VictorJuiz/thesis huggingface dataset:
Synaptic Plasticity in Basal Ganglia Output Neurons in Parkinson's Disease Patients
Keywords: Parkinson's disease
substantia nigra
synaptic plasticity
basal ganglia

Parkinson’s disease (PD) is characterized by the loss of dopamine in the basal ganglia and leads to paucity of movements, rigidity of the limbs, and rest tremor. Synaptic plasticity was characterized in the substantia nigra pars reticulata (SNr), a basal ganglia output structure, in 18 PD patients undergoing implantation of deep brain stimulating electrodes. Field evoked potentials (fEPs) in SNr were measured with one microelectrode using single pulses from a second microelectrode ~ 1 mm away. High frequency stimulation (HFS – 4 trains of 2s at 100Hz) in the SNr failed to induce a lasting change in test fEPs amplitudes in patients OFF medication. Following L-Dopa, HFS induced a potentiation of the fEPs that lasted more than 150s. Our findings suggest that extrastriatal dopamine modulates activity dependent synaptic plasticity at basal ganglia output neurons. Dopamine medication state clearly impacts fEP amplitude, and the lasting nature of the increase is reminiscent of LTP-like changes, indicating that aberrant synaptic plasticity may play a role in the pathophysiology of PD.
Pharmacological Rescue of Nonsense Mutations in Rett Syndrome
Keywords: Rett syndrome
aminoglycosides
MeCP2

Rett syndrome is a neurological condition that affects primarily girls. Approximately 40% of Rett syndrome cases arise from nonsense mutations. Several studies have shown that certain aminoglycosides can suppress some types of nonsense mutations in a context dependent manner, and allow the generation of a full length protein. It remains mostly unclear whether different nonsense mutations of MECP2 will be responsive to aminoglycoside treatment. In this study I tested whether some nonsense mutations of MECP2 seen clinically in Rett syndrome girls can be partially suppressed by aminoglycoside administration. My results show that aminoglycosides allow different mutant forms of MECP2 to be overcome in transiently transfected HEK-293 cells, but with differing levels of efficiency. Furthermore, I also show that aminoglycosides increased the prevalence of full length MeCP2 protein in a lymphocyte cell line derived from a Rett girl with R255X mutation. This study establishes the “proof of principle” that some nonsense mutations causing Rett syndrome can be suppressed by drμg treatment.
Examination of NMDA receptor subunit prevalence and distribution in crude synaptic membranes purified from a mouse model of Rett syndrome.
Keywords: Rett syndrome
MeCP2
epigenetics
neurodevelopment
synaptic maturation
glutamate
NMDA receptor complex
NR2A
biochemical purification of crude synaptic membranes
lipid rafts
postsynaptic density
discontinuous sucrose gradient

In this study we tested whether the prevalence or synaptic distribution of NMDA receptor subunits would be altered in the brain of the MeCP2-null mouse model of Rett syndrome. Detergent resistant membranes (DRMs) and post-synaptic densities (PSDs) were isolated from the synaptic membranes treated with TritonX-100, and resolved by sucrose density gradient centrifugation. Immunoblot analysis of the resulting density gradient fractions revealed that the relative distribution of the different NMDA receptor subunits between the DRM fractions, soluble fractions, and insoluble postsynaptic density fractions was preserved in the MeCP2-null brain. However, analysis of the overall NMDA receptor subunit prevalence within these fractions revealed a significant decrease in the expression of the NR1 and NR2A subunits, but not the NR2B subunit, in the MeCP2-null brain. The preservation of distribution of NMDAR subunits to the synaptic membranes, together with the decrease in NR1 and NR2A prevalence, suggest an imbalance in equilibrium between the mature and the immature synapses in a mouse model of Rett syndrome.
A New Lower Permian trematopid (Temnospondyli: Dissorophoidea) from Richards Spur, Oklahoma
Keywords: Amphbiia
Tetrapoda
Olsoniformes
Trematopidae
Acheloma

A new trematopid amphibian, Acheloma dunni, is reported based on excellently preserved cranial and postcranial elements recovered from the Lower Permian fissure fill deposits of the Dolese Brothers Co. limestone quarry near Richards Spur, Oklahoma. The new taxon is characterized by distinct lateral exposures of the palatine (l.e.p.) and ectopterygoid (l.e.e.) completely enclosed within the suborbital elements. This large, terrestrial adapted carnivore may represent the top predator of the Richards Spur assemblage. A phylogenetic analysis including 11 ingroup taxa and 54 cranial characters yielded a single most parsimonious tree, placing A. dunni within the monophyletic Trematopidae as the sister taxon to Acheloma cumminsi. Furthermore, the analysis supports including the enigmatic Ecolsonia and Actiobates within Trematopidae, forming a clade with the Upper Pennsylvanian Anconastes and the Lower Permian Tambachia. The study is the first to comprehensively analyze all valid and aberrant forms of Trematopidae within the context of broader dissorophoid phylogeny.
SLA-Aware Adaptive Data Broadcasting in Wireless Environments
Keywords: broadcasting
scheduler
data dissemination
wireless network
tardiness
utility
Service Level Agreement
scheduling policy
mobile environment
on-demand broadcast
push-based broadcast
QoS
Quality of Service
soft deadlines

In mobile and wireless networks, data broadcasting for popular data items enables the efficient utilization of the limited wireless bandwidth. However, efficient data scheduling schemes are needed to fully exploit the benefits of data broadcasting. Towards this goal, several broadcast scheduling policies have been proposed. These existing schemes have mostly focused on either minimizing response time, or drop rate, when requests are associated with hard deadlines. The inherent inaccuracy of hard deadlines in a dynamic mobile environment motivated us to use Service Level Agreements (SLAs) where a user specifies the utility of data as a function of its arrival time. Moreover, SLAs provide the mobile user with an already familiar quality of service specification from wired environments. Hence, in this dissertation, we propose SAAB, an SLA-aware adaptive data broadcast scheduling policy for maximizing the system utility under SLA-based performance measures. To achieve this goal, SAAB considers both the characteristics of disseminated data objects as well as the SLAs associated with them. Additionally, SAAB automatically adjusts to the system workload conditions which enables it to constantly outperform existing broadcast scheduling policies.
Small Signal Modeling of Resonant Controlled VSC Systems
Keywords: VSC
HVDC
Resonant Control
Small Signal Modeling

A major issue with respect to VSC based systems is the propagation of harmonics to DC side loads due to AC voltage source unbalance. Standard dq-frame control techniques currently utilized offer little mitigation of these unwanted harmonics. Recently, resonant controllers have emerged as an alternative to dq-frame controllers for regulation of grid connected converters for distributed resources. Although these control systems behave somewhat similar to dq-frame controllers under balanced operating conditions, their behaviour under unbalanced operation is superior. Currently, there are no linearized state space models of resonant controlled VSC systems. This work will develop a linearized small signal state space model of a VSC system, where resonant current controllers are used for regulation of the grid currents. It will also investigate the stability of resonant controlled VSC based systems using eigenvalue analysis for HVDC applications.
The Political Pop Art of Wang Guangyi: Metonymic for an Alternative Modernity
Keywords: Chinese art
Wang Guangyi
art history
cultural studies
contemporary chinese art
political pop art
China
Modern China
cultural history
china neoliberalism
postsocialist
postmodern art

This thesis examines the political pop art of contemporary Chinese artist Wang Guangyi in light contemporaneous shifts within the political, economic, and artistic space of China from 1978 until the present. Through an analysis of the work of art as an historically determined antagonistic aesthetic praxis, this thesis attempts to reveal the sedimented traces of the alternative modernity which the Chinese government is actively attempting to construct. With its evocative juxtaposition of contrasting ideological forms, the artwork of Wang Guangyi seeks to deconstruct the normative and teleological narratives encountered within the dialectic interplay between state sponsored transnational capitalism and Marxist-Leninist communism. An understanding of the discursive structure upon which these dual modernising narratives has been based, and of the fragmented artistic space they have engendered, should serve to enliven the debate concerning the role of cultural production in questioning and revealing narratives of the nation, of the Self, and of modernity.
An Economic Evaluation of HIV-associated Facial Lipoatrophy Treatments: A Cost-utility Analysis
Keywords: facial lipoatrophy
a cost-utility analysis
utility
QALYs

Introduction: Facial lipoatrophy is a stigmatizing hallmark for HIV-positive status, and can lead to poor social functioning. Information gleaned from an economic evaluation of facial lipoatrophy treatments would inform policy decision making concerning potential public insurance coverage. Methods: A decision-analytic model was used to estimate the lifetime costs and Quality Adjusted Life Years (QALYs) gained from treatments using either poly-l-lactic or and polyalkylimide gel for HIV positive patients. Disease progression probabilities and utilities were derived from the literature. Costs were obtained from interviews with physicians and product distributors. Findings: Incremental costs per QALY were $66,409 CAD/$57,352 CAD for poly-l-lactic acid, and $48,715 CAD/$45,457 CAD for polyalkylimide gel® (Societal perspective/Ministry of Health perspective). Sensitivity analysis did not have a significant effect on the lower incremental costs per QALY reported for polyalkylimide gel. Conclusion: Our base-case analysis revealed that treatments using polyalkylimide gel offers lower ICUR than treatments using poly-l-lactic acid.
Cyclooxegenase-2, Matrix Metalloproteinase-2, 9, 11 and CK19 Expression in Intraductal and Invasive Salivary Duct Carcinoma
Keywords: salivary duct carcinoma
COX-2
MMP-2
MMP-9
MMP-11

Salivary duct carcinoma (SDC) is an uncommon neoplasm showing extensive local invasion and metastasis. Histologically it exhibits ductal differentiation without myoepithelial participation and resembles intraductal and invasive ductal carcinoma of the breast. This study investigates the incidence of intraductal disease within invasive SDC and characterizes the expression of CK19, COX-2, MMP-2, 9 and 11 in intraductal and invasive SDC. 21 conventional SDC, 8 SDC arising as carcinoma ex-pleomorphic adenoma (CaExPA), 2 pure low-grade intraductal SDC, 1 pure high-grade intraductal SDC and 1 intraductal SDC with de-differentiation were studied. The presence of intraductal tumor in SDC is relatively common (52.4%) but is not a prominent component. SDC tumor cells were strongly positive for CK19 and COX-2. MMP-2 and 9 expression showed no significant pattern. MMP-11 was expressed by fibroblasts surrounding invasive tumor and was significantly associated with lymph node positivity (p=0.02).
The Role of Intravenous Immunoglobulin Anti-A and Anti-B in Complement Activation and Red Blood Cell Phagocytosis
Keywords: Immunohematology

Intravenous immunoglobulin is a human blood derived product that is used to treat immunodeficiencies and autoimmune disorders. An adverse side effect of IVIg therapy is hemolysis. Patients who experience hemolysis are mainly blood group A or AB. Clinical laboratory studies have demonstrated that IVIg contains ABO blood group antibodies, which can bind complement proteins. This study hypothesizes that anti-A/B in IVIg will bind to A/B antigens and activate complement in a dose dependant manner, which may lead to enhanced RBC phagocytosis. This study observed that the quantity of ABO antigens does not affect the in vitro binding of IVIg to RBCs. IVIg induced C3b deposition at high doses; however, the amount of complement deposition was insufficient to enhance phagocytosis of IVIg-sensitized RBCs by monocytic THP-1 cells in vitro. These studies emphasize that hemolytic reactions involve many factors in conjunction with antibodies and complement proteins.
Caring for Caregivers: Balancing Formal and Informal Care for Frail Older Persons
Keywords: Informal Cargivers
Home and Community Care

The decrease in hospital recovery time created a transition to more care being performed in the home. There is a need to balance care needs from both demand and supply characteristics. This research sets out to address how the presence or absence of informal caregiver(s) impacts on resource allocation decisions made by home and community care case managers. This research used a mixed methodologies approach employing both semi-structured interviews with frontline workers and secondary data analysis of the Central and Toronto Central LIHN Resident Assessment Instrument for Home Care (RAI-HC). Overall total average hours of formal services did not differ between care recipients depending on the presence or absence of a caregiver. It is evident from the responses provided by the participants that street-level bureaucracy plays a large role in service allocation decisions. That is, decisions are being made based on diverse idiosyncratic observations, opinions and feelings.
Optimization of Span-to-depth Ratios in High-strength Concrete Girder Bridges
Keywords: Span-to-depth ratio
High-strength concrete
Bridge aesthetics
Bridge design

Span-to-depth ratio is an important bridge design parameter that affects structural behaviour, construction costs and aesthetics. A study of 86 constant-depth girders indicates that conventional ratios have not changed significantly since 1958. These conventional ratios are now questionable, because recently developed high-strength concrete has enhanced mechanical properties that allow for slenderer sections. Based on material consumption, cost, and aesthetics comparisons, the thesis determines optimal ratios of an 8-span highway viaduct constructed with high-strength concrete. Three bridge types are investigated: cast-in-place on falsework box-girder and solid slabs, and precast segmental span-by-span box-girder. Results demonstrate that total construction cost is relatively insensitive to span-to-depth ratio over the following ranges of ratios: 10-35, 30-45, and 15-25 for the three bridge types respectively. This finding leads to greater freedom for aesthetic expressions because, compared to conventional values (i.e. 18-23, 22-39, and 16-19), higher ranges of ratios can now be selected without significant cost premiums.
Impacts of UV-H2O2 Treatment for Taste and Odour Control on Secondary Disinfection
Keywords: UV-H2O2
disinfection

The Cornwall Water Purification Plant collaborated with the University of Toronto to monitor UV-H2O2 treatment performance. This study includes a review of engineering and operational aspects of UV-H2O2 implementation. A number of operational challenges were experienced with retrofitting UV-H2O2 into the existing treatment plant, and an overview of the challenges and solutions faced at Cornwall is given. The project also includes a thorough water quality analysis. Taste and odour (T&O) events have been monitored for three years and the efficiency of UV-H2O2 on T&O removal is reported. Furthermore, little is known about any potential side effects of the treatment on downstream processes, especially secondary disinfection. The impact of UV-H2O2 on natural organic matter alterations, chlorine stability and disinfection by-product formation is reported using results from full-scale water quality monitoring campaigns at Cornwall, combined with laboratory experiments.
Music Industry v. File-sharing - Why We Need a New Approach to Copyright Protection in the Digital Era
Keywords: digital copyright
music industry

This thesis examines the evolution of digital copyright protection in response to the digital challenges, specifically unauthorized file-sharing, in the context of the music industry. It reviews the different strategies used to fight the peer-to-peer technology and its users so as to assess whether the direction which has been taken is in agreement with the ultimate goal of copyright and with other fundamental values of our modern society. It posits that the effort to strengthen the rights of copyright holders and thus maintain an old system of distribution in the face of new technology not only runs afoul the expectations of the public but also prevents the artists and the public from fully taking advantage of the new opportunities of the digital era. This thesis ultimately suggests that policy makers tackling the digital copyright reform should seriously consider legitimizing the use of file-sharing services as a possible way to better achieve the goals of copyright.
Stress Corrosion Crack Nucleation in Alloy 600 and the Effect of Surface Modification
Keywords: Stress Corrosion Cracking
Alloy 600
SMAT
Indentation

The stress corrosion cracking (SCC) condition for Alloy 600 was determined for various stress modes: constant-strain standard C-ring, and indentation, used to localize cracks for interrogation with x-ray techniques such as micro Laue diffraction (MLD). The SCC cracks nucleated on both the indentation edge, where finite element analysis showed that the maximum residual tensile stresses lie, and the surface in tension (bulge) on 150-kgf conically indented mill-annealed specimens (0.02 wt% C) in de-aerated solution of 10% caustic at 150 mVRE (pseudo-reference: A600), 315 OC for 48 hr. On the C-rings, the cracks nucleated at the lateral outer surface of apex, where maximum tensile stresses lie, in less than 12 hours, and propagated into the cross section. Also, corrosion tests on as-received A600 30-min ZrO2 surface mechanical attrition treated (SMAT) specimens suggested an intergranular attack type of behavior in 50% caustic at 210 mVRE (pseudo-reference: A600), 280°C for 24 hr.
Halogen Activation from Sea Ice: Nitrate Photolysis and Heterogeneous Reaction with Ozone
Keywords: bromine
activation
heterogeneous
ozone
nitrate
photolysis
Langmuir-Hinshelwood
ice
Arctic
halogen

Oxidation of aqueous bromide into reactive, gas-phase bromine species has been of interest since the 1980’s, when the presence of bromine in the Arctic boundary layer was linked to ozone depletion events. We have investigated two different mechanisms for Br2 release from sea ice. We have shown that nitrate in sea ice can photolyze to produce OH, which can go on to form gas-phase Br2. This reaction is analogous to a known reaction that occurs in the aqueous phase. We have also investigated Br2 production from a heterogeneous reaction between gas-phase ozone and sea ice/seawater. We have determined ozone’s reactive uptake coefficient, and have shown how it varies with temperature, bromide concentration, ozone concentration and acidity. We have been able to decouple the bulk aqueous chemistry that occurs from the Langmuir-Hinshelwood surface chemistry, and quantify the relative contribution of each.
Histone Deacetylase Inhibitor MS-275 Inhibits Neuroblastoma Cell Growth by Inducing Cell Cycle Arrest, Apoptosis, Differentiation and by Targeting its Tumor Stem Cell Population
Keywords: Cancer
Histone Deacetylase Inhibitor
Neuroblastoma
cancer stem cell
side population

Objective: MS-275, a phase trialed histone deacetylase inhibitor will be characterized for its ability reduce neuroblastoma (NB) viability and to target the tumor stem cell (TSC) population in neuroblastoma. Methods: Ability of MS-275 to reduce NB growth is characterized using a tumorigenic NB N-type cell line that has high differentiation potential. TSC enriched side population from NB and a reference teratocarcinoma cell line was analyzed as a model of TSC. The potential of MS-275 to modulate functional characteristics and markers of TSC was also investigated. Results: MS-275 induces a G1 cell cycle arrest, the intrinsic apoptosis pathway in NB and can potentially differentiate NB into a more terminal phenotype. NB TSC-like population is reduced following MS-275 treatment by the targeting of their self-renewal and drug pumping ability. Conclusions: By targeting both the NB and its TSC population, MS-275 has therapeutic potential for neuroblastoma. This warrants further in-vivo investigations.
Response of Human Hematopoietic Cells to DNA Double-strand Breaks
Keywords: primitive hematopoietic cell
DNA double-strand break
cell cycle
neutral comet assay
53BP1 foci
H2AX foci

Maintenance of hematopoiesis depends upon rare hematopoietic stem cells (HSCs), which can persist over an organism’s lifetime. It is conceivable that they must maintain a high degree of genetic stability; otherwise recurring exposure to genotoxins and accumulation of genetic changes could result in genomic instability and malignancy or cell death. We have focused on the response of HSCs and primitive hematopoietic cells to highly toxic DNA double-strand breaks (DSBs). Using assays to detect break rejoining and kinetics of early DSB response foci, we determined that non-cycling human HSC-containing cells display delayed break rejoining kinetics and persistent γH2AX and 53BP1 foci compared to cycling counterparts, more differentiated hematopoietic cells and human primary fibroblasts. In contrast, when stimulated to cycle, these HSC-containing cells are quite efficient at repairing breaks and resolving foci. These data suggest that the DNA damage response may be unusually prolonged in non-cycling primitive hematopoietic cells.
Regulation of Vertebrate Planar Cell Polarity
Keywords: Polarity
Development

Planar cell polarity (PCP) provides positional information to a field of cells, coordinating the orientation of polarized structures or the direction of polarized cell movements. An evolutionarily conserved signalling pathway regulates PCP, however, the cue that establishes PCP is unknown. There is a strong precedent for Wnt signalling to act as the cue to establish PCP. Here I perform in vivo assays of cell polarity to examine the role of non-canonical Wnt signalling in regulating PCP, using zebrafish neural progenitor cells and asymmetric membrane localization of GFP-Prickle (a PCP cytoplasmic effector molecule) as a model system. My preliminary evidence suggests Wnt4a provides positional information to cells in the neural tube. In addition, using a membrane-yeast-two-hybrid approach to discover novel regulators of PCP, I identified Ring Finger 41 as a new binding partner to Van-gogh-like-2 (an essential PCP signalling molecule) and a novel regulator of vertebrate PCP.
Role of the Tumor Suppressor ARF and the p53-pathway in Retinoblastoma Development
Keywords: Cancer
Retinoblastoma
INK4a/ARF
p53
Retina
Tumor suppressor
Oncogene
Therapy

Retinoblastoma development is a multistep process, and inactivation of the RB1 gene is not sufficient for tumorigenesis. Previous studies suggest that the p53-tumor suppressor is inactivated due to overexpression of p53-antagonists MDM4 and MDM2. This thesis evaluates the importance of ARF, a p53-activator that inhibits MDM2. In retinoblastomas, ARF protein is nearly undetectable despite robust mRNA expression. Chemical inhibition of the proteasome, which regulates ARF protein-turnover, did not result in ARF accumulation in retinoblastoma cells, indicating that ARF protein was not aberrantly degraded by the proteasome. During mouse retinoblastoma development, Arf protein was expressed at low level, and p53-target genes involved in cell cycle arrest and autoregulation were not activated. Overexpression of ARF in retinoblastoma cells led to growth inhibition, accompanied by increased expression of p53 and p53-transcriptional targets. Taken together, our data suggests that low ARF protein is an important factor in silencing of the p53-pathway during retinoblastoma development.