VictorJuiz/thesis huggingface dataset:
Understanding molecular dynamics with coherent vibrational spectroscopy in the time-domain
Keywords: time-domain Raman
ultrafast spectroscopy
vibronic coupling
conical intersections
nonlinear optics

This thesis describes the development of several spectroscopic methods based on impulsive vibrational spectroscopy as well as of the technique itself.
The first chapter describes the ultrafast time domain Raman spectrometer including the development of two noncollinear optical parametric amplifiers for sub-10 fs pulse generation with 343 or 515 nm pumping.
In the first spectroscopic study we demonstrate, for the first time, that impulsive vibrational spectroscopy can be used for recording transient Raman spectra of molecules in excited electronic states. We obtain spectra of beta-carotene with comparable, or better, quality than established frequency domain based nonlinear Raman techniques.
The following two chapters address the questions on the fate of vibrational coherences when generated on a reactive potential energy surface. We photoexcite bacteriorhodopsin and observe anharmonic coupling mediated vibrational coherence transfer to initially silent vibrational modes. Additionally, we are able to correlate the vibrational coherence activation with the efficiency of the isomerisation reaction in bR. Upon generation of vibrational coherence in the second excited electronic state of beta-carotene, by excitation from the ground electronic state, we are able to follow the wavepacket motion out of the Franck-Condon region. We observe vibrationally coherent internal conversion, through a conical intersection, into the first excited electronic state and are hence able to demonstrate that electronic surface crossings can occur in a vibrationally coherent fashion. Additionally, we find strong evidence for vibronic coupling mediated back and forth crossing between the two electronic states.
As a combination of this work we develop a IVS based technique that allows for the direct recording of background and baseline free Raman spectra in the time domain. Several proof of principle experiments highlight the capabilities of this technique for time resolved Raman spectroscopy.
In the final chapter we present work on weak-field coherent control. Here, we address the question of whether a photochemical reaction can be controlled by the phase term of an electric excitation field, in the one photon excitation limit. We study the systems rhodamine 101, bacteriorhodopsin, rhodopsin and isorhodopsin and, contrary to previous reports, find no evidence for one photon control.
The Seoul of cats and dogs: a trans-species ethnography of animal cruelty and animal welfare in contemporary Korea
Keywords: Korea
food integrity
East Asia
anthropology of Korea
dog
species turn
South Korea
animal cruelty
animal studies
contemporary
zooanthropology
multi-species
ethnography
animal welfare
trans-species
animals
pets
human-animal relations
dog meat
cat meat
livestock
cat
anthrozoology
anthropology
animal ethics

Based on ethnographic fieldwork conducted in Seoul from July 2012 until July 2013, this dissertation offers a novel perspective on human-animal interactions and public discourses regarding livestock versus pet moral boundaries in contemporary Korea. I aim to explore how Koreans struggle to make sense of the tension between the emergence of animal welfare and the perpetuation of traditional health behaviours that involve animal processing. The focus will be on why participants in my study, whether activists or not, defended both animal ethics and cat and dog meat consumption, while including Korean animals in fluid and instrumental conceptions of Koreanness. I have analysed a variety of discourses produced by both Korean and non-Korean, academic and non-academic stakeholders, in order to reveal the on-going tension between these powerful ubiquitous ideas and the lived experience of Koreans today. Moreover, I examine how the aesthetics of cruelty and empathy is employed in order to singularize livestock into companion animals thereby transgressing cultural taboos regarding Western ethics of species separation. I also demonstrate that converging and conflicting economic, political, social and cultural agendas are responsible for making Korea’s public discourses about animal welfare very unsettled. My research thus contributes to key anthropological debates about the cross-cultural circulation and cross-fertilisation of moral values that impact the ethics of post-industrial human-animal interactions; and about the influence of policy dialogue, at both national and international levels, on applied animal ethics, cultural stigmatization and the reinforcement of national sentiment.
Deconstructing the trypanosome cytoskeleton: from structures to functions via components and complexes.
Keywords: flagellum
Kinetoplastid
Trypanosome
cytoskeleton
proteomic

Trypanosomatid protozoan parasites are the causative agents of a number of diseases responsible for the death of thousands of people in developing countries. There is currently little hope for the development of vaccines and existing treatment regimens are associated with high toxicity. Trypanosoma brucei is the etiological agent of devastating parasitic disease in humans and livestock in sub-saharan Africa. The pathogenicity and growth of these parasites are intimately linked to their shape and form which are in turn derived from a highly ordered microtubule-based cytoskeleton. Here I have investigated some of the critical structures of the cytoskeleton in terms of their molecular composition with a view toward interrogating their functions.
I have used a combined reverse genetics/comparative proteomics approach to identify over 20 novel components of the paraflagellar rod, an essential structure for the mammalian infective form of the parasite. I have iterated this approach to define interdependent sub-groups within the cohort which provide clues to the function of the paraflagellar rod.
I next applied the same comparative proteomics techniques to investigate the differences between the protein composition of two life-cycle stages of the parasite. I have identified novel components of a unique mobile transmembrane junction called the flagella connector, and of the flagellum attachment zone, a structure that is essential for cell division. In addition I have defined a pair of paralogous cytoskeletal proteins that show life-cycle stage specificity.
Finally, I have used electron tomography, reverse genetics and in situ protein tagging to define the morphology of the flagellar pocket collar, a critical structure required for parasite viability, and provide new insights into its molecular composition, function and biogenesis.
Development of small molecule inhibitors of the bromodomain-histone interaction
Keywords: organic chemistry
bromodomain
ligand discovery
epigenetics

Bromodomains bind to acetylated lysine residues 1 to mediate a wide range of biological processes, including the assembly of transcriptional machinery at modified histones. This thesis describes the design of small molecule inhibitors of bromodomains, with particular focus on the bromodomain of CREBBP.
A fragment based approach was employed to investigate bicyclic amides as acetyl lysine mimics. Initially the benzoxazinone scaffold (BNZ) 2 was shown to be a novel, ligand efficient bromodomain inhibitor. Structure based elaboration of the BNZ scaffold was employed to direct substitutions towards the region of CREBBP with greatest variability compared to other bromodomains. Ultimately, the compounds in this series were limited to micromolar affinity for CREBBP, but provided useful structure activity relationships.
Subsequently the dihydroquinoxalinone scaffold (DHQN) 3 was also shown to be a novel acetyl lysine mimic. Attachment of the optimum side group identified in the BNZ series led to the discovery of the first sub micromolar inhibitor of CREBBP. A co crystal structure with CREBBP revealed that the side group of this compound bound in a newly identified induced fit pocket, mediated by a cation π interaction. A combination of structural, functional and computational studies confirmed that the cation π interaction contributed significantly towards the binding affinity of these ligands. Further work to elaborate the DHQN core, or develop an alternative acetyl lysine mimic into a CREBBP inhibitor, did not lead to an improvement. However, the optimum compound 4 was shown to displace CREBBP from chromatin in a cell based assay.
Overall, cyclic amide based fragments were developed as CREBBP inhibitors, providing some of the first bromodomain ligands with nanomolar affinity outside of the BET family. In the process, key structural information about binding of ligands to CREBBP was revealed. Compound 4 provides a tool with which to study the biological implications of aberrant CREBBP activity and to investigate the therapeutic potential of bromodomain inhibition.
The outside within: national language and identity in Japanese contemporary discourse on gairaigo
Keywords: Discourse
Identity
Sociolinguistics
Japanese

This thesis is concerned with the relation between the notion of national language and identity, in particular the manner in which a shared sense of national belonging is expressed and reproduced through the display of public attitudes towards foreign loanwords in society. Employing the case study of contemporary Japan, this research seeks to uncover the process by which a national language is conceived of as a symbol of national identity that requires the exclusion of certain loanwords from the perceptual framework of this national language. To this end, contemporary Japanese discourse on language has been scrutinised, drawing on nationwide newspaper entries published between 1991 and 2010 on the subject of foreign loanwords known as 'gairaigo' in Japanese. Through this analysis, the thesis argues that the fierce debate on the use of loanwords can be understood as a particular manifestation of the ongoing (re-)negotiation of Japanese national identity. On the whole, criticism and praise of the use of loanwords are found to be grounded upon a desire to establish specific understandings of Japaneseness in reference to the otherness symbolised by loanwords. Both parties in the debate are, therefore, highly reliant upon notions of national consciousness, challenging the common view that debates over the use of foreignisms are merely that of an opposition between nationalists who argue for the purity of language and internationalists who argue against such normative boundaries in language. In this context, it is argued that loanwords represent a foreignness, or otherness, felt within a society that constructs an 'internal other', or 'outside within', to a Japanese 'self', the identity of which is neither autonomous nor clearly delineated.
DNA origami assembly
Keywords: DNA Nanotechnology
Biological Physics
Self-assembly

This thesis describes my investigations into the principles underlying self-assembly of DNA origami nanostructures and discusses how these principles may be applied. To study the origami folding process I designed, synthesized and characterized a polymorphic tile, which could adopt various shapes. The distribution of tile shapes provided new insights into assembly.
The origami tiles I studied were based on scaffolds derived from customized plasmids, which I prepared using recombinant DNA technology. I developed a technique to monitor incorporation of individual staples in real time using fluorescence, measuring small differences in staple binding temperatures (~0.5-5 degrees C). I examined the tiles using Atomic Force Microscopy and I found that a remarkably high proportion of polymorphic tiles folded well, which suggests that there are assembly pathways, arising from strong cooperation between staples. In order to analyse the tile shapes quantitatively, I developed a specialized image processing technique. For validation of the method, I generated and analysed simulated data, and the results confirmed that I could measure individual tile parameters with sub-pixel resolution.
I studied eleven variants of the polymorphic tile, and I proved that minor staple modifications can be used to change the folding pathway dramatically. The strength of cooperation between staples affects their behaviour, which is also influenced by their length and base sequences. Paired staples are particularly significant in assembly, and there are clear parallels with protein folding.
I describe in an Appendix how I applied origami assembly principles in the development of my concept for an autonomous rotary nanomotor utilizing the sequential opening of DNA hairpins (already used for linear motors). This device represents an advance over non-autonomous rotary motors and I have simulated its performance.
In this thesis I have answered important questions about DNA origami assembly, and my findings could enable the development of more sophisticated DNA nanostructures for specific purposes.
Ionic basis for variability in repolarisaion and its implications in pathological response
Keywords: Population Modelling
Action Potential
Cardiovascular disease
Variation
Ischemia
Computational Biology
Rabbit Ventricular

Sudden cardiac death represents one of the leading causes of death worldwide, with the majority of these deaths caused by arrhythmias derived from ischæmic events. However, the mechanisms leading from ischæmia to re-entry, arrhythmia and eventual death are poorly understood. Furthermore, variability in the action potential of cardiac tissue, while important in determining arrhythmic risk, is only recently being addressed in computational modelling, with little known about the causes and mechanisms underlying it, nor regarding its evolution in response to pathological conditions such as ischæmia.
This dissertation investigates the causes of variability in the repolarisation of the action potential of the rabbit ventricular myocyte, and the response of this variability to ischæmia. The effect of variability in ion channel conductances is investigated by means of a complete search of the parameter space revealed by simultaneous variation in multiple parameters describing ion channel conductances in computational models of the rabbit ventricular action potential. Rabbit data and models are used in this thesis due to the similarities to human data, both in terms of electrophysiology generally, and the response to ischæmia specifically. The response of two different model frameworks is assessed to determine similarities and differences between model frameworks that are designed to reproduce the same system. Those models producing action potential durations that fall within an experimentally derived range at multiple pacing rates are used to define model populations that thus reproduce experimental variability in repolarisation. These model populations are used to investigate the effects of ischæmic conditions on population variability. Variability is measured not only for action potential duration, but also for other biomarkers commonly implicated in the development of re-entry.
The work presented in this dissertation is significant for: (1) presenting a comprehensive study of the effect of simultaneous variation in ion channel conductances, with details regarding the interactions between conductances and how these interactions change depending on the pacing rate; (2) detailed examination of the differences between two models of the same system; (3) production of the largest extant populations reproducing experimentally observed variability in action potential duration; (4) the first time model populations have been used to investigate the effects of ischæmia on variability.
Australian company borrowing, 1870-1893: a study in British overseas investment
Keywords: economic development
Australia
borrowing

In the last three decades of the nineteenth century British capital played a major part in Australian economic development. The flow of capital to the Australian colonies comprised government borrowing on the one hand, and private borrowing by companies on the other. The present study concerns the flow of capital to the private sector of the Australian economy, most which reached the colonies through the medium of finance companies from the mid 'seventies to 1891.
The crux of the study are the new estimates of the annual flow of British capital to the private sector of the Australian economy, excluding mining activity (for which estimates are available), in the 'seventies, 'eighties and 'nineties. Capital reached the colonies through a group of powerful finance companies which employed British capital in the Australian pastoral industry. These companies raised most of their funds in Britain in two ways: first, by issuing short-term debenture bonds, and second, by raising deposits. Debentures were issued by pastoral mortgage and investment companies, and deposits were collected by Australian banks. As the available estimates of this flow of capital are wholly inadequate, the present study contributes a new annual series of Australian company borrowing which was calculated directly from balance-sheets and other data, and not by taking a residual of the balance of payments. In addition, a calculation was made, from 1881 to 1891, on an annual basis, of the total burden of indebtedness of the Australian colonies accruing from government borrowing and this form of company borrowing.
Performing a political shift: avant-garde music in Cold War Spain
Keywords: propaganda
Falla
Spain
Cold War
Opus Dei
Franco
Halffter
avant-garde music

In my thesis, Performing a Political Shift: Avant-Garde Music in Cold War Spain, I argue that towards the end of the 1950s the Spanish ultra-conservative regime of Francisco Franco started to promote avant-garde music. This music contrasted with the aesthetically conservative one that had been promoted since the end of the Civil War (1936-1939). I examine the causes of this shift and reveal for the first time that they are connected to specific trends in Spanish politics and policies.
In terms of national politics, the second phase of the Spanish dictatorship, from the late 1950s until Franco’s death in 1975, was dominated by young ministers who wanted to distance themselves from previous cabinets, mostly controlled by ultra-nationalist fascist politicians. These younger politicians styled themselves as part of a ‘technocratic’ regime. Thanks to its supposed ‘objectivity’ and ‘purely musical’ ideology-free concerns, avant-garde music sat well with these technocrats’ views of modern Spain, that is, a country benefitting from ‘objective’, ideology-free progress. On an international level, the defeat in the 1940s of Mussolini and Hitler, Franco’s main allies, had resulted in isolation for Spain. In order to break this isolation, the Spanish regime started to make a sustained effort at the end of the 1950s to establish diplomatic relations with other Western countries. These relations resulted in cultural, economic and military agreements with European democracies and the US.
I also consider why recent Spanish musicology has failed to confront the political implications of the promotion of avant-garde music under Franco. I connect this void with the Spanish transition to democracy (1975-1978), which recent historians have called an exercise in amnesia, a discourse of forgiveness meant to promote reconciliation between Spaniards. As a result of this transition, the political implications of the activities of the composers and musicologists during the Franco years have been ignored or forgotten.
The results of my thesis challenge the widely accepted view of the European avant-garde as a left-leaning movement. The main contribution of my thesis is precisely its substantial consideration of the cultural and political meanings of the avant garde and its context, using Franco’s Spain as a case in point.
Structural and thermogravimetric studies of alkali metal amides and imides
Keywords: alkali metal imidies
scanning calorimetry
alkali metal amides
gravimetric analysis
neutron diffraction
x-ray diffraction

This work presents an in-depth study of the crystal structures and hydrogen sorption potential of the Li - N - H and Li - Na - N - H systems. The structures of the materials have been studied using X-ray and neutron diffraction, Raman spectroscopy and inelastic neutron scattering. The behavior of the materials during heating was studied using variable temperature X-ray diffraction, intelligent gravimetric analysis in conjunction with neutron diffraction, intelligent gravimetric analysis combined with mass spectrometry and differential scanning calorimetry.
The role of cation disorder in the Li - N - H (D) system has been explored, indicating that crystallographic ordering of the Li+ ions within lithium amide and lithium imide significantly affects the hydrogen sorption properties of the materials. Order-disorder transitions were observed both during hydrogen desorption from ordered LiNH2 and during deuterium adsorption on ordered Li2ND. Such transitions were not observed in disordered samples of the materials. The intrinsic disorder and the stoichiometry of Li - N - H(D) materials was shown to depend strongly on the techniques used during their synthesis.
Studies regarding the synthesis, crystal chemistry and decomposition properties of the mixed Li / Na amides are presented. Two distinct mixed Li / Na amides of formulae Li3Na(NH2)4 and LiNa2(NH2)3 were observed in the LiNH2 / NaNH2 phase space. Na was also seen to be soluble in LiNH2, forming sodium-doped LiNH2 . Li3Na(NH2)4 and Na-doped LiNH2 were found to exhibit significant cation non-stoichiometry, whereas LiNa2(NH2)4 was shown to exist as a line phase material.
Thermogravimetric and calorimetric studies of the mixed Li / Na amides suggested that these materials decompose primarily with loss of H2.
Structure and dynamics of picornavirus capsids to inform vaccine design
Keywords: Picronavirus
Viruses
FMDV
Vaccine

The physical properties of viral capsids are major determinants of vaccine efficacy for several picornaviruses which impact on human and animal health. Current picornavirus vaccines are frequently produced from inactivated virus. Inactivation often reduces the stability of the virus capsid, causing a problem for Foot and Mouth Disease Virus (FMDV) where certain serotypes fall apart into pentameric assemblies below pH 6.5 or at temperatures slightly above 37°C, destroying their effectiveness in eliciting a protective immune response. As a result, vaccines require a cold chain for storage and animals need to be frequently immunised.
FMDV is a member of the Aphthovirus genus of the Picornaviridae. Globally there are seven FMDV serotypes: O, A, Asia1, C and SAT-1, -2 and -3, contributing to a dynamic pool of antigenic variation. As part of collaboration between the Division of Structural Biology, Oxford University, The Pirbright Institute, Reading University and ARC, Ondespoort, South Africa we sought to rationally engineer thermo-stable FMDV capsids either as infectious copy virus or recombinant empty capsids with improved thermo-stability for improved vaccines. In this project, in silico molecular dynamics (MD) simulations, molecular modelling, free energy calculations, X-ray crystallography, electron microscopy and various biochemical/biophysical techniques were used to design and help characterise the capsids.
For the most unstable FMDV serotypes (O and SAT2), panels of stabilising mutants were characterised by MD. Promising candidates were then engineered and shown to confer increased thermo- and pH-stability. Thus, in silico predictions translate into marked stabilisation of both infectious and recombinant empty viral capsids. A novel in situ method was used to determine crystal structures for quality assessment and to verify that no unanticipated structural changes have occurred as a consequence of the modifications made. The structures of the wildtype and two of the stabilised mutants were solved and the antigenic surfaces shown to be unchanged.
Animal trials showed stabilised particles can generate a similar or improved neutralising antibody response compared to the traditional vaccines and may therefore lead to a new generation of stable and safe vaccines.