VictorJuiz/thesis huggingface dataset:
The Effect of Indole-3-Carbinol and 3,3'-Diindolylmethane on Fatty Acid Synthase and Sp1 in Breast Cancer Cells
Keywords: Indole-3-carbinol 3,3'-diindolylmethane Breast Cancer

Fatty acid synthase (FAS), an enzyme that is over-expressed in many cancers, is necessary for cancer cell proliferation. Previously, we have shown that FAS in cancer cells is regulated at least in part, by Sp1. Indole-3-carbinol (I3C) and its acid condensation product, 3,3’-diindolylmethane (DIM) modulate various transcription factors involved in regulating cellular proliferation and apoptosis. The objective of this study was to determine whether reductions in breast cancer cell proliferation caused by I3C and/or DIM occur as a result of reductions in FAS. DIM and, in some cases, I3C reduced FAS expression in three breast cancer cell lines. However, addition of palmitate or oleate to DIM-treated MCF-7 cells did not restore proliferation. DIM-associated reduction in proliferation of MCF-7 cells also results in a reduction of Sp1 expression, and down-regulation of FAS occurs after inhibition of proliferation. Thus, the anti-proliferative effect of I3C and DIM may be due to their effect on down-regulating Sp1, which in turn could modify several Sp1-associated genes, including FAS.
Mechanisms of Erythropoietic Failure in Shwachman Diamond Syndrome Caused by Loss of the Ribosome-related Protein, SBDS
Keywords: Erythropoiesis
Shwachman Diamond Syndrome

Anemia occurs in 60% of patients with Shwachman Diamond Syndrome (SDS). Although bi-allelic mutations in SBDS cause SDS, it is unclear whether SBDS is critical for erythropoiesis and what the pathogenesis of anemia is in SDS. I hypothesize that SBDS protects early erythroid progenitors from p53 family member mediated apoptosis by promoting ribosome biosynthesis and translation. SBDS deficiency by vector-based shRNA led to impaired cell expansion of differentiating K562 cells due to accelerated apoptosis and reduced proliferation. Furthermore, the cells showed general reduction of 40S, 60S, 80S ribosomal subunits, loss of polysomes and impaired global translation during differentiation. An upregulation of the pro-apoptotic p53 family member, TAp73, was found in resting SBDS deficient cells; however, not in differentiating cells. These results demonstrate SBDS plays a critical role in erythroid expansion by promoting survival of early erythroid progenitors and in maintaining ribosome biogenesis during erythroid maturation independently of p53 family members.
Novel Regulatory Mechanisms Underlying the Expression of the Carbohydrate Response Element Binding Protein (ChREBP): the Roles of Insulin and the POU Protein Oct-1
Keywords: ChREBP
Insulin
Oct-1
Liver

ChREBP has emerged as one of the key controllers of hepatic lipogenesis. While the function of ChREBP has been extensively investigated, mechanisms underlying its transcriptional regulation remain largely unknown. We located a conserved POU-binding site within mammalian ChREBP promoters, and demonstrated that the POU homeodomain protein Oct-1 binds to this site in the human HepG2 cell line. Oct-1 transfection significantly repressed ChREBP promoter activity 50-75%. Conversely, knockdown of Oct-1 expression with shRNA significantly increased ChREBP expression levels. Furthermore, insulin treatment resulted in a two-fold activation of ChREBP promoter activity, and stimulated endogenous ChREBP expression. We found that the stimulatory effect of insulin on the ChREBP promoter is at least partially dependent on the presence of the POU-binding site, and that insulin treatment reduced Oct-1 expression. Our observations identify Oct-1 as a transcriptional repressor of ChREBP, and suggest that insulin stimulates ChREBP expression via attenuating the repressive effect of Oct-1.
Identification of Novel Interacting Proteins of Four and a Half LIM Domains Protein 1 from Human Embryonic Kidney 293 Cells
Keywords: protein interactions
protein purification

Four and a half LIM domains protein 1 (FHL1), consisting of 4.5 protein interaction mediating LIM domains, is a predominantly skeletal muscle protein that has consistently been upregulated in a variety of cardiovascular diseases. Since proteins mediate their functions in conjunction with other proteins, it was considered that delineation of interactions would provide insight into FHL1’s regulation and regulatory functions. We performed tandem affinity purification (TAP) from human embryonic kidney 293 (HEK-293) cells to purify tagged FHL1 and interacting proteins. Samples were analyzed using gel-free liquid chromatography mass spectrometry (LC-MS). 61 high confidence potential interactors were identified from multiple experiments. Validation of interactions was then performed by co-immunoprecipitation (co-IP) or streptavidin bead pull down, and supported by immunofluorescent colocalization studies. FHL1 interactions could thus be supported for four novel candidates: non-muscle α-actinin 1 (ACTN1), PDZ and LIM domain protein 1 (PDLIM1), cytoplasmic gelsolin (GSN), and ryanodine receptor 1 (RYR1).
Fragile X Mental Retardation Protein is Required for Chemically-induced Long-term Potentiation of the Hippocampus in Adult Mice
Keywords: FMRP
glycine
LTP
synaptic plasticity
ERK1/2
hippocampus

Fragile X syndrome (FXS) is caused by the lack of fragile X mental retardation protein (FMRP). The animal model of FXS, Fmr1 knockout (KO) mice, shows impairment in hippocampus-dependent learning and memory. However, results for long-term potentiation (LTP), remain inconclusive in the hippocampus of Fmr1 KO mice. Here, we demonstrate that FMRP is required for glycine-induced LTP (Gly-LTP) in the CA1 of hippocampus. The Gly-LTP requires activation of postsynaptic NMDA receptors and metabotropic glutamateric receptors, as well as the subsequent activation of extracellular signal-regulated kinase (ERK) 1/2. However, paired-pulse facilitation was not affected by glycine treatment. Our study provide evidences that FMRP participates in Gly-LTP by regulating the phosphorylation of ERK1/2, and that improper regulation of these signaling pathways may contribute to the learning and memory deficits observed in FXS.
The Effects of MK-801, an NMDA Receptor Antagonist, on Behavioural Performance and Learning and Memory of Zebrafish, Danio rerio
Keywords: zebrafish
learning

Learning and memory are complex phenomena; numerous biochemical and neurobiological mechanisms subserving these functions have been identified. A key molecular component involved in learning and memory, the NMDA-R (N-Methyl-D-Aspartate Receptor) is impaired by MK-801(dizocilpine), an antagonist compound. Here I analyze the effects of MK-801 on the performance characteristics of zebrafish (Danio rerio) as these in turn can significantly influence the outcome of learning tasks. Subsequently, I study the effects of MK-801 on the acquisition, consolidation, and recall of memory in a plus maze, a new task I adapted from zebrafish literature. Although MK-801 seemed to have no effect on acquisition of memory in zebrafish, it disrupted their ability to consolidate and recall in the plus maze, echoing results found in rodent literature. Combined, these results suggest that zebrafish can be used as a tool to further advance the discovery of learning and memory.
Aging and Implicit Memory for Emotional Words
Keywords: emotion
implicit memory
aging
cognitive control
word fragment completion

The present study investigated age differences in implicit memory for positive, negative and neutral words. We also explored how cognitive control and time of testing influence emotional memory. Participants completed a one-back picture comparison task with superimposed distracting emotional and neutral words. Memory for distracting words was tested using an implicit memory test and cognitive control by a flanker task. Priming was significant for negative but not for positive and neutral words. Memory for distracting negative words was greater at non-optimal times of day for young adults but similar across the day for older adults. A high level of cognitive control was related to greater priming for negative words in young adults and lower priming in older adults. Priming for neutral words was enhanced in high cognitive control participants when stimuli contained emotional words that were relevant to one’s goals, implicating the use of emotion regulation at an unconscious level.
Integrating Children's Disclosure and Maternal Accurate Knowledge of Children's Thoughts and Feelings: A Longitudinal Examination
Keywords: parenting
socialization
disclosure
children
accuracy
knowledge
warmth
coping
development
psychology
social development
longitudinal
adolescents

One hundred and eleven mother-child dyads visited the laboratory when children were 10 to 12 years old and again two years later. Children’s self-disclosure to mothers and mothers’ accurate knowledge of effective comforting strategies were examined together in the context of maternal warmth and children’s positive coping. Maternal warmth longitudinally predicted children’s disclosure, and children’s disclosure longitudinally predicted mothers’ accurate knowledge of comforting strategies. Maternal warmth moderated the association between mothers’ accurate knowledge of comforting strategies and children’s positive coping. Specifically, maternal knowledge predicted child coping only in children of cold mothers. Implications for the socialization of coping and the role of child disclosure and parents’ accurate knowledge in parenting interventions are discussed.
Effects of Early Embryonic Alcohol Exposure on Activity Patterns in Zebrafish (Danio rerio)
Keywords: zebrafish
embyronic ethanol
embryonic alcohol
activity patterns

SFWT Zebrafish were exposed to various concentrations of EtOH at 24 hours post-fertilization for a period of two hours. When fish reached maturity they were placed in individual tanks in a larger open field. A preliminary strain comparison was also conducted using control (EtOH untreated) SFWT and AB fish. The behaviour of fish was recorded for 24 hours during a normal light:dark cycle. Motor patterns and general activity were quantified and analyzed and several behaviors were found to change significantly throughout the daytime and nighttime period. Also, fish exposed to the highest concentration of alcohol were found to exhibit significantly reduced amount of thrashing towards other subjects as compared to fish in the control group confirming previous results that demonstrated reduction of shoaling after early embryonic alcohol exposure.
The Eelectrophysiological Effects of Iron Overload on the Heart
Keywords: Cardiac
Electrophysiology
Iron Overload
Calcium

Chronic iron overload (CIO) in patients leads to a cardiomyopathy characterized by conduction defects, including bradyarrhythmias. Using a murine model of CIO, we explored the effects of iron loading on the electrophyisology of the heart. Telemetric heart rate was reduced in conscious CIO mice compared to controls. Similarly, heart rates were depressed in both isolated CIO hearts and CIO mice following autonomic blockade, suggesting an intrinsic impairment of the SA node (SAN). Indeed, spontaneous action potential frequency was reduced in CIO SAN myocytes. The depressed pacing rate in CIO SAN myocytes was linked to reduced L-type Ca2+ current (ICa,L) density and a rightward shift in ICa,L activation, suggesting a selective reduction in α1D-mediated ICa,L. Western blot analysis demonstrates that the α1D isoform was reduced by ~ 89% in CIO atrial tissue. Therefore, the conduction defects under conditions of CIO are due to reductions in Cav1.3 channel expression in atrial tissue.
The Genetic Program of Myc-potentiated Apoptosis: Systems Development
Keywords: Myc
Apoptosis
Cancer
ChIP-chip

Myc is a powerful oncogene frequently deregulated in cancer yet deregulated Myc alone does not lead to cellular transformation due to the intrinsic safety mechanism of deregulated Myc potentiating apoptosis. The mechanism by which Myc potentiates apoptosis remains unclear, however, because the regions of Myc essential for apoptosis are also required for Myc to function as a regulator of gene transcription, it is thought that Myc’s role in apoptosis is a function of its regulation of an apoptotic genetic program. We hypothesize that under apoptotic conditions, Myc differentially binds and/or regulates a specific cohort of genes to potentiate apoptosis. The foremost approach to addressing this hypothesis is the employment of ChIP-chip coupled with expression microarray analyses. Here, using the MCF10A breast epithelial and SHEP neuroblastoma cell lines, we developed and characterized two independent human systems for subsequent ChIP-chip and expression array analyses to elucidate the genetic program of Myc-potentiated apoptosis.
The Impact of Infant Crying and Soothability on Cognition
Keywords: Mother-Infant Relationships

Perception of infant crying has been linked to the brain regions that are activated with stress and conflict monitoring, such as the anterior cingulate and amygdala. Whether the stress of cry perception affects cognitive processes is heretofore unknown. This research combines an experimental paradigm of an unsoothable infant cry task (Donovan, Leavitt, & Taylor, 2005) with a series of Rejection Stroop tasks (Dandeneau & Baldwin, 2004) with the expectation that perception of infant distress would deplete neural resources underlying the regulation of attention. Two studies were conducted on non-parent young adults and two studies were conducted on mothers of infants. Results indicated that the cry task causes negative affect and cognitive interference in non-parent young adults to a greater extent than does a musical stimulus, and that mothers of infants experience negative affect and cognitive interference comparable to the non-parent young adults.
Prospective Hazard Analysis of Patient Identification Processes in the Neonatal Intensive Care Unit
Keywords: Prospective hazard analysis
FMEA
NICU
Patient Identification

Neonatal Intensive Care Unit (NICU) patients present unique patient identification challenges. Prospective hazard analysis (PHA) assesses safety by identifying hazards before an adverse event occurs. This project analyzes a barcoded feeding process in one NICU, and conducts a preliminary evaluation of PHA methods. Observations were conducted to quantify patient identification methods used in one NICU; the unit’s barcoded feeding process was examined for potential failures. The process underwent PHA with two methods, Global Hazard Ratings (GHR), a simplified method developed for this project, and Failure Modes and Effects Analysis (FMEA). FMEA showed greater interrater reliability; there was poor agreement between methods. A list of 21 hazards was developed for the clinical team from the FMEA results. Recommendations are for the unit to formulate and implement mitigation strategies for the identified hazards. Future work involves a more in depth look at FMEA interrater reliability and reliability comparison with other PHA methods.
Sexual Selection on Females: Comparing Two Estimates of Mating Success in a Sex-role Reversed Insect
Keywords: insect behaviour
sexual selection
sex-role reversal
Anabrus simplex
selection analysis

While there has long been interest in the form of sexual selection in males, studies characterizing this selection in females remain sparse. Sexual selection on females is predicted for sex-role reversed Mormon crickets, where males are choosy of mates and nutrient-deprived females compete for matings to gain nutritious nuptial gifts. I used selection analyses to describe the strength and form of sexual selection on female morphology. There was no positive sexual selection on the female body size traits predicted to be associated with male preferences and female competition. Instead, I detected selection for decreasing head width and mandible length. Additionally, I tested the validity of a commonly-used instantaneous measure of mating success (mated vs. unmated) by comparing selection results with those determined using a more detailed fitness measure (cumulative mating rate). The two fitness measures yielded similar patterns of selection, supporting the common sampling method comparing mated and unmated fractions.
Structural Characterization, Optimization, and Failure Analysis of a Human-powered Ornithopter
Keywords: FEA
highly-flexible
ornithopter
Composites
Failure Analysis
Human-Powered Aircraft
HALE

The objective of this work was to develop an analysis framework for the structural design of the Human-Powered Ornithopter (HPO). This framework was used in a kinematicaerostructural optimizer for apping-wing ight (Ornithia), as well as analytically to design the HPO, and focused on three goals. First was the development of an accurate and computationally inexpensive nite-element method, to be integrated with Ornithia, which would capture the geometric nonlinearity of the aerostructural interaction of the wing when subjected the large deformations in ight. Second was the assembly of a model by which the aircraft primary structure, the wing main spar especially, could be exactly characterized and designed. Third was the establishment of a process and toolbox for failure analysis which could be applied universally in the design of the HPO. The validation and tuning of these models involved extensive testing on prototype carbon ber composite components.
The Gentle Way to Docility
Keywords: judo
Kano Jigoro
modern history
docile bodies
moral education
schools

In 1931, judo became a compulsory subject in middle schools throughout Japan, over forty-years after Kanō Jigorō, judo's founder, had initially recommended it to government officials as something which should be included in the schools across the country. While this simple change in middle school curriculum may seem insignificant, it was in fact a watershed marking a new stage of the creation of an able and disciplined populace in Japan. This thesis will explain the significance of the inclusion of judo in schools by investigating the history of judo up to the point of its inclusion in schools, exploring the rhetoric of judo in terms of a larger discourse on "moral education" which was prevalent during the times, and finally an analysis of school judo—in terms of its physical practice as well as the ideology and rhetoric behind it—using the Foucauldian concept of "docile bodies."
XB130: in silico and invivo Studies of a Novel Signal Adaptor Protein
Keywords: adaptor protein
acute lung injury
embryonic development
protein family
AFAP
XB130

XB130 is a relatively unstudied novel signal adaptor protein. In the first phase of this study, an in silico search for proteins related to XB130 was conducted. Two other proteins (AFAP and AFAP1L1) were found to have a significant similarity to XB130 and were compared in detail. After an analysis of these three proteins, it was proposed that they are members of a novel protein family, termed the “AFAP family of signal adaptor proteins”. XB130 has previously been found to regulate cell cycle progression, death, and migration in lung epithelial cells. It was therefore hypothesized that XB130 is protective in acute lung injury (ALI) and important for facilitating repair after injury. XB130 was found to be differentially regulated in ALI depending on the initial insult. Engineering XB130 transgenic mice to further characterize the role of XB130 in lung injury/regeneration revealed that this protein could be essential for early embryo development.
Change in Middle Cerebral Artery Velocity over Time to an Acute and Sustained Stimulus
Keywords: Cerebral Blood Flow
Hypercapnia
Blood Pressure

Little is known of the temporal cerebral blood flow response to a chemical stimulus consisting of increased PCO2 measured over time. Currently, there is only one study suggesting multiple phases in the CBF-CO2 response. Time constants of middle cerebral artery blood velocity (MCAV) response to a change in PETCO2 have been reported to be between 3 and 99.4 s. We studied the MCAV response in 28 subjects (10 females) to a sustained +10 mmHg above baseline (10 min) acute increase of PETCO2. We found that there were three distinct MCAV response patterns among subjects. Additionally, the responses of males and females differed. These studies suggest that there are multiple overlapping mechanisms controlling the chemoresponse of cerebral blood vessels and that these mechanisms may differ between men and women.
Soft Workfare? Re-orienting Toronto's Social Infrastructure Towards Employment
Keywords: Toronto
soft workfare
welfare
social infrastructure
employment services
social services
social citizenship
governmentality
non-profit organizations
Ontario Works

This research tracks the emergence of ‘soft’ workfare in Toronto. This refers to a set of attitudes and practices apparent in the delivery of welfare-to-work programs through the Ontario Works framework, which use compulsion to push people towards employment while simultaneously encouraging limited and specific practices of individual choice. Research findings are derived from eight interviews and relevant policy reports, focusing on the experiences of three non-profit agencies and the City of Toronto, who provide employment assistance and financial assistance through Ontario Works, respectively. These findings indicate that grassroots organizations pioneered employment services for social assistance recipients, and, alongside the municipal government, had been calling for active employment programs. They made use of the distance between policy rules and their own programs to alleviate the most punitive features of OW, but judge compulsion as a means to meet a necessary end. This demonstrates how disciplinary tendencies reside within liberal governmentalities.
Water from the North: Nature, Freshwater, and the North American Water and Power Alliance
Keywords: freshwater
nature
resources
North America
high modernism
the "West"

The North American Water and Power Alliance (NAWAPA), a high modernist continental water diversion project drafted in Los Angeles in 1964, is examined for the impact it had upon social conceptions of nature, the scale of water diversion in North America, and the extent of American Southwestern efforts at sustaining unsustainable Northern lifestyles. Drafted to address the anxiety of perceived ecoscarcity regarding water shortages in the early 1960s, NAWAPA emerged after a century of increasingly large-scale diversion projects, and seemed a logical continuation of such grandiose, “jet-age” type thinking. It proposed to re-engineer the North American landscape to provide water from the North to the arid Southwest. Reasons for the plans failure (including the monumental shift in scale, and Canadian territorial and environmental opposition) are examined in relation to how nature was conceived – or forgotten – in the proposal.
Post Synthesis Rapid Thermal Annealing and Characterization of Colloidal Nanoparticles
Keywords: Rapid Thermal Annealing
Raman Spectroscopy

This Masters thesis investigates the effects of post growth rapid thermal annealing on colloidal CdTe nanoparticles. This novel process has not previously been applied to colloidal nanoparticles. It is found that rapid thermally annealing with temperatures up to 400°C, the number of defect bonds in the semiconductor core will decrease and the zincblende structural phase will prevail. These findings are identified using Raman spectroscopy enhanced in a liquid core waveguide and corroborated using a variety of other analysis techniques. What is also important is that while the semiconductor core is changing, the optical characteristics of the material remain nominally unchanged. Additionally, a circulatory peristaltic pump system that is suitable for future in situ monitoring was developed and used to investigate the length effects of Teflon capillary tubes as a liquid core waveguide for Raman spectroscopy.