SACM - United Kingdom

Permanent URI for this collectionhttps://drepo.sdl.edu.sa/handle/20.500.14154/9667

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    Characterization of peripheral immune dysregulation and brain neuroimmune pathophysiology in the Df(16)A+/- Mouse Model of 22q11.2 Deletion Syndrome, a high genetic risk factor for schizophrenia
    (Saudi Digital Library, 2025) AlFadhel, Hassan Ali H; Jonathan, Craig
    Schizophrenia (SCZ) is a severe and chronic neurodevelopmental disorder that imposes a profound global health burden. Among its complex genetic underpinnings, the 22q11.2 Deletion Syndrome (22q11.2DS) stands out as the highest-known genetic risk factor, with approximately 25-30% of affected individuals developing a psychotic disorder. Recent research in SCZ has undergone a paradigm shift, moving beyond purely neurocentric models to embrace growing evidence that implicates immune dysregulation and neuroinflammation as critical etiological processes. While 22q11.2DS is known to confer a complex immunological phenotype, including foundational T-cell deficits and a high incidence of autoimmune disorders, the functional consequences of this genetic 'first hit' on immune reactivity and central nervous system (CNS) vulnerability is not well understood. Therefore, the primary objective of this thesis was to systematically characterize immune dysregulation in the Df(16)A+/- mouse model of 22q11.2DS to test the hypothesis that the genetic deletion programs a dysfunctional response to subsequent inflammatory challenges, thereby providing a plausible biological substrate for neuropsychiatric risk. This investigation utilized the Df(16)A+/- mouse model, which carries a chromosomal deletion syntenic to the human 22q11.2DS critical region. Our experimental strategy involved a comprehensive profiling of the peripheral and central immune systems at a homeostatic baseline and following provocation with distinct immune stimuli, including a sustained Toll-like receptor 7 (TLR7) agonist (Aldara) and an acute Toll-like receptor 3 (TLR3) agonist (LMW-Poly(I:C)). Given the limited characterization of the Df(16)A+/- immune profile and the incompletely elucidated mechanisms linking 22q11.2DS to psychiatric risk, this thesis employed both hypothesis-driven and exploratory analytical frameworks to systematically characterize the immune phenotype. Primary analytical techniques included multi-plex immunoassays (Luminex), multi-parameter flow cytometry, and quantitative immunohistochemistry. This central analysis was supported by the development of a high-throughput, objective morphometric pipeline to robustly quantify glial reactivity and neuronal cytoarchitecture within the hippocampus. Our results demonstrate that the Df(16)A+/- genotype is not immunologically silent but confers a "first hit" of subtle, multi-system dysregulation. Peripherally, this is defined by a "central deficit, peripheral compensation" model, with foundational T-cell developmental deficits in the bone marrow and thymus that are compensated for in circulating blood and spleen populations. This cellular alteration is mirrored by a rewired baseline molecular milieu, characterized by increased inter-animal heterogeneity and a less interconnected systemic cytokine network. Centrally, this state corresponds to a latent glial vulnerability, defined by a subtle but significant reduction in the morphological complexity of hippocampal microglia, anatomically co-localized to the dorsal CA1 and dentate gyrus. Subsequent immune challenges revealed this vulnerable baseline dictates a "second hit" of a profoundly dysfunctional and uncoupled neuro-immune response. The systemic reaction to the TLR7 challenge was both attenuated in magnitude, with blunted splenomegaly and pro-inflammatory cytokine upregulation, and qualitatively dysregulated, exemplified by the paradoxical downregulation of IFN-alpha and the collapse of the organized inflammatory network. Critically, this peripheral impairment was associated with a complete uncoupling of the glial inflammatory cascade in the dorsal hippocampus: wildtype mice mounted a coordinated neuroinflammatory response, whereas Df(16)A+/- mice exhibited a dissociated cascade where microglia adopted a morphologically reactive state in the complete absence of a canonical astrocyte (GFAP+) response. This microglial response was itself dysfunctional, occurring without the expected upregulation of the functional protein Iba1. This glial uncoupling was directly associated with the neuronal findings: Df(16)A+/- mice exhibited an altered parvalbumin-positive (PV+) interneuron response, lacking the significant change in cell counts observed in wildtype animals following the challenge. Findings from an acute TLR3 challenge, qualified by a severe physiological confound of hypothermia, also pointed towards a rewired inflammatory program by revealing a paradoxical central myeloid response. The central conclusion of this thesis is that the 22q11.2DS-relevant genetic deletion establishes a "first hit" of homeostatic instability that dictates a functionally impaired "second hit" response to immune challenges. This work links this high-impact genetic risk factor to a specific CNS vulnerability, defined by an uncoupled neuroinflammatory cascade, where microglia activate but astrocytes fail to respond, and a corresponding genotype-specific PV+ interneuron response, where the significant change in cell counts seen in wildtype animals was absent in the Df(16)A+/- mice. This integrated phenotype provides a novel and plausible biological substrate for the increased neuropsychiatric risk observed in the human 22q11.2DS population.
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    Developing a virus-like particle (VLP) Polio vaccine
    (Saudi Digital Library, 2025) Altalhi, Sarah; Mulley, Jay
    Poliovirus (PV) is a subtype of the enterovirus C species widely known as the agent responsible for poliomyelitis, a destruction of neurons that can result in paralysis and death. Control of the infection is achieved by vaccination with either a live-attenuated oral poliovirus vaccine (OPV) or an inactivated poliovirus vaccine (IPV), with global coverage reaching nearly 100%. As cases of the natural infection fall, the manufacture of the current vaccines, both of which rely of large-scale virus growth, present a biosafety risk and PV vaccines developed in the absence of live virus are desirable to address vaccine production to maintain PV global vaccination. Virus-like particles (VLPs), which are incapable of infection, made of the assembled viral capsid proteins synthesized in recombinant expression systems, represent a promising infection-free vaccine for PV. This study produced the capsid proteins VP0, VP1, and VP3 in E.coli and baculovirus expression systems and assessed both their expression levels and their ability to assemble into virus-like particles. To avoid protein aggregation in the E.coli system each protein was fused to the SUMO-tag and purified individually for SUMO tag removal and attempted VLP assembly. Novelly, E.coli strains were transformed with all three vectors simultaneously and processed similarly. Despite these modifications, SUMO tagged capsid proteins remained largely insoluble and the low levels present in the soluble fractions failed to be cleaved by the SUMO protease. In the baculovirus system the P1 precursor protein, co-expressed with 3C protease, gave rise to the authentic cleavage pattern and modification at both the N- and C- termini were investigated as a means to improve expression levels. A range of mutations aimed at optimizing the N-myristoylation reaction revealed several that were associated with increased levels of cleaved mature capsid proteins. Further, modification of the C-terminus, including short truncations of the VP1 sequence, was shown to benefit expression level. In a final study, mutations in VP4, previously reported in the live virus to abrogate the virus entry reaction, were investigated in the VLP system. Individual mutations at VP4 residues 24, 28 and 29 were shown to significantly alter expression levels and further analysis of these changes within the VP0 protein only were studied following VP0 fusion to Green Fluorescent Protein (GFP). The outcome of these studies showed that single residue changes in VP4 in the context of VP0 can significantly affect protein expression level and subcellular localization. Overall, these studies suggest that optimization of the P1 sequence can improve the levels of PV protein expressed. However, when tested, the antigenicity of the PV VLPs detected was predominantly in the H (heated) rather than the N (native) form suggesting that none of the alterations tested resulted in a VLP conformation required for vaccine use.
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    Optimising the Regeneration Process of Spent Lithium-Ion Battery Cathode Through a Performance Analysis Model
    (Saudi Digital Library, 2026) Alyoubi, Mohammed; Abdelkader, Amor; Huang, Yi
    The urgent global demand for sustainable energy storage materials has amplified interest in efficient recycling and regeneration methods for lithium-ion batteries (LIBs), particularly in response to the increasing volume of spent batteries generated by electric vehicles and portable electronics. This thesis investigates the potential of machine learning (ML) to optimise the regeneration process of spent LIB cathode materials, aiming to enhance performance recovery while reducing time, cost, and experimental workload. The research focuses on direct regeneration methods, which restore the electrochemical activity of cathode materials by repairing their crystal structure, rather than decomposing them into elemental components, making them highly promising for sustainable battery reuse. While ML has been applied to predict the performance of fresh LIBs, its application to regenerated cathode materials remains unexplored. Unlike fresh batteries, regenerated materials may exhibit residual impurities that affect their electrochemical behaviour, highlighting the need for specialised data-driven approaches tailored to these conditions. The study developed and validated an ML framework that integrated experimental data and predictive modelling to enable the optimisation of regeneration processes of three widely used cathode chemistries: lithium cobalt oxide (LCO), lithium iron phosphate (LFP), and nickel-manganese-cobalt oxide (NMC). A total of eight ML algorithms were evaluated, including Classification and Regression Trees, Support Vector Machine, K-Nearest Neighbours, Random Forest, and Artificial Neural Networks (ANN), to model battery performance and optimise regeneration conditions. Each case study demonstrated how ML can predict the discharge capacity of regenerated materials based on key parameters of the direct regeneration method, including regeneration temperature, duration, and the ratio and amount of added lithium salt. Results show that ANN provides the highest prediction accuracy, with R2 values exceeding 0.99 across all case studies. The ANN model was then employed to identify optimal regeneration conditions, with findings indicating that ML-guided approaches outperform traditional empirical methods in restoring battery performance. This thesis demonstrates the transformative potential of ML in the regeneration of spent LIB cathodes, presenting an accurate and sustainable approach to improving circularity in battery materials.
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    Dual channel amplifier chain at Ka-Band with controllable phase and amplitude
    (Saudi Digital Library, 2025) Alharbi, Rami; Bogusz, Aleksander; Quaglia, Roberto
    This project is to develop a dual-channel amplifier chain functioning at Ka-band, with adjustable phase and amplitude, a subject of increasing significance in contemporary communication systems that require both high efficiency and consistent performance [1]. The principal issue at these frequencies is the considerable insertion losses of interconnects and active components, alongside the manufacturing and mechanical limits inherent to substrates like FR-4 and the constraints of human assembly. A thorough methodology was employed, integrating theoretical design with electromagnetic-based simulations. The system architecture comprised a power splitter, a mixer for phase and amplitude modulation via an external signal source, pre-amplifiers to mitigate initial losses, and primary power amplifiers capable of outputting power levels approaching 30 dBm. Biassing circuits were meticulously constructed, taking into account electrical stability and manufacturing feasibility to ensure alignment with the fabrication capabilities of the chosen PCB manufacturer. The simulation findings confirmed the viability of accurate phase and amplitude control via the mixer’s external input, while also illustrating good loss compensation and stable overall performance. The nonlinear distortion products produced by the mixer were demonstrated to be insignificant, validating the design's robustness. Conversely, the mixer step remained a notable source of loss, indicating potential for enhancement through the utilisation of superior components or different design methodologies. Notwithstanding these achievements, many limits must be recognised, including the hazards linked to human soldering of fine-pitch components and the possible discrepancies in trace shape resulting from fabrication tolerances. These limits, however, do not diminish the project's achievements but rather indicate opportunities for improvement in future endeavours. Possible enhancements are utilising sophisticated substrates like Rogers RO4350B or employing automated precision assembly techniques to reduce variability and improve uniformity. This project exemplifies a feasible and executable architecture that substantiates the concept of phase and amplitude control at Ka-band. It establishes a robust basis for the advancement of more efficient outphasing-based RF systems, representing a significant progression towards next- generation communication technology.
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    Public Awareness, Trust and Perception of Cybersecurity Development in Saudi Digital Governance: A Quantitative Study under Vision 2030 Framework
    (Saudi Digital Library, 2025) ِAlshaeri, Abdulaziz; Knabe-Nicol, Susanne
    Despite extensive digital transformation efforts, Saudi Arabia faces cybersecurity threats, which highlights the need for increased public cybersecurity resilience. This study addresses an important gap in understanding public awareness, trust and perception regarding cybersecurity within Saudi Arabia’s Vision 2030 digital governance initiatives. The primary aim was to analyse the levels of public awareness, trust and perception of cybersecurity practices among Saudi citizens. By employing Technology Acceptance Model (TAM), complemented by literature on institutional trust and digital literacy, this research adopted a positivist, quantitative approach. An online survey of 96 respondents was conducted, analysed through descriptive statistics, Pearson correlation, regression analyses, and independent-sample t-tests. Findings demonstrated formal education significantly improves cybersecurity awareness, whereas technical understanding of cyber threats and risks among citizens alone does not increase further learning motivation. Trust in institutions strongly predicts perceived cybersecurity protection, with notable disparities based on gender and employment sector. Clear government communication strengthens trust, but macro-level cybersecurity threats fail to improve individual data protection confidence. Key recommendations include targeted cybersecurity education programmes for less-educated groups, gender-sensitive cybersecurity initiatives addressing specific threats faced by Saudi women, and personalised, actionable governmental cybersecurity communication.
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    COMPARATIVE ANALYSIS OF INTERPERSONAL MOOD AND CULTURAL-LINGUISTIC VARIATION IN TWO ENGLISH TRANSLATIONS OF THE QUR’ANIC NUH STORY
    (Saudi Digital Library, 2025) ATA, AREEJ ALI M; bin Abdul Jabar, Mohd Azidan
    Thi study addresses the challenges of conveying the rich meaning of the Qur'an across languages, specifically focusing on the interpersonal dynamics in English translations of the Qur'anic Nuh story. The Qur'an, originally in Classical Arabic, presents linguistic and cultural complexities in translation that shape its message. This research comparatively examines two prominent English translations: The Holy Qur’an by Abdullah Yusuf Ali (hereafter referred to as T1) and The Noble Qur’an by Al-Hilali and Khan (hereafter referred to as T2). Using Systemic Functional Linguistics (SFL) to analyze mood structures, complemented by Skopos Theory to contextualize translation choices, the study aims to understand how interpersonal meaning is constructed in these versions. The four main objectives are: (1) to identify mood structures and their associated domain acts, (2) to investigate linguistic similarities and differences in interpersonal mood, (3) to analyze how translators' mood choices reflect different translation strategies and priorities, and (4) to explain how cultural and linguistic factors influence interpersonal mood realization. Employing qualitative document analysis, relevant passages were analyzed. The declarative mood dominates both translations (around 72% of clauses), reinforcing the authoritative tone. However, imperative and interrogative mood usage varies, with Yusuf Ali employing more rhetorical expressions and Al-Hilali & Khan being more direct. These variations signify distinct translation strategies, reflecting different cultural and ideological priorities. The findings highlight the critical interplay of language, culture, and translation in religious texts. This provides valuable insights for linguistics, translation studies, and Qur'anic discourse analysis by underscoring the importance of contextual considerations in translating sacred texts. .SDG: GOAL 4: Quality Education
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    Intracranial Aneurysm Morphology and Hemodynamics: A Controlled CFD Study of Aspect Ratio and Neck Size
    (Saudi Digital Library, 2025) alkhaldi, almaha; Nicolas, Newell
    Intracranial aneurysms are bulges in brain arteries that affect up to 5% of the population and can rupture without warning, often leading to fatal or disabling strokes. Current clinical risk assessments rely heavily on aneurysm size, despite evidence that both small and large aneurysms can rupture. Computational fluid dynamics (CFD) offers a way to assess blood flow–related factors linked to rupture, such as Time-Averaged wall shear stress (TAWSS), oscillatory shear index (OSI), and relative residence time (RRT). However, existing CFD studies are often limited by confounding variables in patient-specific geometries, making it difficult to isolate the role of individual shape features. This study aimed to investigate how Aspect Ratio (AR), the height-to-neck-width ratio of an aneurysm, independently influences hemodynamic behavior. Using a generative model (AneuG), 36 anatomically Realistic aneurysm models were created with systematically varied AR while keeping neck width constant. Unsteady CFD simulations with pulsatile inflow conditions were conducted in ANSYS Fluent, and key metrics (TAWSS, OSI, RRT) were extracted and analyzed. Results showed that increasing AR consistently reduced TAWSS and moderately increased RRT, both of which are associated with rupture risk. However, AR had no consistent effect on OSI, which appeared to depend more on local flow structures than global shape. These findings suggest that AR is a reliable predictor of certain hemodynamic risks but insufficient to explain complex flow patterns. The study demonstrates that controlled, morphology-driven simulations can clarify how shape affects blood flow, and it supports integrating AR into future clinical tools for improved rupture risk assessment.
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    Intracranial Aneurysm Morphology and Hemodynamics: A Controlled CFD Study of Aspect Ratio and Neck Size
    (Saudi Digital Library, 2025) Alkhaldi, Almaha; Nicolas, Newell
    Intracranial aneurysms are bulges in brain arteries that affect up to 5% of the population and can rupture without warning, often leading to fatal or disabling strokes. Current clinical risk assessments rely heavily on aneurysm size, despite evidence that both small and large aneurysms can rupture. Computational fluid dynamics (CFD) offers a way to assess blood flow–related factors linked to rupture, such as Time-Averaged wall shear stress (TAWSS), oscillatory shear index (OSI), and relative residence time (RRT). However, existing CFD studies are often limited by confounding variables in patient-specific geometries, making it difficult to isolate the role of individual shape features. This study aimed to investigate how Aspect Ratio (AR), the height-to-neck-width ratio of an aneurysm, independently influences hemodynamic behavior. Using a generative model (AneuG), 36 anatomically realistic aneurysm models were created with systematically varied AR while keeping neck width constant. Unsteady CFD simulations with pulsatile inflow conditions were conducted in ANSYS Fluent, and key metrics (TAWSS, OSI, RRT) were extracted and analyzed. Results showed that increasing AR consistently reduced TAWSS and moderately increased RRT, both of which are associated with rupture risk. However, AR had no consistent effect on OSI, which appeared to depend more on local flow structures than global shape. These findings suggest that AR is a reliable predictor of certain hemodynamic risks but insufficient to explain complex flow patterns. The study demonstrates that controlled, morphology-driven simulations can clarify how shape affects blood flow, and supports integrating AR into future clinical tools for improved rupture risk assessment.
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    Determining the Views of Families Affected by AI on Required Support
    (Saudi Digital Library, 2025) Farie Ghada; Balmer Richard; Chauhan Amrit; Owen Jenny; Balmer, Richard
    Background: Amelogenesis Imperfecta (AI) is a rare, inherited condition affecting enamel formation, with significant aesthetic, functional, and psychosocial consequences for affected children and their families. Despite the known challenges, there is limited research exploring the specific support needs of these families. Aim: This study aimed to explore the perceptions and experiences of families affected by AI, focusing on the emotional, social, and practical support needed to manage their child’s condition. Methods: A qualitative study design was employed, using semi-structured interviews with twelve parents of children diagnosed with AI, recruited from the Leeds Dental Institute. Interviews were conducted via Microsoft Teams, recorded, transcribed verbatim, and analysed using reflexive thematic analysis within a constructivist approach. Findings: Three overarching themes emerged: (1) The emotional and confusing search for answers, highlighting the diagnostic uncertainty and lack of awareness among healthcare professionals; (2) Parents advocating for their child’s needs, revealing the Social and emotional burden within families; and (3) The perceived invisibility of AI and limited support, illustrating the lack of accessible, accurate information and structured resources. Families consistently expressed the need for tailored guidance, knowledgeable clinicians, emotional reassurance, and peer or digital support networks. Conclusion: AI profoundly impacts not only the child’s quality of life but also the entire family’s emotional and practical wellbeing. This study underscores the need for improved education among dental professionals, the development of structured support resources, and integrated care pathways. Addressing these gaps is critical for reducing the burden on families and enhancing outcomes for children living with AI.
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    Physical Layer Security for Vehicle-to-Vehicle Visible Light Communication Using Artificial Noise
    (Saudi Digital Library, 2025) Ashour, Danah majed Hassan; AlSallami, Farah
    This work addresses the possibility of vehicle-to-vehicle visible light communication (V2V VLC) protection. As one of the most appropriate kinds of artificial noise, Gaussian noise was added through one headlight and the other was used to send data, with Pulse Position Modulation (PPM) on a GNU Radio-based system and Red Pitaya FPGA as it was done. Experiments that were conducted with three levels of noise (0.01, 0.05, 0.07) have shown that growing artificial noise causes the success of data transmission to be reduced, yet the privacy of links improved. The DLH / NRH arrangement reported great success levels and above the NLH / DRH. The obstacles were synchronization errors, anomaly detection and differences in the beam patterns of the headlights. The results reveal that various security layers can be offered by using artificial noise jamming to secure a V2V VLC without the mere use of encryption. This demonstrates how lightweight, hardware-based methods might improve data secrecy in vehicle networks. The solution also shows that physical-layer security measures can be successfully integrated with low-cost platforms in real-world V2V VLC settings. Future research could investigate dynamic beam steering or adaptive noise levels to further balance the trade-off between secrecy and connection reliability.
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