VictorJuiz/thesis huggingface dataset:
The effect of high temperature on polycrystalline diamond
Keywords: thermal behaviour
polycrystalline diamond
thermal breakdown
PCD
fracture
mechanical properties
heating

Polycrystalline diamond (PCD) is an important technological material used in the drilling of rock and the machining of high strength, non-ferrous alloys; composites and wood products. For these applications, no other material surpasses its cutting performance. However, PCD suffers from a degradation in its mechanical properties at the high temperatures caused by frictional heating that limits further advances in its capabilities. The literature presents two potential theories to explain this phenomenon: residual stresses due to differential thermal expansion mismatch between diamond and cobalt and, graphitisation of the diamond catalysed by cobalt. As the evidence for neither theory is strong, this thesis presents an in-depth experimental investigation and quantitative analysis of the mechanisms of breakdown of PCD at high temperature. Neutron diffraction is used to measure the residual stresses in diamond and cobalt as a function of temperature. Whilst the compressive stresses in cobalt are found to have a slight toughening effect at room temperature, differential expansion of the two phases is found to have an insignificant effect on the breakdown of PCD at high temperature. The mechanisms of diamond graphitisation are investigated using neutron and X-ray diffraction and an in-situ heating TEM experiment is used to observe graphitisation occurring in real-time. Graphitisation is found to be a two-stage process with nuclei of graphite first forming from -carbide particles followed by catastrophic graphitisation occurring after an incubation period. A group VII transition metal element is found to increase the length of this period and at some temperatures prevent graphitisation entirely when added to the cobalt binder. An elastic model is presented which explains the sensitivity of this incubation period to temperature and binder chemistry. The literature on the mechanical properties of PCD is also found to contain numerous conflicting reports about the strength of grain boundaries. Microcantilever beam bending is therefore used to show that grain boundaries do not act as weak paths for fracture, that the binder phase is ductile and well adhered to the diamond and that the microstructural features most likely to affect the strength of PCD are processing defects in diamond grains caused by crushing and plastic deformation during manufacture. In summary, this thesis settles some marked inconsistencies and illuminates some poorly understood phenomena in the literature on the room-temperature and high-temperature behaviour of PCD, furthers the mechanistic understanding of graphitisation in PCD and makes possible the design of more thermally robust PCD.
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
Keywords: political philosophy
medical law
disability
state neutrality
jurisprudence

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.
How does the loading complex interact with cohesin?
Keywords: Scc1 cohesion
ATP hydrolysis
crosslink
Scc2

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.
Social decision-making under uncertainty
Keywords: decision-making
uncertainty
social

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.
Identification of a novel regulator of extracellular matrix degradation in chondrocytes
Keywords: ADAMTS-5
Primary cilia
Proteases
Cartilage
Osteoarthritis

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.
Situations, presuppositions, and descriptions
Keywords: Presupposition
Not-at-issue content
Formal semantics
Situation semantics
Definite 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.
Antigen discrimination in primary human T cells
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

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.
Shielded hydrogen plasma: a new hydrogenation method for silicon solar cells
Keywords: patented
passivation
hydrogenation
solar cells
silicon
renewable energy
SHP

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.
The analysis, modelling, and acoustic control of fluidic devices
Keywords: fluidic device
jet
control

Zero-carbon flight represents arguably the biggest challenge of the green revolution. A variety of novel flight concepts have been proposed in response to emissions targets set by the International Air Transport Association (IATA). The common theme to enabling these innovative technologies is efficient, reliable, low-weight solutions to the control of airflow: from controlling aircraft aerodynamics to heat transfer in gas turbines. Active flow control represents a family of such solutions, and is based on the idea of harnessing the natural amplification provided by nonlinearities in fluid mechanics to bring about large-scale system change with only a small energy input. Fluidic devices are a highly-reliable means of controlling high-speed flows and have a small response time.
A analytical, dynamic model of an attached jet, the canonical form of all fluidic devices, is developed from first principles. The jet is excited acoustically, which is modelled as a time-varying component of additional entrainment. The core component of the model is a novel, unsteady jet curvature equation, which finally removes the need for the quasi-steady jet assumption. An accompanying experimental validation is performed, and a strategy for inverting system nonlinearities is presented. The model is linearised so that magnitude and phase frequency responses can be compared with the validation data. Good agreement is found for one roll-off in the data, and explanations for a second, unmodelled roll-off are given.
A closed-loop controller is designed and implemented for an acoustically-driven fluidic amplifier in which the flow is continuously modulated. The attached-jet model provides good agreement with experimentally-identified frequency responses, and a black-box identification is used for control purposes. The performance of the resulting LQG controller is evaluated in several experiments, and is shown either to match or outperform its open-loop counterpart in every respect. However, closed-loop bandwidth is limited by turbulent noise in the region of the system dynamics, and a means of overcoming this fundamental challenge is discussed.
The response of a jet shear layer to a modulated perturbation is explored from a signal processing perspective. The well-known shear layer demodulation property is identified specifically as an envelope detector because of its phase insensitivity. A novel input over-modulation technique is proposed that halves the required actuator bandwidth while suffering only a 2.7 dB reduction in response magnitude. It is further hypothesised that the shear layer response includes a sampler, and an analogy with the Nyquist sampling theorem is made. Early experiments appear to invalidate the analogy, although the experiments are somewhat inconclusive. If the Nyquist theorem does not hold, interesting implications are raised about the current paradigm of the response of shear layers to modulated perturbations.
Exploring interventions to reduce blood loss during and after caesarean delivery in Africa
Keywords: caesarean
obstetrics
haemorrhage
surgery
blood loss
global surgery
Africa

Background
Women in Africa are fifty times more likely to die following caesarean delivery compared to high-income settings and blood loss during and after caesarean delivery is independently associated with mortality. We aimed to (i) identify interventions, and (ii) identify which interventions African clinicians and researchers recommend as feasible and effective to reduce blood loss during and after caesarean delivery.
Methods
(i) We conducted a systematic review and network meta-analysis to identify nonpharmacological interventions. We conducted a comprehensive search from database inception to 31 st December 2019, with no language restrictions. We included studies of women undergoing caesarean delivery, which assess nonpharmacological interventions, and report one of the study co-primary outcomes (blood loss [ml] or risk of post-partum haemorrhage [>1,000 ml]). We excluded retrospective studies, and study cohorts not representative of the general caesarean delivery population.
(ii) We conducted a Delphi Consensus study, including obstetrics and anaesthesia providers from across Africa. Rounds one to three were online surveys, and round four formed a live online discussion.
Findings
(i) We included 51 studies in the network-meta-analysis, forming 13 distinct intervention groups. Thirty studies were not included in the meta-analysis and were synthesised narratively. On random effects model analysis, only three interventions had clinically significant findings, of which one had statistical significance.
(ii) Twenty-eight interventions were considered highly effective and highly feasible. These interventions covered broad domains including community based; antenatal; perioperative; and health system strengthening interventions.
Interpretation
The published trials on the effect of non-pharmacological interventions on blood loss associated with caesarean delivery are inconclusive. There is a need for collaborative pragmatic trials to identify effective and generalisable interventions. The broad range of recommended interventions highlights the importance of a multifaceted systems strengthening approach to reduce morbidity and mortality associated with blood loss during and after caesarean delivery in Africa.