VictorJuiz/thesis huggingface dataset:
Towards extracellular vesicle based gene therapy for Huntington's disease
Keywords: siRNA
Gene Therapy
Huntington's

Huntington's disease (HD) can be regarded as a model neurodegenerative disorder to screen potential genetic based therapeutics and their carriers. It is an autosomal dominant disorder caused by a mutation in a single gene that leads to progressive neurodegeneration caused in part by protein misfolding. The mutation codes for an expanded polyglutamine tract within the Huntingtin gene (HTT) which leads to neuronal loss through a pathological cascade of events. Current treatment strategies include symptom management but no disease-modifying therapies exist.
Research has shown that nucleic acid based therapeutics aimed at decreasing HTT expression can prevent, or reverse, the phenotype. Translating such therapies to the clinic is hindered by the blood brain barrier (BBB) and the lack of an easily administrable, non-toxic, immunologically inert delivery vehicle capable of bypassing the BBB. This study examines a range of nucleic acid based therapeutics for their potency and toxicity, and evaluates extracellular vesicles (EVs) as a delivery vehicle through investigation of the biodistribution of brain targeted EVs and an analysis of EV loading.
A small interfering RNA (siRNA) targeting a region upstream of the repeat induced potent non-toxic silencing of HTT. In examining EVs as a carrier for therapeutics for neurological diseases including HD, it was found that targeting can increase brain accumulation of EVs but that the physiological characteristics of EVs which make them susceptible to clearance by the reticuloendothelial system (RES) must be further evaluated to bioengineer modified EVs to avoid fast clearance. Lastly, loading by electroporation was found to induce siRNA aggregation which can lead to overestimation of loading by increasing siRNA content in an ultracentrifugation pellet, but cholesterol-conjugated siRNA mixed with EVs was capable of generating silencing in vitro.
This thesis examined EV based treatment for HD through the selection of a nucleic acid cargo to silence HTT, and examination of EVs as a delivery vehicle via biodistribution and loading studies. If the loading can be optimised and fast clearance avoided, there is promise in the use of EVs as a carrier of siRNA for HD.
Counterpoint, 'fuge', and 'air' in the instrumental music of Orlando Gibbons
Keywords: Seventeenth-century music
Cadences
Counterpoint
Mode
Keyboard music
Tonality
Imitation
Viol consort music
Fugue
English music

This thesis develops an analytical approach to the instrumental music of Orlando Gibbons (1583-1625) based on close readings of historical theory sources, primarily by Thomas Morley, John Coprario and Thomas Campion. Music of the early seventeenth century can be difficult to analyse, since it falls between the more extensively studied and theorised practices of classic vocal polyphony and common-practice tonality. Although English music theory of this period is recognised as strikingly modern in many respects, innovative aspects of English compositions from the same period receive little attention in standard accounts of the seventeenth century. I argue that concepts taken from this body of historical theory provide the basic terms of a technical vocabulary for analysis, which should be further refined through application to real compositions. Successive chapters deal with common counterpoint models or patterns, imitative invention and disposition, cadential progressions, and overall tonal structure. I argue that these analyses show Gibbons's music to be a contribution to new ways of conceiving of instrumental polyphony and tonal structure, which deserves re-evaluation in the context of broader seventeenth-century trends.
In particular, Gibbons's use of extended cadential expectations as an expressive element, fascination with sequential progressions, and sectional structuring by harmonic area have clear parallels with later practices. At the same time, early seventeenth century style allows the composer considerably more freedom of harmonic procedures and implications than the musical styles which immediately followed it. Analysis grounded in historical theory provides the best approach to understanding and appreciating this unique musical language.
Metabolism of exogenous ketones
Keywords: Metabolism
Ketosis
Ketones
β-hydroxybutyrate
Ketone ester

As metabolic substrates, ketone bodies provide an alternative to glucose in order to pro- long survival during starvation. A low carbohydrate, high fat diet can be used to promote ketogenesis without fasting, but long-term compliance can be difficult. Dietary ketone bod- ies may be an alternative method to induce ketosis, so the aim of the work in this Thesis was to investigate the metabolism of exogenous ketones. In the first experimental Chap- ter, the effects of ketone ester and salt drinks on blood β-hydroxybutyrate (βHB), glucose, lipids, electrolytes and pH were determined in healthy humans at rest. Blood D-βHB levels were higher following ketone ester drinks, but it was found that total βHB levels with ke- tone salts were similar, as over 50% of βHB delivered in the salt was the L-isoform, which was only slowly removed from the blood. Circulating glucose and lipid concentrations fell following both ketone drinks. Blood pH fell following ketone ester consumption, but rose following ketone salt drinks, whilst both compounds raised blood sodium and chloride, and lowered potassium. Work in the second Chapter investigated the repeatability of ketone es- ter metabolism with food, successive drinks or continuous nasogastric (NG) infusion. Peak D-βHB levels were repeatable between- and within- subjects at rest but were lower after a meal, although blood acetoacetate, breath acetone and urine βHB were unaffected by feed- ing. βHB kinetic parameters were not altered by existing hyperketonemia from successive ketone ester drinks and total βHB uptake was identical when isovolumetric amounts of ketone ester were continuously infused through a NG tube. The third Chapter explored side-effects of ketone drinks: ketone ester drinks decreased appetite compared to isocaloric dextrose; which may have been linked to effects of βHB on enteroendocrine cells. Fur- thermore, both ester and salt drinks were found to be unpalatable, and to cause a few, mild gastro-intestinal effects that increased with intake. As exogenous ketones could be a per- formance enhancing supplement in sport, the fourth Chapter used a survey to investigate supplement use by endurance athletes. The results demonstrated widespread supplement use, which was highest at the elite level. In the final Chapter, the effect of glycogen lev- els on the oxidation of βHB was determined in isolated perfused rat hearts. Low cardiac glycogen levels decreased βHB oxidation and levels of the intermediates of glycolysis and the Krebs cycle, whilst increasing muscle amino acid levels, suggesting that low glycogen may have impaired anaplerosis. In conclusion, this work extends current understanding of the novel physiological ketosis that occurs following exogenous ketone consumption.
Representing the Algerian woman in Francophone literature of the late-colonial period: une dissymétrie s'évoque
Keywords: Assia Djebar
Kateb Yacine
representation
Mouloud Mammeri
Mouloud Feraoun
Pierre Bourdieu
Mohammed Dib
Jacques Lacan

This thesis seeks to discuss the ways in which canonical Francophone Algerian authors, writing in the late-colonial period (1945 – 1962), namely Kateb Yacine, Mohammed Dib, Mouloud Feraoun, Mouloud Mammeri and Assia Djebar, approached the representation of Algerian women through literature. The thesis, divided into five chapters, each focusing on the late-colonial oeuvre of one writer, initially makes use of Bourdieusian conceptions relating to a gendered "dissymétrie fondementale" and concomitant Spivakian notions of representation, to argue that a masculine domination of public fields of representation contributed to, if not ensured, a post-colonial marginalization of women and a reduction of their public role. However, it is the principal argument of this thesis that the canonical writers of the period, who were mostly male, both textually acknowledge their inability to articulate the experiences and subjectivity of the feminine Other, to represent women, and deploy a remarkable variety of formal and conceptual innovations in an attempt to tentatively produce evocations of Algerian femininity that seek to upset or highlight the structural imbalance of masculine symbolic hegemony in literary and socio-political milieux. Though this thesis does not shy from investigating those aspects of its corpus that produce ideologically conditioned masculinist representations, it chiefly seeks to articulate a shared reluctance concerning representativity and an omnipresent literary subversion of a masculine subject pole. It deploys formal narrative analysis, Lacanian psychoanalytical frameworks and a conceptualisation of "pessimistic" form to achieve these ends and to argue that the texts of its corpus discreetly militate for a communal feminine self-representation to be inaugurated, before outlining in its conclusion a post-colonial Algerian feminine literary tradition, in particular contemporary symbolic conduits such as la bande dessinée that might serve as effective motors for progression in gender relations.
Urban climate change adaptation pathways for short to long term decision-making
Keywords: Climate risk management
flooding
decision-making under uncertainty
heat risk
water supply
integrated urban planning
Adaptation pathways

Climate resilience is increasingly an attribute of competitive global cities. Cities that are most responsive to change will continue to prosper. To achieve this, governance structures and decision-making approaches that promote flexible and/or robust adaptation action are required. This thesis introduces a framework for urban adaptation planning that links medium-term risk management with the development and appraisal of long-term adaptation pathways. A long-term plan informed by the appraisal of a range of plausible pathways provides the opportunity to retain the flexibility to respond to future uncertainties, whilst also demonstrating how a city could manage future climate risk. This provides stakeholders with confidence that long-term risk is adequately considered, even if there is not a need to act immediately.
To demonstrate how adaptation pathways can support adaptation decision-making in an urban system, the approach and methods developed as part of this thesis are applied in London. Adaptation pathways in response to water scarcity, surface water flood and heat risk were developed, and their appraisal presented as pathways diagrams. These diagrams provide a visual representation of the sequencing of decision points and plausible adaptation actions that may be implemented in the future. Pathways diagrams present climate risk and adaptation information for decision-makers in a salient and actionable manner. The pathways responding to individual risks in London are then brought together to demonstrate how an integrated assessment framework may be used to appraise city-scale adaptation pathways that respond to multiple climate risks.
The growing emphasis within adaptation planning on approaches that can react flexibly to change increases the need to better understand the dynamics of climate risk and embed learning about the effectiveness of adaptation actions. To complement the pathways and adaptation decision-making research presented in this thesis, a framework that links adaptation monitoring and evaluation (M&E;), risk assessment and decision-making is presented and explored to highlight the potential benefits of, and mechanisms for, adaptation M&E; to inform and strengthen iterative risk-based adaptation planning. Demonstrated for the Thames Estuary, where concepts of adaptation planning have been pioneered but the opportunities of linking to monitoring and evaluation have not been extensively explored, we show how the framework can highlight actions and factors that are contributing to improving adaptation outcomes and those that require strengthening.
This thesis contributes to the literature on urban climate change adaptation planning under conditions of uncertainty. This thesis also contributes to the evidence base needed to justify long-term planning and realise the benefits of climate risk reduction through the implementation of flexible, long-term integrated urban adaptation plans.
The cosmological aesthetics of Tomás Saraceno's atmospheric experiments
Keywords: Air
Art
Saraceno
Aesthetics
Experiment
Cosmological
Atmosphere

This dissertation proposes cosmological aesthetics as a critique of and contribution to geologic, geomorphic and geographical aesthetics. This argument is developed in the context of human geographers' growing interests in the dark, imperceptible and unknown forces and fields of Earth and the cosmos. Attention to such cosmic phenomena amplifies the porosity of distinctions between humans, nonhumans and matter; therefore we require an aesthetic theory at the limits of sensing. In developing this aesthetics, this dissertation draws conceptual support in particular from the non-anthropocentric philosophy of Alfred North Whitehead and from Isabelle Stengers' "ecologies of practice". At the same time, the elaboration of cosmological aesthetics emerges from a site-based creative ethnography of Studio Tomás Saraceno in Berlin, and more specifically, from a series of experiments in transdiciplinary collaboration, writing and teaching with Tomás Saraceno. This dissertation interrogates how the surfaces, webs, envelopes and interstices populating and propagating in Saraceno’s artwork affect the transmission and distribution of sensation across spaces and scales: in short, how these forms become technologies of cosmo-aesthetic adventure. By engaging with Saraceno's art projects, from On Space Time Foam to hybrid webs and the Aerocene, and by participating in the atmospheric experiments of aerosolar sculptures, this dissertation articulates two core propositions of cosmological aesthetics: first, that aesthetic experience can create tangible, sensible relations with contexts that are far removed, or much wider than, the particular conditions in which we experiment. And second: such adventures in aesthetics emerge from practices bound together by the forces of obligation, attachment and crucially, imagination. Employing foremost the device of the web, cosmological aesthetics explores propositions for bodies to be creatively extended in a vast and vibrating cosmos.
Crop residue management in oil palm plantations: soil quality, soil biota and ecosystem functions
Keywords: EFB
soil biota
soil ecosystem function
soil quality
empty fruit bunch
crop residue management
oil palm

The application of crop residues is one of the most common agricultural practices used to maintain soil ecosystems and crop productivity. This thesis focuses on the oil palm (Elaeis guineensis) agroecosystem, an important tropical crop that has expanded rapidly over the past four decades. Both land conversion and business-as-usual practices within the plantations have contributed to soil degradation. The application of oil palm residues, such as empty fruit bunches (EFB) and oil palm fronds, are thought to have positive effects on the soil ecosystem; yet there is currently a deficit of knowledge on their effectiveness. This thesis aims to examine the effects of oil palm residue application on soil physicochemical properties, soil biota, and ecosystem functions. It reports the results of extensive field trials, sample collection, and statistical analysis of crop residue applications in oil palm plantations in Central Sumatra, Indonesia.
Four key results emerged from the thesis. First, in this study site land conversion from secondary forest to oil palm does not affect litter decomposition rate, but positively influences soil fauna activity. Second, there is greater soil fauna activity following EFB application than oil palm fronds or chemical fertilizers, and the fauna activity is highly associated with changes in soil chemical properties and soil moisture conditions. Third, EFB application enhances soil ecosystem functions, through the direct provision of organic matter, and by influencing soil biota. Finally, over 15 years of application, EFB appears to be effective in maintaining or increasing annual crop yield in comparison to chemical fertiliser treatment. Temporal changes in crop yield under EFB application appear to be associated with climatic conditions and soil organic carbon. Overall, these findings improve our understanding of the potential of oil palm residue applications to increase soil quality, soil biota, and ecosystem functions. They also provide useful information for a wider audience of soil ecologists, agricultural managers, and policy makers to improve sustainable management of the oil palm ecosystem.
Aspects of early hip osteoarthritis
Keywords: MRI
Osteoarthritis
Surgery
Sport
Hip

Osteoarthritis develops secondary to the action of hostile biomechanics upon susceptible cartilage. Cam morphology describes a loss of concavity at the femoral head-neck junction resulting in femoral impaction against the acetabular rim within a functional range of movement. This impaction is termed femoroacetabular impingement and can result in pain and cause damage to adjacent articular cartilage that progresses to osteoarthritis. Cam morphology is a target for joint preservation strategies.
The first study in this thesis compares hip development in academy football players with controls from local schools. The results provide strong evidence that cam morphology can develop in response to intense sporting activity during adolescence. At present, it is not possible to recommend activity modification as the cardiovascular benefits of exercise are likely to outweigh potentially detrimental effects on hip morphology. Nevertheless, individuals participating in high-level sports during youth may represent a high risk cohort for osteoarthritis warranting surveillance.
Diagnostic tools currently available only allow identification of late joint degeneration when disease is irreversible. Advances in the field of disease biomarkers may overcome this challenge. The second study of this thesis explored the prognostic value of compositional MRI. Baseline delayed gadolinium-enhanced MRI of cartilage was able to predict the development of radiographic hip osteoarthritis in asymptomatic individuals within five years. As well as identifying individuals who are likely to benefit from intervention, compositional MRI may allow the evaluation of treatment efficacy within short timeframes.
A number of interventions aimed at joint preservation are under investigation for treating cam morphology femoroacetabular impingement. Arthroscopic surgery is increasingly performed to restore the concavity at the femoral head-neck junction and prevent impaction against the acetabular rim. A feasibility study was performed for a proposed randomised controlled study comparing operative and non-operative treatment. The study protocol was developed for the 'Femoroacetabular Impingement Trial' (FAIT).
Modelling signalling pathways and cellular dynamics in vascular mechanobiology: a theoretical, experimental and computational study
Keywords: vascular
collagen
TGF-beta
aneurysm
fibroblast
growth and remodelling

Blood vessels are dynamic structures whose properties are continuously adapted by resident vascular cells. Existing mechanobiological models tend to ignore regulatory signalling and cell population dynamics, both key determinants of arterial growth and remodelling (G&R). In this D.Phil., a combined theoretical, experimental and computational approach is used to formulate, reﬁne and implement a novel model of the arterial wall that includes vascular mechanics, microstructure, biochemical metabolism and signalling, and cell phenotype and population dynamics.
A mathematical chemo–mechano–biological (CMB) model is formulated by coupling a biomechanical model of the arterial wall as a cylindrical nonlinear elastic membrane to a system of biologically–informed evolution laws governing ﬁbroblast cell–mediated, transforming growth factor (TGF)-β–regulated collagen metabolism. Model simulation of inﬂammatory aneurysm development suggests that increasing TGF-β levels promotes a cell–driven proﬁbrotic response leading to aneurysm stabilisation, illustrating the model’s ability to couple chemo–biological processes to tissue–level mechanical evolution.
To inform the theoretical framework experimentally, a recent mouse model of post–developmental disruption of medial smooth muscle TGF-β signalling is for the ﬁrst time subjected to hypertension, and characterised by biaxial mechanical testing and (immuno)histological staining. Increased adventitial TGF-β levels following perturbation are associated with strong proﬁbrotic responses (increased cellularity, collagen deposition, thicker walls) altering tissue mechanics (lower biaxial stress, higher structural stiffness).
Simulation of realistic arterial geometries is enabled by coupling the 1D CMB model to a three–dimensional structural solver. Heterogeneous spatial distributions of mechanical, microstructural and chemo–biological variables determining the evolution of complex saccular aneurysm geometries can be simulated with this 3D implementation.
A novel chemo–mechano–biological model of vascular cell dynamics and regulatory signalling governing arterial G&R is formulated, informed by speciﬁcally–generated experimental data, and implemented in an advanced 3D computational framework. This will allow for virtual investigation of therapies acting on chemo–biological agents of arterial G&R, with potential beneﬁts for vascular disease patients.
The mechanics of assignments: functions and form
Keywords: intangible personalty
choses in action
Law of Property Act 1925
equitable assignment
Judicature Act 1873
statutory assignment
Common Law Procedure Act 1854

Choses in action are valuable assets. This has compelled (and been facilitated by) the development of legal devices such as equitable assignment to allow holders of choses to deal with them, inter vivos.
This thesis makes two claims.
First, equitable assignments are best conceived as a composite of a bare trust and an atypical agency where the assignee is authorised to invoke the assignor's entitlements against the obligor to the chose assigned, as the assignee pleases.
On this conception, equitable assignments merely entail generation of a new set of jural relations as between assignor and assignee. Though these affect how the jural relations between assignor and obligor are to be discharged, those jural relations are left intact and unchanged, unless the requirements for 'statutory' assignments have been satisfied.
Second, 'statutory' assignments are regulatory in effect. Where a debt or other chose in action has been validly equitably assigned and the requirements in s 136(1) Law of Property Act 1925 are satisfied, the specific entitlements set out in sections 136(1)(a), (b) and (c) will be passed from the assignor and transferred to the assignee. But that is only true with regards entitlements falling within those provisions, and the set of entitlements listed therein is not exhaustive.
The composite model of equitable assignment, and the clarification of the nature of 'statutory' assignment, reduces confusion over their operation and effects. Accordingly, this thesis tempers the urge towards legislative reform of the law of assignment: reform may not be needed since the law is not incoherent, though it is certainly complex. And if targeted law reform to simplify the law on assignment be thought desirable, it is as well to know what one is reforming.