VictorJuiz/thesis huggingface dataset:
The Role of Beta-Adrenergic Receptors in Mediating Cerebral Perfusion During Acute Hemodilution
Keywords: hemodilution
beta-receptor
cerebral perfusion
beta-blocker
anemia
beta-selectivity
hypoxia

Cerebral perfusion is optimized during hemodilution by both β1- and β2-adrenergic mechanisms. Antagonism of the β2-adrenoreceptor can impair cerebral vasodilation. We hypothesized that treatment with a highly β1-specific antagonist (nebivolol) would minimize the degree of cerebral hypoxia during hemodilution. Anesthetized rats were randomized to receive vehicle or nebivolol (1.25 or 2.5 mg/kg intravenously) prior to hemodilution. In vehicle-treated rats, hemodilution increased cardiac output (CO) and regional cerebral blood flow (rCBF) while microvascular brain PO2 (PBrO2) decreased. Both nebivolol doses reduced heart rate and attenuated the CO response to hemodilution. Only the higher dose of nebivolol attenuated the rCBF response to hemodilution and caused a further reduction in PBrO2. Brain hypoxic protein levels were only increased in the high dose nebivolol group. High dose nebivolol treatment resulted in drug levels near its affinity for the β2-adrenoreceptor supporting the hypothesis that cerebral perfusion is maintained by β2-dependent mechanisms during hemodilution.
Lanthanum-mediated Biomimetic Aminoacylation
Keywords: tRNA
aminoacylation

Methods are being developed to produce “designer proteins” from unnatural amino acids that are added into specific locations by the ribosome using an altered mRNA. To date, over seventy unnatural amino acids have been incorporated at specific sites in proteins by in vitro biosynthetic methods using chemically acylated-tRNAs and in vivo protein mutagenesis based on orthogonal tRNA/aminoacyl-tRNA synthetase pairs. Lanthanum-mediated aminoacylation of cis-diols provides a general and selective method for the one-step preparation of aminoacyl-tRNA. The nature of this biomimetic process was studied for the reaction of ribonucleosides and nucleotides with N-t-Boc-protected aminoacyl ethyl phosphates. Successful aminoacylation was also achieved with unprotected aminoacyl ethyl phosphates. This method was extended for the aminoacylation of tRNA and analyzed by reversed-phased HPLC and MALDI-MS. These results will provide an insight to the ultimate goal of lanthanum-mediated direct acylation of tRNA and its applications in in vitro site-specific incorporation of unnatural amino acids.
Anillin, An Organizer of Cytokinesis
Keywords: Anillin
Septins
Asymmetric cytokinesis
Temporal order
MDCK
Epithelial cells

Anillin is a highly conserved multi-domain cytoskeletal protein that provides a spatial and temporal scaffold for contractile ring proteins to ensure successful cytokinesis. We have looked at the temporal order of anillin and septin recruitment to the cleavage furrow using time-lapse microscopy and found that anillin localizes to the furrow in early anaphase while septins appear there later in an anillin-dependent manner. We also characterized the effect of anillin depletion in different cell lines and observed that septins and myosin delocalize in the absence of anillin in Tet-ON HeLa, AD293 and ARPE-19 cells but not in wild type HeLa cells. Asymmetric furrow formation was also investigated using the epithelial cell model: MDCK cells. Depletion of anillin and SEPT9 in MDCK cells was achieved using lentivirus shRNA constructs and this revealed that anillin or SEPT9 depletion did not affect asymmetric cytokinesis, although localization of SEPT 9 was affected by anillin depletion.
Receptor Binding Profiles of Antipsychotic Medications and Glucose Dysregulation: An Acute Animal Model
Keywords: schizophrenia
antipsychotic
diabetes
glucose
metabolic syndrome
side effects
receptors
pharmacology

Atypical antipsychotics (AAPs) are associated with metabolic sequelae including risk of type 2 diabetes. Evidence points to a weight-gain independent and direct drug effect on glucose homeostasis. While the exact mechanisms remain elusive, the heterogeneous binding profiles of AAPs likely include receptors involved in glucose metabolism. We aimed to clarify weight-gain independent mechanisms of AAP-induced alterations in insulin secretion. Deconstruction of the receptor binding profiles of these agents was done using representative antagonists and the hyperglycemic clamp. We assessed the acute effects of several selective receptor antagonists on glucose metabolism, namely prazosin, idazoxan, MDL100907, SB242084 and WAY100635. Prazosin and MDL100907, selective α1 and 5HT2A antagonists, respectively, caused significant decreases in both insulin and C-peptide secretion. A decreased glucose infusion rate and disposition index was also found in the prazosin group. Antagonism of the α1 and 5HT2A receptors may be involved in AAP-induced glucose dysregulation, however, the responsible mechanisms remain unknown.
Effects of Vitamin D Supplementation on Intestinal Inflammation in Experimental Inflammatory Bowel Disease
Keywords: Vitamin D
IL-10 KO mice
Gut Microbiota
Intestinal Inflammation

Vitamin D may have immunomodulatory effects in the intestine. Our objective was to determine if exposure to vitamin D mitigates intestinal inflammation in IL-10 KO mice. Mice were randomized to a diet containing 25 IU (low) or 5000 IU (high) of vitamin D/kg of diet in utero and offspring were maintained on the same diet or switched to the other diet at weaning. Fecal samples were collected at 3 months of age. Vitamin D did not affect intestinal inflammation in male and female mice and did not affect KC cytokine concentration or regulate colonic gene expression in male mice. Vitamin D modulated the gut microbiota in a sex-specific manner and depending on timing of exposure. Females in the HH group had significantly higher fecal counts of C. coccoides than the other vitamin D interventions. Therefore, vitamin D may favourably modulate microbiota composition without attenuating inflammation.
Development and Application of New Methods for Characterizing the Environmental Fate of Halogenated Organic Contaminants
Keywords: environmental chemistry
method development
halogenated contaminants

This thesis explored new methods for understanding the fate and transport of halogenated organic contaminants in the environment. A theoretical method of hazard assessment of chemical mixtures containing large numbers of components was developed and its application illustrated using polychlorinated alkanes, toxaphene, and halogenated dibenzo-para-dioxins and furans. Partitioning properties predicted by high-throughput quantitative structure property relationships were used to locate mixture constituents on plots displaying equilibrium phase distribution in various environmental compartments and the potential for bioaccumulation and long range transport. Potentially hazardous components were identified graphically for more detailed assessments. The applicability of XAD-resin based passive air samplers (XAD-PAS) for studying neutral polyfluoroalkyl substances (nPFAS) in the atmosphere was tested empirically. XAD-PASs have sufficiently high uptake capacity to yield temporally averaged nPFAS concentrations over period as long as a year. When applied as part of the Global Atmospheric Passive Sampling network, nPFAS were found to be truly global contaminants.
Sterol-based Organogel Drug Delivery Systems
Keywords: organogels
drug delivery
intravitreal
sitosterol
dexamethasone
gels

In this work, transparent and rigid organogels suitable for intravitreal drug delivery applications were produced with pharmaceutical/food grade polar and amphiphilic solvents with HLB values ranging from 0-19. Maximum sterol solubility was obtained with solvents with approximately HLB=6. Solvents with high sterol solubility also required higher sterol concentrations to produce a gel. However, the strength of all the organogels increased with increasing sterol concentration. Furthermore, DSC and SAXS data suggest that the structure of all the organogels was similar. An in vitro release of dexamethasone was performed over a 5.5 month period using novel organogel- dexamethasone implants. The release of dexamethasone varied from 2 to 5.5 months (or more) depending on the organogel used for the implant. These multiple-month release in vitro profiles are comparable and/or exceed the release of commercially available and FDA approved dexamethasone delivery system Ozurdex (~2 month dexamethasone release).
The Cost of Preanalytical Errors in the Context of Inpatient Complete Blood Count Testing
Keywords: Pre-analytical
Pre-analytical error
Laboratory
Laboratory error
Cost
Finance
Patient safety
Medical error
Quality Improvement
Quality assurance
Error
Pre-analytical phase
CBC
complete blood count

The majority of laboratory testing errors originate in the pre-analytical phase. While the causes and frequencies of pre-analytical errors are well characterized, there are few studies investigating the cost of these errors. The objective of this research was to build a model to quantify the cost of pre-analytical errors occurring during inpatient complete blood count (CBC) testing at Sunnybrook Health Sciences Centre (Sunnybrook). The resultant cost model accounts for the costs of materials, resources, and personnel-time consumed in the CBC testing process. In 2011, pre-analytical errors in inpatient CBC testing cost Sunnybrook $43,462, and represented a loss of 775 employee hours due to laboratory test repetition and error-related activities. This cost model represents the minimum cost of a pre-analytical error, as costs extraneous to the laboratory were beyond the study scope. Future studies investigating downstream effects of pre-analytical errors and the costs associated with them should be conducted.
Surfactant and Adhesive Formulations from Alkaline Biomass Extracts
Keywords: Surfactants
Adhesives
Biomass
Alkaline Extract

This work studies the ability to produce effective surfactant and adhesive formulations using surface active biological material extracted from different biomass sources using alkaline extraction methods. Two urban waste biomass sources were used to produce surfactants, Return Activated Sludge (RAS), and solid Urban Refuse (UR). The third biomass source investigated was isolated mustard protein (MP). RAS and MP extracts were investigated for adhesive production. The results indicate that extracts from the waste biomass sources, RAS and UR, can be combined with a commercial surfactant, sodium dioctyl sulfosuccinate (AOT), to produce surfactants with low interfacial tensions against various oils. These highly surface-active formulations were shown to be useful in the removal of bitumen from contaminated sand. RAS and MP showed potential as protein-based wood adhesives. These sources were used in adhesive formulations to produce a strong bond strength under low-pressure, ambient pressing conditions.
The Stomatin STO-6 is a Novel Regulator of the Caenorhabditis elegans Motor Circuit
Keywords: c. elegans
motor circuit
stomatin
locomotion
nervous system

The ability to move is essential to an animal’s ability to interact with and respond to its changing environment. The nematode Caenorhabditis elegans is a commonly used organism in the study of the genetic and neural bases of behaviours, yet the mechanistic explanation for its ability to move in a smooth sinusoidal wave remains elusive. Here, I present studies of an uncharacterized gene, sto-6, encoding a stomatin protein that regulates C. elegans motor behaviour. I show that this gene plays a role in two unexplained and fundamental processes to C. elegans locomotion: wave initiation and wave propagation. Furthermore, I examine the genetic interaction between sto-6 and an innexin gene unc-7, providing support for the hypothesis that stomatins regulate gap junction proteins in C. elegans. Together, these studies push forward our understanding of the mechanistic basis of C. elegans locomotion, and open up avenues of further inquiry.
Application of Hybrid Simulation to Fragility Assessment of Self-centering Energy Dissipative (SCED) Bracing System
Keywords: Hybrid-Simulation
Self-Centering
Fragility Analysis
Model Updation

Substructure hybrid simulation has been actively investigated in recent years. The simulation method allows for the assessment of seismic performance of structures by representing critical components with physical specimens and the rest of the structure with numerical models. In this study the system level performance of a six-storey structure with self-centering energy dissipative (SCED) braces was validated through pseudo dynamic (PsD) hybrid simulation. Fragility curves are derived for the SCED system. The study presents the configuration of the hybrid simulation and discusses some of the practical intricacies in performing PsD hybrid simulations. In addition the study addresses some of the challenges associated with the substructuring process during a hybrid simulation. Two techniques, extensive analytical study and model updation, are discussed to improve the response from the hybrid simulation accounting for the variation in global response of a structural system depending on which structural element was represented as a physical specimen.
Structural and Functional Relationships between Ubiquitin Conjugating Enzymes (E2s) and Ubiquitin Ligases (E3s)
Keywords: Ubiquitin
Ubiquitin chains
RAD6
KCMF1
X-linked mental retardation
Autoubiquitylation
Affinity purification coupled with mass spectrometry
E2
HECT E3
Interactome

The first part of the thesis describes a systematic function analysis that identified in vitro E2 partners for ten different HECT E3 ligase proteins. Using mass spectrometry, the linkage composition for the resulting autoubiquitylation products of a number of functional E2-HECT pairs was determined. HECT domains from different subfamilies catalyze the formation of very different types of Ub chains, largely independent of the E2 in the reaction. The second part of the thesis describes the characterization of the RAD6-interactome. Using affinity purification coupled with mass spectrometry, I identified a novel RAD6-interacting E3 ligase, KCMF1, which binds to a different surface on RAD6 than the other RAD6-associated E3 ligases. KCMF1 also recruits additional proteins to RAD6, and this new complex points to novel RAD6 functions. Interestingly, the RAD6A R11Q mutant polypeptide, found in X-linked mental retardation patients specifically loses the interaction with KCMF1, but not with other RAD6-associated E3 ligases.
Examining Model Predictions of Zinc and Copper Aqueous Speciation and Freshwater Ecotoxicity: Case Study of Ross Lake, Flin Flon, Manitoba, Canada
Keywords: Metals
Modelling
Toxicity

Models of aqueous metal speciation and ecotoxicity have become commonplace due to their ability to estimate metal behaviour. This study evaluated commonly used aqueous geochemical speciation and ecotoxicity models with application to a mine impacted lake in northern Manitoba. The geochemical speciation model Winderemere Humic Aqueous Model (WHAM) was compared with Diffusive Gradients in Thinfilm (DGT) measurements of zinc and copper. DGT measurements in the water column corresponded well with WHAM-estimated Zn2+, Cu2+ was off by up to 100x. Additional metal, either from small organic bound species or dissolution of metal sulphides from resuspended sediment, served to improve model estimates. The single metal Biotic Ligand Model (BLM) predicted acute toxicity to Daphnia magna attributable to copper but not zinc, at low pH (3.55 – 5.5). Comparison of results did not show a significant difference between the single and mixture BLMs, suggesting a non-interactive effect on metal toxicity for measured water chemistry.
Customizable Services for Application-layer Overlay Networks
Keywords: software
engineering
networking

Application-layer overlay networks have emerged as a powerful paradigm for providing network services. While most approaches focus on providing a pre-defined set of network services, we provide a mechanism for network applications to deploy customizable data delivery services. We present the design, implementation, and evaluation of application-defined data delivery services that are executed at overlay nodes by transmitting messages marked with service identifiers. In our approach, a data delivery services is specified as an XML specification that define a finite-state machines that respond to network events, and perform a set of network primitives. We implemented a mechanism to execute these XML specifications in the HyperCast overlay middleware, and have evaluated this mechanism quantitatively on an Emulab testbed. The experiments show that our approach is effective in realizing a variety of data delivery services without incurring unreasonable performance overhead.
Topics in Wind Farm Layout Optimization: Analytical Wake Models, Noise Propagation, and Energy Production
Keywords: wind farm design
operations research

Wind farm layout optimization (WFLO) is the design of wind turbine layout, subject to various financial and engineering objectives and constraints. The first topic of this thesis focuses on solving two variations of WFLO that have different analytical aerodynamic models, and illustrate deep integration of the wake models into mixed-integer programs and constraint programs. Formulating WFLO as MIP and CP enables more quantitative analysis than previous studies could do with heuristics, and allows the practitioners to use an off-the-shelf optimization solver to tackle the WFLO problem. The second topic focuses on another version of WFLO that has two competing objectives: minimization of noise and maximization of energy. A genetic algorithm (NSGA-II) is used. Under these two objectives, solutions are presented to illustrate the flexibility of this optimization framework in terms of supplying a spectrum of design choices with different numbers of turbines and different levels of noise and energy output.
Analysis of the Timber-concrete Composite Systems with Ductile Connection
Keywords: Timber-Concrete Composite
Partial Interaction
Duction Connections
Incremental Method

In timber-concrete composite systems, timber and concrete are inherently brittle materials that behave linearly elastic in both tension and bending. However, the shear connection between the members can exhibit significant ductility. It is therefore possible to develop timber-concrete composite systems with ductile connection that behave in a ductile fashion. This study illustrates the use of an elastic-perfectly plastic analytical approach to this problem. In addition, the study proposes an incremental method for predicting the nonlinear load-deflection response of the composite system. The accuracy of the analytical model is confirmed with a computer model, and numerical solutions of the analytical model are compared to experimental results from the bending tests conducted by previous researchers. Reasonable agreement is found from the comparisons, which validates the capacity of the analytical model in predicting the structural behaviour of the timber-concrete composite systems in both elastic and post-elastic stages.
Effects of Coagulation on the Removal of Natural Organic Matter, Genotoxicity, and Precursors to Halogenated Furanones
Keywords: disinfection by-products
drinking water
MX
MCA
3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone
halogenated furanones
natural organic matter
genotoxicity
DBPs
coagulation
LC-OCD

Disinfectants in drinking water can interact with natural organic matter (NOM) to form disinfection by-products (DBPs). Halogenated furanones (including MX and MCA) are a group of emerging DBPs that can account for a significant amount of the total mutagenicity found in drinking water. Source water characteristics and NOM removal capabilities of coagulation can greatly influence the formation of DBPs. This project examines the effects of bench scale coagulation and chlorination tests on NOM removal, DBP formation, and genotoxicity. NOM was characterized using liquid chromatography-organic carbon detection (LC-OCD). Experiments with Ottawa River, Otonabee River, and Lake Simcoe waters show that DBPs decreased with increases in coagulant dosage, due to the removal of NOM during coagulation. DBP formation and speciation was then compared with NOM content to identify specific fractions that contribute to the formation of these DBPs. Genotoxicity was directly linked to MX presence in chlorinated waters.
FDTD Modeling of Graphene-based RF Devices: Fundamental Aspects and Applications
Keywords: computational electromagnetics
FDTD

Graphene is a single atomic layer of graphite and has many extraordinary properties. Many graphene based applications have been proposed in recent years and the need of a time domain simulation tool for studying graphene based devices emerges. This thesis focuses on developing a simulation framework for graphene based devices using finite-difference time-domain (FDTD) method. Formulation for a perfectly matched layer (PML) for the sub-cell FDTD method for thin dispersive layers has been derived and implemented. Such a PML is useful when thin layers extend to the boundaries of the computational domain. Using the sub-cell PML formulation to model the graphene thin layers significantly reduces the computational cost compared to using the conventional FDTD. The proposed formulation is accompanied by detailed validation and error analysis studies. Several graphene applications are simulated using the new framework and the results show good agreement with the respective analytical models.
Remote Sensing of Tall Grasslands: Estimating Vegetation Biochemical Contents at Multiple Spatial Scales and Investigating Vegetation Temporal Response to Climate Conditions
Keywords: remote sensing
biochemical properties

This thesis estimated vegetation biochemical properties at multiple spatial scales and investigate vegetation temporal dynamics under climate influences in a heterogeneous tallgrass ecosystem in Southern Ontario using remote sensing data. Ground hyperspectral and space multispectral remote sensing data derived Normalized Difference Vegetation Index (NDVI) and Simple Ratio (SR) were used to estimate biochemical properties at the species, canopy and landscape level. Both vegetation indices explained 32% to 56% of the variations in biochemical properties at the species level, 16% to 53% at the canopy level, and over 60% at the landscape level. MODIS NDVI and climate data were also collected to investigate the vegetation-climate relationships during the growing season and the lag effects of climate factors on vegetation at the peak growing season. The findings indicate that temperature is the key climate factor that drives the annual cycle, and there is a time lag effect of climate factors on vegetation.
Automatic Detection of Selective Auditory Attention Via Transient Evoked Otoacoustic Emissions
Keywords: access technology
otoacoustic emission
auditory attention
body-machine interface
TEOAE

Past studies have shown that the effects of selective auditory attention are evident in medial olivocochlear (MOC) activity, manifested as the contralateral suppression (CS) of transient evoked otoacoustic emissions (TEOAEs). This finding suggests the use of TEOAEs in the design of an auditory-based access technology as a potential access solution for children with severe disabilities. Thirteen participants with normal hearing threshold and normal middle ear function completed this study. The participants were instrumented with a TEOAE ear probe and presented with a contralateral acoustic stimulus. They were instructed to alternate auditory attention conditions as visually cued by symbols on an LCD display. Attentive and non-attentive conditions were detected with an overall accuracy of 70.17 +/- 12.54% at 2.44 +/- 0.3 bits per minute in a participant-specific classifier, and 65.92 +/- 13.91% in a participant-independent classifier. Detection of auditory attention exceeded random chance levels for 11 of 13 participants.