VictorJuiz/thesis huggingface dataset:
Hypothalamic AMP-activated Protein Kinase Regulates Glucose Production
Keywords: Diabetes
Nutrient Sensing
Hypothalamic AMPK
Glucose Production

Hypothalamic AMP-activated protein kinase (AMPK) regulates energy homeostasis in response to nutritional and hormonal signals. However, its role in glucose production regulation remains to be elucidated. Here, we tested the hypothesis that bidirectional changes in hypothalamic AMPK activity alter glucose production in rodents. First, we found that knocking down hypothalamic AMPK activity in an in vivo rat model led to a significant suppression of glucose production independent of changes in food intake and body weight. Second, we showed that activation of hypothalamic AMPK negated the ability of hypothalamic glucose- and lactate- sensing to lower glucose production. Collectively, these data indicate that changes in hypothalamic AMPK activity are sufficient and necessary for hypothalamic nutrient-sensing mechanisms to alter glucose production in vivo, and highlight the novel role of hypothalamic AMPK in the maintenance of glucose homeostasis in addition to energy balance.
Multimedia Features in Electronic Health Records: An Analysis of Vendor Websites and Physicians' Perceptions
Keywords: electronic medical record
ehealth
health information technology
technology acceptance model
diffusion of innovations

Electronic health records (EHRs) facilitate storing, organizing, and sharing personal health information. The academic literature suggests that multimedia information (MM; image, audio, and video files) should be incorporated into EHRs. We examined the acceptability of MM-enabled EHRs for Ontario-based software vendors and physicians, using a qualitative analysis of primary and acute care EHR vendor websites, and a survey of physician perceptions regarding MM features in EHRs. Primary care EHR vendors provided more product-specific information than acute care vendors; however, neither group emphasized MM features in their EHRs. Physicians had slightly positive perceptions of image and video features, but not of audio features. None of the external factors studied predicted physicians‘ intention to use MM. Our findings suggest that neither vendors nor physicians are enthusiastic about implementing or using MM in EHRs, despite acknowledging potential benefits. Further research is needed to explore how to incorporate MM into EHR systems.
Probing the Mechanism of Correction in ΔF508-CFTR
Keywords: cystic fibrosis
corrector
biochemistry

Cystic Fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which cause loss function of the CFTR channel on the apical surface of epithelial cells. ΔF508-CFTR, the major mutation in patients, is misfolded, retained in the endoplasmic reticulum (ER) and degraded. Small molecule corrector compounds partially rescue the trafficking defect of ΔF508-CFTR by allowing escape from the ER and trafficking to the plasma membrane where it exhibits partial function. These compounds may bind directly to the mutant protein and rescue the biosynthetic defect by inducing improved protein conformation. We tested this hypothesis by evaluating the consequence of corrector compound on the conformation of each nucleotide-binding domain (NBD) in the context of the full-length mutant protein in limited proteolytic digest studies. We found that VRT-325 was capable in partially restoring compactness only in NBD1. In comparison, ablation of the arginine framed peptide sequence: R553XR555 (ΔF508-KXK-CFTR) modified the protease resistance of NBD1, NBD2 and the full-length protein. Singly, each intervention led to a partial correction of the processing defect. Together these interventions restored processing of ΔF508-CFTR to near wild-type levels. Importantly however, a defect in NBD1 conformation persisted, as did a defect in channel activation after the combined interventions. This defect in channel activation can be fully corrected by addition of the potentiator: VX-770. The experiments performed partly elucidated ii the molecular mechanism of action for drug therapy and suppressor mutation. It is important to understand these basic concepts in hopes to layout a blue print for future drug design.
Experimental and Kinetic Modeling Study of 1-hexanol Combustion in an Opposed-flow Diffusion Flame
Keywords: Combustion
1-Hexanol
Kinetic Modeling
Biofuels
Oppposed-flow diffusion flame

Biofuels are of particular interest as they have the potential to reduce our dependence on petroleum-derived fuels for transportation. 1-Hexanol is a promising renewable long chain alcohol that can be used in conventional fuel blends or as a cosolvent for biodiesel mixtures. However, the fundamental combustion properties of 1-hexanol have not been fully characterized in the literature. Thus, new experimental results, consisting of temperature and concentration profiles of stable species were obtained for the oxidation of 1-hexanol generated in an opposed-flow diffusion flame at 0.101 MPa. The kinetic model consists of 361 chemical species and 2687 chemical reactions (most of them reversible). This experimental data were compared to the predicted values of a detailed chemical kinetic model proposed in literature to study the combustion of 1-hexanol. Reaction pathway and sensitivity analyses were performed to interpret the results. In addition, several improvements were investigated to optimize the proposed chemical kinetic mechanism.
Investigating the Evolution and Functional Diversification of Pseudomonas syringae type III effector HopZ1
Keywords: type III effector
evolution
Pseudomonas syringae
HopZ1a

The pathogenicity of plant pathogen Pseudomonas syringae depends on the type III secretion system which translocates effector proteins into host cells. In response, plants have evolved resistance proteins to detect presence of specific effectors and activate defense responses. The constant host surveillance imposes a strong selective pressure on effector proteins to evolve rapidly in order to evade detection. The P. syringae HopZ1 effector has evolved into three allelic forms as a result of diversifying selection. In this thesis, I aimed to investigate how sequence divergence contributes to the distinct allelic specificities of HopZ1. Mutational analysis of HopZ1a identified three amino acid residues that were potentially involved in dampening host defense responses, and two HopZ1a mutants partially lost the ability to trigger defense responses yet did not lose their virulence functions. These results suggested that distinct host targets could be involved in the defense-eliciting activity and virulence function of HopZ1a.
Formation and Metabolism of Sugar Metabolites, Glyoxal and Methylglyoxal, and their Molecular Cytotoxic Mechanisms in Isolated Rat Hepatocytes
Keywords: Dicarbonyls
Oxidative Stress
Fructose
Protein carbonylation
Diabetes
AGEs

High chronic fructose consumption has been linked to many diseases. Sugar metabolites, especially glyoxal and methylglyoxal can form advanced glycation products, which contribute to the pathology of diabetic complications. Our objective was to study the metabolism of these metabolites and the associated protein carbonyation and cytotoxicity in isolated hepatocytes. In addition, the effect of oxidative stress on the metabolism of these toxins was also investigated. Methylglyoxal and glyoxal can induce protein carbonylation, which contributes to hepatocyte toxicity. Methylglyoxal, but not glyoxal, was detoxified mainly by the glyoxalase system. Both toxins can be metabolized by mitochondrial aldehyde dehydrogenase. The detoxification of glyoxal was impaired under oxidative stress conditions (i.e. increased hydrogen peroxide level). Glyoxal was found to be a common autoxidation product from glyceraldehyde, hydroxypyruvate and glycolaldehyde. Glyoxal and the reactive oxygen species formation during the autoxidation process contributed to the hepatocyte toxicity of glyceraldehyde, hydroxypyruvate and glycolaldehyde.
Hydrogenated Amorphous Silicon Carbide Prepared using DC Saddle Field PECVD for Photovoltaic Applications
Keywords: amorphous silicon carbide
DC saddle field PECVD

Hydrogenated amorphous silicon carbide (a-SiC:H) can provide exceptional surface passivation essential for high-efficiency crystalline silicon solar cells. This thesis reports on the fundamental study of a-SiC:H films deposited using a novel deposition technique, DC saddle field PECVD, in contrast to the conventional industrial use of RF-PECVD. The growth conditions were optimized and correlated with passivating, structural, and optical characteristics. The lifetime has a strong dependency on deposition temperature and improves by over two orders of magnitude as the temperature increases; the maximum lifetime achieved in this work reached 0.5 ms. In addition, the Tauc optical gap can be increased from 1.7 eV to 2.3 eV by varying the precursor gas mixture ratio. Post-deposition annealing experiments demonstrate thermal stability of the samples deposited at 250 °C and in some instances shows improvement in passivation quality by a factor of two with a one-step annealing treatment at 300 °C for 15 minutes.
Modeling and Application of a Thermoelectric Module
Keywords: thermoelectric
modeling

Thermoelectric modules are an important alternative to heat engines in the harvesting of waste heat. Electrical-thermal analogues are often employed when studying heat conduction and this analogue can be extended to develop an equivalent circuit for thermoelectric effects. For the primarily one-dimensional problem of thermoelectricity, the equations can be discretized to create a simple mathematical model. In this document, such a model is developed from first principles and show that the electro-thermal coupling is properly in- corporated. The results of simulations using the model are then presented and validated experimentally. Furthermore, in one possible application of thermoelectric modules, a self-contained cooling unit with an integrated thermoelectric generator is designed. By performing fluid dynamics simulations on a fan and heat sink model, the geometry and operating conditions can be optimized and the start-up and transient characteristics are studied.
A Framework for Aerostructural Analysis of Wind Turbine Blades
Keywords: Wind Turbine
Aerostructural

As international growth in wind energy steadily increases and the world gradually moves away from fossil fuels, advanced computational tools are required to produce accurate and fast predictions in wind turbine performance, and to allow efficient design cycles using advanced materials and manufacturing methods. Currently, aerostructural analysis often employs the relatively fast but inaccurate Blade Element Momentum (BEM) theory, while accurate but slower Computational Fluid Dynamics (CFD) methods are generally used for aerodynamic analysis alone.To bridge the gap between speed and accuracy, a 3D panel code, TriPan, was coupled with an advanced structural Finite Element Method (FEM) code, TACS, to perform aerostructural analysis for wind turbine blades. In addition, the framework allows the replacement of the panel solver by higher fidelity solvers to increase the accuracy of the overall aerostructural solution.
Investigating the Mechanisms of Forgetting in Aging Using Eyetracking
Keywords: forgetting
interference
aging
eyetracking
representational-hierachical model

Recent studies in rodents (McTighe et al, 2010; Burke et al, 2010) have suggested that forgetting is caused by the misidentification of novel stimuli as being familiar, matching the predictions of the representational-hierarchical model of Saksida & Bussey (2010). Here, we tested this idea in humans. Three groups of participants (young, healthy elders, elders at-risk for MCI) viewed novel and repeated stimuli in a continuous viewing task while their eye movements were recorded. According to the eye-movement based memory effect (Ryan et al, 2000) individuals make fewer fixations on items which are perceived as familiar. As interference increased, eye-movements directed to the novel stimuli declined, indicating these novel items were perceived as familiar. This effect was stronger in groups more vulnerable to interference (eg. at-risk elders). These results suggest that forgetting in humans, like rats, is driven by the misidentification of novel items as being familiar.
The Neural Correlates of Implicit Theory Violation
Keywords: implicit theory
N400
theory violation

Implicit theories play an important role in the structure and maintenance of people’s sense of meaning, and violations to one’s theory can create significant distress. Using electroencephalography (EEG), this study examined the neural correlates of implicit theory violation. Participants were primed with one of two implicit theories of success attainment and were then shown a series of words that either confirmed or violated that theory. Analyses revealed that compared to implicit theory confirmations, implicit theory violations produced greater N400 amplitudes, which is a brain wave associated with “semantic violations,” or violations of meaning. Current literature on the N400 has been limited to language-specific semantic violations. Therefore, these results represent a novel extension of the N400 to include violations of complex lay theories of human behavior. Furthermore, these data suggest that implicit theories represent a fundamental type of semantic knowledge that helps perceivers to generate predictions about the social world.
Nonlinear Fault-tolerant Guidance and Control for Damaged Aircraft
Keywords: fault-tolerant guidance and control
damaged aircraft

This research work presents a fault-tolerant flight guidance and control framework to deal with damaged aircraft. Damaged scenarios include the loss of thrust, actuator malfunction and airframe damage. The developed framework objective is to ensure that damaged aircraft can be stabilized and controlled at all times. The guidance system is responsible for providing the airspeed, vertical and horizontal flight path angle commands while considering aircraft dynamics. The control system, designed by the nonlinear state-dependent Riccati equation (SDRE) control method, is used to track the guidance commands and to stabilize the damaged aircraft. The versatility of SDRE allows it to passively adapt to the aircraft parameter variations due to damage. A novel nonlinear adaptive control law is proposed to improve the controller performance. The new control law demonstrated improved tracking ability. The framework is implemented on the nonlinear Boeing 747 and NASA Generic Transport Model (GTM) to investigate the simulation results.
Quantifying Multi-directional Trunk Stiffness During Sitting with and without Functional Electrical Stimulation: Able-bodied Subjects
Keywords: Biomedical

To build an Functional Electrical Stimulation (FES) system that assists individuals with spinal cord injury (SCI) to improve sitting balance, one needs to determine multidirectional stiffness of the trunk during sitting and demonstrates that this stiffness can be influenced by FES. Therefore, the purposes of this study were: (1) to develop a novel protocol to quantify and identify the multidirectional stiffness of the trunk during sitting; and (2) to test the effect of FES on the multidirectional stiffness of the trunk. 15 able-bodied subjects were recruited. Each subject was perturbed in 8 different directions using 8 linear motors during quiet sitting with and without FES applied to his front/back trunk muscles. Stiffness in the lateral directions was the highest and FES increased stiffness of the trunk in the anterior/posterior direction. These results can be used to develop an FES protocol for individuals with SCI to improve their sitting balance.
Development of a Novel Measure of Three-dimensional Bone Connectivity in a Mouse Tibia Fracture Model: Characterizing Torsional Strength and Stiffness Through Failure Surface Analysis
Keywords: fracture healing
strength

The high incidence of long bone fractures and appreciable rate of delayed and non-union (5-10%) necessitates the development of non-invasive tools to monitor healing progression. The objective of this study was to develop a novel µCT-based measure of three-dimensional bone connectivity and to compare its ability to assess fracture callus mechanical stability to previously described measures. Bone connectivity parameters local to the failure surface were found to significantly correlate with mechanical stability, and proved superior to previously developed measures of torsional rigidity. Visualization of the failure surfaces demonstrated a consistent failure pattern indicative of the applied torsional loading, however the locations of the failure surfaces showed varying levels of fracture callus involvement. The results of this proof of concept work indicate the potential utility of bone connectivity analysis in non-invasive assessment of fracture callus stability.
Catalytic Gasification of Pretreated Activated Sludge Supernatant in Near-critical Water
Keywords: Pretreatment, Activated Sludge, supercritical water gasification

Pretreatment of waste activated sludge (WAS) and the subsequent near-critical water gasification (NCWG) is a potential avenue to convert WAS into value added products. Part one of the research investigated thermal and thermochemical pretreatments. No difference was observed in the percentage of sludge liquefied beyond 10min between 200°C to 300°C. It was found that pretreated activated sludge supernatant (PASS) doubled the gas yield compared to untreated sludge when gasified. The order of effectiveness for sludge treatment was thermo-alkali > thermal > thermo-acid for hydrogen production in NCWG. Part two investigated NCWG parameters to identify optimal conditions. High gasification yields were obtained using a commercial catalyst (Raney nickel), with hydrogen content of 65-75% of the gas phase products. Thermo-alkali treated PASS was found to perform well at subcritical temperatures with 25% higher yields than thermally treated PASS. Increased catalyst loading had little additional effect on gas yields above 0.075g.
Development of a Hybrid Linear Actuator
Keywords: hybrid
actuator

This thesis focuses on the development of a novel hybrid linear actuator (HLA). The research includes the optimal design, the particular fabrication, and the experimental validation. The principle of the HLA is based on the integration of the mechanisms of the solenoid actuator and the voice coil actuator. Such integration is achieved by a magnetic circuit consisting of a magnetic flux orientator, a permanent magnet, a composite shell, and a special coil. The HLA is capable of having a high repelling force at one end and a high attractive force at another end. A step-optimization technique is developed and used to determine the key parameters of the HLA, with the aid of sweeping functions in finite element analysis. Moreover, a single-pulse power supply is specially designed and prototyped for driving the HLA. The performance of the HLA is systematically characterized by simulations and experiments.
Effect of G-Jitter on Liquid Bridge Vibrations with & without Marangoni Convection
Keywords: Marangoni
convection
g-jitter

Effects of external vibrations (called g-jitter) on Marangoni convection in a liquid bridge were investigated on the International Space Station (ISS) and in ground-based experiments. In ISS, most dominant g-jitter frequency was noted to be ~110 Hz. ISS experiments suggested that the surface vibrations were mainly affected by the aspect ratio (length/diameter ratio), but not the imposed temperature gradient. Liquid bridge surface vibrations agreed well with Ichikawa et al.’s model. Ground-based experiments confirmed that increasing the volume ratio would cause the resonance frequency to increase. When a temperature difference was imposed between the upper and lower disks, for constant aspect and volume ratios, the resonance frequency tended to increase with the decreasing temperature difference. Furthermore, the shift in the resonance frequency due to a temperature difference, was found to be due to Marangoni convection and not due to reduced viscosity or surface tension of the fluid.
Borinic Acid-catalyzed Regioselective Functionalization of Polyols
Keywords: borinic acid catalysis
diol
carbohydrate

The selective manipulation of hydroxyl groups in di- and polyols is a frequently encountered problem in organic synthesis. Such processes are often tedious and/or moderate yielding, and often necessitate multistep protection / deprotection sequences. Applying boron–diol interactions previously exploited in molecular recognition and based on methods previously developed in our research group, we have developed two classes of chemical transformations: 1. Regioselective sulfonylations of carbohydrate derivatives catalyzed by a borinic ester, providing access to the corresponding mono-tosylates in high yields; 2. Selective monoalkylations and monosulfonylations of structurally diverse 1,2- and 1,3-diol substrates.
The Role of Alternatively spliced Fibroblast Growth Factor Receptor 2 Isoforms in Breast Cancer
Keywords: Fibroblast Growth Factor Receptor 2
Breast Cancer
NF-κB

Recent genome-wide association studies identified FGFR2 as one of breast cancer susceptibility genes. FGFR2 expression was down-regulated in breast carcinomas when compared with paired normal epithelium. Stable retroviral transduction of FGFR2-IIIb and its alternatively spliced FGFR2-IIIc variants was achieved in breast cancer MDA-MB-231, T47D and near normal MCF-10A cells. Our findings revealed a direct reduction of breast cancer cell growth and motility, a significant arrest of transformed morphogenetic changes including the Epithelial to Mesenchymal transition (EMT), anchorage independent growth, and the formation of growth-arrested 3D acinar architectures, and suppressive actions on orthotopically xenografted epithelial neoplasms and surrounding tumor stroma. These tumor protective effects were concordant with physical interactions between the two FGFR2 isoforms and IKKβ. Consistent with these interactions we noted FGFR2 to inhibit NF-κB signaling, including decreased nuclear RelA/p65 NF-κB localization, down-regulation of a transfected NF-κB luciferase reporter, reduced production of NF-κB-dependent transcripts, Interleukin-6 and p-STAT3.
Establishing the Functional Links between Stowaway-like MITEs and Transposases Belonging to the Tc1/Mariner Superfamily in the Yellow Fever Mosquito, Aedes aegypti
Keywords: Transposable element
Miniature inverted repeat transposable elements
Tc1/Mariner
Aedes aegypti
Stowaway

Miniature Inverted-repeat Transposable Elements (MITEs) are a type of transposable element (TE) that lacks coding capacity. It has been established that in rice that certain Stowaway MITEs are mobilized by transposases from the Tc1/Mariner superfamily of TEs. To retrieve all Tc1/Mariner TEs from the genome, bioinformatic approaches were performed. A total of 295 Tc1/Mariner TEs that encoded a full or partial transposase were recorded which 100 were newly described. Sequence alignment, and identification of the catalytic motif placed these transposases into eight groups. A functional link was established by comparing the terminal sequences of the Stowaway-like MITEs to the termini of the terminal sequences of Tc1/Mariner TEs. A yeast excision assay was used to experimentally test these functional links. Majority of the Stowaway-like MITE and transposase combinations tested did not indicate a functional link. However, a possible functional link was observed between the AATp3-13 transposase and AAStow-5 Stowaway-like MITEs.