VictorJuiz/thesis huggingface dataset:
Identification and Characterization of the Interaction between VPS33B and SNAREs
Keywords: SNAREs
Sec1/Munc18
VPS33B
syntaxin-6
megakaryocyte
platelet

VPS33B is a Sec1/Munc18 protein required for the biogenesis of α-granules in megakaryocytes, which give rise to platelets. Mutations in VPS33B cause arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome. Platelets from ARC patients completely lack α-granules, causing a bleeding disorder. VPS33B plays a role in vesicular fusion events through its interaction with the SNARE proteins, though no such interactions have been identified. Here, it is shown that VPS33B interacts with STX6, a member of the syntaxin subfamily of SNAREs. The introduction of ARC mutations into VPS33B completely abrogated binding to STX6. Confocal microscopy studies revealed STX6 co-localizes well with markers of the α-granule biogenesis pathway. This implies a role for the interaction of VPS33B with STX6 in α-granule biogenesis. Based on the known structure of STX6 and that predicted of VPS33B, suggests a novel and unique mode of binding between VPS33B and STX6 compared to other identified SM-STX pairs.
Multispectral Detection of European Frog-bit in the South Nation River using Quickbird Imagery
Keywords: Fuzzy Classification
European Frog-bit
Multispectral Detection
Quickbird

This thesis investigated multispectral detection of the invasive floating macrophyte, European Frog-bit, using Quickbird imagery and fuzzy image classification. To determine if the spectral signature of European Frog-bit were separable from other wetland vegetation, a species level land cover classification was conducted on a 6km section of the South Nation River in Ontario, Canada. Supervised and unsupervised imagery classification approaches were evaluated using the fuzzy classifiers, Fuzzy Segmentation for Object Based Image Classification (FS) and Fuzzy C-Means (FCM). Both approaches were sufficiently robust to detect European Frog-bit. User’s and producer’s accuracies for the European Frog-bit class were 81.0% and 77.9% for the FS classifier and 63.5% and 73.0% for the FCM classifier. These accuracies indicated that the spectral signature of EFB was sufficiently different to permit detection and separation from other wetland vegetation and fuzzy image classifiers were capable of detecting EFB in Quickbird imagery.
The Effect of Zoledronate Pretreatment on BMP Induced Bone Formation in Mice
Keywords: zoledronate
BMP
bone morphogenetic proteins
bisphosphonates
bone graft

Recombinant human bone morphogenetic proteins (rhBMPs) are increasingly used for reconstructing bony defects, fracture non-unions, and augmenting existing bone volumes. For the numerous patients taking bisphosphonates, the impact of prior bisphosphonate treatment on rhBMP bone induction is not well understood. Objective: to evaluate the effect of the prior treatment with zoledronate on rhBMP induced bone formation in mice. Methods: 42 mice were pre-treated with 0, 2, and 20 µg of zoledronate/mouse. The osteoinductive activity of a bioimplant, containing rhBMP-2, was assessed using the mouse muscle pouch assay, and analyzed with micro CT and histology. Results: micro CT demonstrated that BMP bioimplants placed in mice pretreated with 20 µg of zoledronate, formed bony ossicles of greater volume but reduced bone density compared to controls. Histologically, the heterotopic ossicles from the 20 µg group consisted of more immature bone than those from the other groups. Conclusion: bone induced by rhBMP-2 in mice pre-treated with a high concentration of zoledronate was immature as evidenced by radiographic and histologic appearance.
Analysis and Implementation of Fine-grained Distributed Maximum Power Point Tracking in Photovoltaic Systems
Keywords: Photovoltaic
solar energy
distributed maximum power point tracking
partial shading
dc-dc converter
performance analysis
3D modeling
solar forecasting

This thesis deals with quantifying the merits of Distributed Maximum Power Point Tracking (DMPPT), as well as providing solutions to achieve DMPPT in PV systems. A general method based on 3D modeling is developed to determine the energy yield of PV installations exploiting different levels of DMPPT granularity. Sub-string-level DMPPT is shown to have up to 30% more annual energy yield than panel-level DMPPT. A Multi-Input-Single-Output (MISO) dc-dc converter is proposed to achieve DMPPT in parallel-connected applications. A digital current-mode controller is used to operate the MISO converter in pseudo-CCM mode. For series-connected applications, the virtualparallel concept is introduced to utilize the robustness of the parallel connection. This concept is demonstrated on a three-phase boost converter. The topology offers reduced output voltage ripple under shading which increases the life-time of the output capacitor. The prototypes yield output power benefits of up to 46% and 20% for the tested shading conditions.
Patient-centered Perspectives of Communication and Handover between the Emergency Department and General Internal Medicine
Keywords: communication
handover
hospital
information technology
emergency department
general internal medicine
transfer
pager

Effective communication among clinicians is critical for patient safety. This multi-site observational study analyzes inter-clinician communication and interaction with information technology, with a focus on the critical process of patient transfer from the Emergency Department to General Internal Medicine. The study provides insight into clinician workflow, evaluates current hospital communication systems, and identifies key issues affecting communication. It suggests opportunities for improvement: • extending the role of the electronic patient record, • rendering it available on a mobile platform, • developing an improved paging system. It also identifies design trade-offs to be negotiated: • synchronous communication vs. reducing interruptions, • notification of patient status vs. reducing interruptions, • portability vs. screen size of mobile devices, • speed vs. quality of handovers, • information privacy vs. accessibility. The results inform the potential development of an intervention meeting seven principles: interconnectivity, context awareness, accessibility, redundancy, user customization, security, and intuitive user interfaces.
Design and Evaluation of Pressure-based Sensors for Mechanomyography: an Investigation of Chamber Geometry and Motion Artifact
Keywords: microphone
mechanomyography
access technology
acoustics
membrane vibration
muscle vibration
physiological measurement
physiological signal
mechanomyogram
MMG
intensification
amplification
rehabilitation engineering
motion artifact
artefact
signal contamination
SNR
SNSR

Mechanomyography (MMG) has been proposed as a control modality for alternative access technologies for individuals with disabilities. However, MMG recordings are highly susceptible to contamination from limb movements. Pressure-based transducers are touted to be the most robust to external movement although there is some debate about their optimal chamber geometry, in terms of low frequency gain and spectral flatness. To investigate the question of preferred geometry, transducers with varying chamber shapes were designed, manufactured and tested. The best performance was achieved with a transducer consisting of a low-frequency MEMS microphone, a 4 micron thick aluminized mylar membrane and a rigid conical chamber 7 mm in diameter and 5 mm in height. Furthermore, microphone-derived MMG spectra were found to be less influenced by motion artifact than corresponding accelerometer-derived spectra. However, artifact harmonics were present in both spectra, suggesting that bandpass filtering may not remove artifact influences permeating into MMG frequency bands.
Canada’s Patented Medicines (Notice of Compliance) Regulations: Removing Inefficiencies to Encourage Generic Competition
Keywords: patent
pharmaceutical
Notice of Compliance
Hatch Waxman
generic pharmaceutical

Canada’s Patented Medicines (Notice Of Compliance) Regulations fail to achieve the intended purpose of balancing innovation with timely generic market entry. An examination of the inefficiencies created by the Canadian regulations reveals that key features of U.S. pharmaceutical law should be adopted to improve the disjointed regulatory system that impedes generic competition. Specifically, the regulations should be amended to consolidate multiple proceedings into one cause of action that evaluates patent validity. An economic incentive to challenge weak patents should also be introduced in Canada. These features encourage competition without deterring pharmaceutical research and development because only patents that are not truly inventive will be invalidated after a full inquiry. As such, the intellectual property laws will continue to satisfy Canada’s international intellectual property obligations and protect innovative medicines and allow recovery of costs and monopoly profits to new and useful pharmaceutical products.
Role of Fatty Acid Transport Proteins in Oleic Acid-induced Secretion of Glucagon-like Peptide-1
Keywords: oleic acid
fatty acid transport proteins
glucagon-like peptide-1
GLP-1
L cell
diabetes

Glucagon-like peptide-1 (GLP-1) is an anti-diabetic intestinal L cell hormone. The monounsaturated fatty acid, oleic acid (OA), is an effective GLP-1 secretagogue that crosses the cell membrane by an unknown mechanism. Immunoblotting demonstrated the presence of fatty acid transport proteins (CD36 and FATP1, 3 and 4) in the murine GLUTag L cell model. The cells demonstrated specific 3H-OA uptake, which was dose-dependently inhibited by unlabeled-OA. Phloretin and SSO, inhibitors of carrier-mediated transport and CD36, respectively, also significantly decreased 3H-OA uptake, as did knocking down FATP4 by transfection of siRNA. OA dose-dependently increased GLP-1 secretion in GLUTag cells, while phloretin and FATP4 knockdown, but not SSO, decreased this response. OA injected directly into the ileum of wild-type mice increased plasma GLP-1 levels; in contrast, preliminary findings suggest decreased GLP-1 levels in FATP4 null mice at 60 min. Collectively, these findings indicate a role for FATP4 in OA-induced GLP-1 secretion.
Viscous Relaxation Times of the Core and Mantle of Mars from Observations of Tidal Decay of the Orbit of Phobos
Keywords: Mars
Mantle
Core
Maxwell relaxation
Normal modes

The orbit of Phobos exhibits an along-track acceleration, which suggests energy dissipation in the Mars-Phobos system. We hypothesize that the inferred dissipation occurs within Mars. We explore the response of a layered, incompressible Maxwell viscoelastic Mars to tidal forcing by Phobos using normal mode relaxation theory. Our results elucidate the general behavior of a tidally forced viscoelastic body, and have implications for the viscoelastic structure of Mars. We find the real and imaginary part of the degree-two tidal Love number for Mars to be 0.168 and -9.32x10^−4 respectively. Models which satisfy these and other constraints have either: a fluid core with radius 2040 km and density 5410 kg/m^3; or an elastic inner core with radius 1200 km and density 6700 kg/m^3, along with a fluid outer core with thickness 850 km and density 4850 kg/m^3. These findings support previous hypotheses that Mars has at least a fluid outer core.
Catalytic Asymmetric Hydrogenation: Toward Chiral Diamines and Cyclohexanes
Keywords: Hydrogenation
Benzene

As the need for developing environmentally friendly chemistry continues to become more apparent, catalytic asymmetric hydrogenation has risen to the forefront as a reliable and eco-friendly method for enantioselective synthesis. We herein describe our progress toward the synthesis of valuable structural motifs via hydrogenation: chiral 1,2-diamines, 1,3-diamines and substituted cyclohexanes. We propose a strategy whereby protected 1,2-diimine and 1,3-diimine surrogates can be hydrogenated selectively and deprotected to furnish the desired chiral amines. Using this strategy, it was demonstrated that imidazolone precursors could be hydrogenated with >20:1 diastereoselectivity to give latent 1,2-diamines, albeit with no enantiomeric excess. We further propose that substituted benzene rings linked to an oxazolidinone chiral-auxiliary can be diastereoselectively hydrogenated using a heterogeneous metal catalyst. Following hydrogenation, the chiral cyclohexanes could be obtained in up to quantitative yield and 99% diastereomeric excess.
Handling Qualities of a Blended Wing Body Aircraft
Keywords: flight simulation
handling qualities
blended wing body

The blended wing body (BWB) is a tailless aircraft with the potential to use 27% less fuel than a conventional aircraft with the same passenger capacity and range. The primary purpose of the current study was to determine the handling qualities of the BWB, using piloted-handling trials in a moving-base simulator. The secondary purpose was to determine the effect of simulator motion on handling-quality ratings. De Castro conducted piloted-handling trials in a fixed-base simulator. De Castro's tasks and flight model were modified in the current study. In the current study, three subjects rated the handling qualities as Level 1 or 2, depending on the task. Simulator motion did not have a significant effect on the results.
Double Dissociation of Associative and Non-associative Learning following Conditioning to a Single Odorant in the Caenorhabditis elegans AWC Olfactory Neruons
Keywords: C. elegans behaviour
Olfactory learning genetics

Learning can be either non-associative or associative, though the molecular mechanisms underlying both remain enigmatic. The nematode Caenorhabditis elegans can adapt to both the AWC sensed odorants benzaldehyde (Bnz) and isoamyl alcohol (IsoA) and reciprocally cross-adapt. Surprisingly, however, these four adaptation permutations actually represent two distinct forms of learning: non-associative habituation and associative learning by pairing with starvation. Conditioning to the single odorant IsoA leads to both associative and non-associative memory traces, which can be preferentially accessed by choice of a Bnz or IsoA retrieval stimulus, respectively. Furthermore, we show that the molecular mechanisms underlying each form of memory can be genetically double dissociated, with insulin signalling and egl-4 being required for associative learning and osm-9 and arr-1 being essential for IsoA olfactory habituation. This represents the first demonstration where the form of learning displayed after conditioning to a single stimulus is a function of the retrieval stimulus employed.
Computational Study of Volumetric Effects of Hydration
Keywords: molecular dynamics
partial molar volume

Molecular Dynamics (MD) simulations were used in conjunction with the Kirkwood-Buff (KB) theory to compute partial molar volume (PMV) for solutes of various chemical natures. Simulations performed with only the Lennard-Jones (LJ) potential yield PMV for solutes which coincide with the cavity volumes derived from calculations with scaled particle theory (SPT). Whereas, simulations carried out with only the repulsive LJ term produced PMV of solutes closer to their excluded volumes. We also determined the thermal volume, VT, which represents the volume of the effective void created around solutes of varying cavity sizes and applied the spherical approximation of solute geometry to evaluate the thickness of the thermal volume, . Our results reveal an increase in the thickness of thermal volume, , with an increase in the size of the solute. Our theoretical results are in good agreement with the reported empirical schemes for parsing PMV data on small solutes.
CAPS1 (Calcium Dependent Activator Protein for Secretion 1) Role in Catecholamine Secretion: A Structural Functional Analysis
Keywords: Secretion
CAPS1

The CAPS1 protein was initially discovered as a cytosolic soluble 145kDa protein which was necessary to restore calcium dependent norephinephrine secretion in cracked PC12 cells. Recent findings suggest that CAPS may also play a role in synaptic and dense core vesicle exocytosis as well as in the loading of monoamine neurotransmitters. Recently, studies have implicated CAPS1 in the binding to syntaxin-1. However, no studies have identified the key residues of CAPS1 that facilitate this interaction with syntaxin-1. I show that the binding mode of CAPS1 is independent from that of Munc13 such that CAPS1 requires the full length of syntaxin-1 to bind. Moreover, CAPS1 favors the open conformation of syntaxin-1. Interestingly, the Munc homology (MH) domain of CAPS1 is not critical for this interaction while the C-terminal dense core vesicle binding (DCVB) domain plays an important role. Moreover, truncations to this DCVB domain result in decreased binding to syntaxin-1.
Mechanisms of Positive and Negative Epistasis among Three Determinants of Adaptation in Saccharomyces cerevisiae
Keywords: epistasis
yeast

In a previous study, three determinants of fitness were identified as mutant alleles (each designated "e") that arose in yeast populations propagated in divergent environments. In a low-glucose environment, MDS3e and MKT1e interacted positively to confer a fitness advantage. PMA1e from a high-salt environment interacted negatively with MKT1e in low glucose, indicating a mechanism of reproductive isolation. In this thesis, I demonstrated that the negative interaction between PMA1e and MKT1e is mediated by alteration in intracellular pH and likely by a delay of the cell division cycle, while the positive interaction between MDS3e and MKT1e is mediated by changes in gene expression affecting glucose transporter genes. I also confirmed the evolutionary significance of the positive interaction by showing that an MDS3e genetic background is required for the recapitulation of the MKT1e mutation. Collectively, these results illustrate how epistasis can play a central role in both adaptation and speciation.
Justice for All: Ontario's Civil Access to Justice System
Keywords: access to justice
Ontario

This paper argues for increased access to civil justice in Ontario for citizens who cannot privately afford it (“needy citizens,” defined as those unable to engage in meaningful civil legal action due to financial inability). Access to justice is defined as access to trained legal representation as well as access to knowledge about Ontario civil law. The paper first articulates the theoretical underpinnings necessitating access to justice for all citizens. The paper then explores 5 common areas of Ontarian civil law (tort, residential, family, small business, and standard contract law) regarding access to civil justice within these regimes, and discusses 3 potential ways to remedy Ontario’s civil access to justice gap. These reforms are increasing government funding, an increase in activity by the legal profession of Ontario, and finally limited deregulation of Ontario’s law licensing process. The first two reforms are rejected, while the third is recommended.
Modeling of Dielectric Barrier Discharge Plasma Actuators for Flow Control Simulations
Keywords: Fluid Dynamics
Plasma Physics

Single-dielectric-barrier-discharge (SDBD) plasma actuators have shown much promise as an actuator for active flow control. Proper design and optimization of plasma actuators requires a model capable of accurately predicting the induced flow for a range of geometrical and excitation parameters. A number of models have been proposed in the literature, but have primarily been developed in isolation on independent geometries, frequencies and voltages. This study presents a comparison of four popular plasma actuator models over a range of actuation parameters for three different actuator geometries typical of actuators used in the literature. The results show that the hybrid model of Lemire & Vo (2011) is the only model capable of predicting the appropriate trends of the induced velocity for different geometries. Additionally, several modifications of this model have been integrated into a new proposed model for the plasma actuator, introducing a number of improvements.
The Use of Grammatical and Social Cues in Early Referential Mapping
Keywords: word learning
language acquisition
plural inflection
grammatical cues
singular-plural distinction
social cues
eye gaze

The preferential looking paradigm was used to investigate how toddlers integrate recently learned grammatical cues with well-established social cues in a novel word-learning scenario. To test this we examined children’s ability to decipher the referent of a novel noun using the grammatical information from a plural cue and social information from an eye-gaze cue. Experiment 1 is the first study showing that children as young as 24 months of age can rely on plural markings alone to infer the referent of a novel noun. Preliminary results of Experiment 2 suggest that when the plural cue is presented alongside contradicting information from a gaze direction cue, children still map the novel word to the grammatically cued object. Taken together, these results suggest that by the time children reach their second birthday, even newly learned grammatical information, such as plural markings, might already outweigh established social cues.
Characterizing the Mechanism of Cul7-mediated Inhibition of Cell Death
Keywords: Cul7
Myc
Cell Death

Cullin 7 (Cul7) is a member of the cullin protein family that is emerging as a complex anti-apoptotic player in tumourigenesis. We hypothesize that by determining the mechanism through which Cul7 can protect against specific forms of cell death, we will uncover novel molecular pathways important in cancer. We aimed to address mechanism by evaluating which domains within Cul7 are important for its activity. Thus, we have introduced mutations in each of the Cul7 domains and asked whether any of these has an effect on the ability of Cul7 to inhibit cell death. To be able to detect even subtle affects of mutation, we required that mutants be assessed in appropriate experimental systems where ectopic wild-type Cul7 could robustly inhibit death compared to vector controls. We screened multiple cell lines and agonists, and have now indentified conditions in U2OS and SHEP cell lines in which our mutants can be evaluated.
Paleoecological and Carbon Accumulation Dynamics of a Fen Peatland in the Hudson Bay Lowlands, Northern Ontario, from the Mid-Holocene to Present
Keywords: Northern Peatland Paleoecology
Peatland Carbon Accumulation

Pollen assemblages, peat humification and carbon:nitrogen stratigraphy were examined at high resolution in a core from a fen peatland in the Hudson Bay Lowlands, Northern Ontario, to interpret the factors that drive long-term peatland dynamics. Subtle changes in the vegetation community are evident over the record, suggesting both allogenic and autogenic influences, but a fen community appears to have been resilient to external perturbations including isostatic rebound and hydroclimatic changes between 6400 and 100 years BP. Paleoclimatic reconstructions from the fossil pollen assemblages indicate that precipitation increased 3000 years BP at the end of the Holocene Thermal Maximum, and that carbon accumulation in the fen was controlled more by effective surface moisture (precipitation) than by temperature. The pollen record suggests changes over the past century, including increases in shrub Betula, Alnus, Ambrosia, and Cyperaceae and a decrease in Sphagnum spores, consistent with the observed Pan-Arctic shrub increase.