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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Introduction: Methadone hydrochloride (MDN) is an effective pharmacological substitution treatment for opioids dependence, adopted in different countries as methadone maintenance treatment (MMT) programmes. However, MDN can exacerbate the addiction problem if it is abused and injected intravenously, and the frequent visits to the MMT centres can reduce patient compliance. The overall aim of this study is to develop a novel extended-release capsule of MDN using the sol-gel silica (SGS) technique that has the potential to counteract medication-tampering techniques and associated health risks and reduce the frequent visits to MMT centres. Methods: For MDN recrystallisation, a closed container method (CCM) and hot-stage method (HSM) were conduc
... Show MoreThe performance quality and searching speed of Block Matching (BM) algorithm are affected by shapes and sizes of the search patterns used in the algorithm. In this paper, Kite Cross Hexagonal Search (KCHS) is proposed. This algorithm uses different search patterns (kite, cross, and hexagonal) to search for the best Motion Vector (MV). In first step, KCHS uses cross search pattern. In second step, it uses one of kite search patterns (up, down, left, or right depending on the first step). In subsequent steps, it uses large/small Hexagonal Search (HS) patterns. This new algorithm is compared with several known fast block matching algorithms. Comparisons are based on search points and Peak Signal to Noise Ratio (PSNR). According to resul
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An encryption system needs unpredictability and randomness property to maintain information security during transmission and storage. Although chaotic maps have this property, they have limitations such as low Lyapunov exponents, low sensitivity and limited chaotic regions. The paper presents a new improved skewed tent map to address these problems. The improved skew tent map (ISTM) increases the sensitivity to initial conditions and control parameters. It has uniform distribution of output sequences. The programs for ISTM chaotic behavior were implemented in MATLAB R2023b. The novel ISTM produces a binary sequence, with high degree of complexity and good randomness properties. The performance of the ISTM generator shows effective s
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The precise classification of DNA sequences is pivotal in genomics, holding significant implications for personalized medicine. The stakes are particularly high when classifying key genetic markers such as BRAC, related to breast cancer susceptibility; BRAF, associated with various malignancies; and KRAS, a recognized oncogene. Conventional machine learning techniques often necessitate intricate feature engineering and may not capture the full spectrum of sequence dependencies. To ameliorate these limitations, this study employs an adapted UNet architecture, originally designed for biomedical image segmentation, to classify DNA sequences.The attention mechanism was also tested LONG WITH u-Net architecture to precisely classify DNA sequences
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The pancreatic ductal adenocarcinoma (PDAC), which represents over 90% of pancreatic cancer cases,
has the highest proliferative and metastatic rate in comparison to other pancreatic cancer compartments. This
study is designed to determine whether small nucleolar RNA, H/ACA box 64 (snoRNA64) is associated with
pancreatic cancer initiation and progression. Gene expression data from the Gene Expression Omnibus (GEO)
repository have shown that snoRNA64 expression is reduced in primary and metastatic pancreatic cancer as
compared to normal tissues based on statistical analysis of the in Silico analysis. Using qPCR techniques,
pancreatic cancer cell lines include PK-1, PK-8, PK-4, and Mia PaCa-2 with differ
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Nowadays, there is a trend to promote the use of natural materials in dentistry. One of these compounds that has lately grown significantly in relevance in clinical research is
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Research Objectives: The research aims to highlight the approach of Imam Al-Qaradawi in contemporary jurisprudence in the recent issues of the jurisprudence of minorities, and mentioning the foundations of jurisprudence of minorities, along with some of the practical applications of Imam Al-Qaradawi.
Study Methodology: The researcher applied the inductive, analytical and comparative approach by tracking the scientific material related to the subject of the study from the books of Al-Qaradawi in the first place, then by comparing the legal provisions with what had been stated in the four schools of jurisprudence.
Findings: The interest and need of Muslim minorities in non-
... Show MoreIntellectual and material displacement is one of the design strategies through many mechanisms and means, and depends on the idea of changing the shape within the internal spaces at times and has concepts related to the transformation at other times. And represented by the boxes for travelers, the research problem emerged through the following question: (What is the effectiveness of displacement in the formal structures in the interior design of historical sites), and the aim of the study is to reveal the reality of the use of historical internal spaces and to determine the formal displacement that occurs as a result of change and transformation, and it included two topics, the first topic Transformation and the effectiveness of formal d
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Libraries, information centers, and everything related to organizing and preparing information need to be periodically re-evaluated in order to stand on the level of quality, which means improving the general reality of these institutions to ensure sufficient satisfaction from beneficiaries of the services provided. This is what was worked on in this research, as one of the most important quality standards in libraries and information centers, LibQUAL+®, was applied in one of the most important and oldest central university libraries, namely the Central Library of the University of Baghdad at its two locations, Al-Jadriya and Al-Waziriya. The sample of beneficiaries to whom the questionnaire was distributed reached 75 beneficiaries distrib
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