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
This paper analyses the relationship between selected macroeconomic variables and gross domestic product (GDP) in Saudi Arabia for the period 1993-2019. Specifically, it measures the effects of interest rate, oil price, inflation rate, budget deficit and money supply on the GDP of Saudi Arabia. The method employs in this paper is based on a descriptive analysis approach and ARDL model through the Bounds testing approach to cointegration. The results of the research reveal that the budget deficit, oil price and money supply have positive significant effects on GDP, while other variables have no effects on GDP and turned out to be insignificant. The findings suggest that both fiscal and monetary policies should be fo
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The research aimed at identifying the effect of using constructive learning model on academic achievement and learning soccer dribbling Skill in 2nd grade secondary school students. The researcher used the experimental method on (30) secondary school students; 10 selected for pilot study, 20 were divided into two groups. The experimental group followed constructive learning model while the controlling group followed the traditional method. The experimental program lasted for eight weeks with two teaching sessions per week for each group. The data was collected and treated using SPSS to conclude the positive effect of using constructive learning model on developing academic achievement and learning soccer dribbling Skill in 2nd grade seconda
... Show MoreThe issue of penalized regression model has received considerable critical attention to variable selection. It plays an essential role in dealing with high dimensional data. Arctangent denoted by the Atan penalty has been used in both estimation and variable selection as an efficient method recently. However, the Atan penalty is very sensitive to outliers in response to variables or heavy-tailed error distribution. While the least absolute deviation is a good method to get robustness in regression estimation. The specific objective of this research is to propose a robust Atan estimator from combining these two ideas at once. Simulation experiments and real data applications show that the proposed LAD-Atan estimator
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Circular data (circular sightings) are periodic data and are measured on the unit's circle by radian or grades. They are fundamentally different from those linear data compatible with the mathematical representation of the usual linear regression model due to their cyclical nature. Circular data originate in a wide variety of fields of scientific, medical, economic and social life. One of the most important statistical methods that represents this data, and there are several methods of estimating angular regression, including teachers and non-educationalists, so the letter included the use of three models of angular regression, two of which are teaching models and one of which is a model of educators. ) (DM) (MLE) and circular shrinkage mod
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This study included the extraction properties of spatial and morphological basins studied using the Soil and Water Assessment Tool (SWAT) model linked to (GIS) to find the amount of sediment and rates of flow that flows into the Haditha reservoir . The aim of this study is determine the amount of sediment coming from the valleys and flowing into the Haditha Dam reservoir for 25 years ago for the period (1985-2010) and its impact on design lifetime of the Haditha Dam reservoir and to determine the best ways to reduce the sediment transport. The result indicated that total amount of sediment coming from all valleys about (2.56 * 106 ton). The maximum annual total sediment load was about (488.22 * 103 ton) in year 1988
... Show MoreTo damp the low-frequency oscillations which occurred due to the disturbances in the electrical power system, the generators are equipped with Power System Stabilizer (PSS) that provide supplementary feedback stabilizing signals. The low-frequency oscillations in power system are classified as local mode oscillations, intra-area mode oscillation, and interarea mode oscillations. Double input multiband Power system stabilizers (PSSs) were used to damp out low-frequency oscillations in power system. Among dual-input PSSs, PSS4B offers superior transient performance. Power system simulator for engineering (PSS/E) software was adopted to test and evaluate the dynamic performance of PSS4B model on Iraqi national grid. The res
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Geologic modeling is the art of constructing a structural and stratigraphic model of a reservoir from analyses and interpretations of seismic data, log data, core data, etc. [1].
A static reservoir model typically involves four main stages, these stages are Structural modeling, Stratigraphic modeling, Lithological modeling and Petrophysical modeling [2].
Ismail field is exploration structure, located in the north Iraq, about 55 km north-west of Kirkuk city, to the north-west of the Bai Hassan field, the distance between the Bai Hassan field and Ismael field is about one kilometer [3].
Tertiary period reservoir sequences (Main Limestone), which comprise many economica
... Show MoreTo damp the low-frequency oscillations which occurred due to the disturbances in the electrical power system, the generators are equipped with Power System Stabilizer (PSS) that provide supplementary feedback stabilizing signals. The low-frequency oscillations in power system are classified as local mode oscillations, intra-area mode oscillation, and interarea mode oscillations. Double input multiband Power system stabilizers (PSSs) were used to damp out low-frequency oscillations in power system. Among dual-input PSSs, PSS4B offers superior transient performance. Power system simulator for engineering (PSS/E) software was adopted to test and evaluate the dynamic performance of PSS4B model on Iraqi national grid. The results showed
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