VictorJuiz/thesis huggingface dataset:
Hydrophobic Hydration of a Single Polymer
Keywords: single molecule force spectroscopy
atomic force microscopy
hydrophobicity
hydrophobic hydration
hydrophobic collapse
protein folding
polymer model

Hydrophobic interactions guide important molecular self-assembly processes such as protein folding. On the macroscale, hydrophobic interactions consist of the aggregation of "oil-like" objects in water by minimizing the interfacial energy. However, the hydration mechanism of small hydrophobic molecules on the nanoscale (~1 nm) differs fundamentally from its macroscopic counterpart. Theoretical studies over the last two decades have pointed to an intricate dependence of molecular hydration mechanisms on the length scale. The microscopic-to-macroscopic cross-over length scale is critically important to hydrophobic interactions in polymers, proteins and other macromolecules. Accurate experimental determination of hydration mechanisms and their interaction strengths are needed to understand protein folding. This thesis reports the development of experimental and analytical techniques that allow for direct measurements of hydrophobic interactions in a single molecule. Using single molecule force spectroscopy, the mechanical unfolding of a single hydrophobic homopolymer was identified and modeled. Two experiments examined how hydrophobicity at the molecular scale differ from the macroscopic scale. The first experiment identifies macroscopic interfacial tension as a critical parameter governing the molecular hydrophobic hydration strength. This experiment shows that the solvent conditions affect the microscopic and macroscopic hydrophobic strengths in similar ways, consistent with theoretical predictions. The second experiment probes the hydrophobic size effect by studying how the size of a non-polar side-chain affects the thermal signatures of hydration. Our experimental results reveal a cross-over length scale of approximately 1 nm that bridges the transition from entropically driven microscopic hydration mechanism to enthalpically driven macroscopic hydration mechanism. These results indicate that hydrophobic interactions at the molecular scale differ from macroscopic scale, pointing to potential ways to improve our understanding and predictions of molecular interactions. The system established in this thesis forms the foundation for further investigation of polymer hydrophobicity.
Osteoclastogenesis: Roles of Filamin A and SBDS, and their Regulation of Rho GTPases during Pre-osteoclast Migration
Keywords: osteoclast
Rho GTPases

Osteoclasts are multinucleated, bone resorbing cells that carry out their function using specialized actin-based structures called actin rings and podosomes. Rho GTPases function as molecular switches that regulate the actin cytoskeleton in osteoclasts and many other cell types. Filamin A (FLNa) and SBDS are two proteins that have the potential to interact with both F-actin and Rho GTPases, and thus regulate osteoclast formation, differentiation, or function. We found that in FLNa-null pre-osteoclasts, activation of RhoA, Rac1, and Cdc42 was perturbed, leading to defective pre-osteoclast migration prior to fusion. Ablation of SBDS resulted in the blockage of osteoclast differentiation downstream of RANK and defective RANKL-mediated upregulation of Rac2 that is required for pre-osteoclast migration. Therefore, both FLNa and SBDS are required to coordinate Rho GTPase activation during osteoclastogenesis, in addition to a role for SBDS in osteoclast differentiation downstream of RANK.
Sound Source Segregation in the Acoustic Parasitiod Fly Ormia ochracea
Keywords: Sound Localization
Song Recognition
Phonotaxis
Symmetry Detection

Sound source localization depends on the auditory system to identify, recognize, and segregate elements of salient sources over distracting noise. My research investigates sensory mechanisms involved in these auditory processing tasks of an insect hearing specialist, to isolate individual sound sources of interest over noise. I first developed quantitative methods to determine signal features that the acoustic parasitoid fly Ormia ochracea (Diptera: Tachinidae) evaluate for host cricket song recognition. With flies subjected to a no-choice paradigm and forced to track a switch in the broadcast location of test songs, I describe several response features (distance, steering velocity, and angular orientation) that vary with song pulse rate preferences. I incorporate these response measures in a phonotaxis performance index that is sensitive to capturing response variation that may underlie song recognition. I demonstrate that Floridian O. ochracea exhibit phonotaxis to a combination of pulse durations and interpulse intervals that combine to a range of accepted pulse periods. Under complex acoustic conditions of multiple coherent cricket songs that overlap in time and space, O. ochracea may experience a phantom source illusion and localize a direction between actual source locations. By varying the temporal overlap between competing sources, I demonstrate that O. ochracea are able to resolve this illusion via the precedence effect: exploitation of small time differences between competing sources to selectively localize the leading over lagging sources. An increase in spatial separation between cricket song and masking noise does not reduce song detection thresholds nor improve song localization accuracy. Instead, walking responses are diverted away from both song and noise. My findings support the idea that the ears of O. ochracea function as bilateral symmetry detectors to balance sound intensity, sound arrive time differences, and temporal pattern input to both sides of the auditory system. Asymmetric acoustic input result in corrective turning behaviour to re-establish balance for successful source localization.
Interaction between Macrophages and Epithelial Cells in Innate Immune Responses against Adenoviral Vectors
Keywords: innate immunity
virus

Although induction of innate immune responses during viral infection is essential, it can cause acute inflammation and lead to devastating results. The deleterious effect of innate immune responses has been demonstrated in gene therapy where administration of a replication deficient adenoviral vector (Ad) caused fatality during a clinical trial. Despite recent advances in our understanding of the innate immunity, there is a lack of understanding on how different cell types interact to mount inflammatory responses, which may play an important role in regulating immune responses in vivo. In this study, we investigated the interaction between macrophages and epithelial cells, the two major cell types capable of sensing and responding to viral infection in the airway, in induction of inflammatory responses against replication deficient Ads. We show in Chapter 2 that Ad infection of the macrophage-epithelial cell co-culture resulted in synergistic induction of inflammatory responses. Ad infection of the co-culture compared to macrophages alone resulted in higher cytotoxicity and induction of significantly higher levels of inflammatory mediators including pro-inflammatory cytokines, chemokines, nitric oxide, and reactive oxygen species. We found that these synergistic responses require macrophages and epithelial cells to be in close proximity suggesting that a novel mechanism regulates the inflammatory responses. In Chapter 3, we studied whether ATP plays a role in regulating inflammatory responses during acute Ad infection. Using the co-culture system, we found that ATP signaling through P2X7 receptor (P2X7R) is critical as inhibition or deficiency of P2X7R resulted in reduced inflammatory responses. We demonstrate that ATP-P2X7R signaling regulates inflammasome activation and IL-1β secretion. Furthermore, intranasal administration of Ad resulted in high mortality in mice but inhibition of ATP-P2X7R signaling enhanced survival and reduced inflammatory responses. These results suggest that ATP released by the infected cells plays an important role in regulating inflammatory responses during acute viral infection.
Frequency-selective Methods for Hyperpolarized 13C Cardiac Magnetic Resonance Imaging
Keywords: MRI
Hyperpolarized
Cardiac
Metabolism
Carbon-13
Pulse sequence design

Heart failure is a complex clinical syndrome in which the heart cannot pump sufficient blood and nutrients to the organs in the body. Increasingly, alterations in cardiac energetics are being implicated as playing an important role in the pathogenesis of heart failure. An understanding of specific metabolic switches which occur during the development of heart failure in patients would be greatly beneficial as a new diagnostic method and for the development of new therapies for patients with failing hearts. This thesis deals with the non-invasive assessment of metabolism in the heart. New magnetic resonance imaging (MRI) methods for metabolic characterization of the heart using hyperpolarized carbon-13 MRI are presented. Spatially resolved images of hyperpolarized 13C substrates and their downstream products can provide insight into real-time metabolic processes occurring in vivo, within minutes of injection of a pre-polarized 13C-labeled substrate. Conventional 3D spectroscopic acquisitions require in excess of 100 excitations, making it challenging to acquire full cardiac and respiratory-gated, whole-heart metabolic volumes. Each of the developments described in this thesis is intended to advance cardiac hyperpolarized 13C metabolic imaging towards a routine, clinical exam which can be used for prognosis and treatment optimization in patients with cardiovascular disease. The major technical development is a new interleaved-frequency, time-resolved MRI pulse sequence that can provide robust and reliable measurements of cardiac metabolic signals. The technique was applied to several realistic pre-clinical models of cardiac disease and the work presented will hopefully lead towards significant improvement in the management of patients with heart failure.
Child Neurodevelopment following In Utero Exposure to Organic Solvents
Keywords: case-control studies
child
child development
child physiology
child, preschool
developmental disabilities / chemically induced
developmental disabilities / diagnosis
developmental disabilities / epidemiology
female
male
follow-up studies
humans
incidence
linear models
maternal exposure
multivariate analysis
neuropsychological tests
occupational exposure
pregnancy
in utero
prenatal exposure delayed effects
prognosis
psychomotor performance
risk assessment
organic solvents
toxicity
toxicology
policy
reproductive medicine
occupational exposure / prevention and control
women, working
pregnant women
occupational medicine
teratogens
behavior
solvents

BACKGROUND: Many women of reproductive age are employed in industries involving exposure to organic solvents. Animal toxicological studies and human case reports demonstrate that exposure to organic solvents can cause neuropsychological deficits in exposed offspring; however, there is limited data from prospective controlled human studies. OBJECTIVE: To compare neuropsychological functioning between children whose mothers were occupationally exposed to organic solvents during pregnancy with a non-exposed matched comparison group. METHODS: Participants were 48 women who had previously contacted the Motherisk Program in Toronto, Canada during pregnancy regarding occupational exposure to organic solvents and a matched comparison group of women with no known exposure to teratogens during pregnancy. Children (18 months to 8 years 11 months at time of study) were compared in areas of cognitive, language, motor, and behavioral functioning. RESULTS: Children whose mothers were exposed to organic solvents during pregnancy displayed a lower level of functioning when compared with their matched peers in areas of cognitive, language, motor, and behavioral domains. Although the scores on measures of behavioral functioning were not in the clinical range, the mothers of exposed children reported more challenging behavioral problems. In order to determine whether exposure predicted neuropsychological outcomes above and beyond maternal intellectual functioning, hierarchical regressions were run with maternal IQ and maternal education at Step 1and exposure status added at Step 2. In utero exposure to organic solvents predicted lower sores on global measures of Verbal IQ, receptive and expressive language scales above and beyond maternal intellectual functioning. Factors associated with higher levels of exposure (detecting odor, longer duration and total number of toxicity symptoms) was associated with poorer outcome on behavioral and motor functioning tests. CONCLUSION: Despite the fact that the exposed mothers experienced minimal symptoms of toxicity, detrimental effects were still evident in their offspring. Current safety standards for exposure were designed for adults and need to be reevaluated. Further studies addressing exposure to specific organic solvents, dose, and gestational timing of exposure are warranted.
Perceptions of Elementary Mathematics Coaching
Keywords: Professional Development
Mathematics Coaching
Teacher Change

This study investigated elementary mathematics coaching from the point of view of two coaches, five elementary classroom teachers, and two principals in an urban school board in Ontario. Case studies were conducted of the two coaches and their work with their respective teachers. Qualitative data was collected through a series of ongoing observations of both teachers and coaches. Additionally, interviews were conducted near the beginning and end of the study with each coach, teacher, and principal. The teaching experience of the teachers in the study ranged from three to seventeen years and from kindergarten through grade five. The coaching program in the school board was in its fourth year of implementation. One coach had been working as a coach since the inception of the program and the other was in her third year of coaching. Evidence from the study leads to six major findings: (1) all participants indicated that engaging in coaching brought about change in the teachers’ classroom practices; (2) all participants were unable to clearly define a change in student learning due to coaching; (3) trusting and collaborative relationship between teachers and coaches is important to teacher engagement in coaching; (4) co-teaching and model lessons are the coaching structure with most impact; (5) time is the major barrier to coaching; (6) high quality professional development designed to meet the coaches’ learning needs and the existence of a coaching network to offer support are fundamental to sustaining a coaching program over time. Implications from this study suggest that coaching programs that include an emphasis on collaboration through reflective discussion and co-teaching are likely to bring about identifiable changes in teacher practice. School boards will need to find ways to ease the challenges that time presents to working with a coach in order for the changes to spread across the district. This study suggests that it is imperative that school boards identify and provide quality professional development to their coaches in order to sustain the changes that occur in practice. Suggestions for stakeholders implementing coaching programs and future research on coaching are included at the end of the study.
Responding to and Recovering from a Body-related Threat: An Application of Social Self-Preservation Theory
Keywords: Body image
Social Self-Preservation Theory
Women
Psychobiology

Social self-preservation theory (SSPT) suggests that when faced with social-evaluative threat, a set of psychological and physiological responses are elicited concurrently (Dickerson, Gruenewald, & Kemeny, 2004; Kemeny, Gruenewald, & Dickerson, 2004). A series of studies examined the applicability of SSPT to the examination of social-evaluative body-related threats. In the first study, interviews were conducted to identify and describe uncomfortable body-related situations, and typical responses to such situations. Findings provided preliminary evidence of the applicability of SSPT to everyday body-related threats of young adult women – the threats, context of those threats, and responses to such threats were consistent with SSPT. The second study examined psychobiological responses to, and recovery from, a social-evaluative body-related threat. Findings from this study showed that the social-evaluative body-related threat elicited a psychobiological response consistent with SSPT; women in the threat group reported higher social physique anxiety and had higher cortisol following the threat. The third study sought to extend the applicability of SSPT to examine the psychobiological responses to, and recovery from, an anticipated social-evaluative body-related threat. In addition, the potential moderating effect of appearance investment on responses to a threat was examined. Findings from this study showed that women in the threat group reported higher shame and social physique anxiety after anticipating a social-evaluative body-related threat than following a quiet rest period for women in the control group. Results also indicated that both groups showed an index of decrease for cortisol, with the control group showing a significantly greater overall decrease than the threat group. Appearance investment did not moderate cortisol responses to a threat. Findings from the third study provide partial support for SSPT’s applicability to the anticipation of a social-evaluative body-related threat. Together findings from all three studies provide converging evidence for the use of SSPT in understanding the psychobiology of body image.
Three Essays on Foreign Entrepreneurs
Keywords: foreign entrepreneurs
owner-manager
location choice
private benefits
owner-CEO
founder-CEO
firm performance
FDI

My dissertation focuses on foreign entrepreneurs—individuals who establish firms outside of their native countries. Despite the prevalence of foreign entrepreneurs, their strategic choices have received little attention in the research literature. For example, when starting a firm, an entrepreneur must decide whether to manage the business personally or hire a local manager, yet we know little about how this choice affects firm performance. To examine this issue, in the first study I use a novel dataset of foreign entrepreneurial firms in Russia and a visa policy change as an instrument for the owner-manager choice. Contrary to the expectation that foreign entrepreneurs would underperform local managers due to the liability of foreignness, I find that foreign owner-managers can benefit their firms: Exogenous assignment of a local manager in place of a foreign owner-manager reduces profits. Foreign owner-managers benefit their firms by hiring cheap native-country labor as well as through reduced agency costs. The second study examines how private benefits of occupying a managerial position affect an entrepreneur’s choice between owner-management and hiring an agent. I show that foreign entrepreneurs with a strong desire to reside in a host country are more likely to become owner-managers. These results are consistent with the idea that entrepreneurs expecting to gain private benefits from managing their firms are more likely to become owner-managers. Moreover, I demonstrate that entrepreneurs are willing to substitute the non-pecuniary benefits associated with relocation for firm profit. These findings add to a growing literature exploring the role of personal preferences in entrepreneurs’ strategic decisions, such as location choice and ownership structure. The third study examines the impact of media coverage on the location choices of foreign firms. Publicly available media information has largely been ignored by the location literature, perhaps because its impact on location choice is expected to be trivial. This study challenges this assumption: Using a new instrument for media coverage (a major anniversary of a city’s establishment date), I show that extensive foreign media coverage of a city increases the number of foreign entrants. Moreover, this effect is strongest for socially and geographically distant firms and entrepreneurs.
Investigation of Novel Progression-related Methylation Events and HOXD Genes in Prostate Cancer
Keywords: prostate cancer
DNA methylation
homeobox
prognosis

Aberrant DNA methylation in gene promoters causes gene silencing and is a common event in prostate cancer development and progression. While commonly identified methylated genes have been analyzed for their potential clinical utility in a variety of cancers, few studies have attempted a genome-wide methylation approach to discover new and possibly improved biomarkers for prostate cancer. In order to identify DNA methylation changes associated with aggressive prostate cancer, we performed a genome-wide analysis of 40 prostate cancers using Agilent human CpG island microarrays. Methylation profiles of candidate genes were validated using quantitative MethyLight technology in an independent series of 219 radical prostatectomies and compared to clinicopathological parameters. The effects of methylation on expression of HOXD3 and HOXD8 and the possible role of HOXD8 in progression of PCa were also investigated. We discovered previously unidentified methylation in the HOXD cluster of genes, namely HOXD3 and HOXD8, as well as TGFβ2 and GENE X as potential prognostic biomarkers. Furthermore, unsupervised clustering of samples by methylation signature indicated ERG oncogene expression as significantly different between clusters. Within the independent cohort, we observed strong correlations between Gleason score (GS) and HOXD3 as well as GENE X, while HOXD3 and HOXD8 methylation were associated with ERG expresson. TGFβ2 was an independent predictor of disease recurrence using Cox multivariate regression analysis. In gene expression studies, both HOXD3 and HOXD8 were elevated in cancers with poor prognosis, while DNA methylation did not correlate with expression levels. Both genes were found to contain alternative transcription start sites, explaining the poor correlation between methylation and expression. Finally, knockdown of HOXD8 expression did not have any effect on viable cells or cell motility in an in vitro model. These results indicate that a panel of novel DNA methylation markers distinguish indolent prostate cancers from aggressive ones, and that expression of HOXD3 and HOXD8 is regulated by mechanisms including, but not dependent on, DNA methylation.