VictorJuiz/thesis huggingface dataset:
Application of magnetic resonance for non-invasive phenotyping of mice with altered metabolism

Changes in myocardial energetics have been implicated in the pathophysiology of heart failure (HF). However, the precise contribution of creatine (Cr) / phosphocreatine (PCr) / creatine kinase (CK) energy buffer and transfer remains unclear. The aim of this thesis was to study the effects on murine cardiac function of both impairment and enhancement of creatine metabolism.
In order to longitudinally follow the cause and effect relationship of myocardial creatine concentration, a non-invasive method of quantification was required. Cardiac Cr levels measured in vivo by 1H-MRS were therefore compared with gold-standard invasive HPLC and found to correlate over a wide-range (r2=0.91). 1H-MRS was reproducible for measuring Cr levels in the heart, brain, and skeletal muscle.
The cardiac phenotype of a novel model of creatine depletion, the AGAT-/- mouse, was characterized using in vivo MRI, 1H-MRS and LV catheterisation, under conditions of gradually reducing Cr concentrations; zero Cr; and attempted phenotype rescue with dietary Cr. For the first time in the heart, the rate of Cr turnover was quantified (~3 % per day) and demonstrated that cardiac function was preserved even when creatine levels reduced by ~70-90%. Total absence of myocardial Cr induced impairment of inotropic and lusitropic cardiac function and reduced inotropic reserve. Cardiac dysfunction was only partially rescued by replenishment of the Cr pool, suggesting this to be a consequence of long-term adaptations to chronic low Cr.
Finally, we tested the hypothesis that combined elevation of myocardial creatine and ribose would be beneficial in a mouse model of chronic HF by increasing cardiac energy availability. Despite an increase in myocardial ribose concentration, this did not prevent loss of total adenine nucleotides (TAN), and there was no improvement in post-infarct LV remodeling or function. Future studies are needed to explore alternative approaches for maintaining TAN in combination with total creatine.

Keywords: heart failure
MRS
mouse
ATP
adenine nucleotides
ribose
creatine
MRI
AGAT
Advisor: Neubauer, S
Schneider, J
Lygate, C
Citizens at war: the experience of the Great War in Essex, 1914-1918

This thesis examines the experiences and attitudes of civilians in Essex during the First World War, 1914-1918. Through these it explores the reasons for people’s continued support for the war and how public discourse shaped conceptions of the war’s purpose and course and what sacrifices were needed and acceptable in pursuit of victory. This combination kept the war comprehensible and enabled people to continue to support it.
Vital to getting a picture of how the war was understood is an account of the role of the local elites that sought to shape popular knowledge and attitudes about the war. The narratives of the war, the discourse of sacrifice, and elites’ roles evolved with events at home and at the front.
Chapter 1 deals with the initial reactions to the war and growing acceptance of the major war narratives. The second and third chapters address two of their major features: attitudes towards the enemy and volunteering for the armed forces. The fourth chapter addresses the changes to the war's narratives and ideas of sacrifice as casualties and hardships increased from 1916, while Chapter 5 provides an in-depth case study of local military service tribunals. The final chapter deals with the crises of 1917-18, which covered both the expected course of the war and the image of equal sacrifice, and how local and national elites overcame these problems.
The successful depiction of the Great War as necessary, just, winnable, and fought against an evil enemy allowed civilians to accept sacrifices in order to win. An evolving discourse of sacrifice framed what was expected of and acceptable to civilians. Local elites played an essential role: advocating sacrifice and endurance for the national cause while also working to ensure that sacrifices were minimised and borne equally. This combination of framing the war and mitigating its effects was vital in maintaining civilian support for the war effort.

Keywords: civilians
morale
World War I
recruitment
Essex
Great Britain
Advisor: Gregory, A
Boundary layer transition in hypersonic flows

Boundary layers are an important consideration in hypersonic vehicle design, influencing both heat transfer and drag characteristics. It is advantageous to be able to control precisely where turbulent transition in boundary layers occurs in the intake of a scramjet, the propulsion mechanism of choice for hypersonic air-breathing engines.
The present study examined transition on a flat plate representing a scramjet intake at hypersonic velocities. Experiments were carried out with Mach 5.1 flow over the plate, to provide an analogy with the intake design for the air breathing propulsion system of the Long-Term Advanced Propulsion Concepts and Technologies (LAPCAT) Mach 8 configuration. The flat plate was fabricated and mounted in the Oxford University Gun Tunnel, instrumented with thin film heat transfer gauges to measure the heat transfer rate as a proxy for the existence of turbulence in the flow over each gauge. MATLAB simulations of turbulent spot formation and propagation were created in order to design a suitable array of heat-transfer gauges and the necessary analysis software to characterize spots in terms of spreading angle and trailing- and leading-edge velocities. This analysis software was demonstrated on the simulated turbulent spot signals.
The flat plate was tested using the Gun Tunnel’s Ludwieg Tube with Isentropic Compression (LICH) mode both with smooth and cylindrically “tripped” leading edges. Heat transfer data were processed and analyzed. While individual turbulent spots were not detected in the experimental data, the average heat transfer data for the smooth edge can clearly be seen to move from laminar, nearly matching the Pohlhausen laminar result for Stanton number in terms of Reynolds number at hypersonic velocities, to turbulent transition by the end of the plate. The tripped heat transfer data seem to indicate the rapid onset of transition and overshoot, followed by a re-laminarization and ultimately convergence with the untripped result as both approach the Van Driest turbulent solution for Stanton number in terms of Reynolds number at hypersonic velocities.

Keywords: supersonic
transition
boundary layer
turbulent
turbulence
hypersonic
gun tunnel
tripped flow
Ludwieg tube
scramjet
flat plate
laminar
Advisor: He, L
Gillespie, D
The role of DNA polymerase eta in determining cellular responses to chemo-radiation treatment

DNA polymerase η (pol η), a crucial component of the cellular translesion synthesis pathway, allows cells to bypass and thereby temporarily tolerate DNA damage. Inherited deficiency of pol η, as reported in the variant form of xeroderma pigmentosum, predisposes to UV light-induced skin cancers. To date, pol η is the only DNA polymerase shown to exhibit a causal link to the formation of cancers in humans. However, the role of pol η in the cellular response to forms of DNA damage other than UV-induced lesions is largely unknown.
In the first part of this thesis, it is shown that cells deficient in pol η are resistant to ionising radiation. Deficiency in the polymerase was associated with accumulation of cells in S phase of the cell cycle. Cells deficient in pol η demonstrated increased homologous recombination-directed repair of DNA double-strand breaks created by ionising radiation, and depletion of the homologous recombination protein X-ray repair cross-complementing protein 3 (XRCC3), abrogated the radioresistance observed in pol η-deficient cells compared to pol η-complemented cells. These findings suggest that homologous recombination mediates S phase-dependent radioresistance associated with pol η-deficiency.
In the second part of this thesis, it is shown that pol η-deficient cells have increased sensitivity to the chemotherapeutic compound, oxaliplatin, compared to pol η-deficient expressing cells, but not to the drug 5-fluorouracil that is usually administered in combination with oxaliplatin in the clinical setting. Despite the importance of pol η for cellular survival following exposure to oxaliplatin, the drug did not upregulate the enzyme after either short-term or long-term exposure. Inhibition of pol η activity by siRNA-mediated knockdown of the protein sensitised cells to oxaliplatin treatment, and partially reversed acquired resistance in oxaliplatin-resistant tumour cell lines. These data suggest that pol η is an interesting target whose function can potentially be interfered with to optimise oxaliplatin-based chemotherapy.
In the third part of this thesis, clinical samples obtained from oesophageal cancer patients before and after treatment with oxaliplatin-containing chemotherapy were analysed for POLH mRNA levels encoding pol η protein. Malignant tissue specimens obtained before treatment demonstrated a significantly higher level of POLH mRNA than matched normal oesophageal tissue samples. Contrary to the preclinical data, high POLH mRNA expression before therapy was shown to correlate with increased overall and disease-free survival of the patient cohort in the clinical trial. Additionally, patients with high POLH mRNA-expressing cancers had better therapeutic responses (measured by PET-CT) to oxaliplatin-based treatment than those with low levels. These data suggest that POLH mRNA expression should be tested as a biomarker to predict survival and therapeutic responses in oesophageal cancer patients treated with oxaliplatin-containing chemotherapy.

Keywords: oxaliplatin
radiation
DNA polymerase
Advisor: Sharma, R
Helleday, T
Essays in credence goods and repeated games

This thesis presents two chapters on credence goods and one on ongoing partnerships in an infinitely repeated game. The chapters on credence goods focus on the welfare and efficiency of equilibria in overcharging models of credence goods, something which has not been explicitly addressed before. The chapter on partnerships presents a theory explaining ongoing partnerships as solving a commitment problem for clients. There is a small literature on partnerships, and this chapter represents a novel but complimentary approach to that literature. At core, chapters 2, 3 and 4 of this thesis ask the following questions respectively:
Do competition and information increase welfare in credence goods markets?
How do customers in credence goods markets discipline experts from committing fraud? Can these strategies be welfare ranked?
Why do ongoing partnerships exist? What problem do they solve?

Keywords: overlapping generations
competition
partnerships
welfare
asymmetric information
credence goods
repeated games
search
Advisor: Meyer, M
Atomistic to continuum models for crystals

The theory of nonlinear mass-spring chains has a history stretching back to the now famous numerical simulations of Fermi, Pasta and Ulam. The unexpected results of that experiment have led to many new fields of study. Despite this, the mathematics of the lattice equations have proved sufficiently rich to attract continued attention to the present day. This work is concerned with the motions of an infinite one dimensional lattice with nearest-neighbour interactions governed by a generic potential. The Hamiltonian of such a system may be written H=∑
∞
i=−∞
(
1
2
p
2
i
+V(qi+1−qi)), in terms of the momenta pi and the displacements qi of the lattice sites. All sites are assumed to be of equal mass. Certain generic conditions are placed on the potential V. Of particular interest are the solitary wave solutions which are known to exist upon such lattices. The KdV equation has long been known to emerge in a formal manner from the lattice equations as a continuum limit. More recently, the lattice's localized nonlinear modes have been rigorously approximated by the KdV's well-studied soliton solution, in the lattice's long wavelength regime. To date, however, little is known about how, and to what extent, lattice solitary waves differ from KdV solitons. It is proved in this work that a solution (which we prove to be unique) to a particular linear ordinary differential equation provides a correction to the KdV approximation. This gives, in an explicit way, the lowest order effect of lattice discreteness upon lattice solitary waves. It is also shown how such discreteness effects are propagated along the lattice both in isolation (single soliton case), and in the presence of another soliton correction (the bisoliton case). In the latter case their interaction is studied and the impact of lattice discreteness upon lattice solitary wave interactions is observed. This is possible by virtue of the discovery of an evolution equation for discreteness effects on the lattice. This equation is proved to have appropriate unique solutions and is found to be strikingly similar to corresponding equations known in both the theories of shallow water waves and ion-acoustic waves.
Investigating tendon mechanobiology and the potential of high frequency low magnitude loads for tendon repair and remodelling using an novel in vitro loading system

Tendon injuries are ubiquitous in the sporting and occupational environment. Clinically they present a challenge to Orthopaedic surgeons as they account for up to half of all sports injuries and almost half of reported work related ailments. The capacity for tendons to heal subsequent to injury is restricted due to their poor blood supply. Moreover, healed tendon tissue may be inferior to the intact tendon, having diminished biochemical and biomechanical properties and this brings about an ever increasing need for optimized treatment methods for tendon repair.
Mechanobiology is concerned with how mechanical forces influence physiological and pathological aspects of the living tissue. However, the complex and poorly controlled loading environment in living organisms prevent the establishment of direct relationships between mechanical stimuli and tissue response.
By developing a novel in vitro loading system (IVLS), the work in this thesis investigates the potential of a new and exciting biophysical loading intervention, High Frequency Low Magnitude (HFLM) mechanical loading, for stimulation of tendon repair and remodelling.
Following a pre-defined stimulation period, healthy rat tail tendon fascicles (RTTFs) were evaluated for tissue viability and metabolism, Glycosaminoglycan (GAG) content, collagen arrangement and tangent modulus, using staining and biochemical assays, together with microscopy techniques, and mechanical testing.
HFLM mechanically loaded tendons showed a trend for a higher tangent modulus than fresh tissue, and significantly higher modulus than unloaded. Further, when varying mechanical loading parameters of frequencies and dosages over clinically relevant ranges, a frequency dependent response was observed with increased tangent modulus and GAG content with increasing frequency. An association between high tendon crimp pattern and elevated tendon modulus as a result of HFLM mechanical loading was also demonstrated.
Concomitantly, an injury model was developed to evaluate the effects of in vitro static, low frequency cyclic and HFLM mechanical loading conditions on the biochemical and biomechanical properties of in vitro damaged tendons. HFLM mechanically loaded damaged tendons again demonstrated significantly higher modulus and metabolism than unloaded tissue, although these were reduced below those of fresh damaged tissue.
The findings in this thesis together with the newly developed IVLS reveal the potential for an exciting and unique biophysical therapeutic loading intervention for treatment of tendon injuries, and provide a scientific platform for further investigation of the effects of HFLM mechanical loads, potentially leading to an application within the clinic for enhanced connective tissue repair and remodelling.

Keywords: novel
mechanical load
Biomedical Engineering
in vitro
High Frequency
Biophysics
tissue
Medicine
repair
Tendon
Advisor: Thompson, M
A commentary on the tenth book of Lucan

The commentary is intended to provide information and arguments useful to understand and appreciate the poetry on a line by line basis. For this purpose it deals with a wide range of questions (of e.g. text, interpretation, sources, history, geography, atronomy), rather than investigating a single aspect of the poem. To cover the 546 lines of Book 10, it has been necessary to be a little selective. While I have, I hope, looked at most major problems of text and interpretation, I have not dealt with every point of interest or debated every variant interpretation of other scholars. Silence on textual matters may be taken to indicate acceptance of Housman's choice of reading.
There is no introduction. A short appendix examines Lucan's sources and purpose in the Nile section of lines 194-331.
Organometallic chemistry

Transition metal organometallic chemistry is a rapidly expanding field, which has an important relationship to industrial problems of petrochemical catalysis. This thesis describes studies of fundamental organometallic reaction processes, such as C-H and C-C bond formation and cleavage, and investigations of the structure and bonding of organometallic compounds. A number of techniques were used to pursue these studies, including synthesis, X-ray crystallography, and semi-empirical molecular orbital calculations.
[continued in text ...]

Advisor: Green, M
Interplay between chromatin conformation and transcription in eukaryotes

The three-dimensional organization of the genome is important for various processes such as transcription, replication, and repair. Several studies have shown that the genome is organized into long-range and short-range chromatin loops. Gene loops represent a short-range chromatin loop, synonymous with the juxtaposition of promoter and terminator regions of a gene. In Chapter III, I investigate the mechanism of gene-loop formation in a constitutively expressed gene, mouse serum albumin (Alb). The Alb locus appears to exist in a clover-leaf structure, with the promoter in close physical proximity with an upstream enhancer and downstream genic sequences. Furthermore, Alb forms a promoter-terminator gene loop that is dependent on serine 2 phosphorylation of RNA polymerase C-terminal domain. I also investigate the presence of gene loop conformation at the human Nuclear factor NF-kappa-B (NFκB1) gene. In response to cytokine stimulation, NFκB1 transcription proceeds as a wave, with nascent RNA appearing as RNA polymerase traverses along the gene length. This coincides with formation of transient contacts between NFκB1 promoter and genic regions.
The cohesin complex is a key mediator of chromatin loops and sister chromatid cohesion. The association of cohesin with chromatin is dependent on the loading complex, Mis4/Ssl3. In Chapter IV, I provide direct evidence for two functionally different populations of cohesin is Schizosaccharomyces pombe. Cohesin that co-localizes with Mis4 represents "cohesive" cohesin. In contrast, cohesin alone is unable to maintain stable sister chromatid cohesion, therefore, "less-cohesive" cohesin. Cohesive cohesin ensures stable cohesion because it is acetylated by the Eso1 acetyltransferase, which preferentially interacts with Mis4. In contrast, less-cohesive cohesin may function in recombination/repair. In Chapter V, I have identified a novel interplay between cohesin loading and transcription by RNA polymerase II. Inhibition of transcription initiation results in loss of Mis4 and consequently, cohesin binding on chromosomal arms regions. Furthermore, cohesin and Mis4 physically interact with RNA polymerase II. In Chapter VI, I summarize the above findings and propose a model that describes the stepwise loading of cohesin onto chromosomal arms during the fission yeast cell cycle. To conclude, I discuss the importance of understanding cohesin and its functions in health and diseases.

Keywords: chromatin
cohesin
molecular biology
transcription
Advisor: Proudfoot, N
Phenomenology of dark radiation and string compactifications

In this Thesis I explore aspects of dark radiation and its role in String Phenomenology. Dark radiation is any additional hidden type of relativistic matter present in the Universe today, conventionally labelled as an "excess effective number of neutrino species", Δ Neff. It provides a powerful test of hitherto untested theoretical models based on fundamental theories such as String Theory.
I begin by considering dark radiation in the LARGE Volume Scenario, a phenomenologically viable class of string compactifications. First I review how the minimal setup slightly overproduces axionic dark radiation via modulus decay. I then demonstrate that loop corrections to the main competing visible-sector decay process have a negligible effect and are unable to alleviate the tension with observations.
In the following chapter I explore fibred extensions of the LARGE Volume Scenario. The predictions for Δ Neff are qualitatively different: in particular, models with a sequestered visible sector on D3 branes at a singularity are swamped by massless axions and decisively ruled out. I then consider TeV-scale supersymmetry in a model with anisotropic modulus stabilisation. If the Standard Model is realised on D7 branes wrapping the small volume cycle a hierarchy of soft terms is generated, which may have applications to natural supersymmetry.
The final chapter takes a different approach and investigates the proposition that dark radiation, in the form of a Cosmic Axion Background, could explain the long-standing soft X-ray excess from galaxy clusters. I show for the Coma cluster that the morphology of the excess can be reproduced by axion-photon conversion in the intracluster magnetic field, provided the field is allowed to have more structure on smaller scales than typically assumed based on Faraday rotation data. This explanation requires an inverse axion-photon coupling M ∼ 1011 - 1012 GeV and a mean axion energy (ECAB) ∼ 50 - 250 eV.

Keywords: string theory
axions
cosmology
particle physics
Advisor: Conlon, J