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
Continuous escalation of the cost of generating energy is preceded by the fact of scary depletion of the energy reserve of the fossil fuels and pollution of the environment as developed and developing countries burn these fuels. To meet the challenge of the impending energy crisis, renewable energy has been growing rapidly in the last decade. Among the renewable energy sources, solar energy is the most extensively available energy, has the least effect on the environment, and is very efficient in terms of energy conversion. Thus, solar energy has become one of the preferred sources of renewable energy. Flat-plate solar collectors are one of the extensively-used and well-known types of solar collectors. However, the effectiveness of the coll
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The rapid increase in the number of older people with Alzheimer’s disease (AD) and other forms of dementia represents one of the major challenges to the health and social care systems because of a large number of people affected. Early detection of AD makes it possible for patients to access appropriate services and to benefit from new treatments and therapies, as and when they become available, and to plan for the future. The onset of AD starts many years before the clinical symptoms become clear. A biomarker that can measure the brain changes in this period would be useful for early diagnosis of AD. Potentially, the electroencephalogram (EEG) can play a valuable role in early detection of AD. Damage caused to the brain due to AD leads t
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In this work, a test room was built in Baghdad city, with (2*1.5*1.5) m3 in dimensions, while the solar chimneys (SC) were designed with aspect ratio (ar) bigger than 12. Test room was supplied by many solar collectors; vertical single side of air pass with ar equals 25, and tilted 45o double side of air passes with ar equals 50 for each pass, both collectors consist of flat thermal energy storage box collector (TESB) that covered by transparent clear acrylic sheet, third type of collector is array of evacuated tubular collectors with thermosyphon in 45o instelled in the bottom of TESB of vertical SC. The TESB was
... Show MoreBackground: The primary stability of the dental implant is a crucial factor determining the ability to initiate temporary implant-supported prosthesis and for subsequent successful osseointegration, especially in the maxillary non-molar sites. This study assessed the reliability of the insertion torque of dental implants by relating it to the implant stability quotient values measured by the Osstell device. Material and methods: This study included healthy, non-smoker patients with no history of diabetes or other metabolic, or debilitating diseases that may affect bone healing, having non-restorable fractured teeth and retained roots in the maxillary non-molar sites. Primary dental implant stability was evaluated using a torque ratc
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Many carbonate reservoirs in the world show a tilted in originally oil-water contact (OOWC) which requires a special consideration in the selection of the capillary pressure curves and an understanding of reservoir fluids distribution while initializing the reservoir simulation models.
An analytical model for predicting the capillary pressure across the interface that separates two immiscible fluids was derived from reservoir pressure transient analysis. The model reflected the entire interaction between the reservoir-aquifer fluids and rock properties measured under downhole reservoir conditions.
This model retained the natural coupling of oil reservoirs with the aquifer zone and treated them as an explicit-region composite system
This study proposes a new version of the Autoregressive Integrated Moving Average (ARIMA) model using Artificial Neural Networks (ANNs) denoted by ARIMA-NN. The new model incorporates a multi-layer perceptron with matrix multiplication within a feed-forward network. The logistic, hyperbolic tangent (tanh), and sigmoid activation functions are used for weight updates in ARIMA-NN. A new forecasting algorithm is proposed, and one-step and multiple-steps forecasting procedures are rigorously analyzed. The proposed model was evaluated against existing forecasting model using performance metrics such as the Akaike Information Criterion (AIC) and Bayesian Information Criterion (
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Background. In cases of spontaneous subarachnoid haemorrhage (SAH) with multiple intracranial aneurysms (MIAs) detected on angiography, some radiological clues assist in determining the site of a ruptured aneurysm which is bleeding is quite beneficial for the selection of the best treatment strategy. Case description. We report a case of a 60 years old patient who presented with spontaneous SAH, sellar hematoma, and three different aneurysms detected in angiography. Although the right Posterior communicating artery (PcomA) aneurysms showed Murphy’s teat on angiography intraoperatively, we discovered that the right superior hypophyseal aneurysm (SHA) was the source of the index bleeding. Both aneurysms were clipped successfully. Co
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