reconstructing the conditions giving rise to a measurement, a classic inverse problem. The solutions of these inverse problems are under or over determined and not unique. The solutions of these inverse problems can be greatly improved if accurate forward models exist for these characterization experiments. In this thesis, we will be focusing of developing forward models for electron diffraction modalities. Specifically, four different forward models for electron diffraction, namely the Electron Backscatter Diffraction, Electron Channeling Patterns, Precession Electron Diffraction and Transmission kikuchi Diffraction modalities are presented. Further, these forward models are applied to important materials characterization problems, including diffraction pattern indexing using the dictionary approach and forward model based orientation refinement. Finally, a novel pole figure inversion algorithm using the cubochoric representation and model based iterative reconstruction is also presented.

No description available.

To our knowledge this is the first comprehensive study of laser-induced effects generated at intermediate distances using self-channeled femtosecond laser pulses. Studies performed were made both experimentally and theoretically with the use of novel modeling techniques. Peak laser pulse powers above 3 GW allow beam propagation without divergence for up to several kilometers. In this regime, experiments were performed at 30 meters from the laser system in a custom propagation and target range, utilizing the Laser Plasma Laboratory's Terawatt laser system. Experiments included investigations of laser ablation; electromagnetic pulsed (EMP) radiation generation over the 1-18 GHz region; shockwave formation in air and solid media; optical coupling of channeled pulses into transparent media; and, conservation of energy in these interactions. The use of bursts of femtosecond pulses was found to increase the ablation rate significantly over single-pulse ablation in both air and vacuum. EMP generation from near-field focused and distance-propagated pulses was investigated. Field strengths upwards of 400 V/m/[Lambda] for vacuum focusing and 25 V/m/[Lambda] for self-channeled pulses were observed. The total field strengths over 1-18 GHz measured at distance surpassed 12 kV/m. Shockwaves generated in transparent media at 30 meters were observed as a function of time. It was found that the interaction conditions control the formation and propagation of the shock fronts into the medium. Due to the processes involved in self-channeling, significant fractions of the laser pulse were coupled into the target materials, resulting in internal optical and exit-surface damage. Basic estimations on the conservation of energy in the interaction are presented. The results of the experiments are supported by hydrodynamic plasma physics code and acoustic modeling.

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

One of two project reports. Part A can be found at: http://hdl.handle.net/11375/18522 / Recent channeling-backscattering measurements of the disorder induced by heavy ion irradiation of semiconductors has indicated radiation damage far in excess of that predicted by linear transport theory. The present work extends the investigation to TEM and compares the two techniques in an annealing study of ion irradiated silicon (~ 80-200 a.m.u. ions of 15-100 keV) for low fluence (typically 3×10¹¹/cm² for TEM and 10¹²-10¹³/cm² for channeling) bombardment. In addition to showing a good correlation between the techniques, the results indicate that neither does there exist a unique relationship between lattice disordering and cascade energy density, nor that a well defined amorphous structure seems to exist. / Thesis / Master of Engineering (ME)