VictorJuiz/thesis huggingface dataset:
The studies on the mechanism and inhibition of Isocitrate Dehydrogenases 

Isocitrate dehydrogenases (IDHs) are human metabolic enzymes producing NADPH (IDH1/2) or NADH (IDH3). IDHs are involved in cancer metabolism and progress; upregulation and mutations to human IDH1/2 that catalyse reduction of 2-oxoglutarate (2OG) to 2-hydroxyglutarate have been identified in multiple cancers. The work described in this thesis attempted to gain a better understanding of IDH1 and IDH2 biochemistry by studying the inhibition and kinetics of wild type (wt) IDH1/2 and mutant IDH1/2 (mIDH1/2), with the aim of enabling improved IDH1/2 targeting treatments.
By comparison with IDH1, there are only limited inhibition studies reported on IDH2. The work described in this thesis began with profiling of reported mIDH1/2 inhibitors with IDH2 using biochemical and biophysical assays. Allosterically binding mIDH2 targeting inhibitors were found to be Mg2+ or Mg2+-2OG complex competitive, as is the case for IDH1. NaCl was observed to affect the kinetics of both Mg2+ and 2OG (lower their affinities) with mIDH1/2 in a manner that increases the inhibition potencies of mIDH1/2 inhibitors, particularly with R172K IDH2.
In the assay optimisation of the inhibition assays for wt IDH1/2, the results support the proposal that the substrate for wt IDH2 is the isocitrate-Mg2+ complex as recently shown for IDH1. Screening for wt IDH1/2 inhibitors was performed. As a result, several wt IDH1 and wt IDH2 selective inhibitors and a pan-wt IDH1/2 inhibitor were identified. Mechanism of action studies suggested the pan-wt IDH1/2 inhibitors are likely to be Mg2+ or Mg2+-isocitrate competitive.
To date, all potent mIDH1/2 inhibitors and the wt IDH1/2 inhibitors identified here are likely to be allosteric binders; it is of interest to find an active site interacting inhibitor competing with isocitrate/2OG binding. TCA cycle intermediates and their analogues, and synthetic 2OG derivatives were studied with wt and mutant IDH1/2 to identify inhibitors and competitive substrates. A 2OG derivative and N-oxalylglycine were identified as IDH1/2 variant inhibitors. Some synthetic 2OG derivatives bearing C3-substitution manifested substantial activity as substrates with IDH1/2 variants. Mechanistic studies with synthetic 2OG derivatives and R132H IDH1 are consistent with half-site activity and positive cooperativity processes involving the IDH dimers.
Overall, the work described in this thesis reveals that the allosteric inhibition of both wt and variant IDH1/2s leads to Mg2+ or Mg2+-substrate competition. In addition, 2OG derivatives can act as both inhibitors and alternative substrates for IDH1/2 variants; they will be useful as biochemical probes to study IDH catalysis.

Advisor: Schofield, C
Methods for medical device and surgical epidemiology: applications in knee replacement and COVID-19 related tracheotomy

Although medical devices (MDs) and surgery have been part of medicine since its start, the methods for their study in epidemiology have not kept pace with the developments in pharmacoepidemiology. The recent increased attention from society to the potential harms of unsafe implants has led to improved legislation that call for a much closer evaluation of MDs. However, the evaluation of MDs and surgery presents unique caveats and challenges, such as the ascertainment of the indication of the surgery or how to include surgeon characteristics in the analysis, that can greatly influence outcomes.
To advance research on how one can overcome these challenges, I tested several methods. I used Propensity Score (PS) methods, namely PS matching, stratifications and inverse probability weighting (IPW); and Instrumental Variables (IVs), based on surgeon and hospital preference in the study of the effectiveness and safety of partial vs total knee replacement and evaluated them by comparing observational results to those from a randomised controlled trial. I applied the target trial framework to the study of the timing of tracheostomy in patients with COVID-19. I further studied the safety of knee replacements using the self-controlled case series method. I studied the potential heterogeneity by subgroups (on high-risk patients, by gender, by age, and by deprivation) on the safety and effectiveness of knee replacements. I explored the effect of surgical volume on knee replacement outcomes. I finally used simulation studies to examine the flaws and challenges of preference-based IV.
I found that PS stratification and IPW may be able to minimise confounding and bias in the study of partial vs total knee replacement, provided that the study is carefully designed to consider both patient and surgeon characteristics. I also showed how preference-based IVs may not be fit for purpose for this use case.
Future research is needed to examine whether my findings are generalisable to other settings and whether other IVs can be used safely in MD and surgical research.

Keywords: inverse probability weighting
COVID-19
multilevel data
instrumental variables
simulation
epidemiology
observational data
medical device
tracheotomy
plasmode
knee replacement
trial replication
surgery
causal inference
self-controlled case series
propensity score
Advisor: Prieto Alhambra, D
Strauss, V
Collins, G
‘And the system fails us all the time’: Responses to domestic violence against First Nations women in Australia and the case for an integrated rights-based approach founded in self-determination

First Nations women in Australia experience domestic violence disproportionately compared to Australia’s ‘settler’ population. Prior research suggests that domestic violence responses developed with the ‘settler’ population in mind may be problematic for First Nations women, but to date no studies have examined First Nations women’s domestic violence service interactions prior to fatal violence. I accordingly review a whole-of-population sample of domestic violence-related homicide cases from several Australian jurisdictions, alongside findings from yarning and interviews with First Nations Elders, specialist domestic violence workers and survivors, to examine and analyse First Nations women’s service contact histories preceding fatal violence. Viewing findings from a postcolonial, intersectional perspective attuned to Australia’s history of invasion/colonisation and the ongoing violence of ‘settler’ occupation, I argue the domestic violence response system—comprising criminal justice and specialist service responses—is an expression of colonising state power.
I then ask how responses to domestic violence against First Nations women can be improved. While Australia’s domestic violence response system reflects current international standards, my findings suggest that these standards may be problematic for First Nations women in the Australian ‘settler’ context. I review United Nations (‘UN’) guidance to ascertain how, and to what extent, First Nations women’s right to self-determination has been considered relevant to First Nations women’s rights to be safe and free from violence. I conclude that, to date, UN standards and state monitoring of Australia has been insufficiently attentive to the interaction of these rights. I propose enhanced rights-integration (normative integration) as a way to support improved state responses to domestic violence against First Nations women, however I remain cautious about the UN’s ability to transcend its state-centric focus and support meaningful self-determination in its most fulsome sense.

Keywords: self-determination
First Nations women
Domestic Violence Service System
First Nations
Domestic Violence
Advisor: Ghanea, N
Condry, R
The role of social video game play and relatedness in players’ well-being

Video games is one of the most popular forms of entertainment, and there are nearly 3 billion video game players in the world. The popularity of video games has caused a heated discussion about their influence on players’ well-being. Many negative impacts on mental and physical health have been found when problematic video game use or gaming disorder has been reported. However, some studies ignored the motivation for gaming when exploring the relationship between playing video games and well-being. Self-determination theory (SDT) proposes that people’s behaviours are driven by three basic phycological needs, autonomy, competence, and relatedness. Relatedness, or being connected with other people, can be achieved through social video game play, especially as the multiplayer online video games community is getting larger.
Therefore, this study explores the role of social video game play and the need for relatedness in gaming and examined whether it influenced one’s well-being and life satisfaction by analysing three waves of self-reported well-being and motivation data of 87,321 video game players and their game-behaviours data. Results provided evidence that social gamers and gamers with higher relatedness satisfaction scores experienced higher affective well-being and general life satisfaction. It was also found that the effects of social gaming and relatedness on affective well-being were stronger among female players. No moderation effect of gender was found in life satisfaction. This study reveals that playing video games with others and fulfilling social needs are beneficial to one’s well-being, stressing the importance of not only behaviours but also psychological satisfaction in video game studies.
Green ammonia: optimising production and quantifying its potential as an energy vector

The environmental imperative to achieve net-zero emissions quickly to minimise the rise in average global temperature rise due to global warming is clear. To achieve this, variable renewable energy (VRE) needs to substitute existing energy sources in the polluting sectors: electricity, heat, transport and industry. The integration of VRE sources to high levels of penetration however, is difficult: unlike most commodities, supply and demand must be in equilibrium at each moment in time, from the sub-second to inter-annual. This study quantifies the flexibility required by a power network to integrate additional VRE sources as a function of the magnitude and duration of the electrical energy storage required. The original energy storage requirement modelling tool (ESRMT) calculates: 1) the storage magnitude index (SMI), 2) the storage duration index (SDI) and 3) the storage size required. This quantifies the impact of VRE penetration, the mix of VRE sources and the application of other flexibility methods on the storage requirements. The ESRMT is used to consider locations in Japan, the UK, Canada and Australia and shows that, while requirements do increase with VRE penetration, the magnitude and type is location specific and highly dependent on the mix of VRE sources. Medium and long-term storage required at high VRE penetration are difficult to mitigate. The chemical storage of electrical energy, using ammonia, is a promising solution due to its favourable chemical and technical properties. The decarbonisation of the ammonia production is itself an environmental imperative as it accounts for 1.3% of global carbon dioxide emissions and supports over 48% of the global population through nitrogen based fertilisers. The developed islanded ammonia production modelling tool (IAPMT) optimises the mix of VRE sources, plant design and operation to minimise the levelised cost of ammonia (LCOA) at any given location. The IAPMT is used to consider ammonia production at 534 locations in 70 countries. It shows that at the best location a LCOA of 473/tonneiscurrentlyachievable,butthiswilldecreaseto
310/tonne by 2030. Decarbonised production will be highly competitive with conventional production by 2030. Assuming its use for seasonal storage, these LCOA estimates mean that the levelised cost of electricity (LCOE) of power-toammonia-to-power of $252/MWh by 2030.

Keywords: Islanded Production
LCOA
Decarbonised
Haber-Bosch
Ammonia
Variable Renewable Energy
Energy Storage
Network Flexibility
LCOE
Advisor: Bañares-Alcántara, R
Starting a new conversation: constituting institutions in communicative practices of shareholder engagement on environmental and social issues

Increasingly, corporations are expected to create impact, in addition to financial profits. Sustainable investments, and among them especially shareholder engagement, are supposed to support and contribute to corporate impact creation by starting a new conversation about sustainability between shareholders and management of engaged firms. I approach this challenge of starting a new conversation by paying attention to different communication practices in shareholder engagement to examine the earliest moments of change towards environmental and social sustainability in the institutionalized context of traditional shareholders. I start out with a theoretical paper about the fluidity of listening and speaking that constitute the earliest moments of constituting institutions in communication. The empirical context of shareholder engagement provided data for the other two papers of this thesis. I used data from ethnographic observations collected over two years, as well as interviews, reports, an engagement database, and supporting documents. In the first empirical paper I looked at how a new logic is activated in the meetings between the shareholder and firm management and therefore a new conversation is started in an already established context. In the second empirical paper, I examined how the need to report the additional value created in engagement activities, as well as need for collective resources for engagement meetings ultimately affected the shareholder’s ability to perform impact creating practices. In short, this thesis contributes to a better understanding of the earliest moments of institutional constitution in communication, and the earliest moments of institutional change. By better understanding this, it also helps to better understand the obstacles of impact creation for mainstream economic actors, as well as the mechanisms of how financial actors can contribute to a transformation towards more sustainability of the wider economy.

Keywords: Institutional theory
institutional change
Shareholder engagement
Communication
Logics
Advisor: Smets, M
Whittington, R
Voyages to the ‘House of Diversion’: the seventeenth-century water gardens of the Cope family at Hanwell, Oxfordshire

Archaeological investigations, beginning in 2012, have done much to recover, record and interpret the remains of a large garden of the seventeenth century in the grounds of Hanwell Castle, Oxfordshire. The garden is important not only because it is a rare example of an essentially intact garden from the period but also because of a reference made to Sir Anthony Cope by Robert Plot in his Natural History of Oxfordshire where he describes his house, and by extension the contents of his garden, as the real ‘New Atlantis’, referring to a fictional prototype of a science based community posited by Sir Francis Bacon in 1626. Some of the features within the garden are reported on and a number of individuals associated with it documented. The implications of Plot’s record of ‘a society of learned virtuosi living obscurely’ at another Cope family property at Tangley, also in Oxfordshire, are examined.
Beginning with a consideration of the practical and theoretical basis for the study of historic gardens this work goes on to look at the evolution of garden design from the middle ages to the start of the seventeenth century. It emphasises the indigenous tradition of working with bodies of water whilst also considering the effects of continental developments, through the course of the Renaissance, on garden design and especially, hydraulic engineering. A detailed account of the Cope family, their social and intellectual circle and their work on the gardens at Hanwell is accompanied by description and analysis of the physical remains of the garden which are compared and contrasted with other contemporary gardens. Of particular importance is the discovery of a unique assemblage of seventeenth-century terra-cotta garden urns which are reported on and set within the context of the technology and economics of the time. In taking up Plot’s challenging remark possible links with the early scientific community in Oxford are established and the role of the site in the development of contemporary thinking reviewed along with a general consideration of the part played by gardens in the development of science in the early modern period.

Keywords: Hanwell Cope Oxford water garden park history of science pots
Advisor: Healey, J
Munby, J
Measurements of the Standard Model Higgs boson in the WW decay mode with the ATLAS detector

The discovery of a Standard Model-like Higgs boson in July 2012 signalled the beginning of a new realm of high energy physics research at the CERN Large Hadron Collider. The decade since has involved studying this new particle in several final states and in challenging kinematic regimes. Measurements are performed with increasing precision, which help to understand the Higgs boson and its role within the Standard Model of particle physics, narrowing down the possible existence of new physical phenomena.
This thesis presents measurements of the Standard Model Higgs boson production cross sections through gluon-gluon fusion and vector-boson fusion using the H→WW decay mode. The measurements are performed with a data set collected from proton-proton collisions occurring at √s=13 TeV by the ATLAS detector during Run 2 of the Large Hadron Collider (2015–2018), corresponding to an integrated luminosity of 139 fb-1. Given the size of the Run 2 data set, the measurements are extended to measure production cross sections of the Higgs boson in distinct kinematic fiducial regions using the Simplified Template Cross Section framework. Good agreement with the predictions of the Standard Model are observed within the uncertainty of the measurements.

Keywords: Higgs boson
STXS
W bosons
Particle Physics
ATLAS
Advisor: Hays, C
Show your true colours: can the use of colour aid memory for Chinese speakers’ English L2 vocabulary acquisition?

The purpose of this study is to examine the use of colours in aiding memory for English L2 vocabulary acquisition. ‘4-colour memory’ is an innovative vocabulary strategy that encourages language learners to have self-directed learning. By reviewing their word knowledge, learners use a colour-coding system to highlight words in a colour, indicating how well they know the word. For example, blue for full knowledge of the word, green for fundamental knowledge, yellow for only impression but no knowledge, and red for no knowledge at all. This study took the first step to empirically test this method and see if it helped learners to memorise words better. 99 secondary school students in Hong Kong participated in this study and they were assigned into 3 groups. During the reading comprehension task, the ‘multiple-colour’ group used the ‘4-colour memory’ approach to highlight words according to their familiarity with the word, the ‘single-colour’ group only used the colour yellow, and the ‘no-colour’ group did not use any colours. After analysing the results from pre-tests and post-tests, participants improved from the pre-test to the post-test in general. However, there were no statistical differences between the learning session and conditions so it could not be discerned whether colours helped the participants to learn. Based on the observations of participants’ performance in the 3 different groups, this paper discusses some practical pedagogical implications for educators to consider. Future research avenues are also discussed with the hope that learners can grow more independent in L2 vocabulary learning.

Keywords: vocabulary acquisition
vocabulary strategy
short-term memory
colour
long-term memory
working memory
Master practitioner of international law: Japan’s rise through the ranks of international society, 1853-1905

This thesis examines Japan’s rise through the ranks of international society between 1853 and 1905 from the lens of the practice of international law. It pursues two objectives: (1) to present a theoretical integration of the English School and the practice literature in IR; and (2) to analyze how Japan achieved this rise by becoming a ‘master practitioner’ of international law.
The study offers a conceptualization of international society as a universal yet stratified community of practice of international law. It identifies three stages of a practitioner: novice, regular, and master, based on three cumulative criteria of background knowledge and rule acceptance, simple compliance, and ability to exploit the rules for national interests and international reputation, particularly through forward-looking and backward- looking mistake-correcting. Empirically, the study examines how Japan transitioned from a novice practitioner under the Tokugawa regime (1853-68) to a regular practitioner under the Meiji government (1868-1894) and a master practitioner during and after the Sino- Japanese War (1894-1905) by correcting two mistakes: the sinking of the Kowshing and the Port Arthur massacre. I conduct a single-N qualitative research, analyzing Japanese and foreign archival sources and writings of prominent publicists, who served as key recognizers.
Three contributions are made to IR. First, the thesis brings international law to the center of the English School’s notion of international society and shifts the analysis from its passive narrative of socialization and conformity to a more agential narrative of practice. Second, the thesis demonstrates that attaining high position in international society was harder than what has been conventionally suggested by revealing how masterful performance, not simple compliance, accorded high rank. Finally, the thesis brings an agential understanding of Japan’s rise through its historically-grounded analysis. The study furthers the English School, and the larger themes of hierarchy, practice, and agency speak to the broader IR.

Keywords: Japan
international law
international society
Advisor: Keene, E
Exploring the educational experiences and identity of ethnic minority Korean and Yi individuals in China

To explore the intersection of ethnicity, language, and identity, this study examines the educational experiences and identity of 19 ethnic minority individuals in China. 13 participants are ethnic Korean, and 6 participants are ethnic Yi. Through the semi-structured interview, this study investigates the following research questions: What are the similarities and differences between the educational experiences of the ethnic Korean and Yi? How do Korean and Yi individuals perceive that minority education and language exposure to their minority languages, Korean and Yi, has affected their identity? Drawing from the qualitative data, this study reveals that the two groups of participants vary in their educational experiences and heritage language exposure. Nevertheless, their perception of ethnic identity is prominent in a similar way. Under trends of Sinicization, urbanization, and structural discrimination, the ethnic Yi and Korean suffer from inadequate social language affordances, the breakdown of traditional ethnic boundaries, and a crisis of heritage language loss.

Keywords: Chinese Korean
minority language
ethnic minorities
heritage language
Korean
Yi