VictorJuiz/thesis huggingface dataset:
Mercenaries: The Paradoxical Effect of Pay-for-performance on Unethical Tasks

While some organizations, like charities and government agencies, engage in prosocial behavior that upholds the highest prescriptive moral values in our society; others, like those in the tobacco, fossil fuel, gambling, and weapons industries, operate within the confines of the legal system while nevertheless behaving antisocially and violating core moral proscriptions against harming others. Unfortunately our understanding of the psychology that enables collective moral violations is still very limited because scholarship in behavioural business ethics has tended to focus on individual-level antecedents of unethical behaviour as opposed to the interpersonal and organizational factors that lead ordinarily ethical people astray. This dissertation attempts to rectify this imbalance by asking how it is possible to motivate employees to comply with instructions that violate society’s ethical principles. Given that money is generally considered the most powerful motivational tool available to most organizations, this research examines how different financial incentive structures motivate performance of dirty work that is technically legal but violates society’s ethical norms. Surprisingly, and contrary to its well-documented positive effect on the performance of ethically-neutral work tasks, I predict that pay-for-performance incentive structures will have a negative effect on performance of unethical tasks. Existing motivational theories are unable to make similar predictions, so I contribute to our understanding of unethical behavior on behalf of organizations by considering the embedded nature of ethical decision-making and argue that pay-for-performance alters employees’ perceived employment relationships and thereby inhibits moral disengagement from societal norms. Through a series of pilot studies I identify two appropriate experimental paradigms to test my hypotheses. The first reported experiment involves a novel paradigm in which online workers are recruited as part of a marketing study to compose social-media advertising messages in support of a tobacco company. The second experiment adapts an established bug-killing paradigm in which laboratory participants are asked to place either bugs or inanimate objects into a modified coffee grinder that they subsequently activate. In both experiments, participants are either paid for their performance of this moderately unethical task or receive a comparable flat fee. This dissertation reports the results of these experiments and discusses their scholarly contribution.

Keywords: Business ethics
Employment relationship
Experiment
Incentives
Moral identity
Advisor: Zhong, Chen-Bo
DeVoe, Sanford
Development of a Proteomics Platform for Analysis of the Plant-pathogen Interface

Plants possess an elaborate tiered immune system to detect the presence of pathogens. Once triggered, immune responses are sufficient to abrogate pathogen growth. As a result, effective phytopathogens must either evade immune detection or interdict plant immune signalling and responses. The Gram negative bacteria Pseudomonas syringae causes diseases of economically important crops and can also infect the model plant Arabidopsis thaliana. The type III secretion system (T3SS) represents a critical virulence strategy employed by P. syringae to cause disease in hosts. The T3SS functions as a molecular syringe to inject proteinaceous type III secreted effectors (T3SE) into the plant cytosol. After injection, T3SE inhibit plant immunity through direct interaction with host proteins. Because T3SE interact with plant immune components, T3SE can be used as molecular probes for defining novel components of plant immunity. In this role, T3SE have been exploited to discover crucial components of plant immune systems using classical genetics and yeast two-hybrid analyses. However, there have been limited attempts to leverage T3SE as proteomic probes for isolating protein complexes involved in plant immunity. This thesis presents the first successful proteomic identification of a T3SE/Arabidopsis protein complex. The T3SE HopF2 was purified from transgenic Arabidopsis using a combination of gel filtration chromatography and immunoaffinity purification. During gel filtration, HopF2 existed as both a member of a high molecular weight complex and a monomer. Immunoaffinity purification of high molecular weight complexes containing HopF2, and identification of complex members LC-MS/MS, suggested HopF2 complexes contain plasma membrane H+-ATPases. This lead to the hypothesis that HopF2 may manipulate stomatal apertures during infection because plasma membrane H+-ATPases play a role in regulating stomatal aperture. Consistent with this, transgenic expression of HopF2 inhibits stomatal immunity and increases the virulence of surface inoculated P. syringae. Intriguingly, HopF2’s ability to inhibit stomatal aperture is independent of HopF2’s characterized ADP-ribosyltransferase activity, suggesting HopF2 is a multifunctional T3SE. Together this implies a novel virulence function of HopF2 through the manipulation of stomatal immunity.

Keywords: Arabidopsis thaliana
Proteomics
Pseudomonas syringae
Type III secreted effector
Advisor: Desveaux, Darrell
Guttman, David S
The Role of Mechanism of Action of CD200:CD200R1 Interaction in Breast Cancer

Cancer cells can use immune inhibitory receptors to evade the host’s anti-tumour responses and establish immunosuppressive networks in the tumour microenvironment. In this thesis, we investigated the interaction between the immunosuppressive molecule CD200 with its receptor, CD200R1, in breast cancer. We found that CD200 is expressed in the local tumour microenvironment in human breast cancer patients and developed a mouse model to study the effect of CD200 on tumour growth and metastasis. Using mouse-derived EMT6 breast cancer cells and BALB/c female hosts, we explored the effects of overexpressing and silencing the expression of CD200 and CD200R1 in hosts and tumour cells. CD200 expression by host and tumour cells enhanced tumour growth and metastasis to draining lymph nodes (DLN). Silencing CD200 expression in EMT6 tumour cells led to a reduction in primary tumour size and metastasis, as well as an increase in anti-tumour cytotoxic responses in the host. Lack of CD200R1 expression in the host resulted in a marked decrease in breast cancer development and CD200R1-/- mice were able to mount specific anti-EMT6 immune response that could be adoptively transferred to wild type naïve hosts. In addition, we extended our findings to a model in which anti-tumour immunity was explored in EMT6 tumour-bearing hosts lacking CD200 expression and treated with a combination of immunotherapy with the non-conventional chemotherapeutic agent, metformin. The findings suggest that CD200 may be an important prognostic marker and a target for breast cancer treatment that could synergize with other therapies and improve outcomes in patients.

Keywords: anti-tumour immunity
breast cancer
CD200
CD200R
immunology
immunotherapy
Advisor: Gorczynski, Reginald M
Mozart's Orchestral Cantabile Style: Eighteenth-century Origins of String Performance Practices

Mozart’s Orchestral Cantabile Style: Eighteenth-Century Origins of String Performance Practices David Bowser Doctor of Musical Arts (2015) Graduate Department of Music University of Toronto A stylistic change in mid-eighteenth-century compositions inspired a decidedly lyrical concept of string playing characterized by connected bowing manner, sustained tone and legato phrasing. At the same time, string instruments and particularly bows were adapted to the changing performance style and became standardized. Mozart’s letters and other historical documents suggest that vibrato and portamento were characteristic to some degree of the string performance style of the late eighteenth century. While Roger Norrington contends that vibrato was not a feature of orchestral string performance before the mid-1930s, historical texts, score indications, string teachers and scholars imply that string vibrato saw a longer evolution over centuries. The instrumental cantabile style in Mozart’s music is inspired by the voice and its qualities. Two characteristics have bearing specifically on performance practices of the orchestral string repertoire: the voice possesses an innate sense of connectivity and a natural tendency to vibrate. This study examines compositional style and corresponding performance practices in orchestral string playing in the eighteenth century and traces the evolution of string vibrato into the twentieth century. It explores the stylistic changes during the mid-eighteenth century, tracking the development from old to new styles and the emergence of melody, the origins and development of the High Classical style of Mozart and Haydn, and the implications of this stylistic evolution for eighteenth-century performance practices, especially as they relate to compositions of Mozart. Included are an analysis of historical texts and treatises referring to string vibrato, a survey of current scholarly opinion, and a discussion of string vibrato indications in scores composed in the nineteenth century and early twentieth century. This study examines research on vocal vibrato by vocal scientists and pedagogues while appraising Mozart’s statement that “the voice trembles naturally” and that “people imitate it…on stringed instruments.” Finally, this research addresses Norrington’s claims and investigates indicators of orchestral string vibrato application revealed in archival footage of Bruno Walter conducting in rehearsal, and in early twentieth-century archival films of German, French and British orchestras.

Keywords: Archival Film Evidence
Cantabile
Roger Norrington
String Performance Practice
Vocal Science
Wolfgang Amadeus Mozart
Advisor: Parker, Mary Ann
Protein Tyrosine Phosphorylation in Haematopoietic Cancers and the Functional Significance of Phospho- Lyn SH2 Domain

Protein-tyrosine phosphorylation (pY) is a minor but important protein post-translational modification that modulates a wide range of cellular functions and is involved in cancer. Dysregulation of tyrosine kinases (TKs) and protein-tyrosine phosphatases (PTPs) have been observed in multiple myeloma (MM) and acute myeloid leukemia (AML) and is a subject of study. Using recently developed mass spectrometry-based proteomics techniques, quantitative PTP expression and cellular pY profiles were generated for MM cell lines and mouse xenograft tumors, as well as primary AML samples. Integrated comprehensive analyses on these data implicated a subset of TKs and PTPs in MM and AML, with valuable insights gained on the dynamic regulation of pY in biological systems. In particular, I propose a model that describes the cellular pY state as a functional output of the total activated TKs and PTPs in the cell. My results show that the global pY profile in the cancer models is quantitatively related to the cellular levels of activated TKs and PTPs. Furthermore, the identity of the implicated TK/PTPs is system-dependent, demonstrating context-dependent regulation of pY. To further understand pY regulation, I studied the phosphorylation of a conserved tyrosine in the Src homology 2 (SH2) domains of Src family kinases, which was frequently observed in human cancer specimens and regulated in cancer-derived cell lines. Using the Lyn SH2 domain as a model, I discovered that when this tyrosine (Y194) is phosphorylated, the domain has reduced ability to interact in vitro with phosphopeptides and phosphoproteins. Sequence analysis of the binding motifs revealed that phosphorylation at Y194 decreased the selectivity of Lyn SH2 for the third residue C-terminal to the pY of the ligand. Together, these data show that tyrosyl phosphorylation alters the substrate binding profile of Lyn SH2 and may potentially affect Lyn kinase signaling. This may be a general mechanism for all Src family kinases and represents another layer of the complexity of pY regulation.

Keywords: hematopoietic cancer
kinase/phosphatase
mass spectrometry
proteomics
SH2 domain
tyrosine phosphorylation
Advisor: Moran, Michael F
On the Fabrication, Characterization and Mechanical Properties of Melt-stretched Stochastic Honeycombs

This thesis presents a new type of polypropylene (PP) cellular material fabricated through a simple melt-stretching process. Stochastic honeycombs have an open cell, random honeycomb structure, with webs oriented perpendicular to built-in skins. This process has the advantage that, for example, PP pellets can be turned into a sandwich panel in one step. It was demonstrated that despite the randomness in the web structure, the out-of-plane compressive strength of stochastic honeycombs was repeatable, and exceeded that of commercial PP foams and was comparable to commercial PP honeycombs. The key material properties required to produce an this architecture were shown to be a high melt strength and a high viscosity, branched polymer. The viscosity was shown to affect the total length of the webs in cross-section and the relative partitioning of material through the skin, transition region and webs. Web thickness was affected by the areal density of the polymer during fabrication. Mechanical testing methods were adapted from ASTM standards for honeycombs, and the fabrication method was advanced from a manual to a machine controlled process. Stochastic honeycombs were shown to buckle elastically, plastically, and fracture after the peak strength. Elastic and plastic buckling were dominant at lower densities, and plastic buckling and fracture at higher densities. A thin-plate buckling model for the strength of stochastic honeycombs was developed and verified experimentally. The crystallinity of the polymer affected the tensile strength and stiffness, having a linear effect on the buckling strength. The architecture was composed of webs bound on both sides and webs bound on one side and free on the other. A greater fraction of bound webs increased the strength of the structure in the buckling model. A fabrication study showed that melt-stretching the polymer at higher strain rates increased the connectivity and fraction of bound webs. Additionally, higher density led to a less connected structure. Energy absorption could be improved if the drop in stress from the peak to valley strength was minimized. Higher melt-stretching rates during fabrication increased the energy absorbed, and higher viscosity polymers minimized the drop from peak to valley, also increasing the absorbed energy.

Keywords: cellular materials
high melt strength polypropylene
x-ray tomography
Advisor: Hibbard, Glenn D
Identification of Proteins Involved in the Maintenance of Genome Stability

Aberrant changes to the genome structure underlie numerous human diseases such as cancers. The functional characterization of genes and proteins that maintain chromosome stability will be important in understanding disease etiology and developing therapeutics. I took a multi-faceted approach to identify and characterize genes involved in the maintenance of genome stability. As biological pathways involved in genome maintenance are highly conserved in evolution, results from model organisms can greatly facilitate functional discovery in humans. In S. cerevisiae, I identified 47 essential gene depletions with elevated levels of spontaneous DNA damage foci and 92 depletions that caused elevated levels of chromosome rearrangements. Of these, a core subset of 15 DNA replication genes demonstrated both phenotypes when depleted. Analysis of rearrangement breakpoints revealed enrichment at yeast fragile sites, Ty retrotransposons, early origins of replication and replication termination sites. Together, this highlighted the integral role of DNA replication in genome maintenance. In light of my findings in S. cerevisiae, I identified a list of 153 human proteins that interact with the nascent DNA at replication forks, using a DNA pull down strategy (iPOND) in human cell lines. As a complementary approach for identifying human proteins involved in genome maintenance, I used the BioID technique to discern in vivo proteins proximal to the human BLM-TOP3A-RMI1-RMI2 genome stability complex, which has an emerging role in DNA replication progression. I uncovered 45 proximal proteins to the wildtype complex and catalogued the gains and losses of proximal proteins following the expression of three RMI1 mutants and in conditions of DNA replication stress. Altogether, I used a multi-faceted approach to identify a replication-enriched dataset of genes and proteins that collectively safeguard the genome from mutations, which will be invaluable for functional characterization studies in the future.

Keywords: Chromosome rearrangements
DNA repair
DNA replication
Essential genes
Genome instability
Protein-protein interactions
Advisor: Brown, Grant W
Investigating the Role of the Hippo Pathway Member Nf2 in the Segregation of Trophectoderm and Inner Cell Mass

During mammalian development, the first two lineages to be specified are trophectoderm (TE) and inner cell mass (ICM). Proper segregation of these two cell types requires precise spatial control of the Hippo signaling pathway and its downstream transcriptional activator, Yap. In outside, future TE cells of the embryo, Yap is nuclear-localized and can influence the expression of TE-specifying transcription factors such as Cdx2. In contrast, in inside cells, the Hippo pathway kinases Lats1/2 and the adaptor protein Amot induce phosphorylation and cytoplasmic retention of Yap, preventing this transcriptional influence. The factors acting upstream of Lats1/2, Amot and Yap in this context are not well understood. In this thesis, I have investigated the role of the upstream Hippo pathway member Nf2 in TE/ICM segregation. First, using a dominant negative approach, I show that Nf2 is required in a cell-autonomous manner for the proper localization of Yap in inside cells of the embryo. Second, by generating both zygotic and maternal/zygotic Nf2 mutant embryos, I confirm that Nf2 is required for Hippo signaling and demonstrate that this signaling is broadly required for the segregation of ICM from TE. Finally, using maternal/zygotic mutant embryos as a tool, I provide evidence that Nf2 regulates levels of Amot at the plasma membrane of inside cells during active Hippo signaling. Together, these studies demonstrate that Nf2 is essential for both Hippo signaling and lineage specification in the early embryo and provide molecular insights into how these functions are achieved.

Keywords: Hippo signaling
Inner cell mass
Lineage specification
Nf2
Preimplantation development
Trophectoderm
Advisor: Rossant, Janet
Engineering and Production of Glucooligosaccharide Oxidases for Site-specific Activation of Cellulose and Hemicellulose Substrates

Canada has an extensive supply of residual biomass, which comprises plant polysaccharides that represent a renewable resource for the production of biochemicals, polymers and fuels. Enzymatic oxidation of plant oligo- and poly-saccharides can alter the characteristics of these compounds, enhancing their application in food products; enzymatic oxidation could also facilitate site-specific chemical derivatizations of carbohydrates, leading to new bio-based polymers. A glucooligosaccharide oxidase from Sarocladium strictum (GOOX) was engineered in this study using a genetic engineering approach to extend the activity of this enzyme on a wider range of plant polysaccharides and oligosaccharides. For the first time, in addition to the previously reported cello- and malto-oligosaccharides, activity of wild type GOOX on xylooligosaccharides was reported. The catalytic efficiency of two mutant enzymes (GOOX-Y300A, GOOX-Y300N) on cellooligosaccharides and xylooligosaccharides was 2-fold higher than the wild-type enzyme. Notably, the binding affinity of these mutants towards oligosaccharides had decreased, which was correlated to reduced substrate inhibition by cellooligosaccharides. As expected, the GOOX-W351F mutant showed enhanced activity and affinity on galactose compared to wild-type GOOX as a result of reduced steric hindrance. Wild type GOOX exhibited low activity on polysaccharides including konjac glucomannan, and barley β-glucan, and weak activities on carboxy-methyl cellulose, regenerated amorphous cellulose, microcrystalline cellulose (Avicel), and xyloglucan. The specific activity was improved by up to 56 %, 55 % and 30 % for crystalline cellulose (Avicel), regenerated amorphous cellulose (RAC) and glucomannan, respectively, by constructing fusions between GOOX and various carbohydrate binding modules (CBMs). Binding capacities of the fusion proteins on crystalline and amorphous cellulose, as well as glucomannan, β-glucan, and xyloglucan also increased by over 10-fold as determined by SDS-polyacrylamide gel electrophoresis and affinity gel electrophoresis. The immobilized fusion enzyme on a solid cellulose surface remained stable and active. This finding is anticipated to broaden applications of GOOX as an immobilized enzyme used in cellulose-based biosensing devices. In addition to enzyme engineering and biochemical characterizations, three applications of GOOX enzymes were briefly evaluated including production of oxidized oligosaccharides as sugar standards, synthesis of plant oligosaccharides and polysaccharides with enhanced nutraceutical value, and substitution of glucose oxidase used in baking applications.

Keywords: Enzymatic Oxidation
Protein Engineering
Advisor: Master, Emma R
Ontario Colleges and the Introduction of Degrees: Mission Drift or Sustaining the Mission?

This qualitative, exploratory study focused on the introduction of the bachelor’s degree credential in Ontario colleges and whether or not offering degrees constitutes a change in the mission of Ontario colleges, as outlined in the Basic Documents and according to key college and governmental officials. The data was gathered through interviews with senior leaders at five urban colleges, senior government officials, and was focused on a ten year period (2002-2012). In addition, document analysis and the examination of available statistics were undertaken to ascertain the impact the legislative changes enacted in 2000 and 2002 have had on the college mission in Ontario. This study found that three founding tenets of the colleges – labour market responsiveness, access for students, and an emphasis on the functions of teaching and learning – were generally being adhered to between 2002 and 2012. This study also found that the majority of college and governmental leaders believed that the introduction of degrees was a logical extension of the mission, and the progression of the mission itself was essential if colleges were to be responsive to changing labour and community needs. The leadership of two subject colleges, however, did demonstrate a desire to move beyond the original mission in the service of a perceived need for a more differentiated postsecondary education system in Ontario.

Keywords: college
mission drift
Ontario
postsecondary
Advisor: Pascal, Charles