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
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This research has come out with that, function-based responsibility accounting system has harmful side – effects preventing it of achieving its controlling objective, that is, goal congruence, which are due to its un integrated measures, its focus on measuring measurable behaviors while neglecting behaviors that are hardly measured, and its dependence on standard operating procedures.
In addition, the system hypotheses and measures are designed to fit previous business environment, not the current environment.
The research has also concluded that the suggestive model, that is, activity-based responsibility accounting is designed to get ride of harmful side – effects of functi
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A 3D geological model is an essential step to reveal reservoir heterogeneity and reservoir properties distribution. In the present study, a three-dimensional geological model for the Mishrif reservoir was built based on data obtained from seven wells and core data. The methodology includes building a 3D grid and populating it with petrophysical properties such as (facies, porosity, water saturation, and net to gross ratio). The structural model was built based on a base contour map obtained from 2D seismic interpretation along with well tops from seven wells. A simple grid method was used to build the structural framework with 234x278x91 grid cells in the X, Y, and Z directions, respectively, with lengths equal to 150 meters. The to
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Recently Tobit Quantile Regression(TQR) has emerged as an important tool in statistical analysis . in order to improve the parameter estimation in (TQR) we proposed Bayesian hierarchical model with double adaptive elastic net technique and Bayesian hierarchical model with adaptive ridge regression technique .
in double adaptive elastic net technique we assume different penalization parameters for penalization different regression coefficients in both parameters λ1and λ2 , also in adaptive ridge regression technique we assume different penalization parameters for penalization different regression coefficients i
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This paper presents a grey model GM(1,1) of the first rank and a variable one and is the basis of the grey system theory , This research dealt properties of grey model and a set of methods to estimate parameters of the grey model GM(1,1) is the least square Method (LS) , weighted least square method (WLS), total least square method (TLS) and gradient descent method (DS). These methods were compared based on two types of standards: Mean square error (MSE), mean absolute percentage error (MAPE), and after comparison using simulation the best method was applied to real data represented by the rate of consumption of the two types of oils a Heavy fuel (HFO) and diesel fuel (D.O) and has been applied several tests to
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In this paper will be applied to a probability model of inventories periods of multiple stores of raw materials used in the cement industry, cement factory in Samawah and basic materials are limestone, soil normal, iron soil, fuel oil and gypsum. It was built of this model after the test and determine the distribution of demand during the supply period (waiting period) for each subject and independently of the rest of the material as it is not affected by any of the materials above interrelated in the process of supply, this test has been using the Statistical Package of (SPSS) and then was determining the amount of request optimum seeking in each batch and each substance known volume of economic optimization of
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The last few years witnessed great and increasing use in the field of medical image analysis. These tools helped the Radiologists and Doctors to consult while making a particular diagnosis. In this study, we used the relationship between statistical measurements, computer vision, and medical images, along with a logistic regression model to extract breast cancer imaging features. These features were used to tell the difference between the shape of a mass (Fibroid vs. Fatty) by looking at the regions of interest (ROI) of the mass. The final fit of the logistic regression model showed that the most important variables that clearly affect breast cancer shape images are Skewness, Kurtosis, Center of mass, and Angle, with an AUCROC of
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Silymarin, a flavolignans from seeds of ‘milk thistle’ “Silybum marianum†has been widely used from ancient times because of its excellent hepatoprotective action. It has been used clinically to treat liver disorders including acute and chronic viral hepatitis, toxin/drug-induced hepatitis and cirrhosis and alcoholic liver disease. The efficacy and dose-response effect of silymarin (125, 250 and 500 mg/kg) were assessed using egg albumin-induced paw edema in rats as a model of acute inflammation. In this model, 56 rats were used and allocated into 7 subgroups each containing 8 rats. All treatments were given intraperitonealy 30 minutes before induction of inflammation by egg albumin and then the increase
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A genetic algorithm model coupled with artificial neural network model was developed to find the optimal values of upstream, downstream cutoff lengths, length of floor and length of downstream protection required for a hydraulic structure. These were obtained for a given maximum difference head, depth of impervious layer and degree of anisotropy. The objective function to be minimized was the cost function with relative cost coefficients for the different dimensions obtained. Constraints used were those that satisfy a factor of safety of 2 against uplift pressure failure and 3 against piping failure.
Different cases reaching 1200 were modeled and analyzed using geo-studio modeling, with different values of input variables. The soil wa
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