VictorJuiz/thesis huggingface dataset:
Investigating the ERBB Protein Interactome
Keywords: ErbB receptors
LUMIER

The erythroblastoma (ErbB) receptor family consists of four members that are implicated in many human cancers. To gain insight into their biological function, we investigated their interacting partners to derive a comprehensive protein interaction network. Using the membrane yeast two-hybrid (MYTH) system we probed the ErbB2, ErbB3, and ErbB4 interaction space and validated a subset of interacting partners using the luminescence-based mammalian interactome mapping (LUMIER) system. The integrated use of these two complementary protein interaction technologies generated high confidence data and identified many novel ErbB binding partners, a subset of which was supported by co-immunoprecipitation in the breast adenocarcinoma cell line Sk-Br-3 including the GPCR GPRC5B, the cysteine protease CAPN1, and WIF1, a secreted protein containing 5 EGF domains that may represent a novel ErbB ligand. Our systematic approach offers an unbiased systems level view that may identify novel drug targets and contribute to therapeutic research.
microRNAs in the Drosophila Egg and Early Embryo
Keywords: Drosophila
egg
microRNA
embryo
oocyte
miR-309

Posttranscriptional regulation plays a very important role in animal oocytes and embryos. Maternally synthesized mRNAs and proteins control early animal development up until the maternal-to-zygotic transition (MZT). This is the point when the zygotic genome takes control. The maternally deposited mRNAs are posttranscriptionally regulated right from the time they are produced during oogenesis, through egg activation, and in the embryo. microRNAs (miRNAs) are posttranscriptional regulators that have been shown to play a role in both RNA stability and translation. I examined miRNA abundance in Drosophila stage 14 oocytes, activated unfertilized eggs, and embryos and have grouped all the then known Drosophila miRNAs into four distinct temporal classes. Class I and III appear to be maternally deposited, while Class II appears to be both maternally and zygotically transcribed, and Class IV appears to be strictly zygotically transcribed. Follow-up experiments validated three of the four classes.
Translational Regulation of smaug mRNA
Keywords: Translation
mRNA
Pumilio
Smaug
Drosophila
maternal mRNA
oocyte
embryo

In Drosophila, early embryonic development is controlled by maternally loaded RNAs and proteins. For proper development to occur it is vital these maternal transcripts are post-transcriptionally regulated. SMAUG, a major post-transcriptional regulator, has been found to be responsible for the destabilization of two thirds of the unstable maternal transcripts upon egg activation (Tadros et al., 2007). smg mRNA is translationally repressed in stage 14 oocytes, but its translation is activated upon egg activation in a PAN GU kinase dependent manner. Here I show that redundant translational repression elements reside in the smg 3’UTR, and PUMILIO mediates repression through one of these elements. I also show that these elements are sufficient to cause translational repression in stage 14 oocytes. smg mRNA appears to be regulated post-initiation in stage 14 oocytes in a large repression complex which is similar to smg mRNA repression in a png mutant.
Matrix Supplemented Stem Cell Microencapsulation for Regenerative Medicine
Keywords: Biomedical Engineering
Cell Biology
Medicine and Surgery
0564
0379

Previous studies reported that matrix protein supplementation (fibronectin/fibrinogen, FN/FG) of agarose gel microcapsules enhances survival and pulmonary retention of syngeneic rat multipotent stromal cells (MSCs). I hypothesized that additional supplementation of microcapsules with osteopontin (OPN) and transglutaminase 2 (TG2) would enhance cell survival, while stabilizing the provisional matrix. Using monomeric OPN or OPN polymerized with TG2, I examined human MSC adhesion, morphology, focal contact formation and apoptosis. Polymeric OPN induced greater adhesion than monomeric OPN (84.5±10.7 vs. 44.3±10.0cells/field), and also significantly enhanced focal contact formation (351.5±21.2 vs. 45.6±17.6 focal contact sites/cell) and cell spreading (2.7x103±0.20x103μm2 vs. 1.2x103±0.26x102μm2) while preserving MSC pluripotency. Microcapsules supplemented with FN/FG, polymeric OPN and TG2 demonstrated significantly less apoptotic cells than FN/FG microcapsules (14.0±2.34% vs. 28.2±3.22%). Reduced apoptosis was attributed to matrix stabilization by TG2 and the synergistic activity of matrix proteins. It is anticipated that this enhanced survival will maximize the therapeutic potential of MSCs.
The Transmembrane Receptor UNC-40 Directs Muscle Arm Extension in Caenorhabditis elegans
Keywords: UNC-40
C. elegans
muscle arms
cell guidance
membrane extension

In Caenorhabditis elegans, body muscles extend muscle arms in a chemotropic fashion to the nearest nerve cord and serves as a model for the investigation of guided cell migration. I found that the transmembrane receptor UNC-40/DCC is required, and functions cell-autonomously to regulate muscle arm extension. Surprisingly, both the canonical ligand of UNC-40 (UNC-6/Netrin) and the extracellular domains of UNC-40 are dispensable, suggesting that UNC-40 relies on a co-receptor or other polarizing pathways to direct muscle arm extension. Furthermore, through double mutant analyses and the use of a neomorphic phenotype induced by UNC-40 over-expression, I define a distinct UNC-40 pathway in which UNC-73/Trio, the WAVE actin polymerization complex, and components of the dense body likely act downstream of UNC-40 to regulate muscle arm extension. Distinct modes of UNC-40’s function in muscle arm extension compared to its role in neurons provide a more complete understanding of how this conserved guidance receptor functions.
Effects of Bilateral and Unilateral Deafness Observed from Cortical Responses Evoked in Children with Bilateral Cochlear Implants
Keywords: Cortical Development
Hearing
Deafness
Bilateral Deafness
Unilateral Deafness
Cochlear Implants
Neural Development
Neural Plasticity

This study examined the effects of bilateral and unilateral deafness by measuring cortical auditory evoked potential (CAEP) responses in children at initial stages of bilateral cochlear implant (CI) use. We recorded cortical responses evoked by right and left CI stimulation in 127 children with early onset (< 12 months) deafness, with 72 children receiving the two devices in the same surgery (simultaneously implanted) and 55 children receiving the devices in separate procedures (sequentially implanted). Three different types of responses were identified in children with bilateral CIs. No significant effects of duration of deafness, age at implantation, or duration of unilateral CI use were found on response latencies and amplitudes within each type of cortical response, but there were clear differences in responses types between groups and ears. In the context of these findings, the effects of bilateral and unilateral deafness to the auditory pathways were discussed.
Invasive bacteria induce cellular stress that alters the cytoplasmic dynamics of the SMN complex
Keywords: SMN complex
Invasive Bacteria

The course of pathogenic bacterial infection is dependent on the interactions between the host immune response and the bacterial virulence mechanisms. Our lab previously discovered that the Survival of Motor Neuron (SMN) protein complex undergoes a change in subcellular localization during infection with invasive Shigella bacteria, forming novel cytoplasmic aggregates called "U bodies". Similar results were obtained with other intracellular bacterial pathogens suggesting that these U bodies are a fundamental entity in microbial pathogenesis. Notably, the SMN complex normally plays a key role in the assembly of the spliceosomal U snRNA. We have shown during infection that there are changes in U snRNA maturation and splicing patterns. Importantly, we have found that U bodies are downstream of a stress pathway involving the stress-inducible ATF3 protein. Altogether, intracellular bacterial infection induces novel cellular stress pathways that disrupt normal SMN complex function and leads to changes in U snRNA associated functions.
Efficiency Enhancement Techniques for Switched Mode Power Electronics
Keywords: power management circuit
power efficiency
DC-DC converter
dead-time
LED driver
contrast ratio
energy conservation

In the design of the state-of-the-art electronic products, power management circuits play a very important role for the enhancement of overall system efficiency. Switched mode DC-DC converter is an increasingly popular power management circuit due to its superior power conversion efficiency. This thesis introduces two efficiency optimization techniques for switched mode power electronic circuits. One is dead-time optimization. This technique can automatically adjust the dead-time on-the-fly according to the circuit operating conditions. Second, an energy conservation based high-efficiency dimmable multi-channel LED driver is discussed. An auxiliary power switched is use to allow free wheeling of the inductor current during the load disconnect period. The sequential burst mode PWM current sharing scheme with dimming capability can effectively reduce design complexity and cost. The proposed LED driver provides a practical solution for the realization of LED BLU in the flat panel TVs with local dimming capability according to the video content.
The Role of Septin 5 in Exocytosis
Keywords: Septins
Septin 5
Exocytosis
TIRF
Secretion assay

Septins are an evolutionarily conserved family of proteins that have been implicated in a multitude of cellular processes. Septin 5 is mainly expressed in the nervous system and it has been linked to regulated secretion through its binding to the SNARE protein syntaxin 1. However, the exact mechanism of septin 5 function in localized exocytosis remains unknown. Over-expression of septin 5 is known to lead to lower levels of secretion in HIT-T15 cells. Interestingly, in the current study, the knock-down of septin 5 also results in reduced levels of regulated secretion in PC12 cells, suggesting a more complex role of septin 5 that includes both negative and positive effects on exocytosis. Septin 5 knock-down data point to a possibility of septin 5 facilitating formation of a tether between the vesicles and their site of secretion.
Pediatric Dentists’ Behaviour Management of Children with Autism Spectrum Disorders
Keywords: Autism
Dentistry
Behaviour Management

This study assessed which behaviour management techniques, BMTs, pediatric dentists are using, and find effective in treating patients with Autism Spectrum Disorders, ASD and identified influences which contributed to their use. Surveys were mailed and emailed to 1669 members of the American Academy of Pediatric Dentistry. Seven hundred eighty-nine (48.2%) completed surveys were returned. Nearly 60% of respondents treated children with ASD weekly or more frequently. Of the 23 listed BMTs, General Anaesthesia, Tell-Show-Do, Distraction, and Non-verbal Communication, were considered effective. Seventy percent of respondents were primarily users of classical BMTs. Pharmacological and classical techniques, are used frequently, but may not be effective. Time and costs limit the use of modern techniques. Cost efficiency and long-term patient management were the most influential factors in selecting a BMT; patient co-operation was the least influential. Pediatric dentists recognized a need for further education related to behaviour management of children with ASD.
Design and Evaluation of an Improved Patient Information Management System for Emergency Department Physicians
Keywords: human factors
healthcare
emergency department
physician
interface design
usability engineering

Designing a software interface for healthcare requires thorough domain knowledge, and effective user research and benchmark analysis. This thesis examines the requirements for an improved patient information management system for emergency medicine and describes the iterative process of designing and evaluating the system. I conducted observational study of Emergency Department (ED) physicians’ workflow and information needs, from which I derived a set of functional requirements, created scenarios, performed hierarchical task analysis, and developed a preliminary user model for the patient information management system. Based on these, I developed an interface prototype and evaluated the design with a sample of ED physicians. I review the user testing and design iterations carried out and report on the design improvements made based on the user feedback.
Equalization of Integrated Optical Photodiodes using an Infinite Impulse Response Decision Feedback Equalizer
Keywords: optical equalization
decision feedback equalizer

This thesis examines the challenges in creating a fully integrated optical receiver. Due to the nature of silicon, 850nm light exhibits a poor impulse response when directed at an on-die photodiode. Using a modified decision feedback equalizer with an infinite impulse response filter in the feedback path allows to eliminate the long tail of post-cursor ISI that is generated by the photodiode. Due to silicide depositions over the photodiodes, making them opaque, the receiver was tested using an electrical cable with similar frequency roll-off as that of a photodiode. A data rate of 3.7 Gbps was achieved and only limited by the amount of input reflections at the transimpedance amplifier. The receiver occupies an area of 0.23 mm^2 and consumes 51.3mW.
A Parallel Adaptive-mesh Method for Predicting Flows Through Vertical Axis Wind Turbines
Keywords: computational fluid dynamics
wind turbines
low-speed flows

Significant progress has been made towards developing an effective solution method for predicting low-speed flows through vertical-axis wind turbines. A Godunov-type finite-volume scheme has been developed for the solution of the Euler equations in two-dimensions on a multi-block mesh. The proposed algorithm features a parallel block-based adaptive mesh refinement scheme and a mesh adjustment procedure to enable straightforward meshing of irregular solid boundaries. A low-Mach-Number preconditioner is used in conjunction with a dual timestepping scheme to reduce the computational costs of simulating low-speed unsteady flows. A second-order backwards differencing time-marching scheme is used for the outer physicaltime discretization, and an explicit optimally-smoothing multi-stage time-stepping scheme with multigrid acceleration is used for the inner pseudo-time loop. Results are presented for various low-speed flows that demonstrate the suitability of the algorithms for wind turbine flows. Additional theory and discussion are also presented for extension of the schemes to the full Navier-Stokes equations.
New Portable Flow Tube Technique to Investigate the Formation and Aging of Secondary Organic Aerosol
Keywords: SOA
aerosol
oxidation
hydroxyl radical

A new portable flow tube technique, the Toronto Photo-Oxidation Tube v2.0 was developed and characterized to explore its potential to control and monitor the OH-initiated formation and chemical aging of secondary organic aerosol (SOA) in-situ. The first study investigated the different operational parameters of this flow tube technique. TPOT v2.0 can generate oxidizing conditions equivalent to ambient OH exposures of 2.3 – 10.8 days. The transmission efficiency of a model organic aerosol indicated negligible losses in the oxidation tube. Differences in the residence time distribution curves measured for a gas and model organic aerosol showed that particles were subjected to approximately half of the OH exposure compared to gases. The second study examined the capacity of the TPOT technique to generate secondary aerosols due to OH oxidation. High aerosol yield was observed for H2SO4 particles, whereas a low aerosol yield was observed for α-pinene SOA.
Extending Plasmonics in Semiconductors to Higher Operating Frequencies
Keywords: Plasmonics
Semiconductors
Gallium Arsenide
Surface Plasmons
Photonics
Semiconductor-metal transition

This thesis examines the feasibility of using conventional semiconductors, specifically GaAs, as a plasmonic material at the operating wavelength of 1550nm, due to its many merits such as achievable low losses and mature micro-fabrication technologies. A theoretical study is performed on GaAs that yielded the condition for plasmonic behaviour at a minimum free carrier density of 7.2 x 10^20cm^-3 in bulk materials. The most feasible route to achieving this condition is determined to be intense optical excitation, and the required intensity considering a 150fs pulse at the above bandgap wavelength of 870nm is approximately 2.55TW/cm^2. A Bragg reflection ridge waveguide (BRW) using GaAs-AlGaAs is designed and micro-fabricated, and a counter-propagating pump-probe experiment is devised to test the plasmonic effect using the BRW. Results from two different ultrafast lasers include the observation of pump (870nm and 800nm) coupling to fundamental Bragg modes, and the measurement of the pump transmission spectrum.
An Investigation of the Effect of Sports-related Concussion on Verbal Learning and Memory Performance in Youth
Keywords: Concussion
Verbal Memory

The current study was designed to investigate the effect of concussion on verbal learning and memory performance in youth hockey players. Concussed participants completed the Rey Auditory Verbal Learning Test (RAVLT) prior to the start of the hockey season. Following recovery from concussion, six males (10-12 years), with one sustaining two concussions, completed a follow-up assessment. A difference score was calculated for five RAVLT index scores. Each instance of concussion was matched to two controls on age, gender, and testing protocol in order to control for the confounding influences of repeated testing sessions. Independent-samples t-tests revealed a trend towards a significant decrease in change scores for the concussed participants on the Delayed Recall Trial of the RAVLT. These results suggest that long-term verbal memory may be negatively affected by concussion; however, future studies are needed with larger sample sizes and additional follow-up points in order to better understand the impact.
Romancing Reasonableness: An Aspirational Account of the Canadian Case Law on Judicial Review of Substantive Administrative Decisions since C.U.P.E. v. N.B. Liquor Corporation
Keywords: law
administrative law

This thesis surveys the last three decades of Canadian jurisprudence on the standards of review applicable to judicial review of substantive administrative decisions, with a focus on the guidance that is or is not forthcoming on the significance and practical application of reasonableness (deferential) review. My argument is that the doctrinal developments I survey trace out a burgeoning understanding of the purposes of substantive review which is at the same time a particular understanding of administrative state legitimacy. I refer to an account of legitimacy, or the legitimacy proper to law, that conceives of law as an aspirational project aimed at fostering relationships of reciprocity as between legal subjects and legal authorities. On this account (advanced in the work of David Dyzenhaus, and others), common law administrative law principles of procedural fairness and substantive reasonableness function as co-ordinate mechanisms for grounding administrative decision-making in a “culture of justification”.
Numerical Analysis of Ethylene Injection in the Inlet of a Mach Six Scramjet
Keywords: scramjet
ethylene
hypersonic
fuel injection
fuel mixing
computational fluid dynamics

A scramjet inlet was designed for use on a small scale, Mach six, ethylene-fuelled vehicle. The inlet used strut-based cantilevered fuel injectors and a well-defined mixing duct to mix fuel prior to the combustor. Designed using theoretical and numerical analyses, the resulting inlet configuration consisted of a single body shock inlet with vertical fuel injector struts and four cantilevered injectors per strut side. This inlet was 80 cm long and 42 cm high. Numerical analysis of the vehicle was conducted with computational fluid dynamics by solving the Favre-Averaged Navier-Stokes equations; turbulence was simulated using the Wilcox k-ω model. Multispecies simulations in two and three dimensions were used to evaluate the design. Analysis of the simulated flow features, thrust potential and mixing efficiency demonstrated favourable vehicle performance. In particular, the inlet allowed for complete combustion when lean equivalence ratios of less than 0.7 were used.
Squaramides: Investigation of Their Hydrogen Bonding Abilities and Anion Interactions
Keywords: hydrogen bond
anion interaction
squaramide

Squaramides (3,4-diaminocyclobutene-1,2-diones) are known to be strong hydrogen bond donors, and recently have been demonstrated to show unusual responses to anions and the potential to adopt secondary structures. In the first part of the project, a small molecule version of a fluorene-based poly(squaramide) was synthesized to gain insights into the mechanism of the “turn-on” fluorescence response of the polymer in the presence of mono-basic phosphate anions. In the second part, mono and dipyridyl squaramides are examined. Pyridyl squaramides were discovered to form strong intramolecular hydrogen bonds, making the folding process more favorable than their urea counterparts. They are particularly interesting as their urea analogues are capable of taking up helical conformations when folded. The folding properties of these pyridyl squaramides in a range of solvents, and the influence of added anions on the folding process, are described herein.
The F-box Protein FSN-1 Governs Presynaptic Development in Caenorhabditis elegans
Keywords: synapse
FSN-1
carnorhabditis
elegans
neuron

Synapses are specialized sub-cellular junctions that transmit signals between neurons and their targets. In Caenorhabditis elegans (C. elegans) the F-box protein FSN-1 and the PHR family member RPM-1 form the SCFFSN-1 E3 ubiquitin ligase, which plays an important role in regulating synaptic growth factors. This SCF complex is evolutionarily conserved across species, and regulates many cellular processes including axon outgrowth, apoptosis and synaptogenesis. This thesis focuses on identifying targets of SCFFSN-1 that contribute to synaptogenesis. Forward genetics was employed to screens and isolate mutants that exhibit genetic interactions with fsn-1. I have identified an allele of the MAPK pmk-3(hp246) and three alleles of the MAPKKK dlk-1(hp180, hp192, hp195) that suppress fsn-1 defects. In addition, I have isolated five fsn-1 suppressing alleles and evidence suggests that these suppressors are likely novel fsn-1 suppressors.
Body Fluid Analogues and Personal Care Products as Potential DBP Precursors
Keywords: Drinking water treatment
DBP
DBP precursor
Swimming pool DBPs

Disinfection byproducts (DBPs), such as organic chloramines, THMs, HAAs, and nitrosamines, are formed during mandatory disinfection processes in drinking water treatment. Many of these DBPs have been shown to be potentially carcinogenic. Extensive research has been conducted on the occurrence and formation of these DBPs. However, there has been limited research on their relationships with each other, which may be important for the understanding of their formation mechanisms, and the nature of their precursors is still relatively unknown. Ultimately, this information will be key for the development of possible improvements in treatment technologies. Results of this study improve the understanding of DBP formation in swimming pool water. Some BFAs and PCP additives were identified as potential DBP precursors. Influence of BFAs and PCP additives on DBP formation in swimming pool water was also illustrated. Results provided feasible strategies to minimize DBP formation while maintaining the efficiency of disinfection.