VictorJuiz/thesis huggingface dataset:
Enhanced Beneficiation of Ultramafic Nickel Ores Using Novel Reagents
Keywords: Chelating Agents
Decarbonization
Flotation
Nickel
Rheology
Ultramafic Ores

Due to its outstanding physical and chemical properties, nickel (Ni) is used in the manufacture of stainless steel, batteries, catalysts etc. However, high Ni demand has rapidly depleted high-grade sulfide deposits, leading the mining industry to seek alternative Ni sources such as low-grade ultramafic Ni ores. Processing of these ores is difficult due to their high content of the gangue mineral, serpentine, which slime coats the Ni-bearing mineral, pentlandite, and increases slurry viscosity. In response to stringent environmental regulations, process water is recycled, introducing significant amounts of Ca2+ and Mg2+ into flotation unit operations, which exacerbates the slime coating phenomenon. Additionally, the mining industry is under pressure to decarbonize its operations: it currently accounts for 4–7% of global greenhouse gas emissions. To overcome these challenges, the first part of this thesis focuses on decarbonizing mineral processing operations by utilizing carbon dioxide (CO2) in unit operations such as flotation and rheology modification. CO2 conditioning prior to flotation prevented slime coating and mitigated the detrimental impacts of divalent cations by permanently storing CO2 as metal carbonates. Zeta potential measurements and theoretical calculations indicated adsorption of metal carbonates onto the serpentine surface and microflotation experiments demonstrated increased Ni recovery. The second part of the thesis focuses on using sustainable flotation reagents for separation of pentlandite from ultramafic Ni ore. Citrate and Oxalate were shown to chelate with divalent cations to form metal-citrate or metal-oxalate chelates, which desorb from the pentlandite surface and adsorb onto the serpentine surface. Removal of chelates restored the charge and hydrophobicity of pentlandite whereas it reversed the charge of serpentine. The induced electrostatic dispersion among the mineral particles enhanced selective separation of pentlandite. The third part of the thesis explored the use of citrate and oxalate as rheology modifiers during slurry transport operations. Both reagents prevented bridging between serpentine particles and were selectively adsorbed onto the brucite plane of serpentine. Theoretical calculations and AFM measurements showed repulsive/weakened interactions between the brucite plane and silica/edge plane, which broke the mineral microstructure. Rheology investigations confirmed weakened interparticle interactions, manifested as significant decreases in slurry viscosity, yield stress, and storage modulus.
Leveraging Preclinical Pharmacogenomics Studies to Discover Translatable Expression Biomarkers of Drug Response
Keywords: Cancer
Pharmacogenomics
Transcriptomics

Precision oncology trials have demonstrated that matching cancer patients to treatment based on the molecular characteristics of their tumour leads to better response to therapy. Recent evidence suggests that transcriptomic profiling is particularly informative for matching patients to treatments. However, in many clinical studies, the majority of patients could not be matched to a genomically or transcriptomically selected therapy, highlighting a need for more biomarkers predictive of drug response. Preclinical pharmacogenomic studies combine molecular profiling of cancer models with drug sensitivity screening with the goal of discovering novel predictive markers. However, inconsistencies between experiments done in different laboratories raised concerns about the reliability of biomarkers discovered from these datasets. In this thesis, I address three challenges to using such studies for the discovery of transcriptomic biomarkers predictive of drug response. To address differences in data pre-processing and inconsistent nomenclature, I present PharmacoDB, a unified database of preclinical pharmacogenomic studies. I then investigate which statistical approaches are best suited to correlating noisy drug response measurements, both in simulation and real datasets. I propose and investigate the rCI statistic, a semi-parametric extension of the concordance index designed to reduce the impact of noisy drug response measurements. The rCI is shown to be more powerful at detecting correlations than the concordance index or Spearman correlation coefficient, however, it remains less powered than the Pearson correlation in the application to drug response data. Finally, I present a framework using statistical meta-analysis models to resolve technical and biological differences across datasets. I apply this framework to the seven largest preclinical pharmacogenomic studies released to date, discovering 4338 putative robust trancriptomic biomarkers. Using clinical validation data, I demonstrate a novel biomarker, expression of ODC1, is predictive of paclitaxel response for treatment of Breast Carcinoma a neo-adjuvant setting. Together, these contributions provide novel tools and propose novel approaches for analysing preclinical pharmacogenomic screens, as well as initiate the translation of discoveries made in these studies to clinically actionable biomarkers.
The Same River, Together: Theorizing and Assessing Shared Rule in Treaty Federalism
Keywords: federalism
reconciliation
self-determination
shared rule
treaties
treaty federalism

Starting from a query regarding the place of pre-Confederation treaties in the reconciliatory intentions of the contemporary Canadian political order, the primary objective of my dissertation is to consider one possible answer to this challenge by asking whether and how Indigenous peoples’ aspirations for both self-rule and shared rule might be achieved, and what role – if any – the Canadian federal state might play in those aspirations. The theory of treaty federalism, which takes the pre-Confederation treaties as the foundation of a federal relationship between Indigenous peoples and Canada’s colonial authorities, presents one vision for achieving such aspirations. The general aim of this dissertation is to consider both the theoretical basis for a theory of shared rule in treaty federalism as well as its implications for assessing the merit of various institutional models operationalizing shared rule. However, the theory of treaty federalism has been criticized for its under-theorization of the element of shared rule. This dissertation fills the shared rule gap in the theory of treaty federalism by elaborating what I have termed a “sharing protocol” that could feasibly underpin treaty relations in the Canadian federal order. If a functioning, treaty-centered nation-to-nation relationship is ever to be within reach, a coherent and comprehensive theory of shared rule is imperative. The sharing protocol rests on three core principles, derived from historical and contemporary treaty processes and traditions: enacting self-determination, commitment to co-responsibility and reciprocal prosperity. To test the viability of these principles in operationalizing a treaty federal order, the dissertation assesses the core models of political representation employed in service of increasing Indigenous political presence in settler state legislative bodies around the globe. Ultimately, the dissertation finds that both operational and proposed models of Indigenous political representation offer only limited enactments of shared rule from the perspective of a theory of treaty federalism, most often constrained by a lack of affirmation for Indigenous self-determination and the imposition of state-centric and hierarchical, rather than nation-to-nation, relations.
A Systematic Pipeline to Identify Bypass Suppressors of Essential Genes and Gene Pairs in S. cerevisiae
Keywords: suppression
systems biology

Genetic suppression occurs when a phenotype associated with a mutation in one gene is rescued by a secondary, extragenic mutation. Dramatic examples of genetic suppression include bypass of the lethal phenotype associated with mutation in an essential gene, or of phenotypes associated with severe Mendelian disease mutations in humans. Previous efforts to map bypass suppressors of essential genes have involved screening for chemically induced or spontaneous mutations, followed by next generation sequencing which, although biologically informative, can be laborious and time-consuming. Here, I developed a systematic method for identifying bypass suppressors using Synthetic Genetic Array (SGA) (Suppressor-SGA; Sup-SGA) technology to introduce defined loss-of-function mutations from yeast mutant arrays into strains carrying deletion mutations in essential query genes or gene pairs. Because the identity of the suppressor gene on the mutant array is known, this method enables rapid and exhaustive tests for suppressor relationships involving all genes in the genome. Analysis of bypass suppressors identified known suppressors and uncovered novel genetic factors that contribute to conditional essentiality. For example, analysis of bypass suppressors of NAT2 deletion revealed previously unappreciated roles in viral attenuation and mitochondrial function. I also adapted Sup-SGA to identify bypass suppressors of synthetic lethal gene pairs; that is, genes which when deleted alone do not cause a dramatic growth defect but cause lethality when combined as double mutants. I show that the suppressors of different bni1 synthetic lethal gene pairs are distinct and likely act through different mechanisms. In another screen, I identified three independent alleles of the essential cyclin-dependent kinase CDC28 at a semi-permissive temperature that cause G1-delay as suppressors of the synthetic lethal gene pair rpn4∆ ire1∆. Further experiments showed that the suppression occurs due to a bypass of the UPR pathway, likely alleviating the downstream consequences of ER stress. Intriguingly, rpn4∆ ire1∆ mutants were chemically rescued by the presence of low concentrations of α-factor which, like the mutation of CDC28, also causes G1-delay. This result illustrates the potential of small molecules to phenocopy genetic suppression. Altogether, I demonstrate the utility of Sup-SGA to elucidate the mechanisms of gene essentiality, to illuminate cell biology that governs synthetic lethality and to explore the basis of chemical suppression.
The Development and Miniaturization of In-Vivo Nuclear Magnetic Resonance Spectroscopy Towards Mass-Limited Environmental Samples
Keywords: Cryoprobes
Daphnia magna
In-Vivo
Metabolomics
Microcoils
Nuclear Magnetic Resonance Spectroscopy

The continual release of environmental contaminants is a global concern that impacts human and environmental health. To monitor and characterize the risk of contaminants, it is critical to determine their toxic mode of action. Unfortunately, our understanding of toxicity pathways is limited, in large part due to a lack of analytical methods capable of monitoring living organisms at the molecular level. Current methods often rely on apical endpoints; however, metabolomics focuses on characterizing biochemical changes in response to external stimuli. Recently, in-vivo Nuclear Magnetic Resonance (NMR) spectroscopy has demonstrated a distinguished ability to monitor living organisms in real-time with the potential to decipher complex interconnected response pathways. Unfortunately, environmentally crucial specimens, such as aquatic eggs, are challenging to study using in-vivo NMR due to their small size and the low sensitivity of NMR. This dissertation will address this challenge through miniaturization of in-vivo NMR. After an introduction to environmental metabolomics and NMR in Chapter 1, Chapter 2 focuses on optimizing in-vivo NMR using existing technology. This chapter examined NMR probes and experiments to establish that the optimal protocol to monitor 13C enriched living organisms was an inverse 2D experiment and an inverse cryoprobe. In the next chapter, NMR was first miniaturized here using microcoils. Chapter 3 compares two main microcoil designs (surface and 3D volume coils) for their ability to perform complex experiments on intact biological samples, concluding a 3D coil is most beneficial for in-vivo studies. In Chapter 4, a microlitre probe is modified with a separate lock and used to significantly reduce sample size requirements for the analysis of D. magna hemolymph and eggs. Additionally, a L volume flow system is introduced for an in-vivo stress study of neonates at the microcoil level. Lastly, Chapter 5 miniaturizes NMR using a novel Lenz lens design while integrating sensitivity enhancements from cryoprobes. The detection system created here leads to massive reductions in sample requirements and substantial increases in sensitivity for mass-limited samples. This dissertation miniaturizes in-vivo NMR techniques and positions it as an important approach to help improve the fundamental understanding of biochemical processes and for future environmental risk assessments.
Toward a Compact Two-photon Optical Clock based on Calcium
Keywords: optical clock
precision measurement
quantum optics

This thesis presents details on the design, construction, and characterization of a novel compact optical clock based on a two-photon transition in calcium. Optical atomic clocks have reached unprecedented accuracy and precision and have the potential to revolutionize metrology. However, many of the applications of optical clocks, such as the detection of dark matter and gravitational waves, deep space navigation, measurements of variations in fundamental constants, and precision geodetic measurements, require compact portable clocks. Building optical atomic clocks on a scale suitable for most field applications is an ongoing challenge in the precision metrology community. This work describes a clock that can be made smaller and simpler than most existing optical clocks, while still operating with state-of-the-art precision. The basis for these improvements is using a two-photon transition, which eliminates the need for sub-Doppler cooling and tight confinement of the atoms. The design for the calcium two-photon clock is given, and the construction of the clock components is described. Experimental results are presented for the search for the clock transition frequency, which has never before been precisely determined. A detailed uncertainty budget is given, showing that this clock should be able to achieve a fractional frequency uncertainty of $\sim 10^{-17}$. In addition, a novel technique of ``magic polarization'' is presented which can be implemented to mitigate probe laser light shifts, long thought to be a serious impediment to precision two-photon clocks. An experiment in which a two-photon clock based on rubidium was launched and operated on a stratospheric balloon and subsequently recovered is also described. This work represents an advancement in the development of compact portable optical clocks which will further push the boundaries of precision measurement and our understanding of the universe.
"Gathering the Pieces Back Together": The Experiences of Queer Second-Generation South Asians in Counselling and Psychotherapy
Keywords: Counselling and Psychotherapy
LGBTQ+
Mental Health
Second-generation
Sexual Minority
South Asian

Second-generation South Asian sexual minorities endure numerous challenges to their mental health and well-being often arising from their generational, ethnoracial and sexual identities, which are difficult to reconcile and develop into a cohesive and consistent personal identity due to discriminatory ideologies and experiences within ethnocultural/religious communities, mainstream queer spaces and Western society. These individuals must also adhere to the codes of South Asian family life and navigate competing cultural influences. Yet, queer second-generation South Asians seem to underutilize counselling services, suggesting that the mental health needs of this population may be unmet. Furthermore, whether psychotherapeutic practice can effectively address the mental health needs of this community remains unclear given the paucity of research and practice literature. The present study aimed to better understand the mental health and treatment-seeking experiences of this community through the research question: What are the experiences of queer second-generation South Asian clients in counselling and psychotherapy? Participants consisted of thirteen (cisgender) women and men of South Asian descent, who were born in Canada, identified as queer and had experience in counselling and psychotherapy. Research methods involved qualitative interviewing and the use of social constructivist grounded theory. Four key themes emerged: Experience Leading Up to Initial Counselling and Psychotherapy, Experience Inside Counselling and Psychotherapy, Impacts of Counselling and Psychotherapy and The Therapy Relationship. Findings suggest that queer second-generation South Asians first engage therapy in particular conditions, including the presence of multiple issues that overwhelm and isolate them, and when access to therapeutic supports are availed through personal circumstances and resources. Moreover, the presence (or absence) of topics and processes in therapy shape their experiences both inside and outside the counselling space. Ultimately, engaging in psychotherapy impacts these clients personally, relationally and experientially. Notably, all participants were multiple users of psychotherapy, and over time psychotherapeutic engagement was increasingly oriented towards a therapy relationship seemingly capable of supporting the integration of their identities and experiences. A mid-level theory was generated from this study’s findings. Additionally, implications of this research on the field of psychotherapy and directions for future research are discussed.
A Cultural Geography of Gardens in Early Twentieth-Century Viennese Opera
Keywords: gardens
opera
Schoenberg
Schreker
Vienna
Zemlinsky

This dissertation offers a new exploration of music, space, and place in early twentieth-century Vienna, through a focus on gardens as represented in opera and encountered in the city. I provide alternatives to longstanding interpretations of fin-de-siècle Viennese gardens as symbolic of aestheticist escapism by attending to a range of garden types and emphasizing their embeddedness within social and material contexts. I identify various metaphorical, literal, and discursive resonances between my chosen operatic gardens and counterparts in the built environment. Reading musical-dramatic gardens in light of contemporary urban and artistic developments, I argue, recognizes the mutual inflection of physical environments and artistic representations of them, and newly illuminates gardens’ diverse cultural associations and their dramaturgical functions in opera. Following my Introduction, the second Chapter outlines Richard Wagner’s musical-dramatic gardens, which served as precedents for the Viennese operatic gardens at the centre of my project. My third Chapter addresses the spatial dimensions of domestic, enclosed gardens and their entwinement with concerns around gender and psychological wellness in the modern urban landscape, through which I frame the garden in Arnold Schoenberg’s monodrama Erwartung (1909, premiered 1924). Chapter 4 theorizes open-air garden theatres as a locus for understanding the changing significance of neo-Baroque style for Vienna’s self-conception and theatrical ethos before and after World War I. I trace these themes in Franz Schreker’s pantomime Der Geburtstag der Infantin (1908), which premiered at the garden theatre of the Klimt circle’s Kunstschau 1908, and in the self-consciously Wagnerian garden scene in Alexander Zemlinsky’s Der Zwerg (1921, premiered 1922). My fifth Chapter focuses on pleasure gardens—a label I apply to the turn-of-the-century amusement park “Venedig in Wien” and the island of Elysium in Franz Schreker’s Die Gezeichneten (1913-15, premiered 1918)—wherein sound and music evoke otherworldly atmospheres and transport listeners to imaginary spaces. Through a combined historical and interpretive approach, this project deepens musicological understanding of the connections between turn-of-the-century opera and urban environments, explores literal and metaphorical relationships between music and space, and contributes a music-focused cultural geographic perspective on gardens’ significance for Viennese material and artistic life around 1900.
Individual Differences as Predictors of Participation in Sound Change
Keywords: /u/-fronting
individual differences
sound change

Models of sound change rely on individual listeners-turned-speakers to propagate variation which eventually turns into large-scale change. Sociolinguistic research, meanwhile, documents sound changes by aggregating data from a large number of speakers, usually disregarding individuals who deviate from the group norm. Psycholinguistic approaches to speech perception and production offer compelling evidence that individual cognitive differences are implicated in our linguistic behaviour. This dissertation aims to bring together individual difference frameworks and models of phonetically-motivated sound change to explore an instance of linguistic variation in Toronto. The production of /u/ has an allophonic distribution in which it is fronted following coronal segments and less fronted elsewhere. Post-coronal fronting has been documented as a long-term change-in-progress, while recent research indicates that the phonetic conditioning is loosening and fronting is spreading to non-coronal environments. A production experiment testing for correlations between individual cognitive differences and F2 of /u/ in two phonetic environments finds that female speakers who score low on the Empathizing Quotient scale have a significantly further back production of /u/ in the newly fronting environment, meaning that they are less innovative than their high-scoring counterparts. I argue that although this result is the opposite of the hypothesis that high-empathy women lead change, this low-empathy profile is compatible with a canonical description of a leader of sociolinguistic change. A perception experiment tests for correlations between the same cognitive factors and the perception of /u/ in coronal and non-coronal environments, to determine whether listeners at either end of the cognitive scales compensate for environment to different degrees. Women at either end of the empathizing scale do not differentiate between environments, leading to the conclusion that they are less affected by the onset than listeners who score highly on the systemizing scale. I suggest that the innovators are those whose low level of attention to detail allows them to ignore phonetic conditioning in their perception of /u/ providing the opportunity for /u/ to front in traditionally non-fronting environments, and whose low level of empathizing allows them to deviate from their peers. Both attributes are necessary to lead a co-articulatorily motivated sound change.