Abstract Candida albicans is a commensal fungal pathogen that grows in yeast and hyphal forms in the human gut. C. albicans causes mucosal and cutaneous diseases that can result in significant mortality following systematic infections and it also exhibits drug resistance. Zebrafish have been an excellent model to investigate C. albicans infections because of their transparency and the availability of many transgenic lines. However, there is a limitation in using zebrafish as a model because the fish embryos cannot survive at 37°C therefore it is not suitable for studying Candida infections at physiological relevant human body temperature. In this thesis, the normal embryonic development of Arabian killifish (A. dispar) is investigated, revealing that embryogenesis was divided into 32 stages based on diagnostic patterns of development. A. dispar can also found to tolerate a wide range of temperatures and salinities. This suggests that A. dispar could be developed as a novel model to investigate host-pathogen interactions. The tolerance of A. dispar to high temperatures may in part be attributable to brown pigment cells with a highly fluorescent character that may have developed to allow the fish to adapt to live within extreme environmental conditions with strong sunlight and a wide range of temperatures (Chapter 3). In terms of Candida infections, this study examined A. dispar as a model to test C. albicans pathogenicity. The survival of A. dispar embryos following Candida infection showed a dose dependent relationship. We also found that A. dispar can survive longer than zebrafish after infection. Furthermore, C. albicans cells were observed to undergo a transition from yeast to hyphae at 37°C. An investigation of the ability of mutant strains of C. albicans with defects in cell wall mannosylation revealed a significant impact on virulence, host mortality, and the fishes’ immune response. The present study found that although the deletion of O- and N-mannan from the cell wall of C. albicans, affected fungal burden (attenuation), and the survival of the infected embryos per se was significantly decreased in the infections of the mutant strains compared to the WT. This data confirms the importance of the mannosylation state of the cell wall in triggering an immune recognition event (Chapter 4). A. dispar is also shown to be suitable for studying the effectiveness of 3 | P a g e antifungals. Fluconazole treatment of infected embryos and eggs promoted greater rates of survival at high doses, alongside a significant reduction of C. albicans CFUs (Chapter 4). When looking at the Candida-host interaction, we directly observed phagocytosed yeast cells within macrophages. Various detection methods were used to follow macrophages and neutrophils including Western blotting, immunostaining and histological staining (Sudan black and FITC-tyramide) allowing the monitoring of the time course of the immune cells. A biphasic response of macrophages was detected by L-plastin Western blotting, suggesting activation of two different type of macrophage: activated macrophage (M1) and alternative macrophage (M2). We also assayed reactive oxygen species (ROS) within infected embryos using a fluorescent probe (H2DCFDA), revealing the accumulation of the fluorescent probe at the sites of infection. Quantitative and qualitative analyses of the oxidative and immune response using the H2DCFDA and qPCR were also accomplished within A. dispar embryos after infection with both the WT and mutant strains of Candida albicans (WT, pmr1∆, mnt1-mnt2∆, and och1∆). The results confirmed that the mutant strains did not activate a host oxidative stress response nor immune cell accumulation when compared to WT, suggesting that the immune response is less activated against these mutants. Finally, a new transgenic line of A. dispar fish was developed using Betaactin-DsR-LoxP-GFP. The new transgenic A. dispar is suggested to be an ideal model for real time observation of host-pathogen interactions and for investigation of molecular functions of the immune response. Overall these results improve our understanding of the use of a new transparent fish model to study fungal pathogenesis and demonstrates the potential advantages of using this species in future studies of bacterial, fungal and viral pathogens at a physiologically relevant temperature for human infection. Such a model could lead us to investigate in more depth the key interactions between pathogens and their host and permit the screening and development of new antifungal therapies (that might target the pathogens directly or target the host immune system). View full metadata
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Construction projects are characterized as projects with multi phases and activities, complex, unique, and have many different parties and stakeholders. Risks could appear at one or more of the construction project stages and may affect the achievement of project objectives. Therefore, one of the key elements in the planning phase of any project is the risk management process (RMP). This study attempts to understand the terminology of risk in general, risk management, and response to risk in particular. This study is mainly a review of thirty-eight studies that have been published between 1997 and 2020 that demonstrate the importance of the crucial phase of risk response from the risk management process and its impact on
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Fiber-to-the-Home (FTTH) has long been recognized as a technology that provides future proof bandwidth [1], but has generally been too expensive to implement on a wide scale. However, reductions in the cost of electro-optic components and improvements in the handling of fiber optics now make FTTH a cost effective solution in many situations. The transition to FTTH in the access network is also a benefit for both consumers and service providers because it opens up the near limitless capacity of the core long-haul network to the local user. In this paper individual passive optical components, transceivers, and fibers has been put together to form a complete FTTH network. Then the implementation of the under construction Baghdad/Al
... Show MoreThe lack of active 2019 coronavirus disease (COVID-19) pandemic treatment creates a challenge for researchers and scientists to find the most appropriate treatment for this disease. Dexamethasone, according to the findings of the RECOVERY clinical trial, declared mid-June 2020 in print media was one of those therapies. Although the results from retrospective studies are not strongly supportive of corticosteroid routine use in COVID-19 despite the signals for some benefits, the dedicated RECOVERY trial found a significant reduction in death with dexamethasone only in severe cases on a ventilator or moderate cases on supplemental oxygen therapy nevertheless, no benefit observed in mild to moderate cases requiring no oxygen. More studi
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BACKGROUND: Coronavirus current pandemic (COVID-19) is the striking subject worldwide hitting countries in an unexplained non-universal pattern. Bacillus Calmette–Guérin (BCG) vaccine was an adopted recent justification depending on its non-specific immune activation properties. Still the problem of post-vaccine short duration of protection needs to be solved. The same protective mechanism was identified in active or latent tuberculosis (TB). For each single patient of active TB, there are about nine cases of asymptomatic latent TB apparently normal individuals living within the community without restrictions carrying benefits of immune activation and involved in re-infection cycles in an excellent example of repeated immunity tr
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Genetic algorithms (GA) are a helpful instrument for planning and controlling the activities of a project. It is based on the technique of survival of the fittest and natural selection. GA has been used in different sectors of construction and building however that is rarely documented. This research aimed to examine the utilisation of genetic algorithms in construction project management. For this purpose, the research focused on the benefits and challenges of genetic algorithms, and the extent to which genetic algorithms is utilised in construction project management. Results showed that GA provides an ability of generating near optimal solutions which can be adopted to reduce complexity in project management and resolve difficult problem
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