VictorJuiz/thesis huggingface dataset:
The Evolutionary Implication of Gene Expression Variation in Eukaryotes: From Yeast to Human

The expression level of a single gene can vary substantially within and between species, which might facilitate the emergence and fixation of novel expression patterns in the course of evolution. With rapidly accumulating data from genome-wide expression profiling, dense genotyping and individual genome re-sequencing, it is now possible to pinpoint the genetic loci that potentially give rise to gene expression variation. However, what remains elusive is how expression changes could be attributed to the differences in genetic elements, and our understanding of the phenotypic manifestation resulting from gene expression variation is far from comprehensive. In this thesis, I aim to answer these questions in budding yeast and in human. I first studied duplicated genes in budding yeast, which usually shared the identical expression patterns immediately upon duplication events. I searched for the cis-elements, whose divergence might explain the substantial expression variation between the extant paralogs, and established the role of nucleosome occupancy in driving expression differentiation between yeast duplicates. I next investigated the role of trans-factors in establishing species- or population-specific gene expression, and my study was specifically focused on primate microRNAs as a special class of regulators in trans. I first delineated the evolutionary trajectory of an X-linked primate microRNA cluster, and then proposed its function in regulating primate epididymal physiology. I extended this study to human by identifying several microRNAs with highly differentiated regulation among human populations, and such regulatory differentiation was driven by positive selection during recent human evolution. This study for the first time demonstrated high plasticity of the microRNA regulatory interactions in modulating expression variation of their target messengers. Beyond exploring the elements that control gene expression variation, I examined phenotypic manifestation of the observed expression variation in human populations, and my analysis revealed significant implication of expression variation towards differential disease susceptibility among individuals. Lastly, I examined gene expression variation at a micro scale among isogenic cell populations in budding yeast, which is termed “expression noise”. Though expression noise originates from stochasticity, my analysis demonstrated strong topological constraints on expression noise in yeast cellular networks, with which I was able to predict gene expression noise with high accuracy. These observations suggest that the seemingly stochastic gene expression may have been evolutionarily constrained. Taken together, my study presented in this thesis investigates the origin, consequence and evolutionary significance of gene expression variation in eukaryotes.

Keywords: gene expression
expression evolution
natural selection
population genetics
Advisor: Zhang, Zhaolei
Speaking for the Dead: Coroners, Institutional Structures, and Risk Management

Based on interviews and ethnographic fieldwork, this dissertation shows how the Office of the Chief Coroner of Ontario (OCC) – whose object is to speak for the dead to protect the living – is shaped by risk management priorities. It illustrates how the OCC, like many contemporary organizations, has altered its operations and decision making to manage threats to its reputation. The result of these moves has been the privatization of public safety decision making with bereaved families, the general public, and even front line coroners, increasingly excluded from speaking for the dead. This is to say, policy recommendations that shape how life in Ontario is lived tend to be generated in private sessions by OCC managers. While much of this can be attributed to the OCC’s focus on reputational risk management, there are other important factors affecting the privatization of public safety. Drawing on research in the sociology of culture, the dissertation finds that the OCC’s experience of risk management is moderated by other, layered institutional structures. These ‘institutional structures’ are analytic constructs with moral and methodological dimensions that inform the way work in the OCC is carried out. The dissertation demonstrates that the moral priorities and method preferences of doctors, lawyers, managers, families, and modern governments are layered over and under risk management. These layers augment or diminish risk management’s impact on the way death is determined and public safety regimes are developed. In addition to offering a window on death investigators and their work, the dissertation proposes a theoretical toolset for better understanding how contemporary organizations are organized and run.

Keywords: Coroners
Institutions
Death Investigation
Risk Management
Advisor: Levi, Ron
A Feasibility Study of a Bourdieu-informed Parent Briefing Intervention to Improve Parents' Satisfaction with Decision Making for Hospitalized Children with Complex Health Care Needs

Children with complex health problems who are dependent upon medical technology require frequent hospitalizations, during which parents must make difficult decisions regarding their child’s care. Although principles of “family-centred care” have been widely adopted by paediatric hospitals, studies indicate that many parents are dissatisfied with their roles in decisions about their child’s care. Pierre Bourdieu’s Logic of Practice, specifically his concepts of field, capital, and habitus, as they relate to cultural and symbolic capital within the field of pediatric medicine, were used to guide the design of a parent briefing intervention aimed at improving parents’ satisfaction with decision making. Briefings were conducted during daily hospital rounds. Physicians and nurses were asked to sit while using a checklist as a communication guide. A two-part study was conducted to determine feasibility of a randomized controlled trial of a parent briefing. One component was a psychometric evaluation of an instrument to measure parents’ satisfaction with decision making. The other was a phase I single group, post-test study of the parent briefing. Eighty-two parents of children admitted to an in-patient unit in a large metropolitan pediatric health centre, with an expected length of stay ≥ 3 days, completed the Family Satisfaction with Decision Making (FS/DM) subscale and the Decisional Conflict Scale (DCS) prior to discharge. A subgroup of parents participated in the parent briefing study. The Cronbach’s alpha reliability coefficient of the FS/DM was 0.87, and it was inversely correlated with the DCS (r2= -0.635, p<0.0001). Eighteen physicians, 25 nurses, and 31 parents participated in the phase I trial of the briefing intervention. Sixty-eight out of an expected 93 briefings were carried out as per study protocol. Nineteen parents did not receive the required “dose” of the study intervention. Mean time to complete the intervention was 11.9 minutes (SD = 6.9). Parents and nurses rated the acceptability and usefulness of the intervention favourably, whereas physicians’ ratings were mixed. The FS/DM instrument is a suitable primary outcome measure for an RCT. However, more work needs to be done, to ensure the feasibility of the intervention, including more intensive clinician training.

Keywords: children with complex health care needs
physician/nurse-parent communication and decision making practices
parent briefing intervention
parent satisfaction with decision making
Advisor: Hodnett, Ellen
As the Body Unfolds: Examining Girls’ Changing Experiences with the Socially Constructed Labels ‘Tomboy’ and ‘Girly Girl’

This study explored the lived experiences of girls with the socially constructed labels ‘tomboy’ and ‘girly girl’. Using a prospective, life history, qualitative methodology, girls between the ages of nine to fourteen years old were interviewed up to four times over five years for an extensive embodiment project. The present study investigated girls’ narratives of the ‘tomboy’/ ‘girly girl’ dichotomy to deepen an understanding of how gender discourses affect how girls learn to live in their bodies. A total of 87 interviews were collected from 27 girls representing diverse social and cultural backgrounds as well as different urban and rural Canadian locations. The interviews were transcribed and analyzed for themes using the constant comparison method from Grounded Theory. Examining the data from a feminist poststructuralist theoretical approach, three main dimensions emerged that described these girls’ experiences of living with these labels from childhood through adolescence. The first dimension described the shared cultural stereotypes of the ‘tomboy’ and ‘girly girl’ labels. The second dimension delineated the social outcomes in terms of the privileges and consequences associated with each label in childhood and in adolescence. The third dimension highlighted girls own negotiated self experiences and identities in relation to this gender dichotomy. Through its prospective design, this research uniquely delineated the complex range of experiences girls have within gender discourses and explored how labels work to control and restrict girls’ freedom to stay connected to their self and body.

Keywords: gender
girls
tomboy
adolescence
Advisor: Piran, Niva
Local-spin Abortable Mutual Exclusion

Abortable mutual exclusion is a variant of mutual exclusion, in which processes are allowed to abort in the trying protocol. Scott presented the first local-spin abortable mutual exclusion algorithms. They are based on a queue and perform O(1) remote memory accesses (RMAs) when no processes abort. However, they use unbounded space and a process can perform an unbounded number of RMAs, in the worst case, to enter the critical section. The only other local-spin abortable mutual exclusion algorithm is by Jayanti. It has bounded space and RMA complexity, but a process always performs \Theta(log N) RMAs to enter the critical section, where N is the number of processes. In this thesis, three new, bounded space, abortable mutual exclusion algorithms are presented. We give the first local-spin abortable mutual exclusion algorithm that uses only registers. It has \Theta(log N) RMA complexity, even if no processes abort. We also present the first local-spin abortable mutual exclusion algorithm using more general primitives which has bounded space and in which each process performs O(1) RMAs to enter the critical section when no processes abort. However, this algorithm is local-spin only for a certain type of cache-coherent model. Finally, we present an abortable mutual exclusion algorithm which is local-spin in any cache-coherent model and in which each process performs O(1) RMAs to enter the critical section when no processes abort. We develop a new reference counting method to bound the space used in this algorithm.

Keywords: distributed computing
theory
mutual exclusion
algorithms
shared memory
computer science
Advisor: Ellen, Faith
Individual Investors and Financial Disclosure

Using detailed data of individual investors, this dissertation investigates whether and how individuals use financial disclosure and analysts’ signals. Chapter 1 shows that, on average, individuals invest more in firms with readable, concise, and transparent financial disclosures. The results indicate that these relations are less pronounced for overconfident investors, and that individual investors appear to place a greater weighting on such financial disclosure attributes relative to institutional investors. In supplementary analyses, I further examine cross-sectional variations among individuals in their use of disclosure, and find two main subgroups that do not display a preference for accessible and transparent disclosures. The first subgroup is speculative investors, whose investment strategies rely on conjecture rather than knowledge, and the second subgroup is financially literate investors, those with lower information processing costs. These findings support the notion that more accessible and transparent disclosures are used by those individuals who need them the most: i.e., the average American. Lastly, I examine whether individuals’ investment performance varies with financial disclosure attributes and show that individuals’ returns are, on average, increasing in firms with more accessible and transparent disclosures. Chapter 2 examines how individuals react to revisions in analysts’ recommendations and earnings forecasts. First, the analyses show that individuals’ abnormal trading activity increases by 30 percent in response to analysts’ recommendation revisions and by 15 percent in response to analysts’ earnings forecast revisions. Second, the analyses indicate that 47 percent of individuals trade consistently with analyst guidance and 53 percent trade contrarian to analysts’ guidance, which opposes the belief that individuals are a homogenous group of investors. The contrarian behavior is most common in response to analyst downgrades (i.e., purchasing after downgrades) and is most evident among individuals with better prior performance, individuals who trade infrequently, men, and older individuals. Lastly, the study provides evidence suggesting that trading contrarian to analysts is in general hazardous to individuals’ financial health. Taken together, the results indicate that individuals respond to analyst guidance and that individuals’ use of analyst guidance varies significantly with respect to their personal attributes.

Keywords: Individual Investors
Financial Disclosure
Advisor: Hope, Ole-Kristian
Jazzvertising: Music, Marketing, and Meaning

This dissertation examines jazz from the perspective of advertisers and marketers that have used the music with a view to unraveling the complicated web of cultural meanings and values that attend to jazz in the 21st century. Advertising is a critically important and profoundly complex medium for the mass dissemination of music and musical meaning. Advertisers and marketers therefore offer crucial perspectives on the construction, reification, and circulation of jazz meanings and discourses. At the same time, I argue that historically jazz has been a cultural practice that is uniquely situated on the cusp of the binarized cultural categories of “high art” and “popular/commercial”. With that in mind, I suggest that jazz offers an invaluable lens through which to examine the complex and often contradictory culture of consumption upon which North American capitalism is predicated. In a broad sense, then, I examine the confluence of jazz, consumption, and capitalism as they are articulated through the medium of advertising. I contextualize my analysis with a short history of music in advertising and a discussion of jazz’s embeddedness in capitalism and the North American culture of consumption. The core of the dissertation consists of three detailed case studies: an analysis of jazz and luxury in a 2003 Chrysler Canada campaign for the high-end cars Sebring and 300M, featuring Diana Krall; a discussion of the function of jazz in the spectacularization of cultural diversity and individual agency in the television campaign for a 2006 Diet Pepsi product called “Jazz”; and an examination of corporate amorality in the Toronto Dominion Bank’s sponsorship of jazz festivals in Canada. Finally, I consider how both communities and individuals have been subjectively constituted and/or called into being by consumption and, conversely, how they have used the convergence of jazz and consumption to “talk back” to capitalism.

Keywords: ethnomusicology
jazz studies
advertising
media studies
Advisor: Kippen, James R.
Photoacoustic Imaging Using Chirp Technique: Comparison with Pulsed Laser Photoacoustics

The application of photoacoustic (PA) phenomena to medical imaging has been investigated for more than a decade. To implement this modality, one may choose between two types of laser sources, pulsed or continuous wave (CW). This selection affects all features of the imaging technique. Nowadays pulsed lasers are the state-of-the-art technique in the PA research. In this work, various features of the alternative frequency-domain (FD) PA were investigated. An axially symmetric transfer function model of PA wave generation and a Krimholtz-Leedom-Matthaei (KLM) transducer model were developed and used to analyze the experimental results. The controllable parameters of the FD-PA were optimized to improve the signal-to-noise ratio (SNR), contrast, axial resolution and depth detectivity. For example, it was shown that employing the optimal chirp bandwidth can enhance the SNR by more than 10 dB. In addition to the image produced by the cross-correlation amplitude, the phase of the correlation signal was used as a separate channel. A statistical method was introduced to generate an image from this phase channel, and also to filter the PA amplitude channel. A study was also performed to compare FD PA and the prevalent pulsed method. Various features of both methods were examined experimentally using a dual-mode PA system and under the condition of maximum permissible exposure (MPE). The SNRs of both methods were evaluated theoretically and experimentally. It was shown that at low frequencies, both modalities generate comparable SNRs, and at high frequencies pulsed PA produces superior SNRs and depth detetivity. However, by increasing the laser power and decreasing the chirp duration within the safety limits, the SNR and depth detectivity of the FD-PA method are enhanced considerably. The main cause to achieve lower experimental SNRs than theoretical predictions for pulsed PA response was shown to be the oscillating baseline, which can be partially eliminated by filtering.

Keywords: Photoacoustics
Photoacoustic imaging
continuous wave
frequency-domain
optoacoustics
medical imaging
Advisor: Mandelis, Andreas
EGFR in Early Non-small Cell Lung Cancer: Tyrosine Kinase Inhibition in a Neoadjuvant Trial

EGFR TKIs are standard therapy for advanced NSCLC. In order to define their role in early disease, we implemented a phase II trial of neoadjuvant gefitinib in clinical stage I NSCLC. Tumour shrinkage was seen in 43% of patients, with 11% achieving RECIST partial response (PR). Analysis of molecular markers showed EGFR TKD mutations in 17% of cases, being the only associated with PR. For the first time we defined the histopathological response of NSCLC to these agents, characterized by reduction in tumour cellularity and proliferative index as well as presence of non-mucinous BAC histology. Clinical PR tumours also presented large areas of stromal fibrosis with presence of focal residual tumour. In a characterization of intracellular signalling response, EGFR dephosphorylation in the residues Y1068 and Y1173 was not concordant and only the former was significantly reduced. pAkt Ser473/Akt and Thr308/Akt ratios were significantly reduced but observed among both, clinical responders and resistant patients. Interestingly, reduction in pEGFR Y1068 was significantly associated with increase in tumour cellularity (p=0.047), Ki-67 index (p=0.018) and tumour growth (p=0.019) with a residual perinuclear localization been detected, suggesting a novel mechanism of resistance involving receptor internalization. Finally, we determined that the EGFR protein remains stable up to one hour of post resection ischemia but two to three tumour samples are necessary for an adequate tumour representation. Furthermore, EGFR cytoplasmic compartment presented the best association with clinical response in our cohort. Taking all together, we were able to generate the first clinical trial exploring the use of an EGFR TKI in early NSCLC, characterizing for the first time the histopathological and signalling responses to these agents with an evidence of a potential novel mechanism of resistance. Finally, we observed that multiple samples collection for an adequate tumour representation, and assessment of the cytoplasmic compartment, are warrant.

Keywords: lung cancer
NSCLC
neoadjuvant
EGFR
EGFR TKI
response
histopathological response
molecular response
Intratumoural heterogeneity
ischemia
Advisor: Waddell, Thomas K.
Tsao, Ming-Sound
Postprandial Metabolic Responses to Macronutrient in Healthy, Hyperinsulinemic and Type 2 Diabetic Subjects

The literature comparing macronutrient metabolism in healthy and diabetic subjects is abundant; however, little data exists on how non-diabetic subjects with insulin resistance handle macronutrient. We did two studies to investigate the postprandial responses to macronutrient in healthy, hyperinsulinemic and type 2 diabetic (T2DM) subjects. In the first study, twenty-five healthy, non-diabetic subjects [9 with fasting serum insulin (FSI) <40pmol/L; 8 with 40 ≤ FSI < 70pmol/L; and 8 with FSI ≥ 70 pmol/L] were fed eleven test meals (50g oral glucose with 0-30g doses of canola oil or whey protein) after an overnight fast. There were no significant FSI × fat (p=0.19) or FSI × protein (p=0.08) interaction effects on glucose response, suggesting that the effects of fat or protein on glycemia were independent of FSI of the subjects. In addition, the changes in relative glucose response per gram of fat (r = -0.05, p = 0.82) or protein (r = 0.08, p = 0.70) were not related to FSI of the subjects. In the second study, Healthy (FSI < 40pmol/L), Hyperinsulinemic (FSI ≥ 40pmol/L), and T2DM were fed five foods with 50g available carbohydrate. Among the subject-groups, the Glycemic Index (GI) values were not significantly different for each food, and the mean (±SEM) GI values of all foods were not significantly different (p>0.05). However, the mean (±SEM) Insulinemic Index of the foods was higher in T2DM (100±7, n=10) than those of Healthy (78±5, n=9) and Hyperinsulinemic subjects (70±5, n=12) (p=0.05). The Insulinemic Index was inversely associated with insulin sensitivity (r=-0.66, p<0.0001), positively related to fasting- and postprandial-glucose (both r=0.68, p<0.0001) and hepatic insulin extraction (r=0.62, p=0.0002). The oral-glucose data were pooled from the two studies to investigate whether there was any relationship between GLP-1 and insulin sensitivity, β-cell function and hepatic insulin extraction. No significant correlation was observed (p>0.05). The results suggest that the glucose-lowering effect of fat and protein is not affected by insulin sensitivity. GI is independent of the metabolic status of the subjects; however, unlike GI, Insulinemic Index is influenced by the metabolic status of the subjects, and thus may have limited clinical utility.

Keywords: insulin resistance
insulinemic index
Advisor: Wolever, Thomas M. S.