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
S Khalifa E, AR Jamal R, N Adil A, J Munqithe M…, 2009
This research represents a practical attempt applied to calibrate and verify a hydraulic model for the Blue Nile River. The calibration procedures are performed using the observed data for a previous period and comparing them with the calibration results while verification requirements are achieved with the application of the observed data for another future period and comparing them with the verification results. The study objective covered a relationship of the river terrain with the distance between the assumed points of the dam failures along the river length. The computed model values and the observed data should conform to the theoretical analysis and the overall verification performance of the model by comparing i
... Show MoreThe electric quadrupole moments for some scandium isotopes (41, 43, 44, 45, 46, 47Sc) have been calculated using the shell model in the proton-neutron formalism. Excitations out of major shell model space were taken into account through a microscopic theory which is called core polarization effectives. The set of effective charges adopted in the theoretical calculations emerging about the core polarization effect. NushellX@MSU code was used to calculate one body density matrix (OBDM). The simple harmonic oscillator potential has been used to generate the single particle matrix elements. Our theoretical calculations for the quadrupole moments used the two types of effective interactions to obtain the best interaction compared with the exp
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Research aims to shed light on the concept of corporate failures , display and analysis the most distinctive models used to predicting corporate failure; with suggesting a model to reveal the probabilities of corporate failures which including internal and external financial and non-financial indicators, A tested is made for the research objectivity and its indicators weight and by a number of academics professionals experts, in addition to financial analysts and have concluded a set of conclusions , the most distinctive of them that failure is not considered a sudden phenomena for the company and its stakeholders , it is an Event passes through numerous stages; each have their symptoms that lead eve
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This research represents a practical attempt applied to calibrate and verify a hydraulic model for the Blue Nile River. The calibration procedures are performed using the observed data for a previous period and comparing them with the calibration results while verification requirements are achieved with the application of the observed data for another future period and comparing them with the verification results. The study objective covered a relationship of the river terrain with the distance between the assumed points of the dam failures along the river length. The computed model values and the observed data should conform to the theoretical analysis and the overall verification performance of the model by comparing it with anothe
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The study presents a mathematical model with a disaggregating approach to the problem of production planning of a fida Company; which belongs to the ministry of Industry. The study considers disaggregating the entire production into 3 productive families of (hydraulic cylinders, Aldblatt (dampers), connections hydraulics with each holds similar characteristics in terms of the installation cost, production time and stock cost. The Consequences are an ultimate use of the available production capacity as well as meeting the requirements of these families at a minimal cost using linear programming. Moreover, the study considers developing a Master production schedule that drives detailed material and production requi
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Conditional logistic regression is often used to study the relationship between event outcomes and specific prognostic factors in order to application of logistic regression and utilizing its predictive capabilities into environmental studies. This research seeks to demonstrate a novel approach of implementing conditional logistic regression in environmental research through inference methods predicated on longitudinal data. Thus, statistical analysis of longitudinal data requires methods that can properly take into account the interdependence within-subjects for the response measurements. If this correlation ignored then inferences such as statistical tests and confidence intervals can be invalid largely.
In order to obtain a mixed model with high significance and accurate alertness, it is necessary to search for the method that performs the task of selecting the most important variables to be included in the model, especially when the data under study suffers from the problem of multicollinearity as well as the problem of high dimensions. The research aims to compare some methods of choosing the explanatory variables and the estimation of the parameters of the regression model, which are Bayesian Ridge Regression (unbiased) and the adaptive Lasso regression model, using simulation. MSE was used to compare the methods.
Abstract
The current research aims to reveal the extent to which all scoring rubrics data for the electronic work file conform to the partial estimation model according to the number of assumed dimensions. The study sample consisted of (356) female students. The study concluded that the list with the one-dimensional assumption is more appropriate than the multi-dimensional assumption, The current research recommends preparing unified correction rules for the different methods of performance evaluation in the basic courses. It also suggests the importance of conducting studies aimed at examining the appropriateness of different evaluation methods for models of response theory to the
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