VictorJuiz/thesis huggingface dataset:
Exploring the experiences of healthy siblings and parents when a child is diagnosed and treated for cancer

The diagnosis of childhood cancer is recognised as a significant stressor for families. There is a growing body of research exploring the experiences of parents and healthy siblings during the treatment of childhood cancer. The first paper is a systematic review of 28 qualitative studies that explored the experiences of mothers and fathers from different countries and cultures. Key findings included the desire to feel in control, the need to continuously adjust, various coping styles were adopted, emotional and practical support was valued, and gender and cultural differences were reported. Clinical implications include the need to provide clear information and aid the sense of control, care needs to be individualised, and fathers' needs should be acknowledged and met. The second paper aimed to address some of the gaps in the literature on healthy siblings, as few studies have explored the experiences of adolescent healthy siblings. A qualitative study was carried out using grounded theory to explore adolescent healthy siblings' experiences across the duration of treatment for childhood cancer. A semi-structured retrospective interview was completed with eight participants. A grounded theory model was developed, which illustrates how the healthy siblings' experience changed over time, with the most challenging period being the diagnosis and initial phase of treatment. Their experiences appeared to depend on a number of factors including: how they managed the stressors; temperament; family relationships; individual coping strategies; and support received. Developmental changes associated with adolescence appeared to further serve as a potential protective factor. Clinical implications include health care professionals needing to ensure healthy siblings have appropriate support in place and the required coping skills to reduce the chance of psychosocial problems developing. There is a particular need for early support, as healthy siblings are likely to particularly struggle between the diagnosis and initial treatment.
State neutrality in relation to the use of certain medical procedures which end or prevent the lives of disabled human beings, with particular reference to English law

There are a number of medical procedures which end or prevent the lives of disabled human beings, and the use of these procedures has attracted, and continues to attract, much public and academic debate.
This thesis does not seek to comprehensively address relevant ethical concerns in this debate, but rather seeks to examine, and critically evaluate, a different matter: the neutrality of the state in relation to the use of these medical procedures. Although much of the analysis can apply to other states, the thesis examines whether or to what extent the United Kingdom (as an example of a state) is neutral, with particular reference to English law.
I develop the argument in this thesis in three parts. In the first, I evaluate the main philosophical foundations in my enquiry: the concept of state neutrality (Chapter 1), arguments about noncoercive genetic selection (Chapter 2), and definitions of disability (Chapter 3). In the second, I analyse the state’s involvement in regulation and practice: based on an analysis of the law (Chapter 4), of the information provided to parents or prospective parents (Chapter 5), and of public funding (Chapter 6). In the third part of the thesis (Chapter 7), I draw conclusions based on the first two parts considered together, and discuss the difficulties in achieving state neutrality. While it is clear that the United Kingdom is not (and that no state can be) completely neutral, I explore whether it is more narrowly neutral by considering different interpretations of state neutrality based on the state’s intention. I argue that these interpretations all inevitably rely on important normative commitments, and that the United Kingdom appears not to be, in at least a number of instances, truly neutral in even a more limited sense.

Keywords: political philosophy
medical law
disability
state neutrality
jurisprudence
Advisor: Finnis, J
Foster, C
How does the loading complex interact with cohesin?

Cohesin is an SMC complex essential for genome organisation and the accurate segregation of sister chromatids in mitosis. The activity of this ATP dependent ring shape trimer composed of two SMC proteins and a kleisin subunit relies on two additional complexes. While the loading complex made of Scc2 and Scc4 is essential for the recruitment of cohesin at the loading sites, the releasing complex comprised of Pds5, Scc3 and Wapl is necessary to adjust the turnover of cohesin on DNA. During replication, Smc3 is acetylated and cohesion is established between the two newly replicated DNA molecules. Scc2 is essential for the ATPase activity of cohesin, its loading on chromatin and the genome reorganisation by DNA loop extrusion.
In order to better understand the biological role of Scc2, the interaction between Scc2 and the different subunits of the cohesin complex was investigated using genetic mutations combined with in vivo and in vitro protein crosslinking. Scc2 makes extensive contacts with at least three regions of Scc1 whose deletion cause defects in loading and translocation of cohesin. Scc2 competes with Pds5 in order to stimulate the ATPase activity of the complex, but the mutation of the binding site in Scc1, common to Pds5 and Scc2, is not sufficient to abolish cohesin loading. By using different crosslinking strategies, accurate binding sites could be identified between Scc2 and Scc1. Scc2 was also found to interact with a conserved loop in the head of Smc1 that is essential for its engagement with Smc3’s head and ATP hydrolysis. Finally, crosslinking experiments confirmed the existence in vivo of the folded configuration of cohesin that brings the hinge into contact with the coiled coils. This configuration was observed throughout the cell cycle, independently of cohesin acetylation, suggesting that Scc2 is not involved in its stabilisation.

Keywords: Scc1 cohesion
ATP hydrolysis
crosslink
Scc2
Advisor: Nasmyth, K
Sherratt, K
Social decision-making under uncertainty

Social decisions are fraught with uncertainty. In my thesis, I explore how uncertainty shapes social decision-making across three empirical projects (9 studies, total N = 3,346).
I start by comparing social and individual decisions under risk (i.e., choices over outcomes with known probabilities) across a series of online studies. I find that choices for others are markedly more risk-averse than choices for self because they are more attuned to disadvantageous prospects. Supporting the hypothesis that enhanced uncertainty in social decisions might produce such a precautionary pattern, I observe greater indecision and less confidence in social relative to individual choices, while motivational differences cannot explain their divergence.
As a next step, I set out to experimentally manipulate uncertainty about others’ experiences of outcomes in a laboratory experiment. My observations suggest that enhanced uncertainty about others’ experience plays a supporting role in a particular manifestation of precautionary preferences for others, namely a stronger aversion to harm others than oneself.
Finally, I consider how uncertainty shapes interactions between humans and artificially intelligent machines as a broader category of social decisions. I find that people’s need to explain others’ minds and actions extends to interactions with machines. This demand to reduce uncertainty about machines’ inner workings is more pronounced for settings involving high stakes and/or scarcity – a pattern paralleling demand for explanation in realms evading machines.
Two central insights emerge: first, enhanced uncertainty about others’ experience of outcomes in social choices elicits precautionary preferences whereby decision-makers minimise potential harm to others. Second, humans’ notorious need to reduce uncertainty about others’ internal states extends to interactions with artificial social agents, where it translates into a robust demand for interpretability of algorithmic decisions.

Keywords: decision-making
uncertainty
social
Advisor: Crockett, MJ
Faber, N
A success model for cyber threat intelligence platforms

Cyber security information sharing is increasingly playing an important role in improving the organisational and national overall security posture. Efforts in the public and private sectors to foster information sharing initiatives have intensified in recent years resulting in the current complex constellation of sharing organisations, forums, platforms and tools, including threat intelligence management solutions. However, despite the growing interest, a number of questions pertaining to the nature of cyber security information sharing and its success remain unanswered.
This dissertation uses mixed methods to consider How can cyber security information sharing be made more successful? In answering this question we draw on practitioners’ experiences and collect empirical data to ensure that our conclusions can contribute to practice and theory. As with all evaluation efforts, this dissertation relies on the well-established premise that the success of a process cannot be reasonably assessed without a coherent understanding of the goals it is designed to attain.
Our first contribution therefore provides a nuanced conceptualisation of cyber security information sharing. This includes surveying practitioners for their understandings and attitudes towards different aspects of the process and what it is trying to achieve. It also addresses the disparity among them when it comes to distinguishing between the different forms information sharing can take by proposing a high-level classification of these forms and their objectives.
Our second contribution examines the extent to which the benefits and barriers to successful cyber security information sharing mentioned in the literature are reflected in the attitudes of cyber security professionals. A categorisation of the benefits and barriers is introduced followed by a self-administered survey of practitioners. The results show a degree of inconsistency between theory and practice. It also highlights quality issues as a primary concern for practitioners and a hindrance impacting the success of these efforts.
Our third and main contribution is two-fold. First, we investigate the quality problem further in the context of threat intelligence platforms. Through a systematic review of the literature and a modified Delphi study we identify a set of quality dimensions practitioners employ in determining the quality of the platform’s content. Second, we draw together the previous findings, as well as the theories and practices of information systems literature to develop and test a holistic success model — a framework for understanding and measuring the key success factors and their interrelationships — for threat intelligence management platforms.

Advisor: Simpson, A
Identification of a novel regulator of extracellular matrix degradation in chondrocytes

There are currently no drugs that modify the progression of the degenerative joint disease osteoarthritis, which is characterised by protease-mediated degradation of the cartilage extracellular matrix. Identification of molecules that regulate protease activity could therefore lead to the development of new therapies for osteoarthritis. The Wann group previously showed that mutation of Intraflagellar transport protein 88 (IFT88) increased degradation of the cartilage matrix component aggrecan by proteases in vitro. As IFT88 is required for the assembly of a cell surface organelle called the primary cilium, the aim of my thesis was to investigate whether the primary cilium is involved in the regulation of protease activity. Based on the Wann group’s finding that mutation of IFT88 impaired Low-density lipoprotein receptor-related protein 1 (LRP-1)-mediated endocytosis of extracellular proteases, I hypothesised that the primary cilium is a region of efficient endocytosis and thus regulates the extracellular activity of proteases.
To address this aim, I measured protease activity when four genes encoding proteins involved in cilia assembly were knocked down with siRNAs in a chondrocyte cell line. Generation of the AGEG aggrecan neoepitope was used as an indicator of protease activity. I showed that protease activity was not affected by knockdown of three of the ciliary genes tested. However, knockdown of the gene encoding Tau-tubulin kinase 2 (TTBK2) increased the activity of the protease A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5). This increase was not associated with changes in ADAMTS-5 RNA levels during my experiments, constitutive activation of cilia-dependent hedgehog signalling, or reduced levels of the physiological ADAMTS-5 inhibitor, Tissue inhibitor of metalloproteinase 3 (TIMP-3). The effect of knockdown of the TTBK2 gene on ADAMTS-5 endocytosis could not be definitively determined.
Together, these results showed that whilst the primary cilium itself may not be required for protease activity regulation, TTBK2 is a novel regulator of ADAMTS-5 activity. Further investigation of the molecular mechanism of ADAMTS-5 regulation by TTBK2 may help to identify new therapeutic targets in osteoarthritis.

Keywords: ADAMTS-5
Primary cilia
Proteases
Cartilage
Osteoarthritis
Advisor: Wann, A
Troeberg, L
Situations, presuppositions, and descriptions

It is commonly assumed that definite descriptions imply the existence and uniqueness of an entity satisfying their nominal content. But there is no widespread agreement on how this is encoded: do definite descriptions assert, or presuppose, existential import? It is rarer still to find consensus on the status of these implications when the definite article is embedded in a variety of syntactic environments. How should we model the behaviour of definite descriptions within questions and conditionals? Do definite descriptions carry uniqueness implications within appositives and nonrestrictive relative clauses? What can constraints on LF movement and binding tell us about the semantics of definites?
In this thesis I examine these questions. In so doing, I defend an analysis of definite descriptions as expressions of type e, whose uniqueness presuppositions are stage-managed by the manipulation of syntactic situation pronouns. Notably, this approach accurately accounts for the semantic behaviour of singular definites across a range of configurations that tease apart distinct dimensions of meaning.

Keywords: Presupposition
Not-at-issue content
Formal semantics
Situation semantics
Definite descriptions
Advisor: Elbourne, P
Antigen discrimination in primary human T cells

Antigen discrimination is the process by which T cells differentiate self from foreign antigens. They do this using their T cell receptors (TCRs) that recognize peptide antigens bound to major histocompatibility complexes (pMHCs) and this TCR/pMHC interaction is augmented by a host of other co-signaling receptors including adhesion receptors. Despite extensive work, the quantitative ability of T cells to discriminate antigen and the molecular mechanisms underlying it remain debated. We developed an improved binding assay that allowed measurement of ultra-low affinity TCR/pMHC interactions, generated >30 different peptide variants for two different human class I-restricted TCRs and accurately measured their affinities. Surprisingly, we found an affinity floor at a KD of ∼2 mM that could not be further lowered even by changing the peptide sequence dramatically. This could represent the self-pMHC affinity at which T cells are selected during positive selection in the thymus. I utilized the KDs generated by our new binding assay to characterize the ’discrimination power’, which is a measure of a receptor’s ability to discriminate between ligands with different affinities or offrates. I found that the discrimination power of the TCR was much lower than the ’near-perfect discrimination’, previously reported, and that in some settings it was increased by CD2 and LFA-1. Furthermore, these adhesion receptors increased the sensitivity to pMHC, while accelerating pMHC-dependent TCR downregulation, indicating that they likely influence the way the TCR binds pMHC. In the future, this new understanding could be useful for improving the sensitivity and discrimination power of artificial receptor constructs used in immunotherapy, enhancing their safety and efficacy.

Keywords: LFA-1
Mathematical modeling
Antigen sensitivity
T cells
Discrimination power
CD2
Adhesion receptors
Surface plasmon resonance
Ultra-low affinity pMHC
Antigen discrimination
CD58
T cell receptor
Altered peptide ligands
ICAM1
Antigen specificity
Advisor: Davis, S
Dushek, O
Krüger, P
Shielded hydrogen plasma: a new hydrogenation method for silicon solar cells

Improving the efficiency of solar cells will play a key role in ensuring that solar generated power reaches grid-parity across the globe. One of the main challenges in achieving high-efficiency silicon cells is the recombination of minority carriers at defects, both at the silicon surface and throughout the bulk. Introducing hydrogen into silicon is a well-recognised method to achieve excellent chemical passivation of surface and bulk defects.
In this thesis, a novel method for the introduction of hydrogen into silicon is demonstrated, called Shielded Hydrogen Plasma (SHP). SHP is shown to effectively introduce neutral atomic hydrogen into silicon without the drawbacks of other hydrogenation techniques such as plasma damage or high-temperature steps. A palladium membrane is placed between the silicon and the PECVD- generated plasma to avoid plasma-related damage whilst still allowing the release of atomic hydrogen. The potential of converting SHP from a batch process to an in-line process by using cheaper and more resistant metallic shields is also considered, to encourage industry uptake. Palladium-silver and aluminium foils were shown to be effective alternatives to palladium leaf shields.
SHP passivates silicon-oxide/silicon interfaces extremely well, as demonstrated using thermally-oxidised 1W-cm 200 μm n-type silicon where the effective lifetime was found to increase from 12 μs to 1.05 ms after SHP processing and to 6.3 ms upon application of corona charge. This corresponded to a surface recombination velocity of ≤ 0.17 cm/s.
SHP is also shown to be a useful tool for the study of hydrogen-related defects in silicon. These defects are shown to be introduced into n-type silicon in the form of a damaged region with or without a dielectric layer. A new hydrogen-transport model across the silicon-oxide silicon interface is presented, showing that the interface is the main barrier to hydrogen incorporation into silicon. It is observed that the introduction of charged ions at the interface generates a strong field which enables an increased incorporation flux of hydrogen into bulk silicon. This higher concentration of hydrogen in the near-surface silicon is observed to be responsible for the damage layer.

Keywords: patented
passivation
hydrogenation
solar cells
silicon
renewable energy
SHP
Standing down: the logic of security force defection

From Egypt to Venezuela, authoritarian regimes live and die by the sword. Amongst students of democratization, it has become axiomatic that a dictator’s fate in mass upris- ings turns largely on whether the coercive apparatus decides to defend him. Yet, despite its significance, the literature equivocates on the fundamental question of how defection hap- pens. One strand holds that defection is carried through by unhappy soldiers: the defeated, disillusioned, and dispossessed. The other views defection as a strategic coordination game, disconnected from preexisting grievances and fealty to the incumbent.
In this thesis, I seek to produce a more unified way of explaining why and how secu- rity force defections occur. My analytical starting point is the stretch of time before mass uprisings gather full momentum, in which security agents are optimally placed to foresee incoming contention. Anticipating the revolutionary coordination problem, I contend that potential defectors assess the feasibility of sparking seamless defection cascades by using positional factors (such as patronage and ethnic stacking) as proxies for unobservable loy- alties across the coercive apparatus. Positional factors are important not only as first-order motives but as crucial structural context for first-movers.
If grievances are sufficiently acute and prevalent, I argue that defectors face strong incen- tives to engage in coalition-building before the revolution begins. By leveraging their extant professional networks and crystallizing their social capital, first-movers enlist colleagues in ‘defection networks’ to stack the deck in their favour before the uprising starts in earnest. During the revolution itself, defectors and regimes promulgate strategic frames to elicit sup- port from erstwhile loyalists and those caught in indecision. The logic of coalition-building and strategic framing has been overlooked in studies of defection: fast-moving contention occludes dogged work behind the scenes to tip cascades in a particular direction.
To probe these arguments, I analyze the overthrow of Serbian dictator Slobodan Miloˇsevi ́c on 5th October 2000. Drawing on a range of qualitative sources, I adduce evidence of clan- destine coalition-building and strategic framing within multiple branches of the Serbian security apparatus. I also document how the Miloˇsevi ́c regime and the political opposition vied for the loyalty of the security forces. Altogether, the thesis makes three contributions. First, it evinces that positional factors and coordination logics are both germane to the de- fection process once we rethink how they exert causal force. Second, it shows that processes of social mobilization (e.g., networking and strategic framing) are useful for understanding secretive sedition within the ruling coalition. Third, it extends the literature empirically by analyzing non-military security forces and by targeting an unexplored case of defection.

Advisor: Kalyvas, S
Ansell, B