SACM - Ireland
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Item Unknown Biochemical changes of the insulin molecule due to functionalized surfaces: An investigation from a therapeutic perspective(Saudi Digital Library, 2025) Fagihi, Megren; Bhattacharjee, SouravInsulin therapeutics is the cornerstone in current diabetes management, especially while treating Type I diabetes. However, being a protein, insulin is known to demonstrate agglomeration when subjected to alterations in its biochemical environment, such as acidity, temperature fluctuation, coming in contact with hydrophobic surfaces, and agitation. This thesis describes a detailed and systematically designed study to investigate the curious case of insulin agglomeration, understand the mechanism(s) that drive such agglomeration, and realize the therapeutic impacts of such insulin agglomeration. To begin with, a detailed literature survey was conducted on insulin agglomeration, with or without fibrillation, and converge the available knowledge into a single discourse, which is presented as the Chapter 1 (introduction) of this thesis. This literature survey was followed by four experimental chapters (Chapters 2–4) where through a range of systematic and consistent experimental approach the phenomena of acidity-, heating-, and hydrophobic surface-induced insulin agglomeration was investigated. To characterize the insulin agglomerates, a broad range of analytic platforms, such as transmission and scanning electron microscopy, circular dichroism, nanoparticle tracking analysis, and zeta potential were used. Additionally, this thesis work also exploited the promise of advanced optical microscopy platforms, such as the confocal laser scanning microscopy and fluorescence lifetime imaging microscopy to probe the agglomerates and identify the varied segments of fluctuating acidity inside them. Taken together, the data was able to provide vital information on insulin agglomeration with a mechanistic understanding of what drives such agglomeration. An in vitro study was also conducted (Chapter 3) to find out if the insulin agglomerates generated due to heating at high temperatures (50°C and 65°C) were bioactive, and the results came positive. The Chapter 5 then explains another in vitro study where fluorophore-labeled insulin uptake in human hepatocellular carcinomaderived HepG2 cells was investigated with confocal microscopy. Finally, Chapter 6 summarized the findings, provide a few additional perspectives on overall realizations made through these studies, and prioritized some lines of research for future explorations.4 0Item Unknown Private Ordering for non-Muslims in the Gulf States (GCC); Administration of Justice and Constitutionalisation(Saudi Digital Library, 2025) Alqahtani, Nawaf Mutib; O'Dowd, JohnIn recent years, the member states of the Gulf Cooperation Council (GCC) have witnessed several socio-legal changes that coincided with their major economic plans to move away from their primary dependence on natural resources. Consequently, GCC governments are aware that part of the implementation of these plans largely depends on attracting foreign investors, entrepreneurs, and highly skilled workers to reside, not temporarily, but permanently. Several laws have been amended, including those governing residency, naturalization, and even property ownership, to create a favourable, attractive, and friendly environment for recent residents and newcomers (Muslims and non-Muslims). Regarding family matters for non- Muslims, the GCC differ in the applicable law (between Islamic, secular, and conflict of laws). This thesis primarily discusses the extent to which, remaining within the framework of Sharia law, the GCC states can ensure, through arbitration laws, that non-Muslims are adjudicated in family matters according to the law of their choice and thereby contribute to the achievement of their economic plans. To answer this question, the thesis first examines the position of Sharia law on the rights of non-Muslims, including the right to litigate according to their own laws. It then analyses the historical practice of Muslim states (from the rise of Islam until the fall of the Ottoman Empire) towards religious minorities regarding this right. It then examines comparatively the constitutions and laws of the Gulf states regarding the status of non-Muslims in family disputes. Finally, an international practice (specifically, New York and England and Wales) is studied as practical examples of how members of religious minorities can litigate (through arbitration) according to their religious laws. The research methodology used to answer the main question and sub-questions is mainly doctrinal, comparative, and historical- legal and partly socio-legal. The thesis concludes by proposing a constitutional amendment and some legal reforms that would be consistent with the framework of Sharia, while still meeting the economic objectives of the GCC states.6 0Item Unknown Critical Analysis of Public Enforcement of Competition Law in Saudi Arabia with Reference to Egypt and the European Union(Saudi Digital Library, 2026) Alhamami, Abdullah Ahmed T; Maher, ImeldaCompetition law is a recent development in Saudi Arabia, with the first law issued in 2004. Initial enforcement was ineffective due to legislative and institutional shortcomings. Significant reforms established an independent competition authority and updated legislation. Combined with nearly two decades of enforcement experience, these developments make it timely to examine how public enforcement of competition law can be optimised in Saudi Arabia. The research employs legal- doctrinal and comparative methodologies, focusing particularly on Egypt and the European Union as key benchmarks. A socio-legal approach, including institutional analysis and elite interviews, complements the study due to the scarcity of published decisions and academic literature on Saudi competition law. The thesis examines four central aspects of public enforcement: the objectives of competition law, the enforcement toolkit, institutional design and judicial review. The analysis begins with the Saudi legal system's foundational influence on competition enforcement. The Competition Law identifies multiple broad objectives. Yet, these broadly defined goals lack hierarchical order or substantive interpretation by agencies or courts, creating uncertainty in enforcement priorities. The law provides various enforcement tools, including fines, leniency programmes, settlements and compliance mechanisms. Fining policies have evolved from fixed amounts to turnover-based calculations, though fixed fines remain prevalent in practice. Leniency and settlements represent positive steps, but their conflation within a single legal provision has led to operational ambiguity. Compliance programmes are promoted but lack financial incentives such as fine reductions, potentially limiting their uptake. Institutional independence has improved with the establishment of the GAC. However, ministerial representation on its board undermines autonomy. A shortage of academic expertise in competition law and economics further constrains capacity. While the GAC holds exclusive enforcement authority, ineffective cooperation with sectoral regulators risks undermining its efficacy. International engagement remains limited, with only one cooperation agreement signed with Egypt. Judicial review by administrative courts is crucial for ensuring enforcement legitimacy, but the absence of published case law hinders analysis. Specialised training for judges along with specialised court divisions, could significantly improve judicial outcomes. This thesis concludes that, despite progress, strategic refinements in enforcement practice, institutional autonomy and judicial expertise are essential for a robust competition regime in Saudi Arabia.10 0Item Unknown Rank distributions of graphs over the field of two elements(Saudi Digital Library, 2025) Safarji, Badriah; Quinlan, O’Brien; Cian ,RachelA square matrix $M$ represents a graph $\Gamma$ if its nonzero off-diagonal entries encode the adjacencies of $\Gamma$ according to a fixed vertex ordering. Over the field of two elements, we study the distribution of ranks within the affine space of all matrices representing a particular graph. The motivating question is which graphs of order $n$ are represented by more matrices of rank $n-1$ than of rank $n$. This reflects the fact that the most frequently occurring rank is not $n$ but $n-1$ in the space of all $\mathfrak{n} \times \mathfrak{n}$ matrices over $\mathbb{F}_2$, a property which is exceptional to $\mathbb{F}_2$. This thesis focuses on connected graphs that have a path or cycle as a subgraph induced on all but one vertex (called the extra vertex). The path graph $\mathrm{P}_{\mathrm{n}}$ serves as the starting point of this study. The path graph is fundamental in the related and widely studied minimum rank problem, and provides a foundation for our later analysis of the set $\mathcal{G}^{\mathrm{P}}$ of graphs containing an induced path on all but one vertex. A main result is a characterisation of all such graphs that are represented by more matrices of rank $n-1$ than rank $n$ over $\mathbb{F}_2$. This is achieved by first examining the vectors in the nullspace of each matrix representing $P_n$. An expression for the difference $\alpha(\Gamma)$ between rank $n-1$ and rank $n$ representations of a given graph $\Gamma \in \mathcal{G}^{\mathrm{P}}$ is determined in terms of these nullspace vectors. A recurrence is then established, expressing $\alpha(\Gamma)$ in terms of $\alpha$ for graphs in $\mathcal{G}^{\mathrm{P}}$ for which the extra vertex has lower degree than in $\Gamma$. We classify all $\Gamma \in \mathcal{G}^{\mathrm{P}}$ satisfying $\alpha(\Gamma)<0$ by first classifying those for which the extra vertex has degree 1, then using that to simplify and classify the degree 2 case, and continuing like this until it is shown that no such graphs exist for degree $\geqslant 6$. We then turn to the analogous problem for the cycle graph. We show that half of all $\mathbb{F}_2$-matrices representing $C_n$ have rank $n-1$, approximately one-third have rank $n$, and approximately one-sixth have rank $n-2$. We then investigate the set of graphs containing an induced cycle on all but one vertex, denoted by $\mathcal{G}^{\mathrm{C}}$. Our analysis reveals essential structural contrasts between the classes $\mathcal{G}^{\mathrm{P}}$ and $\mathcal{G}^{\mathrm{C}}$ : while the degree of the extra vertex is bounded in the path case, it can be arbitrarily large in the cycle case. An infinite family of graphs called alternating wheel graphs demonstrate this contrast, as there exists an alternating wheel graph $\Gamma \in \mathcal{G}^{\mathrm{C}}$ with an extra vertex of any even degree $\mathrm{d} \geqslant 4$ satisfying $\alpha(\Gamma)<0$.5 0Item Unknown Transcriptomic and Functional Analysis of Two-Component Systems AdeRS, BaeRS, GacAS in Acinetobacter baumannii AB5075(Saudi Digital Library, 2025) Sulimani, Maha; Kröger, CarstenAntimicrobial resistance constitutes one of the most significant global health challenges of our era, with Acinetobacter baumannii becoming a key priority pathogen owing to its extraordinary capacity to withstand various classes of antibiotics. A primary factor contributing to this resilience is the function of regulatory proteins, especially Two-Component Systems (TCSs), which allow the bacterium to detect environmental cues and swiftly modify gene expression. Nevertheless, the overarching regulatory networks of these systems are still not well comprehended. The objective of this thesis was to examine the regulatory functions of specific two-component systems (TCSs) AdeRS, BaeRS, and GacSA in A. baumannii AB5075, as well as to investigate their roles in antimicrobial resistance and various adaptive phenotypes. Through transcriptomic analysis (RNA-seq), I detected genome wide expression alterations in mutant strains that lacked these regulators when compared to the wild-type during exponential and stationary growth phases. Phenotypic assays, which included minimum inhibitory concentration (MIC) determination, disk diffusion, phenotypic microarrays and growth assays, were conducted to establish a correlation between transcriptional changes and antibiotic susceptibility and metabolism. In order to delve deeper into gene regulation, transcriptional start sites (TSSs) were delineated through differential RNA-seq, which facilitated the identification of promoter motifs and offered insights into the structure of transcriptional regulation in A. baumannii. Moreover, chromatin immunoprecipitation coupled with sequencing (ChIP-seq) was utilized to comprehensively map the binding sites of essential transcription factors (AdeR, BaeR, and GacA), uncovering their direct regulons and preferences for DNA binding. The results outlined in this thesis enhance our comprehension of TCS mediated regulation in A. baumannii. They reveal that AdeRS, BaeRS, and GacSA are responsible not only for the regulation of antibiotic resistance factors but also for affecting wider physiological mechanisms that aid in bacterial survival and adaptation. A comparative transcriptomic analysis of the adeRS, baeRS, and gacSA two-component systems has unveiled distinct regulatory effects on gene expression in Acinetobacter baumannii AB5075. Both adeR and adeS mutants exhibited numerous transcriptional alterations, particularly a downregulation of the adeABC efflux pump genes, thereby confirming their involvement in the regulation of antibiotic resistance. In the baeRS system, baeS demonstrated a more extensive transcriptomic influence compared to baeR, especially under the Late Stationary Phase LSP condition, where baeR was found to regulate only two genes. The gacA and gacS mutants revealed the highest number of differentially expressed genes across all systems, with gacA notably regulating the small RNAs sRNA100 and sRNA99, as indicated by peaks observed in chip seq data. The phenotypic characterization conducted through Kirby–Bauer disk diffusion assays indicated that all adeRS, baeRS, and gacSA mutants displayed measurable inhibition zones against specific antibiotics, implying partial changes in their susceptibility profiles. Nevertheless, minimum inhibitory concentration (MIC) testing revealed that these mutants continued to exhibit resistance, suggesting that although the regulatory disruptions influenced gene expression, they were not adequate to completely undermine the antibiotic resistance phenotypes.4 0Item Unknown The Role of PP2A in VE-cadherin Modulation in Human Cerebral Microvascular Endothelial Cells(Saudi Digital Library, 2025) Alenazi, Fawza; Spiers, PaulThesis abstract: Introduction: The blood–brain barrier (BBB) is a highly specialised and dynamic interface that protects the central nervous system (CNS) by tightly regulating the passage of molecules between the circulation and neural tissue. This barrier is primarily maintained by brain microvascular endothelial cells interconnected through tight and adherens junctions. Among the components of adherens junctions, vascular endothelial (VE)-cadherin plays a pivotal role in maintaining endothelial cell–cell adhesion, vascular stability, and BBB integrity. Disruption or internalisation of VE-cadherin has been implicated in numerous neurological and systemic disorders, including stroke, inflammation, and Alzheimer’s disease. The function and stability of VE-cadherin at the plasma membrane are critically influenced by its phosphorylation status. Protein phosphatase 2A (PP2A), a major serine/threonine phosphatase, is recognised as a regulator of junctional protein dephosphorylation and endothelial barrier function. Notably, PP2A has been identified as part of the VE-cadherin interactome, and previous studies suggest that it contributes to the formation of epithelial tight junctions and the maintenance of barrier integrity. However, the specific role of PP2A in regulating adherens junction components, particularly VE-cadherin, at the BBB remains unclear. Aims: This thesis aimed to investigate the role of PP2A in regulating VE-cadherin abundance and the functional integrity of the BBB using in vitro models of human brain microvascular endothelial cells. Specifically, the objectives were to (1) determine how PP2A inhibition affects VE-cadherin abundance and BBB integrity, (2) determine the broader proteomic changes associated with PP2A inhibition, and (3) determine whether metformin, a PP2A activator, can counteract these effects. Methods: Human brain endothelial cells (hCMEC/D3) were treated with the PP2A inhibitor okadaic acid (OA). VE-cadherin protein and mRNA abundance, subcellular distribution, and vi junctional localisation were analysed using Western blotting, RT-PCR, subcellular fractionation, and immunofluorescence. Barrier function was assessed by transwell permeability assays. PP2A activity was quantified with a phosphatase assay, and the involvement of proteasomal or lysosomal pathways was tested using MG132 and chloroquine. Proteomic alterations following OA exposure were examined using microarray analysis and bioinformatic pathway/network tools. The roles of Rab11A and Rab5A were assessed using siRNA knockdown. The impact of metformin on PP2A activity and VE-cadherin regulation was evaluated by cytotoxicity testing, PP2A activity measurement, and time-course analysis of VE-cadherin abundance. Results: OA produced a concentration-dependent reduction in VE-cadherin protein (50–70%), accompanied by its loss from endothelial junctions and a marked increase in paracellular permeability. These effects occurred without cytotoxicity and coincided with a ~60% decrease in PP2A activity. VE-cadherin reduction was prevented by proteasomal inhibition and associated with increased ubiquitination, indicating that OA promotes proteasomal degradation of VE-cadherin. Proteomic profiling identified 104 proteins altered by OA, highlighting pathways related to ubiquitination, membrane trafficking, tight junction regulation, and neurodegeneration. Rab11A upregulation was detected; however, Rab11A and Rab5A knockdown did not prevent OA-induced VE-cadherin loss. Metformin did not restore PP2A activity or reverse VE-cadherin reduction at 24 hours, although early time- course data suggested a partial transient attenuation of OA’s effect at 10 hours. Conclusions: PP2A plays a critical role in maintaining VE-cadherin stability and BBB integrity. Inhibition of PP2A disrupts endothelial junctions by promoting proteasomal degradation of VE-cadherin, leading to increased barrier permeability. These findings reveal a mechanism through which PP2A dysfunction contributes to BBB impairment. Although metformin showed limited restorative capacity, early temporal effects suggest that modulating PP2A signalling may offer therapeutic potential for preserving BBB integrity under pathological conditions.7 0Item Unknown THE ROLE OF SAUDI ARABIC DIALECTAL VARIATION IN THE ACQUISITION OF SPECIFIC ENGLISH AFFRICATE AND FRICATIVE SOUNDS BY SAUDI EFL LEARNERS SPEAKING THE HWAITI AND HIJAZI DIALECTS(Saudi Digital Library, 2025) Alomeri, Haya Nassir Saleem; Pérez, Ana de PradaDespite the multifarious studies investigating the acquisition of English as a second language (L2) by Arabic-speaking learners, very few have examined the influence of learners’ dialects on their pronunciation of English consonants. Therefore, this thesis aims to explore the impact of L2 learners’ dialects on their pronunciation of the English affricative and fricative sounds. To achieve this goal, the articulation of the sounds /ʤ /, /θ/, /ð/, and /v/ by 40 female senior undergraduate Saudi learners (20 Hwaiti Bedouins and 20 Hijazi Urbans) at Tabuk University were recorded and then rated by two English native speakers. The main hypotheses were that Hijazi speakers would mispronounce /ʤ/, /θ/, and /ð/ because they are not part of their dialect yet they are part of the Hwaiti dialect and that both groups would devoice the phoneme /v/ by pronouncing it as /f/ because /v/ is not in the Arabic sound system. This thesis uses quantitative methods: a demographic information questionnaire, LexTALE English proficiency test, Arabic and English production tasks, along with statistical analyses of the collected data by using RStudio (2021). The errors are classified based on Flege and Bohn’s speech learning model (SLM) (2021). The theoretical framework is an amalgamation of milestone theories, mainly cross-linguistic influence (Bild & Swain, 1989; Tati et al., 2015; Odlin, 1989, 2012; De Angelis and Selinker, 2001), Eckman’s markedness differential hypothesis (1985), and Flege and Bohn’s SLM (2021). Each contributes to the analysis of cross-language interaction, phonological transfer patterns, and L2 phonetic learning. The main finding is that the two groups were affected by their dialect sound systems when producing the selected phonemes. Interestingly, the two heterogenous groups had similarities in the type (albeit not the frequency) of sound substitutions: they both pronounced /ʤ/ as [g] or [ʒ], /θ/ as [s] or [t], and /ð/ as [z]. Moreover, the most challenging phoneme to pronounce by the Hijazi group was /ʤ/ in the middle position of words, whereas for the Hwaiti group, it was /θ/, also, in the middle position. Future researchers can expand upon this study to include other dialects.9 0Item Restricted Innovative Visualisation Approaches in Anatomy Teaching(Saudi Digital Library, 2025) Alturkustani, Sarah; Lone, Mutahira; O'Mahony, SiobhainA solid understanding of anatomy is essential for effective healthcare practice. Substantial changes, such as reduced teaching hours, alongside ongoing resource constraints and donor availability, have shaped anatomy education. In response, institutions have adopted time-efficient and cost-effective methods to attempt to maintain educational quality. Multimodal learning approaches have proven effective in enhancing students’ learning experiences and outcomes. Among these, art-based methods and visualisation technologies have shown value in conveying anatomical knowledge, particularly in illustrating spatial relationships and complex anatomical forms, as well as enhancing students' engagement with anatomy. This thesis evaluated the efficacy of innovative visualisation approaches in anatomy education, hypothesising that such methods enhance anatomical understanding, spatial perception, and the overall learning experience. The Haptico-Visual Observation and Drawing (HVOD) method was first examined through student perceptions (Chapter 2), revealing improved spatial understanding through the construction of 3D mental images. Objective assessment (Chapter 3) showed that HVOD-supported learning was associated with higher knowledge retention, and both studies reported positive student perceptions. The effectiveness of a 3D visualisation technology, Complete Anatomy, was then assessed for learning laryngeal anatomy (Chapter 4), which demonstrated improvements in knowledge acquisition, anatomical recognition, spatial understanding, and high levels of student satisfaction. In Chapter 5, students’ perceptions of the Virtual Reality anatomy software 3D Organon for learning anatomy and factors influencing future use were explored using the General Extended Technology Acceptance Model for E-Learning (GETAMEL). Enjoyment and perceived ease of use emerged as the strongest predictors of students’ perceptions of 3D Organon and their intentions to use the software for future learning. Finally, a lymphatic visualisation specimen was developed using subcutaneous injections and clearing methods on a pre-embalmed donor body (Chapter 6), demonstrating practical feasibility and effectively revealing lymphatic structures. As hypothesised, innovative anatomy visualisation approaches positively impacted knowledge acquisition and anatomical understanding while eliciting high levels of student satisfaction. These findings underscore the value of such approaches in complementing traditional anatomy teaching and addressing contemporary educational needs. In summary, each study highlighted distinct advantages of different visualisation approaches in anatomy education. Therefore, combining visualisation methods may offer a more rounded and practical anatomy learning experience. Future research and educational practice should explore integrated, multimodal approaches that support traditional teaching with innovative tools, including art-based methods and visualisation technology, to address educational needs and enhance learning outcomes.8 0Item Restricted Towards An Autonomy-Based Model to Underpin the Legal Rules of Informed Consent in Medical Treatment in Saudi Jurisdiction(Saudi Digital Library, 2025) Alhusayni, Nourah; Cox, NevilleThe thesis employs the normative legal method to analyse the moral foundations of trust and autonomy underlying the legal rules of medical consent in Saudi law. It identifies that maintaining good health is significant in Sharia and that the current Saudi approach has adopted the principle of trust in physicians to make medical decisions in patients' best interests. The thesis analyses the principle of autonomy and whether a movement to an autonomy model would be compatible with Sharia principles. The thesis argues that the principle of autonomy is significant in medical decision-making when the patient's health is concerned. Such relevance stems from the Islamic theological doctrine of taklif, derived from the Islamic framework of dignity associated with humanity's vicegerency on earth, which asserts that the core qualities of humans to fulfil the mission of vicegerency while bearing taklif are rationality, cognitive abilities and free will that enable individuals make moral and autonomous decisions when it comes to their health. Ultimately, patient autonomy must be respected and maximised, as patients are morally responsible for their actions.14 0Item Restricted Synthesis of Fluorinated N-Heterocycles: Analogues of Febrifugine(Saudi Digital Library, 2020) Alkhathami, Fahad Ali S; Evans, PaulThis thesis describes the synthesis and stereochemical investigation of fluorinated analogues of febrifugine and its synthetic derivative halofuginone. In particular, racemic cis- and trans-3- fluoro analogues of febrifugine were prepared using both piperidine and pyrrolidine ring systems as starting scaffolds. Febrifugine and halofuginone provide structurally rich scaffolds for probing stereoelectronic effects of fluorine and in addition possess potentially very useful biological properties. The synthetic route was developed in a modular sequence, beginning with nitrogen protection using a Cbz group, followed by enamine formation. Electrophilic fluorination with Selectfluor introduced fluorine at the β-position to nitrogen, affording cis/trans mixtures of fluorinated intermediates. Sakurai allylation established new carbon–carbon bonds to the α position of the nitrogen heterocycle. Upon separation, the allyl group of each diastereomer underwent a Wacker oxidation followed by functionalization that enabled introduction of the required quinazolinone portion. Finally, removal of the N-Cbz protecting group led to isolation of the 3-fluorofebrifugine analogues as their dihydrobromide salts. Use of 7-bromo-6-chloroquinazolinone, in an otherwise identical sequence, led to the preparation of cis- and trans-3-fluorohalofuginone. Parallel studies using pyrrolidine substrates demonstrated the generality of the approach, leading to analogous cis- and trans-fluorinated derivatives. In these later studies, fluorination of the enamine afforded cis/trans mixtures of 2-methoxy-3-fluoropyrrolidines, which were used for determining the stereochemistry. Finally, the interconversion between the cis- and trans-diastereomers was studied. In DMSO- d6 and as their free-bases, the isomerization of each separate diastereomer gave a common 35:65 ratio of cis- to trans- for the piperidine analogues while a 50:50 ratio of cis- to trans- was observed for the pyrrolidine analogues. Overall, this work establishes robust synthetic routes to fluorinated febrifugine and halofuginone analogues and provides new insight into stereochemical behaviour and isomerisation in β-amino ketone frameworks. The methodologies developed here extend to both piperidine and pyrrolidine scaffolds and lay the groundwork for future asymmetric synthesis and structural diversification of fluorinated heterocycles.6 0