SACM - United Kingdom
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Item Restricted Development of a novel and affordable vaccine against hepatitis A virus(Saudi Digital Library, 2024) Aljanabi, Walla; Groppelli, ElisabettaThis project aimed to develop an inventive and affordable vaccine against hepatitis A virus (HAV) by producing HAV virus-like particles (VLPs) in plant systems. The main objective was to generate the expression plasmids for the structural protein P1 and the non-structural protein 3C, with the addition of an HA-tag, and to validate their expression through several laboratory experiments. The workflow begins with primer designing specific to the P1 and 3C regions of the HAV genome, followed by PCR amplification and the creation of the expression constructs pCMVTnT-P1 and pCDNA3.1-HA-3C. Verification of these plasmid constructs was confirmed via restriction enzyme digestion and ligation. Primary protein expression was carried out in vitro using Rabbit Reticulocyte Lysates (RRL). At around 27 kDa bands were observed in both the HA-3C and control lanes, referring to unexpected bands and non-specific rather than successful protein expression, as shown and confirmed by Western blotting. These findings suggest that while the TnT RRL system did not generate enough amounts of the desired proteins, in mammalian cells the constructs were successful and detectable. The observations of this study integrate with past research on applying heterologous systems for viral protein expression and support the possibility of converting to plant-based expression systems to produce VLPs. This technique has implications of significance for generating affordable and expandable HAV vaccines, specifically for low-income areas where hepatitis A has a high incidence rate. Further studies will focus on enhancing expression protocols and evaluating and analysing the immunogenicity of plant-produced VLPs to progress toward clinical practice.8 0Item Restricted CT Texture Characterisation of Perirenal Fat in Patients with Upper Urinary Tract Cancers(Saudi Digital Library, 2025-05) Al Mopti, Abdulrahman; Chunhui, LiThis thesis investigates the diagnostic and prognostic potential of perirenal fat (PRF) radiomics in upper urinary tract cancers through three interconnected studies. Using computational techniques to extract quantitative features from CT images, the research establishes PRF as a valuable biomarker for tumour behaviour assessment. The first study, examining clear cell renal cell carcinoma in 474 patients, demonstrates that models integrating tumour features, PRF radiomics, and clinical variables achieve high accuracy for tumour grade (AUC 0.780) and stage prediction (AUC 0.829). Analysis reveals that PRF regions at 4-10mm radial distances from tumours contain the most predictive information. The second study on upper tract urothelial carcinoma (UTUC) reveals excellent performance of combined models in predicting tumour grade (AUC 0.961) and stage (AUC 0.852). PRF-only models also show substantial discriminative capability, confirming that PRF contains distinct textural patterns associated with tumour aggressiveness. The final study establishes the prognostic value of PRF radiomics in UTUC through survival analysis, with the combined radiomics-clinical model achieving a C-index of 0.784. Key radiomics features emerge as strong prognostic indicators, particularly when integrated with clinical variables like stage and hydronephrosis. Methodologically, the research develops a semi-automated approach for PRF analysis and implements a standardised radiomics workflow. The findings contribute novel insights by establishing PRF as an independent source of diagnostic information, developing standardised methodology for analysis, identifying specific radiomic signatures of aggressive disease, and creating predictive models that outperform conventional assessment. This work demonstrates that non-invasive analysis of PRF can enhance risk stratification and treatment planning in upper urinary tract cancers.6 0Item Restricted ISLAMIC CIVILISATION AND SAUDI NATIONAL IDENTITY AT ITHRA MUSEUM: CULTURAL HERITAGE AND EXPERIENCES OF DIGITISATION(Saudi Digital Library, 2025) Almalki, Rabab; Hatchwell, SophieThis thesis investigates audience experiences of digitisation at Ithra Museum, Saudi Arabia. It demonstrates the impact of digitisation on the preservation of Saudi cultural Heritage and the production of collective memory through the exhibitions at Ithra. Overall, it reveals Islamic civilisation to be a central aspect of the view of Saudi national identity produced at this museum. Its originality lies in its exploration of the relationship that Ithra constructs between Islamic civilisation and Saudi national identity in the digital age, considering the Museum’s international standpoint. It makes two contributions to museum studies: first, it investigates how the cultural context of a Saudi museum relates to the wider context of global Islamic culture; second, it asks how technology is being used in the context of Saudi museum practise. The thesis uses a mixed-methods approach based on the analysis of primary quantitative and qualitative data collected by means of a questionnaire with both closed- and open-ended questions, a second, closed-ended questionnaire and a structured interview. The first and second chapters of the thesis investigate audience experiences of digitisation at Ithra and how these affect their perspective on national identity. The third and fourth chapters explore the impact of digitisation at Ithra museum on Saudi collective memory by evaluating Ithra members’ approach to heritage preservation. The fifth and sixth chapters further consider the audience experience of digitisation and how this affects their views on the conservation of Saudi Arabian cultural heritage and the authenticity of museum objects.4 0Item Restricted The influence of hydraulic calcium silicate cements (HCSC) composition on the cell behaviour of human dental pulp stem cells (hDPSC)(Saudi Digital Library, 2025-06) AlGhamdi, Saleh; (Longridge, Nicholas), (Hamill, Kevin), (Yamamoto, Kazuhiro), (Jarad, Fadi), (Moawad, Emad)Introduction: There is growing interest in new endodontic materials used during vital pulp treatment (VPT), particularly hydraulic calcium silicate cements (HCSCs) including Biodentine™, TheraCal LC®, and TotalFill® formulations. Human dental pulp stem cells (hDPSCs) play a crucial role in reparative and regenerative pulp therapy through their capacity to differentiate into odontoblast-like cells and form reparative dentine. During VPT procedures, materials are designed to replace dentine and interact directly with viable pulp tissue. Understanding these material-tissue interactions is vital for predicting pulpal responses and optimising treatment outcomes. Aim: To investigate the influence of different hydraulic calcium silicate cements on the behaviour of human dental pulp stem cells. Methods: The study investigated the cellular response of hDPSCs to different HCSCs. The materials evaluated included Biodentine™, TheraCal LC®, TotalFill® BC RRM™ Fast Set Putty and TotalFill® BC RRM™ Putty. A multi-method approach was employed to assess cellular responses through metabolic activity, cell numbers and morphological analyses. Metabolic activity was assessed using the Resazurin assay under two experimental conditions: filtered extraction media and hanging insert methods. Cell numbers were quantified using the CyQUANT® assay, whilst morphological assessment was conducted using inverted microscopy. All analyses were performed at 24 and 48-hour time points. Additionally, scanning electron microscopy (SEM) was employed to evaluate cellular attachment to material surfaces. Results: Biodentine™ demonstrated consistently superior performance across all evaluation parameters. Its ability to maintain high metabolic activity, support normal cell morphology and facilitate cellular attachment suggested it created an optimal microenvironment for hDPSC survival and function. This superior performance was particularly evident in both the extraction media and hanging insert experiments, where Biodentine™ exhibited the highest metabolic activity at both 24 and 48-hour time points. TotalFill® BC RRM™ Fast Set Putty emerged as a promising alternative, showing comparable performance to Biodentine™, particularly after 48 hours of exposure. The material demonstrated good biocompatibility, supporting normal cell morphology and cellular attachment, with metabolic activity levels approaching those of Biodentine™ after 48 hours. Conversely, TheraCal LC® consistently showed inferior biological performance across all assessment methods. The material exhibited significantly lower metabolic activity, altered cell morphology and notably poor cellular attachment. These findings raised concerns about its suitability for direct pulp capping procedures, particularly in cases where maintaining optimal stem cell function is crucial for successful pulp repair. The CyQUANT® assay revealed similar patterns, with Biodentine™ and the control group showing the highest cell numbers at 24 hours. SEM analysis confirmed robust cellular attachment on Biodentine™ and both TotalFill® formulations, whilst TheraCal LC® exhibited poor cellular attachment. Conclusion/ Clinical application: Within the limitations of this in vitro study, Biodentine™ and TotalFill® BC RRM™ Fast Set Putty demonstrated superior biological performance, creating more favourable conditions for hDPSC survival and function compared with TheraCal LC®. The consistency of results across multiple assessment methods provided robust evidence for material-dependent effects on pulp cell behaviour, with important implications for material selection in VPT procedures. These findings have important clinical implications for material selection in VPT procedures. The superior biological performance of Biodentine™ and TotalFill® BC RRM™ Fast Set Putty suggests these materials may be more favourable choices for maintaining pulp cell viability and function. The consistent underperformance of TheraCal LC® indicates that careful consideration should be given to its use in direct pulp capping and pulpotomy procedures, particularly in cases where optimal stem cell function is crucial for successful pulp repair.6 0Item Restricted Effect of Degradation on Long-term Stability of 3D-printed Dental Crowns(Saudi Digital Library, 2025-07-04) Tayeb, Hunaida Khaled; Silikas, Nick3D printing technology in digital dentistry has led to innovative approaches for fabricating indirect dental restorations. However, a comprehensive assessment of the properties and long-term performance of these materials is essential. Therefore, this thesis aimed to evaluate the durability of mechanical, optical and surface properties of novel 3D-printed ceramic-filled resin composite materials indicated for definitive crown restorations. The first experimental chapter assessed the mechanical properties (flexural strength, flexural modulus, Martens hardness, indentation modulus and Vickers hardness) of three 3D-printed resin composites (Permanent Crown Resin, VarseoSmile Crown Plus, and Crowntec) and three milled resin composite blocks (BRILLIANT Crios, SHOFU Block HC and Grandio Blocs). The findings revealed that the 3D-printed definitive resin composites showed clinically acceptable mechanical properties, however, the milled resin composites showed significantly superior mechanical properties. The second experimental chapter explored the impact of immersion in food-simulating solvents on flexural strength, flexural modulus, Martens hardness, and indentation modulus of the same three 3D-printed resin composites and milled Grandio Blocs. Results indicated that exposure to solvents adversely affected the mechanical properties of all materials. Nevertheless, all tested materials showed acceptable mechanical properties after ageing. The third experimental chapter investigated the influence of artificial toothbrushing on surface roughness and gloss of the 3D-printed resin composites and the milled Grandio Blocs. Following 20,000 brushing cycles, both 3D-printed and milled resin composites exhibited increased surface roughness and reduced gloss, with 3D-printed materials exhibited comparatively lower wear resistance. Despite these changes, all tested materials maintained clinically acceptable gloss and roughness levels. The last experimental chapter examined the effects of immersion in various beverages on the colour stability (ΔE00), translucency, gloss and Martens hardness of the 3D-printed resin composites and milled Grandio Blocs. The results highlighted that both material type and beverage had a significant influence on the investigated properties, though ΔE00 of all materials remained within the clinically acceptable threshold of colour change across all beverages and measurement points.2 0Item Restricted Investigation of mechanisms and predictive markers of immune checkpoint inhibitor-induced immune-related adverse events.(Saudi Digital Library, 2025-01-30) Aboheimed, Nourah; Dan, Carr; Dean, Naisbittbstract: Introduction: Immune-related adverse events (irAEs) are significant limitations to the use of immune checkpoint inhibitors (ICIs). Over half of the patients on these medications experience irAEs, which vary in severity and affected organ. The identification of susceptible patients through biological biomarkers and genetic variations, along with an understanding of the immune mechanisms underlying these reactions, is a crucial goal in this field. Method: Our study utilized various methods to detect serum biomarkers, including ELISA, immunohistochemistry, and transcriptomic RNA analyses. We employed in vitro assays to elucidate the modulating effects of HMGB1 on T-cell and Treg suppression functions that affect the immune response. Additionally, TaqMan assays and genome-wide association studies (GWAS) were used to identify single nucleotide polymorphisms (SNPs) of interest. Results: HMGB1 was significantly elevated in the serum of patients with ICI-induced irAEs, particularly in those with gastrointestinal (GI) irAEs. Colon biopsies from these patients showed marked decreases in nuclear staining, indicating cellular death and HMGB1 translocation. Different HMGB1 isoforms varied in their effects on CTLA4 expression on CD3+ T cells, with dsHMGB1 notably reducing it. The effect of dsHMGB1 on CTLA4 expression in Treg populations showed intra-variability between donors and influenced the suppression function of Tregs on CD8+ and CD4+ T cells, which relates back to CTLA4 expression on these cells. Unfortunately, SNPs in the main receptor of dsHMGB1 (TLR4/MD2) were not significantly associated with the phenotype. However, female patients and those with a history of allergic reactions were significantly more likely to develop irAEs. ARG1 – a marker for MDSC and M2, was found to be significantly expresses in patients experiencing irAE. In our GWAS 14 snps exceeded our suggestive threshol d, these SNPs were mapped to regions of genes related to autoimmune disease and cancer. Discussion: Our findings highlight HMGB1's significant role in mediating immune-related adverse events (irAEs) in patients treated with immune checkpoint inhibitors. Elevated HMGB1 levels, particularly noted in gastrointestinal irAEs, suggest its potential as a biomarker for irAE risk. Additionally, the influence of HMGB1 on CTLA4 expression in T cells and Tregs underscores 6 its impact on immune modulation. Despite the lack of significant associations with TLR4/MD2 SNPs, the identification of other genetic variants related to autoimmune conditions hints at a complex genetic underpinning that warrants further investigation to enhance irAE management strategies.8 0Item Restricted Optimization of Close Space Sublimation and Post Deposition Routes for Antimony Chalcogenide Solar Cells(Saudi Digital Library, 2025-06) Sindi, Daniya; Major, JonThis thesis explores the influence of close space sublimation (CSS) growth conditions on antimony selenide solar cells as well as the possible benefits of post-growth processing approaches including an assessment of protective layer annealing. Single and two-step growth approaches involving the use of seed layers to modify film coverage and grain structure were investigated as a way of improving the solar cell performance. Both isolated layers and complete device structures were fabricated to allow investigation of the interrelation of preferred ribbon orientation with device efficiency. It was identified that, whilst the use of a seed layer was an important step to achieve good film coverage and grain morphology, the ribbon orientation appeared to have minimal influence on performance. The developed CSS growth approaches were then expanded to produce antimony sulfoselenide films and devices for a single phase source material. It was demonstrated that the approach was feasible, allowing the formation of material with a notably higher bandgap than for the base selenide. This indicated that material did not completely degrade during sublimation with the resulting devices achieve >4% efficiency and with a notably higher open circuit voltage than selenide counterparts. There were however significant issues with the formation of large oxide phase regions within the absorber. These served to reduce the device performance with the cause being attributed to sulphur loss and reaction with oxygen, the growth ambient during deposition. Post growth annealing approaches to improve antimony selenide solar cell efficiency were systematically investigated. Air, selenium, and nitrogen environments were initially compared across a broad temperature range. The results highlighted the degree of sensitivity of the material to post growth annealing with bot air annealing and selenization causing minimal changes to film morphology but drastic performance loss. Nitrogen annealing appeared more favourable with some minor open circuit voltage increases, both again the overall trend was a decrease in cell performance. To overcome these limitations the nitrogen ambient annealing approach was expanded to a protective layer annealing approach. A series of capping layers CdS, ZnO and P2O5 were deposited on the back surface prior to the annealing process to protect the antimony selenide layers and then etched off prior to device completion. The CdS capping layer was found to protect the surface from oxidation but frustratingly still resulted in performance decreases. There was however one “outlier” device series which showed a marked improvement for all device parameters. This result was not reproducible despite many attempts but seemed to indicate the potential of the approach so other materials were investigated. ZnO was considered but it was quickly determined it was unsuited as a capping layer. P2O5 however was tested and despite the limited number of samples being able to be prepared, it was found to notably improve device performance even with short time and low temperature anneals. Secondary ion mass spectrometry analysis showed significant quantities of phosphorus had been incorporated in the film during annealing. This finding demonstrates there is high potential from the protective layer annealing approach and indicates additional work in this area could leave to improved device efficiencies.7 0Item Restricted (Exploring Sustainable Adventure Tourism Development in Alula , Ksa)(Saudi Digital Library, 2025-05-10) Abuhamod, Manar; Pomfret, GillThe aim of this study is to evaluate AlUla’s viability as a premier locale for sustainable adventure tourism within the context of Saudi Arabia’s Vision 2030 initiative. Primary data was collected via an online survey disseminated to both domestic and international travelers, examining their motivations, perceptions, expectations regarding sustainability, and intentions towards loyalty. The results indicate that visitors exhibit a profound attraction to AlUla’s natural landscapes, cultural heritage, and dedication to sustainable practices. Environmental stewardship emerged as a pivotal factor affecting tourist loyalty. In light of the findings, it is advised that AlUla persist in its investments in eco-friendly infrastructure, community engagement, and cultural tourism experiences. Furthermore, amplifying digital marketing strategies is recommended to bolster AlUla’s reputation and competitive stance in the global adventure tourism sector.2 0Item Restricted Identifying Novel Therapies for Cystinuria Using Genetic Tools(Saudi Digital Library, 2025-03-21) Dakhakhini, Mohammed Hatim; Coward, RichardCystinuria is a rare inherited renal stone disorder that effects 1 in every 2000 people in the UK. Available drug treatment like Tiopronin, D-Penicillamine, and Captopril used to decrease the Cystine concentration in the urine. However, these drugs impose huge disadvantages to patients through agonising side-effects such as: weight gain, excessive fatigue, loss of taste, and breathing difficulties, all of which lead to poor quality of life. This necessitates the need for other therapeutic approaches that can treat the disorder without causing major side-effects. Cystinuria is caused by a mutation in one or both subunits of the Cystine transporter rBAT or b0,+AT which are encoded by SLC3A1 or SLC7A9 genes, respectively. These mutations lead to mis-localization of functioning rBAT and b0,+AT proteins from the plasma membrane which translate into a disruption of urinary Cystine re-absorption. This in turn leads to increased Cystine flow into urine which results in Cystine accumulation that eventually forms Cystine stones in kidneys, ureter, or bladder. This research hypothesizes that repurposing established drug compounds (LOPAC1280) to re-direct b0,+AT protein back into the plasma membrane could be a new and improved therapeutic approach. In this study, transduced human proximal tubule epithelial cells (PTECs) were used to investigate the localisation of fluorescently tagged rBAT and b0,+AT proteins in wild-type and three rBAT-based mutated cell lines. All cellular localization studies showed consistent results. Both rBAT and b0,+AT proteins were found to be trafficked together. In the fluorescently tagged wildtype type expressing cell line, both proteins were located at the plasma memrbane, with the wild-type b0,+AT being the dominant trafficked subunit. All three mutants expessing cell lines suggested that both proteins were predominantly trapped within the ER. A unique screening assay model that can measure the exiting of b0,+AT from the ER using a high content fluorescent microscope system was developed, optimized and validated, and used to screen the LOPAC1280 library of compounds using the p. Met467Thr-rBAT expressing cell line. Nanchangmycin (NCM) was identified as a final target hit as it induced exiting of the b0,+AT from the ER and translocated it to the plasma membrane.18 0Item Restricted Corporate Governance in Hybrid State-Owned Enterprises: From the Theoretical to the Practical.(Saudi Digital Library, 2025-06-30) Alohaly, Asaiel Ahmed; Devenney, James and Miglionico, AndreaThis thesis offers two substantial contributions to the field of corporate governance. First, it provides a comprehensive critical analysis of the existing governance models for partially state-owned enterprises (SOEs). Second, it proposes an innovative new framework for the governance of such companies. Partial SOEs, which involve a mixture of government and private ownership, are identified in this thesis as “hybrid SOEs”. The opening sections present a significant new exploration of current governance models –what this thesis terms the “state model” – for hybrid SOEs. This includes both a full-scale theoretical analysis and case studies of some major companies from around the world. The discussion highlights the diversity of control and ownership structures in hybrid SOEs, the different forms that government influence in these companies can take, and the specific risks and challenges these pose. It demonstrates that there is currently no single state model for hybrid SOEs, and argues the need for a new forward-looking governance model that can cope with the complex nature of these companies, and balance shareholder rights with government authority. The proposed new governance model, the pioneering contribution of this thesis, is then presented. The proposed model provides a practical approach (a toolkit) that reflects the unique risks and challenges faced by hybrid SOEs. The flexibility of this model is crucial, as this is what ensures its relevance across different settings. With its thorough examination of the current situation and proposed new governance model, this thesis presents an important contribution to governance knowledge. It also provides a valuable foundation for future research or initiatives exploring the potential practical implementation of the proposed model.7 0