In situ characterization of additive manufactured 316L stainless steel and copper

Additive manufacturing, particularly laser powder bed fusion (L-PBF), has revolutionized the metal manufacturing industry by offering enhanced design flexibility, reduced material waste, and accelerated production capabilities. L-PBF metals exhibit enhanced strength, hardness, and corrosion resistance, but their durability is still limited by porosity and residual stress. This study aims to determine the underlying deformation mechanisms, deepen understanding of the relationship between microstructure and properties, and improve the reliability of L-PBF metals with heat treatment, specifically focusing on 316L stainless steel and copper. Advanced in situ synchrotron techniques provide a real-time insight of the relationships between microstructural evolution and material properties. The superior strength, ductility, and strain hardening ability of L-PBF 316L stainless steel, is shown to be attributed to its specific microstructural features such as high dislocation densities and crystallographic orientations. Furthermore, the impact of varying heat treatment temperatures on the mechanical behavior and fracture toughness of L-PBF metals is systematically examined. Extending the analysis to L-PBF copper, the study investigates microstructural changes and physical properties post heat treatment. It identifies grain coarsening, twinning phenomena, and improvements in ductility, with high electrical and thermal conductivity achieved after heat treatment. Finally, the nucleation and propagation mechanisms of cracks are revealed

Three essays on the economics of traders and agents

This thesis consists of three chapters on traders and agents. The first chapter analyzes the characteristics of the UK agent market, particularly focusing on their strategic behavior, survival, and growth patterns. The analysis provides several contributions: First, the agents' market structure remains under-explored despite their significant role in handling over 85% of UK export and taking caring of border-related tasks. Our findings reveal a dual market structure, with a small number of dominant agents controlling the majority of the market through expansive operational networks, while numerous smaller agents foster competition by working in their niche markets. Second, qualitative studies fail to capture agents' development and growth. We find that new entrants typically begin with a narrow focus but gradually expand upon survival. The second chapter studies trader-agent relationships, especially their connection characteristics and dynamics. While the importance of cross-border buyer-seller relationships has been recognized in the literature, the relationships between traders and agents have been largely overlooked. This chapter uses granular UK customs data to document the key features of the trader-agent relationships and provide empirical evidence regarding their dynamics. We find that larger traders generally use multiple agents, while smaller ones have limited connections. Though the relationships are short-lived, those of high value and deep cooperation are more likely to sustain. In addition, we empirically confirm that traders are seeking more established agents in response to the Brexit-induced uncertainty. The third chapter examines agents within the framework of Mutual Recognition Agreements (MRAs) for trusted traders, which grant them streamlined customs procedures at foreign borders. Despite the widespread use of MRAs, evident in the fact that over 80% of UK exports occur between trade partners with such agreements in place, there is limited understanding of the effectiveness of this trade policy. We find that the majority of firms are indirectly classified as "safe traders" by working with AEO-certified agents. Building on this, we extend the heterogeneous firm model a la Melitz (2003) by incorporating administrative costs and highlighting the role of agents. Using transaction-level UK customs data, we empirically validate our model's predictions, showing that MRAs enhance firms' export participation and increase their export values through the involvement of certified agents

Chiral perylene diimide containing macrocycles and rotaxanes

This thesis describes an investigation into a class of chiral organic dyes, perylene diimides (PDIs). Specifically, configurationally stable PDI dyes are targeted through the design, synthesis and analysis of PDI-based macrocycles and rotaxanes. Chapter One introduces PDIs and outlines how the synthetic diversity of PDI derivatives impacts their photophysical, redox, supramolecular and chiral properties, with a particular focus on the integration of PDIs into macrocycles and rotaxanes. Chapter Two describes the design and synthesis of a series of novel chirally-locked PDI-based macrocycles, including an investigation into kinetic templation in the macrocyclisation reaction. The successful synthesis of PDI-based macrocycles with πelectron donors in the macrocycle linkers evidences the importance of π-π donor-acceptor interactions. Chapter Three explores kinetic templation in PDI-based macrocycles containing a second chiral aromatic component. Here, the diastereoselective synthesis of a PDI-based macrocycle is realised, in which templating non-covalent interactions between the aromatic units that direct the outcome of the dynamic kinetic resolution are discussed. Chapter Four describes the progress towards a configurationally stable chiral PDI through mechanical bonding by the synthesis of a novel [3]rotaxane containing a PDI-based axle and two macrocycle components. When positioned in close proximity to the chiral PDI, the macrocycles are shown to slow down PDI atropisomer interconversion. The pH-induced molecular shuttling of these macrocycles is also presented. Chapter Five describes the experimental procedures used throughout this work and details the characterisation of novel compounds. Chapter Six provides a summary of the major conclusions from the research described in this thesis

Linking student assessment and graduate employability: a study in the Omani higher education context

In recent years, there has been considerable emphasis on the need for higher education (HE) to facilitate graduate employability and readiness for the modern, fast-changing labour market. Producing employable graduates equipped with essential capabilities and attributes has become a major objective and concern for modern higher education institutions (HEIs). Among the various initiatives and activities leveraged by these HEIs to support this imperative, significant attention has been directed to student assessment (SA) as a critical activity for realising this goal. However, aligning SA with graduate employability development (GED) has proven to be a formidable task. This study explores the relationship between SA and GED, using the University of Technology and Applied Sciences, the largest HEI in Oman, as a case study. Specifically, the study aims to understand how SA relates to and can be effectively aligned with GED, and to identify the barriers and enablers of this alignment from the perspective of HE lecturers. The study utilised a mixed-method sequential case study design, employing a questionnaire, documentary analysis, and reflection-aided semi-structured interviews as data collection methods. It adopted a sociocultural perspective based on Cultural-Historical Activity Theory (CHAT), which views student assessment as a social activity system (SAAS) with GED as its central objective. This framework provided a comprehensive and systematic approach to examining the SA-GED link, thoroughly analysing the interactions between the system components. The novel combination of CHAT and Boud et al.’s (1985) reflection model proved powerful in understanding the operational dynamics of SAAS, recognising its central objective and identifying its systemic contradictions. The study revealed that while SA is a potent facilitator of GED, several factors impede its full alignment with GED at the research setting. The study emphasises the pivotal importance of conceptualising SA as a social activity system with GED as its central objective. This conceptualisation enhances clarity and understanding among SA community members, including lecturers, leaders, and students, by distinguishing the central objective of SA from its short-term goals such as grading student performance and ensuring accountability of assessment processes. The study illustrates how this conceptual framework critically supports the alignment of authentic assessment tools and systemic components – rules, community dynamics, and role distributions – with the overarching objective of SA. The study also revealed that successful implementation of authentic assessment hinges on effectively addressing systemic contradictions across all components of SA. These contradictions pose significant challenges to all community members involved. Specifically, the study underlines the critical role of the community component, which necessitates active and comprehensive engagement of leaders, students, workplace representatives, and lecturers in SA processes. Drawing on these insights, the study introduces an original “Model for Collaborative Engagement in GED-oriented Assessment”, thereby making theoretical and practical contributions to the fields of SA and GED in both the Omani context and similar international settings

Philip Henslowe and John Heminges: profits and the playhouse, 1587—1630

This thesis takes an original approach to a frequently overlooked aspect of professional London theatre in the late sixteenth and early seventeenth centuries: its undoubted commercial success, especially for those who owned the playhouses. A forensic examination of the playhouse careers of Philip Henslowe and John Heminges demonstrates that there was the potential for very substantial profits to be made through owning and operating playhouses. Uniquely, the thesis brings together documentary and archaeological evidence to estimate audience capacities for Henslowe’s Rose and Fortune, and the playhouses of the King’s Men (of which John Heminges was a co-owner), the Globe and the Blackfriars. Using simple spreadsheet templates (contained in an Appendix) current commercial theatre practice is then applied to these audience capacity figures to create estimates of the maximum amount each playhouse could earn at a single performance, or week, or year. Chapter 1, The Context, provides the background for Henslowe’s and Heminges’s playhouse careers with research into their wider lives and networks to determine the relative importance of the playhouse to each. Chapter 2, Philip Henslowe – Playhouse Entrepreneur, traces Henslowe’s development from novice builder of the Rose to intensely disliked owner and operator of the Hope at the end of his life, and offers calculations of the costs of constructing and running his playhouses. Chapter 3, John Heminges – ‘Business Manager’ of the King’s Men, views the well-known narrative of Shakespeare’s acting company through the growing responsibilities of Heminges as actor, business manager, co-owner of playhouses and, potentially, operator of ancillary sales at the Globe and Blackfriars. Chapter 4, Income and Profitability, synthesizes the information from the preceding chapters to produce estimates of income and profit, both corporate and individual. It calculates potential figures for Henslowe and his son-in-law and partner Edward Alleyn at the Rose and Fortune and for individual members of the King’s Men at their playhouses: Richard Burbage, William Shakespeare and John Heminges. The resulting estimates provide an original method of demonstrating the financial success of the industry as a whole and illustrate that, when the playhouses were operating in a period of stability, there was what Heminges himself described as ‘good yearly profit’ to be made

Investigating the role of tetraspanin Tspan15 and ADAM10 in cell invasion and cancer

ADAM10 is a ubiquitously expressed transmembrane sheddase involved in the ectodomain shedding of over 100 substrates. The tetraspanin superfamily is an evolutionarily conserved group of transmembrane proteins, which interact with specific partner proteins to regulate their trafficking, lateral mobility, clustering, and signalling. The TspanC8 subgroup of tetraspanins (Tspan5, Tspan10, Tspan14, Tspan15, Tspan17, and Tspan33) are important regulators of ADAM10, including its substrate specificity, and as such ADAM10 exists as six different ‘molecular scissors’. Further to this, Tspan15 has been reported to promote NF-κB signalling via its interaction with β-TrCP. ADAM10 and Tspan15 have been shown to mediate the invasion of various tumours, and in some malignancies, their role extends to promoting proliferation. However, Tspan15’s role in cancer is not as well characterised as ADAM10’s and very few studies consider the two proteins as a complex. As such, the overarching aim of this thesis was to investigate the role of Tspan15 in cancer and determine whether its mechanism of action is ADAM10-dependent and/or -independent. This thesis provided evidence from the analysis of patient data that ADAM10 and Tspan15 are individually or co-upregulated in a number of cancers, which in some cases is unfavourable for patient survival. However, despite being co-upregulated in pancreatic adenocarcinoma, follow-up in vitro experiments suggested that ADAM10 and Tspan15 do not regulate the invasion or proliferation of this malignancy. In contrast, Tspan15 was shown to promote the invasion of human embryonic kidney HEK-293T cells in an ADAM10-dependent manner, likely through N-cadherin shedding and FGF receptor signalling. Finally, this thesis also provided no evidence to support Tspan15’s involvement in mediating NF-κB signalling, warranting additional follow-up studies. In summary, this work furthers our understanding of the potential role of the Tspan15/ADAM10 ‘molecular scissor’ in tumour progression, and as such could inform the design of future anti-cancer therapeutics

Transfer learning of sentiment analysis between highly dissimilar domains

The aim of this thesis is to improve upon the current state of transfer learning technology in text based problems, with a specific focus on sentiment analysis. This improvement is in the form of increased distance between training and target domains. It proposes a method for defining inter-domain distance. Then examines the shortcomings of classical transfer learning methods, and proposes two novel approaches. The first `TransferGAN' extends on the use of Adversarial Learning Techniques for transfer learning, and the second demonstrates how Grammatical Evolution can be used to optimize existing sentiment analysis techniques to better suit transfer learning between dissimilar domains. Both of these methods demonstrate improvement over the comparison systems for transfer learning sentiment analysis with a high inter-domain distance. Finally these systems are demonstrated to be effective against the Motivational Interview dataset (A dataset of clinical conversations between diabetes patients and clinicians), which was the primary motivator for this work. This work could be further extended by field-testing of the systems against real world usage of the Motivational Interviews, and by working with clinicians to refine the system for automatic assessment of the Interviews

"The spawn of Romish frogs": to what extent were allegations of Roman Catholicism against early Quakers valid?

During the Interregnum, the early Quakers’ critics repeatedly made allegations that Quaker doctrines and practices resembled those of Roman Catholics, and that Quakers were Jesuits in disguise. The objective of this dissertation is to investigate whether there was any merit in these allegations. This is achieved by, first, comparing Quaker and Roman Catholic doctrines relating to the topics which were the subject of the allegations, namely salvation, the priority to be accorded to the Spirit and Scripture, sin, and the sacraments. Thereafter an examination is made of the specific allegations, in each case asking whether Quaker beliefs aligned more closely to those of Roman Catholicism than to those of the Reformed faith. Finally, a comparison is made between the principal characteristics of Quaker and Jesuit spirituality. It is concluded that on the doctrines of salvation, the primacy of the Spirit over Scripture, the possibility of achieving perfection in this life, and the fact of direct communication by God with human beings, Quaker beliefs resembled those of Roman Catholicism and were opposed to those of the Reformed faith. It is additionally concluded that Quaker practices resembled Roman Catholic practices only in minor respects and that there was no merit in allegations that Quakers derived their beliefs from Roman Catholicism, had been taught by Roman Catholics, had been infiltrated by Jesuits or were Jesuits in disguise. Further it is found that there were significant similarities between Quaker and Jesuit spirituality. It is suggested that these conclusions enhance the credibility of Quakers’ claim that they derived their ideas and beliefs from their own spiritual experience. It is further suggested that Quakers should not properly by placed on the extreme radical wing of the spectrum of groups in mid-seventeenth century England within the Reformed faith

'To gowerne þi persoune, crovne, and realme’: The development of advice to Princes in Britain in the High and Late Middle Ages

This thesis traces the development of advice to princes texts in Britain during the High and Late Middle Ages. Advice to princes texts were often produced at particular moments of political crisis, predominately those written by figures operating in the context of royal and aristocratic patronage – from Gerald of Wales and John of Salisbury to John Gower and Thomas Hoccleve. Charting the complex relationship of advisory literature to wider textual traditions, as well as the political world beyond the text, this thesis is concerned also with the multigeneric nature of advisory literature, which operated in relation to prophetic, pastoral, and complaint literature, among others – a selection informed by the specific topicality of these genres in the context of specific periods. While many advice to princes texts provide seemingly similar advice for rulers, such as the need to heed good counsel, eschew flattery, and ensure the stability of the kingdom, they more often than not express this advice as possessing pointed applicability to their king and closely paralleling other contemporary writings which articulate modes of critique conventionally understood as more direct. This thesis aims to contextualise such advice and criticism, providing instances where the language and themes found within the work echo that used by other contemporary authors and appear to react to specific political events. Thus, both the political and textual environments in which these works were written and/or compiled are revealed as formative sites of textual and extra-textual exchange and development in late-medieval political culture

The utility of intact light chain mass spectrometry-based assays for the detection of plasma cell disorders and the assessment of treatment responses

Mass spectrometry (MS) assays have been emerging over the last few years as a new and potentially more sensitive way to track monoclonal proteins in the serum patients with plasma cell disorders (PCD), although limited data on their prognostic utility is available. In addition, no studies have explored their potential utility in patients with multiple myeloma with low-level monoclonal protein production. Despite the use of intact light chain MS-based assays in lieu of immunofixation being approved by the Internal Myeloma Working Group in 2021, MS testing to monitor patients with PCD is currently only available at a single institution who have developed an in-house test. This thesis presents work undertaken alongside the Binding Site Ltd to develop a regulatory approved intact light chain MS-based assay and clinical studies undertaken independently to assess the utility of this assay for monitoring patients with PCD. Assay optimisation work conducted as part of this thesis has shown that the combination of free light chain (FLC) specific reagents in addition to a five bead matrix-assisted laser desorption/ionisation time-of-flight MS (MALDI-TOF MS) assay provides a more sensitive panel for the detection of low-level residual monoclonal FLC. However, the application of MALDI-TOF MS to urine did not provide any additional sensitivity to the serum-based MALDI-TOF MS-based assays. The sensitivity of FLC-MS for the detection of low-level residual monoclonal FLC was also enhanced by on-bead de-glycosylation in patients with light chain N-linked glycosylation. The first clinical study included in this thesis explored the sensitivity and prognostic utility of MALDI-TOF MS in patients being treated with carfilzomib, cyclophosphamide, lenalidomide, and dexamethasone (KCRD) in the Myeloma XI trial. In this work MALDI-TOF MS provided greater sensitivity for the detection of residual monoclonal protein compared to electrophoretic techniques and MALDI-TOF MS negativity was associated improved progression free survival (PFS). In addition, FLC-MS negativity in patients with no residual monoclonal protein detection by immunofixation electrophoresis at the end of induction, day+100 post autologous stem cell transplant (ASCT) and six months post maintenance randomisation was associated with reduced PFS. The second clinical study evaluated the utility of MALDI-TOF MS in patients with non measurable myeloma. This study showed that 91% of patients classified as having non-secretory myeloma using standard techniques have detectable monoclonal protein in the serum using MALDI-TOF MS. MALDI-TOF MS also provided greater sensitivity for monitoring patients with oligo-secretory myeloma. Further studies should therefore be undertaken to establish criteria for measurable disease using MS. The third clinical study included in this thesis evaluated the utility of a FLC specific MALDI-TOF MS assay in patients undergoing treatment for AL amyloidosis in the ALchemy study. This is the first study to evaluate the prognostic utility of a FLC specific MS-based assay in patients with AL amyloidosis and found that achieving FLC-MS negativity at six and 12 months post treatment initiation was associated with improved overall survival. There was also an improved rate of renal responses amongst patients who achieved FLC-MS negativity at 12 months. The final clinical study included in this thesis is the first study to evaluate the prognostic significance of light chain N-linked glycosylation in patients undergoing treatment for PCD. This study included patients treated with KCRD and ASCT for multiple myeloma and bortezomib-based treatment for AL amyloidosis. In contrast to the higher risk associated with light chain N-linked glycosylation in patients with monoclonal gammopathy of undetermined significance previously described by Dispenzieri et al this work found that light chain glycosylation was not associated with inferior responses to treatment or reduced survival