VictorJuiz/thesis huggingface dataset:
Fabrication of an aptamer-functionalised silica nanoparticle construct  and its separation by magnetic capture-hybridisation

Nanoparticles produced with surfaces functionalised by highly specific molecular tags are able to target aberrant cells and detect or eliminate them without causing damage to surrounding healthy tissues. Single-stranded DNA (ssDNA) and RNA which fold to form secondary or tertiary structures, termed aptamers, represent a new class of such molecular tags. The nanoparticles, in turn, may carry therapeutic payload or luminescent entities which enable elimination or visualisation of targeted cells respectively.
This project presents fabrication and isolation of a surface-functionalised nanoparticle construct, namely aptamer-tagged silica nanoparticles. DNA aptamers were chosen with the intention to make them useful for clinical or diagnostic applications of targeting neoplastic cells. Indeed, the ssDNA applied here is known to bind mucin-1 which in turn is a biomarker found on the surface of metastatic breast cancer cells. The separation of the construct was made possible by the inclusion of oligonucleotide-bound superparamagnetic particles in the construct; these enabled separation by magnetic capture.
This project investigates two approaches to fabrication of the construct. In the first approach, aptamers, oligonucleotides and magnetic particles are mixed in solution. In the second, silica nanoparticles are functionalised with aptamers, oligonucleotides are bound to magnetic particles and the resulting two parts are hybridised together. The first approach gives higher yields. This may suggest that binding of silica nanoparticles to aptamers may hinder aptamer hybridisation to oligonucleotide fragments, thus resulting in lower construct synthesis yields. However, it is not known yet how the yield changes upon addition of silica nanoparticles into the solution. Therefore, the second experimental approach provides a starting point for fabrication and purification of an anti-cancer drug targeting platform in a simple bench-top setting.
In addition, this thesis discusses the fabrication of silica nanoparticles which were intended to constitute an element of the construct. The work on nanoparticle fabrication aimed to develop a quick and repeatable synthesis method which would result in monodisperse entities. Despite trying various experimental approaches, suitable particles could not be reproducibly obtained. Agglomeration was identified as a major obstacle in the silica nanoparticle production process.
Finally, this project assesses whether the chosen aptamers bind to the metastatic breast cancer cells, which would be necessary if they were to be used for diagnosis or therapy. FACS analysis indeed indicate that ssDNA aptamers attach to the MCF7 cell line, but the optimum conditions for that attachment remain to be determined.

Keywords: magnetic separation
nanoparticles
aptamers
nanotechnology
Advisor: Darton, R
Lubansky, A
Expression of the genes for arylamine N-acetyltransferases in mice

Arylamine N-acetyltransferases (NATs) are polymorphic enzymes involved in the metabolism of arylamine and hydrazine xenobiotics. Murine NAT isoenzymes are encoded by three Nat genes. Only Nat2 was previously known to be polymorphic, a single nucleotide substitution causing the slow acetylator phenotype in the A/J strain. The present study (Chapter 3) describes novel polymorphisms in all three Nat genes of the wild-derived inbred strains Mus spretus and Mus musculus castaneus. Functional analysis of hepatic and heterologously expressed NAT variants from the two strains demonstrated that M. m. castaneus is a fast and M. spretus a slow acetylator.
A previously isolated 14.3kb Nat-positive mouse genomic clone of 129/Ola strain origin (clone A) was sequenced (Chapter 4). A 8.6kb HindIII fragment, containing the entire Nat2 coding region, was subcloned from clone A and used to generate a targeting construct for the production of Nat2 knock-out mice. Probes and appropriate PCR methodologies were developed for screening of embryonic stem cells for targeted incorporation of the construct (Chapter 4). Computational analysis of clone A sequence revealed a number of important elements around the Nat2 gene, including four microsatellite markers which were found to be polymorphic among different mouse strains. Combined with preliminary physical mapping work (Chapter 4), these markers will assist accurate localisation of the Nat genes on mouse chromosome 8.
A non-coding exon was mapped 6.4-6.1kb upstream of the intronless Nat2 coding region. A functional polyadenylation signal was also identified 0.45kb downstream of the mouse Nat2 coding region. The genomic structure of other genes for mammalian NAT was also analysed, by comparison of ESTs and genomic sequences deposited in electronic databases. Reverse transcription PCR confirmed that Nat2 is expressed in many tissues, while Nat1 and Nat3 are expressed in the liver and spleen, respectively. The Nat2 transcript was also detected in mouse embryonic stem cells, suggesting a possible involvement of murine NAT2 early in development (Chapter 5). The elements constituting the core promoter of Nat2 were characterised, and a preliminary search for other transcriptional regulatory sequences was carried out, using reporter gene assays and electrophoretic mobility shift assays (Chapter 6).

Advisor: Sim, E
Controlling controversial science: biotechnology policy in Britain and the United States (1984-2004)

This thesis addresses the puzzle of variation in first-generation regulatory policies for controversial science and technology, as demonstrated in the cases of agricultural genetically modified organisms (GMOs) and human embryonic stem cell research in the United Kingdom and the United States. Why did policy outcomes vary in each technology case? This study answers this question by placing greater emphasis on institutional factors.
Although works within institutional analysis, bureaucracy and regulation literatures make significant progress in revealing how existing institutions can shape outcomes, how far one can characterize bureaucratic behavior and whether interest groups capture regulation, they nevertheless create an opening for research that: describes a mechanism for path dependence to explain variation in policies; shows the degree to which bureaucratic behaviors can influence outcomes; and, highlights instances in which regulatory officials hold power. This thesis makes an original contribution by providing new historical details relating to these cases, and by providing an extensive elaboration of Pierson’s criteria for increasing returns and a so-called secondary test of path dependence to explain outcomes.
The study recounts the biography of key policy documents in each case by tracing the process of decision-making through government and archival sources, secondary literature and more than 40 elite interviews. In doing so, it details the activities of key governmental bodies within the European Union, UK and US. Moreover, it shows how the Coordinated Framework (1986) and Human Fertilisation and Embryology Act 1990 framework represented decision-making structures which triggered changes in actors and interests and shaped permissive outcomes for GMOs and stem cell research in the US and UK, respectively. Furthermore, lack of comparable structures may help account for restrictive policies for GMOs in Europe and the UK, and for stem cell research in the US.

Keywords: genetic engineering
human embryonic stem cell research
genetically engineered food
genetically modified food
genetically modified organisms
GMOs
biotechnology
stem cell research
Advisor: Hood, C
King, D
State and ritual in a Marxist-Leninist society: East Berlin, 1951

This dissertation examines the relationship between state, ritual, and Stalinism in the context of the Soviet occupation of Germany after 1945, the establishment of the German Democratic Republic, and finally the World Festival of Youth and Students (Weltfestspiele) held in East Berlin in 1951. On the connection between these three phenomena, I take an anti-Durkheimian stance, asserting that ritual, far from being merely epiphenomenal to 'society' or 'the state', is in fact constitutive of them. It is the contention of this thesis that the entity known as 'the state', despite the capacity of some of its organs to project massive physical force, is in ontological term an amorphous, fragile thing. It is a further contention of this thesis that mass public ritual is one of the cornerstones of the ideological work of the state. I argue that the emphasis that the East German state placed on mass ritual was a function of its political and social insecurity. I propose that the German Democratic Republic's fixation on mass displays of unity during the first years of its existence were a function of its insecurity. In 1951, the year in which the Weltfestspiele took place, the German Democratic Republic was barely two years old and was uncertain of its future, wary of both the decidedly limited enthusiasm Germans had displayed for Soviet-backed Marxism-Leninism and the plans its allies in Moscow had for the future of a divided Germany. The East German authorities accordingly set a great deal of store by mass displays of the unity and enthusiasm of 'the people'-yet at the same time, these mass rituals ultimately became carnivals of the regime's insecurity, and demonstrations of its failure to secure authentic political legitimacy amongst its population.

Keywords: Marxism-Leninism
communism
Marx
socialism
German Democratic Republic
ideology
ritual
East Germany
Germany
Lennin
Advisor: Priestland, D
Selfless love and human flourishing: a theological and a secular perspective in dialogue

The point of departure of this thesis is derived from a modern tendency to create a dichotomy between selfless love and human flourishing. Modern attempts to liberate the human being from heteronomous oppression and the moral norms promoting this have sometimes led to the conclusion that selfless love is harmful to human flourishing. Such a conclusion has gained momentum also through modernist re-conceptualisations of the self as an autonomous but empty consciousness which must guard itself against determination by the other. In effect, significant thinkers have replaced the notion of selfless love with a call for self-assertion over against the other, as key to the individual person’s well-being.
This has been matched by Christian dismissals of the individual’s pursuit of human flourishing. In the face of modern insights into the ‘desirous’ nature of the human being, modern Christian theology has equally struggled to sustain the tension between the traditional Christian notion of selfless or self-giving love and human beings’ desire to affirm themselves and to find personal fulfilment in this world. Strands of Christian theology have, for instance, affirmed a self-surrendering love at the cost of dismissing the individual’s worldly desires entirely.
In this thesis, I outline this situation in modern thought and its problematic consequences. With a view to discerning whether selfless love and human flourishing can be re-connected, I then undertake close studies of the theologian Paul Tillich’s and the moral philosopher and novelist Iris Murdoch’s conceptualisations of the self and of love. As I will argue, Tillich’s and Murdoch’s engagement with modern thought leads them to develop accounts of the self, which correspond with understandings of love as both selfless and conducive to human flourishing. On the basis of their thought I thus argue that selfless love and human flourishing can be understood as interdependent even today.

Keywords: self
love
eros
agape
existentialism
Iris Murdoch
Paul Tillich
human flourishing
Advisor: Fiddes, P
Organ reform in England: aesthetics and polemics, 1901-1965

This thesis examines organ reform in England between 1901 and 1965, an arena of practical music-making and intellectual and ideological debates in which a number of related practices surrounding the English organ – notably its scholarship, aesthetics of design, liturgical functions, native and foreign repertoires, including J. S. Bach’s organ music – played a central role in transforming the sound, design, and appearance of the instrument. Whilst influential musicians asserted that the English organ of the first half of the twentieth century was a great work of art, and survived in what could be termed ‘splendid isolation’ from Continental models, others contended that it lacked a logical relationship with more than a home-grown repertory. However, supporters of the English organ claimed that technological and tonal improvements made it the most perfect medium for Bach performance. It was a renewed interest in historical organs and repertory that exposed the limitations of cultural centrism, pointing to the English organ’s weakness as a point of departure for understanding its European repertory. This insistence paved the way for an enthusiastic reception of other organs, which, through their construction and new tonal qualities, won the favour of musicians who had found the English organ too limited and focused on a particular culture. The thesis allows historical actors to populate the discourse, revealing the diverse practices out of which a quest for reform emerged. As such the organ provides a fascinating and preliminary rehearsal case for what in the 1970s and 80s would be termed the early music revival.

Keywords: organ (instrument)
J. S. Bach
early music
Advisor: Dreyfus, L
The origins and development of English medieval townhouses operating commercially on two storeys

Over the last thirty years the study of the English medieval townhouse has not developed on a par with medieval archaeology, or urban history. This thesis combines the evidence of standing buildings, archaeological excavation, antiquarian records, and documentary sources, to reconsider the form of townhouses used in the distributive trades, and, in particular, it examines the evidence for the origins of townhouses operating commercially on two storeys (split-level townhouses), and their relationship to the raised walkways of the Chester Rows.
The Romanesque townhouse in England has not been the subject of original research since the 1930s, so in the early parts of the thesis the corpus of evidence is sorted into broad categories: the urban manor-like property; the stone-built chamber block at the rear of a timber-built range on the streetfront; the grand suburban house; the commercial townhouse on the streetfront (the ground-level townhouse); the split-level warehouse; and the split-level townhouse.
The twelfth-century origins of the split-level townhouse are examined, and it is clear that prototypical or even fully developed examples of the split-level townhouse exist as early as their ground-level counterparts. Despite a general dearth of early thirteenth-century buildings, it can be seen that by the mid to late thirteenth century, the split-level townhouse was dominant in the principal streets of English towns, almost to the total exclusion of other house types. Throughout the thirteenth and fourteenth centuries, the split-level design was adapted to the highly commercial and continuously built-up streets and the unusual topography of Chester, so that the upper-level shops were linked by a raised gallery.
Although split-level townhouses have proved elusive on the continent, examples are known in the Zähringen towns of modern Switzerland: several of these towns have also developed elevated walkways. There can be little doubt that the split-level townhouse and its variants were the result of commercial pressure, and an insatiable demand, not found again after the early to mid fourteenth century, for numerous small-scale retail units and undercrofts.
Novel methods for brainstem FMRI

The brainstem plays a crucial role in a great number of vital functions such as respiratory regulation, visual reflexes, and the perception of pain. The small size and close proximity of the nuclei requires high-resolution functional magnetic resonance imaging (FMRI). However, brainstem FMRI using conventional gradient-echo echo-planar imaging (GRE-EPI) techniques is challenging due to the increased signal dropout and geometric distortions in the brainstem.
The primary aim of the work presented in this thesis was to investigate alternative methods for brainstem FMRI in order to overcome some of the challenges associated with single-shot GRE-EPI techniques. Towards this goal 3D segmented sequences were explored, which have the advantage that the size of the geometric distortions is not proportional to the resolution at which is scanned. In particular, two sequences were investigated: balanced steady-state free-precession (bSSFP) and spoiled gradient echo (SPGR).
First, a set of experiments was conducted, in which each experiment aimed to isolate a limited range of sequence properties in order to characterize and assess the potential of the candidate sequences. It was found that bSSFP has better noise characteristics compared to GRE-EPI when applied with a 2D acquisition, but when 3D readouts were used the signal instabilities increased dramatically.
Based on these findings, experiments that investigate the influence of multishot acquisitions on signal instabilities caused by physiological noise were performed. The signal instabilities were found to mainly originate from regions of CSF and blood and were highly correlated to the cardiac cycle. Several correction methods were explored and one method was identified to be implemented in vivo.
A novel method that allows real-time cardiac synchronization of the k-space acquisition was developed. The developed methods used a custom parallel imaging reconstruction to allow for acquisition with a fixed volume frame rate, which is desirable for FMRI purposes. The method was found to reduce the signal instabilities in 3D SPGR and bSSFP significantly.
A comprehensive assessment of two currently available retrospective correction techniques was conducted and their practicalities were compared. Recommendations are made to improve the robustness of the investigated correction methods. A novel optimization method was implemented, which was developed to determine the optimal regressor set for retrospective corrections. The method can be applied to image based as well as k-space based methods.

Keywords: magnetic resonance imaging
neuroscience
physics
Advisor: Miller, K
Jezzard, P
Electrochemical and infrared spectroelectrochemical methods applied to the NiFe hydrogenases of Ralstonia eutropha

Hydrogenases are a class of metalloenzymes which catalyse H₂ oxidation and its reverse reaction, H⁺ reduction. There is interest in investigating how H₂ as an energy carrier is cycled in biology. Hydrogenases have also been studied extensively because there are potential applications for them as catalysts for H₂ oxidation in fuel cells or H₂ production via light-driven water splitting. For these applications, the ability for the hydrogenase to work in the presence of O₂ is an important issue. The microorganism Ralstonia eutropha is a well-studied model aerobic H₂ oxidiser: it can adopt H₂ as the sole energy source to grow cells in the presence of O₂. It produces at least three distinct O₂-tolerant NiFe hydrogenases: the membrane-bound hydrogenase (MBH), the NAD⁺-reducing soluble hydrogenase (SH) and the regulatory hydrogenase (RH). This Thesis employs protein film electrochemistry (PFE) to study the SH and RH. It is found that the SH is able to work in both direction (H₂ oxidation and H⁺ reduction) with minimum overpotential, which is critical in coupling 2H⁺/H₂ cycling with the closely spaced NAD⁺/NADH potential. Reactions of the SH with O₂ have been investigated, revealing at least two distinct O₂-inactivated states, but consistent with the requirement for the SH to function in air, it can be reactivated in the presence of O₂ at low potentials which could be provided by the NAD⁺/NADH pool in vivo. The affinity of the RH for H₂ was determined by PFE and found to be slightly higher than that of the SH and MBH. This may provide a way for the microbe to regulate hydrogenase expression in response to the H₂ availability. Carbon monoxide and O₂-inactivated states of the RH have been identified for the first time, confirming that a constricted gas channel is not sufficient to explain its O₂ tolerance. Observation of potential dependent reactions in hydrogenases means that it is important to have spectroscopic methods for characterising states triggered by inhibitors and potential. An Infrared spectroelectrochemical approach suitable for studying metalloenzymes has been developed and preliminary spectra on RH recorded. This method should provide many opportunities for future studies of redox states of hydrogenases.

Keywords: protein film electrochemistry
hydrogenase
infrared spectroelectrochemistry
Advisor: Vincent, K
Variability of the polar stratosphere and its influence on surface weather and climate

Research during the last two decades has established that variability of the winter polar stratospheric vortex can significantly influence the troposphere, affecting the likelihood of extreme weather events and the skill of long-range weather forecasts. This influence is particularly strong following the rapid breakdown of the vortex in events known as sudden stratospheric warmings (SSWs). This thesis addresses some outstanding issues in our understanding of the dynamics of this stratospheric variability and its influence on the troposphere.
First, a geometrical method is developed to characterise two-dimensional polar vortex variability. This method is also able to identify types of SSW in which the vortex is displaced from the pole and those in which it is split in two; known as displaced and split vortex events. It shown to capture vortex variability at least as well as previous methods, but has the advantage of being easily applicable to climate model simulations.
This method is subsequently applied to 13 stratosphere-resolving climate models. Almost all models show split vortex events as barotropic and displaced vortex events as baroclinic; a difference also seen in observational reanalysis data. This supports the idea that split vortex events are caused by a resonant excitation of the barotropic mode. Models show consistent differences in the surface response to split and displaced vortex events which do not project stongly onto the annular mode. However, these differences are approximately co-located with lower stratospheric anomalies, suggesting that a local adjustment to stratospheric potential vorticity anomalies is the mechanism behind the different surface responses.
Finally, the predictability of the polar stratosphere and its influence on the troposphere is assessed in a stratosphere-resolving seasonal forecast system. Little skill is found in the prediction of the strength of the Northern Hemisphere vortex at lead times beyond one month. However, much greater skill is found for the Southern Hemisphere vortex during austral spring. This allows for forecasts of interannual changes in ozone depletion to be inferred at lead times much beyond previous forecasts. It is further demonstrated that this stratospheric skill descends with time and leads to an enhanced surface skill at lead times of more than three months.

Keywords: Atmospheric Dyanmics
Annular Mode
Seasonal Prediction
Polar Vortex
Stratosphere
Advisor: Gray, L
Hardiman, S
A mathematical theory of communicating processes

(Brief abstract written by the author in 2011 since I don't have the original to hand.)
This thesis introduced much of the theory for Hoare's CSP, including the failures and failures-divergences model and methods of proving properties of processes based on metric, order and topological structures. The final chapter investigates the structures underlying operational semantics.

Keywords: CSP
Failures
Traces
Semantics
Advisor: Hoare, C
Stoy, J