UNDERSTANDING THE RELATIONSHIP BETWEEN ONCOLYTIC AD5 DELETED E1b55KDA LYTIC INFECTION AND P53 IN MAMMALIAN CELLS

Adenoviruses are the most commonly used in the development of oncolytic therapy. Oncolytic adenoviruses are genetically modified to selectivity replicate in and kill tumor cells. The p53 molecule is a tumor suppressor protein that responds to viral infection through the activation of apoptosis, which is inhibited by adenovirus E1B55kDa protein leading to progressive viral lytic cycle. The non-specificity of replication has limited the use of wild type adenovirus in cancer therapy. This issue was resolved by using an E1b deleted Ad that can only replicate in cells with a deficiency in the p53 protein, a common feature of most cancer cells. Although demonstrating a moderate success rate, E1b55kDa deleted Ad has not been approved as a standard therapy for all cancer types. Several studies have revealed that E1b deleted Ad replication was independent of p53 status in the cell, as the virus replicated better in some p53 deficient cancers more than others. However, this mechanism has not been investigated deeply. Therefore, the objective of this study is to understand the relationship between p53 status, levels and functional activity, and oncolytic Ad5dlE1b55kDa replication efficiency. Firstly, five transient p53 expression vectors that contain different regulatory elements were engineered and then evaluated in H1299, HEK293 and HeLa cell lines. Data indicated that vector that contains the MARs and HPRE regulatory elements achieved the highest stability of p53 expression. Secondly, we used these vectors to examine the effect of various p53 expression levels on the replication efficiency of oncolytic Ad5dlE1b55kDa. We found that the level of p53 in the cell had an insignificant effect on the oncolytic viruses’ replication. However, the functional activity of p53 had a significant effect on its replication, as Ad5dlE1b55kDa was shown to have selective activity in H1299 cells (p53-null). In contrast, a decrease in viral replication was found in HeLa cells (p53-positive). Finally, the effect of p53’s functional activity on the replication efficiency of oncolytic Ad5dlE1b55kDa was examined. Viral growth was evaluated in H1299 cells expressing number of p53 mutants. P53-R175H mutant successfully rescued viral growth by allowing the virus to exert its mechanism of selectivity. The mechanism entailed deregulating the expression of specific genes, cell cycle and apoptosis, in the p53 pathway to promote its production leading to efficient oncolytic effect. These results confirmed that oncolytic Ad5dlE1b55kDa sensitivity is mutation-type specific. Therefore, before it is applied clinically as cancer therapy for p53 deficient tumors, the type of p53 mutation must be determined for efficient antitumor effect.

A Case Study of Disengaged Students' Experiences with Teaching Games for Understanding

The purpose of this research study was to determine if the instructional model, Teaching Games for Understanding (TGfU), would allow for the successful teaching of sport to disengaged female students in Physical Education (PE) classes. An instrumental case study research design was used to determine grade nine female students’ experiences with TGfU, the factors of TGfU that facilitated their engagement, and the ways in which these students resisted engaging in TGfU. Data was collected through a pre and post TGfU unit focus group, participant observation, in-depth interviews, and researcher reflections. Results showed that TGfU caused an increase in the participants’ engagement in PE physically, mentally, and socially/emotionally. Future researchers could structure their entire study holistically and should examine TGfU’s impact on student engagement over the course of an entire semester. Subsequent studies should moreover examine the presence of disengagement within physically skilled students in PE.

University Faculty Members’ Understanding of Their Role: Identity, Power, and Silence

This qualitative study was conducted to explore tenured faculty members’ understandings of their roles as professors. Tenure is an institutional means to enact academic freedom, which allows tenured faculty members to investigate topics of their choosing free from external influence. Academic freedom also enables faculty members to be public intellectuals who shape and critique social policies and make knowledge assertions. In effect, the faculty members are institutionally protected to speak truth to power. Purposeful sampling of 9 participants from 2 universities yielded 3 major themes: professorial identity (shaped by such factors as career stage, university culture, and faculty affiliation), professorial power (powers that participants experienced as well as the ways in which they exercised power), and professorial silencing (as a response to fiscal realities coupled with numerous governance issues). While participants were cognizant of the powers that affected their freedoms, they were less aware of the ways in which their position afforded them powers. Subtle but more potent forms of power were at play for tenured professors, but the participants saw themselves as having to work within institutional and financial constraints that limited their freedom to speak out on controversial issues. Faculty members were, thus, silenced and at times chose to self-silence. The context of the present-day university, governance models, and the financial issues affecting universities and departments worked in concert to silence this critical voice in society.

Motivation and Reading Achievement: Understanding the Needs and Motivation Processes of Adult Literacy Learners

Adult struggling readers are understudied and most evidence-based remedial approaches target youth. This thesis examined relationships among motivation constructs across typical and struggling adult readers. Age was also investigated as a moderator in these relationships. Participants included 198 adults in adult basic education and 138 undergraduate students. Examining the influence of self-efficacy on reading achievement, moderation analyses indicated there were stronger relationships for typical readers. Furthermore, stronger relationships were found for younger participants when moderated by age. Additional regression analyses identified positive relationships between two measures of intrinsic motivation and reading value. This relationship was replicated for avoidance and value. Though age was not uniformly sampled across ability grouping, age did not account for these effects. Despite difficulties with reading, adults still exhibited motivation to engage with texts with equal to greater levels of reading value. Value and intrinsic motivation may have unique developmental courses associated with longstanding reading challenges.

Brand Associations of Minor Hockey Tournaments: Understanding the Rep Hockey Parents' Perspective

Tournaments and other hockey-related activities have been calculated to be a significant driver of tourist dollars for many regions across Canada. The competition to attract teams to participate in tournaments, which benefit the tournament organizers and the communities in which they reside, is significant. Consequently, the purpose of the study was to assess the brand associations that representative (rep) minor hockey parents from Ontario’s Greater Golden Horseshoe Region perceive as relevant when considering ideal tournaments for their child to participate in. Brand associations have been classified as the attributes, benefits, or attitudes one uses to develop a perception of a product or service. To investigate the current study, 30 interviews were conducted using a laddering interview technique. Findings indicate that there are seven attributes and nine benefits that impact a tournament’s brand association including: competition, tournament operations, accommodations, bonding, fun, parity, and time management. The interrelationship between the identified attributes and benefits is discussed while recommendations and directions for future research are presented.

Understanding the Intersection of Reformed Faith and Dutch Immigrant Culture in Ontario Independent Christian Schools: Principals’ Experiences and Perspectives

In the aftermath of World War II, a wave of Dutch Reformed immigrants arrived in Ontario, many of whom joined the Christian Reformed Church. Following familiar cultural patterns, history, and their Reformed Christian faith, these immigrants settled in Ontario with remarkable institutional completeness (Breton, 1964). They quickly established independent, parent-operated Christian schools across Ontario. The primary purpose of the schools was to educate children through a comprehensive biblically based school program, yet this religious purpose often intersected with a Dutch immigrant ethnic culture. Van Dijk (2001) states that “the schools were the most important organization in maintaining the religious and ethnic identity of Calvinists” (p. 66). In this qualitative study I explore the intersection of Reformed faith and Dutch Canadian immigrant ethnic culture in Christian schools through the experiential and professional lens of eight retired principals. Employing a theoretical framework informed by Berger’s (1967) Sacred Canopy, I suggest that the intersection of faith and culture was experienced in the schools and was embodied by the schools themselves. Findings point to this intersection being located in the participants’ experience of (a) Dutchness, (b) the struggle for Christian education, (c) the ties that bound the school community together, and (d) the cloud of witnesses that founded and continues to support and encourage the Christian school community. The study offers insight into a Dutch Reformed immigrant group’s experience carving out a niche for themselves on the educational landscape in Ontario. This study also offers suggestions on how Christian schools can broaden their canopy and become more ethnically and denominationally diverse in the future.

Mackenzie’s Toronto Weekly Message, July 16, 1859

Mackenzie’s Toronto Weekly Message, July 16, 1859.

Mackenzie’s Toronto Weekly Message, July 30, 1859

Mackenzie’s Toronto Weekly Message, July 30, 1859.

Message from the President of the United States, communicating, in compliance with a resolutión of the Senate, the proceedings of thetwo courts of inquiry in the case of Major General Pillow.

UANL

The treaty between the United States and Mexico, the proceedings of the Senate therson, and message of the President and documents communicated therewith : the messages, with correspondence between the executive departament, General Scott and Mr. Trist, and other papers and proceedings of the on Senate in relation thereto, from wich the injuction of secresy has been removed...

UANL

Message from the President of the United State

UANL

Explaining the Great Divergence: Medium and Message on the Eurasian Land Mass, 1700-1850

Between 1700 and 1850, per-capita income doubled in Europe while falling in the rest of Eurasia. Neither geography nor economic institutions can explain this sudden divergence. Here the consequences of differences in communications technology are examined. For the first time, there appeared in Europe a combination of a standardized medium (national vernaculars with a phonetic alphabet) and a non-standardized message (competing religious, political and scientific ideas). The result was an unprecedented fall in the cost of combining ideas and burst of productivity-raising innovation. Elsewhere, decreasing standardization of the medium and increasing standardization of the message blocked innovation.

The Supreme Court’s Understanding of Federalism: Efficiency at the Expense of Diversity

This paper is an examination of the Supreme Court of Canada's interpretation of federalism since constitutional repatriation in 1982. It argues that the lure of centralist efficiency is overpowering a fundamentally important part of our federal order: regionalism. The author contends that changes made by the Court to certain fundamental concepts of Canadian constitutional law now provide Parliament with greater latitude than before in the exercise of its legislative powers. According to the author, these changes are disturbing because they are structured so as to preclude consideration of the legitimate concerns of regional polities. Furthermore, he argues that the Court has reinforced the central government's power to regulate the economy, including intraprovincial matters affecting trade, by resorting to highly functional tests that emphasize economic efficiency over other criteria. This, he claims, makes it more difficult to invoke legitimate regional interests that would lead to duplication, overlapping and even, in the eyes of some, inefficiency. The author the focuses on the Court's treatment of environmental protection in an attempt to show the tension between the Court's desire to use a functional approach and the need to recognize regional interests. Finally, through an examination of recent case law, he attemps to demonstrate that the Court's dominant perspective remains functional despite its endorsement of a more community-oriented undestanding of federalism in Secession Reference. If the Court chooses to proceed in this manner, it will alienate regional polities and may encourage them to choose more radical means of asserting their differences. Further, the author argues that strict adherence to the functional effectiveness approach will undermine the very values that federalism is meant to promote.

Report of the Secretary of War: being part of the message and documents communicated to two houses of Congress at the beginning of the secondd session of the forty-sixth Congress.

UANL