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
Negotiations are distinguished in that they are an easy and simple means between the conflicting parties, and it is an effective means at the same time as the conflicting parties seek understanding on the most effective way to solve their dispute, but negotiations are not always appropriate to resolve international disputes, especially when there is a disparity in power between the negotiating countries, or when it is missing Goodwill, or even when one of the parties is absent or less flexible, and the internal circumstances of one of the conflicting countries may play a negative or positive role in the success of the negotiations, away from the influence of the role of external variables in that, a
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Problem: Cancer is regarded as one of the world's deadliest diseases. Machine learning and its new branch (deep learning) algorithms can facilitate the way of dealing with cancer, especially in the field of cancer prevention and detection. Traditional ways of analyzing cancer data have their limits, and cancer data is growing quickly. This makes it possible for deep learning to move forward with its powerful abilities to analyze and process cancer data. Aims: In the current study, a deep-learning medical support system for the prediction of lung cancer is presented. Methods: The study uses three different deep learning models (EfficientNetB3, ResNet50 and ResNet101) with the transfer learning concept. The three models are trained using a
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The paper tackles two topics. The first is about the term "Ремейк" which is very common in contemporary Russian literature; it has counterparts such as " Обработка" and " Переделка", where these two may indicate any of the following meanings (remake, reformulate, rewrite, treatment, modification, change). It has been shown that this term does not have a stable definition. Also, the role of this term in literary studies has been mentioned along with how it has come to its peak of use in post-modern literature.
The second is that I have taken a sample of well-known works in Russian literature " On the Eve, On the Eve " by the contemporary Russian writer YevgueniBobov, and shown the effort of the writer
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One male specimen of the species Metapenaeus stebbingi Nobili, 1904 was first recorded in November 2021 from the Iraqi territorial waters, Northwest of the Arabian Gulf. Therefore, the investigated shrimp species nominally corresponds to the original description of M. stebbing through the main diagnostic features. It must be adopted in the spread and expansion of species, a new record of the area, and a distinctive addition to the species of commercial shrimp within the Iraqi marine waters.
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Nature and natural beauty have always been the source of inspiration for poets and mystics. For them, nature is one of the most recurrent and celebrated themes. It is a significant symbol of the beauty, righteousness and freshness they are looking for. For religious and mystical poets, it is a reference to God, his beauty, and splendour. Comparing it with the scripture, Thomas Ryan, a Catholic priest and a mystical writer, says ''The Bible is the 'small book', the world of nature is the 'big book'. Both reveal the Creator.''1
For Muslim mystics, God does exist everywhere as the Qur'an states: ''Wherever (Whithersoever) you turn, there is God's face” (Chapter (Surah): 2
... Show MoreIn recent years, Bitcoin has become the most widely used blockchain platform in business and finance. The goal of this work is to find a viable prediction model that incorporates and perhaps improves on a combination of available models. Among the techniques utilized in this paper are exponential smoothing, ARIMA, artificial neural networks (ANNs) models, and prediction combination models. The study's most obvious discovery is that artificial intelligence models improve the results of compound prediction models. The second key discovery was that a strong combination forecasting model that responds to the multiple fluctuations that occur in the bitcoin time series and Error improvement should be used. Based on the results, the prediction acc
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. In recent years, Bitcoin has become the most widely used blockchain platform in business and finance. The goal of this work is to find a viable prediction model that incorporates and perhaps improves on a combination of available models. Among the techniques utilized in this paper are exponential smoothing, ARIMA, artificial neural networks (ANNs) models, and prediction combination models. The study's most obvious discovery is that artificial intelligence models improve the results of compound prediction models. The second key discovery was that a strong combination forecasting model that responds to the multiple fluctuations that occur in the bitcoin time series and Error improvement should be used. Based on the results, the prediction a
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Human interferon as is the case in all kinds of interferon has complex effects but all share their impact on preventing the proliferation of viruses and preventing or reducing human Alantervjørn conversion occurs if the cell is in preventing the growth of the virus when interferon Balnmstqubl connects
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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