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
Mixed-effects conditional logistic regression is evidently more effective in the study of qualitative differences in longitudinal pollution data as well as their implications on heterogeneous subgroups. This study seeks that conditional logistic regression is a robust evaluation method for environmental studies, thru the analysis of environment pollution as a function of oil production and environmental factors. Consequently, it has been established theoretically that the primary objective of model selection in this research is to identify the candidate model that is optimal for the conditional design. The candidate model should achieve generalizability, goodness-of-fit, parsimony and establish equilibrium between bias and variab
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تسعى تركيا ضمن سياساتها المائية ومنذ زمن بعيد وبأصرار على تنفيذ المزيد من بناء السدود والمشاريع التخزينية المائية على حوضي دجلة والفرات، الامر الذي يؤدي بالضرورة الى تناقص معدل الواردات المائية لنهري دجلة والفرات الداخلة للاراضي العراقية .وبالتالي التأثير على مقومات التنمية الزراعية العربية بشكل عام والتنمية الزراعية بالعراق بشكل خاص ومن ثم تهديد الامن الغذائي الوطني.
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The optimal combination of aluminum quality, sufficient strength, high stress to weight ratio and clean finish make it a good choice in driveshafts fabrication. This study has been devoted to experimentally investigate the effect of applying laser shock peening (LSP) on the fatigue performance for 6061-T6 aluminum alloy rotary shafts. Q-switched pulsed Nd:YAG laser was used with operating parameters of 500 mJ and 600 mJ pulse energies, 12 ns pulse duration and 10 Hz pulse repetition rate. The LSP is applied at the waist of the prepared samples for the cyclic fatigue test. The results show that applying 500 mJ pulse energy yields a noticeable effect on enhancing the fatigue strength by increasing the required number of cycles to fracture the
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The media guide is a small-sized printed medium, whose importance is highlighted through the specific information it carriesThe task of the guide lies in the clarity of these indications and making a positive impact on the recipient with understanding so it is a means for the purpose of reaching the effect and effectiveness of the message symbols from the movements of lines in which elements that are supposed to be equal in the performance of their functions and the purpose of their existence gather to achieve the mental response of perception, understanding and enjoyment. It must be in an objective unity based on the balance in this distribution. To form a formal organizational unit and an integrated system, the result of which is to gi
... Show MoreIn front of the serious deterioration of the elements of the environment, new convictions arose the need to integrate into the global environmental concerns as being one and the issue of shared responsibility and the impact of this conviction, the evolution of the environment protection law in many countries, including Algeria. Due to the multiplicity of perceptions about the environmental result of multiple scientific disciplines, the legislative concept emerged to protect the environment, which includes prevention and rational management and conservation and restoration and repair.
Environmental planning for the various governments and countries aims to avert disasters and achieve the
... Show MoreIn this paper, the density of state (DOS) at Fe metal contact to Titanium dioxide semiconductor (TiO2) has been studied and investigated using quantum consideration approaches. The study and calculations of (DOS) depended on the orientation and driving energies. was a function of TiO2 and Fe materials' refractive index and dielectric constant. Attention has focused on the effect of on the characteristic of (DOS), which increased with the increasing of refractive index and dielectric constant of Fe metal and vice versa. The results of (DOS) and its relation with and values of system have been discussed. As for contact system is increased, (DOS) values increased at first, but the relation is disturbed later and transforms into an inve
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LED is an ultra-lightweight block cipher that is mainly used in devices with limited resources. Currently, the software and hardware structure of this cipher utilize a complex logic operation to generate a sequence of random numbers called round constant and this causes the algorithm to slow down and record low throughput. To improve the speed and throughput of the original algorithm, the Fast Lightweight Encryption Device (FLED) has been proposed in this paper. The key size of the currently existing LED algorithm is in 64-bit & 128-bit but this article focused mainly on the 64-bit key (block size=64-bit). In the proposed FLED design, complex operations have been replaced by LFSR left feedback technology to make the algorithm perform more e
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In this work, plasma parameters such as, the electron temperature )Te(, electron density ne, plasma frequency )fp(, Debye length )λD(
and Debye number )ND), have been studied using optical emission spectroscopy technique. The spectrum of plasma with different values of energy, Pb doped CuO at different percentage (X=0.6, 0.7, 0.8) were recorded. The spectroscopic study for these mixing under vacuum with pressure down to P=2.5×10-2 mbar. The results of electron temperature for X=0.6 range (1.072-1.166) eV, for X=0.7 the Te range (1.024-0.855) eV and X=0.8 the Te is (1.033-0.921) eV. Optical properties of CuO:Pb thin films were determined through the optical transmission method using ultraviolet visible spectrophotometer within the ra
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3D models delivered from digital photogrammetric techniques have massively increased and developed to meet the requirements of many applications. The reliability of these models is basically dependent on the data processing cycle and the adopted tool solution in addition to data quality. Agisoft PhotoScan is a professional image-based 3D modelling software, which seeks to create orderly, precise n 3D content from fixed images. It works with arbitrary images those qualified in both controlled and uncontrolled conditions. Following the recommendations of many users all around the globe, Agisoft PhotoScan, has become an important source to generate precise 3D data for different applications. How reliable is this data for accurate 3D mo
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