VictorJuiz/thesis huggingface dataset:
Bayesian Inference Framework for the Analysis of Biological Systems Applied to RNA Activation in Human Cells

In this work, we present in-depth applications of Bayesian probability theory to several problems of inference that are commonly encountered in modern biological research. The resulting inference framework is applied the analysis of kinetic models of a synthetic RNA activation system in mammalian cells. The main test system to which we apply our analysis involves the little-understood phenomenon of RNA activation, wherein small double-stranded RNAs that are transfected into cells increase the transcription rate of genes whose promoters are similar in sequence to the transfected RNAs. We design, build, and validate the first example of a synthetic promoter to be targeted by RNA activation. To model our RNA activation system, we begin by considering the problem of determining a cell population's growth parameters from cell count data collected over a time interval. We derive an approximation to the posterior probability density for the parameters that characterize an arbitrary model growth curve. We show that our approximation works well in most realistic parameter regimes, and that it can be implemented with good speed on modern processors. Our inference framework is applied to several test datasets in the simple case of a logistic growth model, and its results are compared to the commonly used least-squares estimation method. We then explore the fitting of arbitrary kinetic models to sets of flow cytometry data, which contain distributional information on cell fluorescence. We develop a software system that returns posterior probability densities for kinetic model parameters, and allows for different models to be compared for the quality of their fits. Our software allows the experimenter to probe the logical connections between the various parameters a model, and to draw informed conclusions as to its correctness in light of the data. We briefly discuss the conversion of the known literature values of some parameters into prior probability densities that may inform our reasoning. Finally, we show how to synthesize the solutions to these separate inference problems into a singe coherent conclusion that correctly weights the importance of each information source, and apply this holistic approach to model our synthetic RNA activation system.

Advisor: McMillen, David R
Loss of Sbds in Shwachman-Diamond Syndrome Murine Model Leads to Reduction of 80S Ribosomes and Altered Transcript Binding

Shwachman-Diamond syndrome (SDS) is an autosomal recessive disease characterized by growth retardation, exocrine pancreatic dysfunction, skeletal dysplasia, cognitive impairment and bone marrow failure. SDS is caused by mutations in SBDS (Shwachman-Bodian-Diamond syndrome). A recent model proposes that SBDS/Sbds functions together with EFL1/Efl1 to release EIF6/Eif6 from the pre-60S complex, enabling ribosomal subunit joining for translation initiation. To assess the protein synthesis deficiency that has been detected in SDS, I examined ribosomal profiles of murine fetal organs with the SDS-associated missense mutation, R126T (SbdsR126T/R126T). The SDS organ extracts revealed reduced 80S monosomes and preserved polysomes, with no ribosomal subunit imbalance compared to matched controls. Further, Eif6 was found to bind to both the 60S and 80S ribosome complexes in mutants in contrast to only 60S complexes in controls. To investigate these changes and to learn how the SDS translatome is affected, total and polysomal mRNAs of mutant and control samples were studied using cDNA microarray analyses. By comparing individual polysomal transcripts to respective total transcript levels, I found 799 transcripts (of 18,936 analyzed) with altered polysome loading in mutant fetal livers, with 634 being increased. Changes in polysome loading did not correspond with steady state protein levels, as indicated by proteome analysis using label-free mass spectrometry. Rather, these changes correlated with physical features of the transcripts, including 5' untranslated region composition as well as the lengths and nucleotide contents of the open reading frame and the 3' untranslated regions. Together, I conclude that the untimely release of Eif6 due to Sbds deficiency results in ribosomes with compromised translation initiation and that SDS disease phenotypes reflect protein synthesis insufficiency and the formation of sub-populations of â SDS ribosomesâ with non- or poor- translating capability.

Keywords: altered mRNA binding
non-translating ribosomes
polysome profile
Shwachmanâ Diamond syndrome
transcript length
Advisor: Rommens, Johanna M
Impact Behaviour of Hybrid Long Fibre Thermoplastic Composites

Impact strength is a critical property of composites in the auto industry by way of product service life, safety, and liability. The aim of this project is to arrive at a hybrid biocomposites of hemp-glass fibre-PP with high toughness. Long glass fibres are believed to increase impact strength of composites, and current literature has mainly focused on hand layup process of laminates and mats to achieve long fibres, whereas this work investigates the use of extrusion and GF roving. The hypothesis being tested is that the energy absorption of hybrid composites can be improved by increasing glass fibre length using an extrusion process. Process optimization resulted in a hybrid composite with notched impact strength of 131 Âą 12 J/m, tensile strength of 92 Âą 7 MPa, and flexural strength of 160 Âą 15 MPa produced at an optimum shear rate of 62 sec-1 while feeding glass fibre into a port before the vent. To enhance interaction of fibres and matrix, 5% MAPP coupling agent was added to the composite since the other examined surface treatments for natural fibres did not yield significant improvement of impact properties. The last objective for this thesis was to relate the work of fracture of hybrid composites to fibre and matrix properties using a theoretical model, since there is no experimental validation for the available models in literature. The model presented here uses the Rule of Mixtures model to incorporate matrix failure, fibre debonding and fibre pull out for short fibres, in addition to fibre stress redistribution for long fibres. Good agreement between the presented model predictions and experimental data was observed. For the case of hybrid composites with long fibres, the dominant failure mechanisms were fibre stress redistribution and matrix failure, while for the case of short fibre composites fibre pull-out and matrix failure were dominant. In order to produce hybrid composites with high work of fracture, the focus should be on fibre processing to arrive at an optimum length, aspect ratio, volume fraction, and good dispersion.

Keywords: Composite
Extrusion
Impact strength
surface treatment
Work of fracture
Advisor: Sain, Mohini
Digital Materialisms: Information Art In English Canada, 1910-1978

Digital Materialisms: Information Art In English Canada, 1910-1978 Adam Lauder Doctor of Philosophy Department of Art University of Toronto 2016 Abstract Information art has a long history in English Canada. The multidisciplinary production of Bertram Brooker (1888-1955) is paradigmatic of early-twentieth-century English-Canadian artists’ distinctive responses to, and interventions within, the channels of an emergent social formation characterized by an unprecedented circulation of “information.” Brooker’s counter-hegemonic renderings of information as a corporeal and qualitative alternative to the mathematical frameworks embraced by American peers cleared a path for a subsequent generation of information artists inspired by the percepts of Marshall McLuhan (1911-1980), notably the Vancouver-based N.E. Thing Co. Ltd. (1966-1978). Like Brooker before them, NETCO’s co-presidents would attribute somatic and ontological meanings to information that trouble the cognitive, linguistic and structuralist frameworks conventionally mobilized by discussions of Conceptual art. In tracing the sources of this discourse network to the Canadian-born British proto-media theorist Wyndham Lewis (1882-1957), as well as its subterranean legacy in the Postminimalism of Robert Smithson (1938-1973), this study simultaneously troubles essentializing narratives of English-Canadian identity that problematically project representations of Canadianicity onto the territorial borders, and terrain (or “landscape”), of the nation state. Inspired in equal measure by recent developments in media archaeology and a resurgent scholarly interest in McLuhan, detailed investigations of discrete information media and instrumentalities are woven into a trajectory of progressive “informationalization” coterminous with the rise of an information society. Through original readings of archival materials and other primary sources, this dissertation argues for a revised understanding of information art produced in and beyond the borders of English Canada as articulating a critique of transcendence. Artists and thinkers implicated in the common “discourse network” delineated in these pages harnessed information concepts and information media to express shared visions of immanence. This dissertation historicizes and marterializes these non-technological visions of information by undertaking an archaeology of specific media and discourses.

Keywords: Canadian art
Conceptual art
Harold A. Innis
Henri Bergson
Information art
Marshall McLuhan
Advisor: Legge, Elizabeth
User-centered Design Approach to the Development and Pilot Testing of a Smartphone App To Support Real-time Pain Management for Adolescents with Cancer

It is estimated that 49-96% of adolescents with cancer will experience pain related to the disease and/or associated invasive procedures and treatments. Pain negatively impacts adolescent health-related quality of life (HRQL) and is associated with long-term morbidity. In response, a smartphone-based pain app, called Pain Squad+, capable of providing adolescents with real-time pain management support was developed and evaluated. Using user-centered methods, research aims were to utilize iterative cycles of usability testing with adolescents with cancer to refine the app (Study 1), to evaluate the ability to implement the Pain Squad+ app in a hypothesis-testing trial (Study 2), and to obtain estimates of treatment effects on adolescent health outcomes (Study 2). In Study 1, iterative cycles of usability testing with 16 adolescents were used to refine the Pain Squad+ app to ensure it was easy to use, easy to understand, efficient, and acceptable to adolescents. In Study 2, 33 adolescents used the app for 28-days, receiving real-time self-management advice and clinical support from a nurse dependent on self-reported pain. Acceptability of the intervention assessed quantitatively and qualitatively was high. The study accrual percent was 75% and the withdrawal percentwas 3%. Technical malfunctioning of the app was rare. The nurse received pain-related emails from 39% adolescents with a mean time to follow-up of 62.5 hours (SD=55.5). Outcome assessment piloting was successful with a mean of 94.9% (SD=4.3) of baseline and 84.3% (SD=31.0) of post-study questions completed. Adherence to pain reporting was 69.0Âą40.8%. Significant trends in improvement in pain intensity and HRQL were observed (p

Keywords: Adolescent
Cancer
mHealth
Pain management
Pilot study
Usability
Advisor: Stinson, Jennifer N
Principles and Practices of Ontology Reuse

Reusability has always been a defining characteristic of ontologies; it is the key to their supposed benefit of shareability, and the answer to the difficulty of their development. Consequently, reuse is a crucial aspect in the paradigm of ontologies. The vision for reuse is a state in which design via reuse occurs whenever it is possible. In such a state, no unnecessary design work is ever performed, and the supposed benefits of ontologies will naturally result. Unfortunately, the vision for reuse is not feasible at the time of this writing. Reuse is currently a difficult, somewhat ad-hoc process with unpredictable results, therefore it is often not a viable alternative to designing an ontology from-scratch. This thesis addresses these issues by reducing the barriers and increasing the motivation for reuse. These objectives are achieved by way of 3 key contributions: (1) rigorous techniques for reuse, (2) a formal definition of reuse, and (3) a comprehensive architecture for reuse. Rigorous techniques are designed and presented in such a way as to minimize the demands on the developer, thereby reducing the barriers resulting from the difficulty of the task. The formal definition of reuse is applied to make the benefits of shareability and reduced design work more tractable for the developer, thereby increasing the motivation to design via reuse when appropriate. Finally, the comprehensive architecture describes the infrastructure necessary to apply the collection of solutions presented here in order to simplify their adoption. Beyond this, we consider ways in which the solutions presented here might be extended as the practice of ontology reuse evolves. The work contained here provides a solid foundation upon which the vision for reuse may be achieved and sustained.

Keywords: design
logic
ontology
requirements
reuse
Advisor: Grüninger, Michael
Listening to Unheard Voices: Muslim Canadian Perceptions and Experiences of Domestic Violence and Seeking Help

This research was designed to contribute to an understanding of intimate partner violence perpetration and help-seeking behaviours among Muslim immigrants. The mandate of this study is not to ostracize Muslims or cast judgement for or against religious beliefs, but to better understand how religion and culture might interact with other factors to influence domestic violence perpetration. This understanding is critical for the development and implementation of effective intervention. In this study, I used a mixed-method to explore how religious perspectives, patriarchal attitudes toward women, cumulative childhood abuse and acculturation might be related to domestic violence and help-seeking at both attitudinal and behavioural levels. In a quantitative study, survey data was collected from 131 Muslim students. In a qualitative study, semi-structured interviews were conducted with 8 abusive Muslim men. The results of both studies were converging: religiosity predicted acceptance of violence and intimate partner violence via non-egalitarian attitudes toward women. Contrary to intergenerational theories of family violence, cumulative childhood experiences of abuse were not related to either acceptance or experiences of violence or help-seeking behaviours. In the quantitative study, acculturation also moderated the relationship between non-egalitarian attitudes towards women and domestic violence. The relationships were stronger for participants who were at lower levels of acculturation, compared with those at higher levels. Similarly, in the qualitative study, abusive men indicated that women acculturated faster to Canadian society and were empowered by Canadian regulations. Different levels of acculturation were considered threatening to men's positions as heads of the family and seemed to contribute to conflict and violence in the relationship. Non-egalitarian attitudes toward women also predicted beliefs toward help-seeking through acceptance of violence. Participants with higher levels of acculturation showed more egalitarian attitudes and tendencies toward help-seeking behaviours. The qualitative study also revealed that Muslim men were reluctant to seek formal help due to their traditional gender role ideology, their lack of familiarity with available services and their doubts about the effectiveness of those services. Findings around both domestic violence and help-seeking behaviours have applications for effective prevention, as well as community-based and culturally-based intervention programs for Muslim immigrants.

Keywords: Acculturation
Attitude toward Women
Help Seeking
Intimate Partner Violence
Muslim Immigrants
Religiosity
Advisor: Scott, Katreena
Understanding How Life-history Traits and Environmental Gradients Structure Diversity

Determining how diversity is distributed through space and time is a fundamental goal of ecology. My research tested how speciesâ life-history traits structure diversity at landscape and broader scales and over time. I first asked how traits related to seed dispersal shape plant diversity in a naturally fragmented landscape by testing the relationship between diversity and patch characteristics (size and isolation) for species with different dispersal modes. Dispersal mode altered outcomes predicted from theory â while fragment isolation had a negative effect on wind-dispersed species, it did not influence the diversity of animal-dispersed species. I then examined how zooplankton traits (body size and dormancy) correlate with species distributions at a large scale using lakes across an 1800 km north-south gradient in western Canada. Despite predictions that body size should decrease with latitude and low temperatures, I found only weak evidence for any effect of latitude on inter- and intra- specific body size. Zooplankton dormancy dynamics are virtually impossible to test through sampling, yet dormancy underpins seasonal fluctuations in abundance and long term persistence, and it is expected to vary with climate. I therefore used an experimental approach to test how temperature and photoperiod affect hatching rates of dormant eggs from lakes across the latitudinal gradient. My results suggest that mismatches between temperature and photoperiod, as predicted to result from climate change, could drive latitude-dependent shifts in zooplankton emergence. Finally, I examined the temporal stability of diversity across the same latitudinal gradient by examining species colonization and extinction over 50 years. I found that low-latitude communities are increasingly diverse and comprised of small-bodied species despite more rapid temperature change at higher latitudes. Overall, my research has implications for how global changes, such as fragmentation and climate change, alter diversity by changing the viability of specific life-history strategies.

Keywords: climate change
dispersal
dormancy
latitude
metacommunity
zooplankton
Advisor: Gilbert, Benjamin
Does the Public Availability of Market Participants' Trading Data Affect Firm Disclosure? Evidence from Short Sellers

Market transparency affects how much information investors can glean by observing market data, while firm transparency determines the extent to which outsiders can gain access to firms’ inside information. Each type of transparency has been independently studied in the prior literature. The relation between the two, however, is not well understood. By making use of a natural experiment in which the transparency of short selling in the market place improved exogenously, this paper provides initial evidence on the consequences of improving market transparency on a firm’s transparency, and empirically tests recently developed dynamic disclosure theory. Using a unique difference-in-differences design, I illustrate that making short-interest data publicly available increases firms’ voluntary disclosure. This outcome suggests that revealing sophisticated investors’ trading positions has a disciplining effect on firm disclosure. Additional tests reveal that this disciplining effect exists for disclosures both before and after the short-interest release. Finally, to further understand firms’ rationale to disclose more, in cross-sectional analyses I show that the positive effect of making short interest public on firm disclosure increases with short-interest level and litigation risk, but decreases with the real-option value of withholding news. This paper highlights the importance of market transparency in improving firms’ information environment.

Advisor: Hope, Ole-Kristian
Characterization of the Microbial Community Composition and Benzene Activation Mechanisms in Anaerobic Benzene-Degrading Enrichment Cultures

Benzene is a carcinogenic petroleum hydrocarbon that is prevalent and particularly persistent in anoxic aquifers. It can be biodegraded under anaerobic conditions; however, this process is relatively slow compared to aerobic conditions, and the microorganisms and the pathways involved therein remain poorly understood. The objectives of this thesis were to accelerate the microbially-mediated benzene degradation, to characterize benzene-metabolizing microbial communities, and to identify the biochemical mechanisms involved in anaerobic benzene activation. The growth rate and substrate range of the laboratory enrichment cultures were investigated. Conclusive evidence was also obtained to support that a Deltaproteobacterium sp. (ORM2) and a Peptococcaceae sp. are the microorganisms directly involved in benzene activation. The Deltaproteobacterium ORM2 was observed to dominate under methanogenic conditions while Peptococcacceaea sp. dominated only under nitrate-reducing conditions. Syntrophic partners in these cultures were also identified. Organisms belonging to Parcubacteria were identified in all analyzed cultures and observed to grow up to 15% of the total bacteria. This is the first time a member of this clade has been observed to grow in the laboratory. In nitrate-reducing cultures, transcripts related to a putative anaerobic benzene carboxylase (abcDA) were specific to benzene, supporting carboxylation as the benzene activation mechanism in these cultures. The benzene-activating genes and mechanism in the methanogenic cultures remain unknown. Methods to extract protein from the cultures for biochemical assays were developed, and lysis using a French pressure cell press yielded crude extracts with the highest biochemical activity. Assays were developed to test various enzymatic steps, including benzoyl-CoA ligation, benzene carboxylation and carbonylation. Benzoyl-CoA ligase activity was detected in nitrate-reducing, but not in methanogenic cultures, consistent with the absence of this gene in ORM2 genome. Further assay development is required for detecting benzene transformation; however, these first experiments have provided some guidance for the next steps in functional analysis.

Keywords: anaerobic biodegradation
benzene
bioremediation
metatranscriptome
microbial dark matter
petroleum hydrocarbon
Advisor: Edwards, Elizabeth A
Waters of the Exodus: Jewish Experiences with Water in Ptolemaic and Roman Egypt

This study examines how the fluvial environment shaped the writing of Jewish narratives in Ptolemaic and Roman Egypt (300 BCE – 115 CE). It focuses on four texts that narrate the Exodus story and analyzes them in terms of how water in Egypt is described and how elements of the environment—such as the Nile or the Red Sea—are characterized in their retellings. I argue that the natural environment informed Jewish writings through the incorporation of new fluvial terminology, development of different conceptions of water, and the adoption of positive attitudes towards the environment. These features, found specifically in texts composed in Egypt, demonstrate the power of the environment to shape a foundational Jewish narrative. Previous studies on the Jews of Egypt have examined their lives in political, social, or economic terms, with little acknowledgement of the physical environment and its role in daily and religious life. By focusing on water, this work traces the emergence of distinct practices developed in response to the environment, such as the location of places of worship and emerging employment opportunities. Such characteristics distinguish the communities of Egypt from both other Jews and non-Jews. Additionally, the project speaks to larger trends in the field of Biblical Studies that focus on the materiality of everyday life.

Keywords: Biblical Interpretation
Egypt
Environment
Hellenistic Judaism
Jewish History
Water
Advisor: Newman, Judith H