VictorJuiz/thesis huggingface dataset:
Role of Fatty Acid Transport Proteins in Oleic Acid-induced Secretion of Glucagon-like Peptide-1

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.

Keywords: oleic acid
fatty acid transport proteins
glucagon-like peptide-1
GLP-1
L cell
diabetes
Advisor: Brubaker, Patricia
Viscous Relaxation Times of the Core and Mantle of Mars from Observations of Tidal Decay of the Orbit of Phobos

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.

Keywords: Mars
Mantle
Core
Maxwell relaxation
Normal modes
Advisor: Ghent, Rebecca R.
Bills, Bruce G.
Catalytic Asymmetric Hydrogenation: Toward Chiral Diamines and Cyclohexanes

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.

Keywords: Hydrogenation
Benzene
Advisor: Dong, Vy Maria
Handling Qualities of a Blended Wing Body Aircraft

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.

Keywords: flight simulation
handling qualities
blended wing body
Advisor: Grant, Peter R.
Double Dissociation of Associative and Non-associative Learning following Conditioning to a Single Odorant in the Caenorhabditis elegans AWC Olfactory Neruons

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.

Keywords: C. elegans behaviour
Olfactory learning genetics
Advisor: Kooy, Derek van der
Computational Study of Volumetric Effects of Hydration

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.

Keywords: molecular dynamics
partial molar volume
Advisor: Chalikian, Tigran
CAPS1 (Calcium Dependent Activator Protein for Secretion 1) Role in Catecholamine Secretion: A Structural Functional Analysis

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.

Keywords: Secretion
CAPS1
Advisor: Sugita, Shuzo
Mechanisms of Positive and Negative Epistasis among Three Determinants of Adaptation in Saccharomyces cerevisiae

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.

Keywords: epistasis
yeast
Advisor: Anderson, James
Kohn, Linda M.
Justice for All: Ontario's Civil Access to Justice System

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.

Keywords: access to justice
Ontario
Advisor: Yoon, Albert
Modeling of Dielectric Barrier Discharge Plasma Actuators for Flow Control Simulations

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.

Keywords: Fluid Dynamics
Plasma Physics
Advisor: Lavoie, Philippe
The Use of Grammatical and Social Cues in Early Referential Mapping

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.

Keywords: word learning
language acquisition
plural inflection
grammatical cues
singular-plural distinction
social cues
eye gaze
Advisor: Johnson, Elizabeth
Characterizing the Mechanism of Cul7-mediated Inhibition of 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.

Keywords: Cul7
Myc
Cell Death
Advisor: Penn, Linda Z.
Paleoecological and Carbon Accumulation Dynamics of a Fen Peatland in the Hudson Bay Lowlands, Northern Ontario, from the Mid-Holocene to Present

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.

Keywords: Northern Peatland Paleoecology
Peatland Carbon Accumulation
Advisor: Finkelstein, Sarah A.
Semantic Integration of Time Ontologies

Here we consider the verification and semantic integration for the set of first-order time ontologies by Allen-Hayes, Ladkin, and van Benthem that axiomatize time as points, intervals, or a combination of both within an ontology repository environment. Semantic integration of the set of time ontologies is explored via the notion of theory interpretations using an automated reasoner as part of the methodology. We use the notion of representation theorems for verification by characterizing the models of the ontology up to isomorphism and proving that they are equivalent to the intended structures for the ontology. Provided is a complete account of the meta-theoretic relationships between ontologies along with corrections to their axioms, translation definitions, proof of representation theorems, and a discussion of various issues such as class-quantified interpretations, the impact of namespacing support for Common Logic, and ontology repository support for semantic integration as related to the time ontologies examined.

Keywords: Time Ontologies
First Order Logic
Semantic Integration
Ontology Verification
Advisor: Gruninger, Michael John
The Effects of Acute Sodium Ingestion on Food and Water Intakes, Subjective Appetite, Thirst and Glycemic Response in Healthy Young Men

High dietary sodium intake is hypothesized to increase food intake (FI), fluid intake and glycemic response. Two short-term randomized repeated-measures studies measured the effects of acute sodium intake on FI, water intake (WI), subjective appetite (SA), thirst, and blood glucose (BG) in young men. Sodium additions were 740 and 1480 mg to a solid food (beans) in Experiment 1; and 500, 1000, 1500 and 2000 mg to a beverage (tomato juice) in Experiment 2. FI and WI were measured at ad libitum pizza meals 120 and 30 min later, respectively. SA, thirst and BG were measured at intervals before and after pizza. Compared with controls, treatments with added-sodium had no effect on dependent measures. In conclusion, acute intake of sodium in a solid or liquid matrix does not increase subjective ratings of appetite or thirst, ad libitum food or water intakes, or blood glucose in healthy young adults.

Keywords: acute sodium intake
food intake
appetite
thirst
water intake
blood glucose
Advisor: Anderson, G. Harvey
Resolution of Maxillary Sinus Mucositis after Endodontic Treatment of Maxillary Teeth with Apical Periodontitis: A Cone-beam Computerized Tomography Pilot Study

This study characterized maxillary sinus mucositis (SIMS) adjacent to teeth with apical periodontitis (AP), and assessed its resolution three months after endodontic treatment. 29 subjects who maxillary posterior teeth with AP were imaged with cone-beam computed tomography (CBCT). Resolution of SIMS was assessed with CBCT three months after treatment, and periapical healing was assessed using the PAI after six months. Four non-compliant subjects were discontinued and SIMS was identified in 14/25 subjects (56%). Three months post-treatment, SIMS was resolved fully in 3/10 subjects (30%), and partially in 3/10 subjects (30%). Six months post-treatment, 6/10 subjects (60%) were classified as healed or healing. CBCT revealed a lower-than-expected prevalence of SIMS adjacent to teeth with AP. In specific cases SIMS might linger beyond three months after the elimination of the endodontic infection. Due to the low statistical power, association between the resolution of SIMS and periapical healing could not be explored.

Keywords: CBCT
healing
maxillary sinus mucositis
endodontic treatment
Advisor: Lam, Ernest W.
Characterization of the Interface between the Annulus Fibrosus and the Vertebral Bone.

Replacing a diseased disc with a tissue engineered disc has the potential to restore normal spinal biomechanics. However, recreating the interface between annulus fibrosus (AF) and vertebral bone (VB) will be necessary to facilitate proper function of the implant in vivo. This study characterizes the native bovine AF-VB interface and assesses adult human discs. The AF insertion site in humans and cows is uniquely differentiated from other soft tissue-bone interfaces, as AF collagen fibers anchor into the calcified region of vertebral endplate through a zone of hyaline cartilage and have a different organization in inner and outer AF. Mineralization-associated proteins are present in this region and the chondroid tissue undergoes calcification over time. Based on these observations an in vitro AF culture system was developed and demonstrated that AF cells can induce mineralization. Understanding mechanism(s) regulating AF mineralization will help develop conditions to ensure proper integration of bioengineered AF.

Keywords: Annulus fibrosus
cartilage endplate
collagen
vertebral bone
alkaline phosphatase
mineralization
Advisor: Kandel, Rita A.
Santerre, J. Paul
Diels-alder Click Cross-linked Hyaluronic Acid Hydrogels for Tissue Engineering

Hyaluronic acid (HA) is a naturally occurring polymer that holds considerable promise for tissue engineering applications. Current cross-linking chemistries often require a coupling agent, catalyst, or photoinitiator, which may be cytotoxic, or involve a multistep synthesis of functionalized-HA, increasing the complexity of the system. With the goal of designing a simpler one-step , aqueous-based cross-linking system, we synthesized HA hydrogels via Diels-Alder “click” chemistry. Furan-modified HA derivates were synthesized and cross-linked via dimaleimide poly(ethylene glycol). By controlling the furan to maleimide molar ratio, both the mechanical and degradation properties of the resulting Diels-Alder cross-linked hydrogels can be tuned. Rheological and degradation studies demonstrate that the Diels-Alder click reaction is a suitable cross-linking method for HA. These HA cross-linked hydrogels were shown to be cytocompatible and may represent a promising material for soft tissue engineering.

Keywords: click chemistry
hyaluronic acid
tissue engineering
hydrogels
Diels-Alder chemistry
regenerative medicine
Advisor: Shoichet, Molly
Direct Costs of Hip Fractures among Seniors in Ontario

Osteoporosis is a major public health problem resulting in substantial hip fracture related morbidity. Using healthcare utilization data, we determined the 1- and 2-year direct attributable healthcare costs associated with hip fractures among Ontario seniors in comparison to a matched non-hip fracture cohort. Over a four-year period (2004-2008) we identified 22,418 females and 7,611 males with an incident hip fracture. Approximately 22% of females and 30% of males died in the first year after fracture. The mean attributable cost in the first year was $36,929 ($52,232 vs. $15,503) among females and $39,479 ($54,289 vs. $14,810) among males. Primary cost drivers included acute hospitalizations, complex continuing care, and rehabilitation. Attributable costs remained elevated into the second year, particularly among those who survived the first year ($9,017 females and $10,347 males). Results from this study will aid policy decision makers in allocating healthcare resources and help feed into future health economic analyses.

Keywords: Hip Fracture
Cost of Illness
Osteoporosis
Advisor: Cadarette, Suzanne M.
Instruction-set-simulator-less Virtual Prototype Framework for Embedded Software Development

With continuous advancement in silicon technology and high feature demands on consumer electronics, the complexity of embedded software has led the software development effort to dominate System-On-Chip (SoC) design. Virtual Prototype (VP) addresses the problem by enabling early software development before hardware arrival. However, VP still poses challenges: 1) Instruction Set Simulator (ISS) degrades simulation time, 2) Development is restricted to embedded processor specific tools and 3) Applications and drivers are dependent on system software completion. In this work, we propose an abstraction framework which: 1) Removes ISS from VP, achieving native host software execution time, 2) Activates rich suites of desktop development tools in host by compiling embedded software in host binary and 3) Allows system software independent application and driver development. With this framework, we successfully demonstrated up to 2000% speed-up in VP run-time over conventional VP and improved software development productivity significantly.

Keywords: Embedded System
Embedded Software
Virtual Prototype
SoC
ISS
C model
HAL
API
Advisor: Zhu, Jianwen