VictorJuiz/thesis huggingface dataset:
Characterization of CEACAM Binding by Human Specific Pathogens

Human restricted pathogens such as Neisseria gonorrhoeae, Neisseria meningitidis, Moraxella catarrhalis and Haemophilus influenzae, as well as bacteria that are responsible for human specific disease, such as adherent-invasive and diffusely adhering E. coli, have evolved unique mechanisms to target and exploit host cellular CEACAM receptors during the course of infection. To gain further insight into how pathogens interact with CEACAMs, my studies have focused on understanding the molecular basis of bacterial attachment to CEACAMs by M. catarrhalis and N. gonorrhoeae. It is now evident M. catarrhalis and Neisseria sp. use two structurally and phylogenetically unrelated adhesins to bind CEACAMs on host cells; UspA1 and Opa proteins, respectively. In this thesis, I identify the sequence determinants for CEACAM binding in both Neisseria sp. Opa proteins and M. catarrhalis UspA1 proteins and show these sequences exist in distinct structural architectures within each adhesin, with the CEACAM binding regions in UspA1 existing in the context of an α-helical coiled coil structure while Opa sequences are localized to surface exposed loops that are presumably flexible in nature. I also highlight the functional diversity that exists with respect to CEACAM binding, within both the Opa and UspA protein families, a finding important in furthering our understanding of the role of CEACAM in bacterial infections. Finally, these studies show that sequences within Opa are sufficient for adherence to CEACAM, providing important insight into the development of CEACAM-specific therapeutics that have potential applications for a variety of distinct conditions ranging from autoimmunity to cancer.

Keywords: CEACAM
Pathogen
Advisor: Gray-Owen, Scott
Molecular Prediction of Patient Prognosis

Each cancer is unique: it reflects the underlying genetic make-up of the patient and the stochastic mutational processes that occur within the tumour. This uniqueness suggests that each patient should receive a personalized type of therapy. Current predictions of a cancer patient’s outcome or prognosis are highly inaccurate. To aid in the prediction of patient prognosis based on highthroughput molecular datasets I have worked to optimize each step of the experimental pipeline: platform annotation, experimental design, consideration of tumour heterogeneity, data pre-processing and statistical analysis, and feature selection. First, a 12k CpG Island clone library was sequenced and annotated using a BLAT analysis. Second, microarrays built using this library were used in a fully-saturated study to evaluate the importance of ChIP-chip experimental design parameters. Third, intra-tumour heterogeneity was shown to influence specific pathways in a large fraction of genes. Fourth, a systematic empirical evaluation of 19,446 combinations of microarray analysis methods identified key steps of the analysis process and provided insight into their optimization. Finally, the combination of a two-stage experimental design and a novel semi-supervised algorithm yielded a six-gene, mRNA abundance-based classifier that could divide non-small cell lung cancer patients into two groups with significantly different outcomes in four independent validation cohorts. Further, a permutation study showed that millions of six-gene markers exist, but that ours ranked amongst the top 99.98% of all six-gene markers. The knowledge gained from these studies provides a key foundation for the development of personalized therapies for cancer patients.

Keywords: systems biology
prognostic markers
Advisor: Penn, Linda Z.
Jurisica, Igor
The Effect of Mentoring on Leadership Self-efficacy in Nurses

The literature suggests that mentoring is an important factor in the development of nurse leaders. Preliminary evidence suggests that self-efficacy may provide the conceptual link between receipt of mentoring functions and leadership performance. The purpose of this study was to contribute to the scientific knowledge base that informs nursing administration by examining the contribution of mentoring to development of leadership self-efficacy (LSE) among nurses. The conceptual framework that guided the study integrated theoretical perspectives from mentoring, leadership, and self-efficacy theories. A prospective, repeated measures design was used. One hundred Registered Nurses completed measures of LSE at the beginning and conclusion of leadership training and three months following training, and mentoring just prior to the final LSE measurement. Hierarchical regression analysis was used to assess the effect of mentoring on self-efficacy for each of five leadership practices. The change in LSE levels over the course of the leadership training intervention was included as a control for the effect of training. Participant administrative experience and professional education were included as controls. Study results did not support the proposition that protégé exposure to career and psychosocial mentoring would lead to higher levels of LSE. Mentorship did not predict self-efficacy for any of the leadership practices. The impact of participants’ mentoring experiences prior to the study, low statistical power due to a small sample size, homogeneity of respondents with respect to their mentorship experiences, and the possibility of a ceiling effect for LSE are possible explanations for these results. Results did suggest that mentored nurses were able to enhance their LSE during leadership training, and to sustain this increase upon return to their home organizations. Findings also provided insight into the prevalence of mentoring among nurses who are actively pursuing leadership development. Nearly two-thirds of the respondents were mentored during the study period, and these nurses reported that their mentoring relationships were active and positive. Mentoring continues to be advanced as an important contributor to leadership development among nurses. This study reinforces the need for further exploration of this relationship to inform and guide developmental interventions and allocation of resources.

Keywords: Mentoring
Self-efficacy
Leadership
Nurses
Advisor: Hall, Linda McGillis
Specters of "Isolationism"? Debating America's Place in the Global Arena, c.1965-1974

The United States emerged from the Second World War determined to play a leading role in the maintenance of international order. Increasing levels of tension between the United States and the forces of communism after 1945, however, slowly forced a redefinition of what might be more distinctly termed America's "global" responsibilities, such that by 1961 John F. Kennedy declared that the United States would "pay any price. . .in order to assure the survival and success of liberty." An identifiable Cold War consensus took shape based on the assumption that it was America's responsibility to lead, protect, and defend, the "free-world." Since America was effectively waging a battle to ensure the successful spread of its own values, the Cold War consensus also served to severely limit debate—dissent essentially implied disloyalty. By the mid-1960s, however, the Cold War consensus began to crack and a debate over American foreign policy began to emerge. That debate is the focus of this dissertation, which looks at the opposition to Cold War policies which emerged in the Senate, most notably among the members of the Senate Foreign Relations Committee --many of whom had once played a role in developing the very foreign policies they now protested. The war in Vietnam provided the focal point for much of the dissent, but the foreign aid program also became heavily criticized, as did America's NATO policy, particularly the size of the American military presence in Europe. More important, however, Senate dissenters came to question the United States' very position as the principle defender of the free world. They did not dispute the idea that America had a significant role to play in the global arena, but they did not believe that role should consist of being the world's policeman, the self-appointed arbiter of other’s affairs, and the keeper of the status quo. Because of their views, the so-called dissenters were labelled as "neo-isolationists." They saw themselves the true "internationalists," however, believing that the Cold War had led to confusion between internationalism and indiscriminate global involvement.

Keywords: Cold War
American Foreign Policy
Senate Foreign Relations Committee
Vietnam War
Foreign Aid
NATO
Advisor: Pruessen, Ronald W.
Node Selection in Cooperative Wireless Networks

In this thesis, we argue for node selection in cooperative decode-and-forward networks. In a single-hop network with multiple relays, we show that selecting a single node to aid in the transmission between a source and a destination outperforms both traditional orthogonal transmissions and distributed space-time codes. In networks where sources transmit information over multiple hops and relays can communicate with each other, we study the relationship between cooperation and channel-adaptive routing. We show that cooperation is only beneficial if designed jointly with a routing scheme. This motivates a search for optimal algorithms in generalized relay networks. In networks without restrictions on the relays in terms of whom they can communicate with, we study the problem of optimal resource allocation in terms of transmission time. The resource allocation selects the relays to participate in the transmission and optimally allocates time resource between the selected relays. To implement this resource allocation algorithm, we propose a recursive solution which reduces the computational complexity of the algorithm. For large networks, the resulting computational complexity of implementing the algorithm is exponential in the size of the network and is likely to preclude its implementation. We thus propose that the resource allocation be implemented sub-optimally through node selection: a subset of the nodes in the network should be selected and used as input to the optimal resource allocation algorithm. We provide guidelines for selecting the nodes and propose four heuristics which offer various complexity-performance trade-offs. Compared to the optimal resource algorithm, all four heuristics significantly decrease the required computation complexity of the optimal algorithm.

Keywords: Cooperative Diversity
Spatial Diversity
Selection
Resource Allocation
Advisor: Adve, Raviraj
Communicable Disease Control in the New Millenium: A Qualitative Inquiry on the Legitimate Use of Restrictive Measures in an Era of Rights Consciousness

Background: When Canadian public health officials issued thousands of quarantine orders during the SARS outbreak in 2003, it raised difficult questions about the legitimacy and acceptability of restrictive measures to achieve public health goals. While public health interventions have traditionally been justified on utilitarian grounds, this project aims to establish an empirical basis to justify public health action. The objectives are: 1) Descriptive: To describe the views of members of society on the justifiability of using restrictive measures to achieve public health goals; 2) Analytic: To analyze the use of restrictive measures at the intersection of public health policy, human rights norms, and ethics; and 3) Normative: To situate public health ethics within a Habermasian model of communicative ethics that can serve as the basis of justification for the legitimate use of restrictive measures based on the intersubjective recognition of public health and human rights. Methods: Individual interviews were conducted with 62 participants, including 23 health care providers, 16 members of the public, 13 community and/or spiritual leaders from the Greater Toronto Area, as well as six public health officials and four health care regulators at the local, provincial, and federal levels of jurisdiction. Findings: Participant views were analyzed and organized into themes that revolve around the following concepts: 1) common good; 2) types of quarantine; 3) compliance; 4) reciprocity; 5) uncertainty; and 6) communication. Conclusions: Combining empirical research with conceptual scholarship, it is argued that the recognition of and commitment to the common good by participants, which emerged as an overarching theme, provide justificatory power for the use of quarantine during communicable disease outbreaks. But to respect rights, while being committed to the common good, it is argued that we must move beyond the see-sawing between ostensibly competing requirements toward a conception that gives equal weight to public health and human rights; that is, both imperatives – the community and the individual – refer to one another without dissolving into one another. Following a Habermasian account of opening processes of decision-making to a moral-practical discourse, it is argued that public health ethics offers an important site for integrating his model of discourse ethics within public health deliberations to expand the scope of moral argumentation on--and ultimately to ground the justification of--the use of restrictive measures.

Keywords: Public Health
Ethics
Advisor: Upshur, Ross
The Welcome Intrusions of TB Nurses. An Interpretive Phenomenological Study of Relational Work in Public Health Nursing

Nurse-client relationships are inherently valued in descriptions of the nature of public health practice and require consideration as intentional work that demands knowledge, skill, and personal engagement. They are also matters of place. In public health, they are largely taken-for-granted, particularly in the area of infectious diseases and the tuberculosis (TB) program specifically. TB nursing is structured within an explicit population focus, which challenges such relationship ideals as client-centered care, autonomy, and empowerment in everyday practice. This interpretive phenomenological study (Benner, 1994) of the relational work of TB nurses was undertaken to understand the nature of nurses’ relational work, wherever it happened, and how it was understood within the mix of assigned program tasks. Carried out in one of Canada’s largest TB programs, this study involved observing nine nurses and 24 clients in their respective visits over time, and interviewing 16 participants. Visits happened in homes and cars, and other assorted locations, highlighting how place shows up in these relationships and how nurses help clients to make sense of TB and broader life concerns shaping the experience of it. How they involve themselves interpersonally in these situations is the stuff that relational work is made of. Through the use of thematic analysis (Benner, 1994; Chesla, 1994), notes and transcripts were analyzed. The resulting interpretation of the nature of relational work is that of ‘welcome intrusions’, a notion that along with three key thematic dimensions: ‘getting through the door’, ‘doing TB but more than that’, and ‘beyond a professional’, addresses the central control-care tone of relational work. Together these themes identify key areas of knowledge and skill. That is, honesty and respect for privacy, ‘expertise’ in TB, dismantling the effects of stigma and displacement, and socializing-with-purpose. This emphasizes the value of articulating the everyday practices of nurses in population-focused programs that can contribute to successful treatment, and client healing and well-being. This relational work of TB nurses may be supported and enhanced when framed as the skill of involvement (Benner et al, 1996; Benner et al, 1999) and critically examined as part of providing comfort and enacting surveillance.

Keywords: nursing relationships
public health nursing
TB
nursing geography
surveillance
phenomenology
Advisor: Peter, Elizabeth Helen
Microwave Devices and Antennas Based on Negative-refractive-index Transmission-line Metamaterials

Several microwave devices and antennas that are based on negative-refractive-index transmission-line (NRI-TL) metamaterials are presented in this thesis, which exhibit superior performance features compared to their conventional counterparts. These are a Wilkinson balun, a 1:4 series power divider, a four-element printed dipole array, a leaky-wave antenna, and an electrically small folded-monopole antenna. The Wilkinson balun employs +90° and −90° NRI-TL metamaterial lines at the output branches of a Wilkinson divider, to achieve a six-fold increase in the measured differential output phase bandwidth compared to that of an analogous balun employing transmission lines, while occupying only 55% of the area. The 1:4 series power divider comprises four non-radiating 0° NRI-TL metamaterial lines, each with a compact length of λ0/8, to provide equal power split to all four output ports. Compared to a conventional series power divider employing one-wavelength long transmission lines, the metamaterial divider provides a 154% increase in the measured through-power bandwidth, while occupying only 54% of the area. The metamaterial series power dividing concept is also applied to a four-element fully-printed dipole array that is designed to radiate at broadside, in order to demonstrate that the array exhibits reduced beam squinting characteristics. It is shown that the metamaterial-fed array has a measured scan-angle bandwidth that is 173% greater than an array that is fed using a conventional low-pass loaded line. The reduced-beam squinting property that NRI-TL metamaterial lines offer is subsequently exploited to create a leaky-wave antenna that radiates a near-fixed beam in the forward +45° direction, with an average measured beam squint of only 0.031°/MHz. This is achieved by operating the antenna in the upper right-handed band where the phase and group velocities are the closest to the speed of light. Finally, an electrically small antenna comprising four 0° NRI-TL metamaterial unit cells is presented which supports a predominantly even-mode current, thus enabling it to be modeled as a multi-arm folded monopole. This significantly increases its radiation resistance, which allows it to be matched to 50 Ω, while maintaining a high measured efficiency of 70%.

Keywords: Negative Refractive Index
Metamaterial
Transmission line
Phase shifter
Balun
Power divider
Series-fed
Antenna
Array
Dipole array
Leaky-wave
Folded monopole
Advisor: Eleftheriades, George V.
Influence of the Quasi-biennial Oscillation on Interannual Variability in the Northern Hemisphere Winter Stratosphere

Observations show that the interannual variability of the Northern Hemisphere (NH) extratropical winter stratosphere is strongly correlated with the quasi-biennial oscillation (QBO) of tropical stratospheric winds, particularly during early winter. Most current general circulation models (GCMs) do not exhibit a QBO and therefore do not represent this important mode of tropical-extratropical interaction. In this study we examine the QBO-extratropical correlation using a 150-year GCM simulation in which a QBO occurs. Since no external forcings or interannual variations in sea surface temperatures are imposed, the modelled tropical-extratropical interactions represent an internal mode of atmospheric variability. The QBO itself is spontaneously forced by a combination of resolved and parameterized waves. The effects of this QBO on the climatological mean state and its interannual variability are considered, both by comparison with a control simulation (also 150 years in length, but with no QBO) and by compositing winters according to the phase of the QBO. Careful attention is given to the definition of QBO phase. Comparisons of the model results with observations (reanalysis data) are also made. QBO-induced changes in the climatological state of the model are found to have high statistical significance above the tropopause. In the extratropical winter stratosphere, these mean-state changes arise predominantly from the influence of the QBO on the propagation and dissipation of planetary-scale waves. This behaviour is shown to depend on the seasonal cycle, which argues for the usefulness of considering tropical-extratropical interactions in a GCM context. QBO influence on the interannual variability of the extratropical winter stratosphere is also seasonal, and the tropical-extratropical interaction is sensitive to the phase alignment of the QBO with respect to the annual cycle. This phase alignment is strongly affected by the seasonality of QBO phase transitions, which - due to the QBO being spontaneously generated, rather than having an imposed period - is somewhat realistic in the model. This leads to fluctuations in the strength of the modelled tropical-extratropical interaction occurring on a decadal timescale as an internal mode of atmospheric variability.

Keywords: Middle atmosphere dynamics
Quasi-biennial oscillation
Advisor: Shepherd, Theodore G.
Studies of Proteins that Regulate Melanin Synthesis and Distribution

Melanin is the major component of skin-, hair-, and eye pigmentation in mammals. Synthesis of melanin takes place in specialized organelles in melanocytes, called melanosomes. As melanosomes mature during pigment synthesis, they are transported towards the tips of dendrites in the melanocyte, and eventually transferred to neighbouring keratinocytes to distribute pigment throughout the skin. A large number of proteins regulate melanin synthesis and distribution. Over one hundred genes have been associated with coat colour mutations in mice, and many of these genes have also been identified in human pigmentation disorders. Other proteins involved in pigmentation are part of pathways that are not unique to pigmentation alone, such as the Ras/ERK pathway. In mouse B16 cells, cAMP stimulation leads to the upregulation of melanin synthesis and dendrite extension. However, cAMP also activates the Ras/ERK pathway in these cells, which, upon prolonged stimulation, leads to an inhibition of melanin synthesis and dendrite extension. Here I show that the protein CNrasGEF, which was previously identified in our lab, is responsible for cAMP-dependent Ras activation in B16 cells, and therefore a part of the negative regulatory pathway of melanogenesis. In order to find other proteins involved in pigmentation pathways, I have developed a method to detect melanosomes using Cellomics KineticScan (KSR) high-content image analysis. This system could potentially be used in a high-throughput RNA interference screen to identify proteins that affect melanosome formation or transport. However, in a pilot study it appeared that knockdown levels achieved upon transient transfection of knockdown constructs from a mouse shRNAmir library against selected targets were in many cases not sufficient to detect an effect on melanocytes, either by confocal microscopy, or by Cellomics KSR analysis. Further reduction of expression levels is necessary before this system can be scaled up to high-content/high-throughput identification of proteins involved in pigmentation.

Keywords: cell biology
melanin
pigmentation
RNAi
melanocyte
melanosome
Advisor: Rotin, Daniela