EXAMINATION OF VALPROIC ACID-INDUCED PERTURBATIONS TO DNA REPAIR, NF-ΚB SIGNALING AND CBP/P300 TRANSCRIPTIONAL CO-ACTIVATORS

Exposure to the antiepileptic drug valproic acid (VPA) is associated with an increased risk of congenital malformations including heart, skeletal and most frequently neural tube defects. Although the mechanisms contributing to its teratogenesis are not well understood, VPA was previously shown to increase homologous recombination (HR)-mediated DNA repair and decrease protein expression of the transcription factor NF-κB/p65. The studies in this thesis utilized in vivo and in vitro models to evaluate the expression of HR mediators, investigate the implications of decreased p65 including DNA binding and transcriptional activation, and the expression and histone acetyltransferase activity of Cbp/p300 with an aim to provide mechanistic insight into VPA-mediated alterations. The first study demonstrated that following maternal administration of VPA, mouse embryonic mRNA expression of HR mediators Rad51, Brca1 and Brca2 exhibited temporal and tissue-specific alterations. Protein expression of Rad51 was similarly altered and preceded increased cleavage of caspase-3 and PARP; indicative of apoptosis. The second study confirms previous findings of decreased total cellular p65 protein using P19 cells, but is the first to demonstrate that nuclear p65 protein is unchanged. NF-κB DNA binding was decreased following VPA exposure and maybe mediated by decreased p50 protein, which dimerizes with p65 prior to DNA binding. Transcriptional activity of NF-κB was also increased with VPA exposure which was not due to increased p65 phosphorylation at Ser276. Furthermore, the transcriptional activation capacity was unaffected by VPA exposure as combined exposure to VPA and TNFα additively increased NF-κB activity. The third study demonstrated that VPA exposure in P19 cells decreased Cbp/p300 total cellular and nuclear protein attributed primarily to ubiquitin proteasome-mediated degradation. Histone acetyltransferase (HAT) activity of p300 was decreased proportionately to nuclear protein following VPA exposure. Inhibition of Cbp/p300 HAT activity decreased p65 total cellular protein, increased caspase-3 cleavage and ROS similar to VPA exposures. Furthermore, pre-treatment with the antioxidant enzyme catalase attenuated the increase in caspase-3 cleavage, but not p65 protein. Overall, this thesis demonstrates that VPA exposure impacts the expression and activity of the transcription factor NF-κB and transcriptional co-activators/HATs Cbp/p300, which has implications for downstream VPA targets including Rad51, Brca1 and Brca2.

An Examination of Current Approaches to Integrative Indigenous and Western Knowledge System Implementation in Water Research and Management: A Case Study Encompassing the Colonized Geographies of Canada, Australia, New Zealand, and the United States

The commodification of natural resources and the pursuit of continuous growth has resulted in environmental degradation, depletion, and disparity in access to these life-sustaining resources, including water. Utility-based objectification and exploitation of water in some societies has brought us to the brink of crisis through an apathetic disregard for present and future generations. The ongoing depletion and degradation of the world’s water sources, coupled with a reliance on Western knowledge and the continued omission of Indigenous knowledge to manage our relationship with water has unduly burdened many, but particularly so for Indigenous communities. The goal of my thesis research is to call attention to and advance the value and validity of using both Indigenous and Western knowledge systems (also known as Two-Eyed Seeing) in water research and management to better care for water. To achieve this goal, I used a combined systematic and realist review method to identify and synthesize the peer-reviewed, integrative water literature, followed by semi-structured interviews with first authors of the exemplars from the included literature to identify the challenges and insights that researchers have experienced in conducting integrative water research. Findings suggest that these authors recognize that many previous attempts to integrate Indigenous knowledges have been tokenistic rather than meaningful, and that new methods for knowledge implementation are needed. Community-based participatory research methods, and the associated tenets of balancing power, fostering trust, and community ownership over the research process, emerged as a pathway towards the meaningful implementation of Indigenous and Western knowledge systems. Data also indicate that engagement and collaborative governance structures developed from a position of mutual respect are integral to the realization of a given project. The recommendations generated from these findings offer support for future Indigenous-led research and partnerships through the identification and examination of approaches that facilitate the meaningful implementation of Indigenous and Western knowledge systems in water research and management. Asking Western science questions and seeking Indigenous science solutions does not appear to be working; instead, the co-design of research projects and asking questions directed at the problem rather than the solution better lends itself to the strengths of Indigenous science.

A HARD PUSH FOR SOFT SKILLS: AN EXAMINATION OF POLICY AND RESEARCH ON NON-COGNITIVE SKILLS IN CANADIAN K-12 SCHOOLING

Non-cognitive skills have caught the attention of current education policy writers in Canada. Within the last 10 years, almost every province has produced a document including the importance of supporting non-cognitive skills in K-12 students in the classroom. Although often called different names (such as learning skills, cross curricular competencies, and 20th Century Skills) and occasionally viewed through different lenses (such as emotional intelligence skills, character skills, and work habits), what unifies non-cognitive skills within the policy documents is the claim that students that are strong in these skills are more successful in academic achievement and are more successful in post-secondary endeavors. Though the interest from policy-makers and educators is clear, there are still many questions about non-cognitive skills that have yet to be answered. These include: What skills are the most important for teacher’s to support in the classroom? What are these skills’ exact contributions to student success? How can teachers best support these skills? Are there currently reliable and valid measures of these skills? These are very important questions worth answering if Canadian teachers are expected to support non-cognitive skills in their classrooms with an already burdened workload. As well, it can begin to untangle the plethora of research that exists within the non-cognitive realm. Without a critical look at the current literature, it is impossible to ensure that these policies are effective in Canadian classrooms, and to see an alignment between research and policy. Upon analysis of Canadian curriculum, five non-cognitive skills were found to be the most prevalent among many of the provinces: Self-Regulation, Collaboration, Initiative, Responsibility and Creativity. The available research literature was then examined to determine the utility of teaching these skills in the classroom (can students improve on these skills, do these skills impact other aspects of students’ lives, and are there methods to validly and reliably assess these skills). It was found that Self-Regulation and Initiative had the strongest basis for being implemented in the classroom. On the other hand, Creativity still requires a lot more justification in terms of its impact on students’ lives and ability to assess in the classroom.

Asymmetric hydrogen flame in a heated micro-channel: role of Darrieus-Landau and thermal-diffusive instabilities

Present work examines numerically the asymmetric behavior of hydrogen/air flame in a micro-channel subjected to a non-uniform wall temperature distribution. A high resolution (with cell size of 25 μm × 25 μm) of two-dimensional transient Navier–Stokes simulation is conducted in the low-Mach number formulation using detailed chemistry evolving 9 chemical species and 21 elementary reactions. Firstly, effects of hydrodynamic and diffusive-thermal instabilities are studied by performing the computations for different Lewis numbers. Then, the effects of preferential diffusion of heat and mass transfer on the asymmetric behavior of the hydrogen flame are analyzed for different inlet velocities and equivalence ratios. Results show that for the flames in micro-channels, interactions between thermal diffusion and molecular diffusion play major role in evolution of a symmetric flame into an asymmetric one. Furthermore, the role of Darrieus–Landau instability found to be minor. It is also found that in symmetric flames, the Lewis number decreases behind the flame front. This is related to the curvature of flame which leads to the inclination of thermal and mass fluxes. The mass diffusion vectors point toward the walls and the thermal diffusion vectors point toward the centerline. Asymmetric flame is observed when the length of flame front is about 1.1–1.15 times of the channel width.

Examination of stress and strain in glass structures during pressure treatment using FEM simulation and experimental tests

Otto-von-Guericke-Universität Magdeburg, Fakultät für Maschinenbau, Dissertation, 2016

Occupied childhoods: discourses and politics of childhood and their place in Palestinian and Pan-­Arab screen content for children

This thesis explores changing discourses of childhood and the ways in which power relations intersect with socio-cultural norms to shape screen-based media for Palestinian children. Situated within the interdisciplinary study of childhood, the research is an institutional and textual analysis that includes discursive and micro-level analysis of the socio-political circumstances within which children consume media in present-day Palestine. The thesis takes a social constructionist view, arguing that ‘childhood’ is not a fixed universal concept and that discourses of childhood are produced at specific historical moments as an effect of power. The study has a three-part research agenda. The first section uses secondary literature to explore theories and philosophies relating to definitions of childhood in Arab societies. The second employs participant observation and semi-structured interviews to understand the history and politics of children’s media in the West Bank. The final part of the research activity focuses on the impact that definitions of childhood and the politics of children’s media have on broadcasting outcomes through an analysis of (a) discourses on children’s media that circulate in Palestinian society, and (b) local and pan-Arab cultural texts consumed by Palestinian children. The analysis demonstrates that complex ideological and political factors are at play, which has led to the marginalisation, politicisation and internationalisation of local production for children. Due to the lack of alternatives, local producers often rely on international funding, and are hence forced to negotiate competing definitions of childhood, which while fitting with an international agenda of normalising the Israeli occupation, conflict culturally and politically with local conceptions of childhood and hopes for the Palestinian nation. While the Palestinian community appreciates the positive potential of local production, discourses and strategies around children’s media show that Palestinian children are constructed as vulnerable, incomplete and in constant need of guidance. Pan-Arab content presents a slightly less didactic approach and in certain cases presents childhood as a dynamic space of empowerment. However, by constructing children as ‘consumercitizens’, it alienates Arab (and Palestinian) children from disadvantaged backgrounds,as the preferred audience is middle-class children living in oil-rich countries of the Gulf.

Influence of grinding operations on surface integrity and chloride induced stress corrosion cracking of stainless steels

Stainless steels were developed in the early 20th century and are used where both the mechanical properties of steels and corrosion resistance are required. There is continuous research to allow stainless steel components to be produced in a more economical way and be used in more harsh environments. A necessary component in this effort is to correlate the service performance with the production processes. The central theme of this thesis is the mechanical grinding process.  This is commonly used for producing stainless steel components, and results in varied surface properties that will strongly affect their service life. The influence of grinding parameters including abrasive grit size, machine power and grinding lubricant were studied for 304L austenitic stainless steel (Paper II) and 2304 duplex stainless steel (Paper I). Surface integrity was proved to vary significantly with different grinding parameters. Abrasive grit size was found to have the largest influence. Surface defects (deep grooves, smearing, adhesive/cold welding chips and indentations), a highly deformed surface layer up to a few microns in thickness and the generation of high level tensile residual stresses in the surface layer along the grinding direction were observed as the main types of damage when grinding stainless steels. A large degree of residual stress anisotropy is interpreted as being due to mechanical effects dominating over thermal effects. The effect of grinding on stress corrosion cracking behaviour of 304L austenitic stainless steel in a chloride environment was also investigated (Paper III). Depending on the surface conditions, the actual loading by four-point bend was found to deviate from the calculated value using the formula according to ASTM G39 by different amounts. Grinding-induced surface tensile residual stress was suggested as the main factor to cause micro-cracks initiation on the ground surfaces. Grinding along the loading direction was proved to increase the susceptibility to chloride-induced SCC, while grinding perpendicular to the loading direction improved SCC resistance. The knowledge obtained from this work can provide a reference for choosing appropriate grinding parameters when fabricating stainless steel components; and can also be used to help understanding the failure mechanism of ground stainless steel components during service.

COACHES, CLIMATES, “FIELD” GOALS, AND EFFICACY: A “DE-CONSTRUCTION” OF THE MASTERY-APPROACH TO COACHING AND EXAMINATION OF RELATIONSHIPS TO PSYCHOSOCIAL OUTCOMES IN A YOUTH FOOTBALL PLAYER DEVELOPMENT PROGRAM.

In support of the achievement goal theory (AGT), empirical research has demonstrated psychosocial benefits of the mastery-oriented learning climate. In this study, we examined the effects of perceived coaching behaviors on various indicators of psychosocial well-being (competitive anxiety, self-esteem, perceived competence, enjoyment, and future intentions for participation), as mediated by perceptions of the coach-initiated motivational climate, achievement goal orientations and perceptions of sport-specific skills efficacy. Using a pre-post test design, 1,464 boys, ages 10-15 (M = 12.84 years, SD = 1.44), who participated in a series of 12 football skills clinics were surveyed from various locations across the United States. Using structural equation modeling (SEM) path analysis and hierarchical regression analysis, the cumulative direct and indirect effects of the perceived coaching behaviors on the psychosocial variables at post-test were parsed out to determine what types of coaching behaviors are more conducive to the positive psychosocial development of youth athletes. The study demonstrated that how coaching behaviors are perceived impacts the athletes’ perceptions of the motivational climate and achievement goal orientations, as well as self-efficacy beliefs. These effects in turn affect the athletes’ self-esteem, general competence, sport-specific competence, competitive anxiety, enjoyment, and intentions to remain involved in the sport. The findings also clarify how young boys internalize and interpret coaches’ messages through modification of achievement goal orientations and sport-specific efficacy beliefs.

AN EXAMINATION OF HYDROXYL RADICAL: OUR CURRENT UNDERSTANDING OF THE OXIDATIVE CAPACITY OF THE TROPOSPHERE THROUGH EMPIRICAL, BOX, AND GLOBAL MODELING APPROACHES

Hydroxyl radical (OH) is the primary oxidant in the troposphere, initiating the removal of numerous atmospheric species including greenhouse gases, pollutants that are detrimental to human health, and ozone-depleting substances. Because of the complexity of OH chemistry, models vary widely in their OH chemistry schemes and resulting methane (CH4) lifetimes. The current state of knowledge concerning global OH abundances is often contradictory. This body of work encompasses three projects that investigate tropospheric OH from a modeling perspective, with the goal of improving the tropospheric community’s knowledge of the atmospheric lifetime of CH4. First, measurements taken during the airborne CONvective TRansport of Active Species in the Tropics (CONTRAST) field campaign are used to evaluate OH in global models. A box model constrained to measured variables is utilized to infer concentrations of OH along the flight track. Results are used to evaluate global model performance, suggest against the existence of a proposed “OH Hole” in the tropical Western Pacific, and investigate implications of high O3/low H2O filaments on chemical transport to the stratosphere. While methyl chloroform-based estimates of global mean OH suggest that models are overestimating OH, we report evidence that these models are actually underestimating OH in the tropical Western Pacific. The second project examines OH within global models to diagnose differences in CH4 lifetime. I developed an approach to quantify the roles of OH precursor field differences (O3, H2O, CO, NOx, etc.) using a neural network method. This technique enables us to approximate the change in CH4 lifetime resulting from variations in individual precursor fields. The dominant factors driving CH4 lifetime differences between models are O3, CO, and J(O3-O1D). My third project evaluates the effect of climate change on global fields of OH using an empirical model. Observations of H2O and O3 from satellite instruments are combined with a simulation of tropical expansion to derive changes in global mean OH over the past 25 years. We find that increasing H2O and increasing width of the tropics tend to increase global mean OH, countering the increasing CH4 sink and resulting in well-buffered global tropospheric OH concentrations.

Collection-Level Subject Access in Aggregations of Digital Collections: Metadata Application and Use

Problems in subject access to information organization systems have been under investigation for a long time. Focusing on item-level information discovery and access, researchers have identified a range of subject access problems, including quality and application of metadata, as well as the complexity of user knowledge required for successful subject exploration. While aggregations of digital collections built in the United States and abroad generate collection-level metadata of various levels of granularity and richness, no research has yet focused on the role of collection-level metadata in user interaction with these aggregations. This dissertation research sought to bridge this gap by answering the question “How does collection-level metadata mediate scholarly subject access to aggregated digital collections?” This goal was achieved using three research methods: • in-depth comparative content analysis of collection-level metadata in three large-scale aggregations of cultural heritage digital collections: Opening History, American Memory, and The European Library • transaction log analysis of user interactions, with Opening History, and • interview and observation data on academic historians interacting with two aggregations: Opening History and American Memory. It was found that subject-based resource discovery is significantly influenced by collection-level metadata richness. The richness includes such components as: 1) describing collection’s subject matter with mutually-complementary values in different metadata fields, and 2) a variety of collection properties/characteristics encoded in the free-text Description field, including types and genres of objects in a digital collection, as well as topical, geographic and temporal coverage are the most consistently represented collection characteristics in free-text Description fields. Analysis of user interactions with aggregations of digital collections yields a number of interesting findings. Item-level user interactions were found to occur more often than collection-level interactions. Collection browse is initiated more often than search, while subject browse (topical and geographic) is used most often. Majority of collection search queries fall within FRBR Group 3 categories: object, concept, and place. Significantly more object, concept, and corporate body searches and less individual person, event and class of persons searches were observed in collection searches than in item searches. While collection search is most often satisfied by Description and/or Subjects collection metadata fields, it would not retrieve a significant proportion of collection records without controlled-vocabulary subject metadata (Temporal Coverage, Geographic Coverage, Subjects, and Objects), and free-text metadata (the Description field). Observation data shows that collection metadata records in Opening History and American Memory aggregations are often viewed. Transaction log data show a high level of engagement with collection metadata records in Opening History, with the total page views for collections more than 4 times greater than item page views. Scholars observed viewing collection records valued descriptive information on provenance, collection size, types of objects, subjects, geographic coverage, and temporal coverage information. They also considered the structured display of collection metadata in Opening History more useful than the alternative approach taken by other aggregations, such as American Memory, which displays only the free-text Description field to the end-user. The results extend the understanding of the value of collection-level subject metadata, particularly free-text metadata, for the scholarly users of aggregations of digital collections. The analysis of the collection metadata created by three large-scale aggregations provides a better understanding of collection-level metadata application patterns and suggests best practices. This dissertation is also the first empirical research contribution to test the FRBR model as a conceptual and analytic framework for studying collection-level subject access.

An evaluation of surface micro- and mesoplastic pollution in pelagic ecosystems of the Western Mediterranean Sea

This study examines the distribution, abundance and characteristics of surface micro- and mesoplastic debris in the Western Mediterranean Sea. 41 samples were collected in 2011 (summer) and 2012 (summer). Results, firstly, revealed that micro- (<5mm) and mesoplastic debris were widely and uniformly distributed in this area with average concentrations of 130,000 parts/km(2) and 5700 parts/km(2), respectively. Importantly, a strong correlation between micro- and mesoplastic concentrations was identified. Secondly, a classification based on the shape and appearance of microplastics indicated the predominant presence of fragments (73 %) followed by thin films (14 %). Thirdly, the average mass ratio of microplastic to dry organic matter has been measured at 0.5, revealing a significant presence of microplastics in comparison to plankton. Finally, a correction method was applied in order to correct wind mixing effect on microplastics' vertical distribution. This data allows for a comprehensive view, for the first time, of the spatial distribution and nature of plastic debris in the Western Mediterranean Sea.

Running on Rooftops: a novel and critical reflection on writing from an identity of expatriation with an examination of West-meets-East encounters and attitudes depicted in literature

This thesis is in two parts: a creative work of fiction and a critical reflection on writing from an identity of expatriation. The creative work, a novel entitled Running on Rooftops, revolves around a fictitious community of expatriates living and working in China. As a new college graduate, Anne Henry, the novel’s protagonist and narrator, decides to spend a year teaching English in China. Twelve years later, though still unsure of how to make sense of the chain of events and encounters that left her with an X-shaped scar on her knee, she nevertheless tells the story, revealing how “just a year” can be anything but. The critical reflection, entitled Writing on Rooftops, explores the nature of expatriation as it relates to identity and writing, specifically in how West-meets-East encounters and attitudes are depicted in literature. In it, I examine the challenges and benefits of writing from an identity and mindset of expatriation as illustrated in the works of Western writers who themselves experienced and wrote from viewpoints of expatriation, particularly those Western writers who wrote of expatriation in China and Southeast Asia. The primary question addressed is how expatriation influences perception and how those perceptions among Western foreigners in China and Southeast Asia have been and can be reflected in literature. In the end, I argue that expatriation can be a valuable viewpoint to write from, offering new ways of seeing and describing our world, ourselves and the connections between the two.

CREATING ORGANIZATIONAL CITIZENS: A QUASI-EXPERIMENTAL AND QUALITATIVE EXAMINATION OF SUPERVSIOR- AND PEER-BASED INTERVENTIONS

Research suggests that supervisors and peers can help employees make sense of what is important or expected from them at work and, thereby, shape their behaviors. In this dissertation, I examine how employees’ organizational citizenship behaviors (OCB), such as helping and voice, are differentially affected by these two sources of influence over time. In particular, I compare the relative and joint effectiveness of two field interventions to enhance OCB: (a) a role clarification intervention in which supervisors are trained to set expectations for OCB for their employees and encourage them to engage in OCB and (b) a norm establishment intervention in which peers are trained to set expectations for each other and encourage each other to perform OCB. I utilize a mixed methods approach involving a quasi-field experiment to test for changes in OCB and qualitative data to explore the theoretical mechanisms over the course of three months in a large food processing plant. I find that role clarification interventions alone have immediate positive effects on OCB, whereas norm establishment interventions alone take a longer period of time to increase OCB. In addition, in the condition where both interventions were combined, norm establishment interventions weaken the effects of role clarification earlier on; however, at later stages in time, this pattern reverses as norm establishment enhances the effects of role clarification on OCB. Through these findings, I highlight how (a) organizations seeking quick increases in citizenship might be better off focusing on supervisors as sources of influence; (b) organizations need to persist with peer-focused interventions to see positive gains; and (c) despite initial hurdles with peer-focused interventions, over time, they can lead to the highest increases in OCB when combined with supervisor-focused interventions.

An examination of the dynamic validities of cognitive ability and personality measures with performance

Prior research shows that both cognitive ability (Schmidt & Hunter, 1998) and personality measures (Poropat, 2009; Hough & Furnham, 2003) are valid predictors of job performance. The dynamic nature of the relationships between cognitive ability and personality measures with performance over time spent on the job is less understood and thus this paper explores their relationships. Although there is much research to suggest that the predictive relationship between cognitive ability and performance decreases over years of tenure (e.g., Hulin, Henry, & Noon, 1990), other research suggests that the relationship between cognitive ability and performance will increase over time (Kolz, McFarland, & Silverman, 1988). In regard to personality, this study provides a critical test of two competing theories. The first position holds that the validity of personality degrades over time. Support for this position comes from the “ubiquitous” nature of the simplex pattern in individual differences (Humphreys, 1985). It follows that personality validities should perform like cognitive ability in this respect, and thus decline over time. In contrast to this viewpoint, the alternative position contends that the predictive relationship between personality variables and performance increases over time, with the correlation becoming larger in magnitude and more positive in direction over years of tenure. The results of this study support the latter position; personality validities predicted long term performance outcomes.