VictorJuiz/thesis huggingface dataset:
Gait Asymmetry Post-stroke

This thesis examined post-stroke gait asymmetry: a prevalent issue and one that has a number of associated negative consequences (e.g. challenged balance control, gait inefficiencies, increased risk of musculoskeletal injury to the non-paretic limb and decreased overall activity levels). This thesis is comprised of three studies that focused on 1) how gait symmetry should be measured, 2) how gait asymmetry may change in the long term post-stroke and 3) whether gait asymmetry is responsive to a rehabilitation intervention. A comparison of the most common expressions of spatiotemporal gait symmetry revealed that the simple symmetry ratio calculation was most appropriate on the basis of ease of interpretation and clinical usefulness. Swing time, stance time and step length were found to be the most useful gait parameters to assess for symmetry. Although related, swing time, stance time and step length ratios exhibit variation in the discrimination of post-stroke individuals, in their inter-relationships and in their relationship velocity. When when used together, swing time, stance time and step length asymmetry ratios may provide a complementary picture of the gait pattern and the quality of gait control. It was also demonstrated that swing time and stance time asymmetry were worse in later stages post-stroke when assessed cross-sectionally. In contrast, gait velocity did not exhibit this pattern. These results indicate that the control of gait (symmetry) may decline over time post-stroke, independent from the capacity for gait which remains constant (velocity). This dissociation in characteristics supports the concept that these two variables (symmetry and velocity) may represent separate features of post-stroke gait. Finally, individuals with sub-acute stroke are capable of altering the temporal symmetry of their gait in response to visual biofeedback. Individuals with sub-acute stroke differ in terms of the strategy they employ in response to biofeedback and the observed improvements in gait symmetry were not always achieved in the desired manner: increased use of the paretic lower extremity. This thesis presents new information regarding the asymmetrical nature of post-stroke gait. Future work may extend these findings to develop a comprehensive approach to gait measurement as well as gait interventions that encourage increased paretic limb use instead of compensatory behaviour.

Keywords: stroke
gait
Advisor: McIlroy, William E.
The Development of Elastomeric Biodegradable Polyurethane Scaffolds for Cardiac Tissue Engineering

In this work, a new polyurethane (PU) chain extender was developed to incorporate a Glycine-Leucine (Gly-Leu) dipeptide, the cleavage site of several matrix metalloproteinases. PUs were synthesized with either the Gly-Leu-based chain extender (Gly-Leu PU) or a phenylalanine-based chain extender (Phe PU). Both PUs had high molecular weight averages (Mw > 125,000 g/mol) and were phase segregated, semi-crystalline polymers (Tm ~ 42°C) with a low soft segment glass transition temperature (Tg < -50°C). Uniaxial tensile testing of PU films revealed that the polymers could withstand high ultimate tensile strengths (~ 8-13 MPa) and were flexible with breaking strains of ~ 870-910% but the two PUs exhibited a significant difference in mechanical properties. The Phe and Gly-Leu PUs were electrospun into porous scaffolds for degradation and cell-based studies. Fibrous Phe and Gly-Leu PU scaffolds were formed with randomly organized fibers and an average fiber diameter of approximately 3.6 µm. In addition, the Phe PU was electrospun into scaffolds of varying architecture to investigate how fiber alignment affects the orientation response of cardiac cells. To achieve this, the Phe PU was electrospun into aligned and unaligned scaffolds and the physical, thermal, and mechanical properties of the scaffolds were investigated. The degradation of the Phe and Gly-Leu PU scaffolds was investigated in the presence of active MMP-1, active MMP-9, and a buffer solution over 28 days to test MMP-mediated and passive hydrolysis of the PUs. Mass loss and structural assessment suggested that neither PU experienced significant hydrolysis to observe degradation over the course of the experiment. In cell-based studies, Phe and Gly-Leu PU scaffolds successfully supported a high density of viable and adherent mouse embryonic fibroblasts (MEFs) out to at least 28 days. Culturing murine embryonic stem cell-derived cardiomyocytes (mESCDCs) alone and with MEFs on aligned and unaligned Phe PU scaffolds revealed both architectures supported adherent and functionally contractile cells. Importantly, fiber alignment and coculture with MEFs improved the organization and differentiation of mESCDCs suggesting these two parameters are important for developing engineered myocardial constructs using mESCDCs and PU scaffolds.

Keywords: Biodegradable Polyurethanes
Cardiac Tissue Engineering
Matrix Metalloproteinases
Electrospinning
Embryonic Stem Cells
Cardiomyocytes
Fibroblasts
Fibrous Scaffolds
Advisor: Woodhouse, Kimberly A.
A Mass Spectrometry Approach to Ligand Identification for Orphan Fly and Human Nuclear Receptors

The nuclear receptor superfamily is responsible for regulating the expression of genes involved in development, reproduction and metabolism. These transcription factors control the expression of their target genes through the binding of small molecule regulators to their ligand binding domains. Classical nuclear receptors include the steroid receptors, which bind endocrine hormones and have been important targets of pharmaceutical intervention. However, approximately one half of the human nuclear receptors remain orphans and are without known cognate ligands. Focusing on the Drosophila orthologues of these orphan receptors, this project used mass spectrometry to identify the chemical diversity associated with the receptors following expression in recombinant systems. In a genome-wide screen of Drosophila nuclear receptors, this approach identified co-purifying molecules with a number of receptors. The physiological relevance of these putative ligand/receptor pairs was determined through biochemical analysis, in vivo characterization and structure determination. Ligand(s) or the ligand state was identified for the Drosophila receptors: DHR3, DHR96, E75, Ftz-f1 and USP. Of these, three were validated through the efforts of this project, and independent groups confirmed the remaining two. The most significant findings were the discoveries that the fly nuclear receptor E75 is regulated by heme, gas and redox, and that there is a similar regulatory scheme in the human orthologues, Reverbα and β. Furthermore, crystallization of the heme-bound Rev-erbβ ligand binding domain was also achieved, and this provided key insights into the mechanism of ligand regulation for the Rev-erbs. This project highlighted the role of nuclear receptors in metabolic surveillance. The ligands/signals identified in association with these receptors include: cholesterol, dehydrocholesterol, heme, NO, CO, redox and phospholipids. Unlike the classical steroid hormones, these are not dedicated signaling molecules, but instead are key substrates or products of metabolism. In the context of nuclear receptor signaling, I hypothesize that these metabolites serve as metabolic indicators/signals in the regulation of development and metabolism. Furthermore, four of these Drosophila receptors comprise the ecdysone-response pathway in the developing fly. Taken together, this suggests that both the metabolic state of the organism and steroid hormones drive nuclear receptor regulation of development.

Keywords: nuclear receptor
orphan
E75
Rev-erb
heme
nitric oxide
crystal structure
DHR3
DHR96
cholesterol
metabolism
ligand
Drosophila
human
mass spectrometry
Advisor: Edwards, Aled M.
Constructions, Lower Bounds, and New Directions in Cryptography and Computational Complexity

In the first part of the thesis we show black-box separations in public and private-key cryptography. Our main result answers in the negative the question of whether we can base Identity Based Encryption (IBE) on Trapdoor Permutations. Furthermore, we make progress towards the black-box separation of IBE from the Decisional Diffie-Hellman assumption. We also show the necessity of adaptivity when querying one-way permutations to construct pseudorandom generators á la Goldreich-Levin; an issue related to streaming models for cryptography. In the second part we introduce streaming techniques in understanding randomness in efficient computation, proving lower bounds for efficiently computable problems, and in computing cryptographic primitives. We observe [Coo71] that logarithmic space-bounded Turing Machines, equipped with an unbounded stack, henceforth called Stack Machines, together with an external random tape of polynomial length characterize RP; BPP an so on. By parametrizing on the number of passes over the random tape we provide a technical perspective bringing together Streaming, Derandomization, and older works in Stack Machines. Our technical developments relate this new model with previous works in derandomization. For example, we show that to derandomize parts of BPP it is in some sense sufficient to derandomize BPNC (a class believed to be much lower than P ⊆ BPP). We also obtain a number of results for variants of the main model, regarding e.g. the fooling power of Nisan's pseudorandom generator (PRG) [Nis92] for the derandomization of BPNC 1, and the relation of parametrized access to NP-witnesses with width- parametrizations of SAT. A substantial contribution regards a streaming approach to lower bounds for problems in the NC-hierarchy (and above). We apply Communication Complexity to show a streaming lower bound for a model with an unbounded (free-to-access) pushdown storage. In particular, we obtain a nΩ(1) lower bound simultaneously in the space and in the number of passes over the input, for a variant of inner product. This is the first lower bound for machines that correspond to poly-size circuits, can do Parity, Barrington's language, and decide problems in P − NC assuming EXP ≠ PSPACE. Finally, we initiate the study of log-space streaming computation of cryptographic primitives. We observe that the work on Cryptography in NC0 [AIK06a] yields a non-black-box construction of a one-way function computable in an O(log n)-space bounded streaming model. Also, we show that relying on this work is in some sense necessary.

Keywords: computational complexity
cryptography
Advisor: Rackoff, Charles
Making Participation Work: A Grounded Theory Describing Participation in Phase I Drug Trials from the Perspective of the Healthy Subject

A qualitative research study was conducted with people who had participated as healthy subjects in phase I drug trials at commercial research facilities, in order to develop a better understanding of their perspective regarding research participation. The participants were recruited using online advertisements posted on the University of Toronto student website (www.my.utoronto.ca) and NOW Magazine online. Thirty-one subjects were interviewed. The audiotaped interviews were transcribed and analyzed using grounded theory methods. A grounded theory was developed that describes the process of participation and the main factors affecting the experience of participation, from the perspective of healthy subjects. The theory, called Making Participation Work, explains how healthy subjects frame participation as an income earning opportunity, and how this framing shapes their behaviour with regard to participation. Participants expressed a range of attitudes about the experience of participation, from very positive to very negative. The main factor affecting the experience is the perceived net burden, which is in turn affected by the degree to which subjects find personal control over their participation. Net burden and finding personal control were both affected by the degree to which subjects felt valued by research staff, and by whether subjects had trust in the research enterprise. Although subjects framed participation as work, the relationship with the study doctors and nurses was viewed as clinical. Most subjects are generally trusting that participation in phase I drug trials is safe. These findings suggest that models of research participation assuming participation motivated by altruism or potential therapeutic benefit cannot accommodate the attitudes and behaviours of healthy subjects in phase I drug trials. New models must be developed which account for the framing of participation as work, while being sensitive to the trust that healthy subjects place in the research enterprise.

Keywords: research ethics
bioethics
healthy volunteers
payment
research subjects
Advisor: Hebert, Philip
Story Writing Development from Grades 4 to 6: Do Language Status and Reading Profile Matter?

The current longitudinal research examined the story-writing development of students from Grades 4 to 6 (N = 178). All students began formal schooling in English in Grade 1. Students were classified in Grade 4 as typical readers (scoring above the 40th percentile in both decoding and reading comprehension; n = 72), poor decoders (scoring below the 30th percentile in decoding; n = 53), or poor comprehenders (scoring above the 40th percentile on decoding but below the 30th percentile, relative to their language group, in reading comprehension; n = 26). Students who spoke English as a first language (EL1s) and English language learners (ELLs) were proportionally represented in each reading group. A series of repeated measures ANOVAs tested the effects of language and reading group on students’ cognitive, linguistic and literacy development. Despite the fact that ELLs did not achieve native-like English language proficiency, showing delays in vocabulary and reading comprehension, they matched their EL1 peers in all other areas of cognitive and literacy development, including story-writing. Both EL1s and ELLs developed story-writing skills in a similar manner, showing significant growth from Grade 4 to Grade 6. Typically developing ELLs were thus able to attain age-appropriate story-writing levels. Additionally, poor decoders and poor comprehenders generally showed similar profiles of strengths and weaknesses, regardless of whether English was their first or second language. The major difference was that ELL poor comprehenders were more likely to have longstanding reading comprehension problems, while many EL1 poor comprehenders had improved by Grade 6. In general, poor decoders displayed more pervasive difficulties across cognitive, linguistic and literacy domains, while poor comprehenders had specific weakness in nonverbal reasoning, receptive vocabulary and listening comprehension. Nevertheless, both reading disorder groups had significant difficulties in story-writing, struggling with the mechanics of writing, sentence structure, and overall story organization. Regression analyses indicated that cognitive, linguistic and language skills were strong concurrent and longitudinal predictors of story-writing. However, the strongest predictor of Grade 6 story-writing skill was Grade 4 story-writing performance, suggesting that story-writing skills tend to be relatively stable over time. The results generally support the ‘simple view of writing’ (Berninger, 2000). Practical recommendations for assessment and instruction are presented.

Keywords: writing development
reading disorders
English Language Learners
poor comprehenders
poor decoders
Advisor: Geva, Esther
Race, Gender and Colonialism: Public Life among the Six Nations of Grand River, 1899-1939

Six Nations women transformed and maintained power in the Grand River community in the early twentieth century. While no longer matrilineal or matrilocal, and while women no longer had effective political power neither as clan mothers, nor as voters or councillors in the post-1924 elective Council system, women did have authority in the community. During this period, women effected change through various methods that were both new and traditional for Six Nations women. Their work was also similar to non-Native women in Ontario. Education was key to women’s authority at Grand River. Six Nations women became teachers in great numbers during this period, and had some control over the education of children in their community. Children were taught Anglo-Canadian gender roles; girls were educated to be mothers and homemakers, and boys to be farmers and breadwinners. Children were also taught to be loyal British subjects and to maintain the tradition of alliance with Britain that had been established between the Iroquois and the English in the seventeenth century. With the onset of the Great War in 1914, Six Nations men and women responded with gendered patriotism, again, in ways that were both similar to Anglo-Canadians, and in ways that were similar to traditional Iroquois responses to war; men fought and women provided support on the home-front. Women’s patriotic work at home led to increased activity in the post-war period on the reserve. Six Nations women made use of social reform organizations and voluntary associations to make improvements in their community, particularly after the War. The Women’s Institutes were especially popular because they were malleable, practical, and useful for rural women’s needs. Women exerted power through these organizations, and effected positive change on the reserve.

Keywords: Six Nations
history
education
gender
first nations
colonialism
Advisor: Morgan, Cecilia
Visual Object Recognition Using Generative Models of Images

Visual object recognition is one of the key human capabilities that we would like machines to have. The problem is the following: given an image of an object (e.g. someone's face), predict its label (e.g. that person's name) from a set of possible object labels. The predominant approach to solving the recognition problem has been to learn a discriminative model, i.e. a model of the conditional probability P(l|υ) over possible object labels l given an image υ. Here we consider an alternative class of models, broadly referred to as generative models, that learns the latent structure of the image so as to explain how it was generated. This is in contrast to discriminative models, which dedicate their parameters exclusively to representing the conditional distribution P(l|υ). Making finer distinctions among generative models, we consider a supervised generative model of the joint distribution P(υ, l) over image-label pairs, an unsupervised generative model of the distribution P(υ) over images alone, and an unsupervised reconstructive model, which includes models such as autoencoders that can reconstruct a given image, but do not define a proper distribution over images. The goal of this thesis is to empirically demonstrate various ways of using these models for object recognition. Its main conclusion is that such models are not only useful for recognition, but can even outperform purely discriminative models on difficult recognition tasks. We explore four types of applications of generative/reconstructive models for recognition: 1) incorporating complex domain knowledge into the learning by inverting a synthesis model, 2) using the latent image representations of generative/reconstructive models for recognition, 3) optimizing a hybrid generative-discriminative loss function, and 4) creating additional synthetic data for training more accurate discriminative models. Taken together, the results for these applications support the idea that generative/reconstructive models and unsupervised learning have a key role to play in building object recognition systems.

Keywords: machine learning
computer vision
Advisor: Hinton, Geoffrey
Transcriptional Regulation in Synthetic Gene Networks

The study of synthetic gene regulatory networks allows the isolation and investigation of components and motifs in natural regulatory networks. Many synthetic gene networks are regulated at the transcriptional level. In this work, two methods of regulating gene expression at the transcriptional level were studied with the objective of gaining finer control over network behaviour. The first approach focuses on activation and repression of promoters by transcription factors. A synthetic repressor-activator network was engineered using the cI and cro genes and the PRM promoter from bacteriophage λ. The cI and cro genes activated and repressed PRM, respectively, and the monomeric red fluorescent protein (mrfp) gene reported PRM activity. Experimental testing showed an increase in mrfp expression in response to CI, a decrease in mrfp expression in response to Cro, and a differential output that reflected the relative concentrations of CI and Cro when both inputs were applied together. A positive feedback network was then created by placing a cI gene downstream of PRM. The network showed increased expression in response to CI and decreased expression in response to Cro. A negative feedback network was created by placing a cro gene downstream of PRM. Experimental testing showed decreased mrfp expression in response to both inputs. The second approach employed two methods for tuning expression levels without modifying the genes or promoters. First, using a series of networks with tandem mrfp genes under the control of the PLtet0-1 promoter, it was demonstrated that magnitude and range of expression levels could be tuned by adjusting the number of genes in the operon. A network was tuned using this principle by placing luxR genes in tandem to increase the activity of the luxPR promoter. It was then demonstrated that the level of gene expression could be varied through the placement of the gene within an operon. Operons that were three, five and seven genes and contained one green fluorescent protein gene in the first, middle, or end position were created. By comparing green fluorescence levels in induced and uninduced networks, it was found that the gene closest to the promoter was the most inducible.

Keywords: synthetic biology
genetic circuits
Advisor: Truong, Kevin