VictorJuiz/thesis huggingface dataset:
Isolation of Fibrillar Elastin Gel (FEG) and its application in heart valve tissue engineering
Keywords: Tissue Engineering
Elastin
Viscoelastic
Elastogenesis
Biomaterials

Elastin, although a small constituent of heart valves, plays a significant role in its functionality and the maintenance of tissue homeostasis. It is due to its low abundance that its significance has been overlooked in favour of collagen and glycosaminoglycans. However, repeatedly, the failure of biological prostheses has been associated with the disruption of elastic fibres. The incorporation of exogenous forms of elastin has been challenging due to the intrinsic insolubility and poor processability of polymeric forms. This has led to the precedence of applications of soluble forms of elastin, which, although are tailorable, do not offer sufficient structural integrity or bioactivity (once cross-linked).
This thesis reports a method for the isolation of a novel form of natural elastin, termed Fibrillar Elastin Gel (FEG), which was discovered during the course of the DPhil. A method was developed to modify polymeric elastin to a processable form with improved polymer-solvent interactions. FEG is a thermally induced aggregated gel, composed of rod-like fibres (4-6µm) with improved intermolecular interactions as shown by the appearance of a shoulder at 1618cm-1 by infrared spectroscopy. The material exhibits a low loss factor (~0.1 at 1Hz) and has been hypothesised to be applicable as a biomaterial for tissue engineering of heart valves.
Porous (>94%) scaffolds of multiple compositions were fabricated by freeze-casting. Swelling studies revealed a negative thermosensitivity and contraction of FEG above the inverse transition temperature (30°C). Tensile testing showed a strong positive correlation between the concentration of FEG and the strain-to-failure of composites which increased from 37% to 94% as the concentration increased. In vitro studies revealed FEG contains cell-binding sites and did not hinder the attachment or viability of induced pluripotent stem cell-derived cardiomyocytes. The elastogenic capability of FEG was assessed by studying the gene expression of lysyl oxidase (LOX), elastin (ELA), and fibrillin-1 (FIB-1) which upregulated significantly on scaffolds with higher FEG content, suggesting that FEG would be a suitable material to use to design templates that promote elastogenesis. In addition, layer-specific tri-layer scaffolds were shown to stimulate layer-specific gene expression of extracellular matrix markers such as collagen type I (COL), hyaluronan synthase-2 (HAS-2) and ELA. Tri-layer scaffolds exhibited a non-linear mechanical response as well as bending anisotropy, a key deformation characteristic of native valves.
Exploring the factors and mechanisms involved in triggering the alternative lengthening of telomeres pathway
Keywords: ALT
ATRX
RPA
telomere
Cohesion
replication stress
DNA repair
alternative lengthening of telomeres

Maintaining replicative immortality is a crucial step in the development of cancers and is achieved by activating a telomere lengthening mechanism. While the majority of cancers rely on upregulation of telomerase, approximately 10-15% of cancers achieve telomere length maintenance through a telomerase-independent mechanism referred to as the Alternative Lengthening of Telomeres (ALT) pathway. ALT cancers exhibit a number of characteristic markers and recent work has sought to understand the mechanisms that underly the generation of these markers and of ALT telomere maintenance.
Previous work has also highlighted the striking loss of the chromatin remodelling protein ATRX and its histone chaperon partner DAXX in ALT cancers, and the ability of ATRX and DAXX to suppress the ALT pathway. Until now, however, it has remained unclear as to the mechanisms by which ATRX loss drives ALT development given that ATRX loss alone is generally insufficient to generate the ALT phenotype.
In this thesis a novel marker of ALT, the presence of Replication Protein A coincident with telomeric sequences, is shown. This marker is dependent on the presence of the endonuclease Mus81, which is known to cleave stalled replication forks. In conjunction, evidence is presented showing that the telomeric replication stress or lesions on telomeric DNA when combined with loss of ATRX or DAXX are able to trigger ALT pathway induction. This induction can be triggered both through artificial means with genotoxic agents, but also through loss of the histone lysine methyltransferase SETD2, which is responsible for the methylation of Histone H3.3 at lysine 36. Together these observations provide critical understanding of a possible route of ALT development, given the frequent co-occurrence of histone H3.3 G34R/V mutations, which are known to be detrimental to SETD2 activity, and ATRX/DAXX mutations in ALT cancers.
An examination of scar modelling and assessment methods for the evaluation of treatments
Keywords: treatments
silicone
Scarring

Scarring is the final common pathway for healing within the skin irrespective of age, gender and race. Scars can be itchy, painful, tight and above all, cosmetically disfiguring. Despite advances in surgery and trauma management, there is currently no reliably effective treatment for reducing or preventing scarring. The primary aim of this thesis is to assess the currently available models for scarring and evaluate/further develop the utility of current assessment tools, in an effort to design a pilot randomised control trial for silicone gel treatment of scars.
Review of scar models in humans and animals demonstrated the limitations and drawbacks of many existing methods to assess scar treatments. Examination of currently used subjective and objective scar assessment tools in a plastic surgery clinic helped to develop protocols and methodology for a scar treatment research trial. Long-term scar outcomes assessed using a novel subjective patient reported outcome measure for paediatric burn patients demonstrated no statistically significant difference between those treated surgically, and those treated conservatively. A pilot randomised control trial to produce high quality evidence for silicone gel sheeting in the treatment of scars was set up and successful in recruitment.
Scarring remains a difficult condition for clinicians to manage, with many treatments utilised on a poor evidence basis. Here, we have demonstrated difficulties in establishing a scientific scar treatment model; and created a pilot study that will help to provide high quality evidence for the efficacy of silicone gel sheeting as a treatment for scars.
Meditative practices - correlates and consequences for political attitudes
Keywords: political
mindfulness
meditation
compassion
polarization

While meditative practices have become increasingly common in both science and society, many questions remain about their correlates and consequences for political attitudes. This is what will be examined in this thesis.
Part One of this thesis uses survey data from the United States and Britain to investigate awareness and experience of mindfulness, both overall and across groups. The results from the first empirical chapter suggest that five per cent of adults in the United States in 2017 had used mindfulness during the 12 months prior to the survey interview and mindfulness use was less likely among married adults and more likely among women, sexual minorities, young and middle-aged adults, white adults, employed adults, adults without minor children in the family, adults from the West of the United States, adults with access barriers to healthcare, adults with cost barriers to healthcare, adults with mental illness, and adults with physical pain. The results from the second empirical chapter suggest that fifteen per cent of adults in Britain in 2018 had learnt to practise mindfulness and awareness of mindfulness was more likely among women, unmarried adults, adults from middle and high-income households, and adults who voted Remain in the 2016 Brexit Referendum; and higher levels of engagement with mindfulness was more likely among young and middle-aged adults, but otherwise not concentrated in any particular groups.
Part Two of this thesis uses data from randomized controlled trials conducted in the United States and Britain to investigate the causal effects of mindfulness-based and kindness-based interventions on political attitudes. The results show that: (1) participation in an eight-week compassion-based program increased liberal political attitudes; and (2) a brief befriending meditation reduced affective polarization between Democrats and Republicans. Taken together, the findings suggest that kindness-based practices and programs increase tolerant and other-regarding attitudes more generally.
Subjugation angst: memory and Europeanisation of foreign policymaking in Slovenia and Croatia
Keywords: Europeanisation
Collective Memory
EU
Foreign Policymaking
Subjugation

The past and its remembrance possess an incredible power to influence the present. The field of foreign policy is not immune to the forces of history and a vast body of literature invokes collective memory—an intersubjectively shared narrative construction of the past—to explain states’ international and foreign policy behaviour. The European Union is often called a community of memory, yet EU Members’ national collective memories differ substantially and persistently. Similarly, although the EU strives for unity in foreign policymaking, a truly Europeanised foreign policy has not yet emerged. To determine whether the parallel fractures in the EU’s respective memory and foreign policy communities are interrelated, this dissertation investigates the question: How does national collective memory influence EU Members’ Europeanisation of foreign policymaking? Whilst conventional scholarship emphasizes the influence of collective memory on foreign policy outcomes, the remembrance approach advanced in this dissertation reveals its influence on the foreign policymaking process. More specifically, I argue that national collective memory shapes national role conception which influences the extent of EU Member’s Europeanisation of foreign policymaking, as well as its crystallisation through uploading or downloading. The research design features an asymmetric comparative case study of the principal case of Slovenia and supplementary case of Croatia. It utilises a plethora of documentary primary sources, as well as conducts original empirical research in the form of elite interviews and questionnaire responses. Empirical findings support the theorised influence of collective memory on the Europeanisation of foreign policymaking and unveil that it is particularly remembrance of co- opted subjugation in Slovenia and Croatia that is informative for state practice.
‘It would be very much better if they never had children’: Eugenic Ideas and Policy-making in Edwardian Britain
Keywords: Social Science
Boer Wars
Britain
Poor Laws
Public Policy
Mental Health
Eugenics
Edwardians
Ideas
Disability

‘What I want to insist upon is, that a state of things in which not two out of five of the population below a certain standard of life are fit to bear arms is a national danger, which cannot be met by any mere schemes of enlistment, and that true patriotism requires that that danger should be recognised’ (Miles, 1902: 81).1 Thus warned General J F Maurice writing under an alias in 1902 and sounding the alarm that the surprisingly poor performance of the British military in the Second Boer War (1899-1902), and its rejection of a worrying number of volunteers as physically unfit, might signal the end of British hegemony. General Maurice’s pronouncements launched a debate that would transform British politics in the twentieth century: the debate over physical deterioration and national efficiency.
His views were not entirely new. Investigators, philanthropists, doctors and others, had been warning for decades that the physical condition of the British people, and especially its poorer sections, was disconcerting. General Maurice’s contribution was in explicitly linking these concerns to the burning issue of the day: the military setbacks of the Second Boer War and the realisation that Britain’s predominance had become fragile (Gilbert, 1965). Amid this doubt over ‘whether English ways of doing things were any longer invariably the best’ (Ibid: 143), the Balfour government reluctantly initiated a series of thorough investigations on the various failings of British society and politics, among them the Inter-departmental Committee on Physical Deterioration (1903-1904), the Royal Commission on the Care and Control of the Feeble-Minded (1904- 1908), and the Royal Commission on the Poor Laws and Relief of Distress (1905-1909).
[Introduction continued in thesis]
Reasoning and normativity
Keywords: normative reasons
practical reasoning
theoretical reasoning
responding to reasons

This thesis addresses three questions: (I) What is theoretical and practical reasoning? (II) What is it to respond to normative reasons? (III) What are standards of evaluation for reasoning? Regarding (I), I first critically assess two views which have recently dominated the debate on the nature of the mental activity of reasoning. I argue that different versions of the Rule-Following View, according to which reasoning is essentially a rule-following activity, are problematic. Further, I argue that the Reasons View, which holds that reasoning consists in responding to normative reasons, is assumed by many but defended by few and remains underdeveloped. In particular, it is explanatorily unsatisfactory because, while it explains reasoning in terms of responding to normative reasons, it lacks an account of what it is to respond to normative reasons. I then provide a new theory of the nature of reasoning, the Approval Account. Reasoning is a transition in thought from some attitudes to another which the agent approves of. Regarding question (II), I propose a novel account of what it is to respond to normative reasons: it is a mental process that leads an agent from some attitudes to a response, where this process manifests the agent’s implicit conception of what is right to believe and do, and is under the agent’s (virtual) control. This account of responding to reasons allows me to systematically establish the claim that reasoning is a way of responding to normative reasons. With regards to question (III), it follows that correct reasoning is correctly responding to (supposed) normative reasons. I further argue that we must distinguish between the correctness, the goodness and the aim of reasoning.
Ruling reasons: a defense of constructivism about reasons and objectivism about welfare
Keywords: welfare
interpersonal reasoning
reasons
constructivism
objectivism

I argue in this thesis in favor of a position that combines constructivism about reasons and objectivism about welfare. In Chapter 1, I define reasons constructivism, on the basis of the Kantian origin of the view. I argue that reasons constructivism is a claim about the perspective-relativity of normative reasons for action. Furthermore, I argue that reasons constructivism, as I define the view, is distinct from both reasons objectivism and reasons subjectivism. In Chapters 2 and 3, I offer an argument in favor of reasons constructivism. I argue that in interpersonal reasoning, one agent can only offer reasons to another by engaging in the “if I were you” mode of reasoning. I show that these considerations support reasons constructivism, rather than other meta-ethical views about reasons. Finally, in Chapter 4, I argue that reasons constructivism can be combined with welfare objectivism. I show that this approach allows constructivists to generate the right reasons for agents with fundamentally corrupt judgments. Furthermore, I argue that this mixed position is coherent.
Prototyping the spectrograph mechanisms for harmoni@elt, and the drivers of the main sequence positions of 5muses galaxies
Keywords: Instrumentation
Galaxies

HARMONI (High Angular Resolution Monolithic Optical and Near-infrared Integral field spectrograph) is a planned first light integral field spectrograph (IFS) for the Extremely Large Telescope. Each of the two main mechanical modules within the spectrograph, the Fold Mirror Module (FMM) and the Infrared Grating Module (IGM), used for the folding and dispersion of the beam, respectively, must operate within tight repeatability requirements to ensure that daytime calibration frames (wavelengths and flats) can be taken in the same observational setup following on-sky observations the previous night (to increase the accuracy of the calibration). The first part of this D.Phil thesis involves prototyping and testing the first of the two mirrors of the FMM (the Fold Mirror 1, or FM1) and the entire Infrared Grating Module to ensure they meet the required levels of repeatability. Furthermore, a separate method of achieving the required repeatability is prototyped and tested using detents. This method could be incorporated for use with both the FMM and IGM if their original designs do not meet the required levels of repeatability. A thorough evaluation of the causes of the positional errors is given for each of the three main prototype tests. All tests are conducted at room temperature, as well as initial tests of the detent mechanism and Fold Mirror 1 at 130K, the temperature of the HARMONI cryostat. All three mechanisms achieve warm repeatabilities well within their tolerances.
In the second part of this thesis, data from the Oxford SWIFT Integral Field Spectrograph (IFS) is used to study a statistically significant subset of the 24𝜇m flux-limited 5MUSES galaxies sample. Specifically, the dynamical ratio (rotational velocity 𝑉𝑟𝑜𝑡 divided by the intrinsic disk dispersion σ0, a diagnostic of the galaxy’s evolutionary history) and the Active Galactic Nuclei (AGN) contribution to the Infrared Luminosity (𝐿𝐼𝑅) (AGN fraction, or 𝑓𝐴𝐺𝑁) are investigated to help determine whether the high multiplicative offsets from the expected main sequence of star formation (or the offset from the expected level of star formation given a stellar mass and redshift for each galaxy, and later defined as the ‘Main Sequence Multiple’, or 𝑀𝑆𝑀𝐼𝑅) are due to star formation brought on by interactions, or due to luminosity from an AGN. To do this, the SWIFT subset is kinematically modeled to compute the dynamical ratio, and Spectral Energy Distributions (SEDs) of each galaxy are fit with galaxy and AGN templates to determine 𝑓𝐴𝐺𝑁, which is then used to correct 𝐿𝐼𝑅. It is found that 24% of the SWIFT galaxies are interacting, with 71% isolated, and that galactic interactions are the main cause of the high 𝑀𝑆𝑀𝐼𝑅 observed, rather than AGN. The SWIFT subset of the 5MUSES galaxies serve as a generic representation of the bulk of star forming, main sequence galaxies, making the conclusions of this work applicable to many galaxies in the universe.
Novel applications of bifunctional iminophosphorane superbases in enantioselective catalytic methodology
Keywords: Superbase
Organic Synthesis
Catalysis
Enantioselective

Chapter 1 introduces enantioselective organocatalysis with a specific focus on bifunctional catalysts and chiral superbases. Subsequently, the discovery and applications of bifunctional iminophosphorane (BIMP) catalysts will be described.
Chapter 2 focuses on the development of a novel enantioselective sulfa-Michael addition employing alkenyl-benzimidazoles as electrophiles. The work in this chapter will showcase a rare example of organocatalysed enantioselective addition to alkenyl heterocycles for the rapid generation of 3-D druglike scaffolds.
Chapter 3 introduces approaches to enantioselective P(V) synthesis, highlighting the strengths and shortcomings of current methods to then focus on the development of an unprecedented enantioselective nucleophilic desymmetrisation of phosphonate esters. The unique ability of a novel ureidopeptide BIMP catalyst to promote this reaction enantioselectively will be demonstrated against a wide array of other BIMPs as well as Chinchona alkaloid and phase transfer catalysts. The downstream utility of the desymmetrised product will be demonstrated in the synthesis of numerous attractive nucleoside derived compounds.
Chapter 4 will disclose an improved enantioselective nucleophilic desymmetrisation of P(V) containing species. Via a superior BIMP catalyst scaffold and a thiazolidinone leaving group on the P(V) electrophiles, higher enantioselectivities, lower catalyst loadings, and improved nucleophile scope were obtained.
Classifying spaces of low-dimensional bordism categories
Keywords: Bordism categories
Topological cyclic homology
Miller-Morita-Mumford classes
Tropical moduli spaces
Category theory
Quillen's theorem B

The truncated bordism category Cob_d is the symmetric monoidal category whose objects are closed oriented (d-1)-manifolds and whose morphisms are diffeomorphism classes of compact oriented d-dimensional bordisms. In this thesis we study the classifying spaces of Cob1, Cob2, and several related categories.
In the first part we show that the conditions in Steimle’s "additivity theorem for cobordism categories" can be weakened to only require locally (co)Cartesian fibrations, making it applicable to a larger class of functors. As an application, we construct a fiber sequence that relates the classifying space of the (2,1)-category Csp of cospans of finite sets to the classifying space of its homotopy category Csp = h(Csp), where isomorphic cospans are identified.
In the second part we compute the classifying space of Cob1 by exhibiting it as a circle bundle over Ω∞−2 CP-1∞. As part of our proof we construct a quotient Cob1 → Cob1red where circles are deleted and we show that its classifying space is Ω∞−2 CP-1∞. Based on this we construct a bordism model for the topological cyclic homology of simply connected spaces. We also explicitly describe an infinite loop space map B(Cob1red) → Q(Σ2 CP∞+) and use it to derive combinatorial formulas for rational cocycles on Cob1red representing shifted Miller-Morita-Mumford classes κi ϵ H2i+2(B(Cob1); Q)
The third part concerns the classifying space of the surface category Cob2 and its subcategory Cob2χ≤0 subset of Cob2 that contains all bordisms without disks or spheres. We show that, after passing to a refinement Cob2 → Cob2 , the classifying space of the surface category is BCob2 ≃ S1 - proving that a conjecture of Tillmann becomes true in this setting. We also compute the classifying space of Cob2χ≤0 and show that its rational homotopy groups contain the homology of the tropical moduli spaces ∆g, which is known to grow exponentially. The tools we develop can be applied to a large class of symmetric monoidal categories, which we call labelled cospan categories. In particular, we show that B(Csp) is contractible, whereas the classifying space of its homotopy category is B(Csp) ≃ τ≥3Q(S2).