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
In this paper we use Bernstein polynomials for deriving the modified Simpson's 3/8 , and the composite modified Simpson's 3/8 to solve one dimensional linear Volterra integral equations of the second kind , and we find that the solution computed by this procedure is very close to exact solution.
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In this paper, we introduce an exponential of an operator defined on a Hilbert space H, and we study its properties and find some of properties of T inherited to exponential operator, so we study the spectrum of exponential operator e^T according to the operator T.
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The interplay of species in a polluted environment is one of the most critical aspects of the ecosystem. This paper explores the dynamics of the two-species Lokta–Volterra competition model. According to the type I functional response, one species is affected by environmental pollution. Whilst the other degrades the toxin according to the type II functional response. All equilibrium points of the system are located, with their local and global stability being assessed. A numerical simulation examination is carried out to confirm the theoretical results. These results illustrate that competition and pollution can significantly change the coexistence and extinction of each species.
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Media is one of the main and effective factors; and it is a tool of crisis management equipment. Media is one of the most dangerous, effective and decisive weapons in modern conflicts; a tool for making events and influencing their events and trends as a means of reporting as the enormous capabilities of media which help media to move very quickly, and cross borders; and overcome obstacles, through many means of audio, reading and visual. As its ability, moreover, to influence the psychological and intellectual control of communities, and behaviors.
Intelligent media is, then, used in crises management and coverage. Crises have been existed with the presence of man on Earth. Thei
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This paper proposes a new method to tune a fractional order PID controller. This method utilizes both the analytic and numeric approach to determine the controller parameters. The control design specifications that must be achieved by the control system are gain crossover frequency, phase margin, and peak magnitude at the resonant frequency, where the latter is a new design specification suggested by this paper. These specifications results in three equations in five unknown variables. Assuming that certain relations exist between two variables and discretizing one of them, a performance index can be evaluated and the optimal controller parameters that minimize this performance index are selected. As a case study, a third order linear time
... Show MoreFallacies are incorrect reasoning that make an argument seem less logically credible and easier to be identified as unsound. They are widespread; individuals commit them while engaging in various activities, including at work, at home, while creating advertisements, and in the media. This study aims to investigate the rhetorical strategies accompanied with producing the fallacious arguments selected from the American Film “12 Angry Men (1957)”. The study adopts Damer’s (2009) model for the identification of fallacy. As for rhetorical analysis, the study adopts Aristotle’s triangle of rhetoric and McGuigan’s (2007) taxonomy of rhetorical devices. The results uncover that the most violated criteria are relevance, acceptabili
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Assimilation is defined ,by many phoneticians like Schane ,Roach ,and many others, as a phonological process when there is a change of one sound into another because of neighboring sounds.This study investigates the phoneme assimilation as a phonological process in English and Arabic and it is concerned specifically with the differences and similarities in both languages. Actually ,this study reflects the different terms which are used in Arabic to refer to this phenomenon and in this way it shows whether the term 'assimilation ' can have the same meaning of 'idgham' in Arabic or not . Besides, in Arabic , this phenomenon is discussed from&nb
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This paper proposes a new method to tune a fractional order PID controller. This method utilizes both the analytic and numeric approach to determine the controller parameters. The control design specifications that must be achieved by the control system are gain crossover frequency, phase margin, and peak magnitude at the resonant frequency, where the latter is a new design specification suggested by this paper. These specifications results in three equations in five unknown variables. Assuming that certain relations exist between two variables and discretizing one of them, a performance index can be evaluated and the optimal controller parameters that minimize this performance index are selected. As a case study, a thir
... Show MoreAbstract Lateral Epicondylitis (LE) which has been referred to as the Tennis Elbow as well is a lesion affecting common tendinous origins of wrist extensors due to chronic overuse injury that results in damaging common extensor tendons which join forearm extensor muscles to humerus. The aim of the present evidence-based clinical statement is reviewing scientific evidences for efficacy of a variety of the rehabilitation methods, chronic lateral epicondylitis management. It is focused upon treating chronic lateral epicondylitis and the latest developments in physiotherapy area for managing chronic lateral epicondylitis. Due to the fact that primary physical impairments in the LE are decreased is the strength of the grip, fundamentally due to
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