VictorJuiz/thesis huggingface dataset:
Development of a braided electrospun suture to augment tendon repairs

Tendon tears are common and often require surgical repair. However, many surgical repairs fail, despite continued advances in surgical materials and techniques. Rotator cuff surgery, the clinical focus of this thesis, has particularly poor outcomes. Repair failure can be partially attributed to the inappropriate repurposing of sutures from use in other tissues, which fail to integrate with the specialised tendon tissue. The overall aim of this study was to develop a novel polydioxanone suture that has the potential to provide both biological and mechanical support to torn tendons. It is hypothesized that electrospun submicron fibres, which mimic native tendon extra-cellular matrix (ECM), can provide biological support to tendon. Meanwhile, larger and more robust melt-extruded microscale fibres can mechanically support surgical tendon repair. It is further hypothesized that a suture containing both electrospun and extruded fibres will overcome structural limitations associated with electrospun-only sutures, while still providing biological improvements over current sutures. This thesis describes a process to fabricate and evaluate translatable suture biomaterials deliberately designed for tendon, by engineering materials on the fibre, filament, and multifilament level. On the fibre level, annealing enables tailoring of the degradation rate of electrospun fibres, which could allow for biomaterial degradation kinetics to match new tissue deposition. On the filament level, melt-extruded materials had superior strength and stiffness to support surgical repair. Electrospun filaments had a higher surface area, porosity, and faster degradation rate, making them more suitable as biological support. On the multifilament level, industrial braiding enabled further control over suture size, porosity, and mechanical properties by altering braiding design and component ratios. A hybrid braided suture with an electrospun sheath and melt-extruded cores was designed to meet the demands of tendon: electrospun fibres on the outside approximate ECM and will be in contact with the biological milieu, while the melt-extruded fibres in the core provide prolonged mechanical support. The hybrid suture had a similar size and tensile strength to currently used sutures, but was less stiff and more porous. It induced differential serum protein binding and promoted more favourable tendon fibroblast attachment and proliferation, when compared to currently used sutures. This novel hybrid suture has potential to improve current treatment options for tendon repair. Future work should investigate its local surface properties, followed by a dynamic culture and in vivo study, to bring the device to the standard needed for pre-clinical and clinical trials. The design process and pipeline of characterisation methods developed in this thesis could be applicable and adaptable to biomaterials for other soft tissues in need of improved treatments.

Advisor: Snelling, S
Mouthuy, P
Carr, A
Looking to the North Sea: isotopic and osteological evidence for medieval diet, mobility, and health at Stoke Quay, Ipswich

The North Sea trading emporia of the early medieval period were instrumental in the redevelopment of overseas exchange networks in post-Roman Britain, southern Scandinavia, and Western Europe. These trade centres catalysed the process of urbanisation that intensified throughout the subsequent centuries, giving rise to the social and economic landscape of pre-modern England and Europe. Studying the emporia and their evolution into towns can provide insights into the factors that fuelled urbanisation, and can demonstrate the effect of this phenomenon on human diet, health, and mobility in the medieval period.
This thesis approaches issues of medieval urbanisation and its effects through chemical and osteological analyses of skeletal remains from 363 humans and 99 animals from the recently excavated site of Stoke Quay, Ipswich (late 6th-late 15th centuries AD). Through stable carbon, nitrogen, oxygen, and radiogenic strontium isotope analysis, paired with osteological and palaeopathological observations, this research characterises the degree and timing of urbanisation at Ipswich, and its impact on the population buried at Stoke Quay. Specific research questions address the timing and extent of the ‘fish event horizon’ in England, the effects of urbanisation on health, and the extent of mobility and treatment of foreigners in medieval English towns.
The paired isotopic and osteological findings challenge the current view that men were the only early consumers of marine fish, but support the hypothesis that intense marine fish consumption was linked to maritime trades. The results indicate that foreigners were subject to higher rates of violence than locals, and that this violence increased over time along with nonspecific stressors and infectious disease. This thesis demonstrates that Ipswich was an exceptional location from the outset, with significantly higher and more widespread consumption of marine resources than contemporary sites across England and around the North Sea, and with a more diverse and dynamic population than was previously imagined.

Keywords: carbon isotope analysis
medieval
archaeology
early medieval
strontium isotope analysis
oxygen isotope analysis
nitrogen isotope analysis
paleopathology
Advisor: Lee-Thorp, J
Hamerow, H
Virginia Woolf and literary objects: description, philosophy, and affect

This thesis offers a philosophical and affective history of the subject-object encounter in Virginia Woolf’s writings, examining how she negotiates the relationship of the (writing) subject to objects. It extends recent literary materialism(s) that emphasise how thoughts and subjects are entangled with things. The desire for such intimacy emerges in pertinent trends in Woolf’s intellectual milieu – the late-Victorian and Edwardian approach to objects as signifiers of personality, continental theories of empathy, and the continuing allure of Romantic unity between self and world. However, Woolf is ambivalent about subject-object intimacy because objects tacitly inculcate a doctrine of the “real” by reifying social forms; furthermore, many traditions of subject-object intimacy cloak a radical subjectivism that threatens the object qua object by defining the object as a private sense-impression. Woolf’s father, Leslie Stephen, powerfully summarised how eighteenth-century empiricism’s emphasis on psycho-sensory privacy led to a rejection of mind-independent objects that, in turn, ultimately attenuates language, time and intersubjectivity. I argue that empiricism’s lonely worlds of experience and subject-object intimacy both raise the problem of radical subjectivism. Skilfully negotiating this dilemma, Woolf replaces subject-object intimacy with impersonality, suggesting that the ontological autonomy of objects is necessary to intellectual freedom, acknowledgement of otherness, and the alleviation of human loneliness. Distance and difference between subjects and objects becomes the ground of Woolf’s ethics, as shared attention to objects becomes a synecdoche for a shareable world. Subjectification and art itself are reformulated in terms of a non-appropriative “pointing towards” that recentres and demythologises the artist’s role by gesturing at the limits of description.
This study uncovers complex dialogues with contemporary authors, theorists, and philosophers and illuminates the significance of objects to larger modernist preoccupations. Furthermore, it foregrounds the difficult relationship between materiality, language, and representation, contributing towards a theoretical reappraisal of objects in fiction.

Keywords: objects
Virginia Woolf
intellectual history
philosophy
affect
Advisor: Wakelin, D
The effects of an exogenously-induced ketosis on human exercise physiology, metabolism and capacity

Ketosis is a pivotal metabolic adaptation to starvation that prolongs survival by altering fuel utilisation. If harnessed outside the context of starvation, ketosis may provide a method to enhance physical performance. Therefore, this Thesis explored the effects of an exogenously-induced ketosis on human exercise physiology, metabolism and capacity. First, how the mild-ketoacidaemia associated with ketone supplementation affects the physiological response to incremental-intensity exercise and athletes’ perceptions of exercise exertion were determined (Chapter 3). To compensate for ketoacidaemia, exercise ventilation was increased by 5% and exercise-induced hyperventilation was at a 20 W lower intensity. Perceptions of exertion were greater during ketosis, primarily due to the increased acid load. Chapter 4 determined the effects of blood β-hydroxybutyrate (βHB) concentration and exercise intensity on βHB oxidation rates. Increasing blood βHB concentration from ≈2 mM to ≈4.5 mM did not affect βHB oxidation rates. βHB oxidation rates peaked during 50% maximal power (WMax) intensity exercise, although the greatest relative contribution to overall energy expenditure was during 25% WMax intensity exercise and just 4.5%. Despite this, delta efficiency was increased during ketosis. Finally, in Chapter 5, the effects of prolonged exogenously- and endogenously-induced ketoses on exercise capacity and adaptive responses to exercise training were compared. Ketone supplementation improved exercise capacity by 4 - 6% on 50% of training days versus a carbohydrate (CHO) control, but markedly impaired whole-body insulin sensitivity. Conversely, a ketogenic diet substantially increased fat oxidation by ≈60% during exercise. In part, this was caused by changes in skeletal muscle protein content, most notably a 5-fold increase in pyruvate dehydrogenase kinase 4. However, exercise capacity was decreased by 41 - 48%. In conclusion, despite increased awareness of exercise exertion, and low βHB oxidation rates, supplementing athletes with ketones may enhance exercise efficiency and capacity in athletes. However, prolonged supplementation during exercise training may result in unfavourable metabolic adaptations to CHO metabolism, without reciprocal increases in fat metabolism, as observed with an endogenously-induced ketosis.

Keywords: metabolism
exercise
ketosis
physiology
ketone
Advisor: Clarke, K
Evans, R
Sea ice effects on the upper ocean: internal waves, ice-covered gyres and the seasonal ice zone

The polar oceans are currently experiencing significant changes. Arctic and Antarctic sea ice extent and volume are changing, with a poorly constrained implication for future climate. Understanding the interactions between sea ice and the underlying ocean is fundamental for understanding current changes, and predicting future ice-states.
In this thesis I study several aspects of the under-ice boundary layer and the coupling to the deeper polar ocean. First, I conduct numerical simulations of fluid flow using the Lattice Boltzmann Method to investigate the effects of stratification and roughness on ice-ocean drag and heat flux below a ridged ice floe overlaying a stably stratified ocean. It is found that sea ice generated internal waves can cause order of magnitude variations in the simulated drag coefficient and modest variations in area-integrated heatflux and its spatial distribution.
A parameterization is developed for wave drag as a scaling law in terms of upper ocean velocity, stratification, and ridge geometry. To understand the potential impact, this parameterization is applied to an idealized conceptual model of an ice-covered ocean gyre. The model extends previous descriptions of ocean density variation subject to applied wind stress to account for ice-ocean wave drag and a simple treatment of ocean surface stress redistribution within the ice via a viscous ice rheology. I find that in certain stratification regimes, inclusion of internal wave effects significantly alters ice-velocity and ice-ocean stress with implications for the freshwater content of the gyre.
I also explore how seasonal variations in ice cover impact the water mass properties of the Southern Ocean. A 1D ice-ocean model is adapted and compared to oceanographic float observations in the Antarctic seasonal ice zone. I find that Ekman upwelling has a leading order impact on the seasonal evolution of the upper ocean water masses and stratification.

Keywords: stratified shear flow
Antarctic
Ekman pumping
internal waves
sea ice
polar oceanography
Arctic
rheology
Advisor: Wells, A
Wnt secretion, trafficking and pathway activation: towards a structure-based understanding and modulation

The Wnt pathway is a key morphogen route during embryonic development, regulating tissue organization, patterning and organ growth. In adult life, when maintained in a homeostatic range it controls stem cell self-renewal and regenerative processes, while its dysregulation promotes diseases like cancer and neurodegeneration.
A peculiar feature of the Wnt protein is its lipid modification by a palmitoleic acid, crucial for receptor engagement and functionality at the target cells. This acylation, however, reduces Wnt solubility, dictating the need for a dedicated machinery upstream of receptor engagement, to shield the lipid from the aqueous environment and promote the formation of concentration gradients.
The work presented here focused first on the elucidation of the structural and molecular mechanisms allowing Wnt to overcome this “solubility problem”. In particular, solving the structure of the Drosophila melanogaster heparan-sulfate proteoglycan Dlp in complex with a lipidated Wnt peptide, I showed that this class of membrane-anchored proteins, glypicans, has a novel role in the extracellular shielding of the Wnt lipid. The functional relevance of the interaction in modulating the extracellular Wnt spreading was confirmed by mutational and in vivo experiments in flies. The work has been published in Nature.
Additionally, upon thorough troubleshooting, I optimized a protocol for the recombinant production of the transmembrane protein Wntless - the main intracellular Wnt carrier - embedded in polymer-based nanoparticles, to use in future structural studies.
Moreover, given its importance in pathway activation, I also focused on the Wnt lipidation for therapeutic purposes in Alzheimer’s disease. To the goal, a structure-based drug development campaign was set up to find inhibitors of Notum, an extracellular modulator that specifically removes the Wnt palmitoleate from the morphogen, therefore downregulating the signalling. The work led to the identification of a patented compound with optimal pharmacological properties, currently undergoing in vivo preclinical testing.

Advisor: Jones, E
Zhao, Y
The limits of intangible property rights

A large proportion of our wealth comes from utilizing intangible resources — technologies, knowledge, literature, etc. — left to us by past generations. Does anyone have a right to exclude others from accessing these resources? How should the benefits they make available be distributed? This thesis aims to answer these two questions. The thesis proceeds in three chapters. The first chapter advances an account of when rights are justified, which builds on the interest theory of rights tradition. The second chapter aims to address the first question. It evaluates the normative status of exclusion rights to intangible goods and concludes that although some exclusion rights are justified, they need to be limited in scope and duration. The third chapter aims to answer the second question. It focuses on the economic rent portion of income that derive from intangible goods. It ultimately argues that transactors have no right to this portion of income and the latter, therefore, ought to be redistributed. The results of the thesis challenge the IPR policies and institutions that have prevailed in the last century. It urges us to imagine a more open and equal future that intangible goods have made possible.

Keywords: philosophy
political philosophy
cultural appropriation
philosophy of rights
intellectual property rights
distributive justice
economic rent
Advisor: Sinclair, T
Raising capital with purpose: challenges and opportunities in using corporate debt for environmental sustainability

Through a set of four empirical chapters, this research provides insights into and understandings of corporate finance in relation to its environmental exposure and pricing in financial markets. After considering the nature of the relationship between stakeholders and the firm, as well as the nature of the power that these stakeholders possess, I decided to focus this thesis on the creditors.
In the first part of this thesis, therefore, I investigate the relationship between debt structures and environmental sustainability. The outcomes of the first study suggest that companies are sensitive to the cost of debt when deciding whether to invest in environmental sustainability projects. The outcome of the second study finds a negative association between the cost of debt and the environmental sustainability of a company, implying that firms with higher environmental sustainability scores are perceived as less risky and therefore awarded cheaper costs when issuing new debt. Drawing on these theoretical insights, the second part of the thesis is dedicated to the green bond market, a distinct debt security created to raise financing for environmental projects. The third study, therefore, focuses on the supply side of green bonds, identifying major drivers for their surge among developed and developing countries. Finally, having investigated the existence of the yield premium of green bonds, I found that the market appears to perceive green bonds issued later by the same issuer as riskier and with higher levels of yield spread over the government bonds compared with those issued earlier.

Keywords: green financing
greenbond
green debt
Advisor: Clark, G
McElroy, C
Genomic single molecule analysis of chromatin structure around DNA replication origins in Saccharomyces cerevisiae

Origin licensing initiates DNA replication by loading proteins on to DNA. In eukaryotes origin licensing varies among inactive replication origins and can be analysed by looking at chromatin structure. This has predominantly been studied using population-based approaches including MNase-seq. These mask the heterogeneity in interactions between DNA-binding events that occur on the same DNA molecule.
In this thesis the development of a single molecule genomic footprinting approach will be discussed, with a focus on identifying an appropriate marker of accessible DNA. Firstly, two chemicals, 4,5’,8-trimethylpsoralen (TMP) and angelicin, were assessed using polyacry- lamide denaturing gels and mass spectrometry, which showed that TMP could modify DNA while angelicin modification of DNA was not observed. Subsequently, nanopore sequencing did not detect the TMP modification. Secondly, DNA methylation was investigated which involved validating the sequence specificity of M.EcoGII, a non-specific adenine methyltrans- ferase, and developing a Droplet Digital PCR assay to quantitatively assess methylation levels at individual loci. Finally, methylation was used in combination with nanopore sequencing to analyse chromatin structure in Saccharomyces cerevisiae through both in vitro chromatin preparations and novel in vivo inducible Dam and M.EcoGII systems. These showed that S. cerevisiae tolerates expression of an adenine methyltransferase, methylation in a variety of sequence contexts is detectable by nanopore sequencing and some chromatin structure can be observed however further optimisation is required.

Keywords: chromatin
genomic footprinting
DNA replication
budding yeast
methylation
single molecule
nanopore sequencing
Saccharomyces cerevisiae
Advisor: Nieduszynski, C
Hypothermic preservation of cellular products for advanced therapies

Cell and gene therapies (CGT) are showing positive results in managing a range of healthcare challenges, and one of the exciting examples is the successful treatment of relapsed acute lymphoblastic leukaemia using adoptive transfer of chimeric antigen receptor (CAR) T cells. Many of the processes in CGT product preparation and administration require optimisation, with the preservation of the therapeutic products being identified as a main challenge. Cryopreservation is the current practice, but it leads to losses in viability and functionality.
This research focussed on development of a novel process, hypothermic preservation, for short-term preservation (days rather than months) between manufacture and application to the patient at the clinic to avoid cryopreservation during transport. This study adopted Design of Experiments (DoE) as a method to rigorously establish a suitable base preservation medium using a fractional factorial design to minimise the number of trials performed, and assessing the responses by viable cell counts and measurement of metabolic activity at the end of the preservation period. Components with negative effects were identified and discarded, which significantly improved the preservation outcome. Optimisation of the medium composition by central composite DoE methods found that antioxidants played a role in the metabolic response of T cells after hypothermic preservation but were unable to maintain the cell functions themselves. Pre-treating T cells with interventions to inhibit cell proliferation forcibly reduced their metabolic activity before exposure to hypothermia and maintained complete functions after recovery. An investigation into cell sedimentation found that gelatin could avoid cell sedimentation but effectively paused T cell activity, which did not recover after preservation. The Ficoll® PM70 additive only slightly reduced the settling velocity but stimulated T cell activity on recovery. The experimental results indicated, however, that sedimentation during preservation did not negatively affect T cell function. A mass transfer computational model showed that oxygenation by conventional cell culture methods maintained suitable oxygen concentrations during preservation. A final study investigated the limitation on the duration of the proposed preservation methods.
Overall, it was concluded that T cells could be preserved up to 3 days using hypothermic preservation at 4oC if their proliferation is paused before the procedure.

Keywords: hypothermic preservation
cell therapy
T cells
Advisor: Cui, Z