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- Resource Type:
- Thesis
- Creator:
- Nagaraj, Shruthi
- Abstract:
- Application Programming Interface(API) form an important part of software development. Eye tracking is an interesting and emerging field which is gaining wide popularity. The goal of the thesis is to collect and utilize eye tracking data to better understand how software developers summarize code. We perform a study that measures the effects of complex information sources on summarization tasks. In this work, we conduct a controlled experiment with 12 professional and student software developers to better understand how they perform code summarization tasks. These tasks aimed at summarizing a set of APIs based on source code, Stack Overflow, Bugzilla, or a combination of them. We used iTrace, a plugin for Eclipse, to record the developers' eye movements.
- Thesis Degree:
- Master of Computer Science (M.C.S.)
- Thesis Degree Discipline:
- Computer Science
- Date Created:
- 2018
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A role for LRRK2 and Neuroinflammatory Processes in Multi-Hit Toxicant Models of Parkinson’s Disease
- Resource Type:
- Thesis
- Creator:
- Rudyk, Christopher
- Abstract:
- Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra (SNc) leading to a range of motor behavioral deficits. In addition to motor features, non-motor behaviors are also evident in many cases. Although it has been suggested that genetic mutations represent a cause or risk factor for the disease, there is evidence to suggest that PD arises as a result of the interaction between multiple factors. In the current dissertation, one overarching theme we were interested in was how the behavioral and neurochemical effects of the PD relevant herbicide paraquat might be impacted when combined with different stressors including psychological stress, immune stress, or age induced alterations. We were also highly interested in providing further understanding regarding the role of neuroinflammatory processes (as occurs in PD) in the paraquat induced death of SNc dopamine neurons. In these instances, we focused on the inflammatory regulatory gene (and number one gene implicated in PD), leucine rich repeat kinase 2 (LRRK2). Accordingly, in our study combining paraquat exposure with a chronic unpredictable stress regimen, we found that psychological stressor exposure did not influence the degeneration of midbrain dopamine neurons or accompanying microglia activation induced by the toxin; however, it did influence motor coordination. Conversely, exposure of the pesticide in combination with the inflammatory agent lipopolysaccharide (LPS) augmented SNc cell loss. In these studies using LPS, we found that knocking out LRRK2 protected against the loss of midbrain dopamine neurons and behavioral deficits, induced by LPS priming followed by paraquat exposure. In fact, knocking out LRRK2 altered the pro-inflammatory microglia phenotype that is typically induced by LPS exposure. Likewise, LRRK2 deficiency protected against the paraquat induced peripheral and central toxic effects in mice older than what we typically use. Taken together, our results support the hypothesis that the interaction between different stressors can impact behavioral and biological outcomes relevant for PD, and LRRK2 is important for the toxic effects of paraquat, and LPS priming with later paraquat exposure. The data presented herein may also provide important implications for the development of treatment strategies that target inflammatory processes in PD.
- Thesis Degree:
- Doctor of Philosophy (Ph.D.)
- Thesis Degree Discipline:
- Neuroscience
- Date Created:
- 2018
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- Resource Type:
- Thesis
- Creator:
- Farmer, Kyle
- Abstract:
- Parkinson's disease is an age related neurodegenerative disease. Current treatments do not reverse the degenerative course; rather they merely manage symptom severity. As such there is an urgent need to develop novel neuroprotective therapeutics. There is an additional need to stimulate and promote inherent neuro-recovery processes. Such processes could maximize the utilization of the existing dopamine neurons, and/or recruit alternate neuronal pathways to promote recovery. This thesis investigates the therapeutic potential of the mGluR5 negative allosteric modulator CTEP in a 6-hydroxydopamine mouse model of Parkinson's disease. We found that CTEP caused a modest reduction in the parkinsonian phenotype after only 1 week of treatment. When administered for 12 weeks, CTEP was able to completely reverse any parkinsonian behaviours and resulted in full dopaminergic striatal terminal re-innervation. Furthermore, restoration of the striatal terminals resulted in normalization of hyperactive neurons in both the striatum and the motor cortex. The beneficial effects within the striatum were associated with an increase activation of mTOR and p70s6K activity. Accordingly, the beneficial effects of CTEP can be blocked if co-administered with the mTOR complex 1 inhibitor, rapamycin. In contrast, CTEP had differential effect in the motor cortex, promoting ERK1/2 and CaMKIIα instead of mTOR. Together these data suggest that modulating mGluR5 with CTEP may have clinical significance in treating Parkinson's disease. In addition to the CTEP work, extensive appendices are included in this thesis outlining the optimization of animal models and tools used in the present thesis, as well as other potential therapeutic avenues.
- Thesis Degree:
- Doctor of Philosophy (Ph.D.)
- Thesis Degree Discipline:
- Neuroscience
- Date Created:
- 2018
-
- Resource Type:
- Thesis
- Creator:
- Brumar, Daniel Sebastian
- Abstract:
- Found in cannabis, cannabidiol (CBD) holds promise as a nonpsychoactive cannabinoid in treating a number of conditions, including anxiety, schizophrenia, and some forms of epilepsy. However, large scale studies on the therapeutic use of CBD are lacking, and more research is needed to precisely establish its safety and efficacy. Extraction of CBD from cannabis is challenging, and past methods of synthesizing CBD have suffered from at least one of the following: poor selectivity, low yields, complex and laborious reaction sequences, or unavailable starting materials. We report here a concise approach to CBD synthesis from readily available nerol. This route uses directed orthometallation to regioselectively allylate olivetol dimethyl ether, followed by a biomimetic oxidative cyclization with Mn(III) to cleanly generate dimethyl CBD in low yield. We also demonstrate that using cationic polyene cyclization as the key ring-forming step produces a similar yield of dimethyl CBD in a complex mixture of isomers.
- Thesis Degree:
- Master of Science (M.Sc.)
- Thesis Degree Discipline:
- Chemistry
- Date Created:
- 2018
-
- Resource Type:
- Thesis
- Creator:
- Hunt, Vernon
- Abstract:
- Aptamers designed to target α-synuclein, a protein implicated in the pathogenesis of Parkinson's disease due to its propensity to aggregate, were investigated to probe their affinity for the protein as well as their ability to hinder the aggregation of the proteinin vitro. Aggregation assays have proven that the presence of the aptamer candidates targeting monomeric α-synuclein stunt the formation of protein fibrils. One promising aptamer from the research, a-syn-1, was successfully packaged into a liposome vesicle modified to cross the blood-brain barrier and used in in vivo applications. Analysis of the liposomes used for the packaging and delivery of the aptamer has provided insight into the loading efficiency and production efficiency of liposome batches.
- Thesis Degree:
- Master of Science (M.Sc.)
- Thesis Degree Discipline:
- Chemistry
- Date Created:
- 2018
-
- Resource Type:
- Thesis
- Creator:
- Guzman Nieto, Michelle
- Abstract:
- The current state-of-the-art design optimization of airframes is tightly wounded to its loads analyses as the process is usually conducted employing a deterministic set of critical load cases. The sheer number of scenarios required to estimate the critical loading conditions prevent these two processes from integrating. In this thesis, we address the problem of an efficient estimation of critical dynamic aeroelastic loads. The method is based on the Kriging metamodeling technique and the Expected Improvement Function, known formally as the Efficient Global Optimization (EGO) algorithm. Furthermore, different inexpensive metrics, based on the concept of Modal Contribution Factors, are investigated as indicators to determine if a substantial change in the loads has occurred during the design optimization, triggering the re-exploration of the design space. A case study is presented to evaluate the performance of the proposed methodology, where a reduction of 84 percent in the total time of execution was achieved.
- Thesis Degree:
- Master of Applied Science (M.App.Sc.)
- Thesis Degree Discipline:
- Engineering, Aerospace
- Date Created:
- 2018
-
- Resource Type:
- Thesis
- Creator:
- Abu-AlHawa, Maha
- Abstract:
- In Multiple Sclerosis (MS), cognition is directly affected by neural integrity and secondary disease characteristics (anxiety, depression and fatigue). Mesenchymal stem cell therapy (MSCT) has been recently studied due to its potential for neural repair in MS. It is hypothesized that cognitive improvement will be seen after MSCT. The change in cognition is expected to be correlated with changes in secondary disease characteristics and neurophysiological measures (neural conduction time). Ten participants received MSCT. Cognition, secondary disease characteristics, and conduction time were evaluated pre- and post- (12 month) therapy. Eight participants demonstrated cognitive improvement in at least one test. Secondary disease characteristics and conduction time were not associated with cognition in our sample. In conclusion, MSCT appears to be safe with regards to cognition and does not worsen secondary disease characteristics. Future efficacy studies have the potential to show greater cognitive improvement than the current preliminary study.
- Thesis Degree:
- Master of Cognitive Science (M.Cog.Sc.)
- Thesis Degree Discipline:
- Cognitive Science
- Date Created:
- 2018
-
- Resource Type:
- Thesis
- Creator:
- Dunford, Matthew Gordon
- Abstract:
- The DEAP-3600 Dark Matter detector, located 2 km underground at SNOLAB, uses up to 3600 kg of natural atmospheric argon as its detection medium. The isotopes 36Ar and 39Ar are present in small quantities in argon found in the atmosphere, and so are present within DEAP-3600. These isotopes can be examined in data collected for a Dark Matter search. 36Ar could undergo an exotic decay process called neutrinoless double electron capture. This decay violates lepton number conservation and its observation would provide a clear indication of physics beyond the Standard Model of Particle Physics. Three modes of this decay with different final states could be detected with DEAP-3600 if they occur. A search for this decay was performed on an isotopic exposure of 6.67 kg-years with the DEAP-3600 detector. A fit to this data has yielded lower limits on the half-life of 36Ar of T > 4.78e20 years. 39Ar is a beta-emitting isotope and is a major background for DEAP-3600 and other argon-based dark matter experiments. A measurement of the specific activity of 39Ar in natural atmospheric argon has been performed on a total argon mass exposure of 2200 kg-years taken over a period of 12 months; 185 individual measurements were made. The specific activity is determined to be (0.953 +/- 0.028)Bq/kg, corresponding to a concentration of (7.6 +/- 0.2)e-16 g(39Ar)/g(atmAr).
- Thesis Degree:
- Doctor of Philosophy (Ph.D.)
- Thesis Degree Discipline:
- Physics
- Date Created:
- 2018
-
- Resource Type:
- Thesis
- Creator:
- Hassan, Oluwasegun Abayomi
- Abstract:
- A growing desire for granular network control, automation, virtualization and much more, has contributed to the emergence of Software Defined Networking (SDN) as a prominent research area. Though originally developed for wired networks, benefits of the centralized routing approach are now being leveraged for wireless network applications. These include SDN-based Multi-hop Wireless Networks (MWNs), as potential alternatives to traditional MWNs. This thesis presents a Software Defined Multi-hop Wireless Network (SDMWN) solution, with standard centralized routing characteristics and full mobility capabilities, evaluated against distributed routing in an equivalent traditional MWN architecture. Our emulation results, obtained with Mininet-WiFi, demonstrate a good degree of potential for SDMWN, when operating under controlled (mobile) network conditions. By guaranteeing the availability of potential links between every node, SDMWN outperforms the traditional MWN, by about 15% and 65 ms, for Ping Success Rate and Round-Trip Time respectively. However, this comes at a relatively high cost of overhead.
- Thesis Degree:
- Master of Applied Science (M.App.Sc.)
- Thesis Degree Discipline:
- Engineering, Electrical and Computer
- Date Created:
- 2018
-
- Resource Type:
- Thesis
- Creator:
- Mattice, Christopher Matthew Colin
- Abstract:
- The ability of an aptamer to catalyze a chemical reaction under selective conditions presents a novel avenue for the exploration of biosensors and molecular payload delivery. To date, limited research exists for pairing oligonucleotide-templated reactions with the selective nature of DNA aptamers. A system can be designed wherein the conformational change in aptamer structure associated with target binding brings two previously spatially isolated reactants into proximity, thereby catalyzing their reaction through an increase in effective molarity. A rationally designed aptamer-mediated SN2 displacement of a sulfonyl-based fluorescence-quencher resulted in an effective increase in fluorescence upon mixing of the aptamer with two appropriately modified complementary oligonucleotides. This increased fluorescence could be slowed by the presence of the aptamer target, permitting the development of an aptamer-based sensor for ochratoxin A with a linear dynamic range of 100 μM to 100 pM and a limit of detection of 1.5 pM.Similar aptamer-based sensor systems were also developed that could take advantage of the fluorogenic copper catalyzed azide-alkyne cycloadditions between two labelled probes controlled by the aptamer target. This has been demonstrated using the thrombin structure switching aptamer to produce a linear response to thrombin between 100 nM and 10 pM with a limit of detection of 3.9 fM. These fluorogenic click modifiers were also incorporated directly into a structure switching thrombin aptamer such that the G-quadruplex formed upon thrombin binding brings the two modifiers into proximity. This constitutes a turn-on sensor for thrombin, with detection of thrombin between 1 μM and 1 nM possible.As a final proof of concept, the fluorogenic azide and alkyne modifiers were incorporated on either side of a split aptamer for cocaine, such that the presence of cocaine will result in a detectable fluorescent signal from ligation of the split aptamer sequences. Using this system, a qualitative cocaine sensor in the range of 100 μM to 10 pM was established. This project has demonstrated the first steps towards controlling chemical reactions using DNA aptamers. Having demonstrated preliminary functionality through these applications, future applications in drug delivery, enhanced sensors, and selective chemical synthesis constitute intriguing new avenues in aptamer research.
- Thesis Degree:
- Doctor of Philosophy (Ph.D.)
- Thesis Degree Discipline:
- Chemistry
- Date Created:
- 2018