VictorJuiz/thesis huggingface dataset:
Characterising dynamical systems models of tumour-immune interactions
Keywords: bifurcations
cancer
modelling tumour-immune interactions
parameter estimation
dynamical systems
asymptotics
inverse problems
immuno-oncology
bistability
excitable systems

Despite clinical successes, data from trials of cancer immunotherapies continue to highlight non-responders. A better understanding of tumour-immune interactions is needed to explain outcome variability. In this thesis, we investigate whether tumour-immune interaction models can explain variation in mouse tumour volume time series data, focusing on a well-known mathematical model by Kuznetsov et al. (1994).
Exploiting a separation of timescales in the original model, and using matched asymptotics, we derive a new long-timescale approximation of the model, which differs from the quasi-steady-state approximation (QSSA) introduced by Kuznetsov et al. (1994), but is in good agreement with numerical solutions of the original model. As well as exhibiting the three stages of immunoediting – elimination, equilibrium and escape, together with complex bifurcations and bistability, our reduced model highlights excitability, a feature not traditionally associated with tumour-immune models. We also identify different biophysical parameters that could be targeted with immunotherapy in order to control tumour size.
As the QSSA model is simpler, but still exhibits immunoediting, we use it for case studies investigating parameter identifiability for complex bifurcating and bistable models using in silico data, generated from the model with variable parameters, observables and noise levels. Using profile likelihoods, we show that identifiability varies across dynamically different datasets. Parameters related to the immune system are highly correlated, and can result in large parameter confidence intervals and bimodal likelihood surfaces.
We then explore a population approach, where the model is simultaneously calibrated to dichotomous data from two individuals, noting that variation in tumour outcomes can arise from bistability or bifurcations, representing distinct hypotheses for heterogeneous tumour responses. We demonstrate the hypotheses can be distinguished for most synthetic datasets considered, except for highly noisy tumour data, by comparing Bayesian population fits under each hypothesis.
This thesis provides a new perspective on how qualitative differences between tumour growth dynamics of responders and non-responders may be explained by bifurcating and/or bistable models. At the same time, it illustrates how integration of mathematical and statistical methods can facilitate development of simplified models, their analysis and calibration.
The world according to PEN and UNESCO: Makers of world literature, 1921-1996
Keywords: UNESCO
Book History
Sociology of Translation
PEN International
World Literature
ICIC

This study charts for the first time the complex, always evolving relationship between PEN International (PEN) and the United Nations Educational, Scientific and Cultural Organization (UNESCO), including its precursor the International Committee on Intellectual Cooperation (ICIC), from 1921 to 1996, focusing on their joint translation policies. Over these 75 years, the three international organisations collaborated with each other to develop and implement literary translation programmes that would foster mutual understanding among peoples and nation-states, though the way they conceptualised ‘world literature’ diverged over time. Drawing on multiple archives and official publications, this study argues that their joint translation policies concretely shaped, and were shaped by, their official and informal partnerships as PEN championed the role of living writers, and UNESCO the role of literary books, in these programmes. Their collaboration during the 20th century succumbed to and resisted interventions from member states and the pressure of the international marketplace, yielding unexpected or mixed outcomes. Part 1 examines the interwar period when PEN and the ICIC, despite the brevity of their collaboration, set the terms for the prehistory of translation programmes, especially through their debates on national literary languages. Part 2 examines PEN and UNESCO’s collaborative projects that prompted each other to engage with Eastern and Western literatures, shaping their post-war world literary visions. Part 3 turns to the most controversial period for PEN and UNESCO when the two, goaded by international politics, began to actively intervene in each other’s policymaking while articulating their own independent understanding of world literature and literary rights. Investigating multiple institutional and individual crossings, this study overall reflects on the role of PEN and UNESCO as makers of world literature, tracing their tangled historical developments, fraught implementations of their translation programmes, and competing imperatives underlying their long-running collaboration.
Sociological applications of positive mental health
Keywords: WEMWBS
dual-continua model of mental health
eudaimonia
well-being
positive mental health
mental health

This thesis tests the conceptual relevance and empirical usefulness of the positive mental health (PMH) framework for quantitative sociological research. The PMH approach postulates mental health to be inherently multidimensional and to consist of the tripartite domains of hedonic (affective, emotional, and cognitive), psychological (eudaimonic) and social well-being. It stipulates that the presence of PMH does not merely mirror the absence of mental disorders and illnesses (dual continua model), and it proposes that eudaimonic well-being, in particular, can be meaningfully distinguished from other forms of mental health. Even though versions of the PMH approach have gained considerable popularity in academia and public policy, they are often still limited by a lack of longitudinal evidence and a shortage of advanced statistical modelling that would demonstrate their broader importance. In response, this thesis employs state-of-the-art PMH indicators, primarily the Short Warwick-Edinburgh Mental Well-Being Scale (SWEMWBS), on high-quality nationally representative data and strategically contrasts the finding of PMH scales with more established NMH ones over a broad array of sociological conditions and outcomes.
The first empirical chapter tests the empirical prevalence, predictors and consequences of the dual continua model and sheds light on the psychometric and sociological differences between the SWEMWBS, the GHQ and life satisfaction and uses allostatic load measures as a physiological benchmark. The subsequent two empirical chapters analyse how neighbourhoods, as an important meso-level consideration, and how religiosity, as an eminent individual-level factor, distinctly affect PMH while jointly controlling for NMH, both cross-sectionally and over ten years (with four measurement occasions of the SWEMWBS). Finally, the fourth paper establishes the link between PMH and mortality risk over a 21-year span while controlling for the influences of other mental health and psychological measures.
Throughout the thesis, an extensive set of statistical techniques such as event history, fixed and random effects, and structural equation modelling are employed. While the thesis finds somewhat of an expected overlap between the PMH scales and the competing mental health measures, the dual continua model of mental health is supported, and striking differences emerge in reference to the SWEMWBS’ sub-dimensions of feeling optimistic and feeling usefulness. Each chapter also portrays meaningful differences in the relationships of the mental health variables with life course conditions. The thesis demonstrates that sociological researchers must deliberately choose the right psychological scale or sub-dimension with care and that, in certain applications, differentiating between negative and positive mental health according to the dual continua model of mental health can provide new insights.
Host gene expression change during viral stress
Keywords: RNA biology
Bioinformatics
Influenza
APA
Viruses
Alternative cleave and polyadenylation

Viral infection induces extensive changes in the host transcriptome. One crucial way in which the transcriptome is remodelled is via changes to host mRNA 3’-end processing, but how virus infection induces these changes, and to what extent, is poorly understood. Over 70% of human genes have the potential to be cleaved and polyadenylated at multiple sites, and differential usage of these sites can regulate gene expression by affecting transcript properties and by altering transcript coding capacity.
In this investigation, we used two strains of influenza A virus as models to study host alternative cleavage and polyadenylation (APA) changes induced by viral infection. Influenza A is an RNA virus that replicates in the nuclei of host cells, and has previously been reported to interact with host 3’-end processing factors. We utilised a powerful experimental approach, combining 3’RNA-sequencing with a custom-built bioinformatic pipeline, to analyse APA changes in the nuclei and cytoplasms of host cells during viral infections.
We identified widespread APA changes in the 3’-untranslated and coding regions of mRNAs in viral-infected cells. We also extracted many physiologically relevant APA changes which have the potential to influence viral replication, suggesting that APA is another layer of gene regulation defined by competition between the host and virus. Additionally, we examined the mechanistic basis for APA during viral infection by analysing cis-element sequences surrounding poly(A) sites and uncovered highly significant frequency biases, suggesting that cis-element differences play a critical role in viral-induced differential poly(A) site selection.
Overall, this thesis characterises host gene expression changes during influenza infection, with further exploration of differences in host poly(A) site usage. It identifies APA changes which are likely to be of physiological importance for viral propagation, and it examines the underlying mechanisms directing APA in an infection context.
The anatomy of unbelief: a critical assessment of the cognitive science of (non)religion

Keywords: embodied cognition
biocultural
nonreligion
material secularisms
CSR
cognitive science of religion
material religion

A number of scholars of (non)religion and secularity have argued in recent years for the need to get beyond the neat binaries and the negative identities signalled by atheism and agnosticism (e.g., Taves, Asprem and Ihm 2018). However, these binaries are deeply ingrained in the landscape of ideas that have shaped the way we do scholarship.
In this thesis, I critically investigate the approach called cognitive science of religion (CSR), which Justin Barrett and Emily Burdett describe as "the scientific approach to the study of religion that combines methods and theory from cognitive, developmental and evolutionary psychology with the sorts of questions that animate anthropologists and historians of religion" developed to further the understanding of "the reasons for initial acquisition, recurrence, and continued transmission of religious concepts and behaviour" (2011: 252). My main focus is the way CSR defines and studies nonreligion. This work consists of the two moves: the deconstructive and the reconstructive. In the deconstructive part, I challenge the "C" (cognition) and the "R" (religion and nonreligion) models employed by this field. In the reconstructive part, I propose a biocultural approach that replaces the computational paradigm with 4E cognition theories, and the belief/ unbelief binary with material religion and secularisms.
One of the "umbrella" problems I focus on in this thesis is the issue of disembodiment that I have discovered to be central to the majority of the CSR approaches to nonreligion. Therefore, the word "anatomy" in the title of this thesis is meant to highlight the theoretical and methodological concern of my approach, which is focused on materialising the field of CSR. My focus on the "anatomy of unbelief" aims to challenge the current CSR approach by bringing the body and the culture back into the scientific study of nonreligion.
Leonora Carrington and Goliarda Sapienza: anarchic bodies
Keywords: embodiment
Goliarda Sapienza
surrealism
gender
Leonora Carrington
autobiography

This thesis brings together two little-know figures in the history of 20th-century literature: Leonora Carrington (1917-2011) and Goliarda Sapienza (1924-1996). Building on recent academic and public interest in both women, this research offers a new perspective by reading their literary work outside of its immediate cultural context.
Despite their differences, Carrington and Sapienza encounter many of the same cultural phenomena, and they share a sense of embodied, individual resistance to institutional power. Restraint enters the works of both authors via the Catholic church, psychiatric treatment, gender norms, and the rigidity of written language. In addition to closely analysing these themes through the comparison of several key texts, this thesis has a broader scope of considering the roles of autobiography, embodiment, and gender in the expression of identity.
Both Carrington and Sapienza, I find, evoke a sense of limitlessness in their depiction of personal identity. This resistance to restraint is carried over into the methodological approach of this comparison, bringing Carrington away from her Surrealist label, and bringing Sapienza toward it, and therefore casting their work in a new light.
Disability's cost and coasts in Mombasa, Kenya
Keywords: mobility studies
liminality
Africa
disability
(new) kinship
ritual studies

This project tracks the intimate and social dimensions of disability in Mombasa to explore the impasses people with disabilities face, and how they navigate and transform constraints for and before survival. It details socio-historical conditions that figure disability as a cost showing how people with disabilities face impasses within four ethnographic sites: Africa’s largest disability school, constructed and managed by a cement company; a rehabilitation and education center for neurodevelopmental disabilities frequented by a Muslim minority of Indian descent; a “sheltered workshop” offering disability employment, housing, welfare, and activism; and itinerant sites an litigious insurgency group uses to lay claim on the sheltered workshop. Against these costs I highlights patterns of coasting, which are non-negative practices of living precipitated by, but irreducible to, these impasses. Coasting gestures to the ways people with disabilities work within, around, and at the limits of an impasse, movements made without wholly relying on power or resistance to what blocks the continuity of life. Four coasting patterns are detailed across the life course: drifting within institutional captivity, by which disabled children wander off from scenes of initiation and build other forms of life; brooding as a prospective orientation for parents charting paths around uncertainties; oblique mobility by which disability activists cunningly mobilize within development, state, and market discourses to open pathways and solidarities outside them; and insurgent motility which enables recurring aggressions against, and ingressions into, institutions that have disposed elderly people with disabilities and rendered them jobless and homeless.
Functional adaptation in Toll-like receptors of wild and domesticated animals
Keywords: adaptive evolution
comparative immunology
Toll-like receptors
host-pathogen interactions

Animals sense their pathogens through detection of conserved pathogen-associated molecules by pattern-recognition receptors (PRRs). The best characterised family of PRRs is the Toll-like receptors. TLR subfamilies retain specificity for particular agonist classes over great evolutionary distances. This does not, however, mean that TLRs are evolutionarily static. TLRs, along with other pathogen-facing immune genes, frequently undergo directional selection to maintain leverage in the perpetual arms race between hosts and pathogens.
In this thesis, I argue that TLRs are critical determinants of disease susceptibility and resistance, and are therefore under strong selective pressures. To support this, I provide evidence of adaptive evolution operating over multiple nested timescales. For instance, I show that, even in the few thousand years since the domestication of chickens, TLRs have undergone adaptation, likely to better deal with higher pathogen loads in denser, commercialised populations. At the other extreme (hundreds of millions of years), I document the repurposing of the CpG-DNA-recognising TLR21 between fishes and birds, arguing that this compensated for the loss of the unrelated CpG-recognising TLR9 in the birds and reptiles.
To contextualise and reinforce my bioinformatic findings, I provide evidence from laboratory experiments to confirm changes in TLR function. For instance, I demon- strate that two positively selected sites in Gentoo penguin TLR5 are sufficient to change the responsiveness of the receptor to its agonist, flagellin. Furthermore, I demonstrate that the ancestor to the Eudyptes (crested) penguins had a cryptic pseu- dogene for TLR15 that was then overtly pseudogenised several independent times in the genus. Functional evidence was crucial in both of these conclusions, and neither could have been deduced from bioinformatic methods alone.
Taken together, this body of work provides several lines of evidence that TLRs are key targets for natural selection across multiple evolutionary scales, and that functional evidence plays an important role in interpreting bioinformatic predictions. In addition to contributing to the fundamental understanding of how hosts cope with changing pathogen landscapes, this work provides important information for conservation and sustainable food production.
The role of cyclic nucleotide signalling in L. mexicana flagellar motility
Keywords: second messenger signalling
flagellar motility regulation

Cyclic AMP (cAMP) is a ubiquitous conserved second messenger involved in diverse biological function across the Eukaryotic kingdom. Here we explore components of the divergent cAMP signalling pathway, including divergent protein kinase A (PKA), in the early diverging protozoan Leishmania mexicana, with an aim to understand how cAMP contributes to its canonical motile flagellum. While cAMP may transduce external signals, it is ultimately the regulation of dynein activity that determines the waveform. Therefore, we assessed the contribution of all 10 axonemal dyneins to gain a deeper understanding how each one contributes to L. mexicana waveforms. To tackle these aims, we used CRISPR-Cas9 gene deletion and endogenous fluorescent tagging combined with microscopy techniques to localise our proteins of interest and assess their contributions to flagellar wave shape and direction. We found that 24 of 35 putative cyclic nucleotide signalling components were present in the flagellum, notably in either the distal, proximal or entire axoneme. We identified cAMP at the flagellar tip serves as the main regulator of parasite swim speed. Sequence analysis, homology modelling and predicted cAMP docking suggested that only CARP1, firmly embedded in the flagellar cytoskeleton, binds cAMP via classical binding mechanisms. △CARP1 flagella demonstrated reduced beat frequencies and a higher propensity for ciliary beating. Moreover, we described the pairing preferences of PKAR1 with PKAC1/ PKAC2 in the flagellar cytoskeleton, and PKAR3 with PKAC3 to the cell body. Loss-of-function phenotypes showing distinct effects on motility with loss of PKAC1 being the most severe. Lastly, we found that the double headed axonemal dyneins were indispensable for cell displacement, however the single headed dyneins contributed more specifically to either beat frequency or amplitude. Ultimately, the findings of this thesis have systematically pinpointed the contributing components of the divergent cAMP signalling pathway to flagellar motility. What remains, is to unpick the mechanistic details of how CARP1 is interacting within its local axoneme environment to affect wave shape and direction of travel.
Using local and indigenous ecological knowledge to examine local-scale perceptions, effects of, and resilience and adaptation to, climate change on human/landscape interactions on the Pacific coast of North America
Keywords: Pacific Northwest coast
local knowledge
adaptation
climate change
ethnoecology

The aims of this research were to investigate the perceptions and impacts of climate change on the ecological and cultural aspects of landscape through understanding local and Indigenous knowledge. Key cultural and ecological species were chosen for study by bridging Traditional Ecological Knowledge (TEK) and western scientific knowledge in a constructive, equitable, and practical way. These Cultural Keystone Indicator Species (CKIS) provide a novel and cross-culturally meaningful analytical framework for investigating the socio-ecological effects of environmental change.
In 2013 and 2014 I interviewed 96 resource users in 11 Indigenous communities in Northern British Columbia and Southeast Alaska. TEK data was collected on weather and landscape changes, resilience and adaptation techniques, and changes in biodiversity. I also reviewed the scientific and ethnoecological literature, and meteorological data. Three CKIS groups were chosen for monitoring: five species of salmon, five species of berries, and Sitka black-tailed deer, all key species highly impacted by weather changes.
The findings from the research show that these communities are observing and adapting to significant environmental changes, including more rain, warmer temperatures, and less snow, which have been accelerating over the last 15–20 years. These weather changes are impacting the terrain (e.g. isostatic rebound, erosion), the distribution and availability of marine and terrestrial resources, and people’s confidence and ease in moving about their territory and ability to harvest and preserve resources. This research suggests that delineating CKIS is an efficient way of understanding the impacts of climate change, envisioning potential adaptation opportunities, and creating resilient social-ecological ecosystems.