Tuberculosis is a major public health problem in Ethiopia. The aims of this study were (i) to investigate the recovery rate of M. tuberculosis from smear positive single morning sputum specimens subjected to long-term storage at -20°C, (ii) to assess the level and risk factors for first- and second-line anti-TB drug resistance, (iii) to evaluate the performance of the GenoType®MTBDRplus and GenoType®MTBDRsl assays for drug susceptibility testing compared to the BacT/ALERT 3D system as reference method, (iv) to analyze the frequency of gene mutations associated with resistance to isoniazid (INH), rifampicin (RMP) and ethambutol (EMB) among M. tuberculosis isolates, and (v) to study the population structure and transmission dynamics of M. tuberculosis isolates from patients in Amhara region, Northwest Ethiopia. The median specimen storage time was 132 days. Of 319 specimens, 90.0% were culture positive. The length of time of sputum storage had no significant effect on the recovery rate of M. tuberculosis. Of 260 M. tuberculosis isolates, 15.8% were resistant to at least one first-line drug, 5.0% were multidrug resistant (MDR) and 3.5% were resistant to all first-line drugs. Any resistance to INH, RMP, streptomycin (STM), EMB and pyrazinamide (PZA) was 13.8%, 5.8%, 10.0%, 7.3% and 4.6%, respectively. All isolates were susceptible to second-line drugs. The GenoType®MTBDRplus assay had a sensitivity of 92% and specificity of 99% to detect INH resistance, and 100% sensitivity and specificity to detect RMP resistance and MDR. The GenoType®MTBDRsl assay had a sensitivity of 42% and specificity of 100% to detect EMB resistance. According to the molecular methods, mutations conferring resistance to INH, RMP, or EMB were detected in 13.5%, 5.8%, and 3.1% of the isolates, respectively, while mutation conferring MDR was present in 5.0% of the isolates. Of 244 M. tuberculosis isolates, 59.0% were classified as known lineages; Dehli/CAS (38.9%), Haarlem (8.6%), Ural (3.3%), LAM (3.3%), TUR (2.0%), X-type (1.2%), S-type (0.8%), Beijing (0.4%) and Uganda II (0.4%) lineage. Interestingly, 31.6% of the isolates were grouped in to four previously undefined phylogenetic lineages and were named as Ethiopia_3 (13.1%), Ethiopia_1 (7.8%), Ethiopia_H37Rv like (7.0%) and Ethiopia_2 (3.7%) lineages. The remaining 9.4% of the isolates could not be assigned to the known or new lineages. Overall, 45.1% of the isolates were grouped in clusters, indicating high rate of recent transmission. Similarly, 66.7% of MDR strains were grouped in clusters.

Includes vita. / Title from PDF of title page. / Document formatted into pages; contains 173 pages. / Thesis (Ph.D.)--University of South Florida, 2003. / Includes bibliographical references. / Text (Electronic thesis) in PDF format. / ABSTRACT: N-Methylthio beta-lactams represent a promising new family of antibacterial agents whose in vitro activity is confined largely to Staphylococcus species, including multidrug-resistant forms of S. aureus. Originally developed in the 1980's for use as synthetic intermediates, N-methylthio beta-lactams have recently been shown in these laboratories to possess intriguing biological properties which are addressed in Chapters I-IV. In terms of the antibacterial activities, the structural features and species specificities exhibited by these compounds are unlike those of any existing family of beta-lactam drugs. The lactams seem to exert their effects intracellularly, requiring passage of the bioactive species through the cellular membrane, rather than acting extracellularly on cell wall components in the manner of penicillin and related antibiotics. / ABSTRACT: The lipophilic nature of these molecules, which lack the polar side chain functionality of all other microbially-active Beta-lactams, suggests the compounds do not target the penicillin binding proteins within bacterial membranes. The most active members of this Beta-lactam class appear to be those bearing an aryl (Ar) substituent at C4 of the ring. The synthesis and structure-activity relationship of these analogues is discussed in Chapter III. Moreover, microscopy and 3H pulse-labeling studies, which are described in Chapter IV, demonstrate that N-methylthio beta-lactams appear to be inhibitors of protein biosynthesis. / System requirements: World Wide Web browser and PDF reader. / Mode of access: World Wide Web.

Thesis (Ph.D.)--University of Wollongong, 2009. / Typescript. Includes bibliographical references: leaf 188-214.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2009. / Härtill 6 uppsatser.

Thesis (Ph.D.)--University of Alberta, 2010. / A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Doctor of Philosophy, Medical Sciences - Medical Genetics. Title from pdf file main screen (viewed on March 19, 2010). Includes bibliographical references.

Thesis (Ph. D.)--University of Missouri-Columbia, 2000. / Typescript. Vita. Includes bibliographical references (leaves 185-226). Also available on the Internet.

Thesis (Ph. D.)--University of Missouri-Columbia, 2000. / Typescript. Vita. Includes bibliographical references (leaves 185-226). Also available on the Internet.

Thesis (Ph. D.)--University of Washington, 2001. / Vita. Includes bibliographical references (leaves 92-99).

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2009. / Härtill 4 uppsatser.

In this dissertation, an exosome capturing ciliary micropillar array microfluidics is introduced and applied to evaluate the response of resistant cancer cells under nanoparticle encapsulated chemotherapy. Cancer cells are able to develop different mechanisms to resist therapeutic treatment, frequently causing chemotherapy failure. Active drug expulsion is one of the usual resisting schemes to reduce intracellular drug accumulation to a non-effective level. Evidence has suggested a potential exosomal pathway is used by multi-drug resistant (MDR) cancer cells to expel drugs. Here I study the exosomes derived from MDR cancer cells treated by nanotherapeutics aiming to establish the correlation between nanotherapeutics and exosomal pathway for drug expulsion. The outcome would boost further understanding of cancer MDR, and in turn direct the development of pharmaceutical nanoparticles to overcome MDR cancer. To effectively isolate exosomes for drug expulsion evaluation, a ciliary micropillar structure is fabricated employing microelectromechanical systems (MEMS) and metal assisted chemical etching (MACE) techniques. The ciliary micropillar is fabricated in two major steps: deep silicon etch (DSE) for pillars followed by a MACE process to etch nanowires on the pillars. The concept of using MACE as an alternative to DSE is also explored to reduce fabrication cost. With optimized parameters, it shows a comparable result to DSE. COMSOL simulation revealed that ciliated micropillars exhibited a unique advantage as a unit structure for capturing small particles in fluid flow, according to particle filtration theory. A nanowire layer with high permittivity allows fluid streamlines to pass through, and increases interaction with particle carrying fluid to increase the probability of particle interception. Nanowires on the pillar can trap specific sized particles due to their characteristic dimension. Thanks to the weaker stability of porous silicon nanowires, trapped particles can then be released by dissolving these nanowires without damage to the particles themselves. A microfluidic chip is fabricated with an optimized circular micropillar arrangement for resistance reduction, and its particle filtration performance is demonstrated by processing model cell culture medium. The device is applied to study MDR cells’ response to micelle encapsulated paclitaxel treatment. Cell culture medium from sensitive and MDR variant of MDA-MB-231 cells treated with pure and capsulated drugs are processed through the device for exosome isolation. Drug volume in collected exosomes is determined after measurement. By measuring drug efflux through exosomes, it is determined that MDA-MB-231MDR cells do use an exosomal pathway to expel drugs, but other mechanisms are also at play. Nanoparticle encapsulation results in higher drug concentration in exosomes partly because the origin of exosomes and nanoparticle intake through endocytosis share some similar route. / text