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Decolonising the curriculum within UK higher education: a case study of academic perceptions in a post-1992 university
Get PDFDecolonising the curriculum became the focus of UK Higher Education (UKHE) following student campaigns to change the dominant Eurocentric focus in terms of pedagogy, learning experiences and intellectual contributions. The influence of UK government initiatives, from Prime Minister Initiatives (PMI) in 1999 and 2006, through to AimHigher Excellence Challenge (2001) were examined and provide a historical background within which the case study organisation, Peak University, is situated. The theoretical framework of Postcolonial Theory and Interest-convergence were used to examine the UKHE system to illustrate where issues of knowledge, power, complicity, and resistance are present within its structures. Interviews with academics across business and humanity disciplines were undertaken together with a student focus group and survey. Data revealed that heavy workloads, limited support, and direction from senior management, as well as access to marginalised and underrepresented knowledges were barriers to transformative change. Academics displayed a good understanding of the need for change to the curriculum to address the increasing diversity of the student body, but also demonstrated frustration in relation to the leadership and direction provided. As such this study extends previous theoretical understandings of race in education and the interplay with knowledge and power. It is recommended that this study be extended beyond Peak University to other institutions and organisations engaging in anti-racism work
The psychological impact and clinical outcomes associated with testing for ovarian cancer in symptomatic women
Get PDFAims: To investigate the psychological and clinical impact of symptom-triggered testing for ovarian cancer (OC).
Method: To investigate the psychological impact of symptom triggered testing for OC, a systematic review (SR) was undertaken to identify variables that were associated with psychological morbidity in patients undergoing testing for any cancer. The association between variables identified in the SR and anxiety and distress levels in women undergoing diagnostic testing for OC was subsequently explored in the dataset from a single-arm prospective diagnostic test accuracy study (Refining Ovarian Cancer Test accuracy Scores (ROCkeTS). To estimate the prevalence of psychological morbidity following testing for OC. To investigate the clinical benefit of symptom triggered testing for OC, the true positive rate of OC diagnosis by age, menopausal status and referral pathway was estimated in the ROCkeTS dataset. Finally, the oncological outcomes (performance status, stage at diagnosis, cytoreduction rate, extent of disease) in women diagnosed with high grade serous OC, the most lethal form of OC was evaluated.
Results: Findings from our SR demonstrated that the contribution of some factors to anxiety in cancer testing and their specificity of effect remain inconclusive. Targeting young women or those who are unemployed or who have low levels of educational attainment may offer a means to mitigate anxiety. Some studies suggested that one-stop clinics and patient navigators may be beneficial to mitigate anxiety. Most women
experienced moderate-to-severe distress and anxiety following a referral for OC testing. The severity of anxiety and distress levels remained unchanged or worsened in the majority of women at 12 months post OC testing despite a non-cancer diagnosis. Younger women and those who presented via the emergency pathway reported higher distress levels but were less likely to receive a diagnosis of OC. Symptom triggered testing facilitates the diagnosis of high grade serous OC at an early stage when women are in generally good health. Even in women with advanced
stage OC, the tumour load is relatively not extensive and complete surgical clearance can be achieved in a high proportion.
Conclusion: Younger women have a lower risk of developing OC but are at especially high risk of psychological harm from testing and should be targeted for support. Improving awareness of the symptoms of OC will facilitate the institution of early investigations and evidence demonstrates that surgical intervention at an early stage improves outcomes
PBF phosphorylation in endocrine cancer
No full textPituitary tumor-transforming gene-binding factor (PTTG1IP/PBF) is a proto-oncogene that is upregulated and associated with tumour progression in various cancers including thyroid, breast, colorectal, liver, and lung. The impact of PBF varies across different cancers; predominantly heightened PBF expression is linked to cancer metastasis and recurrence in cancers such as breast and thyroid, while the downregulation of PBF has been linked with aggressive breast cancers. PBF is engaged in diverse cellular pathways in both normal and disease mechanisms, influencing processes such as cell proliferation, cell migration, cell adhesion, and cell invasion. Notably, PBF phosphorylation at tyrosine 174 is one of the most highly phosphorylated residues in the human proteome, and initial investigations have demonstrated that it may mediate PBF function in breast and thyroid cancer cell invasiveness. This study sought to elucidate the importance of PBF and its regulatory phosphorylation in the induction of cell motility.
Key elements of the C-terminal regulatory tail of PBF were evaluated in the migration and invasion of thyroid and breast cancer cells. Our findings indicate that not only phosphorylation but also endocytosis from the plasma membrane plays a crucial role in facilitating PBF-stimulated migration and invasion.
A potential relationship between PBF phosphorylation, endocytosis and protein stability was investigated. A role for Y174 phosphorylation in mediating PBF plasma membrane localisation and stability could not be determined. However, mechanisms of PBF protein turnover were elucidated with degradation via proteasomal and lysosomal pathways demonstrated.
Increasing evidence of PBF stimulation of cancer cell motility and interaction with related molecules and pathways led us to hypothesise that PBF has a physiological role in the regulation of cell motility.
To investigate this, mouse embryonic fibroblast (MEF) cells were isolated from a novel Pbf knockout (KO) mouse model and characterised. Pbf-KO MEF cells demonstrated significantly impaired migration and invasion capacity. KO cells heterozygous for Pbf deletion demonstrated an intermediate reduction in cell motility, suggesting a potential gene dosage effect. To establish an intermediate model bridging primary and cancer cells, primary MEF cells were immortalised. Functional assays once again showed a notable downregulation of MEF cell migration with Pbf deletion. Collectively, these findings strongly indicate a physiological role for Pbf in normal cell motility. Additionally, through RNA sequencing, molecular alterations downstream of Pbf-depletion in primary MEFs were identified, and cellular processes and pathways in which Pbf is involved in normal physiology were delineated. In addition to the involvement in cell motility as expected, a strong link with immune regulation was apparent.
In conclusion, this thesis highlights the significance of PBF as a crucial regulator of cell motility, impacting both normal physiology and dysregulation in disease, such as cancer progression. These findings contribute to our understanding of the function and regulation of this proto-oncogene in the critical cellular process of motility. A comprehensive understanding of the nature of PBF is essential for considering its potential utilisation as a biomarker or as a target in therapeutic approaches
Ethics of nonviolent politics -a critical 21st century analysis
Get PDFThere has been extensive literature written on nonviolence as a strategy for securing political change. The general tenor is that nonviolence is considered ethically preferable due to the absence of direct violence. To what extent is this assumption valid, and is it right to believe that nonviolence is always ethically unproblematic and, therefore, justifiable? The existing literature concentrates mainly on the feasibility and achievements of nonviolent actions, leaving sufficient room for debates on ethics, morality and the concept of power in nonviolent theory in politics. Also, the discussions and works surrounding violence and nonviolence often treat the topics as separate entities. The research explores whether violence and nonviolence are entirely different things or similar under certain circumstances. The existing differences or similarities will be elucidated. Further, this research will explore the ethical questions concerning the moral legitimacy of nonviolent actions using coercion, manipulation and control. An ethical framework to address the morality of political actions will be proposed.
The thesis does not research the success or failure of political goals using nonviolent actions as a political strategy. Neither is it an examination of whether violence or nonviolence is preferable for certain kinds of goals. Instead, the presented research solely explores the motivations behind actions defined as ‘nonviolent politics’ and discuss morality and ethics regarding these actions. This thesis shall analyse the concepts of violence and nonviolence and study real-world examples to see whether they are distinct. The concept of power and coercion in terms of violence and nonviolence will illuminate how violent and nonviolent political actions resemble each other. Moreover, this research will examine 21st-century political circumstances and apply nonviolence theories to determine whether and how advanced information technology has shifted the ethics of nonviolent politics
A fault detection and diagnosis methodology for railway turnout systems based on parameter estimation
Get PDFRailway turnout systems are one of the most important signalling elements in railway operations, such that their failure during service hours can adversely impact service reliability and safety. Thus, effective maintenance must be applied to ensure that their failure is prevented. For such purposes, data-driven fault detection and diagnosis (FDD) methodologies have been commonly proposed as viable solutions. However, regardless of their exceptional accuracy, they usually
employ advanced data analysis algorithms which are difficult for maintenance staff to comprehend. Moreover, their overfitting nature requires them to undergo a sophisticated re-training process before they can be effectively transferable to diagnose other railway turnout systems.
Due to these difficulties in their practical applications, this thesis proposes an FDD methodology developed from a parameter estimation technique instead, where underlying system knowledge is used to simplify diagnostic reasoning. Once the proposed FDD methodology is applied to a real turnout, it can estimate physically interpretable turnout parameters. These parameters exhibit changes in patterns when a particular fault mode is present in the turnout system. Due to the interpretability of estimation results and specific changes in the parameters, an interpretable and comprehensible classifier can consequently be developed.
The classifier achieves more than 80% overall accuracy when it is applied to the training turnout system. For every diagnostic decision, the skilled personnel can also re-assess it based on the interpretable parameter estimates used in the classification. However, when the proposed methodology is immediately applied to diagnose a different turnout system, it only achieves approximately 60% overall accuracy. Due to the interpretable and traceable diagnostic reasoning used in the
classifier, a simplified cross-training and tuning procedure can be implemented. This improves the accuracy to nearly 90% in diagnosing the test turnout system.
In summary, this thesis proposes and develops a parameter estimation-based FDD methodology for railway turnout system applications, which realises interpretability and traceability as well. Achieving transferability is also possible, but the FDD methodology must undergo some degree of cross-training first for its application to be effective on different turnout systems
A sociolinguistic study of sign language(s) in Algeria: exploring the situation of sign language(s) in Algeria and the attitudes of the signing community towards signers and sign language variation
No full textThe research at hand is a sociolinguistic study that aims to shed light on the present situation of sign language(s) in Algeria. It explores the current situation of sign languages in Algeria and the deaf community due to the lack of literature on this issue in the field of sociolinguistics. Equally important, the study aims to explore the social factors that came into play in shaping sign language variation in Algeria by highlighting the factors that influenced the emergence, development, maintenance, and use of sign language varieties in Algeria.
The conceptual framework of the study lies in adopting aspects of the variationist sociolinguistic approach which explores the effect of social factors on variation in spoken and signed languages (e.g., Lucas et al., 2001). The research explores the effect of social factors on sign language use in Algeria by interviewing seven hearing and six deaf Algerian signers who shared their experiences of sign language use and the signing community.
Furthermore, the research applies a qualitative methodological approach in which semi-structured online interviews were used in order to collect data. In order to test the feasibility of the study, a pilot study was first conducted in order to investigate the current sociolinguistic situation of sign language varieties in Algeria. From this, two main research questions were raised: (a) what are the social factors that came into play in shaping sign language use in Algeria? And (b) what are the experiences of deaf and hearing members of the signing community? Thematic Analysis has been applied to analyse the data gathered after transcribing, translating and coding the data.
Results, according to the participants’ responses, showed that there are other varieties of sign language in Algeria than the widely used Algerian Sign Language (LSA) and French Sign Language (LSF). The presence of this variation its emergence, development, and use, are affected by a range of factors, which include (a) historical factors that cover the rich history of Algeria and the long period of colonisation that it underwent, (b) cultural aspects such as food, traditions, dress, (c) recent appearance of new illnesses and viruses, (d) political aspects such as the language planning and policy conducted by the Algerian government and the attempts to unify and standardise LSA in order to detach the country from a history of use of LSF and to spread Arabisation, (e) religious aspects such as the borrowing of new Islamic signs from the sign languages of Middle Eastern countries such as Qatar and Saudi Arabia, (f) technology, such as naming new objects and inventions, (g) regional variation and geographical boundaries, (h) social media (mainly Facebook) such as borrowing new signs from other countries when communicating online with other deaf people from those countries, (i) socio-economic status.
Finally, after analysing the narratives of the experiences of these members of the signing community, results revealed that there were varying attitudes expressed by the signing community towards both the signing community itself and the sign language varieties, including both positive and negative attitudes depending on the situation discussed. It is noteworthy that the study showed that those social factors that came into play in shaping LSA are reflected in the attitudes of the signing community as well
Shaping the future of prisons in Europe, and Europe in prisons
Get PDFStructural shortcomings across EU prison systems give rise to systemic risks of human rights violations. This constitutes an issue for the EU on a principled and functional basis both. The prison reality undermines the EU values, objectives, and anti-crime judicial cooperation policies. The EU has acknowledged and responded to the problem. Actual EU initiatives in prison, while commendable, do not satisfactorily address the issue. A functionalist approach dominates, with the principled task of rescuing the EU values assuming secondary place. Going forward, the EU should reframe its current strategy, placing individual prerogatives at the heart of the discussion. It should further examine the potential of harmonising detention standards via an EU Prison Charter – though it is doubtful whether the current form of the Treaties legally allows for such a possibility. Finally, the EU should account for the indirect, yet significant impact of its judicial cooperation and criminal justice policies on the individual detainee
Investigating the relationship between USP50 and WRN in DNA replication
Get PDFUSP50 is a poorly understood deubiquitinase with emerging roles in replication. Previous work in the laboratory revealed an epistatic relationship between USP50 and the RECQ helicase WRN in preventing replication-associated DNA double-strand breaks. In this thesis we probed the relationship between USP50 and WRN further and examined their shared and independent roles in replication fork progression and restart, DNA double-strand break formation, and response to replication stress. We found that USP50 and WRN co-operate to support fork progression in replicating cells, with USP50 promoting WRN localisation to stalled forks. We found that RECQL4 and RECQL5 rescue DNA replication in cells depleted of USP50 and WRN. We saw that USP50 promotes formation of DNA double-strand breaks near transcription start sites, indicating a novel role in promoting transcription. Investigation of the roles of USP50 and WRN in microsatellite unstable colorectal cancer cells revealed that USP50 is not a synthetic lethal target in these cells, unlike WRN. WRN loss in microsatellite unstable cells leads to loss of D NA damage repair proteins and cell death. Together the data presented in this thesis deepens our understanding of the USP50-WRN relationship in microsatellite stable and unstable cancer cells, and reveals the surprising ability of RECQ helicases to compensate for each other in DNA replication
Investigating the role of HEB and its interaction with GFI1 in t-cell acute lymphoblastic leukaemia (T-ALL)
Get PDFAn intricate network of transcription factors determines gene expression patterns that define cellular identity. Development of T-cells involves dynamic changes, including the activation and silencing of transcription factors. As part of the transcriptional landscape, TAL1 forms a heterodimer with E-proteins such as E2A, E2-2, and HEB, which bind DNA and activate transcription as part of a complex, including LIM-only protein 2 (LMO2), Lim domain-binding protein 1 (LDB1), and GATA proteins. The overexpression of LMO proteins, as well as an abnormal expression of TAL1, has been identified as hallmarks of T-cell Acute Lymphoblastic Leukaemia (T-ALL). Considering the high relapse rates, drug resistance, and poor prognosis of T-ALL, it is imperative to investigate the molecular mechanisms underlying T-ALL in order to develop effective therapeutic strategies.
E-proteins have important roles in the progression of haematopoiesis, orchestrating thymocyte maturation and developmental progression. HEB, a member of the E-protein protein family, plays a pivotal role in guiding thymocytes toward the double positive stage and beyond. HEB exists in two isoforms: HEB canonical and HEB alternative. A previous study of HEB immunoprecipitation followed by mass spectrometry identified the transcription factor GFI1 as a potential new member of the complex. Recent research has shown that GFI1 has dual functions, acting as a transcriptional activator in conjunction with IKAROS and as a transcriptional repressor by recruiting KDM1A. However, the role of GFI1 in T-ALL remains unexplored.
This study identified the interaction between HEB and GFI1, particularly with the HEB alternative isoform, in four human T-ALL cell lines (ARR, DU528, HSB2, and CCRFCEM), using proteomic analysis and genome-wide studies. The genomic distribution of GFI1 was examined using chromatin immunoprecipitation (ChIP)followed by next generation sequencing (ChIP-seq). Comparisonof these data with previous ChIP-seqdatarevealed that distinct binding complexes exists in ARR and in the other three cell lines.
The role of HEB in T-ALL was further dissected using CRISPR-Cas9 gene editing. Targeting , the gene encoding HEB, led to the loss of the expression of the canonical isoform of HEB. This reduced the expression of its alternative isoform, providing evidence for a regulatory interaction between the two isoforms, as well as reduced the expression of GFI1. There was no significant morphological change or chromosomal instability in the ARR cells following HEB deletion, indicating that deletion does not cause overt cellular abnormalities. In response to the loss of HEB, LMO2 is observed to possess increased association with the DNA, increasing chromatin accessibility, and potentially compensating for the loss of HEB through enhanced DNA-cofactor interactions. Overall, these findings provide valuable insight into the molecular basis of T-ALL, which could lead to the development of targeted therapeutic interventions
The ecomorphology and musculoskeletal biomechanics of wild western lowland gorillas (Gorilla gorilla gorilla)
Get PDFWestern lowland gorillas are the largest and most sexually dimorphic ape. Their heavily robust musculature and adaptations towards terrestrial quadrupedal locomotion makes them suitable models for understanding the relationship between morphology, ecology and behaviour in arboreal environments. The arboreal environment is characterised by supports that vary in availability, size and compliance, but it was not previously understood how western lowland gorillas find solutions to the challenges of feeding and travelling in the trees. This thesis addresses this gap in our knowledge by presenting new comprehensive data on the arboreal locomotor repertoire of wild western lowland gorillas. A group of fully habituated wild western lowland gorillas were followed for twelve months in the Loango National Park, Gabon. Walking and vertical climbing dominated the gorillas’ arboreal locomotor repertoire, but gap-crossing behaviours made up a considerably larger proportion of their locomotor repertoire than expected. Overall, the gorillas minimised the risk of falling in the supports and hand postures they used when addressing the ecological challenges of accessing different heights, moving in the canopy and dealing with discontinuity.
Despite being phylogenetically close, great apes vary in postcranial morphology and the ecological niches that they inhabit. In order to identify what separates, and what links the locomotor ecology of great apes, focus was then directed towards comparing the arboreal locomotor repertoire of the gorillas with wild chimpanzees and orangutans. The orangutans engaged mostly in suspension, whereas the chimpanzees mostly used vertical climbing, and the gorillas engaged mostly in walking. Interspecific comparisons of support use for gorillas and orangutans revealed that each species differed in the size, type and number of supports that they used when addressing different ecological challenges. Body size also influenced the arboreal locomotor behaviours of the great apes, but in patterns that did not align with classic predictions. Overall, the results suggested that evolutionary selective pressures have shaped the locomotor behaviours used in complex arboreal environments to reduce energy expenditure. However, the variation in support use reflected many aspects, including their morphology, ecological niche, degree of arboreality and strategies to mitigate the risk of falling.
The next step in developing an understanding of how great apes interact with their environment is to study their locomotor biomechanics in natural habitats. Kinematic analysis of great ape locomotion is used to understand the mechanisms of movement. Recent technological advances in deep learning software to recognise and track objects is revolutionising the way in which we can study animal locomotion. Pose estimation uses this framework to detect body landmarks but very few studies have applied this framework in wild settings. Using video footage of wild gorillas, two open-source markerless pose estimation frameworks were compared to manual identification of body landmarks to assess the accuracy of machine learning software packages, DeepLabCut and Open Ape Pose. Overall, it was determined that they are not yet ready to be applied to wild footage because of the complexities of natural habitats and focus should now be directed towards exposing these software packages to more wild footage so that this can be possible in the future.
These studies highlight the importance of studying primates using the ecomorphology framework. Furthermore, by integrating data on the arboreal locomotor behaviour of apes with locomotor kinematics, this makes them suitable referential models for understanding the evolution of hominoid locomotion
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