VictorJuiz/thesis huggingface dataset:
Microbial role in dolomite formation in hypersaline sabkha and Miocene mud volcano outcrop in Kuwait

The origin of dolomite has remained the subject of an ongoing debate for over a century and is known as “the dolomite problem”. The essence of this problem is the inability to explain the disparity of dolomite abundance in sedimentary carbonate records and in modern depositional environments. Previously conducted laboratory experiments have demonstrated the ability of microbes to mediate dolomite formation; yet microbial involvement in large scale worldwide dolomitization is poorly understood. This dissertation attempts to expand the knowledge on the microbial role in dolomite formation by investigating modern and paleo environments in Kuwait where dolomite exists. Microbes live in interactive communities where ecological interactions can possess properties of positive cooperation or negative antagonism, thereby affecting microbial composition. In Chapter 2, proto-dolomite was formed by microbial consortia dominated by Halomonas strains alongside a considerable increase in pH which is required for increasing the dolomite saturation index. Although microbes are important to overcome the dolomite kinetic barrier, Chapter 3 showed that aerobic halophilic heterotrophic microbial consortia enriched from Al-Subiya sabkha in Kuwait were unable to replace calcium carbonate by magnesium carbonate to form any of dolomite’s metastable phases. This inability suggests that dolomitization is a lengthy process at Earth’s surface temperature and the factors controlling microbial ability to precipitate dolomite from saturated solutions are dissimilar to microbial ability to dolomitize precursor calcium carbonate. In Chapter 4, crustacean burrows in Early-Middle Miocene coastal mud volcano outcrop provided channels for the mixing of the seeped methane and the downward seawater flux. The anoxic channels provided the preferential conditions for dolomite formation carried by consortia of methanotrophic archaea and sulphate reducing bacteria. In Chapter 5, organic microanalysis of microbial signatures in the mud volcano showed the immediate proximity of methanotrophic archaea and sulphate reducing bacteria to dolomite in contrast to calcite. This observation is in agreement with microbes as a nucleation site for dolomite to overcome the dolomite kinetic barrier as opposed to calcite formation.

Keywords: biomarkers
carbonates
dolomite
halophiles
Miocene mud volcano
sabkha
Advisor: Dittrich, Maria
The Nucleation, Growth and Surface of PbS Nanocrystals

Despite being studied for the past 40 years, the chemistry and photophysics of colloidal nanocrystals (NCs) remain rich with mysteries. Nonetheless, NCs are now part of commercialized technologies and synthetic and engineering advances continue to facilitate and further this endeavour. In this thesis, I will explore various facets in the synthesis and surface of PbS NCs. In 2003, Margaret A. Hines and Gregory D. Scholes developed a synthetic route to PbS NCs that is nearly ubiquitously employed for the assembly of PbS NC devices. Later in 2006, Ludovico Cademartiri and his colleagues in the group of Geoffrey A. Ozin, reported a new synthetic route to PbS NCs using completely different precursors than Hines Scholes. Since then, both routes have been refined to offer facile size-tuning and yield NC ensembles with extremely narrow size dispersities. However, several questions remained unanswered and differences in the synthesis and surface chemistry of particles made by both routes were apparent, even if infrequently acknowledged explicitly in the literature. In Chapter 2 and 3, I investigate how small PbS NCs can be made with significantly improved size dispersities. Particularly, I show that a metastable cluster is present in the synthesis and can be controlled to give exquisite size control. Next, in Chapter 4, I establish that NCs made through the two synthetic routes mentioned above are structurally different. In particular I identify that an insulating shell is present on NCs made from Cademartiri-type reactions. Finally, I attempt to understand where ligands go on the surface of PbS NCs after a ligand exchange procedure. I show that this depends on the nature of the ligand, with bulky aromatic ligands preferentially positioning on facet edges and resulting in an anisotropic coverage. Finally, while this work answers several questions on the synthesis and surface of PbS NCs, several more challenges remain. In chapter 6, I attempt to give an outlook on how the presented work might influence future research.

Advisor: Wilson, Mark W.B.
A Variance-centric Approach to Statistical Analyses of Large-scale Genetic Data

The ever more complex and larger datasets that statisticians can routinely access have prompted the modi cation of traditional statistical methodology. Notably, genomic data have different representations at the gene, exon, and sequence level, which require both customized quality controls to remove technological artefacts and tailored statistical methods to make real discoveries. This thesis focuses on understanding the sources of, and decomposing variance as well as its role in modelling high-dimensional genetic data. Eigenvalue decomposition, factor analysis, and singular value decomposition are variations of variance based transformation techniques that help us understand how data are structured according to variance contribution. A crucial aspect of these techniques is the number of transformed variables to retain, which is closely related to other statistical constructs such as a low-rank approximation, dimension reduction, effective degrees of freedom, and effective sample size. I propose to tackle the estimation of dimension of high-dimensional genomics data via a penalized profile likelihood criterion within the probabilistic principal component analysis framework. Leveraging the existing two-stage regression framework for detecting variance heterogeneity, I propose a simple-to-implement testing strategy for X-chromosome that is robust to confounding and can be used to indirectly infer the presence of genetic interactions. Finally, building on the singular value decomposition, I introduce a novel severity measure of multi-collinearity for high-dimensional data that can be used to construct high-dimensional variance estimators.

Advisor: Craiu, Radu
Sun, Lei
Evaluating and Predicting the Performance of Granular Activated Carbon Filter-adsorbers: Adsorption and Biodegradation Processes

Drinking water treatment plants use granular activated carbon (GAC) to adsorb micropollutants, but the GAC has a limited adsorption capacity and needs to be replaced before it is exhausted. A minicolumn test technique was developed by Gillogly et al. (1999) to monitor the saturation of GAC beds, which enables the determination of GAC replacement schedules. However, this tool has not been fully validated. The first part of this research was to validate and refine the minicolumn test protocol by exploring fundamental questions related to operating GAC in an adsorption mode. These questions include evaluating the effect of water temperature on the adsorption of 2-methylisoborneol (MIB) and geosmin in GAC contactors, and understanding the effect of the mass transfer zone (MTZ) on the accuracy of the minicolumn test protocol. Temperature was found to be an important factor that should be considered for the minicolumn test. Full-scale GAC contactors were observed to have a broad MTZ for micropollutants, which verifies the minicolumn test protocol. When GAC is in operation, some biofiltration may be occurring, where biodegradation becomes an alternative removal mechanism. Operating GAC in a biological mode can extend GAC lifetime. However, GAC biofiltration remains poorly understood. Thus, the second part of this research was to evaluate the biodegradation potential of GAC. This research developed an approach that can differentiate between adsorption and biodegradation in GAC. The approach revealed that substantial MIB and geosmin biofiltration was occurring at one water treatment plant, and that GAC in some cases had significant adsorption capacity even after 9 years of operation. The final part of this research was to evaluate the removal of perfluorooctanic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) in GAC filter-adsorbers. It was observed that GAC could achieve approximately 20% to 55% of PFOA and PFOS removal even after a long period of operation (e.g., 6 years). This provides operational information for utilities that have installed GAC filter-adsorbers for taste and odour control but may wish to consider poly- and perfluoroalkyl substances (PFAS) removal as an additional treatment objective.

Keywords: Adsorption
Biodegradation
Drinking water treatment
Granular activated carbon
Advisor: Hofmann, Ronald
Community Conceptualizations of Women’s Everyday Mental Distress: The Importance of Social Contexts, Power and Agency in Shaping Women’s Distress Experiences in Eldoret, Kenya

Common Mental Disorders are the leading neuropsychiatric causes of disease burden in low and middle-income country (LMIC) settings. Women also demonstrate a higher burden of everyday distress globally, representing an extraordinary challenge for women in LMICs (WHO, 2017). Dominant assessment/treatment responses have been critiqued for lacking local cultural information about social contexts, experiences, and determinants of distress. This study responds to these concerns in Eldoret, Western Kenya, a context with strong mental health policy and primary care services, but limited resources and community-level data on women’s mental health. In partnership with Moi University and the AMPATH Consortium, I investigated the perspectives and experiences of women, the primary social determinants, and the community-level needs and assets around Eldoret women’s distress. This was an exploratory qualitative research study in which I drew on methodological frameworks for Community Health Needs Assessment and ethnography. I employed a critical cross-cultural theoretical stance informed by social ecological theory, cultural psychiatry, and Black and African feminisms. Over two years living in Eldoret, I generated primary data via community observation, key informant interviews, focus group discussions, and asset mapping, alongside the collection of relevant pre-existing secondary data. I found that “stressed up”, a severe form of everyday common mental distress, was the foremost mental health problem for Eldoret women. Key social determinants included: insufficient resources; primary partner relationships; household gender role stress; cultural norms; and gender-based violence. Women’s greatest mental health assets were their own coping skills (including ‘being brilliant’, hustling and persevering), female support networks, chamas (women’s groups), and religious institutions. Key needs included increased opportunities for pragmatic/economic support, and a centralized community women’s centre in town. This study contributes to the literature on socio-cultural models for understanding the burden of women’s distress, and offers a methodology for cross-cultural community mental health assessment. My findings suggest that severe stress is common and highly normalized, many women may therefore not seek help from primary care. Innovative social interventions are needed that build on community assets, champion women’s strengths, and offer pragmatic economic, relationship and violence-prevention supports that could address the core social determinants of Eldoret women’s distress.

Keywords: Common Mental Distress
Context
Global mental health
Stress
Women and mental health
Advisor: Forman, Lisa
A Systems-level Study of Effector-triggered Immunity in Arabidopsis thaliana

Despite the continued prevalence of agricultural crop failures due to pathogen attack, any given plant host is resistant to most pathogen diversity. This phenomenon, often described as “broad-spectrum disease resistance,” is well-documented though poorly understood in terms of how various facets of defense contribute to its overall potency. Effector Triggered Immunity (ETI) is a major branch of plant innate immunity which entails the recognition of pathogen virulence factors, termed effectors, by intracellular Nucleotide-Binding Leucine Rich Repeat (NLR) proteins. We used the Arabidopsis thaliana-Pseudomonas syringae pathosystem to explore the contribution of ETI to broad-spectrum resistance. Though most P. syringae strains utilize a type III secretion system to translocate effectors into host cells, there is extensive genetic diversity across strains at effector-coding loci. We hypothesized that the effector sequence diversity of P. syringae, most of which has never been cloned and studied, contains hitherto unidentified ETI responses. We thus developed PsyTEC (P. syringae Type III Effector Compendium), a collection of 529 effectors from across 494 genetically diverse P. syringae strains, to screen for interactions between P. syringae effectors and the A. thaliana immune system, ultimately identifying 59 effectors spanning 19 protein families which elicit ETI. We found that the majority of P. syringae strains have the capacity to elicit ETI on A. thaliana, and that this broad-spectrum resistance to P. syringae diversity is conferred by a small repertoire of NLRs. Two NLRs, ZAR1 and CAR1, can potentially recognize 94.7% of strains due to their recognition of multiple broadly distributed effectors. We further explored ZAR1’s recognition of 5 P. syringae effectors and identified other genetic requirements for these ETI responses. We propose that ZAR1’s capacity for broad effector recognition is achieved by monitoring several cytoplasmic kinases for perturbation by effectors. This indirect monitoring enables a single NLR to guard against many virulence factors from diverse pathogen backgrounds. These systems-level insights into the ETI landscape of A. thaliana-P. syringae highlight its importance to the plant host’s broad-spectrum resistance strategy: ETI is ubiquitous in this system, and sophisticated mechanisms of indirect recognition enable immune responses to be disseminated through a small repertoire of NLRs.

Advisor: Desveaux, Darrell
Guttman, David S
Tracing the Cellular Origins of Brain Cancers using Single-cell Transcriptomics

Brain cancers are one of the leading causes of cancer-related deaths among children and adults. The cellular and molecular heterogeneity of brain cancers at the time of diagnosis renders the identification of the cell-of-origin very challenging. Recent technological advancements have paved the way for the development of high throughput single-cell transcriptomics, which can be exploited to resolve the cellular identities of these cancers, trace developmental origins, and identify transcriptomic differences between the tumor and its cell of origin. Here, I analyze single-cell transcriptomic data from the developing mouse brain with collaborators to identify novel cell populations and re-construct developmental lineages from the embryonic stage to adulthood. First, through a novel approach combining single-cell transcriptomics and gene expression deconvolution methods, I establish a pipeline to map bulk and single-cell human brain tumor transcriptomes from hundreds of patients to normal developmental lineages of the mouse brain. I then show that the different molecular subgroups of childhood cerebellar tumours mirror the transcription of cells from distinct, temporally restricted cerebellar lineages. I next analyze single-cell transcriptomes of human childhood cerebellar tumours and show that many bulk tumours contain a mixed population of cells with divergent differentiation. Together, this work highlights cerebellar tumours as a disorder of early brain development and provides a proximate explanation for the peak incidence of cerebellar tumours in early childhood. Lastly, I extend this method to adult cerebral tumors and show that glioblastoma multiforme contains cells with a transcriptional signature that highly resemble embryonic and juvenile radial glial cells. Together, my research identifies candidate cells of origin for childhood and adult brain cancers through a novel approach, provides novel insights into tumour biology and heterogeneity, and will promote the development of novel targeted therapies based on differences between the tumor and its cell of origin.

Keywords: Brain Cancer
Cancer Genomics
Single-Cell Transcriptomics
Advisor: Stein, Lincoln D
Rethinking the use of Evidence in Decisions to Scale up Healthcare Interventions

Scaling up proven healthcare interventions is a common strategy for addressing global health system challenges. However, scale-up efforts have shown mixed results, with many interventions, shown to be effective at small scale, not moving beyond pilot projects. Though the use of scientific evidence has been promoted as playing a critical role in scaling up healthcare interventions, we currently have a limited understanding of how such evidence is understood and applied. Through this dissertation, I explore how different forms of evidence are applied to decision-making related to healthcare intervention scale-up, with a focus on the social, political, and structural factors that influence these practices. The aim is to inform and enhance current approaches to scale-up to better apply a range of scientific evidence. Two different methodological approaches inform this dissertation: a multiple qualitative case study of the evaluation and scale-up efforts of three healthcare intervention and a scoping review of frameworks or models providing actionable guidance for scale-up. I applied two separate analytical approaches to the case study data: 1) social theory informed thematic analysis, using elements of Bourdieu’s theory of practice as a theoretical lens, and 2) an interpretivist critical analytic approach to further explore how qualitative research is used in scale-up efforts. The findings demonstrate that there are gaps in the use of a range of evidence types in scale-up efforts, influenced, in part, by the prioritization of quantitative effectiveness data in the healthcare context and the challenges of incorporating different forms of evidence in practice. I suggest ways to address these gaps, such as better supports for qualitative and social scientists to engage in intervention evaluation and scale-up, broadening the scope of what is considered legitimate evidence, addressing limitations in funding programs to better incorporate different scientific approaches, and working towards a ground shift in terms of how we value, and reward, success and failure related to scale-up. These changes will better position our healthcare system to ensure that the most valuable and appropriate interventions are supported and scaled to meet the needs of the patients and the wider healthcare system.

Keywords: Health Services Research
Qualitative Research
Scale up
Social Theory
Advisor: Webster, Fiona
Exotic Phenomena Emerging from Localized Multipolar Degrees of Freedom

The rich diversity of building blocks in condensed matter systems offers the opportunity for exotic macroscopic quantum phenomena. Multipolar moments, higher order generalizations of the familiar dipole, present a unique avenue for the discovery of a variety of exotic and novel phases of matter. These anisotropic charge and magnetization densities provide additional internal degrees of freedom for localized electrons, allowing an expansion of nature's microscopic toolbox.In this thesis, we examine the nature of emergent multipolar phases, and propose experimental protocols to detect their existence and properties. We first examine the multipolar Kondo effect, where conduction electrons equipped with spin and orbital degrees of freedom scatter off a quantum impurity that hosts electric quadrupolar and magnetic octupolar moments. Using renormalization group methods, we uncover a number of stable non-Fermi liquid ground states. We next examine the nature of these fixed points using boundary conformal field theory techniques, to provide a non-perturbative description of their transport and thermodynamic properties. We then consider the development of unconventional superconductivity mediated by multipolar Kondo interactions. Employing group theoretic methods, in partnership with mean-field theory, we characterize the higher-angular momentum nature of the superconducting pairing states with point nodal quasiparticle excitations. Finally, motivated by recent experiments on rare-earth metallic compounds and insulating pyrochlore oxides, we propose the implementation of lattice-based probes -- magnetostriction -- to unveil hidden multipolar orderings and multipolar-based quantum spin liquid states.

Keywords: Conformal field theory
Hidden ordering
Kondo effect
Multipolar physics
Quantum spin ice
Unconventional superconductivity
Advisor: Kim, Yong Baek
The State as Polluter Challenge in Climate Law

It is commonly assumed that private actors cause climate change. This assumption problematizes international environmental law and suggests that the conduct of private actors should be the principal focus of climate law. This thesis challenges the empirical predicate and legal implications of this common assumption. The assumption is empirically wrong because states-controlled polluters are responsible for much of the global greenhouse gas emissions. The assumption is also legally misleading because it obscures a state’s obligations under international climate change law. Acknowledging the state’s direct contributions to climate change and its attendant legal consequences justifies litigation against states and their entities, or ‘state as polluter’ litigation. The trajectory of state as polluter litigation, however, will be shaped by the law of state attribution and the law of state immunity. These jurisdictional hurdles limit the scope —but do not foreclose — the possibility of state as polluter litigation before international and foreign tribunals.

Keywords: Climate Law
Climate Litigation
State attribution
State immunity
State-owned enterprise
Advisor: Brunnée, Jutta