VictorJuiz/thesis huggingface dataset:
The development and application of new hyperpolarized magnetic resonance spectroscopy techniques for the non-invasive assessment of metabolism in the rodent heart

The aim of this thesis was to develop and apply new hyperpolarized magnetic resonance spectroscopy techniques, to assess in vivo metabolism in the rodent heart. Initial work using rat models of heart disease has provided key findings, such as significant increases in pyruvate dehydrogenase flux in the hypertensive rat heart and metabolic alterations in the TCA cycle during the progression into heart failure. Both could provide future non-invasive markers for the metabolic alterations associated with hypertrophy and heart failure in patients. Whilst both of these models provided useful information regarding the metabolic abnormalities of the diseased heart there is also a need to better characterize the individual metabolic pathways that are modified during heart disease. This requires the study of genetically modified animals, namely transgenic mouse models. However, the translation of the hyperpolarized technique from rat to mouse is particularly challenging, mainly due to the mouse heart being a tenth of the size of the rat heart and with a heart rate at least twice as fast. Work in this thesis details the development of mouse cardiac dynamic nuclear polarization (DNP). The development of this technique allowed interesting insights in to differences in the in vivo metabolic phenotype of commonly used “control” mouse strains, and of mouse models of defects associated with β-oxidation. This work also demonstrated that hyperpolarized [1-13C]pyruvate could be used to monitor anaplerotic pathways in the stressed mouse heart, potentially increasing its power for clinical use. In combination with cine-MRI and 31P MRS, this work has highlighted that DNP could play an important role in the diagnosis and prognosis of cardiovascular diseases.

Keywords: metabolism
MRS
MRI
cardiovascular
hyperpolarized
Advisor: Tyler, D
Ashrafian, H
Watkins, H
Casadei, B
Evaluation of new therapies in Niemann-Pick type C disease

Niemann Pick type C (NPC) disease is a rare autosomal recessive neurodegenerative lysosomal storage disease caused by a mutation in the NPC1 or NPC2 genes. The functions of the proteins these genes encode are not fully understood, but are thought to be involved in free cholesterol egress from the acidic compartment. The pathogenic cascade in proposed to begin with sphingosine accumulation followed by reduction of acidic store calcium levels. This results in impairing intracellular trafficking and storage of multiple lipid substrates in the late endosome/lysosomal compartment.
In this thesis, multiple potential therapies have been tested in a mouse model of NPC1 disease including neuroprotective compounds. Positive effects were observed with some compounds, as reflected by increased life span and/or improved neurological function. In the course of these studies, I discovered another factor that affects the outcome of treatment with liver metabolised drugs. In the NPC1 mouse the cytochrome P450 system is impaired as is the case in the NPC1 cats and in patients. This thesis therefore sheds light on the impairment of this system at the genetic and functional level and presents data on why this aspect of pathology must be considered when designing therapeutics for this fatal neurodegenerative disease. This defect was partially corrected with bile acid supplementation, resulting in an unexpected functional improvement suggesting benefit in the CNS. Another aspect of NPC disease investigated was Crohn's-like intestinal inflammation that occurs in some NPC patients. This has been investigated in the Npc1-/- mouse model using two colitis models showing a partial protection by the Npc1 mutation with different infection kinetics and secretory cytokine profiles. Taken together, this thesis therefore provides insights into two novel aspects of pathogenesis (Crohn's-like intestinal inflammation and a drug metabolism defect) and provides new leads on treatments that target unique aspects of the pathogenic cascade.

Keywords: Lysosomal storage disease
Niemann-Pick type C
Inflammatory bowel disease
Advisor: Platt, F
Exploiting stable isotope imaging with high resolution secondary ion mass spectrometry for applications in biology

This thesis presents applications of high resolution secondary ion mass spectrometry (NanoSIMS) analysis for stable isotope imaging in biological samples. These projects were designed to explore the potential applications of NanoSIMS analysis, and to develop protocols and novel methodologies to visualize and quantify biological processes. Working with collaborators in the UK and USA, I have applied NanoSIMS analysis to study 3 research areas, including molecule interactions, single cell metabolisms and lipid imaging in tissues. Antimicrobial peptides (AMPs) play important role in the immune system, and understanding how AMPs interact with cell membranes can provide useful information to design new therapies to control infection. The pore structures and dynamics of the interaction of AMPs with membranes has been visualized for the first time and confirmed with combined AFM and NanoSIMS analysis. A correlative backscattered electron (BSE) imaging and NanoSIMS analysis methodology has been developed to study glutamine metabolism in single cancer cells. This method enables us to measure the chemical information in specific organelles in these cells and can be widely applied to study metabolisms and to trace the uptake of labelled molecules in biological matrices. Quantitative analysis on the effects of hypoxic conditions and the PYGL gene were studied. Applying correlative BSE and NanoSIMS analysis, I also studied lipid uptake mechanisms in various mouse tissues, including brown adipose tissue, heart, intestines, liver and skeletal muscle, mainly focused on a recently discovered protein, GPIHBP1, and its function in the lipid uptake process. TRL margination was proved to depend on the GPIBP1-LPL complex, and 3 stages of lipid transport from capillary lumen to lipid droplets was also visualized by combined BSE and NanoSIMS analysis.

Keywords: stable isotope
correlative analysis
antimicrobial peptide
NanoSIMS
lipid imaging
glutamine metabolism
Advisor: Grovenor, C
Kinks in a model for two-phase lipid bilayer membranes

In the spontaneous curvature model for two-phase lipid bilayer membranes the shape of vesicles is governed by a combination of an elastic bending energy and an interface energy that penalises the size of phase boundaries. Each lipid phase induces a preferred curvature to the membrane surface, and these curvatures as well as phase boundaries may lead to the development of kinks.
In a rotationally symmetric setting we introduce a family of energies for smooth surfaces and phase fields for the lipid components and study convergence to a sharp-interface limit, which depends on the choice of the bending parameters of the phase field model. We prove that, if kinks are excluded, our energies Gamma
-converge to the commonly used sharp-interface spontaneous curvature energy with the additional assumption of C1
-regularity across interfaces. For a choice of parameters such that kinks may appear, we obtain a limit that coincides with the Gamma
-limit on all reasonable membranes and extends the classical model by assigning a bending energy also to kinks.
We illustrate the theoretical result by some numerical examples.

Keywords: 49Q10
82B26
92C10
49J45
Advisor: Niethammer, B
Some shorter satirical poems in English from the thirteenth to the early sixteenth centuries

The aim of this thesis is to provide a thorough introduction to shorter satirical poetry in Middle English, and also to provide stimulus and material for further study in this somewhat neglected area of medieval English literature. The thesis presents 83 newly transcribed, edited and annotated shorter (approximately 200 ll. or less) poems, which have never before been collected. Strictly political poems, more properly the subject of a separate study, are not included, nor are the poems of Dunbar, Skelton, Henryson and Hoccleve, which are available in excellent editions. The poems are loosely grouped according to the subjects they satirize: clergy, women and marriage, money and venality, rogues and fools, specific people, and medical recipes. A lengthy introduction briefly discusses the problem of defining satire in the Middle English period before going on to discuss the background of medieval satire for each group. For each poem there are notes which clarify difficult points as well as give information on the manuscripts and editions in which the poem appears. Appendix A prints a not hitherto recognized parody of Lydgate's A Valentine to Our Lady with the text of Lydgate's poem facing, and discusses some of the difficulties of recognizing parody in Middle English in light of this particular example. Appendix B is an index which attempts to list all nonnarrative satirical verse in English which appeared between the thirteenth and early sixteenth centuries. A glossary of difficult words in the texts is included.
Measurements of the Higgs Boson in the H - τ τ decay channel

The generation of vector boson mass via the Higgs mechanism in the Standard Model has been confirmed by the 2012 discovery of a candidate Higgs boson in the H→WW, H→ZZ, and H→γγ decay channels. In contrast, the Yukawa couplings hypothesized to provide the mass of fermions in the Standard Model have yet to be observed. The H→ττ decay channel currently provides the best opportunity for observing these couplings.
This thesis describes two separate but related searches for Higgs boson decays in the H→ττ decay channel using proton-proton collisions recorded by the ATLAS detector. The first analysis is a general search for all Higgs boson production mechanisms leading to a H→ττ decay using 4.5 fb−1 of 7 TeV and 20.3 fb−1 of 8 TeV proton-proton collision data. A deviation from the background-only hypothesis is observed with a significance of 4.5σ for a hypothetical Higgs boson mass of mH = 125 GeV — a strong indication of a H→ττ signal. For the same mass point, the best fit value for the signal strength is found to be 1.43 &plus;0.43−0.37 × the Standard Model expectation. The second analysis is a search for Higgs boson production in association with a vector boson using 20.3 fb−1 of 8 TeV proton-proton collision data. Results in the ZllH→τlτh channel indicate limits of 9.14 × the Standard Model expectation for VH signal production at mH = 125 GeV. In addition, two studies on enhancement of computing performance in the ATLAS trigger and data analysis pipeline are presented.

Keywords: vector boson
computing
tau
associated production
higgs boson
GPU
Advisor: Hays, C
Was Byzantine Egypt a legal anomaly? Looking at testamentary documents for evidence using modern tools

Modern scholars are deeply divided over whether Byzantine Egypt (350 to 650 CE) followed Roman law, with some saying that the effect of Roman law on Egypt was significant and others saying that it was superficial at best. There are a number of reasons for this schism, including the very general references to law in the surviving documents and the differences between Egyptian legal practice and some fundamental elements of Roman legal practice. This thesis seeks to provide additional evidence about the Egyptian adoption of Roman law by using a more systematic approach that looks at testamentary documents and donations mortis causa over a period of time, focusing on whether changes in the law are reflected in changes in the documents. It also uses the newly available word search capability of the papyri databases to look at when Roman legal terms are introduced into Egypt and how they are used.
The conclusion of this thesis is that lawyers and notaries in Byzantine Egypt understood and used elements of Roman law in their testamentary practices that were useful in accomplishing the goals of their clients. They were generally very careful to ensure compliance with procedural requirements. They regularly used concepts such as waivers of the requirement for guardians for women based on 'the right of children,' the confirmation of codicils, and et cetera disinheritance clauses. They did use stipulation clauses in ways that Roman legal practitioners would not, and donations mortis causa developed into a simpler alternative to a will. Cultural practices, such as the inclination to leave property to a surviving spouse with inheritance by the children after the death of the surviving spouse, remained. The impact of Roman law on Egyptian legal practice appears to have accelerated in the sixth and seventh centuries. This information is important to historians because of the light it sheds on the success of the early Byzantine emperors to create one Roman world with shared values and norms.

Keywords: Egypt
Late Antiquity
Testamentary Documents
Byzantine
Advisor: Whittow, M
Type-II superconductors in high magnetic fields

Superconductivity in high magnetic fields has attracted considerable atten- tion in recent years. The topic is important both for our fundamental un- derstanding of superfluids and for numerous practical applications. In this thesis, we consider several effects originating from the interplay between the Landau level structure of the normal state quasiparticle spectrum, and the tendency of the quasiparticles to form Cooper pairs below the critical tem- perature.
A formalism designed to describe extreme type-II superconductors close to the upper critical field Hc2 is developed. The theory which utilizes the selection rules coming from the symmetry properties of the vortex lattice, simplifies the algebra describing a superconductor in the mixed state signifi- cantly. We are, on the mean field level, able to include the quantizing effects of the magnetic field on the electron motion exactly. A main achievement is the exact calculation of the expansion coefficients giving the grand canonical potential of a superconductor in terms of a power series in the size of the or- der parameter. The result is an expression for the grand canonical potential in terms of a polynomial in a finite set of variables close to Hc2.
Using this formalism, a theory for the experimentally observed damped de Haas-van Alphen (dHvA) oscillations in the mixed state of a 2-dimensional (2D) superconductor is presented. The theory is compared with numerical results and the agreement is found to be good. A simple physical interpreta- tion of the damping is provided. The dependence of the damping on a finite Zeeman term, temperature, and the magnetic field is considered. A compar- ison of the theory with experimental data for the quasi-2D superconductor K-(ET)2Cu(NCS)2 yields good agreement.
The attenuation of a longitudinal sound wave in the mixed state is then calculated. In analogy with the dHvA effect, we predict that there should be damped oscillations in the sound attenuation in the mixed state as the exter- nal magnetic field is varied. Furthermore, the dependence of the oscillations on the sound frequency and temperature is shown to yield information on the low lying quasiparticle spectrum. Especially, the presense of gapless excita- tions due to the magnetic field makes the attenuation qualitatively different as compared to the attenuation in the Meissner state.
Some formal convergence properties of the Gor'kov theory for type-II su- perconductors close to Hc2 are derived. We show that the theory is essentially a high temperature expansion; the convergence radius of the Gor'kov series is proportional to kBT when there is a Landau level at the chemical potential.
A study of damage clusters produced by heavy-ion irradiation of nickel and its alloys

The damage clusters produced by low dose, 80 keV Ni+ and W+ heavy-ion bombardment of pure nickel; of two nichrome alloys (with 8% and 17%Cr); and of a ternary alloy and 321 stainless steel which have the same base composition (Fe/Ni10%/Cr17%) have been studied by means of transmission electron microscopy. In all cases where the defects could be identified with confidence they were found to be vacancy in nature. Most of the defects were identified as Frank loops, some of which had partially dissociated. The number of loops that were identified as dissociated and the average degree of dissociation were dependent on the stacking fault energy γ, being greater in the low-γ ternary alloy and the stainless steel than in the high-γ nickel and nichrome alloys. In the high-y materials a small proportion (< 5%) of perfect loops was also observed. Defect yield values were between a factor of 2 and 5 higher for W+ ion bombardment than for the corresponding Ni+ ion irradiations, but the effect on the mean defect size and cascade efficiency was much less pronounced. In the case of the Ni+ ion bombardment, the defect yields in the two nichrome alloys were lower than in pure Ni. No such effect was observed for the W+ ion irradiations, when defect yield and cascade efficiency values very similar to those of pure nickel were obtained. The defect yield in the W+ ion irradiated ternary alloy was considerbly smaller than in the nichrome alloys and there was a further major decrease in the stainless steel. These reductions in defect yields were not accompanied by a change in the mean defect size nor in the distribution of the defect sizes which were very similar in all the materials for irradiation by a given ion species. The defect yield in W+ ion irradiated Ni remained constant with increasing irradiation temperature up to ~450°C and then decreased sharply at higher irradiation temperatures. The defect yield in W+ ion irradiated Ni/Cr17% remained constant up to at least 500°C. Possible physical explanations for these results are discussed.

Advisor: Whelan, M
Jenkins, M
The musicological portions of the Saṅgītanārāyaṇa

The Saṅgītanārāyaṇa, attributed to the Gajapati king Nārāyad nadeva of Parlākhimidi but almost certainly composed by his guru Kaviratna Purud sottamamisra, is the most extensive surviving Sanskrit treatise on music to have been composed in the eastern region of India now known as Orissa. The treatise contains four chapters, gītanirnaya (on vocal music), vādyanirṇaya (on instruments), nāṭyanirṇaya (on dance and the mimetic art), and śuddhaprabandhodāharaṇa (sample compositions of the śuddha and sālaga varieties). The thesis contains a critical edition of the first, second and fourth of these chapters with an English translation, commentary and introduction. Though the whole text was issued in a printed edition by the Orissa Sangeet Natak Akademi in 1966, the new edition offers substantial revisions and corrections to the published version. Eleven manuscripts have been examined; these are in Nagari, Bengali and Oriya scripts and are held in collections in Orissa, in other South Asian libraries, and in two British libraries. All of the manuscript evidence has been presented in a critical apparatus and in a section of supplementary textual notes. The commentary examines the technical contents of the work in detail and places the treatise within its Eastern Indian context. Special attention is drawn to certain subjects, for instance the account of compositional forms and metres, which represent a regional tradition, but all topics are placed also against the background of Sanskrit musicological traditions from other parts of India; some topics in the traditional sastra are thereby re-examined. In the introduction, the historical setting of the work is assessed, and the manuscript evidence is summarised. The proposed stemma codicum shows two groups of manuscripts, one from Orissa and one based in North India; manuscripts discovered in the future are expected to fit into one of these two.
Comparison of biodiversity between plantation and natural forests in Sabah using moths as indicators

The Malaysian state of Sabah, in northern Borneo, started massive monoculture forest plantations of fast-growing introduced tree species in the mid-1970's to replace part of the harvested tropical rain forest. Many people, particularly conservationists in the West, are very much against this sort of reforestation as they fear it would spell a permanent loss to the Bornean rain forest biodiversity. This project was carried out at the more established forest plantations of Sabah Softwoods Sdn. Bhd. in Brumas from 1991 to 1993, where fast-growing exotics namely Acacia mangium, Eucalyptus deglupta, Gmelina arborea, Paraserianthes (=Albizia) falcataria, Pinus caribaea, were studied to assess their biodiversity and these plantations were compared with the natural regenerating logged-over secondary forest in Brumas, as well as the primary forest in Danum Valley, by using light-trapped macromoths as indicators. The method of light-trapping as a reliable means of capturing moths was supported by canopy knockdown in the form of mist-blowing.
Results obtained showed that for the year-long (January-December 1991) light-trap samples, the biodiversity values, as represented by Williams alpha (higher the value, higher the diversity), were unexpectedly high in the various plantation forests. Their alpha values ranged from the lowest in Acacia mangium with 208.14+-9.22, to the highest in Eucalyptus deglupta with 330.85+-16.37 which was even higher than the natural secondary forest with 314.53+-11.99, and certainly not inferior to the published values (300 to 350) from undisturbed Bornean forest of similar altitudes (below 500m). For the shorter month-long subsidiary samples (October/November 1992, January/February 1993), the alpha values of the samples from the lowland primary forest in Danum were not necessarily higher when compared with the similarly sampled disturbed forest habitats in Brumas, but despite its small samples, Danum produced some 33 species of macromoths which were never collected out of the 1680 species obtained from Brumas in the entire project.
The main reason behind the surprisingly good diversity measures (as indicated by moths) in these forest plantations was the presence of an understorey of varying diversity under the canopy. It would appear that with the fast-growing introduced trees acting as light-demanding pioneers, many plant species ranging from herbs, shrubs, to saplings of native tree species, managed to germinate and grow more or less efficiently in the understorey. Eucalyptus deglupta had a more diverse understorey both in terms of plant species and architecture, which in turn supported a more diverse moth fauna. These findings are encouraging in terms of biodiversity conservation, as plantation forestry seems to be the only way forward for many developing countries like Malaysia.