VictorJuiz/thesis huggingface dataset:
Limiting the Collateral Damage of SARS: The Ethics of Priority Setting
Keywords: priority setting
public health
SARS
emergency management
public health ethics
collateral damage
Canada
emergency planning
decision making
resource allocation

The 2003 Severe Acute Respiratory Syndrome (SARS) outbreak in Canada highlights a broad range in ethical challenges, particularly in priority setting. Presently, a leading theory in ethical priority setting is Daniels’ and Sabin’s Accountability for Reasonableness (A4R), which enhances fair and legitimate procedural decision making in typical healthcare settings. A4R attempts to mitigate conflicting interests and facilitate fairness in deliberations over priority setting issues. Whether this framework may be applied to public health emergencies has yet to be examined. This qualitative study describes the outbreak through the lens of A4R and explores the applicability of A4R in atypical or emergent circumstances. Findings from 25 structured key informant interviews of public health officials suggest refinements to the framework may be required for emergency events. The presence of such a framework may minimize collateral damage during and after a response. The lessons may guide future preparedness efforts such as pandemic planning.
Retinal Vascular Reactivity Capacity in Healthy Subjects
Keywords: retina
blood flow
autoregulation
vascular reactivity
vision
inhaled gas provocation

Purpose: To determine the vascular reactivity (VR) capacity and visual function (VF) response to potent vasoconstrictor and vasodilatory provocations of retinal arterioles in healthy subjects. Methods: One hyperoxic hypocapnic and two graded hypoxic hypercapnic stimuli were administered. VR in response to gas provocation was assessed using the Canon Laser Blood Flowmeter. VF was assessed using high and low contrast ETDRS logMAR charts, Medmont C-100, and H.R.R. Pseudoisochromatic Plates. Results: Flow reduced by 23% (p=0.0001) during hyperoxic hypocapnia and increased by 18% (p=0.0129) during hypoxic hypercapnia. During hyperoxic hypocapnia, high contrast VA improved by -0.026 (p=0.0372). During hypoxic hypercapnia, high and low contrast VA were reduced (+0.033, p=0.0110; +0.025, p=0.0058, respectively). Colour vision was unaffected. Conclusions: The retinal arterioles demonstrated a greater capacity for vasoconstriction than vasodilation in response to the stimuli used in our study. Hyperoxic hypocapnia improved high contrast VA while hypoxic hypercapnia reduced high and low contrast VA.
Characterization of Forest Harvest Residue from the Great Lakes-St Lawrence Forests of South-eastern Ontario
Keywords: Forest harvest residue
Great Lakes-St Lawrence forests
Moisture content
Bulk density
Energy value
Proximate analysis
Ultimate analysis

The use of fossil derived products and the environmental and economic problems associated with them have made a shift to abundant renewable resources such as forest biomass more attractive. However before forest biomass can be used as a resource, its properties must be known. This study determined the physical properties of heterogeneous biomass residues produced during harvesting on two operational forest sites within the Great Lakes-St Lawrence forest of south-eastern Ontario. Properties measured were moisture content, size distribution, bulk density, and wood-to-bark ratio; also thermo-chemical properties including elemental composition, thermal reactivity and energy content were measured. The effects of forest site and harvest type, storage and position in storage pile, on the properties of biomass were also investigated. Results of the study showed that the various heterogeneous forest harvest residues differed more physically than thermo-chemically for the different variables, and this affected biomass procurement more than the potential utilization options.
Investigation of Adult Retinal Precursor Cell Behaviour In Response To Soluble Factors And Varying Substrate Stiffness in Two and Three Dimensional Scaffolds
Keywords: stem cell
retina

We have studied the factors that are important for producing functional retinal neurons from adult derived retinal stem and progenitor cells (RPCs) investigating the role of substrate stiffness or soluble factors in 2D and 3D culture on the differentiation and survival of RPCs. RPCs were cultured on agarose scaffolds modified with the adhesive peptides of varying stiffness. We observed that cell survival in the 0.75% matrix was greater in 3D than in 2D by a factor of 50% irrespective of the time in culture. We observed the presence of photoreceptors exclusively in 0.75% agarose, while the stiffer matrices (1.75%) led to retinal ganglion cell and glial cell differentiation with no significant difference in the differentiation profiles when cells were cultured in 2D vs. 3D. These data indicate that substrate stiffness, more than growth factors, has a significant impact on both the survival and differentiation profile of retinal precursor cells.
Predictors of Partial Nephrectomy Utilization and Inequities of Care in the Treatment of Renal Cell Carcinoma in Canada
Keywords: Kidney Cancer
Nephrectomy

Compared to radical nephrectomy (RN), partial nephrectomy (PN) leads to improved renal function preservation. However, PN may be infrequently utilized, particularly in patients susceptible to chronic kidney disease. We conducted a population-based, retrospective, observational study using the Canadian Institute for Health Information Discharge Abstract Database. All patients treated for a renal mass with either RN or PN from April 1, 1998 to March 31, 2008 were included in the analysis. Using descriptive statistics and multivariable regression modelling, we demonstrated low uptake of PN (17.5% overall); year, age, geographic region, Charlson score, hospital volume, and physician volume were independently associated with PN use, whereas DM, HTN and income quintile were not. In this contemporary analysis PN continues to be underutilized, and the rate of PN in DM, HTN and the elderly was less than expected given their known relationship to chronic renal failure.
Effect of Dopamine Receptor DRD2 and ANKK1 Polymorphisms on Dietary Compliance, Blood Pressure, and BMI in Type 2 Diabetic Patients
Keywords: dopamine receptor
Glycemic Index
DRD2
ANKK1
addiction
diabetes
BMI
blood pressure
dietary compliance
reward
obestiy
weight
genetic
glucose
C957T
TaqIA
polymorphism
triglycerides
cholesterol
linkage disequilibrium
DNA
single nucleotide polymorphism
HbA1c
insulin resistance
eating
gene
dopamine
behaviour
nutrition
neuroscience
Reward Deficiency Syndrome
HDL
LDL
exercise
fatty acid
LOD
neurogenetics

Reduction in dopamine receptor D2, has been associated with insufficient brain reward, food addiction, obesity, and type 2 diabetes (T2D). Our aim was to assess whether the genetic variability responsible for this reduction is associated with poor dietary compliance and life style habits in T2D patients. Genetic-analysis was done for 109 T2D individuals who completed a 24-week randomized clinical trial and were assigned to follow either a low-GI or a high-fibre diet. Polymorphisms of TaqIA and C957T were compared with physical and biochemical measures. Regardless of dietary treatments, individuals with the C957T-T allele and the TaqIA-A2 allele were significantly associated with blood pressure reduction. Carriers of the T allele significantly lowered their body mass index (BMI) over the 24-week trial. Our findings suggest that the presence of the TaqIA-A2 allele is associated with a decrease in blood pressure. The C957T-T allele was associated with decrease in pressure and body weight.
Divergent Synthesis of scyllo-Inositol Aldoxime Derivatives as Potential Inhibitors of Amyloid-Beta(1-42) Aggregate Formation
Keywords: inositol
alzheimer's disease
amyloid
aggregation

scyllo-Inositol is currently in phase II clinical trials as a therapeutic for Alzheimer’s disease (AD). Previous work from our lab has shown that scyllo-inositol prevents Ab1-42 fibril formation instead leading to the formation of small Ab oligomers in vitro. To further understand the molecular details of Ab-scyllo-inositol binding interactions, a library of scyllo-inositol derivatives was prepared. A sequence of protecting group transformations afforded a hydroxylamine functionalized scyllo-inositol. Subsequent oxime formation with aromatic aldehydes generated a novel class of inositol derivatives in good yield and high purity. The effects of these compounds on the Ab aggregation cascade were evaluated by a biotin-avidin Ab1-42 oligomer assay and atomic force microscopy (AFM). Preliminary plate assay data indicated that several of these derivatives increased peptide oligomerization and the corresponding AFM images showed altered fibril formation. These results suggested that this class of scyllo-inositol derivatives is active in the Ab aggregation cascade.
Structural and Biophysical Studies of the Role of Stromal Interaction Molecules STIM1 and STIM2 in Initiating Store-operated Calcium Entry
Keywords: STIM
store-operated calcium entry
structure
EF hand
sterile alpha-motif
NMR
CRAC
Orai

Store-operated calcium entry (SOCE) is the major Ca2+ entry pathway in most non-excitable cells maintaining prolonged elevation of cytosolic Ca2+ levels required for gene transcription. SOCE is activated by the loss of endoplasmic reticulum (ER) Ca2+ through stromal interaction molecules (STIM), ER-membrane associated Ca2+ sensors. In humans, STIM1 and STIM2 share 65% sequence similarity but differentially regulate SOCE. Biophysical studies on the luminal Ca2+-binding region suggests that STIM2 EF-SAM is more stable than STIM1. The NMR structure of Ca2+-loaded STIM2 EF-SAM determined in this work suggests a more stable SAM and a tighter EF-hand and SAM interaction in STIM2 may be account for its higher stability. Chimeric swapping of the EF-hand and SAM domains generates an unstable ES211. Introducing ES211 into cherryFP-STIM1 shows constitutive puncta which activate SOCE independent of ER depletion. The current work demonstrates that the instability of the EF-SAM plays an important role in regulating SOCE initiation.
Positive Orthogonal Code-based Cooperative Forwarding for VANETs
Keywords: VANET
Multihop
Multi-Relay
Forwarding
Cooperative
Positive Orthogonal Code

Vehicular Ad hoc Networks (VANET) consist of radio-equipped vehicles and roadside units (RSU) and support many safety and commercial applications. Multi-hop forwarding can extend the communication range of both RSUs and vehicular broadcasts. Recently, the use of Positive Orthogonal Codes (POC) as transmission patterns of repetition-based broadcast medium access control (MAC) for safety messages has been proposed. This thesis proposes a cooperative forwarding protocol in which multiple relays at each forwarding hop form a virtual relay and coordinate their transmission times to correspond to a POC codeword. The protocol thereby exploits spatial diversity while conforming to the POC-based MAC, resulting in fewer collisions and mitigating the effect of hidden terminals. The design is validated through NS2 simulations, which show comparable performance with other forwarding schemes while producing significantly less performance degradation for safety message broadcasts on the same channel.
Cdh11 Acts as a Tumor Suppressor in a Murine Retinoblastoma Model by Facilitating Tumor Cell Death
Keywords: Retinoblastoma
Cdh11
Apoptosis

Retinoblastoma, a rare childhood cancer of the retina, is characterized by loss of both alleles of the RB1 gene. However, additional mutational events are required for malignancy. CGH studies described common chromosomal changes indicating potential oncogenes and tumor suppressor genes. Previous work in the lab implicated Cadherin-11 (Cdh11) as a tumor suppressor after analysis in human retinoblastomas and in the simian virus 40 large T-antigen induced murine retinoblastoma model (TAg-RB) showed loss of Cdh11 expression. TAg-RB mice crossed with Cdh11-/- mice, revealed faster growing tumors in mice null for Cdh11. This thesis focused on defining the tumor suppressor role of Cdh11 in retinoblastoma progression. The results showed in vitro and in vivo evidence that Cdh11 was promoting apoptosis and not suppressing proliferation. We also observed an increase in invasion markers upon the loss of Cdh11. We conclude that Cdh11 acts as a tumor suppressor in retinoblastoma, through promotion of apoptosis.
The Role of the Coxsackie-adenovirus Receptor in the Pathogenesis of Heart Disease and Coxsackieviral Myocarditis
Keywords: immunology
virology
cardiomyopathy
coxsackie-adenovirus receptor
innate immunity
coxsackievirus B
MAP kinase signaling

The coxsackie-adenovirus receptor (CAR) is a viral receptor for Group B coxsackieviruses (CVB). Physiologically, CAR is a cellular adhesion protein. I report that upregulation of cardiac CAR in the young adult mouse (CAR+/MtTA+ ) caused a cardiomyopathy that was characterized by inflammation and hypertrophy. In the hearts of CAR+/MtTA+ mice c-Jun N terminal kinase (JNK) was specifically activated. JNK activation is known to promote hypertrophy of cardiomyocytes, and disrupt proteins at the intercalated disc. CVB3-infected CAR+/MtTA+ mice did not exhibit increased cardiac viral load or myocarditis severity, but did demonstrate a greater cardiac interferon-γ (IFN-γ) response when compared to littermate controls. CAR-induced expression of this antiviral cytokine may have prevented the increase in myocarditis susceptibility. Further investigation into the activation of protein kinase signaling, and antiviral signaling will provide better understanding of how CAR participates in the pathogenesis of both viral and non-viral heart diseases.
Interaction of P1 Plasmid Partition Components with the Bacterial Chromosome
Keywords: P1 plasmid
partition system
plasmid localization
bacterial chromosome

P1 is a low copy number plasmid that uses a dedicated partition system that actively ensures each daughter cell inherits a copy of the plasmid. P1 plasmid partition is a positioning reaction, ensuring that each plasmid copy is correctly localized to the one-quarter and three-quarter position or midcell in an E. coli cell prior to partition. The factors involved in this positioning process are not well understood. I utilized cell biology techniques and E. coli mukB mutants that produce cells with chromosomal condensation defects to study the role of the bacterial chromosome and P1 ParA as possible localization signals. P1 plasmid prefers to localize to the bacterial nucleoid even when the chromosome is perturbed. ParA is necessary for plasmid localization to the chromosome. In this study, live cell microscopy analysis of ParA indicates that an interaction between P1 ParA and the E. coli nucleoid may underlie the localization mechanism of the plasmid partition system.
A Subset of Retinoblastoma Lacking RB1 Gene Mutations have High-level MYCN Gene Amplification
Keywords: Retinoblastoma
Genetics
MYCN
aCGH

Retinoblastoma is the prototype genetic cancer caused by mutations disrupting the RB1 tumor suppressor gene. Following loss of RB1, retinoblastoma acquires further genetic changes in a characteristic set of oncogenes and tumor suppressors including gains of the oncogenes KIF14, DEK, E2F3, and MYCN and loss of the tumor suppressor CDH11. The constellation of genetic changes is the postulated genetic pathway leading to retinoblastoma. However, advances in molecular diagnostic testing for RB1 gene mutations allows detection of at least one RB1 mutation in 98% of unilateral retinoblastomas leaving 2% of cases with undetectable RB1 mutations (RB1+/+ retinoblastoma). RB1+/+ retinoblastomas have high-level MYCN gene amplification (>30 copies) and few other genetic changes. In addition, RB1+/+ retinoblastoma present earlier than conventional RB1-/- retinoblastoma and show histologic features similar to MYCN-amplified neuroblastoma. Altogether, this study describes a distinct genetic subset of retinoblastoma characterized by wild-type RB1 gene and high-level MYCN gene amplification.
Effects of Rho-kinase Iinhibition on Established Chronic Hypoxic Pulmonary Hypertension in the Neonatal Rat
Keywords: Pulmonary hypertension
rho-kinase inhibition
Y-27632

Rationale: Vascular remodeling and right-ventricular (RV) dysfunction are features of refractory pulmonary hypertension (PHT) in human neonates. These features are replicated in rats chronically exposed to hypoxia (13% O2), in which increased pulmonary vascular resistance (PVR) was acutely normalized by Y-27632, a Rho-kinase (ROCK) inhibitor, but not by inhaled nitric oxide. Objective: To examine the reversing effects of sustained ROCK inhibition on haemodynamic (RV dysfunction and increased PVR) and structural (RV hypertrophy and arterial wall remodeling) changes of chronic hypoxic PHT. Methods: Rat pups were exposed to air or hypoxia from birth for up to 21 days and received Y-27632 (15 mg/kg/b.i.d.) or vehicle from day 14. Results: Y-27632 normalised RV dysfunction and reversed remodeling secondary to chronic hypoxia. These changes were accompanied by increased apoptosis of smooth muscle and attenuated endothelin-1 expression in pulmonary arteries. Conclusion: ROCK inhibitors hold promise as a rescue therapy for refractory PHT in neonates.
High Throughput Prediction of Critical Protein Regions Using Correlated Mutation Analysis
Keywords: Correlated Mutation Analysis
Covariation
Coevolve
Contact Prediction
Dependency
PatchD

Correlated mutation analysis is an effective approach for predicting functional and structural residue interactions from protein multiple sequence alignments. A prediction pipeline over the Pfam database was developed to predict residue contacts within protein domains. Cross- reference with the PDB showed these contacts are spatially close. Furthermore, we found our predictions to be biochemically reasonable and correspond closely with known contact matrices. This large-scale search for coevolving regions within protein domains revealed that if two sites in an alignment covary, then neighboring sites in the alignment would also typically covary, resulting in clusters of covarying residues. The program PatchD was developed to measure the covariation between disconnected sequence clusters to reveal patch covariation. Patches that exhibited strong covariation identified multiple residues that were generally nearby in the protein structures, suggesting that the detection of covarying patches can be used in addition to traditional CMA approaches to reveal functional interaction partners.
A Hierarchical Analysis of Trial of Labour in Ontario: Do Women, Doctors or Hospitals Choose?
Keywords: Trial of Labour
Vaginal Birth After Cesarean
Cesarean section, repeat
physicians
hospitals
patient satisfaction

Background: Few studies have determined the contribution of maternity care provider and hospital factors to the variation in Trial of Labour (TOL) and successful TOL rates. Objective: To determine sources of variation in TOL and successful TOL rates at the provider and/or hospital level. Methods: Retrospective cohort study of 12,170 women with previous caesarean who gave birth in Ontario in 2007. Hierarchical linear model was used to determine variation in rates by provider and hospital characteristics, adjusting for maternal characteristics, and for clustering of data. Results: TOL rate was 23%; successful TOL rate 75%. Women attending family doctors and female doctors for prenatal care were more likely to have TOL. There were no provider factors associated with successful TOL. Women giving birth at teaching hospitals were more likely to have TOL and successful TOL. Conclusions: Policies aimed at prenatal care providers and hospitals could impact the low TOL rate.
Aluminum Doped Zinc Oxide Thin Film for Organic Photovoltaics
Keywords: Aluminum Doped Zinc Oxide
Photovoltaics

Aluminum Doped Zinc Oxide (AZO) produced by radio frequency (RF) magnetron sputtering is thought to be the prospective replacement of the de facto standard indium tin oxide (ITO) anode in organic solar cells. In order to achieve a proper resistivity and transmittance of AZO thin film compared to ITO, a systematic study was done to optimize the sputtering conditions. In this work, two primary parameters: target-substrate distance and sputtering power, were optimized, and a optimized film thickness was determined. A poly(3-hexylthiophene) (P3HT) and [6,6]-phenyl C61 butyric acid methyl ester (PCBM) bulk-heterojunction organic solar cell was fabricated based on the optimized parameters and the power conversion efficiency reached 0.83%. A theoretical analysis is given to explain the optimization process. This work provides a clear pathway to substitute AZO for ITO in organic solar cells for future mass production.
Nanocrystalline Metal Enabled Conductors for Enhanced Strength-to-weight Aerospace Electrical Wiring
Keywords: Nanocrystalline
Strength-to-Weight
Aerospace
Conductors
Electrodeposition
Composite
Wire

High strength-to-weight nanocrystalline alloy enabled conductor (NEC) prototypes were successfully developed by reinforcing an oxygen-free copper core material with electrodeposited cobalt phosphorus (CoP) coatings. A rule of mixtures approach was utilized to design the NEC prototypes to meet materials performance indices. Three unique NEC prototypes were produced with CoP coatings composed of alternating nanocrystalline (11 nm) and coarse-grained layers. The tensile properties were dependant on the coating microstructures, with tensile strengths of 1000 MPa, 970 MPa, and 900 MPa, respectively, and corresponding tensile elongations of 4.6%, 6.1%, and 10%, respectively. The electrical conductivity of the NEC prototypes was ~58 %IACS (resistivity of ~2.96 µΩ-cm). The rule of mixtures approach effectively predicted the tensile strength and conductivity. The NEC samples were significantly stronger than the incumbent high-strength aerospace conductor material, Be-Cu alloy CS95, which exhibits a tensile strength of only 655 MPa and conductivity of 63 %IACS.
Critical Factors Involved in Intestinal Chylomicron Assembly
Keywords: apolipoprotein B
lipids
CD36
FABP1

Assembly of intestinal chylomicron particles (lipid-protein complexes) is the fundamental mechanism by which we absorb dietary fat. Two intestinal lipid transporters, Cluster of Differentiation 36 (CD36) and fatty acid-binding protein 1 (FABP1), have been shown to play a role in lipid absorption, however, it remains unclear how knockdown of these proteins bleads to aberrant intestinal chylomicron secretion. In an enterocyte-like cell culture model, Caco-2 cells, we hypothesized that knockdown of CD36 or FABP1 using short-hairpin RNA interference techniques would impair triacylglycerol (TG) and apolipoprotein B (apoB) secretion. Surprisingly, knockdown of these lipid transporters lead to an increase in TG and apoB secretion that was associated with an increase in fatty acid synthase and fatty acid transport protein 4 (FATP4) protein levels. De novo fatty acid synthesis was slightly increased in CD36-, but not FABP1-knockdown Caco-2 cells. This study highlights the importance of fatty acid targeting in regulating chylomicron production.