VictorJuiz/thesis huggingface dataset:
Macrophage-matrix interactions in the breast tumour microenvironment: the case of tenascin-C
Keywords: scRNAseq
TNC
tumour microenvironment
breast cancer
macrophage
TAM
epigenetics
tenascin-C
extracellular matrix
KDM6B
single-cell RNAseq
tumour-associated macrophage
ECM

Tumour-associated macrophages (TAMs) are key immune-suppressive constituents of the breast tumour microenvironment (TME) and correlate with poor prognosis. Tenascin-C (TNC) is an immunomodulatory extracellular matrix (ECM) protein which is upregulated in breast tumours, and is associated with increased metastasis and worsened prognosis. Our previous work showed that perturbation of the breast TME by tumour-derived TNC skews macrophages towards an immune-suppressive phenotype featuring downregulated antigen-presentation. Using TNC as an exemplar perturbant, this thesis sought to understand how macrophage effector functions such as antigen presentation become enhanced or suppressed within the TME. To achieve this, single-cell RNA sequencing (scRNAseq) was performed on infiltrating myeloid cells derived from syngeneic, orthotopically-engrafted, murine breast tumours that were engineered to express high or low levels of TNC. scRNAseq revealed marked heterogeneity in the intra-tumoural myeloid compartment with 7 distinct subsets observed, 5 of which were macrophages (Mac1-5). Notably, macrophages delegated key effector functions including antigen presentation (Mac2) and chemokine production (Mac3) to discrete subsets that were phenotypically, spatially and temporally distinct at the protein level by flow cytometry and confocal immunofluorescence imaging. The role of TNC was predominantly exerted at the level of subset abundance (rather than gene transcription), with 4 out of 7 myeloid subsets exhibiting TNC-dependent changes in abundance, including two macrophage subsets (Mac1 & Mac2). Over time, TNC modestly weakened the segregation of Mac2 and Mac3 phenotypes, suggesting it may drive dysfunctional delegation of effector functions. Pseudotemporal analysis of scRNAseq data implicated the epigenetic regulator, Kdm6b, in governing the acquisition of Mac3 effector function, and pharmacological inhibition of KDM6B in vivo shifted the proportion of Mac3 via TAM reprogramming. Finally, mouse-derived myeloid subsets were well-conserved in the most comprehensive scRNAseq atlas of human breast cancer, and gene signature analyses in bulk clinical datasets demonstrated significant differences in prognosis for patients with distinct myeloid ‘ecotype’ profiles. Together, these data demonstrate functionally divergent roles for TAM subsets in breast tumour progression and metastasis, while providing mechanistic insights into the impact of ECM-derived cues such as TNC on shaping the myeloid compartment, with potential therapeutic and prognostic implications for breast cancer patients.
The microvariation of post-verbal negative particles in Old Gallo-Romance: a comparative study
Keywords: Medieval
Langue d'oïl
Syntax
Gallo-Romance
Linguistics
Grammaticalisation
Negation
Middle French
Occitan
Post-verbal
Old French
Langue d'oc

This thesis is a microvariational analysis of post-verbal negative particles in varieties of Old Gallo-Romance between the years 1100 and 1500 A.D. It examines the internal and exogenous factors contributing to the survival of certain particles and the disuse of others. Using a mixture of verse and prose data from six oïl varieties and ten oc varieties of Old Gallo-Romance, it draws comparisons between them from the following perspectives: rates and degrees of grammaticalisation; the influence of discourse-pragmatics and information-structure on their presence, absence and frequency of occurrence; their diatopic and diachronic spread; and the effect that standardisation, linguistic prestige, and a scribal koiné had on the diminishing number of competing post-verbal negative particles in the grammar. In essence, it seeks to clarify why pas, as one of several hundred so-called ‘minimisers’, came to be the default sentential negator in French, rather than any other competing variant.
Experience teaches? How can the orientations to learning from experience framework (Hagger et al. 2008) be used by mentors and teachers to explore learning to teach on employment-based routes?
Keywords: Initial teacher education
employment-based initial teacher education
mentoring conversations
teacher learning
double stimulation
mentorin

Recent changes within teacher education policy in England present a timely opportunity to consider the nature of teachers’ learning through experience on employment-based routes. This thesis draws on the Orientations to Learning from Experience Framework ((OLEF) Hagger et al. 2008), which uses five dimensions to describe the dispositions of beginning teachers to learning from experience, as identified in a three-year longitudinal study. In this study I investigated if and how this research product could be used by mentors and beginning teachers to explicate and develop participant teachers’ learning.
In the secondary school site of this qualitative study the majority of the teachers in their first or second years as teachers were undertaking, or had undertaken, ‘employment based’ routes of initial teacher education. Nine beginning teacher participants and their mentors were involved in data collection and analysis during their first years as teachers on School-Direct Salaried and Teach First routes. As a ‘Close-to-Practice’ study focussed on employment-based initial teacher education, it offers a fresh perspective on the complex, contextualised and idiosyncratic process of learning to teach.
The OLEF framework and other re-presentations of their practice stimulated rich data regarding the beginning teachers’ learning, thereby demonstrating the potential for OLEF to act as second stimulus in formative interventions. Furthermore, I developed the conceptual framework of OLEF by drawing in contemporary research through citation analysis as well as cross- and within-case analysis of the conversational data. Intentionality, one of the socio-cultural concepts of OLEF is considered in relation to self-efficacy, professional agency, self-regulation, adaptive expertise and deliberate practice. Five conditions which support high levels of Intentionality were found.
Few research studies have captured conversations between beginning teachers and their mentors in the recent English context. These conversations were recorded and analysed by participants, opening up their semi-private world. The role of mentors as mediators in supporting self-regulation and the development of a broader Frame of Reference is explored. The data contributes to discussion about the nature of teachers’ knowledge, learning, self-regulation and professional agency. Practical implications for beginning teachers and their mentors are offered.
The memory of Ignatius of Antioch: the martyr as a locus of Christian identity, remembering and remembered

Keywords: Remembering
Patristics
Ignatius of Antioch
Sacrifice
Girard
Memory
Remembrance
Theology
Martyr

The fundamental argument of my thesis is that the concept of ‘memory’ provides remarkable insight into the early second-century bishop and martyr, Ignatius of Antioch; my thesis seeks to explore the nature of this insight and unpack its significance. His palimpsestic literary legacy and personal preoccupation with remembering and its correlates make Ignatius uniquely suited among early Christians to be unlocked by the key of memory. This endeavour broadly takes its lead from Elizabeth Castelli’s Martyrdom and Memory (2004). She argues that ‘memory work’ done by early Christians on the experience of persecution and martyrdom was a form of ‘culture making’; Christian identity is coloured by memory of the religious suffering of others. My focal question is an extension of hers, and has three parts. Given that remembering in community is central to the development of the early church, its theology and self-understanding: 1) What is the nature of the memories inherited by Ignatius and his communities, and how are they engaged in the rhetorical and polemical context of his letters? 2) How does Ignatius construct himself as a figure to be remembered by Christian interpreters? 3) How was Ignatius in fact memorialised in early Christian history?
This thesis spans three centuries and three distinct parts. I therefore establish my argument by a combination of means: close reading of the ‘authentic’ middle recension letters, select and critical interaction with sociology and anthropology, and thorough analysis of the long recension and Ignatian martyrological accounts. The long recension has received only meagre scholarly attention, so my work constitutes a significant contribution to Ignatian scholarship with regard to this corpus in particular. Memory is demonstrated to afford a previously unnoticed hermeneutic from which to approach Ignatius, who is at once one remembering, one aspiring to be worthy of remembrance, and one indeed remembered.
Examining ‘The eye of the earth’ the Pan-Pacific idea & the British dominions, c. 1910-1940
Keywords: Asia
Australasia
United States
Commerce
Ethnology
Imperial History
Canada
Pan Pacific
Hawaii
Economic History
Trans-Pacific
World History
Australia
Transnational History
Pacific History
British Empire
Global History
Geopolitics
Indo-Pacific
New Zealand
Imperialism

This thesis examines the emergence and influence of the ‘Pan-Pacific’ idea from the 1910s-1940s. It makes the case that to a diverse demographic globally, it proved a compelling regional geo-paradigm; the institutions it inspired, significant inter-imperial spaces for representatives from the former British Dominions to consider their society’s place in the world and the region’s globality.
Situated at the intersection of ‘British’ and ‘Pacific’ World historiographies, the thesis is organised as a multi-thematic intellectual history, demonstrating the capacious appeal and ideological multiformity of the Pan-Pacific in educational, ethnological, leftist, commercial and geopolitical contexts respectively. Chapter 1 explores the intellectual roots of the Pan-Pacific, examining the institutional archives and private papers of figures associated with the Institute of Pacific Relations and Pan-Pacific Union. It argues that a ‘Honolulu nexus’ in inter-imperial affairs emerged, influencing a greater appraisal of the Dominions’ own interests, including a form of ‘rooted regionalism’, largely neglected in the extant literature. Chapter 2 examines how the Pan-Pacific proved a conduit for the examination of race relations through the ethnological research programme of Honolulu’s Bishop Museum and its investigations into the ‘Polynesian Question’ (the then disputed origins of the peoples of Oceania). Chapter 3 examines the attractions of the ‘political left’ to the Pan-Pacific, exploring the affiliation of trade unions in the Dominions to the Comintern-backed Pan-Pacific Trade Union Secretariat. Chapter 4 explores how the Pan-Pacific idea boosted a regional commercial imaginary, whilst shedding light on the emergence of the Dominions’ own nascent regional trade representation in the form of regional ‘Honorary Agents’. The final chapter considers the emergence of trans-Pacific aviation and its influence upon conceptions of Dominion defence from sites spread across a Pan-Pacific cartography – from the atolls of the Phoenix Islands to the Kermadecs, spaces which found renewed significance in the ‘Air Age’.
What is the justification for subrogation to extinguished rights?
Keywords: subrogation
remedies
unjust enrichment
private law
private law theory
marshalling

Subrogation to extinguished rights ('subrogation') describes a particular form of rights: C's new rights against D resemble X's extinguished rights against D. This thesis resolves four controversies surrounding subrogation: is subrogation redundant; what is the justification for subrogation; when should subrogation occur; and is subrogation a remedy for unjust enrichment? The thesis is divided into two parts. Part I considers what the law is and Part II considers what the law ought to be.
Part I asks whether, as the law stands, subrogation is redundant. Contrary to orthodoxy, it argues that subrogation is available in different circumstances and has a different effect compared to a 'direct unjust enrichment claim'. Consequently, subrogation does not duplicate a 'direct' claim and so subrogation is not redundant.
Part II asks what justifies subrogation and, in light of that, when should subrogation occur? Contrary to orthodoxy, it argues that there is not one justification for subrogation but two, each of which is sufficient on its own. Subrogation can be justified by a duty not to use a right for one’s own benefit. Alternatively, subrogation can be justified by C bearing the burden of a debt which ought to be borne by D. Each justification mandates a different test for when subrogation should occur, explaining why different subrogation cases apply apparently contradictory rules.
The question of whether subrogation is a remedy for unjust enrichment is addressed in Parts I and II. Part I shows that subrogation does not duplicate a 'direct unjust enrichment claim'. Part II argues that, once the justifications for subrogation are understood, unjust enrichment is a distraction. It is therefore concluded that subrogation is not a remedy for unjust enrichment.
The lived experiences of claiming wrongful conviction in prison
Keywords: Wrongful conviction
Criminology
Prison life
Maintaining innocence

This thesis examines the lived experiences of prisoners who believe themselves to be wrongfully convicted. It is based on the written accounts of sixty-four prisoners who are currently maintaining innocence and offers a comparison to their ‘rightly’ convicted counterparts, as evidenced in the academic literature. What these accounts illustrate is that although this population do largely adjust to the prison environment, their experiences are constantly framed by notions of injustice and illegitimacy and it is these feelings that become the lens through which they navigate prison life.
These people are adept at tailoring their coping strategies to suit their unique situation. Through campaigning, subtle acts of resistance, and refusal to internalise the criminal label, they are able to signal their discontent and significant resentment. Relationships too, are capable of being moulded to meet their needs. Although participants appear relatively solitary, remaining on the fringes of the prison social system and maintaining distinctions between themselves and the ‘criminals’ they are forced to live with, they create unique support networks. Such networks are dominated by prisoners who similarly maintain their innocence and charitable organisations, and draw heavily on the considerable support offered by their families.
There are, however, institutional consequences to maintaining innocence within the prison environment. A myriad of areas, ranging from everyday living conditions, risk assessment, progression, and ultimately parole, are all impacted by claims of wrongful conviction. As this thesis illustrates, such a position is often inconsistent with Prison Service Orders and Instructions. Relatedly, there also appears to be a distinct lack of support and a pressure to ‘admit’ guilt displayed by certain members of staff. Nevertheless, due to lack of viable alternatives and a desire to obtain release at the earliest opportunity, these prisoners must engage with the prison authorities and are thus required to work within a system that is not designed for them and largely ignores their needs.
Structural and functional characterisation of properdin and properdin-binding complement inhibitors from ticks
Keywords: Immunology
Structural biology
Complement system
X-ray crystallography

The complement system is a major effector of the immune response which can lead to opsonisation and inflammation, as well as the removal of immune complexes and damaged self-cells. The complement system requires many regulatory proteins to prevent inappropriate activation towards healthy self-cells and to only target invading pathogens. This thesis focuses on a complement regulator/activator called properdin, which has primarily been associated with the alternative pathway (AP). Properdin functions by stabilising the AP C3 convertase (C3bBb).
In this thesis, I investigated the molecular basis of AP inhibition by a novel set of properdin-binding complement inhibitors from the salivary glands of the tick Rhipicephalus pulchellus, CIRp-A1 and homologs. These proteins were recombinantly expressed in insect and bacterial systems for functional and structural characterisation. ELISA-based complement activation assays showed that CIRp-A1 specifically inhibits the AP and has an IC50 of 13 nM. AP haemolysis assays using different animal sera showed that CIRp-A1 and homologs have different inhibitory activity profiles in different animals. To understand the molecular basis of host specificity, crystal structures of CIRp-A1 and homologs were solved. The structures of these inhibitors, in combination with mutagenesis studies of CIRp-A1, suggested that a loop contributes to the inhibitory activity of CIRp-A1.
Pulldown assays using CIRp-A1 and mammalian cell-expressed recombinant properdin suggested that CIRp-A1 binds to the final domain of properdin (TSR6), which had been implicated in C3b-properdin interaction. Pulldown assays using C3b showed that CIRp-A1 inhibits the binding of properdin to C3b and displaces properdin already bound to C3b. By binding to TSR6, CIRp-A1 might sterically hinder the interaction between properdin and C3b, or change the conformation of properdin such that it can no longer interact with C3b. The exact molecular mechanism behind properdin inhibition by CIRp-A1 remains to be elucidated in future studies, particularly with structural studies of the properdin-CIRp-A1 complex.
The politics of natural law from Milton to Swift
Keywords: natural law
Dryden
Milton
nature
Swift
law
Bunyan

Since its earliest origins in antiquity, the idea of natural law, as an innate and universal moral code grounded in human reason, has been a recurring concept in legal, moral, and political philosophy. During the last few decades, interest in the historical development of natural law has grown steadily. However, this thesis is the first study of the literary significance of natural law philosophy within the political upheavals and debates of the late seventeenth and early eighteenth centuries (from Milton to Swift). It exhibits how the notion of natural law was a pervasive yet often deeply problematic feature of political debate within this period - functioning not as an immutable doctrine, but rather as a malleable language through which a range of often conflicting ideologies could be both articulated and legitimised. It demonstrates the ways in which literature provided a unique medium through which this protean concept could be manipulated and interrogated. It also displays how an examination of the literary performance of natural law arguments serves to complicate and enrich certain conventional paradigms regarding the politics of various canonical writers. In elucidating the literary expression of this discourse, the thesis takes the shape of four studies - on Milton, Dryden, Bunyan, and Swift - illuminating the unrecognised significance of natural law within the context of their work.
Content learning in Japanese and English medium instruction: comparing chemistry learning outcomes in Japanese higher education
Keywords: Japan
Higher education
English Medium Instruction
Pedagogical challenges
Chemistry
Proficiency

English Medium Instruction (EMI) is rapidly gaining momentum in line with internationalisation of higher education trends. However, this growth in provision is outpacing empirical research. Research has reported the lack of evidence on the impact of the medium of instruction on students’ content learning outcomes. This study thus drew comparisons between EMI students (n=27) and Japanese medium instruction (JMI) students (n=26) in terms of their directly measured and self- perceived content knowledge acquisition. Data were collected at a research site university where the Chemistry courses were available in both Japanese and English as part of a parallel program offering the same curriculum in either of two languages of instruction. An analysis was made of students’ content learning outcomes measured by a novel pre-post course content tests created by the EMI Chemistry professor for the purpose of the research. These measurable test outcomes were triangulated with data from student interviews to identify further differences in their perceived learning experience according to the language of instruction. These student interviews in addition to teacher interviews and lecture observations were used subsequently to discern the differences in the EMI and JMI course implementation as well as to elucidate academic challenges associated with medium of instruction. Subsequently, factors previously attested as crucial for content learning through EMI, such as proficiency, challenges, and prior content knowledge were explored to investigate the impact of these factors on students’ success in content learning in the EMI program.
Methodologically, this study responds to calls for quasi-experimental research by adopting a longitudinal design of a course over three months, pairing in-depth quantitative analysis of the pre-post test scores with teacher and student interviews and lecture observations. The study found that while the quantitative findings unveiled no differences in content learning outcomes according to the medium of instruction, the qualitative evidence revealed that EMI students encountered a greater level of challenges than their JMI counterparts. The study also found that EMI students with lower English language proficiency faced considerably more onerous challenges than their more proficient counterparts when learning through EMI. Meanwhile, a range of factors also emerged as crucial facilitators for success in EMI, such as previous exposure to EMI education, motivation, revision and preparation, and learning strategies. This study will be one of the first attempts to investigate the effects of the medium of instruction on students’ content learning outcomes in Japan.