Saudi Cultural Missions Theses & Dissertations
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Item Restricted Incorportation of Caesium into Potassium-Silicate Geopolymers(University of Sheffield, 2024-01-23) Alkhateeb, Khaled; Walkley, BrantThis dissertation explores the process of incorporating caesium into potassium silicate activated geopolymers providing insights into its effects. Geopolymers, known for their potential in construction serve as the context for examining the challenge of integrating caesium. The focus is on understanding the implications of caesium’s radius within geopolymerisation chemistry and kinetics. To investigate the geopolymer matrix, these two powerful analytical techniques are utilized; isothermal conduction calorimetry (ICC) and Fourier transform infrared (FTIR) spectroscopy. These tools enabled the team to uncover the relationship between caesium and the geopolymerisation process. They clarify how caesium interacts with the structure and evolution of geopolymers. The study also examines the characterization of geopolymers with an emphasis on how alkaline earth cations (Ca2+ and Sr2+) influence their molecular configurations and properties. Advanced analytical methods such as X ray Diffraction (XRD) Solid state Nuclear Magnetic Resonance (NMR) and Fourier Transform Infrared Spectroscopy (FTIR), and Isothermal Conduction Calorimetry (ICC) were employed to analyse geopolymers consisting primarily of metakaolin and alkali activators. XRD analysis revealed that the geopolymer structure was amorphous. Subtle changes were observed due to the presence of alkaline earth cations. Various solid state NMR techniques, including 29Si MAS, 1H 29Si CP MAS, 27Al MAS and 23 Na MAS NMR revealed changes, in the Si environments caused by the presence of Ca2+ and Sr2+ ions. These changes indicated alterations in polymerization states and connectivity. The analysis of aluminium species and local environment interactions was carried out using 27Al MAS and 23Na MAS NMR techniques, which were supported by absorption bands identified through FTIR spectroscopy. This combined approach provided insights into how composition molecular configuration and cation influence affect geopolymers. It also offered promising avenues for customizing these materials for construction and future advancements in the field. In summary this thorough review represents an understanding of the relationship between caesium and geopolymers. Its significance extends beyond academia as it aligns with efforts to improve containment and storage methods for waste. This signifies a step towards solutions, in construction, environmental preservation and nuclear energy safety.28 0Item Restricted HISTONE H3K27ME3 IN PREIMPLANTATION MOUSE EMBRYO DEVELOPMENT(Saudi Digital Library, 2023-06) Harasani, Ahlam; Pennings, Sari; Taylor, JaneDuring the developmental stages of the mouse preimplantation embryo, totipotent blastomeres generate the first three cell lineages of the embryo: trophectoderm (TE), epiblast (EPI) and primitive endoderm (PrE). The first cell fate decision consists of the separation of cells that will comprise the TE and the ICM (inner cell mass). Then, further segregation of ICM cells takes place into EPI-fated cells and PrE-fated cells. It is thought that this cell lineage specification is mediated in part by epigenetic processes, in which genes are regulated both temporally and spatially without any changes in the genome. Certain transcription factors such as Oct4, Sox2, Cdx2, Gata6, Nanog, and Fgf4 coordinate pluripotency and early cell fates during development. They are part of a network of pluripotency and associated genes that control each other’s expression as well as that of other major transcription factors through epigenetic mechanisms and simultaneous signalling pathways. Epigenetic mechanisms such as DNA methylation and post-translational histone modifications play a critical role in regulating gene expression in preimplantation embryos. During the embryonic development process, methylation of DNA is required for overall development. Similarly, trimethylation of lysine 27 on histone 3 (H3K27me3) is required to regulate developmental genes. This histone modification is facilitated by the polycomb repressive complex 2 (PRC2) subunit named enhancer of zeste homolog 1/2 (EZH1/2), an enzyme that epigenetically modulates chromatin structure and gene expression through H3K27me3 and may be involved in recruitment of DNA methyltransferases for gene silencing. The SET domain of EZH2 is thought to serve in the mechanism for transferring methyl groups from S-adenosylmethionine (SAM) to H3K27. EZH2 has a pivotal role to play in cancer progression and malignancy, but it also plays a vital role in the renewal, maintenance and differentiation of stem cells into specific cell lineages. Several recent studies have shown that blocking PRC2-EZH2 alone is not enough to suppress cancer-related genes. The dual inhibitors of both PRC2-EZH2 and PRC2-EZH1 were found to suppress H3K27me3 completely in cells after treatment. It is also suggested that Ezh1 may be involved in enhancing the maintenance of ES cell identity when EZH2 is not present. In this study, two small molecules, GSK-126 and EPZ-6438, have been used to inhibit the catalytic subunit of EZH2 in preimplantation mouse embryos in vitro to study the contribution of this enzyme through its inhibition in the embryos' developmental process. The objectives of this study are to determine the role of PRC2 complex methyltransferase EZH2 and the H3K27me3 epigenetic mark in the development of pluripotent ICM cells and other early cell fates in the mouse preimplantation embryo, based on morphology, epigenetic and cell fate markers and gene expression. This study was carried out using cultured preimplantation embryos from superovulated B6CBA F1 mice. Fertilised zygotes were collected at embryonic day 0.5 (E0.5). Embryos were cultured from age E0.5 (1-cell stage), to E1.5 (2-cell stage), E2.5 (8-cell stage) or until E4.5 (blastocyst stage) in the presence of either GSK-126 (1μM, 3μM), EPZ-6438 (0.5μM, 0.75μM, 1μM) or dimethyl sulfoxide (DMSO) as a vehicle. The effect of EZH2 inhibition was assessed based on morphology and using two techniques: reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for determining gene expression and immunocytochemistry (ICC) for measuring protein abundance. Quantitative analyses of the gene expression data of the relevant genes were conducted using the housekeeping genes GAPDH and H2Afz as endogenous controls. Indirect immunofluorescence staining was used in embryos, images were captured using confocal microscopy, and analyses were performed using MATLAB, IMARIS, and ImageJ software programs. The findings showed that inhibition of EZH2 reduced H3K27me3 levels in blastocysts. Also, the number of blastomeres was lower in the treated blastocysts than in control. EZH2 appears to influence developmental delay in the preimplantation mouse embryo. Furthermore, ICC results showed a decrease in the number of blastocyst cells expressing CDX2, the trophectoderm marker, compared with the control group. In conclusion, the results of this study will contribute to our understanding of the role H3K27me3 plays in early mammalian embryos during the specification and maintenance of cell fates.24 0