VictorJuiz/thesis huggingface dataset:
Withdrawing from international regimes: bargaining power in the investment treaty regime

Why do some states withdraw from international regimes? How do others successfully renegotiate the terms of international cooperation? This thesis investigates whether, and how, the changing bargaining power relations impact treaty-based cooperation in the international investment treaty regime. The institutional architecture to govern investments consists of a web of bilateral investment treaties (BITs). The investor-state dispute settlement (ISDS) mechanism embedded in most BITs has resulted in an accumulation of arbitration cases between host governments and foreign investors, and states have increasingly begun to question their investment treaties.
I argue that while states have learned about the true risks of investment treaties through ISDS, they must have sufficient bargaining power to act in response. Bargaining power is best understood as alternatives to the existing agreements. Alternative economic treaties and domestic investment laws facilitate foreign investment and decrease dependency on the existing agreements. Economic improvement can also bring confidence for a government that such alternatives can be developed. When sufficient alternatives are in place, a state can either exit the agreement, demand renegotiation, or conduct a strategic exit with intentions to renegotiate at a later stage. The optimal strategy for a revisionist state depends on the bilateral relationship between the states, and how important they consider their partnership.
I employ a mixed methods approach to provide evidence for my argument. I use data on bilateral investment treaties to show that bargaining power is associated with greater risk of BIT termination and renegotiation. Relative changes in economic power also condition the effects of ISDS on BIT outcomes. Interviews conducted with Ecuadorian and Indonesian policymakers show that governments are strategic in reflecting on their outside options when considering BIT reform. By examining the dynamics of investment treaty reform, this thesis contributes to a better understanding of change in international regimes governing the world economy.

Keywords: international regimes
bilateral investment treaties
bargaining power
international cooperation
Advisor: Snidal, D
Leveraging genomic annotations to uncover latent components in gene expression data

Over the last decade single cell genomics has transformed research in genetics, resolving transcriptional activity at an unprecedented resolution. Over 1000 single cell studies have been published to date and the scale of single cell data is increasing, cell atlases of complex organisms are being curated, and experimental sample sizes are increasing exponentially.
Standard analyses for single cell data include a hard clustering of cells and an investigation of these clusters to identify cell-specific marker genes. This approach is powerful and identifies transcriptomic differences between cells. However, such analyses fail to account for biological heterogeneity present in continuous developmental processes taking place in cells, or to use relevant prior information that may be available to the researcher. In this thesis we investigate incorporating prior information into factor analysis for gene expression analyses, which infers components of genes that are coexpressed or co-repressed across cells, and their expression in each cell. First, we consider structural features of the data, extending an existing tensor decomposition method to four dimensions, facilitating analysis of gene expression data indexed by cell, time, tissue and gene. We demonstrate the relative benefits of the method against a lower dimensional method. Secondly, we develop a widely applicable new prior structure and inference algorithm that allows for incorporating external prior information into factor analysis. The new algorithm automatically selects important annotations and leverages this information to infer biologically meaningful components. Comparing two likelihood models, we evaluate their strengths and weaknesses on simulated data, and the benefit of incorporating prior information into the algorithm. We demonstrate the power of the method to capture meaningful components of expression on a well-studied single cell RNA-seq dataset from cells undergoing spermatogenesis, using transcription factor binding affinities as prior information, and demonstrate the utility of the new prior structure in leveraging such annotations.

Keywords: statistical learning
single cell RNA-seq
statistics
variational inference
statistical modelling
Advisor: Myers, S
Too weak for biophysics: Prioritising and progressing fragment hits from X-ray crystallographic screening.

In the last decade, X-ray crystallography has matured to a powerful primary screening technique for fragment hit identification in structure-based drug discovery. Unmatched in its sensitivity, it provides valuable knowledge of precise fragment binding location in a protein-fragment complex. The comparison to 19F NMR fragment campaign conducted in this work emphasises the strength of crystallographic screening by revealing additional binding sites and interactions for the breast cancer target NUDT5.
The high sensitivity of X-ray crystallography allows to identify even weakly binding fragment hits, which are often undetectable by commonly used biophysical methods. The lack of orthogonal tools with sufficient detection limits to quantify their interactions impedes prioritisation of fragment hits for elaboration. For this purpose, the use of both NMR-based techniques as well as concentration-dependent crystallographic soaking are explored. While further investigation of relaxation-based T1rho NMR for rapid ranking of weak binders is necessary, the crystallographic approach demonstrates a correlation between the lowest detectable soaking concentration (LDSC) and fragment binding affinity. A low-concentration counter-soak is proposed as a simple solution to triage fragment hits according to their binding strengths, streamlining their selection for further elaboration.
Weak fragment hits can be informative for lead discovery: they can reveal unknown binding sites and can be progressed into more potent compounds. For the target NUDT5, crystallographic screening identified a novel, previously unreported binding pocket. The elaboration efforts utilising SAR by catalogue approach and crystallographic soaking as readout highlight the value of crystallography for the progression of weak binders in absence of other assays.

Keywords: crystallographic soaking
NUDT5
fragment-based drug dicovery
crystallographic fragment screening
fragment elaboration
Advisor: von Delft, F
Curing through questioning? A cross-cultural analysis of Pyrrhonism, Madhyamaka, and their potential as philosophical therapy

This thesis shows what we may learn about ancient Pyrrhonian scepticism, Indian Madhyamaka Buddhism, and their potential as philosophical therapy, by examining the two traditions in conjunction. It aims to accomplish three goals: present a robust comparison of Pyrrhonism and Madhyamaka; demonstrate that significant insights may be gained from this juxtaposition; and show that these two traditions challenge current ways of doing philosophy.
The thesis starts by examining the preconditions of fruitful cross-cultural research; it is shown that ascribing too much or too little importance to context (radical relativism and universalism, respectively) is problematic. Previous comparisons of Pyrrhonism and Madhyamaka have paid little attention to such methodological considerations, which has led to crucial shortcomings. This is unfortunate, because their remarkable parallels demand a representative, accessible overview. Having laid the necessary foundations, the thesis presents such an overview. A therapeutic framework is employed to systematically compare the two traditions, including their diagnoses of disturbance, their proposed cures, and their promised cured conditions. Such themes allow for systematically outlining their similarities and differences and to limit arbitrariness and bias.
Despite their striking similarities, very few attempts have been made to learn about Pyrrhonism and Madhyamaka by studying them in conjunction. This thesis corrects this oversight by demonstrating that such cross-cultural research enables us to shed new light on persistent ambiguities and allows us to bolster and defend both traditions. For example, it is demonstrated that Madhyamaka can shine a new light on one of the, if not the most vexed question regarding Pyrrhonism: what is the scope of suspension of judgment?
Finally, this thesis shows that Pyrrhonism and Madhyamaka challenge the practice of philosophy itself. It is demonstrated that contemporary schools of thought akin to Pyrrhonism and Madhyamaka may share their therapeutic potential. If so, then certain contemporary philosophies are able to alleviate distress and instil a sense of tranquillity. This means we must expand our understanding of what philosophy can do. After all, if contemporary philosophy can change our experience of the world for the better, it has a much greater potential than is currently believed—both in terms of audience and impact.

Keywords: Philosophy as therapy
Madhyamaka
Pyrrhonism
Scepticism
Advisor: Westerhoff, J
Castagnoli, L
Unveiling the protein-protein interactome of the RNA-binding
protein Rev in HIV-1 infected T CD4+ lymphocytic cells

Human immunodeficiency virus type I (HIV-1) is a retrovirus that causes acquired immunodeficiency syndrome (AIDS) and affects ~38 million people worldwide. The HIV-1 protein Rev escorts under-spliced viral RNAs to the cytoplasm, overriding nuclear retention imposed by the host cell. Thus, Rev permits full viral gene expression and particle production. However, Rev is challenging to study as it is highly disordered, expressed at low levels and encoded by an open reading frame that overlaps other viral genes. Therefore, previous Rev research was largely performed under non-physiological conditions, leaving the physiological interactions and functions of Rev uncertain. Here, I engineered HIV-1 constructs that encode tagged Rev protein expressed to physiological levels. I used these constructs to immunoprecipitate Rev interactors in CD4+ cells, revealing the physiological interactome of Rev. Through meta-analysis of this novel interactome and previously published datasets, I provide evidence for a new connection between Rev-mediated export and HIV-1 virion assembly. Furthermore, I investigate the interactions of two packaged proteins, PURA and PURB, during HIV-1 replication, to reveal possible therapeutic targets. My research uncovers the localisation, interactions and functions of Rev during HIV-1 replication under conditions better approximating physiological conditions than previously used. This work thus provides highly valuable datasets to instruct new avenues of research on the HIV-1 infection cycle.

Keywords: HIV-1
protein
Rev
interactions
virus
Advisor: Castello, A
The efficacy of a teacher-led vocabulary intervention for third graders in rural china: using lexical compounding awareness to support vocabulary depth

Approximately 80% of the Chinese modern vocabulary are compound words. Because of this characteristic, Chinese lexical morphology also focuses highly on compound words. The study’s purpose was to investigate a Mandarin Chinese vocabulary intervention that trained lexical compounding awareness in third-graders to explore if targeted lexical compounding awareness training can improve vocabulary depth. The study was conducted in a low-income community in rural China where academic achievement falls below the national average. The study hopes to provide insight into the feasibility of vocabulary interventions in diverse settings in China. Participants were 57 third-grade students from rural China. A mixed-methods design was adopted to address research questions: a within-subject quasi-experimental design aimed to evaluate the effectiveness of the intervention of morphological awareness and vocabulary depth, and a thematic analysis of teacher interviews explored teachers’ experiences of the intervention. The research questions looked at: 1. Does an intervention that focuses on systematically instructing on Chinese compound lexical structures affect third graders’ Chinese vocabulary knowledge? Specifically, a) Does targeted training in Chinese compound lexical structures increase children’s compound lexical awareness and vocabulary depth? b) Does the vocabulary knowledge of taught words from targeted training in compound lexical structures transfer towards novel words? c) Is there a relationship between initial skills in vocabulary depth and morphological compound awareness and their improvement post-intervention? 2. What are teachers’ perspectives and experiences of the Lexical Compounding Awareness? A paired samples t-test showed that there was an improvement between pre and post-test assessment performance. ANOVA showed a strong transfer effect from morphological awareness and vocabulary knowledge of taught words to other novel words. Significant strong correlations also showed that initially low-performing students showed the greater improvement after intervention. The teachers who delivered the intervention also expressed an overall positive experience of the intervention. Implications for future research and practice in literacy interventions and morphological training for vocabulary growth are discussed.

Keywords: CDE2021
Morphology
CDE
Intervention
Pilot study
Literacy
Vocabulary
Mixed methods research
Advisor: Nag, S
The epidemiology of hand osteoarthritis

Background
Radiographic osteoarthritis most commonly affects joints in the hands, with osteoarthritis at the finger interphalangeal joints (IPJs) thought to be a different subset to that at the first carpometacarpal joint (CMCJ). The thesis aimed to identify risk factors for hand (particularly IPJ) osteoarthritis.
Methods
Systematic reviews and Delphi studies were performed to identify risk and prognostic factors for incident and progressive IPJ osteoarthritis. A risk prediction model for incident radiographic IPJ osteoarthritis (Kellgren Lawrence (KL) ≥2 in ≥1 IPJ), and a prognostic model for the progression of IPJ osteoarthritis (increase of KL ≥1 in ≥1 IPJ), in the Chingford 1000 Women Study were developed. As the prognostic model performance was poor, the model was revised in the Johnston County Osteoarthritis (JoCo) Project. The burden of hand injury requiring hospital admission, and the association between hand injury and osteoarthritis was investigated in cricketers.
Results
From the systematic review and Delphi study for incident IPJ osteoarthritis, older age in women, female sex, family history, and injury were important risk factors. Whilst for the progression of IPJ osteoarthritis, older age and family history were important prognostic factors. The prediction model included 459 participants (257 with osteoarthritis at 10 years). Older age, manual occupation, and first CMCJ osteoarthritis were important predictors. The prognostic model included 195 participants (181 progressing at 10 years), with no prognostic factors found to be important. Following revision, female sex was found to be an important factor. Over ten years, 9,188 cricketers presented with hand injuries, most commonly in young adults, with thumb and little finger injuries, particularly fractures and dislocations. Hand injury was associated with osteoarthritis.
Conclusion
IPJ osteoarthritis might be a continuum of first CMCJ osteoarthritis. Manual occupation and injury could be targeted to decrease disease risk, whilst older age is an unmodifiable risk factor.

Keywords: hand osteoarthritis
epidemiology
prediction model
Advisor: Furniss, D
Arden, N
Collins, G
Silman, A
Parents’ and teachers’ responsibility assignments for Chinese primary school children’s education

To build a supportive learning environment for children, healthy and cooperative relationships between parents and teachers can be built through understanding each other’s roles and responsibilities. Effective home-school collaborations may be contingent on a sense of shared responsibility between parents and teachers. However, current understandings of obligations in children’s education remain implicit and ill-defined. In this exploratory study, responsibility assignments between parents and teachers for Chinese early primary school children’s education were investigated.
A mixed design study was conducted. First, twelve individual semi-structured interviews were conducted with Chinese parents and teachers of children in grade one through three. Thematic analysis revealed five responsibility themes: 1) communication between parents and teachers; 2) help with children’s learning; 3) help with children’s behaviour and socialemotional wellbeing; 4) awareness towards children’s development; 5) encouraging the holistic development of children. Although both groups shared the opinion that cooperation between two groups is essential, some discrepancies in the assignment of responsibility were identified. The second part of the study contained a quantitative survey developed with the results from the qualitative interviews. 100 parents and 85 teachers participated in the second part of the research. A total of 27 responsibility items covering the five themes were presented. Participants were asked to indicate how responsible do they think parents and teachers are on each item. The stress and difficulty relating to fulfilling responsibilities was also investigated. The results suggested that in children’s education, parents were generally rated as more responsible than teachers in four out of five themes. However, discrepancies in ratings were observed in terms of parents’ and teachers’ ratings of their own group. Parents rated their own group as highly responsible when it came to helping with children’s learning, and teachers tended to assign themselves greater responsibility than how parents rated their group. Finally, teachers reported higher stress levels than parents.
Findings of the current research demonstrated areas of responsibility believed to be important in children’s early education. Also, some potential tensions between parents and teachers were explored and both groups’ perceptions about the Chinese educational system were addressed. Future research in the area can extend from the current study with more diverse samples, higher grade levels, and factors related to perceived responsibility.

Keywords: Responsibility in children's education
Chinese parents and teachers
Perceived responsibility
Mixed methods research
CDE
Parent-teacher relationship
Responsibility assignment
Primary school education in China
CDE2021
Advisor: Dulay, KM
Relationships between teacher ratings of behavioral adjustment in school and language skills

Behavioral adjustment has been recognized as an essential ability for people to thrive in society, and the inability to properly adjust one’s behaviors may lead to life-long harmful consequences. Previous research has identified multiple factors that are believed to affect this ability. For example, the home environment, gender, parenting styles, and Language ability are known to be related to ratings of behavioral adjustment, yet, this relationship was examined primarily on adolescents or children above age 4. This present study aims to investigate whether the association between language skills and behavioral adjustment is present in children during their nursery school year (i.e., around age 3 to 4). In this secondary data analysis, we measured 545 children in this age band on their language skills using three standardized language assessments including LanguageScreen, CELF P-2, and RAPT, and used a teacher-rated questionnaire to evaluate their behavioral adjustment. We also investigated and controlled for effects associated with the participant’s age, gender, and family income level. Results revealed that older students and girls tended to receive significantly higher behavioral adjustment scores, which means they displayed fewer behavior problems. However, surprisingly, children from the lowest household income group exhibited significantly fewer behavioral adjustment issues than their peers from the most privileged group, which was in contrast with our hypothesis as well as previously established studies. Language ability, as we expected, was a significant predictor of children’s behavioral adjustment and this relationship existed in both boys and girls. This dissertation provides evidence indicating the association emerges as early as at the age of 3. Findings from this dissertation raise the possibility that externalizing problems in young children may be at least partly a reflection of impaired language skills in some children.

Keywords: CDE
CDE2021
Behavioural adjustment
Nursery school
Education
Language ability
Quantitative research
Advisor: Hulme, C
Ideas of identity and investment in language communities among multicultural AAVE speakers learning foreign languages

Imagined communities and investment have both been identified as dynamic forces in the process of learning a foreign language, yet few studies have explored these concepts in relation to Black foreign language learners, and even fewer still have touched on AAVE speaker status and Black multiethnic backgrounds. To address this gap in the literature, this case-study utilizes narrative interviews and short story analysis to examine the relationship between imagined communities and investment in the language learning journeys of three AAVE speaking and multiethnic, monoracial participants. Results suggest that the nuances of Black ethnic identity and the identity struggle bilingual AAE speakers in the US face have an impact on learners’ assessments of speech communities, as well as how they invest in their imagined communities. Given these findings, further research is necessary to determine how best to accommodate Black foreign language learners with differing linguistic profiles and different ethnic backgrounds in the foreign language classroom.

Keywords: Narrative inquiry
ALSLA
Short story analysis
Sociolinguistics
Foreign language learning
Imagined communities
Identity
ALSLA2021
African-American Vernacular English and education / AAVE
Ethnicity
Qualitative research
Investment theory
Interviews
Advisor: Rose, H