VictorJuiz/thesis huggingface dataset:
Onco-proteogenomic exploration of variant peptide detection in disease models and clinical specimens

This thesis describes the efforts of integrating nucleotide sequencing results with mass spectrometry-based proteomic results to identify variants predicted from sequencing and being expressed at the proteome level within a proteogenomic framework. Specifically, the study was carried out in three levels. The first was a proof of concept study to demonstrate the feasibility of variant peptide detection in clinical specimens and reveal intrinsic strengths and weaknesses of the onco-proteogenomic pipeline. Subsequently, sequencing-predicted variants were tracked at the proteome level in cancer cell lines and breast cancer tissues. The results from both homogeneous and heterogeneous cell populations reveal the proportion of sequencing-predicted variant peptides detected at the proteome level, how different variant calling filtering criteria from sequencing raw data and alternative ways to search for variant peptides influence this number, a correlation between transcript abundance and variant peptide detection and how the translated mutant versions of the proteins may influence the observed phenotype. Overall, the results of the present dissertation provide promising evidence that the combination of the well-established sequencing technologies and the excellent capabilities of state of the art mass spectrometry instruments can effectively detect variant peptides in clinical specimens and that this approach has the potential to be optimized to harness its full potential and realize precision medicine translational applications.

Keywords: Mass spectrometry
Onco-proteogenomics
Precision medicine
Proteogenomics
Advisor: Diamandis, Eleftherios P
Charames, George S
Photochemical and Photothermal Reduction of Carbon Dioxide for Solar Fuels Production

Abstract Catalytic conversion of greenhouse gas carbon dioxide to value-added chemicals and fuels powered by solar energy is envisioned to be a promising strategy to realize both energy security and environmental protection. This work demonstrates that earth abundant, low cost nanomaterials based on silicon and iron can be used to harvest both light and heat energy from the sun to reduce CO2 and generate solar fuels. Herein, we have demonstrated that ruthenium supported ultra-black silicon nanowires can drive the Sabatier reaction both photochemically and photothermally where both incident photons absorbed by and heat generated in the black silicon nanowires accelerate the photomethanation reaction. This allows the reaction to be activated at ambient temperatures removing the need for external heating that could cause sintering, mechanical degradation and eventual catalyst deactivation and therefore improves the overall energy efficiency of the process. Additionally, we have shown that the rate of photomethanation is greatly enhanced when highly dispersed nanocrystalline RuO2 is chemically deposited onto the black silicon nanowires support. Furthermore, we have demonstrated that other silicon structures such as three-dimensional silicon photonic crystals can be used as an efficient support for CO2 hydrogenation. Unlike other insulating supports, these silicon nanostructured supports are particularly attractive for solar-powered catalysis because, with a band-gap of 1.1 eV, they can potentially absorb 80% of the solar irradiance. Moreover, they exhibit excellent absorption strengths and low reflective losses across the entire solar spectral wavelength range of the ultraviolet, visible and near-infrared portion of the solar spectrum. Finally, we demonstrated a comprehensive comparative study of the physical, electronic, and photocatalytic properties of ironoxyhydroxide (FeOOH) polymorphs by studying the extent of methylene blue photodegradation. This work led to the transformation of these FeOOH polymorphs into magnetite (Fe3O4) which effectively reduced CO2 to CO via the reverse water gas shift (RWGS) reaction.

Keywords: Catalysis
Photochemical
Photomethanation
Photothermal
Reverse Water Gas Shift Reaction
Solar Fuels
Advisor: Perovic, Doug D.
Ozin, Geoffrey A.
Embodied knowing and measured deficits: Whose knowledge counts in adult literacy?

My dissertation examines the (dis)connections between current policy about the meaning and measuring of literacy and learning and the self-knowledge of adult basic literacy learners. In particular, it explores the importance of reclaiming learning as an embodied process in adult literacy education. Drawing on concepts from New Literacy Studies and Disability Studies my thesis explores how the prevailing norming practices in adult literacy policy discourse objectify and shame learners, treat them as bodies of deficiency, and obscure the embodied process of learning. I use Narrative Inquiry approaches that bring together my lived experience as a literacy practitioner and personal learning in critical feminist studies to examine learner experiences and the power relations embedded in teaching and learning. My fieldwork explores how adult literacy learners understand themselves and how they make meaning of their own literacy and learning. I contrast these embodied ways of knowing with the objectifying knowledge constructs used for measuring adult literacy within current policy structures and texts, and explore the impact of the gap between them.

Keywords: adult literacy
Disability Studies
Embodied knowledge
measurement and assessment
narrative inquiry
New literacy studies
Advisor: Jackson, Nancy
Preclinical Evaluation of TEX101 Protein as a Male Infertility Biomarker and Identification of its Functional Interactome

TEX101 is a testis-specific cell surface protein expressed exclusively in the male germ cells, and it was previously suggested as a biomarker for the differential diagnosis of male infertility. Molecular function of TEX101 is not known, but previous studies demonstrated that murine TEX101 was a cell membrane chaperone, essential for fertilization. In this work, we employed quantitative proteomic strategies to investigate the clinical and the functional aspects of human TEX101 protein. To facilitate translation of TEX101 into clinic, we first developed and optimized an immunoassay for TEX101 measurement in biological fluids. We then evaluated the performance of TEX101 ELISA in 805 seminal plasma samples of fertile, sub-fertile, and infertile men. We demonstrated the clinical utility of TEX101 to evaluate vasectomy success, to stratify azoospermia forms and subtypes, and to predict the success of sperm retrieval in patients diagnosed with non-obstructive azoospermia. To gain insights into human TEX101 function, we employed mass spectrometry approaches to investigate the physical and the transient TEX101 interactome. Co-immunoprecipitation-mass spectrometry revealed a testis-specific complex TEX101-DPEP3 which was validated by hybrid immunoassay in testicular tissues and spermatozoa. In addition, we discovered a TEX101 rs35033974 homozygous knockdown model, which carried a missense variation leading to near-complete protein degradation. We then performed global proteomic analysis of TEX101 knockdown spermatozoa, and we identified the transient interactome of TEX101. New knowledge on TEX101 will provide insights into reproductive biology, facilitate better diagnostics of male infertility, contribute to rational selection of assisted reproduction treatments, and offer new protein targets to develop non-hormonal male contraceptives.

Keywords: Biomarkers
Human Reproduction
Interactome
Male Infertility
Testis expressed protein 101
Advisor: Diamandis, Eleftherios P
Belonging to Lake Nipissing: Knowledge, Governance, and Human-Fish Relations

Fishing constitutes an essential relation through which Nipissing peoples belong to Lake Nipissing. Belonging in and through human-fish relations is an affective, embodied, and dynamic relation. It is a reciprocal relation that expresses an Anishinaabe cosmology and rich knowledge and governance traditions. The diverse ways that Nipissing peoples belong to the lake are not represented in provincial fisheries policy and dominant epistemic frameworks; on the contrary, current provisions for Aboriginal Traditional Knowledge, ecosystem-based management, and Aboriginal partnerships preserve what Douglas Harris calls the legal capture of fish. In this dissertation, I write beyond the question of how Indigenous Knowledge Systems can improve Canadian fisheries management to center the diverse ways that Nipissing peoples value fish, know the lake, and enact their laws. Theorizing with difference, with that which seems contradictory and fragmented, my research performs important bridging work. Drawing on Nipissing and Anishinaabe theories and embodiments of power, change and transformation, my work seeks to interpret the efforts by Nipissing First Nation members to maintain relations with a hotly contested resource in a deeply challenging historio-legal environment.

Keywords: Environmental governance
Fisheries
Indigenous geography
Indigenous knowledge
Indigenous law
Lake Nipissing
Advisor: McGregor, Deborah
Towards an Integrated Model of Athletic Cognition - The Representational Shift Hypothesis

This exploratory study sought to situate athletic cognition within an integrated theoretical framework, the Representational Shift Hypothesis (RSH). Developed by the author, the RSH attempts to integrate the research and phenomenology of athletic cognition, including both the “hard” aspects of athletic cognition such as motor learning and control, attentional focus, cognitive load and performance, and the “softer” aspects such as affect, motivation and sense of self-capacity and control. A similar “mental representational” model, the RSH, posits that athletic cognition is the result of an embodied integration of the sensory, perceptual, knowledge, motoric and affective components supporting athletic performance, and that the holistic representations that underlie the athlete’s performance and self-conceptions undergo synchronized shifts. These shifts are necessarily episodic, reflecting the neural consolidation required to encode new skills, knowledge and affect. A longitudinal repeated measures exploratory study was conducted to determine if support for the RSH could be determined during the execution of a stable athletic task, stationary cycling. A broad range of cognitive, affective, and motoric execution data were collected during each session, utilizing both established and study specific self-reported inventories, automated performance data collection, and gaze tracking to assess attentional focus and cognitive load. Statistical and observational analyses were conducted to determine if synchronous shifts in the chosen measures could be determined, and their degree of synchronicity. Results provided mixed support for the RSH. While changes in inventory scores for self-efficacy, self-regulation and motivation did not show significance, the predicted trajectory of decreasing cognitive load over sessions, coupled to increasing fixation percentages on a decreasing number of data feedback points was partially expressed. Correlation and observational analyses of the data suggest some synchronization in shifts across measures, and a potential marker for representational shift was identified. The implications for additional research are discussed, including the potential for establishing empirically derived markets for skill acquisition and their role in supporting dynamically adaptive training systems.

Keywords: athletic cognition
data feedback
expertise
human performance
mental representation
skill acquistion
Advisor: McEwen, Rhonda
Excess Heart Disease Risk Associated with Arthritis in the Canadian General Population

This thesis, through three manuscripts, aims to clarify to what extent arthritis may be an independent risk factor for developing heart disease in the general population, underlying mechanisms of the relationship, and who may be most at-risk. Manuscript 1 is a systematic review and meta-analysis of population-based studies that estimated risk of incident myocardial infarction (MI) associated with five major types of arthritis. Results showed that MI-risk was consistently increased across arthritis and was partially explained by a higher prevalence of traditional heart disease risk factors in each type of arthritis. Knowledge gaps from the review were used to inform subsequent secondary analyses of the longitudinal Canadian National Population Health Survey (NPHS) with 16-years of follow up. Manuscript 2 used discrete time survival analysis with time-varying lagged predictors to estimate effects of arthritis on first heart disease event occurrence. Potential variations by age, sex and activity limitation were examined. Results showed that arthritis was independently associated with incident heart disease in all women, with more marked risk in women who also reported activity limitation, but only in men with activity limitation. Manuscript 3 used a novel approach to estimate potential mediating and moderating effects of activity limitation in the arthritis-heart disease relationship and possible differences by obesity and sex/gender in the same longitudinal health survey as manuscript 2. Results showed the proportion of heart disease risk explained by activity limitation varied between men and women, and between obese and non-obese women. Activity limitation explained nearly all of the heart disease risk associated with arthritis in men (90%), most of the heart disease risk in obese women (54%), and part of the heart disease risk in non-obese women (23%). Overall, the thesis results are important for increasing public and healthcare-provider awareness of excess heart disease risk generally associated with arthritis, highlighting sex/gender disparities, and identifying activity limitation as a modifiable intermediate target for prevention strategies to help reduce heart disease risk in people with arthritis.

Keywords: Arthritis
Heart Disease
Advisor: Badley, Elizabeth M
Prevention of Iron-Polyphenol Complex Formation in Iron Fortified Tea

The fortification of black tea with iron has the potential to reduce the prevalence of iron deficiency in the developing world. Tea is an ideal vehicle for food fortification because it is centrally processed, is the most consumed beverage globally, aside from water, and is consumed in regular quantities by those of all socioeconomic strata in many regions. Unfortunately polyphenolic compounds present in tea, which are responsible for colour and flavour, form complexes with iron which reduce the bioavailability of both compounds and cause strong unattractive colour development. The objective of this study was to develop a technique for the fortification of tea with iron such that these complexes do not form. A spectrophotometric method was developed and validated for the quantification of iron-polyphenol complex formation. Iron-polyphenol complex formation was further investigated with a variety of iron sources, temperatures, and polyphenol concentrations using a gallic acid model system and tea extract. Analysis and modeling of iron-polyphenol complex formation prompted the investigation of predicted inhibitors, specifically reducing and chelating agents. Reducing agents were able to hinder iron complex formation at pH 5 (the pH of brewed tea) but not at pH 7 (an approximation of the small intestineâ s pH). Chelating agents were successful at preventing iron-polyphenol complex formation at both pH 5 and pH 7. Due to its superior performance, disodium ethylenediaminetetraacetate (EDTA) was optimized for use in black tea. In summary, a technique has been developed for producing iron fortified tea based on a comprehensive framework for understanding the formation and inhibition of iron-polyphenol complexes in the presence of black tea polyphenols. This tea maintains its visual acceptability while providing iron in a bioavailable form. A process for effective iron fortification based on our laboratory technique is ready for in-vivo evaluation of its effectiveness and pilot scale testing.

Keywords: chelation
EDTA
fortification
iron
polyphenol
tea
Advisor: Diosady, Levente L
The Molecular Action of Actinorhodin, an Antibiotic Produced by Streptomyces coelicolor

Actinorhodin is a blue-pigmented, redox-active secondary metabolite that is produced by the bacterium Streptomyces coelicolor. Although actinorhodin has been used as a model compound for studying secondary metabolism, its biological activity is not well understood. Indeed, redox-active antibiotics in general have not been widely investigated at the mechanistic level. In this work, I have conducted a comprehensive chemical genetic investigation of actinorhodinâ s antibacterial effect on target organisms. I show that actinorhodin is a potent, bacteriostatic, pH-responsive antibiotic and that its redox activity, but not its in vitro organocatalyst activity, is important for its antibacterial activity. In the presence of actinorhodin, cells activate at least three stress responses, including those responsible for managing oxidative damage, protein damage, and selected forms of DNA damage. I find that mutations in the Staphylococcus aureus walRKHI operon can confer low level resistance to actinorhodin, indicating possible targeting of the cell envelope. This study indicates a complex mechanism of action for actinorhodin that is distinct from other redox-active compounds.

Advisor: Nodwell, Justin R
Development of Passive Samplers for Measuring Indoor Air Concentrations, and Measurement of Physical and Chemical Properties of Semi-Volatile Organic Compounds

Human exposure to semi-volatile organic compounds (SVOCs) including flame retardants (FRs) and plasticizers used in consumer products from indoor sources is a serious concern. These compounds are then advected to the outdoor environment which leads to regional and long-range transport and exposure to the ecosystem. This thesis aims to improve our understanding of exposure to selected SVOCs by developing tools, methods and providing data to facilitate exposure assessment particularly regarding indoor air. Three new passive air samplers (PAS), namely silicone rubber (polydimethylsiloxane, PDMS), styrene-divinylbenzene copolymer (XAD)-Pocket and XAD-PDMS were calibrated against an active air sampler and compared to the more popular polyurethane foam (PUF) PAS. Although the indoor sampling rates vary, we recommend from these studies a generic sampling rate of 1.7 m3 day-1dm-2 and 0.94 m3 day-1dm-2 for PDMS and PUF, respectively. The active air sampler was also used to assess the gas-particle distribution of the target compounds. The particle-phase partitioning fractions of SVOCs is a key determinant of their environmental behaviour and potential for exposure thus toxicity. A key finding here, is that some relatively volatile organophosphate ester FRs are present in the gas-phase where most published studies of active air sampling report them largely in the particle phase, indicating a sampling artifact. To improve chemical screening and modelling of the transport and fate, this thesis provides experimentally determined values of vapour pressures and octanol-air partition coefficients for over 50 SVOCs measured here using the well-established gas chromatography retention time method. Deployment of PDMS and PUF in residential homes gave comparable estimates of air concentrations for SVOCs in the gas-phase, although PUF was more able to capture compounds with higher fractions in the particulate phase. PDMS shows promise as a tool for estimating exposure to a wide range of SVOCs indoors, although its particle sampling efficiency warrants further work.

Keywords: Passive air sampling
Polydimethylsiloxane
Polyurethane Foam
SVOCs
Vapour pressure
Advisor: Diamond, Miriam L
Jantunen, Liisa M
Oxygen Bubble Propagation in Polymer Electrolyte Membrane Electrolyzer Porous Transport Layers

Identifying the physical properties related to the primary functions of the porous transport layer (PTL) (thermal, electrical, and mass transport) is necessary for understanding the impact of PTL design choices on electrolyzer performance. In this thesis, two-dimensional (2D) representations of three common PTLs were fabricated on microfluidic chips in order to study the impact of PTL microstructure on multiphase transport via visualization of air bubble transport in liquid-saturated porous networks. Air bubble patterns and breakthrough gas saturation were used to characterize the impact of porosity and average throat size on displacement patterns and oxygen saturation values. Next, a multiphase computational fluid dynamics (CFD) simulation tool was developed and validated with experimental results to simulate the dynamic displacement process of oxygen gas injection into liquid water saturated porous media. Using this CFD tool, a comprehensive phase diagram was developed through a parametric characterization of the porous media in terms of material hydrophobicity and gas flow rates. In addition to calculating the saturation of the invading gas, gas pressure variations were calculated and used to identify the locations of the phase diagram boundaries. The proposed phase diagram serves to inform the design of efficient PTL for improved polymer electrolyte membrane (PEM) electrolyzer performance.

Keywords: Bubble
Computational
Electrolysis
Fuel Cell
Multiphase
Porous
Advisor: Bazylak, Aimy
Montazeri, Hanif
The Problem of Political Authority in the Philosophy of Plato and Hegel

This dissertation examines the problem of political authority in Plato and Hegel. It is animated by an interest in the disavowal of authority characteristic of political culture today, and serves to fill gaps in the existing literature on German and Greek political philosophy. Contemporary scholarship on German Idealism follows Hegel in comparing 19th century critical philosophy to Greek philosophy, which it claims to surpass on account of its emphasis on subjective freedom. At the same time, contemporary reappraisals of Greek political thought hold up Plato and the classical teachings on rhetoric as promising alternatives to philosophy from Kant to Hegel, which is found to be overly rationalistic and insufficient in its treatment of political passion. Due to the division of scholarly labor, an adequate confrontation between classical political thought and German idealism remains wanting. Through a rigorous textual analysis of the Philosophy of Right and Gorgias, the dissertation expounds the Platonic and Hegelian approaches to the problem of political authority, and supplies the grounds for a dialogue between the two thinkers. On the basis of this preparatory work, it proceeds to take up the consolidation of political authority, or the production of obedience by the regime, insofar as Plato and Hegel disagree profoundly on that subject and its significance to political right. The dissertation presents the political philosophy of Plato and Hegel as robust and contesting alternatives, and concludes by returning to the challenge of political authority as it faces us today.

Keywords: German Idealism
Hegel
Plato
Political Authority
Rhetoric
Sophistry
Advisor: Orwin, Clifford