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
Wellbore instability is one of the most common issues encountered during drilling operations. This problem becomes enormous when drilling deep wells that are passing through many different formations. The purpose of this study is to evaluate wellbore failure criteria by constructing a one-dimensional mechanical earth model (1D-MEM) that will help to predict a safe mud-weight window for deep wells. An integrated log measurement has been used to compute MEM components for nine formations along the studied well. Repeated formation pressure and laboratory core testing are used to validate the calculated results. The prediction of mud weight along the nine studied formations shows that for Ahmadi, Nahr Umr, Shuaiba, and Zubair formations
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The effects of three different additives formulations namely Lubrizol 21001, HiTEC 8722B and HiTEC 340 on the efficiency of VII namely OCP of three base lubricating oils namely 40 stock and 60 stock and 150 stock at four temperatures 40, 60, 80 and 100oC were investigated. The efficiency of OCP is decreased when blended with 4 and 8 wt% of Lubrizol 21001 for all the three base oil types. But it is increased when adding 4 wt% and 8 wt% of H-8722B in 40 stock. While for 60 stock and 150 stock the OCP efficiency decreased by adding 4 and 8 wt% of H-8722B. In the other hand, it is decreased with a high percentage by adding 4 and 8 wt% of H-340 for 60 stock and 150 stock and for 40 stock it is increased by adding 4 wt% of H-340 and decreased
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The purpose of current study is to analyze the computer textbooks content for intermediate stage in Iraq according to the theory of multiple intelligence. By answering the following question “what is the percentage of availability of multiple intelligence in the content of the computer textbooks on intermediate stage (grade I, II) for the academic year (2017-2018)? The researcher followed the descriptive analytical research approach (content analysis), and adopted an explicit idea for registration. The research tool was prepared according the Gardner’s classification of multiple intelligence. It has proven validity and reliability. The study found the percentage of multiple intelligence in the content of computer textbooks for the in
... Show MoreIn order to promote sustainable steel-concrete composite structures, special shear connectors that can facilitate deconstruction are needed. A lockbolt demountable shear connector (LB-DSC), including a grout-filled steel tube embedded in the concrete slab and fastened to a geometrically compatible partial-thread bolt, which is bolted on the steel section's top flange of a composite beam, was proposed. The main drawback of previous similar demountable bolts is the sudden slip of the bolt inside its hole. This bolt has a locked conical seat lug that is secured inside a predrilled compatible counter-sunk hole in the steel section's flange to provide a non-slip bolt-flange connection. Deconstruction is achieved by demounting the tube from the t
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Due to severe scouring, many bridges failed worldwide. Therefore, the safety of the existing bridge (after contrition) mainly depends on the continuous monitoring of local scour at the substructure. However, the bridge's safety before construction mainly depends on the consideration of local scour estimation at the bridge substructure. Estimating the local scour at the bridge piers is usually done using the available formulae. Almost all the formulae used in estimating local scour at the bridge piers were derived from laboratory data. It is essential to test the performance of proposed local scour formulae using field data. In this study, the performance of selected bridge scours estimation formulae was validated and sta
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The consumption of fossil fuels has caused many challenges, including environmental and climate damage, global warming, and rising energy costs, which has prompted seeking to substitute other alternative sources. The current study explored the microwave pyrolysis of Albizia branches to assess its potential to produce all forms of fuel (solid, liquid, gas), time savings, and effective thermal heat transfer. The impact of the critical parameters on the quantity and quality of the biofuel generation, including time, power levels, biomass weight, and particle size, were investigated. The results revealed that the best bio-oil production was 76% at a power level of 450 W and 20 g of biomass. Additionally, low power levels led to enhanced
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Background: One of the most prevalent procedures in oral surgery is the removal of impacted mandibular third molars, typically accompanied by trismus, edema, and pain. Several methods and biomaterials were implemented to mitigate or avoid these surgical problems. Objectives: To evaluate the efficiency of chlorhexidine gel (WISDOM®) in minimizing postoperative sequelae associated with the impacted mandibular third molar that will be surgically extracted and its role in promoting early soft tissue closure of the surgical site. Methods: The study design was a double-masked and randomized, controlled clinical study that included healthy patients needing the removal of a mandibular third molar through surgery. The participants were rand
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Discussion dealt with the independent factors critical such us success factors and the risk management process, and dependent factor of the general competitive strategies, and began searching the dilemma of thought, as crystallized his problem in the light of the need for organizations to philosophy and deeper vision of a more comprehensive understanding of the concept of risk management, assessment and management to maximize the competitive strategies of public, and on this basis, Search queries formulated problem of the gap between the knowledge-based intellectual propositions farcical for the purposes of interpretation of the relationship between the critical success factors and the risk
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This study examines strategies of cultural domestication in Muravyov and Kistyakovsky’s Russian translation of (The Fellowship of the Ring). It documents transformations of character names, toponyms, dialogues, and cultural references, highlighting systematic Russification and the infusion of Soviet political commentary that reshape the text into cultural rewriting.