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The use of highly active antiretroviral therapy (HAART) has significantly decreased the mortality rate of HIV-1 patients, however the increased survival has led to the development of complications associated with the persistence of the viral infection. Nearly half of HIV-1-infected individuals develop HIV-associated neurocognitive disorders (HAND) as the effects of the chronic infection leads to neuronal injury and synaptic loss in the central nervous system (CNS). The neurotoxicity of HIV-1 has largely been attributed to the inflammation caused by viral replication and the altered signaling of astrocytes, microglia, and macrophages. Although HAART has improved the control of viral replication, the effects from inflammation remain a concern, particularly those of the pro-inflammatory cytokine, tumor necrosis factor alpha (TNF-α). TNF-α has been a therapeutic target for other diseases associated with chronic inflammation, such as rheumatoid arthritis, but emerging evidence has suggested that TNF-α signaling can have a dual role, especially in the CNS, proving the complexity in the modulation of the TNF-α pathway. Although the detrimental effects of TNF-α have been well-characterized, we lack a complete understanding of the beneficial role of TNF-α. TNF-α signaling has largely been considered to be neurotoxic but has been able to regulate neurite outgrowth in the context of neural development. Since TNF-α is upregulated in various neurodegenerative conditions, we considered potential outcomes of TNF-α on neurite outgrowth following injury. Initially, most would assume that TNF-α would prevent neurite outgrowth as apoptosis is a common outcome of TNF-α-induced signaling. If TNF-α signaling strictly prevents neurite outgrowth, anti-TNFα therapies could be considered to reverse this effect. However, upon induced injury, we observed an increase in neurite regrowth following induced injury in human primary fetal neurons, demonstrating a strong need for a deeper understanding of this dual role of TNF-α. Anti-TNF-α therapies have been considered for HIV-1-infected patients to reduce the chronic inflammation, however inhibiting TNF-α signaling could have side-effects that could prevent neuronal recovery from HIV-1 effects. Targeting pathways downstream of TNF-α signaling would be more advantageous to mediate the beneficial role of TNF-α in the CNS. We investigated the transcriptional effects of TNF-α treatment on neurons to uncover a potential pathway to promote neurite outgrowth. One pathway we have discovered to be beneficial in primary human fetal neurons is TNF-α-induced Ephrin B2 upregulation. Ephrin B2 (EphB2) receptors are important mediators of neuronal development and synaptic plasticity, however little has been established in regards to their role in HIV and inflammation, particularly in the CNS. EphB2 can mediate axonal development by providing retractive cues to assist the axon to reach the target, but EphB2 can also promote dendritic branching to improve learning and memory, which would be particularly beneficial for HAND patients that experience cognitive deficits. We observed a correlation between the upregulation of EphB2 in response to TNF-α and neurite outgrowth, which provides a potential pathway to repair damaged neurons and re-establish lost neuronal connections. Dendritic pruning and neuronal loss has been observed in HAND patients, so this ability to promote repair could prevent, improve, or recover the cognitive deficits experienced by HIV-patients with HAND. TNF-α, although primarily known to induce neurotoxicity, strongly activates the nuclear factor-kappaB (NF-κB) pathway, which can have a very wide range of transcriptional effects. Therefore, our hypothesis is that the TNF-α-induced neurite regrowth occurs through an upregulation EphB2 in an NF-κB-dependent pathway. TNF-α has been well established to induce NF-κB signaling, mostly by promoting the translocation of the NF-κB p65 DNA binding factor to the nucleus for transcriptional regulatory effects. NF-κB can regulate neuronal growth and process development of both dendrites and axons, which would correlate to the neurite regrowth observed following TNF-α upon induced injury. The regulation of EphB2 by NF-κB has not been extensively studied, but EphB2 can be negatively regulated by an NF-κB family member, c-Rel. We analyzed the EphB2 promoter and identified three NF-κB p65 binding sites upstream from the transcriptional start site, which provided insight to our hypothesis. We established that p65 directly binds to and can regulate EphB2 promoter activity in response to TNF-α. Since the dual role of TNF-α can be dependent on the receptor through which the signaling proceeds, either TNF-α receptor 1 (TNFR1) or TNF-α receptor 1 (TNFR2), we investigated if this upregulation of EphB2 is receptor dependent and determined EphB2 is induced primarily through activation of TNFR2. Neurons express both receptors, however, the effects of TNF-α to promote neuroprotection and repair primarily occur through the TNF-α/TNFR2 regulatory axis. Although we have been established the mechanism of TNF-α-induced EphB2 and there is a strong correlation with neurite outgrowth following induced injury, we considered the possibilities to modulate EphB2 in the absence of TNF-α to demonstrate the direct effects of EphB2 expression. Several approaches could be used to mediate EphB2 activation or inhibition in vitro. RNA interfering techniques, such as small interfering RNA (siRNA), are useful, but we were interested in a complete knockout strategy. Since our approach was to assess the effects of EphB2 knockout only on neurite outgrowth following induced injury, a knockout animal model would not be appropriate, as a lack of EphB2 would affect the development of the neurons, unless an inducible knockout model was established. This is a lengthy and elaborate process and, more importantly, would only be available in a non-human model. Other techniques, such as transcription activator like effector nucleases (TALENs), can generate knockout systems that are targeted to specific regions of a gene, but specific binding proteins must be created to recruit the endonucleases to the target. Clustered regularly-interspaced short palindromic repeats/CRISPR associated protein 9 (CRISPR/Cas9) has emerged as a specific and relatively easy technique to knockout genes of interest and uses short RNA sequences to guide Cas9 endonucleases to target regions to create double stranded breaks in the DNA to silence the gene. Once concern with Cas9 is specificity to target only the desired region of the gene, as off-target effects can occur and may result in unwanted gene silencing. A Cas9 mutant, Cas9 nickase (Cas9n), has been created to have more specificity by requiring two guide RNAs to recruit two Cas9 nickases to generate a double stranded break as they function as nickases to only create a nick in one DNA strand. We developed this strategy to remove exon 1 of the EphB2 gene by using two pairs of Cas9 nickases, with four guide RNAs, to eliminate any chance for off-target effects but retaining the desired outcome of and EphB2 knockout. We validated the system by demonstrating that a knockout of EphB2 increases adhesion and prevents migration in human embryonic kidney 293T (HEK293T) cells. Although this cell model is not a neuronal cell model, the migration assay demonstrates the functional loss of EphB2. We also created an inducible Ephb2 system to overexpress EphB2. Together these provide essential tools to verify the direct involvement of EphB2 in neurite outgrowth. Taken together, our studies characterize a novel mechanism for neurite outgrowth following injury in neurons: TNF-α/TNFR2-induced EphB2 signaling in an NF-κB p65-dependent manner. In addition to the established mechanism, we developed a technique to assess the effects of EphB2 knockout and overexpression in the context of neurite outgrowth: EphB2-targeted-Cas9n and EphB2 inducible construct. This mechanism yields insight into a potential downstream pathway to be utilized to repair damaged regions in the brain and reverse cognitive deficits in neurodegenerative conditions, especially in a chronic inflammatory environment, such as HIV-1 infection. The strategies created provide a valuable toolset to demonstrate the direct effects of modulating EphB2 signaling, not only in neurons for effects on neuronal health and synaptic plasticity, but also in other disease models, such as glioblastoma, in which EphB2 was demonstrated to promote invasion and migration of tumor cells. These observations and the usefulness of the modulatory strategies likely extend to multiple neurodegenerative diseases that demonstrate cognitive deficits that correlate to neuroinflammation. / Biomedical Neuroscience

A recent line of inquiry has examined a specific question about how an observer's own experiences with actions may change how his or her brain processes those actions when they are subsequently observed. In short, how does prior experience with action affect the subsequent perception of others' actions? The current study investigated this question using electroencephalography (EEG) to test the hypothesis that receiving experience with an action would subsequently lead to different activation of sensorimotor cortex depending on the predicted consequences of observed actions. While EEG was recorded, three groups of participants watched video clips showing an actor lifting objects, and then each group received information about the sensorimotor properties (i.e., weight) of the objects. One group received extended sensorimotor experience with the objects (EE group), a second group received brief sensorimotor experience with the objects (BE group), and the third group read written information describing the objects' weights (semantic information, SI group). Following the experience, participants again viewed the video clips. Time-frequency analyses showed that for participants in the EE and BE groups, EEG during the observation of action was sensitive to the predicted sensorimotor consequences of the observed action. This was not found for the SI group. As well, all three groups showed increased alpha and beta suppression following experience. Overall, these results lead to two main conclusions: 1) experience with action facilitates subsequent neural mirroring processes, and 2) sensorimotor experience leads to differential activation of the sensorimotor cortex depending on the predicted consequences of observed action. / Psychology

I have submitted another pdf file which is my permissions for figures used in my thesis. The name this file is Clearance. / Nickel Hydroxide is one of highly active materials used in various energy conversion applications. One of the key factors in the deposition of Ni(OH)2 is the active surface area which plays an important role in improving the efficiency of transformation reactions. There are various methods to enhance the active area. One method that can be used to modify the morphology of deposited Ni(OH)2 is to generate porous structures. Ni(OH)2 can be formed in two different phases namely alpha and beta. The main objective in our work is to optimize the synthesis conditions and characterize structures at the nanoscale, and also demonstrate unequivocally the presence of alpha and beta phases. For this work, a combination of electron microscopy and electrochemistry is needed to modify the morphology of nickel hydroxide and for detailed structural characterization. Various characterization techniques are used to investigate different electrochemical depositions conditions of Ni(OH)2 in alpha and beta phase forms using Direct and Indirect methods, respectively. Kinetically, alpha-Ni(OH)2 is easier and faster to be synthesized and can be deposited directly in one step. During cyclic voltammetry of alpha-Ni(OH)2 in KOH, the volume of material involved in the oxidation reaction increases in every cycle. Scanning Electron Microscopy and Transmission Electron Microscopy characterization shows that this may be due to microbubble formation that transform deposited sheets to particulate shapes. On the other hand, conversion of nickel metal to beta-Ni(OH)2 during cyclic voltammetry causes an expansion of particles. Effectively, nickel hydroxide is formed on the shell while nickel remains in the core. High Resolution Transmission Electron Microscopy is then used to identify the distribution of these phases. Another foremost feature for the beta phase is to make nickel metal in any desired shape, which can then be converted to beta-Ni(OH)2 through Cyclic Voltammetry in KOH. The presence of both phases is demonstrated with electron diffraction. Finally, as future work, all experiments will be performed in-situ TEM using liquid cell to observe structural changes in real time. / Thesis / Master of Science (MSc)

Matting, which aims to separate the foreground object from the background of an image, is an important problem in computer vision. Most existing methods rely on auxiliary information such as trimaps or scibbles to alleviate the difficulty arising from the underdetermined nature of the matting problem. However, such methods tend to be sensitive to the quality of auxiliary information, and are unsuitable for real-time deployment. In this paper, we propose a novel Attention-based Multi-scale Matting Network (AMMNet), which can estimate the alpha matte from a given RGB image without resorting to any auxiliary information. The proposed AMMNet consists of three (sub-)networks: 1) a multi-scale neural network designed to provide the semantic information of the foreground object, 2) a Unet-like network for attention mask generation, and 3) a Convolutional Neural Network (CNN) customized to integrate high- and low-level features extracted by the first two (sub-)networks. The AMMNet is generic in nature and can be trained end-to-end in a straightforward manner. The experimental results indicate that the performance of AMMNet is competitive against the state-of-the-art matting methods, which either require additional side information or are tailored to images with a specific type of content (e.g., portrait). / Thesis / Master of Applied Science (MASc)

Constant stress creep tests were performed in vacuo on alpha titanium in various thermomechanical treatments. At 500°C and 527°C annealed alpha titanium exhibits an anomalous creep arrest in the initial portion of the creep curve. After this creep arrest the creep curves swept up to a true steady state creep rate. This anomalous behavior is attributed to dynamic strain aging. The effect vanishes due to interstitial solute depletion as the interstitials are swept from the lattice by moving dislocations. The prestrained and recovered samples tested at 60006 did not show a creep arrest. This is attributed to even distribution of interstitials on the recovered dislocation substructure making dynamic strain aging less effective. Additionally, transmission electron microscopy indicates that the tilt boundaries of the recovery structure can break down during the initial portion of the creep curve releasing mobile dislocations. In steady state all conditions tested developed a dislocation subgrain substructure. The tendency for dislocation subboundaries to inhabit specific planes is not as marked as it is in the recovered structure. / Master of Science

In this thesis, the morphology, crystallization and melting behavior of polypropylene copolymers (propylene/ethylene, propylene/1-butene, propylene/1-hexene and propylene/1-octene) has been examined. The multiple melting behavior has been correlated with the presence of alpha and gamma phases and with the occurrence of cross-hatching morphology. The Crystallization and melting behavior of propylene/ethylene and propylne/1-butene are qualitatively similar and compatible with the expectations that the ethylene and butene comonomers are partly included in the propylene lattice. Propylene/1-hexene and propylene/1-octene copolymers exhibit remarkably similar behavior and morphologies consistent with the expectations that the hexene and the octene comonomers are rigorously excluded from the crystal lattice. The origin and the crystallization time dependence of the multiple melting behavior is very different for these two pairs of copolymers. For PE and PB it is consistent with the melting of parent a-phase lamellae and alpha or gamma-phase daughter lamellae. For PH and PO copolymers it is very similar to that observed for ethylene-octene(EO) and ethylene-styrene(ES) copolymers and compatible with the melting of primary lamellae and secondary mosaic or fringed micellar structures. / Master of Science

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