VictorJuiz/thesis huggingface dataset:
Exploring DNA Damage Induced Foci and their Role in Coordinating the DNA Damage Response
Keywords: DNA damage
signaling
foci
DNA repair
checkpoint
recovery

DNA damage represents a major challenge to the faithful replication and transmission of genetic information from one generation to the next. Cells utilize a highly integrated network of pathways to detect and accurately repair DNA damage. Mutations arise when DNA damage persists undetected, unrepaired, or repaired improperly. Mutations are a driving force of carcinogenesis and therefore many of the DNA damage surveillance and repair mechanisms guard against the transformation of normal cells into cancer cells. Central to the detection and repair of DNA damage is the relocalization of DNA damage surveillance proteins to DNA damage where they assemble into subnuclear foci and are capable to producing a signal that the cell interprets to induce cellular modifications such as cycle arrest and DNA repair which are important DNA damage tolerance. In this work, I describe my quest to understand the mechanisms underlying the assembly, maintenance, and disassembly of these DNA damage-induced foci and how they affect DNA damage signaling in Saccharomyces cerevisiae. First, I describe phenotypic characterization of a novel mutation that impairs assembly of the 9-1-1 checkpoint clamp complex into foci. Second, I describe my work to further understand the roles of the histone phosphatase Pph3 and phosphorylated histone H2A in modulating DNA damage signaling. Third, I include my work to uncover the possible mechanism by which the helicase Srs2 works to enable termination of DNA damage signaling. In summary, this thesis documents my efforts to understand the cellular and molecular nature of DNA damage signaling and how signaling is turned off in coordination with DNA damage repair.
In Situ Observation of Plastic Foaming under Static Condition, Extensional Flow and Shear Flow
Keywords: Plastic Foaming
Visualization
Extensional Stress
Shear Stress
Cell Nucleation

Traditional blowing agents (e.g., hydrochlorofluorocarbons) in plastic foaming processes has been phasing out due to environmental regulations. Plastic foaming industry is forced to employ greener alternatives (e.g., carbon dioxide, nitrogen), but their foaming processes are technologically challenging. Moreover, to improve the competitiveness of the foaming industry, it is imperative to develop a new generation of value-added plastic foams with cell structures that can be tailored to different applications. In this context, the objective of this thesis is to achieve a thorough understanding on cell nucleation and growth phenomena that determine cell structures in plastic foaming processes. The core research strategy is to develop innovative visualization systems to capture and study these phenomena. A system with accurate heating and cooling control has been developed to observe and study crystallization-induced foaming behaviors of polymers under static conditions. The cell nucleation and initial growth behavior of polymers blown with different blowing agents (nitrogen, argon and helium, and carbon dioxide-nitrogen mixtures) have also been investigated in great detail. Furthermore, two innovative systems have been developed to simulate the dynamic conditions in industrial foaming processes: one system captures a foaming process under an easily adjustable and uniform extensional strain in a high temperature and pressure environment, while the other achieves the same target, but with shear strain. Using these systems, the extensional and shear effects on bubble nucleation and initial growth processes has been investigated independently in an isolated manner, which has never been achieved previously. The effectiveness of cell nucleating agents has also been evaluated under dynamic conditions, which have led to the identification of new foaming mechanisms based on polymer-chain alignment and generation of microvoids under stress. Knowledge generated from these researches and the wide range of future studies made possible by the visualization systems will be valuable to the development of innovative plastic foaming technologies and foams.
The Recorded Voice and the Mediated Body in Contemporary Canadian Electroacoustic Music
Keywords: music
Canada
electroacoustic
analysis
gender
sexuality
technology
ageing
voice
body
aesthetic

Henry Wadsworth Longfellow once declared: “the human voice is the organ of the soul.” As a powerful signifier, with deep links to human presence, the voice can indicate psychological, emotional and physical states. In the works of contemporary Canadian electroacoustic composers Christian Calon, Robert Normandeau, Tanya Tagaq, Barry Truax, and Hildegard Westerkamp, the mutability of the recorded voice initiates an aesthetic process that constructs this human presence and expresses the composer’s own preoccupation with the body, namely the ageing, social, and erotic (homosexual and heterosexual) body. Through an application of research on electroacoustics, studio technology, gender, sexuality, linguistics, epistemology, and human physiology, I examine how specific works incorporate and modify the voice, and thus construct or conceal its physical origin (i.e., the body); I consider how composers variously highlight, re-construct, or even disentangle the expressive and communicative associations between the voice and the body. Rather than summarize numerous electroacoustic works, this dissertation focuses on the aesthetic, technological, and expressive elements of a small number of contemporary Canadian electroacoustic works. I first examine Normandeau’s Onomatopoeias cycle as an artistic exploration of the ageing process that considers both emotional and physical aspects specific to certain developmental stages, including childhood, adolescence, and old age, all with a lens of ironic nostalgia. Next I explore social and sensuous relationships, the unseen interactions between bodies as heard through the recorded voices in Barry Truax’s homoerotic Song of Songs (1992) and Tanya Tagaq’s two studio albums, Sinaa (2005) and Auk/Blood (2008). Finally, I consider how the voice is employed as a vehicle for storytelling and constructing identity in Christian Calon’s Minuit (1989) and Hildegard Westerkamp’s Für Dich – For You (2005) and MotherVoiceTalk (2008). The works are varied, but from the young girl in Éclats de voix (the first work in Normandeau’s Onomatopoeias cycle [1991-2009]) to the grown child and her elderly mother in MotherVoiceTalk, they find a link in human experience.
Development and Testing of an Instrument to Measure the Quality of Children’s End-of-life Care from the Parents’ Perspective
Keywords: instrument development
pediatrics
end-of-life
quality of care
psychometric testing
health services research
parents
outcomes

Background: The Senate of Canada asserts that quality end-of-life care is the right of every Canadian. Yet, little is known about the quality of end-of-life care for dying children and their families. Purpose: The study purpose was to develop and test an instrument to measure parents’ perspectives on the quality of care provided to families before, at the time of, and following the death of a child. Methods: In study Phase I, key components of quality pediatric end-of-life care were synthesized through a systematic review of research literature then validated and extended through focus groups with bereaved parents. In Phase II, instrument items were developed to assess structures, processes, and outcomes important to quality end-of-life care, then tested for content and face validity by health professionals and bereaved parents. In Phase III, the instrument was administered to bereaved mothers from across Canada and psychometric testing conducted. Results: Instrument items were developed based on review of 67 manuscripts and 3 focus groups with 10 parents. The Content Validity Index for the instrument was 0.84 as assessed by 7 health professionals. The instrument was assessed by 6 bereaved parents for face and content validity as well as their cognitive understanding of the items. In the final phase, 128 mothers completed the instrument and 31 of those completed it twice. Initial evidence for test-retest reliability, internal consistency, and construct validity was demonstrated for 7 subscales: Connect with Families, Involve Parents, Share Information with Parents, Share Information among Health Professionals, Support Parents, Provide Care at Death, and Provide Bereavement Follow-up. Additional items with demonstrated content validity only were grouped into three domains: Support the Child, Support Siblings, and Structures of Care. Implications: This study is a significant step forward in comprehensive measurement of the quality of children’s end-of-life care. The instrument provides a mechanism for feedback to health professionals, health systems, and policy makers to improve care provided to families facing the death of a child.
Global Changes in Activity and Interactivity of Brain Regions Supporting Contextual Fear Memory over Time in Mice
Keywords: memory
network

While the hippocampus may play an essential role in the expression of memories soon after training, over time these memories are thought to become increasingly dependent on coordinated activity in a broad network of cortical and subcortical brain regions. However, the distributed nature of this representation has made it challenging to define the neural elements of the memory trace, and lesion and electrophysiological approaches provide only a narrow window into what is appreciated to be a much more global network. Here global mapping approaches are used to identify networks of brain regions that are activated and co-activated following recall of recent and remote contextual fear memory in mice. Analysis of Fos expression across 84 brain regions allowed for the description of brain-wide activity and interactivity of brain regions associated with memory expression. Activity analysis revealed that remote memory engages a broad collection of cortical and subcortical regions in comparison to recent memory expression. Interactivity analyses revealed that functional connectivity associated with fear memories depends on memory age and is altered in mutant mice that exhibit premature forgetting. In-depth functional connectivity analysis of remote long-term fear memory indicates that memory recall engages a network that has a distinct thalamic-hippocampal-cortical signature. This network is concurrently integrated and segregated and therefore has small-world properties as well as a resilient core of highly inter-connected regions. Centrality measures identify a collection of regions that may play a critical role in the function of the network including expected regions such as the anterior cingulate cortex and prelimbic cortex as well as novel regions including the reuniens thalamic nucleus. Post conditioning lesions of the reuniens lead to mild deficits in contextual fear memory expression providing support for the idea that identified hub regions may play a critical role in the function of the network. These results identify and describe functional activity and interactivity of brain regions underlying recent and remote fear memory expression and provide strong evidence for reorganization and distribution of the functional organization of memories over time.
Low-sulfide PGE-Cu-Ni Mineralization from Five Prospects within the Footwall of the Sudbury Igneous Complex, Ontario, Canada
Keywords: Low-sulfide
Sudbury
Platinum-group element
Platinum-group mineral

North Range low-sulfide mineralization is dominantly hosted by Sudbury breccia, with amphibole-plagioclase equilibrium metamorphic temperatures of 440 to 533 ± 75oC, produced by the SICs thermal aureole. Mineralization led to increases in the bulk halogen content of the host Sudbury breccia and the formation of Ni-enriched ferromagnesian silicates. South Range low-sulfide mineralization is typically hosted by metabasalts of the Huronian Supergroup. Garnet-biotite-plagioclase-quartz geothermobarometry produced equilibrium metamorphic conditions of 513 to 645 ± 50oC and 2.0 to 7.7 ± 1.0 kbar, probably corresponding to a late-Penokean overprint of peak Blezardian/Penokean metamorphism. Silicates associated with South Range mineralization are compositionally similar to the host rock equivalents and no alteration selvage is commonly observed due to subsequent recrystallization. Platinum-group minerals (PGM) from the North Range comprise platinum and palladium tellurides and bismuth-tellurides, with Sb-bearing palladium bismuth-tellurides and sperrylite from the South Range. Kotulskite-sobolevskite from the North Range shows a previously unreported Ag-Pd substitution, with michenerite from irregular veinlet style mineralization showing the substitution of Se and Sb for Bi. Two unknown PGMs were identified from the South Range, along with kotulskite-sobolevskite-sudburyite crystals displaying extensive Te-Bi-Sb solid-solution not noted before at Sudbury. A new Se-bearing variant of pilsenite was identified at McKim. Polyphase aggregates from both Ranges indicate that Bi-Te melts may have been widespread at some stage postdating the emplacement of the main magmatic sulfides. Normalized plots for low-sulfide mineralization show enrichments in the precious and semimetals relative to contact and sharp-walled vein mineralization. This enrichment has resulted in elevated concentrations of Ag and Se in chalcopyrite and Pd+Ag and Se in pentlandite from the North Range. The mass balance for North Range samples found that a significant fraction of Ag and Se occurs in sulfides with all other elements preferring discrete phases. A substantial fraction of Pd is hosted by pentlandite on the South Range, with gersdorffite also a major host despite its low abundance. The enrichments observed reflect the formation of low-sulfide mineralization from a fractionated sulfide liquid and hydrothermal fluids that have interacted with a fractionated sulfide source, and suggest that the precious and semimetals behave incompatibly with crystallizing sulfide.
A Study of Organizational Culture in Ontario Colleges with High Student Satisfaction
Keywords: organizational culture
performance effectiveness
change management
leadership
management skills

Academic institutions face countless pressures within a context of ongoing globalization, societal change, and increased accountability measures. The use of organizational culture assessment can assist organizations to understand their current culture and, consequently, to inform strategies for change management. This study examined the perceptions held by administrators at four Ontario colleges with above average Student Satisfaction (KPI) about their institution’s current and preferred organizational culture and their own management competencies. A descriptive research method was employed using a modified version of Cameron and Quinn’s (2006) Organizational Culture Assessment Instrument (OCAI) and Management Skills Assessment Instrument (MSAI). Different culture types were found in the current state at the four colleges. Two colleges exhibited a dominant Market or ‘competing’ type culture, one a dominant Hierarchy or ‘controlling’ type culture and, one a dominant Clan or ‘collaborative’ type culture. Evidence of strength and congruence of organizational culture was found at some of the four colleges. Results from all colleges combined exhibited meaningful influence of both Clan and Hierarchy type cultures. Dominant culture type differed by gender and number of years’ experience in the job. Administrators at all four of the colleges reported use of Clan type management skills (i.e., Managing Teams, Interpersonal Relations, and Development of Others) most frequently. This was followed by Adhocracy, Hierarchy and Market type skills. Three colleges ranked Managing Competitiveness as their lowest. OCAI dominant culture type differed from MSAI dominance at three of the colleges and one exhibited the same Clan type OCAI and MSAI. Desire in the preferred state to increase collaboration was evident with dominant Clan type culture and focus on flexibility. Focus was split equally with two internal and two external, and culture strength was found at two colleges. Consistency exists between preferred dominant culture type and management skills of administrators, suggesting administrators’ skills at each of the colleges are aligned with where they desire their college’s organizational culture to be heading. This study identifies implications for leadership of college culture linked to effective performance. The results build on existing evidence that dominant type, strength and/or congruence of culture is linked with performance effectiveness.
Discriminating Fracture Status in Men and Women with Stage 3-5 Chronic Kidney Disease: Cytokines, Neuromuscular Function and Daily Activity Levels
Keywords: chronic kidney disease
fractures
osteoprotegerin
neuromuscular function
daily activity

Bone disease and fractures are common in men and women with chronic kidney disease (CKD). The etiology of fractures in CKD is multi-factorial; identifying risk factors for fracture is important in CKD, so that patients who are at high risk can be treated before they fracture. The majority of studies have focused on risk factors associated with fracture in patients with stage 5 CKD on dialysis–there is a need for studies in pre-dialysis CKD. Three novel, non-radiological factors were assessed in 211 men and women with stage 3-5 CKD: cytokines osteoprotegerin (OPG) and receptor activator of nuclear factor kappa beta ligand (RANKL); tests of neuromuscular function including the timed up and go (TUG), 6 minute walk (6MW), and grip strength; and daily activity levels by accelerometry. Fractures were defined as self-reported low-trauma fractures since the age of 40 and/or prevalent vertebral fractures identified by morphometry. Logistic regression and receiver operating characteristic curves (ROC) were performed using STATA version 11.0. Those with fractures had elevated OPG compared to those without fractures (9.37±4.23 vs. 8.13±3.04 pmol/L, p=0.03), however, after adjusting for age OPG did not differ by fracture status. After adjusting for age, weight, and sex, impairments in both the TUG and 6MW tests were associated with fractures (TUG odds ratio (OR): 1.68, 95% confidence interval (CI): 1.40-2.02; 6MW OR: 0.53, 95% CI: 0.52-0.54). The diagnostic tests characteristics of the TUG and 6MW tests were excellent; both could discriminate fracture status (TUG AUROC: 0.90, 95% CI: 0.84-0.95; 6MW AUROC: 0.87, 95% CI: 0.84-0.95). Overall, subjects were primarily sedentary. After adjusting for stage of CKD, increased sedentary activity and decreased light intensity activity could discriminate fracture status (sedentary AUROC: 0.72, 95% CI: 0.56 to 0.87; light activity AUROC: 0.71, 95% CI: 0.55 to 0.87). In conclusion, non-radiological, novel factors including the TUG, the 6MW, and daily activity, but not OPG or RANKL were able to discriminate fracture status in men and women with stage 3-5 CKD.
Determining the Effective Parameters of Metamaterials
Keywords: Metamaterials
Negative index
Homogenization
Effective medium

In this dissertation the proper determination and allowable signs of the effective parameters of metamaterial structures will be examined. First, a method that was commonly used to determine the presence of a negative index of refraction will be discussed. It will be shown that this method, which relies on the appearance of transmission peaks in the region where the real parts of the effective permittivity and permeability are expected to be negative, does not provide sufficient evidence that a negative index exists. Two alternate methods will then be presented that can be used to properly determine the sign of the index. Then, the form of the index in media that exhibit backward wave propagation will be examined from a purely three dimensional wave propagation point of view. It will be shown that in an isotropic medium backward wave propagation requires that the index be negative and in an anisotropic medium it requires that the index be negative along at least one of the three principal axes. In short, the necessary and sufficient condition for the negative index of refraction is the existence of the backward wave. Next, a technique commonly used to retrieve the effective parameters in metamaterials from transmission and reflection data will be considered. It will be shown that this retrieval technique can lead to unphysical claims that the imaginary parts of the effective permittivity or permeability can be negative even though the medium remains passive. By comparing the effective parameters obtained analytically and from the retrieval technique it will be shown that these unphysical claims are the result of error in the numerical simulations. The concepts of causality and analyticity will also be discussed by considering the Lorentzian model and it will be shown that this model does not allow the imaginary parts of the permittivity or permeability to be negative in the metamaterials consisting of split ring resonators and split wires.
Functional Interactions between Chromatin-associated Proteins and Epstein-Barr virus Nuclear Antigen 1 (EBNA1)
Keywords: chromatin-associated proteins
EBNA1
interaction

Epstein-Barr virus (EBV) is a gammaherpesvirus that persistently infects more than 90% of the human population and its latent infection is associated with several malignancies. EBNA1 is the only viral protein required for the persistence of EBV episomes through its contributions to the replication, mitotic segregation of EBV episomes, and transcriptional activation of viral latency genes. These functions require EBNA1 binding to the DNA elements within the EBV genome that are important for transcription and replication, and interactions of EBNA1 with cellular factors. The aim of this thesis is to characterize the functional significance of the interactions between EBNA1 and chromatin-associated proteins NAP1, TAF-I, and Brd4, particularly in EBNA1-mediated transcription and DNA replication. Here I investigated the interactions of EBNA1 with NAP1 or TAF-I that were previously discovered in our laboratory by proteomic methods. I found that EBNA1 binds directly to NAP1 and to the β isoform of TAF-I, resulting in increased solubility of EBNA1 in vitro. Brd4 was also found to bind to EBNA1 and this interaction is mediated by an EBNA1 sequence essential for transactivation. Brd4, NAP1 and TAF-I all localize with EBNA1 to the transcriptional element and alteration of their levels inhibits transcriptional activation, suggesting that these proteins contribute to EBNA1-dependent transactivation through protein complex formation at the transcriptional element. On the other hand, only TAF-I is recruited to the origin of replication by EBNA1 and acts as a repressor for EBNA1-mediated DNA replication. My data suggest that this negative regulation is linked to TAF-I’s ability to interfere with histone methylation and thus to alter chromatin structure at the origin of DNA replication. Finally, I showed that NAP1 and TAF-I are required for expression of lytic protein BZLF1 and that TAF-I associates with the BZLF1 promoter during lytic reactivation.