VictorJuiz/thesis huggingface dataset:
Disruption of imprinted transcription regulation of the Mash2 gene by targeted DNA insertion

Mash2 is an imprinted gene, expressed only from the maternal but not the paternal allele. When transmitted maternally, a loss-of-function mutation or a hypomorphic mutation in Mash2 results in embryonic lethality at midgestation. Recently we discovered that when a Pgk-neo-pA cassette was inserted 4.5kb downstream of Mash2 and inherited paternally, it could rescue the lethal maternal hypomorphic allele. The hypothesis was that the otherwise silent paternal Mash2 allele was expressed; therefore imprinting was relaxed. To study the site-specificity and sequence-specificity aspects of the rescue phenomenon, I developed a coherent system consisting of several different modified Mash2 alleles by targeting different insertion cassettes into two different sites. Abilities of these modified alleles to rescue the lethal phenotype were studied. Results showed that the rescue phenomenon was specific to the insertion site 4.5kb downstream of Mash2. This opens the possibility that some imprinting regulatory elements silencing the paternal Mash2 allele were interrupted.
Impact response of reinforced concrete: an experimental and numerical investigation

Impact and impulsive loading on reinforced concrete structures have been a topic of investigation for many decades. The research program described in this report implemented strength-increase relationships from various researchers into a nonlinear finite element analysis (NLFEA) program that is currently in development. Modifications to this numerical tool and the overall performance of the numerical tool itself were verified with experimental data from published literature as well as data from the pilot study experiment of this research program. The pilot study program showed support loads were close to four times higher than the static capacity and the dynamic displacement differed from the static displacement during the initial stages of impact. In addition, it has been determined that strength-increase relationships are functioning properly within the finite element code and the inertial effects of reinforced concrete beams are captured properly.
The role of proinflammatory cytokines and drug delivery strategies in the regulation of multidrug resistance

Multidrug resistance efflux transporters encoded by the MDR1 (mdr1a and mdr1b in rodents) and MRP genes play an important role during physiological and disease states. Understanding the regulation of these transporters will allow us to determine the disposition of various drugs during health and disease. Our goal was to delineate the mechanisms responsible for regulating these drug transporters during two disease states: inflammation and cancer. Firstly, we investigated the impact of pro-inflammatory cytokines and endotoxin on the transcriptional regulation of the rat mdr1b and mrp3 genes. We report for the first time that the rat mdr1b promoter contains a kruppel-like zinc finger protein 6 (KLF6) binding site which is important for its basal transcriptional activity and is required for IL-1beta and LPS-mediated induction. In the case of mrp3, novel CCAAT/enhancer binding protein beta (C/EBPbeta) and heat shock factor 4 (HSF4) binding sites were identified. Deletion of the HSF4 site enhanced TNF-alpha mediated induction of mrp3 transcriptional activity. Furthermore, LPS treatment significantly suppressed transcriptional activity in the mrp3 C/EBPbeta/HSF4 double deletion construct. These studies suggest that KLF6, C/EBPbeta, and HSF4 may be important in cytokine and endotoxin-mediated transcriptional regulation of the rat mdr1b and mrp3 genes. In ovarian cancer, it has been shown that over-expression of PGP confers drug resistance rendering chemotherapy to be ineffective. Currently, no studies have investigated the impact of localized sustained delivery of paclitaxel (PTX) on the development of drug resistance in vivo. As a result, we examined the impact of sustained versus intermittent dosing of PTX on MDR1/PGP expression in ovarian tumors. Sustained delivery was provided using a novel biocompatible PTX implant (PTXfilm). In vitro and in vivo studies with this delivery system demonstrated release of active PTX over 14 days. Compared to controls, intermittent IP dosing with the commercial PTX formulation (PTXCrEL) induced a two-fold increase in mRNA levels of MDR1 in xenografts. On the other hand, sustained IP delivery of PTX with the PTXfilm did not significantly affect MDR1 expression. Immunodetection of PGP in isolated xenografts supported the mRNA data. Overall, our findings suggest that sustained IP administration with PTXfilm attenuates development of MDR.
Link-layer design and throughput optimization to mobile hotspot in railway systems

Two general transmission schemes are proposed. In the information raining approach, all repeaters in the train vicinity blindly broadcast segments, and each vehicle antenna tunes to one of the repeaters in attempt to receive segments. In the second approach, we seek for the optimal transmission scheme, in terms of system throughput, by controlling power and matching between repeaters and antennas. Individually, power control and matching problem are both shown to be NP-complete; three matching and two power allocation heuristics are proposed. Simulations show that information raining is inferior to heuristics, particularly in interference-limited environment. With the ever-growing need for mobile high-speed access, there is an apparent demand to extend access towards mass transportation vehicles. We propose a novel networking paradigm for the railway system. The architecture realizes spatial diversity and transparency to mobile devices. A link-layer design approach of the architecture, with the use of erasure coding, is investigated.
Characterization of p53-mediated transcriptional regulation ofc-myc andklhl26

The p53 tumor suppressor protein reacts to a number of genotoxic and oncogenic signals. Upon activation, p53 can promote various cellular processes including cell cycle arrest, differentiation, and apoptosis via its ability to regulate the transcription of target genes. In this thesis, two of these genes, c-myc and klhl26, were examined for their regulation and physiological significance to the p53 pathway. c-myc is repressed in a number of mouse and human cell types in a p53-dependent manner. p53 binds to the c-myc gene and mediates transrepression through a mechanism that involves historic deacetylation. This repression is required for the efficient induction of G1 cell cycle arrest and differentiation by p53. As cell cycle regulation is believed to be a mechanism by which p53 mediates tumor suppression, the transcriptional repression of c-myc by p53 may restrain tumor development. In contrast to c-myc, klhl26 is transcriptionally-activated by p53. This is also associated with the binding of p53 to the klhl26 gene. klhl26 possesses prosurvival activity and confers cytoprotection against both p53-dependent and p53-independent apoptosis. The significance of this antiapoptotic function to the p53 response, however, is presently unclear. Taken together, c-myc and klhl26 are bona fide p53 target genes and their regulation impacts upon the ability of p53 to mediate various processes in the cell.
Bicycles traveling in the rain: A participatory, arts-informed account of Mexican farmworkers in Canada

This participatory, arts-informed study examines the experiences of workers from Mexico that live and work in the Niagara-on-the-Lake region of Ontario, Canada under the Commonwealth Caribbean and Mexican Seasonal Agricultural Workers program (SAWP). Whereas previous literature on the experiences of SAWP workers has relied on researcher-driven interviews and observations, this study looks at how workers themselves choose to tell their stories using collage and drama in a series of interactive workshops. This document begins by outlining the research problem and goes on to review existing literature on guestworker programs like the SAWP and the global context surrounding them. An overview of the participatory, workshop methodology follows. Data collected in this study is then presented and analyzed, including a number of new findings. Finally, the effectiveness of the methodology is evaluated, along with recommendations for further research and community organizing with SAWP workers.

Keywords: Migrant labor, Social
Migrant labor, Ontario
Mexicans, Social conditions
Mexicans, Ontario
Agricultural laborers, Social conditions
Agricultural laborers, Ontario
Art and society
The identification and characterization of N-terminal C-Myc oncoprotein interactions using the novel repressed transactivator (RTA) system

The Myc oncoprotein is a nuclear phosphoprotein whose function is intimately involved in controlling cellular proliferation, apoptosis and differentiation. When deregulated, Myc is a powerful transforming agent. Indeed, Myc's potent transforming potential and pervasive role in human malignancies has inspired intense research into the mechanisms that govern its cellular functions at the molecular level. The N-terminal domain (NTD) encodes two highly conserved sequences that serve as critical contact points for protein interactions that are essential to Myc function and activity. Currently, the study of Myc NTD-interacting proteins relies heavily on labour intensive biochemical strategies. However, due to expanding interest and increased urgency in the field to dissect Myc NTD function, a simpler and more efficient method to identify and characterize Myc NTD-interacting proteins is highly desirable. Therefore, I established a novel high throughput system, termed the Repressed Transactivator (RTA), specifically for the study of Myc NTD-interacting proteins. Using this new technology, I mapped the domains required for interaction with TRRAP and Bin1, two recently identified Myc NTD-interacting proteins. A new model for Myc and Bin1 interaction was proposed based on combined data from RTA and nuclear magnetic resonance (NMR) analysis. I next constructed a RTA-specific cDNA library and undertook a series of specialized screening steps to successfully identified a panel of novel Myc NTD-interacting proteins and confirmed their ability to specifically bind the Myc NTD in vitro. Notably, the identification of the GSK3α kinase domain provides proof-of-principle for the utility of the RTA system in isolating biologically relevant Myc NTD interactions, since GSK3α is strongly implicated in the phosphorylation of a conserved Myc NTD site in vivo. Future studies include the continued analysis of Myc NTD interactors by RTA and NMR to formulate structural models of Myc interaction at the molecular level. Further identification and characterization of Myc NTD-interacting proteins will be paramount to a full understanding of Myc protein function. The RTA is a high efficiency tool that will, in conjunction with biochemical and structural techniques, lead to the identification of biologically relevant Myc NTD interactions.
Do school councils empower students?: two Japanese case studies

The findings for each case study is described and analyzed separately, in both narrative and tabular form. The case studies were also cross analyzed to determine significant similarities and differences in the student empowerment function of school councils, and what were the factors of school councils that brought about student empowerment. Many of the findings are tied to the context of each school. (Abstract shortened by UMI.)The primary purpose of this study is to uncover whether school councils empower students, and if so, how they empower, by comparing two high schools in Japan. The establishment of school councils is a common agenda in the ongoing education reform in many parts of the world. However, many of the previous studies have not revealed what influence school councils have on student growth. Many reforms attempt to improve student academic performance through school councils, yet no evidence of a relationship between the two has been discovered. This study focuses on the empowerment function of school councils on students. Empowerment in this study is broadly categorized into two aspects: personal and organizational. Although students' involvement in school councils and their empowerment are the main focus, how other stakeholders such as teachers and parents are related to student empowerment through school councils is also examined. The role of principals in school councils is also investigated in terms of empowerment of stakeholders. The collection of data for this study was carried out over a period from October 2001 to February 2002. Collecting documented data was accomplished by visiting the schools, as well as the school websites. This study is based upon qualitative case study methods, which include observations of school council meetings, interviews, and documented data related to the schools. A school council meeting was observed at each school. Nineteen individuals were interviewed at each school. The list of the interviewees at each school included three school council student representatives, nine non-representative students, three teacher representatives, three parent representatives, and the school principal. Thirty-eight individuals in total were interviewed. One of the school councils in this study was instituted voluntarily, while the other was mandated.

Keywords: Student participation in administration, Japan
Citizens' advisory committees in education, Japan
Transcriptional profiling of resting and actively cycling long-term and short-term hematopoietic stem cell populations identifies genes potentially involved in the specification, maintenance, and execution of self-renewal

Lifelong hematopoiesis depends on hematopoietic stem cells (HSCs) sustaining self-renewal. RholoKit+Sca1 +Lin- murine marrow was separated into two functionally homogeneous subpopulations based on alpha2-integrin (Cd49b) surface expression. Both generate multilineage grafts but whereas CD49b - cells (LT-HSCs) sustain reconstitution>32wks, reconstitution by CD49b+ cells (ST-HSCs) fades beyond 8wks. I compared transcript-level expression in these populations while quiescent and while actively cycling. Four expression patterns emerged: (1) expression differing strongly between LT- and ST-HSCs regardless of cell cycle [Ez1, Hoxa5, Tek (CD49b- ); Ezh2, Bmi1 (CD49b+)], possibly specifying maintenance or loss of sustained self-renewal potential; (2) expression exclusively [Hoxa4, Hoxb4], and (3) expression predominantly [Hoxa9, Mll, Gata2], in cycling HSCs, suggesting participation in executing self-renewal; (4) most marked expression in cycling LT-HSCs [Eng, Phc1, Tie1], possibly responsible for maintaining HSC identity through division. Genes in these groups include homeobox, polycomb and trithorax family members, supporting their involvement in specifying, maintaining and executing self-renewal.
Women, sodomy and sexual abuse in late-Renaissance Lucca

In the mid-sixteenth century, the oligarchic government of the small city-state republic of Lucca responded to concerns over moral crime by setting up or re-vamping various magistratures to control the behaviour of its citizens. One of these magistratures was the Offizio sopra l'Onestà, the Office of Decency, which maintained the authority to try and condemn those suspected of participating in the “nefarious vice of sodomy.” Although this court was mainly occupied with cases involving male same-sex relations, a surprising number of women appeared before the court. The records of the trials show women appeared as victims of abuse, culprits of sodomy for erotic purposes, mothers of pedophile victims, and key witnesses. As sodomy was anathema to the authorities, women seeking redress found that their complaints were taken seriously by the Onestà. Given the chance to tell their story in court they appear resourceful, confident, feisty and sometimes manipulating. The oligarchy's fear that the young men of the city were turning to sodomy meant that the government recruited prostitutes as “soldiers in the war on sodomy” and gave them full citizenship and protection. This protection, however, did not extend to toleration of prostitutes offering their clients erotic sodomy. The court records reveal a wealth of detail about those who appeared before them. Cases were seldom straightforward. Sometimes the guilty were innocent and the innocent guilty, as can be seen in cases involving some very young sexual offenders. Spontaneous information volunteered in the testimony and the interaction between the people and the courts provide rare glimpses into the lives of ordinary men, women and children in sixteenth- and seventeenth-century Lucca. This information contributes a new facet to the understanding of family dynamics in premodern society as well as both elite and popular attitudes to sexuality and gender relations.

Keywords: Sex crimes, History
Sodomy, History
Women
Applying a formative ecological framework to simulator design challenges

Human-in-the-loop interactive simulators are widely recognized as a cost-effective and safe way to train workers in challenging work situations, and to more tractably research human performance. Designing cheaper, lower fidelity and more tractable computer-based simulators has been proposed as a way to widen simulator adoption and extend training and human performance research benefits. There is currently no systematic method to design simplified simulations while retaining psychological fidelity. Design decisions are typically based on common tasks and simulator designers' intuition and expertise. This is difficult to replicate, complicates comparisons between simulators, and presents problems for scientific defensibility of research. This thesis demonstrates how Cognitive Work Analysis (CWA)'s phases can be applied to support designers both in systematic, defensible design of simplified simulators, and also in ongoing scenario design and development. A subset of CWA design methods are demonstrated in a petrochemical domain case study.
From TT to T.O.: second generation identities in the Caribbean diaspora

The diasporic and transnational construction of identities by migrants who make "home" in a new land has increasingly been the focus of interest and study by academics. However, the construction of identities by the offspring of these migrants---the second generation---has often been overlooked in the scholarship. Being born and/or raised in the diaspora, the experiences of identity among second generation experiences are very diverse, sometimes markedly different from the first generation's, and at other times echoing the first generation's sentiments of a longing for "home", nostalgia, and alienation. In this study, I examine identities and identity-making among second generation people who are of Trinidadian descent living in Toronto. I combine in-depth interviews with key individuals along with textual analysis of "sites" in which identity is performed and expressed: Caribana, soca fetes, websites, literature, as well as the consumption of music, food and clothes. My objective is to address the complexities of identity formation and negotiation in a multicultural yet white-dominant society such as Toronto. The study explores why and how certain individuals may choose to maintain and cultivate a distinct "Trinidadian" identity in a locale far-removed from Trinidad, while attending to the range of meanings they attach to being "Trini". I argue that new forms of creolization that are occurring among second generation people in the diaspora, a continuation of a tradition fostered in the Caribbean experiences of colonialism, slavery, indentureship and newer postcolonial trans-nationalisms.

Keywords: Group identity, Ontario
Identity (Psychology), Ontario
Children of immigrants, Ontario
Trinidadians, Canada
Trinidadians, Ethnic identity
Immigrants, Cultural assimilation
Immigrants, Ontario
Determinants of self-perceived managerial effectiveness in the Canarian Health Service

Theoretical and practical implications of the findings were explored. Theoretically, this study supported and extended the development of a model of managerial effectiveness. For the practitioner, the study proposed that an understanding of the factors that influence managerial effectiveness could have dramatic practical implications for management and organizations. Health care managers are key players in achieving organizational goals. How well managers manage determines, to a large extent, how effectively personnel, work units and organizations will perform. Research asserts that managers' effective performance in the workplace results from three factors: managerial competencies, motivation and work environment. This study investigated the determinants of self-perceived managerial effectiveness in managers of the Canarian Health Service (CHS) by examining the mediating effect of psychological empowerment on the relationship between two predictors, managerial competencies and social-structural factors of the work unit environment, and the criterion of managerial effectiveness. A sample of 590 managers participated in a survey conducted in hospitals, primary care centres and central services from the CHS. Factor analysis and Cronbach alpha reliabilities were conducted on all scales revealing adequate psychometric properties. The managerial competency scale showed two factors, labelled "managing people and change" and "managing activities and results". Seven social-structural factors of the work unit environment were identified, namely "role ambiguity", "sociopolitical support", "access to information", "access to resources", "participative work unit climate", "physical structure" and "pressure from stakeholders". The psychological empowerment and the managerial effectiveness scales each yielded a single factor. A series of multiple regression analyses was conducted to test the mediational model. The "managing people and change" competency was the strongest predictor of managerial effectiveness, followed by empowerment and social-structural factors of the work unit environment. Managers' perceptions of empowerment mediated the relationship between managerial competencies and effectiveness, and between social-structural factors and effectiveness. Empowerment partially mediated the relationship between the "managing people and change" competency and effectiveness. In addition, empowerment mediated the relationship between social-structural factors and effectiveness. Specifically, empowerment only partially mediated the relationship between access to information and managerial effectiveness. It completely mediated the relationship between both sociopolitical support and participative unit climate and managerial effectiveness.
Spatially explicit distribution models for predicting species occurrences

Species distribution modeling is an essential tool for conservation planning. These models utilize the species-environment relationship to formulate a spatial depiction of its distribution pattern. Often these models are developed aspatially. That is they do not consider the spatial context of the species occurrence. Thereby, ignoring spatial components that contribute to the species distribution pattern such as species endogenous processes and the species dependence on its spatially structured physical environment. Species distribution modeling methods have been developed that explicitly account for these spatial processes. Spatially explicit modeling methods are reviewed and the importance of carefully considering interactions between the ecological, data and statistical components of the model is highlighted. A comparative evaluation of five spatially explicit methods and an aspatial method was performed to investigate their relative abilities to accurately predict three songbird occurrences. Results were mixed and dependent on characteristics of the species ecology and model data.