VictorJuiz/thesis huggingface dataset:
Coarse-grained modelling of a DNA origami force sensor
Keywords: DNA modelling
coarse-grained modelling
molecular dynamics

We have simulated large-scale DNA nanostructures using the oxDNA software which uses coarse-graining at the nucleotide level. These simulations can complement experiments as they typically allow greater structural resolution and give access to a range of properties that are otherwise hard to measure (e.g. internal forces).
To address the challenges associated with parallelised force spectroscopy, we report the development of a bottom-up approach for manipulating the mechanical forces experienced by target biomolecules. We have used molecular dynamics simulations to study the mechanical unfolding of DNA hairpins using an origami-polymer force clamp which allows ensemble scale parallelisation. The target molecules are sandwiched between a rigid DNA origami and a thermo-responsive polymer particle that shrinks upon a rise in temperature. This technique does not need any dedicated single-molecule force spectroscopy instruments or surface tethering. The key features of the origami-polymer force clamp are discussed along with the characterisation of the mechanical unfolding of DNA hairpins, and how these simulations aid in the interpretation of experimental results from these devices.
In eukaryotic cells, the basic structural unit into which DNA is packaged is a nucleosome. We have developed models of the nucleosome in its fully wrapped and partially unwrapped states to enable the design of DNA origami force clamps that will allow the structure of the nucleosome to be determined by cryoEM while subject to force. Our work focuses on molecular dynamics simulations of the nucleosome core particle obtained from a species of African clawed frogs (Xenopus laevis). We have looked at the response of our nucleosome models to external force and determined the parameters needed to simulate it in a partially unravelled state. The next step in this study would be to optimise clamp designs that utilise the entropic spring behaviour of ssDNA to exert forces that stabilise the nucleosome in the partially unwrapped state. The ultimate goal of this project is to develop a DNA origami based force-sensor that can exert the appropriate force to cause unfolding of nucleosomes.
The equilibrium structure of a DNA origami can be manipulated in a controlled way using engineered defects within the design. We have explored how to use the insertion or deletion of base pairs to generate complex structures out of a 6 helix-bundle DNA origami. The particular target is a three-dimensional trefoil knot. The designs considered involve a complex interplay between twist and curvature and we report the progress we have made towards that target.
Anticommunism in French society and politics, 1945-1953
Keywords: middle classes
trades unions
peasants
Cold War
anticommunism
scouting
working class
France
familialism
Fourth Republic

This thesis examines the role of anticommunism in French politics and society from the end of the Second World War to 1953. While previous historians have analysed anticommunism among politicians and intellectuals, few have addressed its wider social ramifications. I evaluate the prevalence of anticommunism among the French population, and examine its causes, character, and consequences through a series of case studies on different segments of French society. These include the French scouting movement; family organisations; agricultural associations; middle-class groups; and, trade unions and other working-class organisations.
I contend that anticommunism was more widespread and deeply rooted in French society than previously believed, and had a substantial impact both on national politics and on the social groups and organisations studied. Furthermore, by examining how French citizens responded to anticommunism, I argue we can gain a deeper understanding of the values that different individuals, groups, and organisations regarded as the most important to defend. Although anticommunism was a diverse phenomenon, I identify common discourses which connect to wider anxieties of the period. These include portrayals of communism as a threat to the nation; the colonial empire; the traditional family; private property; religion; the rural world; and, Western civilisation. I also highlight common aims (such as the rehabilitation of wartime collaborators) and tactics (such as the invocation of apoliticism). While acknowledging the importance of the Cold War, I reject the assumption that anticommunism was an American import or foreign to French society and demonstrate links between anticommunism and anti-Americanism.
I conclude that anticommunism drew its strength from the connection or even conflation of communism with perceived negative social changes and consequences of modernity that were seen to threaten traditional French civilisation, interacting with the postwar international and domestic environment and the personal experiences of individual anticommunists.
Monitoring heart and lung function using in-line laserspectroscopy
Keywords: respiratory physiology
laser spectroscopy

Current techniques of assessing respiratory health and cardiovascular function have inherent limitations. Commonly used methods of assessing lung function are generally insensitive to early stage respiratory disease, while techniques for evaluating cardiac output are highly invasive. The aim of this thesis is to demonstrate new techniques for assessing respiratory function and cardiac output that exploit the information encoded within breathing profiles, and which can address these shortcomings.
A molecular flow sensor (MFS) has been developed that utilises laser absorption spectroscopy to measure the number densities of O2, CO2, and H2O every 10 ms in the main airway. Respiratory flow is measured using a custom pneumotachograph. The highly-accurate respiratory profiles recorded by this device during a nitrogen washout procedure are fit to a computational model of lung to provide estimates of lung inhomogeneity. This thesis presents the first applications of this technique in clinical settings, describing a series of studies that evaluated lung inhomogeneity in patients with asthma, chronic obstructive pulmonary disease, and pneumothorax.
A compact Herriott cell was integrated into the MFS, facilitating the measurement of CH4 and C2H2 in addition to the pre-existing spectroscopic systems. C2H2 is soluble in blood, whereas CH4 is relatively insoluble. Thus, analysis of the relative uptake rates of these gases by the body, when small amounts are included in the inspiratory gas, can provide insight into an individual’s cardiac output. This strategy was utilised, with cardiac output assessed by fitting a model of CH4 and C2H2 uptake to MFS recorded data. This method was validated in a study that evaluated healthy volunteers at rest and during moderate exercise on five consecutive days.
Quantifying redox metabolism in the plant metabolic network
Keywords: 13C
metabolism
flux analysis
deuterium
arabidopsis
nad
isotopic labelling
ISNT-MFA
nadp
plants
MFA
redox
nadph

The aim of this thesis was to develop and evaluate methods for quantifying redox metabolism in plants. Current methods suffer from a lack of: quantitative measurement; specificity between different redox carriers; and subcellular resolution. Three approaches were explored to address these limitations including, deuterium labelling, genetically encoded fluorescent biosensors for redox metabolites, and isotopically non-stationary metabolic flux analysis (INST-MFA). Deuterium labelling strategies for quantifying NADPH production fluxes were found to be ineffective in plants due to hydrogen exchange between NADPH and water, catalysed by flavin-enzymes. Fluorescent biosensors were effective at quantifying changes in NADH:NAD+ ratios and NADPH concentrations in Arabidopsis leaves, and identified dynamic responses to pathogen elicitation, hypoxia, nitrogen supply and menadione treatment. INST-MFA using [13C]glucose was used to quantify changes in subcellular fluxes of heterotrophic Arabidopsis cells under menadione induced oxidative stress; major changes in flux through anaplerotic reactions were identified and coenzyme balancing suggested the majority of biosynthetic NADPH demand could be met by isocitrate dehydrogenase. Of the methods evaluated, INST-MFA has the potential to make the largest contribution to quantifying redox metabolism in plants by providing measurement of specific subcellular fluxes, although this approach remains limited by a lack of coenzyme specificity. Further development of fluorescent biosensors to allow quantitative calibration will provide critical information for kinetic or thermodynamic models of plant metabolism. The methods developed in this thesis provide a set of tools for quantifying redox metabolism in plants that can be applied to improve our fundamental understanding of plant biology and meet biotechnological aims.
Sensory-motor integration in Gnathonemus petersii
Keywords: sensory ecology
weakly electric fish
neuroethology
object recognition
Gnathonemus petersii
animal behaviour

Animals are inundated by stimuli as they undergo the challenges of daily life. To cope, they possess senses which allow them to obtain information from their environment. They can tune into important aspects of this information and decide on the most appropriate response, requiring coordination of the animal’s sensory and motor systems. This interaction is not one directional. Animals can actively shape their perception with self-driven motion. Weakly electric fishes are an excellent group of animals to study this bidirectional interaction because they possess a unique active sensing system (their electric sense) which seems to be closely coupled with their own body movements. The aim of this thesis was to investigate sensory-motor integration in the weakly electric fish Gnathonemus petersii (G.petersii). In data chapter one, we found that electric organ discharges were generated during forwards and backwards swimming, suggesting that G.petersii have the capacity to collect electrical information bidirectionally. Importantly, we found that electrical activity generated in the two swimming modes only differed when they were investigating objects, indicating that the movements had a role in sensory acquisition. In data chapter two, we found that egocentric motion is important for object recognition, specifically movement-induced modulations (MIMs), which seem to provide information regarding an object’s shape. Lastly, we found in data chapter three that MIMs is not always a robust cue for shape recognition, especially when the objects differ subtly in shape and scanning space is compromised. Some evidence suggests that individuals might be able to use other movement related cues instead, e.g. electrical snapshots. This thesis reinforces the importance of self-generated motion in enhancing perception, especially in environments where information is difficult to extract (e.g. the murky rivers that G.petersii inhabit). These findings not only improve our understanding of active electrolocation, but of active sensing more generally.
Regulation of innate immune signalling by hypoxia
Keywords: hypoxia
innate immunity
uORF
immune signalling
translation

Innate immunity is the first line of defence against invading pathogens and is also required for the initiation of adaptive immunity. Innate immune responses and inflammation are stimulated by pattern recognition receptors and cytokine receptors. A well-functioning immune defence is crucial for clearance of invading pathogens, but the knowledge of how the immune system is influenced by microenvironmental cues such as hypoxia is still limited. Hypoxia is a common feature in inflammatory sites as well as in solid tumours. In this thesis, I describe a mechanism that hypoxia suppresses immune signalling by receptors such as TNFR1, NOD2, IL-1R and IFN-γR2 that are encoded by uORF-containing mRNAs. This finding unveils an immunological mechanism for desensitisation by hypoxia.
The mechanism may be applicable to different physiological or pathophysiological processes, such as autoimmune diseases and cancer. In this thesis, I describe how this mechanism affects tumour immune evasion. Specifically, hypoxic-inhibition of TNF and IFN-γ signalling results in suppression of MHC-I expression levels on the cell surface, which are essential for activation of CD8 T cell dependent anti-tumour immunity. Genetic deletion of uORFs in TNFRSF1A and IFNGR2 counteracts hypoxic inhibition of the expression of MHC-I induced by TNF and IFN-γ in Yumm1.7 mouse melanoma cells, leading to enhanced CD8 T cell-dependent anti-tumour immunity in this syngeneic mouse model. Consistently, higher TNF and IFN-γ signatures predict better clinical outcomes and tumour hypoxia negatively correlates with T cells infiltration and disease specific survival rates in melanoma patients. These data indicate that targeting uORFs counteracts hypoxia-mediated immune suppression in cancer.
The finding of oxygen level regulating immune signalling activity may contribute to our understanding of inflammation regulation and development of therapeutics against cancer.
Edmund Spenser and the spatiality of allegory
Keywords: personification
night
early modern Ireland
ecocriticism
Edmund Spenser
spatiality
cartography
allegory
Renaissance architecture
prosopopoeia

This thesis considers the relationship between space and allegory in the poetry of Edmund Spenser. It argues that Spenserian allegory is an inherently spatial conceit. In The Faerie Queene, the figurative nature of metaphors seems to be deliberately forgotten, as spatial metaphors take on literal existence. Fairyland reifies ethical concepts, and these reifications tend to possess spatial characteristics ‘other to’ the ‘spatial consequences’ of those concepts outside the allegory. I adopt from Christopher Burlinson’s instructive earlier study (2006) a Lefebvrian critique of the idea that space signifies like a text. This anticipates the second major claim of the thesis: that taking action in Fairyland is not analogous to reading The Faerie Queene. Spenser’s figures are only similar to the poem’s readers, rather than simple transpositions of them. The thesis is divided into three parts. The first is about the spatiality of persons. Surveying classical and Renaissance theories of prosopopoeia and contemporary theories of personification, I argue that personification should be considered as a kind of allegory, because of the ‘spatial otherness’ it entails. In the second part, I examine embodiments of nature, focusing on Spenser’s neglected figure of Night, and his famous personification of the world’s rivers. I argue that personification exchanges natural motion for human mobility, thus compounding the illegibility of the natural world. The final two chapters examine two locations, caves and houses, by which concepts in Fairyland are reified. I show the spatial distortions effected on ethical concepts by these locations, their characteristics and cultural connotations. The thesis provides extended readings of episodes and motifs in The Faerie Queene which have received very little critical attention. It re-assesses the relationship between reading the poem and action in Fairyland. Its account of allegory as a spatial conceit also adjusts a tendency to pose allegory and space in antithesis.
High pressure turbine blade platform cooling and feed architecture
Keywords: Linear Cascade
Turbine cooling
Turbomachinery
Experimental

In this thesis, novel cooling systems for gas turbine blade platforms were developed and assessed experimentally. A new highly modular facility was designed, manufactured, and commissioned to support investigations of a variety of different platform cooling systems. The facility is a high pressure, high temperature, transonic, linear cascade. A high degree of engine fidelity is achieved by: operating at scaled engine conditions; using test blades with full platform and fir tree root geometry; and including engine-representative internal hub seal structures and coolant feeds. The inclusion of hub seals, realistic coolant feeds, and full test blades allowed engine-feasible systems to be tested and representative leakage flows to be reproduced.
Two novel platform cooling systems were developed, using low-order numerical models, which utilise internal cooling features embedded directly into the platform surface. These systems are: a convective cooling passage design which draws coolant from the front seal, passes it through the platform, and exhausts into the rear seal; and an impingement jet array design which draws coolant from the shank cavity and similarly exhausts into the rear seal. Each system was integrated into cascade geometry rotor blades, manufactured in titanium via additive manufacturing, and used to experimentally determine metal effectiveness distributions across mainstream platform surfaces. Metal effectiveness distributions are determined from IR measurements of surface temperature. The cooling performance of each concept was quantified and compared to a baseline case with no cooling features, cooled solely by leakage flows.
The film cooling performance of front seal purge flow was investigated experimentally, to determine adiabatic film effectiveness, at a range of purge flow angles and mass ratios. The aerodynamic impact was assessed using a downstream area traverse system to determine total pressure loss coefficient distributions. A practical design to alter the purge flow angle in engine architectures was proposed and the viability of the system demonstrated using numerical modelling. A new experimental data processing technique was developed to correct adiabatic film effectiveness distributions determined from experiments with a non-uniform inlet temperature profile, such as that caused by a time-varying inlet thermal boundary layer.
‘Medici ‘cross roads’: the intersection of warfare and politics in the Tyrrhenian Sea and Duke Cosimo I’s path towards the Order of Santo Stefano (1544-1563)’
Keywords: Habsburg
Duke Cosimo I de Medici
Galley
Charles V
Warfare
Pisa
Tuscany
Florence
Crusade
Early Modern
Order of Saint Stephen
Italian Wars
Philip II
Corsair
Order of Santo Stefano

Recent scholarship has emphasized the socio-economic aspects of the Medici crusading Order of Santo Stefano – especially regarding its establishment and early history (c. 1562-1621). Additionally, focus is almost always drawn to Santo Stefano’s famous corsair voyages in the late sixteenth and seventeenth centuries – or the artwork and other cultural aspects related thereto. Yet, Cosimo I de Medici’s overwhelming and intricate experiences during the Habsburg-Valois Italian Wars (1494-1559) and the subsequent campaigns in North Africa also directly influenced his plans to establish a military religious order. On the rare occasions that they have been discussed by historians, the first two decades of the Medici galley squadron and coastal fortresses (c. 1544-1563) are examined in their own right and completely separated from Santo Stefano and vice versa. The political and military triangle of Cosimo, his Habsburg ‘allies,’ and threats by his enemies – the Valois, Ottomans, and Barbary corsairs – during the Italian Wars was not only the impetuous towards an expanded naval infrastructure but was important in shaping the emergence of the order. Moreover, Cosimo’s Levantine ‘crusades’ pre-date the order by at least three years. These ‘voyages against the infidel’ undoubtedly impacted and further shaped Cosimo’s strategies towards increasing his maritime presence and founding a military religious order. While connecting Santo Stefano to these rarely-mentioned and arguably neglected events, this thesis sheds light on the intricate tapestry of warfare, politics, and crusading in the early modern Mediterranean as it pertained Cosimo I, duke of Florence and eventually Siena. The Habsburg-Valois conflict’s naval and amphibious aspects; the ambitious projects and struggles related to building a Tuscan naval infrastructure and Medici sovereignty; ‘crusading’ and religious warfare; and Cosimo’s political interactions with the Habsburgs, the Valois, and other powers ultimately contributed towards his decision to found the Order of Santo Stefano in 1562.
To retaliate or not: a matter of cyber risk perception
Keywords: risk society
international security
deterrence
international relations
cybersecurity
retaliation

This thesis investigates variation in state responses to hostile cyber operations. The central argument is that states’ strategic cultures and historical experiences shape their risk attitudes in cyber attack scenarios, with important consequences for their willingness (or not) to carry out meaningful punishment. To guide the empirical investigation, the thesis develops a conceptual framework drawing from and adapting the “risk society” theory in Sociology – an approach that has not yet been applied in cyber studies. The thesis explains weak state responses as a result of cultural and historical forces that produce sensitivities to the inherent risks and uncertainties of the operational environment of cyberspace. It explains strong state responses as the result of a different sensitivity: preoccupation with an existential threat, which produces a willingness to accept operational risks.
Conceptually, the thesis contributes to domestic-level constructivism in International Relations by elaborating upon the historical and cultural roots of national risk profiles in cyber conflict scenarios. Empirically, it applies the risk framework to three case studies. It argues that as a risk society, the United States failed to punish cyber attacks meaningfully due to concerns about risks arising from the operational environment – particularly the risk of conflict escalation. By contrast, Israel – a threat society – carried out strong punishment because of its preoccupation with the existential threat posed by Iran, which prompted Israel to tolerate operational risks. Although Estonia was also a threat society, it moderated its response to cyber attacks because of its membership within NATO, a risk community whose sensitivities Estonian officials decided to appease because of their desire to retain alliance support in face of the perceived existential threat posed by Russia.