VictorJuiz/thesis huggingface dataset:
Regulation of Anti-viral Immunity by Dendritic Cells and Natural Killer Cells

4-1BB and its ligand, 4-1BBL, are costimulatory members of the tumor necrosis factor receptor (TNFR)/TNF family. The 4-1BB/4-1BBL pathway has been shown to potently enhance T cell responses in models of viral infection and cancer, thereby identifying this pathway as a target for immunotherapy. In addition to T cells, 4-1BB is expressed on dendritic cells (DCs), which also express 4-1BBL. The precise nature of 4-1BB/4-1BBL expression on DCs is not known and the endogenous function of 4-1BB/4-1BBL on this cell type has remained largely elusive. Here, I show that LPS-activated bone marrow-derived DCs express both 4-1BB and 4-1BBL, and that these molecules constitutively interact on DCs. Survival, upregulation of key costimulatory molecules, cytokine/chemokine production, antigen presentation, and the ability of DCs to generate primary influenza-specific CD8 T cell responses were normal in the absence of 4-1BB and/or 4-1BBL on DCs. Thus, the biological implications of 4-1BB/4-1BBL interactions on DCs remain to be elucidated. It was previously demonstrated in the Watts lab that the 4-1BB pathway on T cells becomes desensitized during persistent infection with lymphocytic choriomeningitis virus (LCMV) clone 13 through loss of the signaling adapter TRAF1. In the course of these studies, it was found that 2 months following LCMV clone 13 infection, a time point at which virus is largely cleared from the spleen and other organs, C57BL/6 mice showed dramatic splenic atrophy. Here, I show that this atrophy persists for up to 10 months following initial infection and that it does not occur with the acutely infecting strain, LCMV Armstrong. I go on to show that splenic atrophy is mediated in part by natural killer (NK) cells, and implicate NKG2D-MULT1 interactions as contributing to late-stage B cell depletion. Compared to isotype control antibody treatment, type I interferon receptor 1 (IFNAR1) blocking antibody treatment at the onset of splenic atrophy increased the proportion of NK cells in the spleen, and was correlated with exacerbated splenic atrophy. Lastly, splenic atrophy following LCMV clone 13 infection was associated with delayed clearance of a bacterial pathogen. These findings implicate NK cells in the pathophysiological mechanisms underlying splenic atrophy following viral infection.

Keywords: 4-1BB
CD137
dendritic cells
LCMV
natural killer cells
splenic atrophy
Advisor: Watts, Tania H
Women and Reproduction: An Exploration of Factors Affecting Folate Status and Other Select Micronutrients Involved in One Carbon Metabolism

Optimal function of one carbon (1-C) metabolism is necessary during reproduction as it supplies 1-C units for purposes of synthesis or methylation of nucleic or amino acids. Maintaining nutrient status of the methyl vitamins folate, choline, vitamins B6 and B12 is crucial to prevent the nutrient imbalances linked to increased risk of neural tube (NTD) and other birth defects. There is little understanding of whether or not pregnancy and folic acid (FA) supplementation influence 1-C metabolism--for example shunting toward DNA synthesis in pregnancy. Using red blood cell forms as a mechanism to evaluate partitioning of folate early in erythropoiesis we examined the RBC folate forms in pregnant women consuming 1 mg of FA and non-pregnant women consuming 0, 1 and 5 mg supplemental FA (n=26). We found that neither pregnancy nor level of FA altered the relative distributions of the folate in RBC indicating no preferment for DNA synthesis. We then investigated if a comprehensive list of socio-demographic and lifestyle factors would improve our ability to predict if a woman was more likely to have RBC folate concentrations associated with NTD protection in women of childbearing years (WCBY), thereby removing the necessity for a blood sample (n=101). We found that a FA supplement of 200 Âľg/d or a multivitamin consumed every other day, taking into account alcohol intake while controlling for ethnicity, can effectively discriminate RBC folate concentrations associated with NTD protection 73% of the time. Lastly, since the majority of women do not use multivitamins regularly, we systematically investigated the specific foods that contribute to dietary folate, vitamin B12, vitamin B6 and choline intakes of WCBY using nationally representative data from the Canadian Community Health Survey 2.2 (n=4308). We found heavy reliance on FA fortified foods for folate intake and animal products (37- 94%) for B6, choline and B12 intakes. The mean daily choline intake in WCBY was 238 mg with ~99 % of WCBY having intakes below Adequate Intakes. Our investigation suggests that status of the methyl nutrients is sensitive to a number of factors influencing 1-C metabolism.

Keywords: folate
folic acid supplementation
micronutrients
one-carbon metabolism
reproduction
women
Advisor: O'Connor, Deborah L
Listening to the Fur Trade: Sound, Music, and Dance in Northern North America 1760-1840

The fur trade in northern North America during the period of 1760-1840 introduced both Europeans and First Nations peoples to new sounds, musical forms, and dances. Permeating nearly every aspect of the fur trade's operation, from travel and transportation, cross-cultural encounters, establishing and strengthening relationships, exchanging material goods, and celebrating holidays and special occasions, a distinct soundscape and musical culture developed. First alerted to the presence of Europeans by the sounds of gunpowder, customs of saluting and signaling by firing weaponry were soon adopted and adapted by First Nations peoples in their activities and interactions with fur traders. The colonial warfare that characterized the Great Lakes for much of this period introduced military instruments such as drums, bugles, and bagpipes to the trading posts, which gradually shed their disciplinary associations and were employed instead in fur trade rituals and recreational activities. While music and dance served as a pastime for the gentlemen and servants of the Hudson's Bay Company (HBC) and North West Company (NWC), it operated most crucially in engagements with First Nations peoples on whom they relied for their profits and livelihood. Fur traders had to navigate dances associated with the calumet pipe and war, which functioned to establish and strengthen trading relationships. Fur traders were agents of change as well as early ethnographers who described First Nations' musical traditions. They observed similarities and differences between various nations' musical traditions, while also recording instances of cultural and material adaptation. Significant locations along the trading routes elicited ritualized responses, layering meanings onto the landscape with sounds, stories, and songs. Singing regulated paddling, pushing its pace and duration while also providing a creative outlet for the expression of sensory desires. A vibrant instrumental dance music culture developed in and around the trading posts especially before the amalgamation of the HBC and NWC in 1821. After this date dances became increasingly restricted due to concerns over profitability and morality. Yet the fur trade gestated hybridized fiddle and dance styles that left a lasting legacy especially in First Nations and MĂŠtis communities.

Keywords: Dance
Encounters
Fur Trade
History
Music
Sensory
Advisor: Greer, Allan
Bohaker, Heidi
Rhodium-catalyzed Asymmetric Carbon-Carbon Bond Formation Leading to the Development of Rhodium/Palladium Multi-metal Catalysis

This thesis describes the development of rhodium-catalyzed asymmetric ring opening of strained alkenes and the subsequent use of rhodium and palladium catalysis in the development of domino reactions. The contents are divided into 4 chapters. Chapter 1 describes the rhodium-catalyzed asymmetric ring opening (ARO) of strained bicyclic alkenes using silyl enolates. The development of this method achieved a highly enantioselective addition of alkyl fragments onto bicyclic alkenes, affording broad scope, mild reaction conditions, and high functional group tolerance. The synthetic utility of the method was demonstrated through functionalization of the ARO products to a number of core scaffolds of natural products. Chapter 2 describes the development of a domino rhodium/palladium-catalyzed synthesis of dihydroquinolines. The use of two different ligands in the reaction led to a mechanistic investigation that revealed metal-ligand interactions that were crucial to the success of this domino reaction. The mechanistic insights facilitated reaction optimization, leading to an expansion of the reaction scope, including the synthesis of chromenes. Chapter 3 describes the importance of time resolution and ligand interference in the development of enantioselective domino rhodium/palladium catalysis employing chiral and achiral ligands. The development of this method provided access to chiral C4-substituted dihydroquinolinones in a direct manner, affording high yields and enantioselectivities. Current work on developing multicomponent enantioselective rhodium/palladium catalysis is also disclosed. Chapter 4 describes the development of multi-metal-catalyzed multicomponent reactions (MC)2R. The development of a highly compatible rhodium/palladium catalyst system allowed the incorporation of a third catalyst, copper, achieving a three-component one-pot reaction. Current work on the development of the use of other metal combinations to achieve (MC)2R is also disclosed.

Advisor: Lautens, Mark
Why They Are Not Painters: Ekphrasis and Art Criticism in the Twentieth Century

This study of twentieth-century poetry proposes a re-examination of how we interpret ekphrasis, or poems that address existing works of visual art, by tracing a historical trajectory of these poems as responses to the art and critical climate of their time. Though much scholarship has elaborated the stakes of ekphrasis as a confrontation between the "sister arts," between narrative time and visual stasis, and between desiring self and its enigmatic other, many modern iterations of the genre suggest its hybridity as a work of art and of criticism that poets use to consider the value and function of images in their world. The representative poets in this study - Marianne Moore, W. H. Auden, William Carlos Williams and Frank O'Hara - were not only adapting strategies gleaned from their encounters with Cubist, Surrealist, Dadaist, Abstract Expressionist, Neo-Dadaist, and Pop art and artists, but were also actively involved in critical debates about how this art was being interpreted, at times in their prose essays, but more frequently in their ekphrastic poems. These poets were especially interested in, and often suspicious of, the critical trend of formalism, which became increasingly orthodox in its interpretation of modern art in the postwar period. The intervention of this study is to demonstrate how these ekphrastic poems function as an alternative discourse to formalism, challenging not only the orthodoxy of its increasingly rigid tenets, but also its underlying preoccupation with values of order, purity and unity. These poetic appraisals of art exploit the resources of their medium, such as Moore's literary and archeological allusions to jars, which critique Roger Fry's separation of form from function, Auden's parody of the art critic that suggests the dangerous allure of art divorced from political life, Williams' resistance to interpretation through pastiche and O'Hara's blending of ekphrasis and elegy to expose the emotional repression inherent in Clement Greenberg's authoritarian rhetoric. These poets suggest that writing about visual art often reveals as much about the observer as it does about the art, and thus they turn to ekphrasis for its potential to multiply the lenses through which to do that seeing.

Keywords: ekphrasis
Frank O'Hara
Marianne Moore
W. C. Williams
W. H. Auden
Advisor: DuBois, Andrew
The Dependence of Global Chromatin Architecture on the Histone Chaperone DAXX

An essential component of gene regulation is the organization of eukaryotic genomes into functionally and spatially discrete domains. One such domain is the chromocentre, which is a cluster of pericentric heterochromatin enriched in methylated histone H3 (H3K9me3), major satellite repeat DNA, and the histone variant H3.3 specifically deposited by the death-domain- associated protein (DAXX) chaperone. While studies relying on biochemical-based approaches have provided insight into the mechanistic details of the DAXX-dependent chromatin assembly pathway, they have not yielded a comprehensive model of the consequences of this deposition on global chromatin organization. Using electron spectroscopic imaging (ESI), I show that in the absence of DAXX, there is a breakdown in chromocentre structure and a loss of morphological distinction between the repressive histone modification H3K9me3 and chromatin compaction. In addition, I demonstrate that the structural integrity of the nucleolus requires DAXX-dependent heterochromatin organization as its loss causes an increased number of "mini" nucleoli and the dispersal of ribosomal DNA genes. As well, I investigated the role of DAXX in the C2C12 muscle differentiation model and found that concomitant with the formation of terminally differentiated myotubes is the relocalization of DAXX from promyelocytic leukemia nuclear body (PML NBs) to constitutive heterochromatin domains. Taken together, these data reveal that DAXX is a regulator of heterochromatin organization and for the first time, shows the direct consequences of its loss on the global nuclear landscape.

Keywords: DAXX
Heterochromatin
Hisone variants
Microscopy
Nuclear organization
Advisor: Bazett-Jones, David P
Characterization of the Biological Roles and Biochemical Properties of Triphosphate Tunnel Metalloenzyme Superfamily Members in Plants

The triphosphate tunnel metalloenzyme (TTM) superfamily comprises a group of enzymes that hydrolyze organophosphate substrates in a metal-dependent manner. Members of this family have diverse biological functions in different organisms. Arabidopsis encodes three TTM genes, called AtTTM1, AtTTM2, and AtTTM3. Previous work showed that AtTTM3 is a tripolyphosphatase requiring Mg2+ where its crystal structure reveals the signature TTM catalytic tunnel. In this thesis, I present my findings on the biological and biochemical characterization of AtTTM1 and AtTTM2. A reverse genetics approach using T-DNA insertion knockout lines revealed that AtTTM2 is a negative regulator of the SA amplification loop in defense responses. ttm2 plants exhibit enhanced defense responses to virulent and avirulent pathogens, enhanced hypersensitive response (HR), elevated SA, and enhanced SAR. ttm2-mediated enhanced resistance requires the key defense regulators, PAD4, ICS1, and NPR1. Furthermore, AtTTM2 is transcriptionally downregulated in response to pathogen infection and flg22, SA, and BTH treatment. While ttm2 exhibits enhanced resistance, it is not an autoimmune mutant, suggesting that it is not a conventional negative regulator of defense responses. Phenotypic characterization of ttm1 did not reveal any alterations in defense responses. Instead, ttm1 exhibited delayed senescence by showing enhanced chlorophyll retention after dark-induced senescence, which is concomitant with the delayed expression of senescence markers. Furthermore, AtTTM1 is transcriptionally upregulated in response to dark-induced senescence, suggesting that it is a positive regulator of senescence. Interestingly, functional complementation of ttm1 and ttm2 phenotypes in promoter swap analyses revealed that the distinct biological roles of AtTTM1 and AtTTM2 are governed by their expression patterns. These results indicate that their biochemical functions are likely highly similar or identical, which was supported by the observation that both AtTTM1 and AtTTM2 possess pyrophosphatase activity in the presence of Mg2+. The findings presented in this thesis not only depict the first characterization of TTM superfamily members in plants, but they also represent one of the first accounts of the importance of TTM proteins in a biological context.

Advisor: Yoshioka, Keiko
State Repression and Political Deportation in Canada, 1919-1936

Section 98 of the Criminal Code of Canada was in force from1919 to 1936. The dissertation traces the way in which Canada incorporated emergency law, created during the First World War under the War Measures Act, into the Criminal Code as Section 98 after the war to combat political radicalism from 1919 to 1936. In contrast to existing scholarship, this work not only explains how a liberal democracy like Canada can legally use emergency legislation outside of a state of emergency through a process of `normalization' but it also examines the effects of such laws on their human targets through case studies of criminal trials and deportation hearings. Targets included political activists, immigrants and women. It makes contributions to Canada's legal, immigration, labour and intelligence history. The study also examines the international influences on Canadian policy makers in creating such laws and the complex international identities of the transnational activists at whom these laws were often directed. The work examines how culture played a crucial role in underpinning the intelligence cycle that led to the prosecution of leading Communist Party of Canada (CPC) members. It also complicates our understanding of the CPC during Moscow's `Third Period.' It was a party that both marginalized and welcomed immigrant workers. The dissertation provides an in-depth examination of the trial of Rex v. Buck et al and the ways in which political ideology was interpreted by the court as a criminal act. It examines cases of deportation that resulted from the trial, such as the case of the `Halifax Ten,' and traces what happened to the deportees after their deportation making use of Finnish, Polish, Croatian, and German primary sources. In addition, this work demonstrates how the communist led organization, the Canadian Labour Defense League (CLDL) initiated Canada's civil rights movement by joining with moderate leftists during the `Third Period,' and before the Communist International's shift to the `United Front' policy, to repeal Section 98. It demonstrates how the normalization of emergency law continued after Section 98's repeal when its core elements were retained and folded into Canada's sedition laws where it remains today.

Keywords: communism
deportation
national security
Section 98
state of emergency
state of exception
Advisor: Radforth, Ian
An Intellectual History of Early-Pahlavī Demonology, 1921-41/1299-1320 sh.

This historiographical dissertation details how ancient and medieval Iranian demonology, including its avatars, motifs and styles of discernment, went through a radical conceptual revolution during the span of modernity, being informed by and impinging all domains of activity in which the demonic can be traced, such as the political, social, economic, technological, philosophical, and moral. Through an analysis of discourses and literatures pertaining to these domains, this study divulges the logic, mechanisms and movements behind the persistent deployment of traditional characterological signifiers of unholiness during a period of the twentieth century that is customarily argued to be a time generally preoccupied with notions of modernization inherited from the European Enlightenment tradition. In this work of inquiry, there is a focus on the early years of Pahlavī rule (1921-41/1299-1320 sh.) when a whole cluster of demonological notions and understandings entered a stage of hitherto unrealized clarity and coalecsed struggle for hegemonic supremacy. Demonological analysis positions adjacent to the assembly of oft-discussed modes of periodization, including mytho-secular nationalist, Perso-Islamic, and modern temporalities, the relatively unexplored natural history of man and its description of humanity's early confrontation with and gradual civilizational overcoming of Nature's perilous and almost insurmountable forces. Since the inception of modernity, the demonic came to be infused with attributes associated with Nature, including inexorability, purposelessness, and illogicality, and insofar as traditional scions of evil were described as being situated in said Nature, their conceptual potency heightened, relative to both their previous forms and the Iranian populous. The demonism of Nature violently struggles against the analogical reasoning and absolute monotheistic commitment of the Perso-Islamic Shayṭān and the antinomic status of Zoroastrianism's Ahrīman. Adopted strategies utilized to engage with this newly reorganized demonic landscape were varied during the early-Pahlavī period, coordinated as they were by the different social positions, philosophies, and lived experiences of their devisers. However, out of all the texts covered, it was those by the modernist author Ṣādiq Hidāyat that came to a full and heady recognition of the novel demonic paradigm, ushering all together the end of the first Pahlavī period.

Advisor: Tavakoli-Targhi, Mohamad
Production of Biodiesel and Protein Isolates from Dehulled Yellow Mustard Flour

Aqueous extraction is an emerging alternative to hexane-based oilseed extraction since it eliminates the dangers associated with processing, and allows the simultaneous recovery of high-quality protein products and vegetable oils. Five different non-enzymatic and enzymatic aqueous extraction processes (AEP/EAEP) were developed for dehulled yellow mustard flour with the aim of producing food-grade protein isolates and fuel-grade biodiesel. The oil released in these processes was tied up in oil-in-water emulsions that must be destabilized to recover free oil prior to biodiesel production. The remarkable stability of the released emulsion was due to the presence of protein emulsifiers of high molecular weight along with the mixed phospholipid-oleosin layer. pH adjustment and enzymatic treatments with different proteases and phospholipases for emulsion destabilization were relatively inefficient; therefore, a novel chemical approach was developed based on dissolution of the emulsion in tetrahydrofuran (THF) or dioxane to recover the released oil in the form of single-phase oil-solvent-water miscella suitable for direct conversion to biodiesel through single-phase base-catalyzed transmethylation after reducing the water content to the quality standards required for biodiesel feedstock. The emulsion destabilization using organic solvents was optimized, based on experimentally prepared ternary phase diagrams of THF/oil/water and dioxane/oil/water, and the results suggest that this technically viable approach can successfully recover essentially all of the oil from the emulsion. The resulting miscella phases were successfully dehydrated by adsorption over zeolite 4A using either batch or fixed-bed systems. The dehydrated miscella phases were finally reacted with methanol in a single-phase transmethylation process with high yields (99.3 wt%) to fatty acid methyl esters (FAME). The resulting FAME satisfied the international standards for use as biodiesel fuel. Finally, our integrated process consisting of aqueous contact of mustard flour to recover protein as the main product followed by dissolution of the resulting emulsion with THF could produce high-quality protein products free of solvent contact/residues, while biodiesel could be efficiently recovered using a less flammable solvent than conventional hexane extraction. We believe that this study will help Canada to balance food and biofuel production that can lead to lower food prices, benefiting many poor people in the world.

Advisor: Diosady, Levente L.L.