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 paper generates a geological model of a giant Middle East oil reservoir, the model constructed based on the field data of 161 wells. The main aim of the paper was to recognize the value of the reservoir to investigate the feasibility of working on the reservoir modeling prior to the final decision of the investment for further development of this oilfield. Well log, deviation survey, 2D/3D interpreted seismic structural maps, facies, and core test were utilized to construct the developed geological model based on comprehensive interpretation and correlation processes using the PETREL platform. The geological model mainly aims to estimate stock-tank oil initially in place of the reservoir. In addition, three scenarios were applie
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Churning of employees from organizations is a serious problem. Turnover or churn of employees within an organization needs to be solved since it has negative impact on the organization. Manual detection of employee churn is quite difficult, so machine learning (ML) algorithms have been frequently used for employee churn detection as well as employee categorization according to turnover. Using Machine learning, only one study looks into the categorization of employees up to date. A novel multi-criterion decision-making approach (MCDM) coupled with DE-PARETO principle has been proposed to categorize employees. This is referred to as SNEC scheme. An AHP-TOPSIS DE-PARETO PRINCIPLE model (AHPTOPDE) has been designed that uses 2-stage MCDM s
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Somerset Maugham is known mainly as a novelist . This paper presents Maugham the dramatist . Many critics have found him a promising dramatist . He has written 30 plays , then he turns his back upon the theater and writes his autobiographical and most successful novel Of Human Bondage ( 1915) .
Maugham's writing is clear , precise , and simple . He is described as a realist who is keenly aware of human nature , its concentration and frustration . His only tragedy A Man of Honour is a play in 4 acts . This paper concentrates mainly on this play to show Maugham as a dramatist and to show his concept of " honour " .
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... Show MoreSkin drug administration is the method used to provide drugs for local or systemic therapy, which is recognized for clinical usage. It is the third-largest method of medication delivery, after only intravenous administration and oral administration. Using a transdermal delivery method makes the administration easy, and blood concentration and adverse effects can be reduced. A microneedle is a micron-sized needle with a short height of no more than 500 micrometers and a width of no more than 50 micrometers. The needle comes into contact with the epidermal layer of the skin before it gets to the dermal layer, where there is no discomfort. Several materials, such as metals, inorganic, and polymer materials, are used to create microneed
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Purpose - This study relies on the descriptive and analytical approach through collecting and analyzing the necessary data, as this approach focuses on polling the opinions of the research sample and its directions, and aims to develop a model that studies the relationship between knowledge creation and organizational ambidexterity in Iraqi private banks and verifying its validity experimentally.
Design / Methodology / Introduction - A survey was conducted through a questionnaire form to collect data from a sample of (113) managers in private commercial banks. In addition, this study used the AMOS program and the ready-to-use statistical program package (SPSS V.25) to test the proposed hypotheses of the t
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Abstract
This research deals will the declared production planning operation in the general company of planting oils, which have great role in production operations management who had built mathematical model for correct non-linear programming according to discounting operation during raw materials or half-made materials purchasing operation which concentration of six main products by company but discount included just three products of raw materials, and there were six months taken from the 1st half of 2014 as a planning period has been chosen . Simulated annealing algorithm application on non-linear model which been more difficulty than possible solution when imposed restric
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This study aims at suggesting flow as a strategy for training female EFL student-teachers in the teaching training course and finding out the effect of this strategy on their performance and their flow state. The training course syllabuses will be constructed according to the flow nine factors and the teaching skills. The measurement tools are the student-teacher performance checklist that has already been used by the department of English language and SHORT Flow State Scale (S FSS-2). The study population is represented with the (60) female student-teachers/ fourth stage/ evening studies at theEnglish department /college of education for women/the University of Baghdad. The study is used the experimental design in that (30) of the student-
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