VictorJuiz/thesis huggingface dataset:
Regulation of Cyclic Nucleotide-Gated Channels and Plant Calcium Signaling
Keywords: calcium
calmodulin
CNGC
immunity
signaling

Plants must coordinate developmental processes and responses to environmental stimuli via signaling at the cellular level. Ca2+ serves a common second messenger in many signal transduction pathways, wherein increases in cellular Ca2+ levels are interpreted by a suite of downstream Ca2+-binding sensor proteins, such as calmodulin (CaM). While Ca2+ is known to mediate responses to diverse stimuli in plants, including biotic stress, less is known regarding the channels involved in Ca2+ signaling or their regulation. Cyclic nucleotide-gated channels (CNGCs) represent one of the major classes of Ca2+-permeable channels thought to mediate Ca2+ flux in plants, and several isoforms of the 20-member Arabidopsis CNGC family, including CNGC12 and CNGC2, have been implicated in immune responses. In this thesis, I present a thorough analysis of the regulation of Arabidopsis CNGCs by CaM, and demonstrate that CNGC12 function is both positively and negatively regulated by CaM-binding to multiple, distinct sites at the cytosolic termini of the channel. My results with CNGC12 indicate that plant CNGCs are likely subject to complex regulation by Ca2+, suggesting that CaM is required for both channel function and feedback inhibition. My findings with CNGC12 are expanded to the entire 20-member CNGC family, and I have shown that Arabidopsis CNGCs possess diverse CaM-binding sites, both in terms of number and mode of CaM-binding. In particular, the IQ motif appears to be broadly conserved across the CNGC family, and in most members, mediates permanent association with CaM via Ca2+-independent interaction with the CaM C-lobe. These data indicate that CaM functions as a Ca2+-sensing subunit of CNGC complexes in plants. Finally, I developed transgenic Nicotiana benthamiana and Nicotiana tabacum (tobacco) lines expressing the fluorescent Ca2+ indicator, GCaMP3, which can be used to visualize and measure Ca2+ signals in response to diverse abiotic or biotic stimuli. I examined the dynamics of Ca2+ signaling in response to stimuli including cold-shock, mechanical wounding, and pathogen-associated molecular patterns (PAMPs). These plants represent an excellent tool to dissect the molecular components of Ca2+ signaling via gain- or loss-of-function studies.
“In Unknown Languages”: Investigating the Phenomenon of Multilingual Acting
Keywords: acting
Canadian theatre
multilingualism
phenomenology
practice as research
second language

Despite the growing presence of multilingual theatre in large multicultural cities like Toronto, research on stage multilingualism remains at the nascent stage, particularly in English Canada. Using the Practice as Research methodology, as proposed by Robin Nelson (2013) and the principle of interdisciplinarity (Repko 2012) this dissertation investigates stage multilingualism that does not use translation. Specifically, it focuses on multilingual actors, multilingual dramaturgy, and multilingual audiences. The artistic practice at the centre of the study involved 25 professional and amateur performers, both mono- and multilingual, who were engaged in a six-week creation period of devising scenes in their dominant, non-dominant, and unfamiliar languages. The devised scenes were later compiled into a multilingual show entitled “In Sundry Languages” and performed twice to a multilingual audience. This study first offers an analysis of the actors’ phenomenology of performing in various languages, as captured in the actors’ journals, the researcher journals, and the researcher’s post-performance interviews with the actors. Second, it reveals the specifics of the dramaturgical devices of “In Sundry Languages” through the show’s script and video recording. Finally, through a qualitative analysis of 182 post-performance audience surveys, the study shows a vast diversity of audience responses to the presence of multiple languages on stage. Using Sara Ahmed’s queer phenomenology (2006) as its theoretical framework, the study conceptualizes untranslated stage multilingualism as a queer object which has the potential to cause re-orientation (or queering) of the subject, especially a monolingual subject. It also investigates how and why certain multilingual subjects (both actors and audiences) may challenge dominant monolingual frameworks, relying on a clear distinction between one single mother tongue and additional languages. Finally, the study proposes multilingual dramaturgy as “diversity work” (Ahmed 2014), confronting the monolingual paradigms of Toronto’s mainstream theatre.
Emerging Logics of Citizenship: Activism in Response to Precarious Migration and Gendered Violence in an Era of Securitization
Keywords: Citizenship
Gender
Immigration
Postnationalism
Social Movements
Violence Against Women

Postnationalism is a theory of citizenship that emerged in the 1990s, which rejected national membership as an exclusionary or limited way of organizing rights and belonging, and sought instead to re-imagine citizenship beyond the nation-state. The approach was largely discredited at the time for underestimating the persistent influence of nationalism and for lacking empirical evidence. In this project, I join a small group of scholars who argue for a reconsideration of postnationalism, particularly for scholarship examining the production of illegality and securitization of borders across countries in the global north. I add to this scholarship by offering an extended case analysis of postnational activism in Toronto, in response to major restructuring of Canada’s refugee and immigration system and expanded deportation regime between 2006 to 2015. Using ethnographic fieldwork, qualitative interviews, and discourse analysis, I show how some activists used postnational human rights frames to restrict immigration authorities from entering schools, women’s shelters, and other city spaces for the purposes of investigating and deporting non-status migrants. Theorized as postnational acts of citizenship, such approaches were useful for exposing the structural violence produced through state regulation of borders and citizenship, leading to the articulation of a ‘no borders’ politics. However, as a social movement strategy, postnational claims were also limited in their capacity to imagine alternatives to state protection, particularly for non-status women in situations of gender-based violence. My findings also point to the erosion of citizenship for a group of activists working as service providers within state-funded institutions, where processes of securitization altered their working conditions and produced feelings of fear, despair, and even terror in how they interpreted the actions of the Conservative party in power at the time. Overall, this research draws attention to the increased salience of postnationalism for studies of social inequality in the contemporary immigration context.
Evaluation and Validation of Novel Methods for the Diagnosis of Invasive Aspergillosis
Keywords: Biomarkers
Diagnostics
Droplet digital PCR
Fungal immunology
Infectious diseases
Invasive aspergillosis

Aspergillus is a ubiquitous soil-dwelling fungus known to cause significant infection in immunocompromised patients. The incidence of invasive aspergillosis (IA) has dramatically increased during the past two decades due to widespread use of chemotherapy and immunosuppressive agents involved with the management of malignancy, organ transplantation, and autoimmune and inflammatory conditions. Individuals at high-risk of IA include chemotherapy and hematopoietic stem cell transplantation (HSCT) recipients, solid organ transplant (SOT) recipients, and those with advanced human immunodeficiency virus (HIV)/AIDS, hyperimmunoglobulin E (Jobâ s) syndrome, and chronic granulomatous disease. Early diagnosis and treatment of infection are crucial; however, definitive diagnosis is not straightforward as symptoms are nonspecific and require invasive procedures that are often difficult or impossible to complete. Due to the difficulties in diagnosing IA, the European Organization for Research and Treatment of Cancer (EORTC) Invasive Fungal Infections Cooperative Group and the Mycoses Study Group (MSG) of the National Institute of Allergy and Infectious Diseases have established consensus definitions for defining opportunistic invasive fungal infections. While the EORTC/MSG criteria are important in the standardization of definitions used for IA in clinical research studies, much work still remains to be completed. Many established improvements have been made in the field of diagnosis (galactomannan antigen, beta-glucan antigen, PCR, computed tomography); however, they still lack sensitivity and are often only detectable later in the course of infection. Early detection of IA would be greatly enhanced if accurate, practical, and cost-effective diagnostic biomarkers for this infection were available. Whereas much of the research and available diagnostic tests focus on fungal-derived biomarkers, the aim of some of the work described in this thesis is to identify novel host-derived biomarkers (Chapter 4) that differentiate IA from non-infection, as well as validate novel noninvasive sampling methods for IA diagnosis using droplet digital PCR and ELISA techniques (Chapters 2 and 3).
Unraveling the Molecular Mechanisms of Munc18 and Munc13 in Mast Cell Exocytosis
Keywords: Exocytosis
Mast cell
Munc13
Munc18
SNARE

Exocytosis is a fundamental cellular process in which contents stored in vesicles are released out of cells via fusion of membranes. Exocytosis of secretory granules from immune cells such as cytotoxic T-lymphocytes, natural killer cells and mast cells play crucial physiological roles in protecting individuals from pathogens. The exocytosis is known to be mediated by Soluble N-ethylmaleimide sensitive factor Attachment protein REceptor (SNARE) complex where intertwined helix bundles provide energy to fuse lipid membranes. Furthermore, this process is regulated by indispensable proteins such as Munc18 and Munc13 through physically interacting with SNARE proteins. Disruption of proteins that are involved in the secretory granule exocytosis causes serious immune disorders including familial hemophagocytic lymphohistiocytosis. However, compared to vastly investigated mechanisms of neuronal exocytosis, natures of proteins and their precise molecular mechanisms involved in immune cell exocytosis remain elusive. It has been revealed that the immune cells employ Ca2+-triggered SNARE-mediated exocytosis, but how such processes are being regulated in the immune cells needs to be investigated thoroughly. Using Rat Basophilic Leukemia-2H3 (RBL-2H3) mast cells, the structure and interactive properties of Munc18 and Munc13 in respect to mast cell exocytosis were examined. Through knockdown and rescue approaches, results indicate that Munc18 protein is crucial for exocytosis of mast cells partly through regulating its cognate syntaxin partners such as syntaxin-3 and -11 for their protein level and trafficking. Independent knockdowns of syntaxin-3 and -11 demonstrate that syntaxin-3 is the key cognate syntaxin whose level and intracellular localization are regulated by Munc18. In addition, our data demonstrate that Munc13-4 plays an essential role in mast cell degranulation; mutational studies revealed that point mutations in C2 domains of Munc13-4 dramatically alter Ca2+-sensitivity of degranulation, whereas absence of Munc13-4 or multiple mutations in C2 domains result in almost complete loss of exocytosis from mast cells. Moreover, Munc13-4 mediates Ca2+-dependent regulation of fusion pore opening of single granule fusion events. Taken together, we postulate that both Munc18 and Munc13-4 are essential for mast cell exocytosis albeit their functions, therefore molecular mechanisms, are exerted in different stages of exocytosis.
Horticultural Hybrids: Plants, Women, and Rhetoric in Early Modern England
Keywords: ecocriticism
gender
horticulture
literature

This dissertation examines the rhetorical transformation of female bodies into plants and the gendering of plants in early modern English literature and science. Bringing gardening manuals and obstetrical treatises into conversation with a wide range of literary texts, such as Isabella Whitney’s A Sweet Nosgay, Mary Wroth’s The Countess of Montgomery’s Urania, John Milton’s Paradise Lost, and William Shakespeare’s The Winter’s Tale and Titus Andronicus, I argue that these horticultural metamorphoses occur when the generative potential of the female body threatens to elude patriarchal containment. Yet, I contend that the plant-women resist objectification by defying the conflation entirely, by wielding authority to metamorphose themselves into female-horticultural hybridity, or by discovering the surprising opportunity to embody new forms of discourse. Early modern ecocriticism and history of science typically detail the relationship between humans and nature, but my research reconceives that link by examining what happens when these two categories are rhetorically conflated. The resulting breakdown of boundaries reveals how early modern women and nature might evade patriarchal restrictions by becoming newly hybrid vegetal bodies capable of speaking from a dual subject position. The intermingling of horticulture and language in early modern England – where books could be gardens, forests, and posies, flowers could be powerful rhetoric, and grafting could be a graphic act of writing – creates room for this evasion to occur. I structure the project thematically, with an opening chapter on books as gardens, and subsequent chapters focusing on the female body as an enclosed garden, a flower, a fruit tree, and a forest tree. Metaphorical language creates these hybrid vegetal-female bodies, but this dissertation argues that the blurring of horticultural generation and literary or linguistic generation allows these feminized plant objects to regain authority over language and to remake themselves as subjects.
Employing Gas Challenges and Breathing Manoeuvres to Assess Microvascular Functional Dynamics
Keywords: Gas Challenge
Ischemic- Reperfusion Injury
Magnetic Resonance Imaging
Microvasculature
Vasomodulation
Vasoreactivity

Proper blood vessel function entails the transport of blood and modulation of perfusion in response to stimuli. This serves to maintain adequate blood pressure and nutrient delivery. The ability of blood vessels to modulate perfusion in response to demand is a key feature of microvascular integrity (MI). Loss of MI is a characteristic feature of endothelial dysfunction (ED) and is found in several conditions, including hypertension, chronic kidney disease (CKD) and diabetes. To date, most of the research on ED diagnosis has focused on the brain and although there is a clear link between cerebrovascular dysfunction and microvascular pathologies, little work has been done to diagnose extra-cranial ED. Assessment of MI necessitates two steps: a vasoactive stimulus to generate a response (i.e. vasoconstriction/ vasodilatation) and an imaging method to continuously monitor the response. The works presented in this thesis aim to further our understanding of microvascular reactivity with the aim of creating a non-invasive Magnetic Resonance Imaging (MRI) based technique to diagnose extra-cranial MD with the aid of a vasoactive gas challenge stimuli. To achieve this aim, we used a series of hypercapnic and hypoxic gas challenges to induce maximal hemodynamic responses so as navigate the spectrum of vessel calibre. We also employed a long life blood pool agent (Gadofosveset) to allow us to track the changes in vessel calibre. Using this agent, we could navigate the spectrum of vessel calibre in the high perfusion organs such as the kidney and low perfusion skeletal muscle. Furthermore, by employing a specific sequence of vasoactive gases we were able to assess the degree of ED in a hind limb ischemic rat model. Though still its infancy the works presented in this thesis offer us an introduction to the utility of using a gas challenge algorithm in conjunction with MRI to be used for the assessment of vessel health in a number of pathologies.
Search and Join Algorithms for Tables in Data Lakes
Keywords: data discovery
data lakes
data management
data science
query processing
search algorithms

Data lakes are repositories of data sets stored in their raw formats. Data lakes can be dumping grounds if users cannot find and utilize the data in them. In this thesis, we describe two problems in managing data lakes: searching for tables that can be joined, and auto-generating syntactic transformations for joining tables with join values of different formats. Given a query table and a join column, the first problem is defined as searching for tables that can be joined with the query table on the join column. Our contributions toward solving this problem are twofold: 1) an approximate search index (based on locality sensitive hashing) to support threshold-based search queries -- find tables that can join with more than a threshold percentage of the distinct join values in the query table; and 2) an exact search index that supports top-k search queries -- find the best k tables that cover the largest number of distinct join values. Both approaches use new data-aware optimizations to provide interactive query performance over real data lakes with millions of tables including many large tables (e.g., millions of rows). Ours is the first approach for searching for joinable tables and we show that it greatly outperforms previous approaches for computing set intersection (used for keyword search and other applications). We also published open source implementations of the joinable table search algorithms and benchmarks created using real data lakes. For the second problem, we propose a technique that generates transformations, without human input, for joining tables with different formats on the join columns. The technique uses a novel approach to pinpoint highly promising joinable row pairs, before using the pairs as input/output examples to perform a greedy search to find a good transformation. The technique scales to tables as large as 10K rows while still maintaining interactive speed. The solutions presented in this thesis make data lakes more searchable and usable, and allow data scientists to be efficient. These experimentally-validated solutions also create an avenue for new data science discoveries that are important in business and government decision-making.
Optimized PN Junctions and Three-dimensional Integration for Carrier-depletion Silicon Optical Modulators
Keywords: Flip-chip integration
Integrated optics
Modulators
Silicon photonics
Waveguide junctions

Silicon (Si) optical modulators are used for high speed electrical-to-optical conversion in transceivers for data communications. However, since the plasma dispersion effect in Si is weak, efficient Si modulators remain an outstanding challenge. Typical Si Mach-Zehnder modulators (MZMs) with lateral PN junctions have VpiL values around 2.5 V*cm and require a drive signal swing of 4-5 V peak-to-peak (Vpp). This leads to large device footprint, high power consumption, and a drive signal swing that is not usually complementary metal oxide semiconductor (CMOS) compatible. This thesis studies two approaches to advance the state of the art of Si optical modulators: vertically-engineered PN junctions to improve the modulation efficiency and three-dimensional (3D) integration to reduce the parasitics in photonic-electronic integration. For the first approach, we study the efficiency, loss, and bandwidth trade-off of different vertically-engineered junction profiles. Simulations show that the modulation efficiency is improved by folding the junction line in Si waveguide at the cost of a higher junction capacitance. Experimentally, a novel U-shaped PN junction is demonstrated to have a VpiL of 0.26 V*cm at -0.5 V bias, which is about 10 times more efficient compared to the typical lateral PN junction. The measured optical insertion loss is similar to that of a lateral junction. The designed U-shaped junction has been implemented in Si MZMs and Si microring modulators (MRMs). On-off keying and pulse amplitude modulation formats have been tested using Si MRMs with the designed U-shaped junction. For the second approach, a flip-chip bonded transmitter consisting of a CMOS driver and a Si MZM is demonstrated. The designed Si MZM, based on lateral PN junctions, has an electro-optic bandwidth of 26 GHz. The drive signal used to drive the 3D transmitter is no higher than 1 Vpp. High-speed operation of the transmitter at up to 50 Gb/s with a record-high extinction ratio of 8 dB is demonstrated with a power consumption of 553 mW. Overall, this thesis shows lumped electrode, high bandwidth, micron-scale Si MZMs can be realized. This development can lead to power efficient Si photonic transmitters with energy consumption around 140 fJ/bit supporting >100 Gb/s per channel.
Structural Investigations of Saposin/Hydrolase Systems
Keywords: acid ceramdiase
acid sphingomyelinase
interfcial catalysis
lipid storage disorder
saposin
sphingolipids degradation

The degradation of sphingolipids (SLs) in mammals relies on the interplay between a set of lysosomal hydrolases and their cofactor proteins, the saposins. The saposins are a group of small, non-enzymatic proteins that possesses strong lipid binding/solubilizing properties. They function as biological detergents that assist the soluble acid hydrolases in accessing to their membrane-bound lipidic substrates by two proposed modes of action. In the “solubilizer” model, saposins extract SLs into soluble saposin-lipid complexes that act as the substrates for the corresponding enzymes, and in the “liftase” model, the saposins remodel bilayer surfaces to enhance the activity of membrane-associated hydrolases. In this thesis, I first present the crystal structure of human acid sphingomyelinase, the enzyme responsible for the lysosomal degradation of sphingomyelin. This enzyme has a built-in saposin domain that is crucial for its membrane-binding ability, and the elucidation of this crystal structure provides valuable molecular details of a “liftase” system. Next, I described crystal structures of acid ceramidase (AC), a lysosomal enzyme that facilitates the degradation of ceramide at the water-membrane interface. This enzyme enters the lysosome as an immature precursor protein and undergoes a self-cleavage process to yield the catalytically active mature form. A comparison of the crystal structures of immature and mature AC reveals a dramatic structural rearrangement resulting in the exposure of a large hydrophobic surface for membrane binding. Finally, I place the work described in this thesis in the context of previously described saposin/hydrolase systems, leading to novel insights into the modes of action of these protein complexes on different types of target SLs. Collectively, these findings advance our understanding of the molecular mechanisms of lysosomal saposin/hydrolase systems in the degradation of SLs.