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
Finding communities of connected individuals in complex networks is challenging, yet crucial for understanding different real-world societies and their interactions. Recently attention has turned to discover the dynamics of such communities. However, detecting accurate community structures that evolve over time adds additional challenges. Almost all the state-of-the-art algorithms are designed based on seemingly the same principle while treating the problem as a coupled optimization model to simultaneously identify community structures and their evolution over time. Unlike all these studies, the current work aims to individually consider this three measures, i.e. intra-community score, inter-community score, and evolution of community over
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In this research, the multi-period probabilistic inventory model will be applied to the stores of raw materials used in the leather industry at the General Company for Leather Industries. The raw materials are:Natural leather includes cowhide, whether imported or local, buffalo leather, lamb leather, goat skin, chamois (raw materials made from natural leather), polished leather (raw materials made from natural leather), artificial leather (skai), supplements which include: (cuffs - Clocks - hands - pockets), and threads.This model was built after testing and determining the distribution of demand during the supply period (waiting period) for each material and completely independently from the rest of the materials, as none of the above mate
... Show MoreThe services provided by the municipal institutions of the basic things needed by the man in his daily life and the evolution of cities basically depends on these services and therefore has paid most of the world's attention to this vital facility and give him the biggest concern for the welfare of the citizens, as is the research problem that there is no program scrutiny to evaluate the performance of municipal institutions contribute to measuring the efficiency and effectiveness of the services provided and was based on research on the premise that the preparation of the existence of audit program to evaluate the performance of municipal institutions contribute to measuring the efficiency and effectiveness of services provided has reac
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In this paper an estimator of reliability function for the pareto dist. Of the first kind has been derived and then a simulation approach by Monte-Calro method was made to compare the Bayers estimator of reliability function and the maximum likelihood estimator for this function. It has been found that the Bayes. estimator was better than maximum likelihood estimator for all sample sizes using Integral mean square error(IMSE).
When writing a text, such as a newspaper article, various types of discourse markers are frequently used to group sentences into paragraphs and parts in order to establish a discourse with certain functions, such as coordination, orientation, emphasizing the concepts presented, etc. It should also be noted that this type of mark exists in both written and spoken language. Therefore, it is convenient to dedicate a chapter to these linguistic elements to clarify their use and their classification, which is mainly based on Jose Portolés (2001), as well as the main features, specifically their features (prosodic, morphological, semantic and pragmatic).
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The research specified with study the relation between the market share for the sample research banks and the amount of the achieved revenues from the investment, where the dominated belief that there potentiality enhancing the revenue on investment with the increase of the banks shares in their markets after their success in achieving rates of successive growth in their sales of sales and to a suitable achieve market coverage for their products and they have dissemination and suitable promotion activity, the market share represented the competition for the banks, and the markets pay attention to the market share as a strategic objective and to maintain them also increasi
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This study aim to identify the concept of web based information systems since its one of the important topics that is usually omitted by our organizations, in addition to, designing a web based information system in order to manage the customers data of Al- Rasheed bank, as a unified information system that is specialized to the banking deals of the customers with the bank, and providing a suggested model to apply the virtual private network as a tool that is to protect the transmitted data through the web based information system.
This study is considered important because it deals with one of the vital topics nowadays, namely: how to make it possible to use a distributed informat
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Background: Glass ionomer restorations are widely employed in the field of pediatric dentistry. There is a constant demand for a durable restoration that remains functional until exfoliation. This study aimed to measure and compare the effect of a novel coating material (EQUIA Forte Coat) on the microleakage of glass hybrid restoration (EQUIA Forte HT) in primary teeth. Material and method: Thirty cavitated (class-II) primary molars were allocated randomly into two groups based on the coat application; uncoated (control) and coated group (experimental). Cavities were prepared by the use of a ceramic bur (CeraBur) and restored with EQUIA Forte HT with or without applying a protective coat (EQUIA Forte Coat). Samples went through the therm
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Background: Glass ionomer restorations are widely employed in the field of pediatric dentistry. There is a constant demand for a durable restoration that remains functional until exfoliation. This study aimed to measure and compare the effect of a novel coating material (EQUIA Forte Coat) on the microleakage of glass hybrid restoration (EQUIA Forte HT) in primary teeth. Material and method: Thirty cavitated (class-II) primary molars were allocated randomly into two groups based on the coat application; uncoated (control) and coated group (experimental). Cavities were prepared by the use of a ceramic bur (CeraBur) and restored with EQUIA Forte HT with or without applying a protective coat (EQUIA Forte Coat). Samples went through the
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