VictorJuiz/thesis huggingface dataset:
Identifying Adaptations that Promote Softwood Utilization by the White-rot Basidiomycete Fungus, Phanerochaete carnosa

Softwood is the predominant form of land plant biomass in the Northern hemisphere, and is among the most recalcitrant biomass resources to bioprocess technologies. The white rot fungus Phanerochaete carnosa has been isolated almost exclusively from softwoods, while most other known white-rot species, including Phanerochaete chrysosporium, were mainly isolated from hardwoods. Accordingly, it is anticipated that P. carnosa encodes a distinct set of enzymes and proteins that promote softwood decomposition. To elucidate the genetic basis of softwood bioconversion by P. carnosa, its genome was sequenced and transcriptomes were evaluated after growth on wood compared to liquid medium. Results indicate that P. carnosa differs from P. chrysosporium in the number and expression levels of genes that encode lignin peroxidase (LiP) and manganese peroxidase (MnP), two enzymes that modify lignin present in wood. P. carnosa has more genes for MnP with higher expression levels than LiP, while the reverse has been observed for P. chrysosporium. The abundances of transcripts predicted to encode lignocellulose-modifying enzymes were then measured over the course of P. carnosa cultivation on four wood species. Profiles were consistent with decay of lignin before carbohydrates. Transcripts encoding MnP were highly abundant, and those encoding MnP and LiP featured significant substrate-dependent response. Since differences in modes of lignin degradation catalyzed by MnP and LiP could affect the ability of each to degrade lignin from different types of wood, their activity on various hardwoods and softwoods were tested. Results suggest that MnP degrades softwood lignin more effectively than hardwood lignin, consistent with high levels of this enzyme in P. carnosa.

Keywords: Phanerochaete
Basidiomycete
qRT-PCR
genome
transcriptome
RT-qPCR
white-rot
enzyme
lignin
lignocellulose
lignin peroxidase
manganese peroxidase
fungi
transcript
Advisor: Master, Emma
Strong-Coupling Quantum Dynamics in a Structured Photonic Band Gap: Enabling On-chip All-optical Computing

In this thesis, we demonstrate a new type of resonant, nonlinear, light-matter interaction facilitated by the unique electromagnetic vacuum density-of-state (DOS) structure of Photonic Band Gap (PBG) materials. Strong light localization inside PBG waveguides allows extremely strong coupling between laser fields and embedded two-level quantum dots (QD). The resulting Mollow splitting is large enough to traverse the precipitous DOS jump created by a waveguide mode cutoff. This allows the QD Bloch vector to sense the non-smoothness of the vacuum structure and evolve in novel ways that are forbidden in free space. These unusual strong-coupling effects are described using a "vacuum structure term" of the Bloch equation, combined with field-dependent relaxation rates experienced by the QD Bloch vector. This leads to alternation between coherent evolution and enhanced relaxation. As a result, dynamic high-contrast switching of QD populations can be realized with a single beam of picosecond pulses. During enhanced relaxation to a slightly inverted steady state at the pulse peak, the Bloch vector rapidly switches from anti-parallel to parallel alignment with the pulse torque vector. This then leads to a highly inverted state through subsequent coherent "adiabatic following" near the pulse tail, providing a robust mechanism for picosecond, femto-Joule all-optical switching. The simultaneous input of a second, weaker (signal) driving beam at a different frequency on top of the stronger (holding) beam enables rich modulation effects and unprecedented coherent control over the QD population. This occurs through resonant coupling of the signal pulse with the Mollow sideband transitions created by the holding pulse, leading to either augmentation or negation of the final QD population achieved by the holding pulse alone. This effect is applied to ultrafast all-optical logic AND, OR and NOT gates in the presence of significant (0.1 THz) nonradiative dephasing and (about 1%) inhomogeneous broadening. Further numerical studies of pulse evolutions inside the proposed devices demonstrate satisfactory population contrast within a PBG waveguide length of about 10 micro meter. These results provide the building blocks for low-power, ultrafast, multi-wavelength channel, on-chip, all-optical computing.

Keywords: Photonic band gap
Quantum Dot
Strong Coupling
Population inversion
All-optical computing
Advisor: John, Sajeev
A Digital Microfluidic Approach to Proteomic Sample Processing

Proteome profiling is the identification and quantitation of all proteins in biological samples. An important application of proteome profiling that has received much attention is clinical proteomics, a field that promises the discovery of biomarkers that will be useful for early diagnosis and prognosis of diseases. While clinical proteomic methods vary widely, a common characteristic is the need for (i) extraction of proteins from complex biological fluids and (ii) extensive biochemical processing (reduction, alkylation and enzymatic digestion) prior to analysis. However, the lack of standardized sample handling and processing in proteomics is a major limitation for the field. The conventional macroscale manual sample handling requires multiple containers and transfers, which often leads to sample loss and contamination. For clinical proteomics to be adopted as a gold standard for clinical measures, the issue of irreproducibility needs to be addressed. A potential solution to this problem is to form integrated systems for sample handling and processing, and in this dissertation, I describe my work towards realizing this goal using digital microfluidics (DMF). DMF is a technique characterized by the manipulation of discrete droplets (100 nL – 10 L) on an array of electrodes by the application of electrical fields. It is well-suited for carrying out rapid, sequential, miniaturized automated biochemical assays. This thesis demonstrates how DMF can be a powerful tool capable of automating several protein handling and processing steps used in proteomics.

Keywords: microfluidics
proteomics
Advisor: Wheeler, Aaron
Diabetes Care and Serious Mental Illness: An Institutional Ethnography

People with serious mental illness are genetically predisposed to diabetes. Their risk is heightened with the use of atypical antipsychotic medications. Contextual conditions also influence diabetes care and outcomes. There is a lack of research on diabetes care for the mentally ill in residential care facilities. Therefore, there is little understanding of the social relations that contribute to this group’s health disparities. Institutional ethnography was chosen to explore this phenomenon in a group of 26 women in a rural for-profit group home in southern Ontario. Work activities of residents and providers were examined to map out the social organization of health inequities. Interviewees included residents with diabetes, care providers, field workers, and health professionals. Observations and analysis of coordinating texts were further methods used to reveal disjunctures between discourses embedded within diabetes care guidelines and the actualities of living within imposed constraints of group home care. The overarching State interest in cost containment creates rationing that limits the care afforded residents, resulting in poor dietary intake and lack of quality of life opportunities. Further, group home policies regulate systems of safety, reporting, and financial accountability, but do not promote health. The medical and psychiatric divide also contributes to health disparities. Diabetes care provision supports ‘self-care,’ which is challenging for this group, and health providers lack understanding of contextual constraints. Combined, these social circumstances perpetuate disease development and make illness management difficult. These findings warrant the need for State financial support and policy changes that give primacy to illness prevention, health promotion, and medical management so the mentally ill can realize health and wellbeing. A linkage between mental and physical health care is also crucial. Further, health providers are urged to be critical of social ideologies that sustain health inequalities, and to deliver services that are sensitive to unique particularities.

Keywords: diabetes
serious mental illness
group home care
institutional ethnography
Advisor: Angus, Janet Elizabeth
Cervical Cancer Screening Among Ontario's Urban Immigrants

Aisha Kamilah O. Lofters Cervical Cancer Screening Among Ontario’s Urban Immigrants Doctor of Philosophy, 2012 Institute of Health Policy, Management and Evaluation University of Toronto Background: The majority of cervical cancers can be prevented because of the highly effective screening tool, the Papanicolaou (Pap) test. Relevant guidelines recommend routine screening for nearly all adult women. However, inequities in screening exist in Ontario. This dissertation, consisting of three studies, uses administrative data to advance knowledge on barriers to cervical cancer screening for Ontario’s urban immigrant population. Methods: First, we developed and validated a billing code-based algorithm for cervical cancer screening. We then implemented this algorithm to examine screening rates in Ontario among women with various sociodemographic characteristics for 2003-2005. Second, we compared the prevalence of appropriate cervical cancer screening in Ontario in 2006-2008 among immigrant women from all major geographic regions of the world and Canadian-born women. Third, we used a stratified multivariate analysis to determine if the independent effects of various factors that could serve as screening barriers were modified by region of origin for immigrant women for 2006-2008. Results: Our first study showed that our algorithm was 99.5% sensitive and 85.7% specific, and that screening inequities in Ontario’s urban areas are largest among women 50 years and older, living in the lowest-income neighbourhoods and new to the province. In our second study, we determined that immigrant women had significantly lower screening rates than their peers, with the most pronounced differences seen for South Asian women aged 50 years and above. In the final study, we demonstrated that living in the lowest-income neighbourhoods, being younger than 35 years or older than 49 years, not being enrolled in a primary care enrolment model, having a male provider, and having a provider from the same region of the world each significantly influenced screening for immigrant women regardless of region of origin. Conclusion: These results add to the literature on health equity in cancer screening. Our findings demonstrate that Ontario’s urban immigrant women experience significant inequities in cervical cancer screening, and may offer guidance toward targeted patient and physician interventions to decrease screening gaps.

Keywords: equity
immigrant health
women's health
cancer screening
cervical cancer
Advisor: Glazier, Richard H.
Studies on Angiotensin Converting Enzyme 2, Angiotensin-(1-7), and p47phox-Dependent NADPH Oxidase and their Roles in Diabetic Nephropathy

Diabetic nephropathy is the leading cause of end-stage renal disease, yet the mechanisms responsible for hyperglycemia-induced kidney injury have not been fully elucidated. Activation of the renin-angiotensin system and NADPH oxidase-dependent generation of reactive oxygen species are important mediators of chronic kidney disease. I first studied the effect of ACE2, an important enzyme in the renin-angiotensin system, in diabetic kidney injury in the Akita mouse and related the effect to angiotensin peptide and NADPH oxidase. I then demonstrated the interaction between Angiotensin II, the main substrate, and angiotensin-(1-7), the main product of ACE2, respectively, on cell signaling in mesangial cells to better understand the in vitro effect of ACE2. Finally I studied the effect of deletion of p47phox, a regulatory subunit of the NADPH oxidase, on initiation and progression of diabetic nephropathy in the Akita mouse and mesangial cell. Administration of human recombinant ACE2 decreased angiotensin II levels, increased angiotensin-(1-7) levels, normalized NADPH oxidase activity in the Akita mice, and ameliorated diabetes-induced kidney injury. In vitro, hrACE2 attenuated both high glucose and ANG II–induced oxidative stress and NADPH oxidase activity in mesangial cells. Ang-(1–7)-induced ERK1/2 phosphorylation in mesangial cells in a mas receptor-cAMP-PKA-dependent manner. This effect of ang-(1-7) on ERK1/2 phosphorylation is not mediated by AT1R, AT2R, epidermal growth factor or NADPH oxidase. Pre-treatment with Ang-(1-7) attenuated Ang II-induced NADPH oxidase activity and ERK1/2 activation also in a cAMP-PKA-dependent manner. Deletion of p47phox not only reduced diabetes-induced kidney injury but also reduced hyperglycemia by increasing pancreatic and circulating insulin concentrations. p47phox-/- mice exhibited improved glucose tolerance but modestly decreased insulin sensitivity. Deletion of p47phox attenuated high glucose-induced activation of NADPH oxidase and pro-fibrotic gene expression in mesangial cells. There was a positive correlation between p47phox and collagen Iα1 mRNA levels in renal biopsy samples from control subjects and subjects with diabetic nephropathy. The data generated in this thesis strongly suggest a protective role of ACE2, via Ang-(1-7), and a deleterious role of p47phox in diabetic nephropathy. Future therapeutic strategies should include enhancing ACE2 activity in the kidney and inhibiting p47phox-dependent activation of NADPH oxidase in both the kidney and the pancreas.

Keywords: Diabetes
Diabetic nephropathy
Advisor: Scholey, James
An Empirical Analysis of Publicity and Advertising under Quality Uncertainty

Quality of a prescription drug is uncertain to patients, physicians and even the manufacturer of the drug. Because this uncertainty can deter physicians from prescribing the drug, it is important to investigate how various marketing communication activities help reveal the true quality of its product. In particular, this study investigates publicity and advertising under quality uncertainty. Chapter 1 studies the effect of publicity on consumer demand with a reduced form approach. Chapter 2 structurally investigates the roles of detailing and publicity when the information spill-over is present. Both chapters study the market of anti-cholesterol drugs (statins). Chapter 1 investigates the effects of publicity (media coverage) on consumer demand. The main obstacle to measuring the impact of publicity is that data on media coverage are difficult to interpret. To overcome this obstacle, we propose a new way to code information presented in news articles, mapping the information to a multi-dimensional attribute space. We combine our publicity data with data on sales, detailing, medical journal advertising, direct-to-consumer advertising (DTCA) and landmark clinical trial outcomes, and estimate a demand model. Our results suggest that not all forms of publicity are equal. In chapter 2, we study consumer learning about scientific evidence and its impact on demand for pharmaceutical products by using the Bayesian learning model. Unlike previous literature, our learning model allows consumer’s prior quality perceptions to be correlated across brands. This unique feature of the model allows us to investigate information spill-over effects across brands. The information spill-over allows late entrants to free-ride on first movers’ investment in clinical trials and marketing activities and to gain late mover advantage. In addition to using product level market share data, we supplement them with switching rates and discontinuing rates. The switching rate data are particularly useful for taking the presence of switching costs into consideration, which has been ignored in the literature using product-level data. Our estimated structural model has implications for managers in allocating resources to various types of marketing activities more efficiently and helps forecast returns of clinical trials that are sponsored by pharmaceutical firms.

Keywords: Statin
publicity
correlated learning
Late Mover Advantage
switching cost
detailing
advertising
pharmaceutical marketing
prescription drugs
demand
Advisor: Ching, Andrew
Horstmann, Ignatius
Comprehensive Robustness via Moment-based Optimization : Theory and Applications

The use of a stochastic model to predict the likelihood of future outcomes forms an integral part of decision optimization under uncertainty. In classical stochastic modeling uncertain parameters are often assumed to be driven by a particular form of probability distribution. In practice however, the distributional form is often difficult to infer from the observed data, and the incorrect choice of distribution can lead to significant quality deterioration of resultant decisions and unexpected losses. In this thesis, we present new approaches for evaluating expected future performance that do not rely on an exact distributional specification and can be robust against the errors related to committing to a particular specification. The notion of comprehensive robustness is promoted, where various degrees of model misspecification are studied. This includes fundamental one such as unknown distributional form and more involved ones such as stochastic moments and moment outliers. The approaches are developed based on the techniques of moment-based optimization, where bounds on the expected performance are sought based solely on partial moment information. They can be integrated into decision optimization and generate decisions that are robust against model misspecification in a comprehensive manner. In the first part of the thesis, we extend the applicability of moment-based optimization to incorporate new objective functions such as convex risk measures and richer moment information such as higher-order multivariate moments. In the second part, new tractable optimization frameworks are developed that account for various forms of moment uncertainty in the context of decision analysis and optimization. Financial applications such as portfolio selection and option pricing are studied.

Keywords: Robust Optimization
Moment Problems
Advisor: Kwon, Roy H.
Hydrophobic Hydration of a Single Polymer

Hydrophobic interactions guide important molecular self-assembly processes such as protein folding. On the macroscale, hydrophobic interactions consist of the aggregation of "oil-like" objects in water by minimizing the interfacial energy. However, the hydration mechanism of small hydrophobic molecules on the nanoscale (~1 nm) differs fundamentally from its macroscopic counterpart. Theoretical studies over the last two decades have pointed to an intricate dependence of molecular hydration mechanisms on the length scale. The microscopic-to-macroscopic cross-over length scale is critically important to hydrophobic interactions in polymers, proteins and other macromolecules. Accurate experimental determination of hydration mechanisms and their interaction strengths are needed to understand protein folding. This thesis reports the development of experimental and analytical techniques that allow for direct measurements of hydrophobic interactions in a single molecule. Using single molecule force spectroscopy, the mechanical unfolding of a single hydrophobic homopolymer was identified and modeled. Two experiments examined how hydrophobicity at the molecular scale differ from the macroscopic scale. The first experiment identifies macroscopic interfacial tension as a critical parameter governing the molecular hydrophobic hydration strength. This experiment shows that the solvent conditions affect the microscopic and macroscopic hydrophobic strengths in similar ways, consistent with theoretical predictions. The second experiment probes the hydrophobic size effect by studying how the size of a non-polar side-chain affects the thermal signatures of hydration. Our experimental results reveal a cross-over length scale of approximately 1 nm that bridges the transition from entropically driven microscopic hydration mechanism to enthalpically driven macroscopic hydration mechanism. These results indicate that hydrophobic interactions at the molecular scale differ from macroscopic scale, pointing to potential ways to improve our understanding and predictions of molecular interactions. The system established in this thesis forms the foundation for further investigation of polymer hydrophobicity.

Keywords: single molecule force spectroscopy
atomic force microscopy
hydrophobicity
hydrophobic hydration
hydrophobic collapse
protein folding
polymer model
Advisor: Walker, Gilbert C.
Osteoclastogenesis: Roles of Filamin A and SBDS, and their Regulation of Rho GTPases during Pre-osteoclast Migration

Osteoclasts are multinucleated, bone resorbing cells that carry out their function using specialized actin-based structures called actin rings and podosomes. Rho GTPases function as molecular switches that regulate the actin cytoskeleton in osteoclasts and many other cell types. Filamin A (FLNa) and SBDS are two proteins that have the potential to interact with both F-actin and Rho GTPases, and thus regulate osteoclast formation, differentiation, or function. We found that in FLNa-null pre-osteoclasts, activation of RhoA, Rac1, and Cdc42 was perturbed, leading to defective pre-osteoclast migration prior to fusion. Ablation of SBDS resulted in the blockage of osteoclast differentiation downstream of RANK and defective RANKL-mediated upregulation of Rac2 that is required for pre-osteoclast migration. Therefore, both FLNa and SBDS are required to coordinate Rho GTPase activation during osteoclastogenesis, in addition to a role for SBDS in osteoclast differentiation downstream of RANK.

Keywords: osteoclast
Rho GTPases
Advisor: Glogauer, Michael