VictorJuiz/thesis huggingface dataset:
Applying Mathematics to the Natural and Social World
Keywords: Applied mathematics
Counterfactual explanation
Explainable Artificial Intelligence
Mathematical explanation
Philosophy of science
Scientific explanation

My dissertation explores the roles that mathematics plays in explanations and action-guidance. In particular, I address epistemic and ethical aspects of applying mathematics in empirical and normative inquiry. In Chapter 2, I examine whether mathematical explanations can be analyzed in terms of counterfactual conditionals. I offer three challenges for such analyses and tentatively conclude against countermathematical explanations. In Chapter 3, I extend the epistemic resources of a popular framework for applying mathematics in sciences. In particular, I use two case studies from biology and physics in order to argue that this framework for applying mathematics in the empirical sciences must be complemented by a distinct role, which I name the bridging role. I show how considering the bridging role would capture mathematical practice in the sciences in a more holistic way. In Chapter 4, I investigate and compare the conditions for applying mathematics in the empirical sciences and normative inquiry. Using two case studies from fair algorithmic decisions and the allocation of scarce resources, I identify two typical sets of different conditions for the applicability of mathematics. Finally, in Chapter 5, I explore the ramifications of the arguments from Chapter 4 to a novel field of research known as Explainable Artificial Intelligence.
Dissecting Genetic and Cellular Heterogeneity in Glioblastoma at Single Cell Resolution
Keywords: cancer stem cells
glioblastoma
single cell RNA-sequencing

Glioblastoma (GBM) is the most common and aggressive form of adult primary brain cancer. Therapeutic resistance in GBM is rooted in its layered genetic and cellular heterogeneity, including rare glioblastoma stem cells (GSCs) that drive tumour growth and disease relapse. Despite extensive profiling of primary tumours, heterogeneity within the GSC fraction and its relationship to the tumour bulk remains poorly characterized. To address this gap, I used whole genome sequencing of 44 GSC-tumour pairs to demonstrate that purified GSC cultures recapitulate the somatic landscape of tumours. I then performed single-cell RNA-sequencing (scRNA-seq) on >69,000 GSCs isolated from 26 tumours to characterize functional diversity within the tumour-initiating fraction of GBM. GSCs exhibited extensive transcriptional heterogeneity that translated to variable, subpopulation-specific drug sensitivity profiles. Although a portion of intra-GSC heterogeneity was explained by subclonal somatic alterations at the DNA level, we found GSCs mapped to a unifying transcriptional gradient spanning two cellular states reminiscent of normal neural development and inflammatory wound responses. Genome-wide CRISPR–Cas9 dropout screens independently recapitulated this observation and identified targetable sensitivities within each GSC state. Additional scRNA-seq of >56,000 malignant cells from primary tumours found that the majority organize along an orthogonal astrocyte maturation gradient yet retain expression of founder GSC transcriptional programs. Finally, to investigate transcriptional programs and cellular dynamics underpinning disease progression in glioma, I performed single nuclei RNA-sequencing on >270,000 cells isolated from 52 cryopreserved gliomas, including a subset of patients with longitudinal samples before and after therapy. Compositional analysis revealed gliomas separated into distinct groups based on the frequency of malignant phenotypes, each with an associated microenvironmental niche and GSC state mirroring the Developmental to Injury Response gradient. Collectively, this work has two important consequences. First, gliomagenesis may be explained by a single biological model that involves mixtures of inflammatory wound-healing cells and neurodevelopmental-like cells that cause aberrant neural growth and underpin therapeutic resistance. Second, the heterogeneity discovered at the GSC level suggests combination therapies must be developed to simultaneously target both developmental and inflammatory subpopulations. This paradigm may help identify new approaches to target treatment-refractory cells that reside at the apex of GBM cellular hierarchies.
Carbohydrate-based Inhibitors of PNAG-dependent Biofilm Formation
Keywords: Biofilms
Biological chemistry
Carbohydrate chemistry
Chemical biology
Enzymology
Glycobiology

Many bacteria form biofilms, surface-attached communities within an extracellular matrix. They are medically significant since they provide pathogens with increased tolerance to antibiotics and protection from the host immune response. The biofilms of various bacterial pathogens contain a common exopolysaccharide, PNAG: a partially de-N-acetylated polymer of β-1,6-linked N-acetylglucosamine (GlcNAc). PgaABCD and IcaADBC comprises the biosynthetic machinery which assembles, modifies, and exports this polymer In E. coli and S. epidermidis, respectively. Here, synthetic carbohydrate derivatives are used to probe the mechanisms of these biosynthetic components and study PNAG biosynthesis. First, GlcNAc derivatives were evaluated as inhibitors of the PNAG de-N-acetylases PgaB, IcaB, and related peptidoglycan deacetylase PgdA. In one study, GlcNAc analogs bearing substitutions at the C3 position were examined, replacing the hydroxyl with metal chelating groups including amine and thiol. Though most of this series was inactive, a 2-thioacetamido 3-thio GlcNAc analog was identified as a potent, mechanistically unusual PgdA inhibitor. Additionally, α-hydroxyphosphonamidate transition state analogs were investigated. These compounds had limited activity, providing insights into substrate recognition and active site differences between the CE4 enzymes. Next, PNAG metabolic labelling was attempted using azido and thio GlcNAc analogs. Though metabolic labelling was not observed, 3-thio and 3-azidoGlcNAc were identified as inhibitors of gram-positive PNAG-dependent biofilm formation. Lastly, C6-substituted UDP-GlcNAc analogs were evaluated as inhibitors of the glycosyltransferase complex PgaCD. These compounds inhibited through chain termination, providing evidence that PgaCD elongates PNAG from its non-reducing end. Furthermore, a method to deliver these inhibitors into E. coli was developed by introducing an unnatural GlcNAc salvage pathway. These substrate analogs reduced PNAG-dependent biofilm formation, primarily through disruption of PgaCD.
Genealogies of Transnational Religion: Translation, Revelation, and Discursive Technologies in Two Female Gurus of Esoteric Vedanta
Keywords: Alfassa
Mirra
Blavatsky
Helena Petrovna
History of modern yoga
Translation theory
Transnational religion
Universalism

This project investigates the role of translation within Theosophy and Integral Yoga, focusing on translational discursive devices in the work of the movements’ respective female preceptors—Helena Petrovna Blavatsky (1831-1891) and Mirra Alfassa (1878-1973), better known as the Mother. This research, using translation as a hermeneutic lens, examines the discursive structures of the women’s teachings, and especially the ways in which both had leveraged translation to articulate their universalist visions. Translation, both linguistic and idiomatic, permeates the underlying logic of these late-colonial transnational movements, giving rise to a peculiar universalism and a constellation of teachings I have termed Esoteric Vedanta. The contribution of this paper is twofold: first, it demonstrates that ‘thinking with translation’ is an effective entry into the multidirectional traffic of ideas, practices, and epistemologies that have given rise to these movements, allowing a better understanding of ideological commitments at the fin-de-siècle, including affective, hybrid, and radical political alignments. This, in part, is made possible by examining the two women side by side, since, while the content of their teachings differs, the logic of translation permeating their thought allows one to excavate a deeper genealogy of ideas. Secondly, this thesis argues that the universalist thrust of transnational movements such as Theosophy and Integral Yoga is itself a function of translation practice—translation at multiple registers and in an expanded sense of the term—emerging in a specifically heterolingual idiomatic context. The utopian, evolutionary, esoteric, and broadly Vedantic (or else, Buddhist) currents in Blavatsky and Alfassa’s teachings continue to reverberate and inform not only their respective traditions but also the broader fields of modern yoga and New Age spirituality. In attending to processes and discourses of translation in both women’s thought, this project both traces the connections between Theosophy and Integral Yoga, and seeks to reframe the ideological history of contemporary transnational religion and the sort of universalist thinking it offers.
A Comparative Inquiry Into Religious and Secular Students’ Perspectives on Peace and Conflict Resolution through Science Education in Bangladesh
Keywords: Bangladesh
conflict resolution
peace
secondary science
secular religious

This ethnographic study based in Bangladesh analyzed Grade 10 students’ perspectives on the learning of science regarding peace and conflict resolution, and the use of science in their everyday lives to negotiate peace and resolve conflicts. The in-class delivery of the secondary science curriculum in Religious and Secular educational streams was documented, including the teachers’ pedagogical approaches to teaching science; the students’ preferred approaches to learning science; and the students’ conception of science in everyday life with reference to the sociocultural factors affecting peace and conflict resolution. A theoretical framework, which I termed the integrated theory of pedagogy, was constructed using Tagore’s comprehensive models of learning that promote peace through science, juxtaposing the models with Gandhi’s non-violent approach, Dewey’s experiential learning, and J. P. Miller’s holistic pedagogy, frameworks that also support peace education. Twenty-four Grade 10 science students from the two educational streams were selected using purposive sampling. Data collection tools included classroom observation, in-depth interview, focus group discussion, and field journal. Six science teachers and two head teachers were consulted for contextual information and to corroborate findings from the students. Information was also gathered from science textbooks. Data were analyzed using an inductive approach. The findings indicate that peace and conflict resolution through science education was not taught in those classrooms. There was also a lack of transactional and transformational pedagogical approaches to teaching science. The predominant teaching approach was teacher- and textbook centred, echoing the need to cover the syllabus for impending standardized examinations. For learning science, the students from both streams preferred hands-on activities. Students explained their awareness of conflict in society and were eager to explore the role of the science curriculum in peace, conflict resolution, tolerance, and indirect peace states. This dissertation offers an analysis that may be helpful to local and international peace and science educators, curriculum designers, administrators, teachers, and policy makers interested in developing peace through science pedagogy. The study recommends “school approach” in peace education, including the concept of peace and conflict resolution as an additional emphasis in the science curriculum, and a peace-and-spirituality-based, science-pedagogy-engaging, action-centred education: PEACE.
Deciphering the Arabesque: Genre Mixture and Formal Digression in the Early Romantic Piano Concerto
Keywords: Arabesque
Digression
Friedrich Schlegel
Genre
Piano Concerto
Romantic

This dissertation uses Friedrich Schlegel’s (1772–1829) literary concept of the arabesque to analyze genre mixture and formal digression in the early Romantic piano concerto. Drawing on both John Daverio’s adaptation of the arabesque for nineteenth-century music (1987;1993) and contemporary theories of musical form (Caplin, 1998; Hepokoski and Darcy, 2006; Vande Moortele, 2009; and Horton, 2017), I identify four procedures in which elements of ritornello form, variation form, song, or fantasy engage with, interrupt, or supplant sonata-form functions. Using examples from a corpus of 24 piano concertos by Bennett, Chopin, Field, Henselt, Herz, Kalkbrenner, Liszt, Mendelssohn, Moscheles, Schumann, Taubert, Thalberg, and Wieck, I demonstrate that seemingly supplementary embellishments, ritornellos, and lyrical interludes proliferate and fragment the central sonata form to produce a distinctly Romantic genre. Chapter 1 surveys the history of the arabesque as it developed from an ornate framing device for pictorial artworks to a metaphor for the chaotic genre fusions of the Romantic novel, and, later, as an analytical tool for disruptive characteristics in nineteenth-century music. Chapter 2 establishes the concerto as a hybrid genre in which the ritornello framework interrelates with the interior sonata form to varying degrees depending on subgenre. The virtuoso concerto, for example, maximizes the distinction between the orchestral framework and solo sonata form, while the symphonic concerto minimizes the distinction. The chapter then outlines four arabesque procedures that further complicate these paradigms. Chapter 3 examines the first arabesque procedure, in which solo bravura, passagework, and dominant embellishments pervade the sonata form proper in lieu of an interpolated cadenza. This process, which is characteristic of the virtuoso concerto, transfers virtuosity from the exterior to the interior of the concerto form, enlarging the solo domain. Chapter 4 covers local ritornello statements that participate in the sonata form, eroding the textural framework and producing a topical likeness with the symphonic genre. Chapter 5 studies local digressions that require the mediating judgement of an interpreter to decipher hidden formal logic, while Chapter 6 covers large-scale lyrical episodes that intrude upon single movements or overarching sonata forms in continuous cycles, conflating formal levels and introducing elements of fantasy.
The Genetic Architecture of Pigmentation Traits in Modern Human Populations
Keywords: eye colour
GWAS
hair colour
human evolution
pigmentation
skin pigmentation

Pigmentation traits, here defined as hair, eye and constitutive skin pigmentation are some the most variable phenotypes among human populations. They have a complex genetic basis, in which interactions among genes and pleiotropy are common. Several genes involved in the pigmentation pathway have been described across mammalian species, which explain a significant proportion of the normal pigmentation variation in humans. However, the full understanding of the genetic architecture of pigmentation in human populations has not yet been achieved. Major effect genes are known to explain a relatively high proportion of the variance for each pigmentation trait at a population-basis level, but a substantial number of genetic loci modulating pigmentation in several populations have small effects and remain unknown. The objective of my thesis was to contribute to and improve the state of knowledge of the genetic architecture of pigmentation traits in modern humans. To achieve this, I have taken advantage of novel approaches at different stages of the research program, such as the use of large sample sizes and different cohorts, the application of diverse statistical approaches, and the use of genomic and epigenomic databases and computational advances to follow-up putative causal loci. I have identified a complex genetic architecture across known pigmentation regions such as TYR and OCA2, in which a combination of missense and non-coding SNPs are independently associated with pigmentation traits. These associations seem to vary among populations and among pigmentation traits to certain extent, as evidenced by fine-mapping and genetic correlations in a Canadian cohort of European ancestry. Finally, I explored the putative regulatory role of pigmentation loci. I have identified shared causal signals between hair or eye colour and quantitative trait loci (i.e. methylation and expression), and I have identified significant associations between hair or eye colour and the expression of pigmentation genes such as OCA2 and SLC24A4. Overall, my research has nominated several candidate causal variants across loci, and has provided insights to further explore the biological role of these SNPs in human pigmentation.
eHealth Antenatal Coparenting Intervention to Prevent Postpartum Depression among Primiparous Women, Karachi, Pakistan: A Pilot Randomized Controlled Trial
Keywords: co-parenting
Coparenting
Intervention
partner support
Pilot Randomized Controlled Trial
postpartum depression

Background: Postpartum depression is highly prevalent among women and a lack of partner support is a strong risk factor for PPD. Partner support has been shown to decline significantly during the transition to parenthood. The primary objective of this pilot randomized controlled trial was to examine the feasibility and acceptability of an eHealth antenatal coparenting intervention called eACoP and obtain preliminary estimates on clinical outcomes for a future larger trial. Methodology: 212 primiparous couples were recruited from the Aga Khan University Hospital and randomly allocated into the intervention group or the control group using sequentially numbered opaque sealed envelopes. Couples in the intervention group received the eACoP intervention during pregnancy which consists of eight 45-minute online videos. Primary outcomes were feasibility and acceptability measured through enrollment rates, intervention adherence rates, follow-up rates, and intervention satisfaction. Secondary outcomes were depressive symptomatology, anxiety, postpartum partner support, coparenting relationship, relationship satisfaction, postpartum childcare stress, child development, extrafamilial support, and healthcare services utilization. Results: Primary outcomes: The enrollment rate of eligible participants in this pilot study was 83.5%. One in five couples completed the minimum intervention dosage of watching at least five videos. Complete follow-up data was collected from 66.5 (n=137) of women and 56.7% of partners (n=117) at 4-6-weeks, decreasing slightly to 60.7% (n=124) of women and 50.4% of (n=104) partners at 12-weeks postpartum. The 24 couples who watched at least five videos and completed the satisfaction forms felt that the content of the videos was helpful and provided appropriate strategies for managing situations or problems. Participants provided important recommendations, including the inclusion of Pakistani cultural and religious aspects in the videos and making the videos shorter. Secondary Outcomes: At 4-6-weeks postpartum, 22.1% of women and 3.5% of partners in the intervention group showed depressive symptomatology while 32.8% of women and 7% of partners had anxiety symptoms. At 12-week postpartum, 14.1% of women and 5.7% of partners had depressive symptoms while 21.9% of women and 11.3% of partners had anxiety symptoms. Similarly, 13.11% of women and 9.6% of partners reported relationship dissatisfaction. There was no difference found between the intervention group and control group with respect to other secondary outcomes. Conclusion: This pilot trial found that a future randomized controlled trial of eACoP intervention is not feasible nor acceptable in the Pakistani context without modifications. .
Tools to Live by: Starch Grain Analysis on Jomon Period Ground Stone from Southern Hokkaido, Japan
Keywords: Foodways
Ground stone
Hokkaido
Jomon Period
Residue analysis
Starch

Over the past few decades of research on Jomon Period (ca. 16,500 – 2,300 BP) subsistence, many have come to accept that various edible tree nuts were central to everyday practices and foodways throughout this period. Despite palaeoethnobotanical research from southern Hokkaido challenging this generalization, studies continue to assume the importance of nuts based on macrobotanical remains, site features, and artifactual proxies. Ground stone technology is one artifact class that is consistently associated with nut processing, but research programs designed to explicitly evaluate this relationship have been relatively few for Jomon sites. In this dissertation, I examined the larger interaction between starchy plant species and grinding implements from Jomon sites across southern Hokkaido through the application of starch grain analysis on extracted residues. The ground stone implements sampled here did not yield clear evidence for nut species considered important to Jomon peoples in this region, such as Castanea crenata and Juglans ailanthifolia, and many artifacts had no visible starch to report. These results challenge the suggestion that handstones and netherstones, such as suri-ishi and ishizara respectively, were primarily for processing plant foods, and are particularly indicative of cracking and grinding nuts in Jomon communities. This leads to further questions about the potential of ground stone to be used beyond subsistence studies, turning the focus to discussions of foodways, resource processing, and the intersections of different activities within daily life at Jomon sites in Hokkaido.
Drivers of Holocene Carbon Uptake and Release in Peatlands of the Hudson Bay Lowlands, Canada
Keywords: carbon
Holocene
Hudson Bay Lowlands
methane
peatlands
testate amoebae

Northern peatlands are a key component of the terrestrial carbon cycle, acting as both a source and sink of carbon. Therefore, to predict impacts from anthropogenic climate change and create effective land management policies, constraining how environmental factors impact peatland carbon fluxes is critical, especially in peatland-rich regions such as the Hudson Bay Lowlands (HBL), Canada. This thesis aims to understand how local-scale factors impacted Holocene carbon uptake and release in the HBL using paleoecological and geochemical analyses of radiocarbon-dated peat cores. Paleoecological analyses of a site on the southern HBL margin demonstrate that landscape position controls local hydrology and can subsequently limit Holocene carbon accumulation rates (CARs). This record also demonstrates a summer bias in temperature and validates pH reconstructions from lipid biomarker proxies. Paired treed fen and bog sites from the western HBL margin show markedly high carbon masses owing to deep peat accumulation with old initiation ages. Mean testate amoeba trait values reflect hydrology and food web structure and are also influenced by vegetation shifts and peatland type. Further, mixotrophic taxa are not related to higher millennial-scale CARs, suggesting a minor role for their primary production in long-term carbon storage. The above records were synthesized with other hydrological records derived from testate amoebae across the HBL to reconstruct paleo-methane fluxes via a linear regression model developed from modern relationships between methane fluxes and water table depths. Land availability controlled by glacial isostatic adjustment was an important control on Holocene emissions when fluxes were scaled to regional emissions. The combined hydrological reconstructions also suggest that peatlands were drier under warmer Middle Holocene conditions. A charcoal record collected from the western HBL margin supports drier conditions, as warmer Middle Holocene conditions were related to higher fire frequency. Although higher fire frequency did not have a significant impact on millennial-scale CARs, carbon loss from combustion was potentially doubled, which has implications for atmospheric carbon budgets. Overall, this thesis advances our understanding of the complex interplay between climate and local processes in long-term carbon dynamics that is of fundamental importance for conservation priorities and constraining future carbon emissions.