VictorJuiz/thesis huggingface dataset:
Exploring palaeoaridity using stable oxygen and carbon isotopes in small mammal teeth: a case study from two Late Pleistocene archaeological cave sites in Morocco, North Africa

Revised chronologies from Moroccan cave sites have raised questions concerning the timing of changes in human cultural behaviour in relation to past climate shifts. However, many of the inferences about past moisture regimes are based on external records. Therefore, this thesis aimed to develop a palaeoclimate record using oxygen and carbon isotope values (δ18O and δ13C) in Gerbillinae (gerbil) teeth from two Late Pleistocene cave sites, El Harhoura 2 and Taforalt, in Morocco. Since small mammals are not commonly used to construct proxy climate records, a modern isotope study was undertaken in northwestern Africa to understand the influences on the stable isotope composition of small mammal tissues in semi-arid and arid settings.
The results from the modern study show that δ18O composition of gerbil teeth is strongly correlated with mean annual precipitation (MAP), and therefore in arid settings reflects moisture availability. Predictably, the δ13C values of the gerbil teeth reflected C3 and C4 dietary inputs, but arid and mesic sites could not be distinguished because of the high variability displayed in δ13C. The δ18O isotope-based MAP reconstructions suggest that the Mediterranean coastal region of North Africa did not experience hyper-arid conditions during the Late Pleistocene. The δ13C values of the gerbil teeth show that C3 vegetation dominated in the Late Pleistocene, but there was a small amount C4 vegetation present at Taforalt. This indicates that small mammals are extremely sensitive to discreet shifts in past vegetation cover. Both the modern and archaeological studies demonstrated that the isotope values of molars and incisors differed. The results indicate that tooth choice is an important consideration for applications as proxy Quaternary records, but also highlights a new potential means to distinguish seasonal contexts. Comparisons of proxy climate records and cultural sequences at Taforalt and El Harhoura 2 show that Middle Stone Age occupations of both sites occurred during relatively humid and arid climate phases. The transition to the Later Stone Age appears to have taken place during a period of increased aridity, hinting that this cultural transition may be related to changing environmental conditions.

Keywords: oxygen
carbon
isotope
Advisor: Lee-Thorp, J
Barton, N
Cell biology and genetic regulation of secondary cells in the Drosophila accessory gland

The Drosophila adult male accessory gland (AG), which secretes many components of seminal fluid and modifies many behaviours of mated females, is a surprisingly understudied organ compared to many other fly tissues. This has been partly because of a lack of genetic tools allowing manipulation of the cell types that make up the AG epithelium. I have defined a set of transcriptional GAL4 drivers that display specific expression in a subset of AG epithelial cells known as secondary cells (SCs), and used these to investigate SC cell biology and whether there are biological parallels between SCs and the secretory cells of the human prostate. I show that these cells grow in an age-and mating-dependent manner relative to the rest of the epithelium. Furthermore, I have observed that these cells display the remarkable ability to delaminate apically from the epithelium after mating, migrate proximally within the gland in a directional manner, and can even be transferred intact to females during mating.
A small-scale genetic screen was performed which established that BMP signalling plays a crucial role in these interesting features of SC biology. Specifically, BMP signalling activity is required for normal SC growth and migratory activity. Hyper-activation of the BMP signalling pathway drives SC overgrowth and promotes spontaneous delamination and migration at a high frequency. Intriguingly, I have also shown that ecdysone receptor (EcR) signalling, a steroid hormone signalling pathway, is an important positive regulator of SC growth. This is of particular interest given an analogous role that the androgen receptor (AR), also a steroid hormone receptor, plays as a potent driver of cell growth in the prostate epithelium. I also show that BMP signalling activity increases EcR expression levels in a cell type-specific fashion, via a potential protein stabilisation mechanism. A surprising discovery has been the observation that the cell cycle regulators, Rbf and E2F1, also genetically interact with EcR and promote SC growth. E2F1 activation drives normal SC growth and positively regulates EcR expression and activity. Many of these findings are reminiscent of biology observed in the human prostate and prostate cancer, where for example, AR expression and activity is driven by E2F1 activity. This mechanism is postulated to be of importance in the progression of prostate cancer to a disease that no longer responds to androgen deprivation therapy.
In summary, my research in the Drosophila AG highlights several novel features of adult SC biology, including growth and migration, which are regulated by BMP and steroid hormone signalling activity. Much of this biology appears to closely parallel equivalent cell physiological phenomena in the prostate epithelium and in prostate cancer. In addition, as a consequence of this research, the Drosophila AG is emerging as an important model to study a number of conserved aspects of cell biology, particularly membrane trafficking, relevant to human diseases, including cancer.

Advisor: Wilson, C
Hamdy, F
Using magnetic resonance imaging to investigate early brain injury after aneurysmal subarachnoid haemorrhage

Aneurysmal subarachnoid haemorrhage (SAH) is a devastating disease frequently leading to death or poor functional outcome and the pathophysiological changes that occur acutely post-rupture remain poorly understood. The work presented here describes a series of studies correlating serial magnetic resonance imaging (MRI) scanning and bedside saccadometry with neurocognitive outcomes to investigate early brain injury after SAH. Further experiments investigate the potential of saccadometry as a bedside biomarker of cerebral ischaemia post-rupture and use MRI in a model of cerebral hypoxia to explore the mechanisms underlying the therapeutic effects of nimodipine.
Firstly, results demonstrated significantly increased apparent grey matter volume and restricted diffusion in the first 72 hours post-SAH in patients, suggesting the presence of undiagnosed and significant global cerebral oedema. Furthermore, structural images acquired at this stage enabled us to predict with high accuracy and specificity which patients will develop poor neurocognitive outcomes at three months.
Next we investigated the impact of early brain injury on functional connectivity after SAH. Patients showed significantly increased functional connectivity compared to healthy controls in a number of functional networks associated with complex cognitive or emotional functions at all timepoints post-SAH. Neurocognitive impairment was associated with increased and decreases in functional connectivity and all differences were independent from any effect of altered grey matter volume.
Improving the prediction of which patients are most at risk of developing secondary ischaemia following SAH remains a key area for research focus. We therefore used a portable beside saccadometer to acquire serial measurements of eye movements acutely post-rupture with results demonstrating faster eye movements are correlated with higher cerebral blood flow in the first 72 hours post-SAH. Finally, we used MRI to quantify the changes in cerebral structure, perfusion and function associated with a healthy volunteer model of acute hypoxia, and the effect of calcium channel blockade with nimodipine on these changes. Results suggest a preferential effect of calcium channel blockade in reversing regional MRI changes under conditions of hypoxia. These changes may help explain the outcome benefit seen in aneurysmal subarachnoid haemorrhage.
This thesis highlights the potential of MRI imaging to offer biomarkers of early brain injury in the acute period post-SAH, to improve prediction of patients most at risk of neurocognitive impairment and to offer new insight into the mechanisms behind the therapeutic benefit seen with nimodipine.

Advisor: Pattinson, K
Jezzard, P
Investigating the interactions of travel behaviour and wellbeing: a mixed-methods case study of Penarth and Cardiff, Wales

Transport systems are essential to trade, globalisation, communication and other forms of interaction between people and societies (Banister, 2013). Yet they can also have negative impacts including decreased quality of life or health impacts arising from pollutants, environmental damage including climate change and a range of wider socio-economic effects (Glanz et al., 1990). Given that most car journeys are short however (57% of UK trips are under five miles), there is particular potential for active travel (i.e. walking and cycling) to both reduce the environmental externalities of modern transport systems and stimulate improved quality of life and societal wellbeing (Banister, 2013; Martin et al., 2014). Unfortunately, there is a paucity of robust evidence that examines how infrastructural interventions (i.e. those aimed at making the physical environment more conducive to active travel) actually impact on active travel levels in specific communities. In addition, there is very limited evidence of the wider effects that such interventions have on wellbeing and levels of happiness overtime.
This thesis details mixed-method research undertaken in Cardiff, UK, during 2011/2012, which examined the impacts of a new piece of infrastructure – the Pont-y-Werin walking and cycling bridge – on the local community's levels of active travel and subjective wellbeing. It provides insights into the nature of constraints preventing travel behaviour change from taking place, and – through the use of the novel, 'Day Reconstruction Method' - into the consequences that different modes of travel can have for travel and wellbeing, including on moment-to-moment moods and emotions. Overall by contextualising and measuring and evaluating wellbeing, the research suggests that people experience less pleasant emotions during travel than when undertaking everyday activities, and also that for certain modes there is a decrease in happiness before and after travel compared to everyday activities. Additionally greater monitoring, evaluation and promotion of combined hard and soft measures - focusing on travel behaviour change - is needed alongside providing travellers with accessible information on the wellbeing impacts of different modes (Elvik, 2009).

Advisor: Brand, C
Jones, T
Interaction between polyphonic motets and monophonic songs in the thirteenth century

Interactions between polyphonic motets and monophonic trouvère song in the long thirteenth century have been characterised in a number of different ways. Mark Everist and Gaël Saint-Cricq have focused on motets' use of textual and musical forms usually thought of as typical of song. Judith Peraino, on the other hand, has explored the influence of motets on a range of pieces found in manuscripts that mainly contain monophonic songs. This thesis re-examines motet-song interaction from first principles, taking as its basis the 22 cases in which a voice part of a polyphonic motet is also found as a monophonic song.
The thesis's analysis of this corpus has two central themes: chronology and quotation. In addressing the first, it develops a music-analytical framework to address the compositional processes involved in these case studies, arguing that in some of them a monophonic song was converted into a motet voice, while in others a motet voice was extracted from its polyphonic context to make a song. It also emphasises, however, that chronology is often more complicated than these two neatly opposed categories imply, showing that different song and motet versions can relate to each other in ways that are dynamic, complex, and often hard to recover from the extant evidence.
The conversion of song material for motets and vice versa is placed within a larger context of musical quotation and re-use in the thirteenth century, showing that many of these case studies play with the pre-existence of their song or motet material: some transfer their voice parts from one medium to another in a way that consciously foregrounds their previous incarnations, whereas others mask the pre-existence of the voice part by absorbing it into new textual and musical structures.
The thesis closes with a consideration of the wider implications of the motet-song interaction it analyses. It examines the generic boundary between songs and motets and suggests a model of generic analysis that centres on the complexities of manuscript transmission. Finally, it considers the use of refrains within its corpus of motets and songs, demonstrating that these short passages of music and text are often quoted in ways similar to those analysed in motets and songs earlier in the thesis.

Advisor: Leach, E
Quantitative regulation of inducible genes: comparing models of 'on/off' against continuously variable switches

In order to respond rapidly and appropriately to their environment, cells activate internal signalling pathways, such as the mitogen-activated protein kinase (MAPK) pathways, which elicit appropriate responses through quantitative modulation of gene expression. Conceptually, gene expression may be regulated by a bistable switch or a continuously variable switch. The bistable switch considers the gene in either a stable 'on' state, where transcription happens at a constant rate intrinsic to the system, or a stable 'off' state, where transcription is not permitted. By contrast, the continuously variable switch considers gene transcription as a dynamic process, where the rate of transcription initiation varies with the intensity of the signal perceived. The work in this thesis focuses on the interface between the well-understood MAPK pathways and immediate-early (IE) genes and shows that a continuously variable switch would be more appropriate to convey quantitative regulation. Immunoblotting analyses of MAPK pathways after treatment of synchronised C3H 10T½ cells with the specific PP1 and PP2A protein phosphatase inhibitor, okadaic acid, revealed the presence of turnover of phosphorylation of transcription factor (TF) in the stress-activated MAPK pathways, suggesting dynamic regulation of these MAPK pathways. Analyses of the induction of IE genes c-fos and c-jun after perturbations of the turnover of phosphorylation by phosphatase or kinase inhibitors suggest that rather than static phosphorylation state dynamic turnover of phosphorylation may regulate IE gene induction. Finally, a simplified computational model of the interface is presented, which confirms that dynamic regulation linking rate of initiation to the turnover of phosphorylation of TFs would better convey quantitative responses.

Keywords: Immediate Early Genes
RNA
c-jun
Protein
transcription
c-fos
MAPK pathways
Advisor: Mahadevan, L
Kwiatkowska, M
Bibliographia Historica Byzantina: a historical and bibliographical description of the early editions of the Corpus Historiae Byzantinae (1556-1645)

This thesis is concerned with the editorial, printing and marketing history of four Byzantine historical narratives, published between 1556 and 1645, and soon collectively identified under the name Corpus Historiæ Byzantinæ (hereinafter, 'Byzantine Corpus'). The four Byzantine historians – Ioannes Zonaras, Niketas Choniates, Nikephoros Gregoras and Laonikos Chalkokondyles – enjoyed considerable popularity in early modern Europe, with a peak of interest in the second half of the sixteenth century. This thesis aims at highlighting how these four texts, despite being so popular in a number of early modern European countries (particularly in the German-speaking area, in Italy and in France), did not do so for the same reasons: in fact, depending on the country in which these books were printed, they were marketed, perceived and read in very different ways. This element is particularly relevant in light of the fact that the Byzantine Corpus represents the earliest predecessor of the Corpus Fontium Historiæ Byzantinæ, the modern resource for the study of Byzantine historical sources.
Chapter 1 analyses the early formation of the Byzantine Corpus and, in particular, the figure of Hieronymus Wolf, first editor of the Byzantine Corpus, often considered the 'father' of Byzantine studies; his relation with his patrons, the Fuggers of Augsburg; finally, his relation with his publisher, the Basel printer Johannes Oporinus. It then provides contextualised bibliographical and paratextual descriptions of the editiones principes of the Byzantine Corpus, all printed in Basel.
Chapters 2-5 reflect the same comparative approach, used to investigate how the later editions of the Byzantine Corpus were prepared and marketed in different European countries: each chapter provides a bibliographical and paratextual analysis of the subsequent German, Italian, French and Genevan editions respectively.
The Conclusions draw together all the information collected in the previous chapters and investigate three pivotal aspects of the Byzantine Corpus: i) the formation of the Byzantine Corpus and the individual popularity of each of the four Byzantine historians based on the frequency and popularity of both individual and collective editions; ii) the distinctive reasons of their popularity, analysed through a comparison of the different approaches with which editors and publishers have presented these texts to their respective audiences in Germany, Italy and France; iii) the reasons for the rise and decline in popularity of the Byzantine Corpus in the early seventeenth century.

Keywords: Zonaras
Gregoras
choniates
early modern history
Renaissance history
Byzantine historiography
chalkokondyles
book studies
Renaissance printing
Advisor: Lauxtermann, M
Dondi, C
Reconstructed meanings of gender violence in postwar Liberia

The central question guiding this study is, how can Liberia’s historical context of colonial state formation and reformation help explain public discourses surrounding gender violence in the postwar decade, 2003-2013? This question is addressed using original data from mixed qualitative methods including participant observation, visual methods, and semi-structured interviews. The research identifies narratives and meta-narratives produced by liberal institutions (including the Government of Liberia and international agencies), as well as informal discourses from adult Liberians of different backgrounds living in Greater Monrovia. Using critical discourse analysis, the argument identifies connections between the narratives that recur, the social realities they recall, and the power dynamics they perpetuate.
These discourses are best understood in reference to liberal and colonial/imperial dynamics from Liberia’s settlement period. Liberal institutions addressing gender violence in the postwar period face dilemmas in which universalist humanitarian ideals work in tandem with, and provide justification for, imperialism as a set of discursive and material relations. Nonelite Liberians instrumentalise and subvert both privileged donor discourses as well as long-standing colonial hierarchies of 'civilised' and 'country'.
Additionally, the thesis examines how liberal institutions, traditional institutions, and Liberian citizens interact as agents of discursive construction. It will be shown that this pattern of discourse production is at times harmonious, as in the interactions around promoting male head-of-household responsibilities, and at other times adversarial, as in conflicts surrounding excision as an initiation practice for girls. Liberal institutions, non-elite Liberians, and traditional authorities both collude and compete in this era of dynamic normative contestation.
Both the major discourses and the interactions that produce them can be explained in part by the liberal imperialism and its specific form of settler colonialism that propelled the founding and subsequent stages of state formation in Liberia. The consequences of that residual history indicate inherent – though, not irredeemable – structural limitations to a robust institutional response to gender violence. In this manner the study demonstrates the utility of historicising Liberia’s contemporary gender violence discourses, and how doing so can address the longstanding bifurcation between rights and culture in international development and transnational feminist geography.

Advisor: Daley, P
Fiddian-Qasmiyeh, E
Molecular mechanisms of repulsive guidance molecule signalling

Repulsive Guidance Molecules (RGMs) control fundamental and diverse cellular processes including axon guidance, immune cell regulation and systemic iron metabolism. RGM dysfunction has been linked to diseases such as multiple sclerosis, cancer and the iron overload disorder juvenile hemochromatosis (JHH). RGMs signal by binding directly to the transmembrane receptor Neogenin (NEO1) to trigger cytoskeleton rearrangements and subsequent axon repulsion. Additionally, RGMs are important activators of the essential developmental Bone Morphogenetic Protein (BMP) signalling pathway. RGM-activated BMP signalling is crucial for the regulation of iron metabolism and mutations in RGMC cause JHH. This thesis outlines structural and functional studies of the molecular mechanisms of RGM signalling. In Chapter 3, an analysis of an RGMB-NEO1 crystal structure is presented. Combined with mutagenesis studies, analytical ultracentrifugation experiments and neurite outgrowth assays, this allowed a mechanism for RGM signalling through NEO1 to be proposed. RGM acts as a molecular staple, bringing together the juxtamembrane regions of two NEO1 receptors to activate downstream signalling. In Chapter 4, crystal structures of the N-terminal domains of all RGM family members in complex with the BMP2 ligand are presented. Together with biophysical and cellular assays these structures allowed an endocytosis-linked mechanism for RGM-activated BMP signalling to be proposed, which is dependent on the subcellular localisation of the BMP-receptors. The work outlined in both of these chapters also revealed a molecular rationale for the disease-causing mechanism of RGMC JHH-linked mutations. In Chapter 5, the crystal structure of the ternary BMP2-RGMBNEO1 complex is described along with super-resolution uorescence microscopy data demonstrating BMP-induced clustering of RGM-NEO1 complexes in the membrane. In summary, this work sheds light on the molecular mechanisms of RGM signalling through NEO1 and BMPs, and demonstrates for the first time that RGM forms a structural bridge between these two fundamental signalling pathways.

Advisor: Siebold, C