VictorJuiz/thesis huggingface dataset:
The role of epithelial cells in COPD
Keywords: Infection
Virus
Lungs
Epithelial
Respiratory
Bacteria
Immunology
COPD

Chronic Obstructive Pulmonary Disease (COPD) is a complex disease of the airways that results in the decline of lung function with patients having emphysema or chronic bronchitis pathologies and is responsible for 7% of global deaths per year. Smoking is the largest risk factor for causing COPD and COPD patients can experience exacerbations which is defined as worsening of the symptoms which often leads to hospitalizations. The strongest risk factors for exacerbations are bacterial or viral infections. Non-typeable haemophilus Influenzae (NTHi) and Rhinovirus (RV) in particular are associated with up to half of COPD exacerbations. The epithelium is the first line of defense against pathogens and responsible for keeping the microbiome in check. COPD patients have been shown to have a dysfunctional epithelium.
In this thesis, I investigate the role of bronchial epithelial cells in healthy, smokers, and COPD patients to assess any difference in host immune responses and barrier integrity. They are examined under the context of an infection by the common pathogens that are found, NTHi and RV. In particular, I study type I and type III Interferon (IFN) production as well as the production of alarmins and pro-inflammatory cytokines. In addition, I assess the expression and spatial changes of Tight Junction (TJ) proteins Claudin (CLDN)-3, CLDN-4, and Junctional Adhesion Molecule A (JAM-A) in HBECs post-infection as well as barrier integrity. Finally, HBECs from basal and differentiated HBECs are infected and sequenced to capture gene expression of HBECs and assess for any differences.
COPD human bronchial epithelial cells (HBECs) immune and anti-viral responses are dysregulated as well as TJ protein expression compared to healthy HBECs post-infection with either NTHi or RV16. NTHi infected COPD HBECs had significantly higher concentrations of IFNλ1 and an significant increase in TNFα but did not upregulate TJ molecules during infection unlike in healthy HBECs. Smoker and COPD HBECs however had significantly higher levels of all TJ proteins measured at basal levels compared to health HBECs. My RNA-seq data demonstrated that COPD HBECs express significantly higher amounts of inflammatory genes post-infection with NTHi compared to healthy HBECs and smoker HBECs upregulate anti-viral genes post-infection with NTHi in basal cultures. Together, the data shows that COPD HBECs behave differently than heathy HBECs and are dysfunctional as well as smoker HBECs post-infection in certain contexts.
Assessment of the availability and accessibility of rehabilitation services in a rural district of South Africa
Keywords: disability
accessibility
health policy and systems research
priority setting and resource allocation
rehabilitation
capability framework

This research examines the availability and accessibility of rehabilitation services in South Africa from a health policy and systems perspective and uses the Capability Approach as the theoretical framework for the whole study. The key components of this research are: 1) rehabilitation policies 2) rehabilitation service capacity and 3) perspectives from people with disabilities as users of the service. My study employs both quantitative and qualitative designs to address the research questions. The policy component qualitatively examines the extent to which South Africa's policies facilitate access to rehabilitation services in the public sector through a review of policies for the period 1994-2019. The rehabilitation service capacity complements the policy review by establishing the readiness of district hospitals in a rural district of South Africa to provide these services using an adapted health facility assessment tool. The health facility assessment includes a quantitative descriptive assessment of the infrastructural accessibility of the health facility, and the availability of assistive devices, equipment, and the rehabilitation workforce. The combined findings from the policy review and the service capacity then inform a qualitative description of the implementation gap. In order to understand the contributing factors to this implementation gap, interviews with health facility rehabilitation managers were conducted to explore these further. Finally, interviews with people with physical disabilities uncover the barriers and facilitators to accessing the rehabilitation services in the included district hospitals. The findings point to important gaps in rehabilitation services in the district across all components of the services. Further, these supply-side gaps reinforce each other and interact with prevailing demand-side barriers to constrain access to rehabilitation services for people with physical disabilities. My study makes a theoretical contribution by expanding the Capability Framework, and then concludes with key recommendations.
'A terrible war of defence' - examining the role of dehumanisation in genocidal mobilisation
Keywords: discourse analysis
securitisation
dehumanisation
genocide

This thesis provides an account of the role played by discourses of dehumanisation in mobilising genocidal violence. While scholars of ethnic conflict, social psychology, and genocide have extensively studied dehumanisation, this has focused on it as a phenomenon that reduces moral restraints on violence. Other forms of dehumanisation, however, do something different, designating target populations as an existentially threatening, monstrous, or contaminating threat, and thus a valid target for ‘defensive’ violence. What literature has addressed this latter understanding has been limited by its lack of (political, historical, and societal) contextualisation of these discourses – where were they articulated? By whom? To what audiences? – as well as limited examination of their internal logics.
To address this, I engage in an extended archival examination of three main case studies (Germany, Rwanda, and Serbia), followed by several smaller cases to demonstrate the broader applicability of my model. By building an extensive corpus of examples of dehumanisation, locating them in their historical and social contexts, and tracing their spread and impact, I develop a clearer account of the role of dehumanisation in genocidal violence.
I find that this form of securitising, threat-designating dehumanisation was remarkably consistent across a wide range of cases, and played a significant role in shaping violence. Distinctive views of the enemy – portraying them as diseases and vermin, existentially threatening to the body politic but also easily destroyed or ‘cured’ – were repeated across all three cases, and linked with distinctive violent responses. Based on the correlation between the incidence of dehumanisation and the forms of genocidal violence, as well as relevant social psychology scholarship, I argue that it was effective in promoting campaigns of mass extermination. I conclude by considering how these findings might contribute to genocide early warning regimes, by providing an account of a common precursor to genocide.
Training curricula and structured representations in human and machine learning
Keywords: compositionality
learning
curriculum learning
neural network
representation learning
computational modeling

Humans display a remarkable ability to learn from previous experience. Far from being passively received, however, the training experiences we encounter in modern life are often chosen by ourselves or other people. Existing work shows that some training schedules (“curricula”) work better than others in specific situations, but our understanding of when and why these curricula work is limited, making it difficult to predict curriculum success in novel settings. Compounding this issue, the curricula that subjectively feel most effective are not always optimal for promoting long-term retention or generalization. The main aim of this thesis is to contribute towards the development of computationally-informed theories of curriculum efficacy and mechanism. For this purpose, we make use of behavioral experiments, neural recordings and supervised neural network models.
A key focus of the thesis is on curricula that “start small” by constraining the information that is initially available to the learner. This premise is evaluated in three distinct learning domains. For continuous discriminations such as parametric category structures, initially limiting training to prototypical examples helps. We show that this is at least in part because human internal representations are inherently noisy, and prototypicality acts as a buffer against noise-induced distortions. In tasks that require integrating information from multiple cues, the cue properties emphasized by the training curriculum predict the type of decision rule that human learners use. In a compositional rule learning setting, human learners, but not artificial neural networks, benefit from training on individual rules one at a time. A second aspect of study relates to the fact that in most settings, it is not memorization of training examples, but generalization and transfer to novel problems that are most crucial to adaptive behavior. In this regard, we revive an old idea in cognitive science, that human thought and action are fundamentally compositional. Evaluating models with an explicitly modular structure on the same compositional rule learning task as humans, we establish several correspondences. These include sensitivity to training curriculum, and generalization patterns exhibited by humans, but not by traditional artificial neural networks. Taken together, it is hoped that the work presented in this thesis provides a small step forward in understanding the training schedules that facilitate successful learning.
Short- and long-term memory: effects of ageing and genetic risk and resilience to Alzheimer's disease
Keywords: ageing
short-term memory
long-term memory
apolipoprotein E
APOE

Healthy memory processes are essential for leading a normal life. In particular, this thesis will focus on short-term memory (STM) and long-term memory (LTM). STM is our ability to store limited amounts of information over short periods of time, while LTM refers to our capacity to retain near-unlimited amounts of information over prolonged periods of time. Traditionally, these two types of memory have been studied independently. As a result, our knowledge of the relationship between them has remained limited. In this thesis, I develop well-controlled tasks to compare STM and LTM for the same type of information, formed during equivalent encoding circumstances, and reported in similar ways. Results show that STM and LTM for the same type of information are indeed related. Furthermore, by studying both STM and LTM in cognitively healthy young, middle-aged and older adults, I show that the relationship between these two memory functions remains stable across normal ageing, suggesting some degree of overlap in the underlying neural mechanisms. I also attempt to characterise this relationship in individuals who are at an increased genetic risk of developing Alzheimer’s disease, namely, carriers of the apolipoprotein E gene (APOE) ε4 allele, although limited sample size hinders the interpretation of findings. In Chapter 1 of this thesis, I review the literature that supports STM-LTM dichotomy, in addition to studies that suggest similarities between these memory functions. I also provide an overview of the effects of healthy ageing on STM and LTM, and how these memory functions change in the presence of different APOE alleles. In Chapters 2 and 3, I focus on healthy ageing and its effects on STM and LTM. In Chapter 2, these effects are studied in APOE ε2 carriers and non-carriers. In Chapter 3, I introduce two novel continuous-report tasks that enable analogous probing of both types of memory in order to measure the relationship between them. This task is employed in Chapter 4 to assess memory performance in middle-aged APOE ε4 carriers and non-carriers, with an aim to use similar tasks to characterise the effects of this allele on memory in the future. In Chapter 5, I discuss the implications of my findings and the areas in which this research could be extended and improved.
The origins of subnational democracy: how colonial legacies and labor incorporation shaped regime heterogeneity within Latin American countries
Keywords: politics
democracy
Argentina
regime
democratization
subnational
Brazil
Latin America
Mexico

Despite recent contributions, subnational democratic variation has received little systematic attention in comparative politics and continues to be a grave omission (Dahl 1971, 12) in the literature on democratization. Moreover, current explanations are at fault of ignoring the intricacies of time. Consequently, our understanding of the regime heterogeneity observed within countries has hitherto remained ahistorical. To overcome this and other limitations, using evidence from the largest federations of Latin America, I put forth the first comparative, and historically grounded explanation of the origins of subnational democracy.
The project tackles the following question: What explains subnational democratic variation across Latin America? In other words, why is it that some provinces within countries are more democratic than others? I contend that economic development is at the core of the puzzle. More specifically, building on the work of Mahoney (2010) and Collier and Collier (1991), I articulate a two-step argument contending that, across the region, the subnational unevenness observed today was configured by territorially distinct development trajectories which were triggered during colonization and that, once set, conditioned the timing of local labor incorporation.
My two-step, path-dependent argument is bound by a probabilistic notion of causality. Empirically, I adopt a mixed-methods approach. Weaving together quantitative and qualitative evidence, I present original data for all the subnational units of Argentina, Brazil, and Mexico. In addition, I track the experiences of Jalisco, Rio Grande do Sul, Guerrero, and Salta, as cases that illustrate the processes at play. I conclude this project by exploring the portability of my argument to the Indian case. My cross-national, longitudinal, and historical exploration of the origins of subnational democracy contributes to the discipline by contextualizing all other existing explanations of subnational regime variation.
Entity comparison in knowledge graphs
Keywords: RDF graphs
entity comparison
similarity queries
SPARQL
knowledge graphs

Knowledge graphs (KGs) represent information in a simple, interlinked format and are used in a variety of applications. Besides the standard reasoning tasks such as query answering, there has been an increasing need for new types of analysis. One such fundamental analysis task is entity comparison, i.e., determining what two entities have in common and how they are different. The importance of such a task can be seen in various applications such as product comparisons, and explainable recommender systems. This thesis studies the problem of entity comparison over knowledge graphs and presents a novel framework that models comparisons via similarity and difference queries. It is the first declarative comparison framework for linked data that treats both similarities and differences as first-class citizens.
We first define the syntax and semantics of various types of comparison queries, motivating each type with examples and establishing important relations between different query types. Next, we study the complexity of the two fundamental decision problems over queries, namely the existence and verification problems, for basic comparison queries and for most specific similarity queries (MSSQs). We consider two underlying fragments of SPARQL, with and without arithmetic comparisons, and we show how they affect the complexity of the above problems, and which types of data they suit most. We then study practical aspects of computing the MSSQ. In particular, we establish an important uniqueness result for MSSQs and propose an efficient approximation algorithm. We implement an algorithm for computing acyclic similarity queries and evaluate its performance on large-scale KGs; our empirical results demonstrate the practical feasibility of our algorithm.
Protein modulation of ion channels
Keywords: protein modulation
structure-function
electrophysiology
ion channels

Ion channels lie at the heart of electrical excitability. They represent attractive targets for treatments of a range of pathophysiological conditions, including pain, ischemia and epilepsy. To date, small molecule approaches have dominated ion channel drug discovery, but small molecules often lack the appropriate safety and specificity, ultimately leading to their rejection in the clinic. One way in which to overcome this is to use proteins which use large molecular scaffolds to very precisely place a few key residues in order to modulate ion channel function. To this end, we characterise α-scorpion toxin binding to Nav channels, showing α-scorpion toxin AahII binds to VSDIV and inhibits upward voltage sensor movement. We interrogate the pharmacology of these naturally occurring toxins and probe electrochemical coupling involved in the fast-inactivation process of Nav channels which was uncovered in our work, in order to gain insights into the gating cycle of the channels. Better understanding of this process may allow development of novel therapeutics targeting inactivated Nav channels. Additionally, we characterise VHH domain antibody binding to K2P channels, showing they are capable of both activation and inhibition of channel activity and show high selectivity towards their target. We postulate a mechanism of action through the external pH-sensing pathway and show their activity on rodent channels, uncovering analgesic potential. Additionally, we develop the VHH antibodies as tools to allow visualisation of TREK-2 in native cells, showing selective binding against their target over closely related channels and provide some preliminary data to show localisation of TREK-2 within neurons of rat sympathetic cervical ganglia but not in the glial cells, consistent with RNA-seq data.
The role of non-state actors in foreign policy decision-making processes in the non-western world
Keywords: foreign policy

This thesis investigates the involvement of non-state actors (NSAs) in foreign policy decision-making processes in the non-Western world in order to find answers to why, how, and under what conditions such entities become engaged in foreign policy-making and influence state behaviour. Based largely on primary sources, it offers an exclusive and original data set, organised around a set of hypotheses and according to an organically developed conceptual framework. This allows for an unprecedented insight into the modus operandi of different non-state actors and contributes to an analytical diversification away from a prevailing Western-centrism in the scholarly literature.
The thesis demonstrates that non-state actors, assuming a variety of different operational roles, are able to become informally but nonetheless meaningfully involved. Thus, by adopting a networked analysis of international relations, the dissertation is able to shed analytical light on a grey area, existing alongside the formal, state-driven initiatives. This ultimately reveals a hybrid form of foreign policy at work, blurring the boundaries between the actions of states and non-state actors.
Hence, whilst informality in foreign policy might raise questions of legitimacy, the thesis suggests that hybridity should be acknowledged and perhaps welcomed – especially when it proves to be more efficient than more formal and supposedly legitimate forms of diplomacy. The thesis offers a conceptualisation of informal networks and adopts a methodology able to illustrate their inner functioning. It concludes that coordinated policies of state and non-state actors, capable of recognising and utilising the formal and informal networks they are embedded in, are already prevalent in distinct regional settings, determining the international rules of the game.
Maternal infections during pregnancy and the risk of childhood leukaemia in the offspring: Evidence from large-scale cohort studies
Keywords: Cohort study
Maternal infection
Childhood leukaemia

Background: Leukaemia is the most common childhood cancer, but its aetiology remains unclear. Maternal infection during pregnancy might lead to chromosomal or immunological alterations in the fetus and could be a risk factor for childhood leukaemia. Clarifying the roles of maternal infections in the development of childhood leukaemia would be helpful for the prevention of this disease.
Objectives: This thesis aims to investigate the association of maternal infections during pregnancy with childhood leukaemia using data from different sources, including previously published reports, prospective cohort studies and population-based registries. Integrating results from different sources might enhance the robustness of the evidence.
Methods: Three analyses were conducted: (1) A systematic review and meta-analysis was firstly conducted to summarise findings in previous studies on maternal infections during pregnancy and childhood leukaemia. (2) Analyses using data on 312,879 mother-child pairs from the six prospective cohorts in the International Childhood Cancer Cohorts Consortium (I4C) was then performed to assess the association between self-reported maternal infections and childhood leukaemia. (3) A national registry-based investigation was further carried out among 4.9 million mother-child pairs in Denmark and Sweden to examine the association for hospital-diagnosed infections during pregnancy. A sibling analysis was also conducted to account for unmeasured familial confounders.
Results: In the systematic review and meta-analysis of previously published 32 articles from 20 studies (primarily case-control studies), I found that maternal influenza (pooled OR, 1.77; 95% CI, 1.01- 3.11), rubella (pooled OR, 2.79; 95% CI, 1.16-6.71) and varicella (pooled OR, 10.19; 95% CI, 1.98-52.39) during pregnancy, but not other infections, were associated with a higher risk of childhood leukaemia. In the I4C analysis, maternal urinary tract infection (HR, 1.68; 95% CI, 1.10-2.58) and respiratory tract infection (HR, 1.54; 95% CI, 1.05-2.26) were associated with increased risk of childhood leukaemia. Influenza-like illness showed a similar pattern but with less precise estimates (HR, 1.62; 95% CI, 0.76-3.42). The analysis based on Danish and Swedish registry data shows that urinary tract infection (HR, 1.55; 95% CI, 1.10-2.18), genital tract infection (HR, 2.32; 95% CI1.49-3.60) and influenza (HR, 4.42; 95% CI, 1.42-13.72) were associated with increased risk of childhood leukaemia. There is no evident association between other types of maternal infections during pregnancy and childhood leukaemia. A sibling analysis demonstrated similar results after controlling for familial confounding.
Conclusions: Maternal infections during pregnancy are associated with an increased risk of childhood leukaemia in the offspring. Maternal infections might be considered a candidate cause of childhood leukaemia in future aetiologic and mechanistic research.