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
The increasing availability of computing power in the past two decades has been use to develop new techniques for optimizing solution of estimation problem. Today's computational capacity and the widespread availability of computers have enabled development of new generation of intelligent computing techniques, such as our interest algorithm, this paper presents one of new class of stochastic search algorithm (known as Canonical Genetic' Algorithm ‘CGA’) for optimizing the maximum likelihood function strategy is composed of three main steps: recombination, mutation, and selection. The experimental design is based on simulating the CGA with different values of are compared with those of moment method. Based on MSE value obtained from bot
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Abstract
The vegetative filter strips (VFS) are a useful tool used for reducing the movement of sediment and pesticide in therivers. The filter strip’s soil can help in reducing the runoff volume by infiltration. However, the characteristics of VFS (i.e., length) are not recently identified depending on the estimation of VFS modeling performance. The aim of this research is to study these characteristics and determine acorrelation between filter strip length and percent reduction (trapping efficiency) for sediment, water, and pesticide. Two proposed pesticides(one has organic carbon sorption coefficient, Koc, of 147 L/kg which is more moveable than XXXX, and another one
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This research aims to solve a problem in the field of accounting and financial knowledge in the world today, that is, the problem of creative accounting. Especially after the global financial crisis and the collapse of many large companies in the world, people find that they use creative accounting methods to distinguish them from reality, showing the results of their activities and their financial status. This research discusses the concept of creative accounting, the most important methods used in financial statements and its relationship with external auditing, and procedures to limit accounting creativity. This study uses descriptive analysis methods after confirming its theoretical aspects in practice. Using the statistical
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Polyacrylonitrile nanofiber (PANFS), a well-known polymers, has been extensively employed in the manufacturing of carbon nanofibers (CNFS), which have recently gained substantial attention due to their excellent features, such as spinnability, environmental friendliness, and commercial feasibility. Because of their high carbon yield and versatility in tailoring the final CNFS structure, In addition to the simple formation of ladder structures through nitrile polymerization to yield stable products, CNFS and PAN have been the focus of extensive research as potential production precursors. For instance, the development of biomedical and high-performance composites has now become achievable. PAN homopolymer or PAN-based precursor copolymer can
... Show MoreTo determine the abilities of salivary E‐cadherin to differentiate between periodontal health and periodontitis and to discriminate grades of periodontitis.
E‐cadherin is the main protein responsible for maintaining the integrity of epithelial‐barrier function. Disintegration of this protein is one of the events associated with the destructive forms of periodontal disease leading to increase concentration of E‐cadherin in the oral biofluids.
A total of 63 patients with periodontitis (case) and 35
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Polyacrylonitrile nanofiber (PANFS), a well-known polymers, has been extensively employed in the manufacturing of carbon nanofibers (CNFS), which have recently gained substantial attention due to their excellent features, such as spinnability, environmental friendliness, and commercial feasibility. Because of their high carbon yield and versatility in tailoring the final CNFS structure, In addition to the simple formation of ladder structures through nitrile polymerization to yield stable products, CNFS and PAN have been the focus of extensive research as potential production precursors. For instance, the development of biomedical and high-performance composites has now become achievable. PAN homopolymer or PAN-based precursor copol
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Breast cancer constitutes about one fourth of the registered cancer cases among the Iraqi population (1)
and it is the leading cause of death among Iraqi women (2)
. Each year more women are exposed to the vicious
ramifications of this disease which include death if left unmanaged or the negative sequels that they would
experience, cosmetically and psychologically, after exposure to radical mastectomy.
The World Health Organization (WHO) documented that early detection and screening, when coped
with adequate therapy, could offer a reduction in breast cancer mortality; displaying that the low survival rates
in less developed countries, including Iraq, is mainly attributed to the lack of early detection programs couple