VictorJuiz/thesis huggingface dataset:
A Comparative Study of Quality of Life in Patients with Low-and Intermediate-risk Prostate Cancer Treated at a Single Institution: Stereotactic Radiotherapy vs. High dose-rate Brachytherapy Monotherapy vs. High dose-rate Brachytherapy Boost

This retrospective cohort analysis aims to compare health-related quality of life (HRQoL) deterioration at 12 months in 648 low-and intermediate-risk prostate cancer (PCa) patients treated with three radiation strategies: stereotactic ablative radiation therapy (SABR), high dose-rate brachytherapy (HDR) monotherapy and HDR boost. Urinary, bowel and sexual HRQoL were prospectively measured at baseline and 12 months using the Expanded Prostate Index Composite (EPIC). A minimally important difference (MID) was defined as a deterioration of HRQoL scores at 12 months compared to baseline â Ľ 0.5 standard deviation of baseline score. Univariate and multivariable logistic regression analyses using generalized estimating equations were used to compare the proportion of patients having MID between groups. SABR and HDR monotherapy were associated with less deterioration in the urinary (OR:0.543, 95%CI:0.320-0.922, p-value=0.024, OR: 0.468, 95%CI:0.432-0.507, p-value

Keywords: prostate cancer
Quality of life
radiation therapy
Advisor: Bezjak, Andrea
Loblaw, Andrew
Ileal Fatty Acid Sensing Mechanisms Regulate Glucose Homeostasis In Vivo

Long-chain-fatty acids (LCFAs) are found in the diet, whereas short-chain fatty acids (SCFAs) are byproducts of fermentation in the distal intestine. It remains to be determined if the ileum regulates glucose production (GP). Since the GLP-1 receptor (GLP-1R) on vagal afferents is near intestinal GLP-1 secretion, receptor activation and vagal firing may mediate the effects of FAs. Intraileal LCFAs oleic acid (OA) and linoleic acid (LA), and SCFA propionate infusions decreased GP during the basal insulin-euglycemic clamp. The GP lowering effect of OA and LA required LCFA-CoA formation where the GP lowering effect of propionate was dependent on ileal GPR43 signaling, demonstrated by inhibitor co-infusion or targeted knockdown approaches, respectively. The effects of FA infusions were diminished with coinfusion of exendin-9, a GLP-1R antagonist, or tetracaine, a local anesthetic. Collectively, LCFAs and SCFA activate an ileal GLP-1R dependent neuronal network to lower GP via LCFA-CoA formation or GPR43 activation, respectively.

Keywords: Diabetes
glucagon-like peptide-1
glucose production
ileum
intestine
rats
Advisor: Lam, Tony KT
Controlled Release as a Strategy to Prevent Solution-mediated Phase Transformation in Amorphous Solid Dispersions: Effect of Dosage Form Design

The purpose of this study was to define the limits of developing a controlled-release amorphous solid dispersion (CRSD) system intended for enhancing the bioavailability of poorly water soluble drugs. Feasibility of multiple solid oral CRSD dosage form designs, such as spray dried powders, coated beads and compressed matrices (dry granulations and tablets) was evaluated. Solid dispersion powders were characterized in terms of ability to establish and maintain amorphicity in the dry form (by DSC and XRD) and ability to circumvent events leading to solution-mediated phase transformation (SMPT), or recrystallization during dissolution. While all dosage forms could successfully be produced with the amorphous dispersion, great differences in dissolution/recrystallization profiles were found, depending on how the controlled release agent was incorporated. These studies reveal that when designing a solid dispersion system, greater benefit can be derived by selecting the appropriate dosage form design, granting the formulator the much sought-after control over the challenge of SMPT.

Keywords: controlled release
dosage form design
poorly soluble drugs
solid dispersion
Advisor: Wu, Xiao Y
Defining the Role of Hedgehog-GLI Signaling in the Renal Cortical Stroma

In the mammalian kidney, Foxd1-positive stroma interacts with nephron progenitors to control nephrogenesis. Here we establish a non-cell autonomous role for stromal-Hedgehog (HH) signaling in controlling nephron progenitor differentiation and self-renewal. Stromal-specific inhibition of Smo, the HH signal transducer, results in an expanded domain of nephron progenitors and an increase in cell proliferation. Smo-deficient kidneys exhibit a specific inhibition in the formation of renal vesicles, a nephron intermediary structure. In parallel, Lim1 expression, a requirement for the progression of nephrogenesis, is decreased. HH signaling mediates its downstream effects by promoting GLI transcriptional activator levels while inhibiting GLI3 processing to a transcriptional repressor (GLI3R). Deletion of Gli3 in Smo-deficient mice normalized kidney volume and nephron number. Stromal-specific expression of Gli3R (obligate and conditional) phenocopies Smo-deficient mice, thus further supporting a deleterious role for GLI3R in the stroma. Together, our results provide novel insight into HH-GLI dependent interactions within the nephrogenic niche.

Keywords: Foxd1
hedgehog
kidney development
nephrogenesis
stroma
Advisor: Rosenblum, Norman D
Processing of Emotions in Speech in Healthy Older and Young Adults

Emotions in speech are conveyed through the lexical content and prosody. With increasing age, healthy older adults have trouble recognizing affective prosody, however, literature pertaining to the concurrent role of lexical content and prosody in emotion processing is scarce. Therefore, this study examines the role of lexical content and prosody in emotion recognition in healthy older and young adults. Two different versions of a novel tool, the Test for Recognition of Emotions in Speech or T-RES, were used to study emotion processing in spoken language and specifically, to examine how emotion processing is influenced by selective attention and a potential positivity bias in healthy older adults. The results gathered from these tools demonstrate impairment in selective attention, particularly when attending to the prosody and stronger positivity bias in healthy older adults compared to young adults. Moreover, both tools can be used for emotion processing assessments, as they provide similar data.

Keywords: Aging
Emotion processing
Lexical content
Prosody
Speech
Advisor: van Lieshout, Pascal H.M.M.
A MICROARCHITECTURAL ANALYSIS OF MACHINE LEARNING ALGORITHMS ON SPARK

Analysis of large data sets utilizing Machine Learning Algorithms (MLAs) is an important research and application area. This thesis resents a comprehensive performance analysis of MLAs on the ApacheTM Spark platform, identifying bottlenecks at the microarchitectural level, and associating them to higher-level code constructs. In addition, we propose solutions to address the discovered performance issues. Our results indicate that: 1) The majority of MLAs are backend-bound, in particular memory-bound. 2) The dot product is the main bottleneck in a considerable number of MLAs. 3) Garbage collection and high-level abstractions are a major source of overhead in Spark. 4) Enabling Hyper-Threading is a recommended feature that improves performance up to 52%. 5) The improved data representation of the Dataset API results in performance improvements of up to 64% over the RDD API. 6) Enabling software caching in the right place improves the performance between 6%-23%.

Keywords: Apache Spark
Computer Engineering
Hardware
Machine Learning
Microarchitecture
Software
Advisor: Moshovos, Andreas
Timing and Location of Brain Areas Involved in Cognitive Theory of Mind in Children with Autism Spectrum Disorder

Cognitive theory of mind (ToM), or the ability to recognize the different mental states of others, is a social cognitive skill that is often impaired in children with autism spectrum disorder (ASD). This study enriches our understanding of ToM in ASD by using magnetoencephalography (MEG) to determine the temporal properties of brain regions active during a false belief task, a domain that has not been explored in this field, and yet is a significant component of brain activity. We found that whereas typically-developing children activate familiar ToM regions, such as the precuneus and the left temporoparietal junction, children with ASD appear to rely more on working memory and inhibition regions, such as the right dorsal temporoparietal junction and the right inferior frontal gyrus. This atypical activation suggests that children with ASD make use of alternative strategies to compensate for their deficits in ToM.

Keywords: autism
development
MEG
theory of mind
Advisor: Taylor, Margot J
Confucian Multiculturalism: A Communitarian Theory of Intercultural Dialogue

This paper argues that the liberal-communitarian debate in political philosophy is still significant today. While some have argued that communitarian concerns have been absorbed by liberal approaches to the accommodation of moral and cultural diversity, I show that such efforts are not properly sensitive to and respectful of other cultures because they do not acknowledge the particularity of the liberal tradition. To emphasize this, I draw on the intellectual resources of a particular communitarian tradition – Confucianism – to develop a more sensitive and respectful accommodation of cultural diversity called Confucian multiculturalism. I show that Confucian multiculturalism can be realized through an intercultural dialogue that, in the modern context, should take place in universities which can provide the right intercultural education and environment. I conclude that the liberal-communitarian debate, when taken seriously, can be expanded to take the form of an intercultural dialogue that enriches all cultures and probes our common humanity.

Keywords: Communitarianism
Confucianism
Intercultural Dialogue
Liberalism
Multiculturalism
Advisor: Shen, Vincent T
Apolipoprotein A-IV: Novel αIIbβ3 Integrin Ligand and Endogenous Thrombotic Inhibitor

Apolipoprotein A-IV (apoA-IV) is a lipid binding protein that is synthesized in the small intestine during lipid absorption. Although reports suggest that plasma apoA-IV levels are inversely correlated with coronary artery disease (CAD), its role in platelet function and thrombosis, the major cause of CAD, is unknown. Here, I demonstrated that apoA-IV inhibited platelet aggregation and thrombus growth - with enhanced inhibition at higher shear rates - while lacking apoA-IV resulted in accelerated thrombosis. Using intravital microscopy, I found a unique pattern of apoA-IV deposition on thrombi. Through collaboration, we found the direct binding force between apoA-IV and platelet αIIbβ3 integrin. ApoA-IV competitively inhibited pro-thrombotic fibrinogen binding to αIIbβ3. We demonstrated apoA-IV N-terminal aspartic acids (D5 and D13) are required for αIIbβ3 binding and the inhibition of platelet aggregation and thrombosis. Thus, apoA-IV is a novel αIIbβ3 ligand and endogenous thrombotic inhibitor, representing the novel mechanisms of prevention for CAD.

Keywords: Apolipoprotein A-IV
Inhibitor
Ligand
Platelet
Thrombosis
αIIbβ3 Integrin
Advisor: Ni, Heyu
Expression of and Regulation by Nanos in Drosophila Early Embryos

Three categories of cytoplasmic post-transcriptional regulation that modulate mRNA stability, subcellular localization, and translation are coordinated to precisely control when and where a protein is expressed. In Drosophila oocytes and early embryos, subcellular mRNA localization and local translation play fundamental roles in determining the body axes and specifying the germline. Nanos protein is one of the determinants whose subcellular localization is accomplished through local translation of its transcripts in the posterior germ plasm. I quantified Nanos protein in early embryos at closely spaced stages and revealed that nanos mRNA is indeed translated at the posterior pole of embryos. I then tested the role of an RNA-binding protein, Staufen, as a nos translational activator competitive binding with the RNA-binding protein Smaug. I further started to uncover the role of Nanos in target transcript regulation as a co-factor together with the RNA-binding proteins Pumilio and Brain Tumor.

Keywords: Drosophila
embryogenesis
local translational regulation
nanos
post-transcriptional regulation
RNA binding protein
Advisor: Lipshitz, Howard
Intestinal microRNA Response to Citrobacter rodentium in the Presence and Absence of Bifidobacterium bifidum MIMBb75

The continuous crosstalk between gut microbiota and the host epithelium is essential for intestinal homeostasis. Presence of harmful or beneficial bacteria can impinge host gene expression and affect homeostasis. Yet, the molecular basis underlying host-bacterial crosstalk is unclear. The objectives of this project were to determine if pathogen infection impacts microRNA-mediated posttranscriptional regulation of gene expression in mouse intestine and if probiotic treatment improves pathogen-induced pathologies and microRNA alterations. It was found that Citrobacter rodentium infection alters murine colonic microRNA signature with implications in modulating host gene expression involved in the apoptosis pathway, contributing to the epithelial hyperplasia in response to Citrobacter rodentium pathogenicity. Probiotic Bifidobacterium bifidum MIMBb75 supplementation did not attenuate intestinal pathology nor normalize microRNA alterations. Overall, these findings indicate that host-bacterial crosstalk is potentially mediated by microRNA modulation, and this particular strain of Bifidobacterium bifidum did not confer apparent benefits in Citrobacter rodentium infection.

Keywords: enteropathogen
gene expression regulation
intestine
mouse
probiotic
Advisor: Comelli, Elena M
The Role of LXR in Glucocorticoid-Induced Osteoporosis and Muscle Wasting

Synthetic glucocorticoids (GCs) have unparalleled anti-inflammatory and immunosuppressive properties that are crucial for the treatment of many inflammatory diseases. Unfortunately, a remaining limitation for the long-term therapeutic use of GCs is the development of major metabolic side effects, including Cushing’s syndrome, a disease characterized by metabolic dysregulations such as hyperglycemia, muscle wasting and osteoporosis. The glucocorticoid receptor (GR) and liver X receptor (LXR) are members of the nuclear receptor superfamily that regulate distinct but overlapping transcriptional programs. Using a Cushing’s mouse model of GC excess, as well as in vitro cell lines treated with synthetic GCs, we find that LXR antagonism is protective from GC-induced osteoclast activation, but not from the anti-osteoblastogenic or muscle atrophy effect of GCs; suggesting a cell type specific effect. Together, these studies show the selective regulation of LXR antagonism may be useful in preventing GC-induced osteoclast activation.

Keywords: Bone
Cushing's syndrome
Glucocorticoids
Liver X Receptor
Muscle
Nuclear Receptor
Advisor: Cummins, Carolyn L
Antisaccadic Eye Movements as a Correlate for Response Inhibition and White Matter Integrity in Mild Traumatic Brain Injury

Antisaccades are thought to involve higher level inputs from neural centers involved in rapid eye movement inhibition and control. Previous work has demonstrated that performance on the antisaccade task can help in assessment of injury in acute and/or chronic Mild Traumatic Brain Injury (mTBI). We validated antisaccade performance in mTBI assessment against gold standard assessments of symptom burden, diffusion tensor imaging, and a neuropsychological test of response inhibition. Significant deficits in antisaccade median latency and prosaccade mean duration were found between patient groups and controls, despite overall integrity of the pupillary light reflex; the former was correlated with loss of white matter integrity in the splenium of the corpus callosum in acute mTBI. Furthermore, antisaccade median latency was also associated with poor performance on executive functioning tasks, and greater symptom burden in the acute patients. This research suggests that the antisaccade task is useful as a neurological marker for mTBI.

Keywords: Antisaccades
Diagnosis
Executive Functioning
Magnetic Resonance Imaging
Mild Traumatic Brain Injury
Symptom Burden
Advisor: Cusimano, Michael D.
The Safety of Diclectin® in Breastfeeding

Background and Rationale: Diclectin® is a delayed-release medication indicated for nausea and vomiting of pregnancy. Some mothers who are concurrently pregnant and breastfeeding also take Diclectin®. Hence, components of Diclectin® in breast milk may cause adverse events in the breastfed infants. This had not been studied before. Objective: To determine the safety and clinical significance of doxylamine exposure through breast milk in infants breastfed by mothers taking Diclectin®. Methods: 41 mothers concurrently taking Diclectin® and breastfeeding completed a telephone questionnaire regarding occurrence of adverse events in themselves and their breastfed infants. Data were analyzed and compared with results from other studies. Results: Maternal adverse events included sedation (29), dizziness (2), weakness (4), constipation (2), reduced lactation (2), abdominal pain (1), and increased appetite (1). Infant adverse events included sedation (5), constipation (1), slept less (1), and loose bowel (1). Conclusion: Mothers taking Diclectin® and their breastfed infants may experience sedation.

Keywords: adverse drug reaction
breastfeed
breast milk
diclectin
doxylamine
pyridoxine
Advisor: Koren, Gideon
Ito, Shinya
Grey and White Matter Density on Computed Tomography in Pediatric Traumatic Brain Injury: Automated Digital Measurement Algorithm Classifying Cerebral Injury

Background: This project assessed an automated digital measurement algorithmâ s ability to predict pediatric functional outcome after traumatic brain injury by quantifying detectable cerebral edema on computed tomography scans. Methods: Developed with consideration to brain maturity and time from injury to scan, the algorithm was applied to day-of-injury computed tomography scans of 118 children (age: 0-17 years) with traumatic brain injury. Regions of interest median Hounsfield units were analyzed using Medical Image Processing, Analysis and Visualization software. Results: Grey-white matter ratio (p = 0.019) and age (p = 0.034) were significantly associated with functional outcome. The most predictive algorithmic model (area under the curve = 0.868) included samples from the caudate nuclei, thalami and putamen; frontal, temporal and occipital lobes; and grey-white matter ratio. Conclusions: Cerebral edema can be measured quantitatively using digital methods and the model from this study has high predictability for functional outcome following pediatric traumatic brain injury.

Keywords: cerebral edema
cerebral swelling
computed tomography
digital measurement
grey white matter
traumatic brain injury
Advisor: Guerguerian, Anne-Marie
Phosphorus and Potassium Content of Commonly Consumed Meat, Poultry and Fish Products in Patients with Chronic Kidney Disease

Patients with chronic kidney disease (CKD) are advised to limit their intake of phosphorus and potassium, yet there is uncertainty concerning the actual content of these minerals in the Canadian food supply. In order to gain insight into the contribution of food additives to phosphorus and potassium intake, we chemically analyzed phosphorus, potassium, sodium and protein content of commonly consumed meat, poultry and fish (MPF) products. A food frequency questionnaire administered to patients receiving dialysis (n=67) identified unbreaded chicken, ground beef, steak, white fish, beef burgers, deli ham, shrimp and bacon as commonly consumed MPF. Phosphorus and potassium content was significantly (P

Keywords: Additives
Chronic Kidney Disease
Meat
Phosphorus
Potassium
Poultry
Advisor: Darling, Pauline B
Derivation of Patient-specific Alveolar Type II Cells from Surfactant Protein-B Deficient Induced Pluripotent Stem Cells

Surfactant protein B (SFTPB) deficiency is a fatal disease affecting newborn babies. A mutation in the surfactant protein B gene results in the inability to reduce surface tension and ultimately, death. This thesis shows that induced pluripotent stem (iPS) cells derived from patient specific SFTPB deficient fibroblasts can be differentiated into alveolar type II cells using a variety of methods including 2D and 3D culture. The iPS cells are also a target for gene therapy with a lentivirus vector containing the wild type sequence of the SFTPB gene, inserted into both wild type and SFTPB deficient iPS cells. These cells were differentiated into lamellar body containing, surfactant expressing alveolar type II cells and the transfected SFTPB deficient cells showed gene and protein expression of surfactant protein B. These findings suggest that a lethal disease can be targeted and reversed, the first step towards a potential cure for a vulnerable population.

Keywords: gene therapy
induced pluripotent stem cells
lung biology
surfactant deficiency
Advisor: Post, Martin
Manufacturing and Characterization of Chitin Nanowhisker/Polyolefin Nanocomposites

This thesis discusses the potential large scale production of polymer nanocomposites using polypropylene and high density polyethylene with chitin nanowhiskers (CNW). Fabrication of the nanocomposites with and without compatibilization were prepared over a range of CNW loading through melt compounding. The processing techniques tested included direct melt compounding, and a two step masterbatch dilution process. Three studies were investigated to build an understanding of the composite structure-property relationship based on morphological, thermal, water barrier, mechanical, and rheological properties. The addition of CNW and compatibilizer provided mechanical reinforcement and improvements in water barrier. However, the CNW significantly affected the crystallinities of the composites, which impacted its overall properties. Finally, the masterbatch diluted composites maintained good mechanical and water barrier compared to the neat polymer, but the directly compounded composites were still better. Therefore, further optimization of this process is required to maximize CNW dispersion, which also greatly affected the composite properties.

Keywords: chitin
crystallinity
masterbatch
nanocomposite
polyolefin
water vapor barrier
Advisor: Naguib, Hani
Application of Chemical Structure-based Parameters of Drug Substances and Polymers to Predict Kinetics of Drug Release from Polymer Coated Pellets

The purpose of this thesis is to correlate drug substance properties that are easily calculated or obtained in literature with drug-polymer partition and permeability values. Initially, partition and permeability values were determined experimentally using a side-by-side diffusion cell and values were correlated with drug substance properties mentioned above. The drug-polymer squared solubility parameter, aqueous solubility and molar volume resulted in the best correlations. The empirical correlations, paracetmaol dissolution data (obtained from literature) and AP-CADÂŠ software were utilized to predict the release profile of a similarly coated metoprolol pellet. Verification took place with a comparison of the predicted metoprolol AP-CADÂŠ release profile and metoprolol dissolution data obtained from literature. Results met equivalence criteria outlined by the F1 and F2 difference and similarity factor. Therefore, the methodology and correlations identified could be used as a starting point in formulation studies, thus eliminating various experiments.

Keywords: Drug-Polymer
Group Contribution Method
Partition
Permeability
Polymer
Solubility
Advisor: Wu, Shirley X. Y.