This thesis explores teacher wellbeing in two post-primary schools in the West of Ireland. The research was conducted using a qualitative case study methodology, through semi-structured interviews with twenty-six newly qualified and experienced teachers in two urban schools, one located in a disadvantaged area and the other in a middle-class area. Research on wellbeing suggests that it is a multi-dimensional concept and difficult to define despite a steep increase in scholarly research across a myriad...

The lack of robustly validated drug targets in Leishmania spp. is a major impediment to the discovery of new drugs and effective treatments for leishmaniasis. Here, 6 phenotypically-active anti-leishmanial compounds were selected from GSKs Kinetobox compound collections for subsequent target deconvolution studies. The principal aim of these studies was to identify molecular targets that can be exploited by subsequent target-focused anti-leishmanial drug discovery. Using multiple orthogonal genome-wide genetic, chemical proteomic and biochemistry-based approaches, two compounds...

This study set out to investigate social orphanhood through narratives of young people with experiences of growing up in care in Latvia. The study uses the life histories of participants to explore the phenomenon of social orphans. To date, narratives about the lived experiences of social orphans in Latvia have been told in the third person as most studies have used methodologies that kept participants passive rather than active. In this study the research process...

E3 ligase enzymes are key regulators of many aspects of eukaryotic biology via the promotion of the ubiquitylation and subsequent degradation of proteins. There have been over 700 E3s identified within the ubiquitin system with diverse mechanisms of E3 ligase activity, however, significantly less have been identified for ubiquitin-like proteins. Recently developed activity-based probes allowed for the identification of novel E3 ligase proteins involved in the ubiquitin system that carry out unconventional ubiquitylation. The development...

This thesis utilises the materiality concept of accounting to investigate institutional investor and assuror practitioner perspectives on sustainability reporting in the Nigerian oil and gas sector. The outcome of this investigation is expected to provide some insight into the prospects of success for the Nigerian financial sector’s drive to normalise sustainability reporting. For this purpose, a qualitative case study research was undertaken, which involved interviews of investors in decision making roles and auditors with social...

This thesis looks at the practical application of medical discourse to women found insane at London’s Old Bailey between 1863 and1913. Through in-depth analysis of all cases of women found insane at the Old Bailey, 1863-1913, this PhD thesis analyses the various discourses, medical, legal and cultural which appear to have been applied to these women in order to achieve a successful insanity plea. Using trial transcripts, newspaper reports, and published medical discourse the thesis...

This PhD thesis investigated the interaction between normal and reverse dip-slip faults and jack-up rigs. Finite-element methodologies (FEM) have been developed and validated against geotechnical centrifuge experiments which were specifically conducted by the author for this thesis. The PhD investigated the fault rupture–soil–foundation–structure interaction (FRSFSI) of a complete three-legged jack-up with spudcan foundations in sand. During an earthquake two events occur, the ground permanently displaces along the fault and dynamic oscillations (i.e. seismic shaking) propagate...

Thermo-active geo-structures are becoming more common as a renewable energy solution that both reduces carbon emissions and reduces the whole-life cost of building and civil infrastructure projects. These structures have an added benefit, which is that the additional cost to install is relatively small since the geo-structure is already required for structural stability. Thermo-active geo-structures can significantly reduce CO2 emissions from building and civil infrastructure and can have a significant impact on the Government’s attempts...

Cardiovascular diseases (CVDs) are the principal cause of death in people with diabetes. Initially, this was attributed to chronic hyperglycaemia and reduced insulin sensitivity. However, clinical trials have revealed that aggressive glycaemic control does not necessarily improve macrovascular outcomes in these individuals. One possible explanation for this is an increased occurrence of hypoglycaemia associated with intensive glucose lowering therapy. Hypoxic (HPC), ischaemic (IPC) and remote ischaemic preconditioning (R-IPC) are phenomena in which a degree of...

Over the last 30 years, mitochondrial dysfunction has emerged as a common feature of age-related neurodegenerative disease like Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s disease (HD) or amyotrophic lateral sclerosis (ALS). Parkinson’s disease is the second most common neurodegenerative disorder resulting from loss of dopaminergic neurons of the substantia nigra, in part due to mitochondrial dysfunction. In recent decades, the identification of numerous genes linked to PD have highlighted the importance of mitochondrial quality...

The independent regulatory model has been instrumental and applied in different developed and developing countries in the electricity sector. Reforms initiated through this regulatory model have been evaluated in different peaceful countries using an evaluation questionnaire to ascertain whether the reforms help or hinder the sector outcomes. In addition, the rule of law worldwide governance indicator has been considered as the most important indicator to measure the level of commitment and capacity to carry out...

Digital forensics suffers from a communication and knowledge sharing challenge. Various actions have been undertaken to solve this problem, such as the creation of glossaries or ontologies. However, those solutions usually have a narrow scope, are not publicly available and/or do not alo the reuse of the knowledge by artificial agents. Those restrictions have led to a limited use by the practitioner community and, therefore, have not resolved the communication challenge that the digital forensics...

Snf2 proteins are a large family of proteins present across all eukaryotes that have many roles in remodelling chromatin to regulate gene expression. Analysis of cancer tumour sequencing datasets has shown that several Snf2 proteins are included in the top 200 tumour suppressor genes, particularly SMARCA4, the Snf2 ATPase subunit of the human SWI/SNF complex. Most mutations in Snf2 proteins found in tumours are missense mutations; however, the mode of action through which these mutations...

The cornea, a transparent avascular tissue, is essential for human vision by accounting for approximately two-thirds optical power of the eye. Also, it plays as a structural barrier and protects the eye from infections. Corneal injuries or diseases are a leading cause of visual loss and even blindness. It is reported that 45 million people are affected by corneal blindness. The transplantation of a donor cornea to change the injured one is the gold standard...

Multiparametric magnetic resonance imaging (MP-MRI) and MRI targeted biopsies (TB) are a new standard in prostate cancer (PCa) screening and diagnosis. Guidelines already include this approach for patients at risk. First, this thesis aimed to assess whether pre-biopsy MRI can narrow the discrepancy of histopathological grades between biopsy and radical prostatectomy (RP) using the Prostate Imaging Reporting and Data System (PIRADS). Second, this thesis aimed to develop a prediction model to identify patients who will...

The gut is exposed constantly to invading bacterial populations and dietary antigens. To protect it from harm, a complex and diverse network of patrolling immune cells can be found spread throughout the gut and in specialized lymphoid structures. One immune cells type playing a key role in the protection and homeostasis of the gut, are the intraepithelial T-lymphocytes (IELs). This population of T cells, reside within the epithelial layer of the gut and are primarily...

Type 2 diabetes (T2D) is a complex disease characterized by insulin deficiency, due to pancreatic beta cell dysfunction, and insulin resistance (IR) leading to hyperglycemia. The management of hyperglycemia in T2D has become extraordinarily complex with a large number of medicine regimes being available which creates a major challenge in determining the best approach to achieve and maintain the appropriate level of glycaemic control. Response to anti-hyperglycaemic agents is conditional on phenotypic and pharmacogenetic effects....

Background: In the United Kingdom 2,460 per 100,000 nurses reported high work stress (Health & Safety Executive, 2020). The prevalence of work stress in critical care nurses (CCNs) is unknown. Despite a large literature base, the causes, and consequences of CCN work stress cannot be determined. Little is known of the effects of CCN work stress on patient outcomes. Methods: Phase I explored the work-related stress literature and identified measures to capture work-related stress and...

Recently, researchers have reported the potential value of CMR texture, especially for evaluation of ischemic and non-ischemic cardiomyopathy. However, these studies were mostly based on more advanced CMR sequences, and focused on myocardial disease at a later stage. Just one paper reports the application of TA using conventional CINE CMR sequences, and only one paper mentions healthy population myocardial TA with a small cohort. There are three main aims of this thesis. Firstly, to explore...

Targeted protein degradation (TPD) is a promising strategy for both therapeutics and research, providing new opportunities to overcome some of the current limitations associated with traditional small-molecule therapeutics, RNA interference (RNAi) and genome editing approaches. Proteolysis-targeting chimeras (PROTACs) are typically heterobifunctional molecules which bring a protein of interest (POI) into spatial proximity of an E3 ubiquitin ligase, triggering POI ubiquitylation and proteasomal degradation. The Sapkota lab previously developed an affinity-directed protein missile (AdPROM) system for...

Trypanosoma brucei is a protozoan that causes Human African Trypanosomiasis and nagana in cattle. The bloodstream form (BSF) of T. brucei has a dense surface-coat of variant surface glycoprotein (VSG) that acts as the first line of defence against the host immune system while the main cell surface glycoproteins of the procyclic form (PCF) are the procyclins. VSGs and procyclins are attached to the cell membrane through glycosylphosphatidylinositol (GPI) anchors. Despite its importance, the GPI...

Datasets in support of the paper Leptin-based hexamers facilitate memory and prevent amyloid-driven AMPA receptor internalisation and neuronal degeneration