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
Extractive multi-document text summarization – a summarization with the aim of removing redundant information in a document collection while preserving its salient sentences – has recently enjoyed a large interest in proposing automatic models. This paper proposes an extractive multi-document text summarization model based on genetic algorithm (GA). First, the problem is modeled as a discrete optimization problem and a specific fitness function is designed to effectively cope with the proposed model. Then, a binary-encoded representation together with a heuristic mutation and a local repair operators are proposed to characterize the adopted GA. Experiments are applied to ten topics from Document Understanding Conference DUC2002 datas
... Show MoreIn this paper, we construct a new mathematical system as Multiplicative Cyclic Group (MCG), called a New Digital Algebraic Generator (NDAG) Unit, which would generate digital sequences with good statistical properties. This new Unit can be considered as a new basic unit of stream ciphers.
A (NDAG) system can be constructed from collection of (NDAG) units using a Boolean function as a combining function of the system. This system could be used in cryptography as like as Linear Feedback Shift Register (LFSR) unit. This unit is basic component of a stream cipher system.
A study on solvent extraction of Tellurium with Anthranilic acid in
water has been made. The effect of different parameters such as type of medium, time of equilibration, concentration of metal ion, solvent polarity and effect of anions and catins distribution ratio of tellrim (IV) were evaluated. The stoichometric ratio of the extracted species is determined by using two methods suh as slope analysis and mole ratio method and found to be (M: L) (1:4). The instability constant of complex was calculated as well.
In this study, a new theoretical method for the estimation of absorption and fluorescence spectra is accomplished. These estimations were established following experimental measurements of absorption and fluorescence spectra for the solutions of fluorescein laser dye mixed with titanium dioxide (TiO2) nanoparticles
in distilled water. The used concentration of fluorescein dye was 1x10-5 M, whereas the masses of titanium dioxide nanoparticles were 0.0003g, 0.0005g, 0.001g and 0.002g. An absorption spectra improvement was observed upon raising the mass of TiO2 nanoparticles, which specifies that doping the fluorescein dye with TiO2 nanoparticles have an essential influence on the dye absorption spectra. On the other side, all fluorescen
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The research is summarized in the construction of a mathematical model using the most common methods in the science of Operations Research, which are the models of transportation and linear programming to find the best solution to the problem of the high cost of hajj in Iraq, and this is done by reaching the optimum number of pilgrims traveling through both land ports and the number Ideal for passengers traveling through airports by Iraqi Airways, instead of relying on the personal experience of the decision-maker in Hajj and Umrah Authority by identifying the best port for pilgrim's travel, which can tolerate right or wrong, has been based on scientific methods of Operations Research, the researcher built two mathematical models
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In this paper, a compact genetic algorithm (CGA) is enhanced by integrating its selection strategy with a steepest descent algorithm (SDA) as a local search method to give I-CGA-SDA. This system is an attempt to avoid the large CPU time and computational complexity of the standard genetic algorithm. Here, CGA dramatically reduces the number of bits required to store the population and has a faster convergence. Consequently, this integrated system is used to optimize the maximum likelihood function lnL(φ1, θ1) of the mixed model. Simulation results based on MSE were compared with those obtained from the SDA and showed that the hybrid genetic algorithm (HGA) and I-CGA-SDA can give a good estimator of (φ1, θ1) for the ARMA(1,1) model. Anot
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A total of 1346 hard ticks (863♂ and 483 ♀) infested 104 camels, 60 alive camels with 93.33% infestation rate and 44 carcasses of camels had 79.54% infestation rate The total infestation rate was 87.5 %. The current study results revealed ten species of hard ticks family Ixodidae Koch, 1844 related to genus Hyalomma as following: H. dromedarii Koch, 1844, H. schulzii Morel, 1969, H. turanicum Pomerantsev, 1946, H. excavatum Koch, 1844, H. truncatum Koch, 1844, H. scupense Schulzii, 1919, H. marginatum Koch, 1844, H. anatolicum Koch, 1844, H. rufipes Koch, 1844, H. impeltatum Schulze & Schlottke, 1930 from camel Camelus dromedarius Linnaeus, 1758 collected from 21 regions belonging to six provinces in middle, w
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This study includes synthesis of some nitrogenous heterocyclic compounds linked to amino acid esters or heterocyclic amines that may have a potential activity as antimicrobial and/or cytotoxic. Quinolines are an important group of organic compounds that possess useful biological activity as antibacterial, antifungal and antitumor .8-Hydroxyquinoline (8-HQ) and numerous of its derivatives exhibit potent activities against fungi and bacteria which make them good candidates for the treatment of many parasitic and microbial infection diseases.
These pharmacological properties of quinolones aroused our interest in synthesizing several new compounds featuring heterocyclic rings of the quinoline derivatives linke
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