Saudi Cultural Missions Theses & Dissertations
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Item Restricted Antifungal tolerance in clinical isolates during the development of drug resistance(University of Birmingham, 2024-08-27) Alnafisi, Bassam; Ji Tsai, HungThe increasing prevalence of fungal diseases, particularly those caused by Candida albicans, presents a significant challenges for healthcare due to the rising number of immunocompromised individuals. C. albicans, an opportunistic pathogen, often transitions from a harmless commensal organism to a virulent pathogen under conditions of immune suppression, leading to a spectrum of infections from superficial to life-threatening systemic diseases. Despite advancements in antifungal therapies, infections caused by C. albicans remain associated with high mortality rates, highlighting the organism's complex mechanisms for evading host immune responses and developing drug resistance. This study investigates the evolution of drug tolerance and resistance in C. albicans clinical isolates, particularly in the context of fluconazole treatment. The research focuses on understanding the role of aneuploidy, heat shock response, and subpopulation dynamics in the development of tolerance. Through a series of experiments involving clinical isolates, the study tracks how C. albicans adapts over time in response to antifungal treatment. The results indicate that tolerance mechanisms are more pronounced at 37°C, a temperature reflective of the human body, underscoring the importance of thermal adaptation in the pathogenicity of C. albicans. Additionally, C. albicans clinical isolates exhibit tolerance in both broth and agar plate assays, a phenomenon attributed to a combination of specific genotypic and phenotypic characteristics. Our data support the initial hypothesis that the drug tolerance of C. albicans varies over different time points, reflecting the fungus's adaptive response to fluconazole exposure, particularly as influenced by temperature and subpopulation dynamics.44 0Item Restricted GaAs-Based Integration Photonics Waveguides and Splitting Elements(Cardiff University, 2023-05-07) AlBiladi, Tahani; Smowton, Peter; Beggs, DarylWith the development of long lived, epitaxially grown InAs quantum dot lasers in GaAs on silicon, GaAs-based photonics has become a promising system for integrating large numbers of small footprint active and passive components on the same substrate. To ensure high performance of a circuit, each component or building block, needs to be individually investigated so a library of optimised components can be developed. In this thesis, several GaAs-based passive integrated photonic components are proposed and analysed by employing commercially available multi-dimensional simulation tools with the aim of understanding the performance and tolerances of the important component functions prior to the manufacturing stage. These components will be useful as basic and composite building blocks in future GaAs-on-silicon photonic integrated circuits. Deeply etched waveguides are investigated, and single mode operation is shown to be maintained under -0.1 to +0.1 micrometre variation in width, etching depth, core height and variation in wavelength between 1.2 and 1.4 micrometre, making the waveguides tolerant against typical fabrication errors. Single mode operation is also mapped as a function of core width, height and etching depth for shallow etched waveguides. Efficient tapers are optimised for the propagation of light between multimode and single mode waveguides. The tapers are tolerant of width, etching depth and wavelength changes of -0.1 to +0.1 micrometre with transmission higher than 98%. Two compact splitters: multimode interferometer, MMI, and Y-branch are optimised at 1.3 micrometre. The multimode interferometer has efficiency up to 99% with reduction of about 4% over spectral and geometrical changes of width, length and etching depth of -0.1 to +0.1 micrometre. An efficient Y-branch is designed with efficiency up to 94% with less stability, compared to the multimode interferometer, against variations like etching depth and wavelength. It is found that waveguides of single mode operation at 1.3 micrometre are achievable and efficient tapers and splitters can be obtained within the fabrication capabilities available in a university facility. Hence, these components are appropriate for on-chip integration.31 0