VictorJuiz/thesis huggingface dataset:
Investigating the Mechanism of Programmed Nuclear Destruction during Yeast Sporulation

In the presence of a non-fermentable carbon source, nitrogen-starved diploid cells of the yeast Saccharomyces cerevisiae undergo a meiotic program called sporulation to form gametes called spores. While four spores are produced under standard laboratory sporulation conditions, spore number is known to be regulated by carbon availability: under carbon-depleted conditions, yeast cells package a portion of the four haploid meiotic nuclei into spores. Our lab has demonstrated that these unpackaged meiotic products undergo programmed nuclear destruction (PND) that is associated with apoptotic-like DNA fragmentation. Nevertheless, the mechanism that mediates PND remained to be elucidated. Here, I describe the execution of PND through an unusual form of autophagy that has not been documented previously in yeast. This form of autophagy is most similar to megaautophagy in plants and lysosomal membrane permeabilization in mammals. My results demonstrate further diversity in cell death programs in unicellular microbes that is potentially conserved across eukaryotes.

Keywords: autophagy
programmed cell death
yeast
sporulation
meiosis
megaautophagy
Advisor: Meneghini, Marc
Influence of Rock Boundary Conditions on Behaviour of Arched and Flat Cemented Paste Backfill Barricade Walls

Current design of cemented paste backfill (CPB) barricades tends to be of unknown conservativeness due to limited understanding of their behaviour. Previous work done to characterize barricade response has not accounted for the effects of the surrounding rock stiffness, which can have significant impact on the development of axial forces which enhance capacity via compressive membrane action. Parametric analyses were performed with the finite element analysis program Augustus-2 to determine the effects of various material and geometric properties on barricade capacity. Equations based on Timoshenko and Boussinesq solutions were developed to model rock stiffness effects based on boundary material properties. An iterative simulation process was used to account for secondary moment effects as a proof of concept. It was found that, for a range of typical rock types, barricade capacity varied significantly. The commonly made design assumption of a fully rigid boundary resulted in unconservative overpredictions of strength.

Keywords: cemented paste backfill
barricade
reinforced concrete
secondary moment effects
rock stiffness
boundary conditions
finite element analysis
parametric analysis
Advisor: Bentz, Evan
Grabinsky, Murray
Evaluation of Dynamic Prosthetic Alignment Techniques for Individuals with Transtibial Amputation

Although dynamic prosthetic alignment is an important process for the rehabilitation of transtibial amputees, such alignment technique is subjective and inconsistent. Using biomechanical variables and questionnaire assessments, this study compared an instrument-assisted dynamic alignment technique using the Compas™ system and conventional alignment techniques on nine adults with unilateral transtibial amputation. A focus group discussion was conducted with six prosthetists to understand clinical practice of dynamic alignment and their perception of the Compas™ system. Results found that Compas™ produced more anterior weight line displacement and greater varus moment on the prosthesis than conventional alignment techniques. Alignment changes did not affect pelvic acceleration, and the instrument-assisted alignment technique produced certain biomechanical changes but not necessarily better alignments. Although the current version of the Compas™ system is not clinically feasible, it can be used as a teaching/justification tool. Further investigation with larger sample size and ankle alignment or moment measures is needed.

Keywords: prosthetic
biomedical engineering
alignment technology
transtibial amputation
biomechanic
mobility
prosthesis
lower limb
rehabilitation
alignment technique
focus group
prosthetist
amputee
gait
Compas™ system
moment
weight line
pelvic acceleration
Advisor: Andrysek, Jan
Role of the SDF-1/CXCR4/eNOS Signaling Pathway in Chronic Kidney Disease

Loss of the renal microvasculature is a common feature of almost all forms of chronic kidney disease (CKD). Here we explored the role of the angiogenic chemokine stromal cell-derived factor-1-alpha (SDF-1) and its cognate receptor CXCR4 in experimental and human CKD. CXCR4 was present on endothelial cells and podocytes, while SDF-1 was detectable on podocytes, arteriolar smooth muscle cells, interstitial fibroblasts and occasional endothelial cells. CXCR4 mRNA was elevated in the kidneys of rats with CKD and chronic antagonism of CXCR4 accelerated renal decline and capillary loss. Acute SDF-1 infusion activated glomerular endothelial nitric oxide synthase (eNOS) in vivo, while functional response to SDF-1 was impaired in glomerular endothelial cells derived from eNOS-/- mice. Finally, CXCR4 mRNA was also found to be increased in biopsies of patients with secondary focal segmental glomerulosclerosis. These observations indicate that local eNOS-dependent SDF-1/CXCR4 signaling exerts a compensatory reno-protective effect in the setting of CKD.

Keywords: chronic kidney disease
SDF-1
CXCR4
eNOS
nephrology
focal and segmental glomerulosclerosis
Advisor: Advani, Andrew
Carbohydrate Oxidation in Fueling Hovering Flight in the Ruby-throated Hummingbird (Archilochus colubris)

Nectarivorous hummingbirds subsist almost exclusively on a mixture of sucrose, glucose and fructose found in floral nectar. Previous studies have shown that hummingbirds can fuel hovering flight almost exclusively using recently ingested sucrose. However, the relative capacities for the direct utilization of glucose and fructose by hovering hummingbirds remain unknown. 13C-enriched solutions of glucose and fructose were administered separately. Exhaled breath samples were collected using feeder-mask respirometry and sent for subsequent mass spectrometric analysis. I found hovering hummingbirds transition from exclusively oxidizing endogenous fatty acids when fasted, to oxidizing newly ingested carbohydrates when given access to either glucose or fructose solutions. Interestingly, the amount ingested, fractional turnover of stable carbon isotope signatures, amount oxidized, energy expended and proportion of hovering metabolism supported by each hexose, were each similar between glucose and fructose. These results demonstrate hovering hummingbirds’ ability to utilize fructose and glucose equally.

Keywords: hummingbird
metabolism
carbohydrate
hovering flight
sucrose
fructose
glucose
stable carbon isotope
feeder-mask respirometry
respiratory quotient
energy
fuelling
Advisor: Welch, Kenneth
Do Proprioceptive Head-on-trunk Signals Modulate Spatial Cognition? – Probing Influences of Body Schema on Working Memory and Spatial Attention

Body schema is indispensable for sensorimotor control and learning, but it remains unclear whether it is associated with cognitive functions. Data from patients with spatial neglect support this view; yet observations in healthy participants are inconsistent. Here I conducted two sets of experiments examining influences of trunk position: the first probed attention and spatial working memory using a change detection task and a two-back task; the second used different versions of the Posner paradigm to examine whether head-on-trunk position governs disengagement of attention. In none of the experiments did I observe that trunk turns altered performance in the left versus right visual field in an ipsiversive fashion as reported in neglect. Nevertheless, I found that trunk-right position improved performance at eccentric locations of the visual field. The data are inconsistent with previous findings of head-on-trunk effects in normal participants. Further studies are required to clarify these discrepancies.

Keywords: head-on-trunk signals
spatial attention
spatial working memory
body schema
spatial neglect
Advisor: Niemeier, Matthias
Schmuckler, Mark
The Resurfice Exception: Causation in Negligence Without Probability

Resurfice Corp. v. Hanke, [2007] 1 S.C.R. 333, 2007 SCC 7, creates a new causation doctrine in Canadian negligence law that is available to plaintiffs only in exceptional cases. Under this doctrine, negligence and the possibility of specific factual causation may be sufficient to satisfy the causation requirements of a cause of action in negligence. Proof of specific factual causation on the balance of probability is not required. The justification for this doctrine is fairness and justice. The application of the doctrine does not produce a decision that the negligence did cause the injury. Where the requirements of the Resurfice doctrine are satisfied, the causation requirements of the cause of action are deemed to be satisfied despite the finding that factual causation was not established on the balance of probability. The authorities cited are current to June 21, 2012.

Keywords: Canada
tort
negligence
cause
causation
material contribution
risk
Advisor: Weinrib, Ernest
Regulation of Planar Cell Polarity and Vangl2 Trafficking by Tmem14a

Planar cell polarity (PCP) refers to the coordinated orientation, movement, or structure of cells within the plane of a tissue. Zebrafish PCP mutants such as the vangl2 mutant exhibit defects in convergent extension, neural tube morphogenesis, and ciliary positioning. Tmem14a is a putative tetraspanin protein that was identified as an potential interactor of Vangl2 in a membrane yeast-two hybrid screen. GFP-tagged versions of Tmem14a are localized to the trans-Golgi network in zebrafish neuroepithelial cells. Knockdown of Tmem14a activity results in convergent extension defects, an ectopic accumulation of cells in the neural tube, and disorganized cilia. The localization of GFP-tagged Tmem14a to the trans-Golgi network suggested that Tmem14a plays a role in the trafficking of core PCP components to the cell membrane. Indeed, the membrane localization of GFP-Vangl2 was disrupted in Tmem14a morphants. Thus, Tmem14a is an interactor of Vangl2 and a novel regulator of vertebrate planar cell polarity signaling.

Keywords: neural tube development
zebrafish
cilia
planar cell polarity
Golgi trafficking
Vangl2
Tmem14a
Advisor: Ciruna, Brian Garrett
Environmental Clean-up in Bankruptcy and Insolvency: What Priority for the Environment?

The lack of clarity of Canadian insolvency legislation with respect to the treatment of environmental claims has left Canadian courts wondering whether they should advance the public order policies embodied in the environmental legislation or promote creditors' interests and the private relief afforded by bankruptcy. This thesis examines the state of the law on the question and provides a critical assessment of the legislation and the relevant case law. The author points to the flaws of the legislation and its judicial interpretation, while uncovering the underlying reasons for the existence of such a confused body of jurisprudence. Building on these findings, the author proposes a reform of the insolvency legislation that would uphold the protection of the environment as a fundamental value in Canadian society.

Keywords: Bankruptcy
Insolvency
Environment
Companies' Creditors Arrangement Act
Bankruptcy and Insolvency Act
Priority
AbitibiBowater
General Chemical
Panamericana
Advisor: Green, Andrew
Cerebral Blood Flow Assessment in Children with Sickle Cell Disease

This thesis investigated the role of CBF assessment in the management of stroke in children with sickle cell disease (SCD). It is divided into two parts. In the first part, a systematic review of CBF assessment using different imaging modalities in SCD children was designed. The prevalence of CBF abnormalities was found to be equal to or higher than those of structural MRI and transcranial Doppler (TCD) in SCD children who have not experienced stroke. Studies reviewed suggested CBF assessment in SCD could aid in addressing brain abnormalities at the tissue level. In the second part, the arterial spin labeling (ASL) technique was used to depict CBF abnormalities in SCD children. ASL demonstrated perfusion abnormalities that seem to remain invisible in TCD measurements; CBF interhemispheric asymmetries were associated with clinically silent infarctions with no corresponding flow velocity interhemispheric asymmetries assessed with TCD.

Keywords: Cerebral blood flow
sickle cell disease
MRI
Transcranial doppler
Advisor: Kassner, Andrea
Polymeric Micelles for SiRNA and AON Delivery

Immuno-nanoparticles of poly(ᴅ,ʟ-lactide-co-2-methyl-2-carboxytrimethylene carbonate)-g-poly(ethylene glycol) (poly(LA-co-TMCC)-g-PEG) have been used to target breast cancer cells through the specific binding of trastuzumab antibodies to over-expressed human epidermal growth factor receptor 2 (HER2). Small interfering RNA (siRNA) and antisense oligonucleotides (AONs) disrupt the synthesis of select proteins. It is hypothesized that oligonucleotides coupled to polymeric immuno-nanoparticles can be used for gene silencing and specifically to target luciferase. The first objective is to demonstrate the capacity to create dual functional micelles with antibodies and oligonucleotides. The second objective is in vitro testing of the nanoparticle for gene silencing activity. Oligonucleotides are conjugated to the nanoparticle by sequential click reactions of Diels Alder chemistry and copper catalyzed azide-alkyne cycloadditions, respectively. A luciferase assay is used to quantify knockdown of luciferase levels in SKOV-3luc cells (HER2+, luc+). When used in conjunction with a targeted drug delivery vehicle, the nanoparticles provide selective interactions with SKOV-3luc cells.

Keywords: polymer nanoparticles
targeted delivery
gene therapy
drug delivery
Advisor: Shoichet, Molly
Acquisition and Responding for Conditioned Reinforcement in the Mouse: Effects of Methylphenidate, and the Role of the Dopamine Transporter

This work characterized the ability of mice to respond for conditioned reinforcement, a phenomenon that can be used to investigate neural substrates of incentive learning. In both C57Bl/6 and CD1 mice, a reward-associated stimulus acted as a conditioned reinforcer (CR). Responding was stable over multiple test days, enhanced in CD1 mice by the dopamine transporter (DAT) blocker methylphenidate, and was extinguished when responding no longer produced the CR. However, transgenic C57Bl/6 mice overexpressing DAT, which decreased striatal dopamine by 40% responded normally for CR. Therefore, these results suggest that mice can be used to study brain mechanisms of incentive motivation. However, the choice of mouse strain in this paradigm is important as outbred CD1 mice appeared more susceptible to a DAT blocker compared to the inbred C57Bl/6 strain. These results also suggest that selective responding for a CR remains intact in a chronically hypodopaminergic state.

Keywords: Behavioural neuroscience
Psychopharmacology
Advisor: Fletcher, Paul J.
A Comparison of Different Regulatory Appraoches, Analysis of the Relative Benefits of Command and Control, Reflexive Law and Social Licencing in Ensuring Oil Industry Compliance with Environmentally Sustainable Practices and Obligations

This paper explores the relative benefits of command and control, reflexive law and social licensing in ensuring oil industry compliance with environmentally sustainable practices and obligations. Recognizing why oil sands and their development are significant, the background and development are reviewed first, and then the focus is shifted to look at its economics including the benefits, uncertainties and environmental costs of development. This paper examines how lawmakers in Canada have failed to meet their respective obligation. Drawing on environmental provisions, case law and legal scholars’ articles, books and reports, this paper examines the very problematic issue of oil sands regulation. It proposes to provide an in depth analysis of each regulatory forms and their application to the oil sands. It concludes that in order to solve the oil sands regulation challenges, a collaborative stringent enforcement of regulation from both federal and provincial governments, oil industry and public Pressure is required.

Keywords: regulating Oil Sanda
Advisor: Green, Andrew
The Problem with the Human Rights Act 1998: Section 2(1)

The Human Rights Act 1998 incorporated the European Convention on Human Rights. With incorporation, Parliament and the government of the United Kingdom believed that human rights would reflect British values, there would increase support for human rights and a human rights culture would develop. However, the goals of incorporation did not occur. One reason for the failure of the Human Rights Act 1998 is the UK courts interpretation of section 2(1). Courts in the United Kingdom have been unwilling to provide more extensive and less extensive protection of rights than Strasbourg. The effect of the court’s interpretation has been public, political and media backlash. Consequently, to resolve this problem, there must be a reinterpretation of section 2(1).

Keywords: human rights
United Kingdom
Advisor: Lee, Ian B.
The Human Rights Act 1998: Failure in a Post 9/11 World

In 1997 the Labour Party introduced the White Paper Rights Brought Home: The Human Rights Bill. Bringing rights home was considered necessary to significantly influence rights conception in the UK and internationally. Rights Brought Home argued that incorporation would allow human rights to become a more prominent feature of society. The Human Rights Act 1998 (HRA) was brought into force with optimism and expectations. However, the war of terror has significantly impacted the way in which rights have been understood and appreciated. National security issues have clashed with Convention rights. There is mounting concern that British judges must blindly follow the rulings established by the European Court of Human Rights. There have been problems of public disengagement and hostility. The HRA is characterized by a story of failure. Understanding the relationship between the war on terror and the HRA is central to human rights development.

Keywords: Human Rights Act 1998
Post 9/11 World
Media
Public interest
Advisor: Knop, Karen C.
Jaw Bone Changes on Panoramic Imaging after Head and Neck Radiotherapy

Gnathic changes after head and neck radiotherapy have not been thoroughly characterized radiographically. The objectives of this study are to characterize changes to the teeth and jaws on panoramic images following intensity modulated radiotherapy (IMRT), and to determine whether subject comorbidities and radiation dose affect these changes. This retrospective analysis reviews the charts and panoramic images of 126 head and neck cancer patients who received IMRT at Princess Margaret Hospital between January 1, 2005 and December 31, 2008. Of the 126 subjects, 75 (60%) showed changes on panoramic radiographs; 66 (88%) of which consisted of widened periodontal ligament spaces (WPLS). The median time to WPLS was 29 months after IMRT. Female sex and dose correlated with decreased time to WPLS. These results suggest that WPLS is a common radiographic sign following IMRT that may not require endodontic intervention as post-IMRT WPLS is unrelated to the pulpal status of the tooth.

Keywords: Radiotherapy
Jaw Bone Changes
Advisor: Pharoah, Michael John
The “Gist” of Early Visual Processing

Visual information is processed by two separate visual pathways. One is the magnocellular visual pathway (M-pathway), which carries high temporal frequency information but low spatial frequency information. The other is the parvocellular visual pathway (P-pathway), which carries low temporal information but high spatial information. Kveraga and colleagues (2007) presented participants with high and low spatial frequency images and found that participants made faster and more accurate categorization responses to the low spatial frequency images. They hypothesized this was due to low spatial frequency “gist” information being rapidly carried by the M-pathway. Using diffuse light and hand posture manipulations, we replicated the advantage for low spatial frequency (LSF) images in both experiments, and also found a larger advantage for LSF information when biasing the M-pathway (using hand posture). We were unable to inhibit the M-pathway using red diffuse light. Thus, it does appear “gist” processing is uniquely carried by the M-pathway.

Keywords: Cognition
Vision
magnocellular
parvocellular
Advisor: Pratt, Jay
The Observed Stable Carbon Isotope Fractionation Effects of a Chloroform and 1,1,1-Trichloroethane Dechlorinating Culture

Little is known about the enzyme-substrate interactions occurring during the dechlorination of chloroform (CF) and 1,1,1-trichloroethane (1,1,1-TCA) by the enrichment culture containing Dehalobacters, hereafter called DHB-CF/MEL. Compound specific isotope analysis (CSIA) is used to investigate the factors which may affect the isotope fractionation observed for CF and 1,1,1-TCA dechlorination. This thesis reports the first isotope enrichment factors observed for CF biodegradation at -27.5‰ ± 0.9‰, thus providing fundamental information for comparing isotope enrichment factors observed during trichlorinated alkane degradation by DHB-CF/MEL. The thesis also reports how the presence of CF and 1,1,1-TCA influences isotope fractionation and explores the possible influence of substrate inhibition on isotope fractionation during 1,1,1-TCA dechlorination. The data suggests that substrate inhibition during 1,1,1-TCA dechlorination by DHB-CF/MEL may not affect carbon isotope fractionation. The results suggest that CSIA is a promising monitoring tool even for the simultaneous biodegradation of CF and 1,1,1-TCA at different 1,1,1-TCA starting concentration.

Keywords: compound specific isotope analysis
chloroform dehalogenation
dehalobacter
groundwater remediation
Advisor: Lollar, Barbara Sherwood
Mitochondria-targeted Doxorubicin is Active and Resistant to Drug Efflux

Several families of highly effective anticancer drugs are selectively toxic to cancer cells because they interfere with nucleic acids synthesis. Many such drugs are pumped out of cells faster than they can reach their targets, which limits efficacy and renders many tumors drug-resistant. By delivering a drug to the mitochondria of mammalian cells – an organelle where nucleic acids synthesis also occurs – efflux could be prevented through sequestration. Doxorubicin, a topoisomerase II inhibitor, was used as proof-of-principle for this concept due to its susceptibility to resistance. When doxorubicin is attached to a peptide that specifically targets mitochondria, its efficacy is not attenuated by various resistance mechanisms to which doxorubicin is normally susceptible. These results indicate that targeting drugs to the mitochondria provides a means to evade the most common mechanism of drug resistance.

Keywords: Doxorubicin
Drug Resistance
P-glycoprotein
Drug Efflux
Topoisomerase II
Mitochondria
Mitochondria Penetrating Peptides
Advisor: Kelley, Shana O.
X-ray Investigations of PEMFC Gas Diffusion Layers (GDLs)

In this thesis, synchrotron radiography was utilized to image liquid water distributions in the porous polymer electrolyte membrane fuel cell (PEMFC) gas diffusion layers (GDLs). GDLs were compressed in an ex situ flow field apparatus with 1mm x 1mm channels, and injected with liquid water to study the effect of current density and microstructure on through-plane GDL liquid water distributions. The effect of the size of the water inlet on GDL liquid water distribution was also investigated. Micro-computed tomography was employed to characterize the effect of flow field compression on commercial and non-commercial GDLs. Porosity distributions of compressed GDLs were compared with those of uncompressed GDLs, and the effect of microstructure on the porosity was discussed. The experimental techniques documented in this thesis will inform future research, while the results will help modellers generate realistic GDL pore structures for multiphase flow simulations and validate their models.

Keywords: PEMFCs, GDLs
X-rays
Advisor: Bazylak, Aimy