VictorJuiz/thesis huggingface dataset:
Control of Multiple Magnetic Microrobots for Biomedical Applications

My PhD dissertation takes an innovative approach to using the fundamental tools of robotics and control to solve the underactuated control problem of multiple magnetic microrobots for biomedical applications. The ability to use a team of microrobots to run a task can offer many advantages. However, the integration of on-board powering and sensing circuitry has not yet become possible at the microscale. Therefore, all magnetic microrobots (micro-agents) of the team have to share a single driving signal, whereas the system has multiple states to be independently controlled. Another major challenge with magnetic team control is that when multiple magnetic microrobots work together in close proximity, the agents tend to irreversibly stick together due to strong magnetic inter-agent forces. Previous studies either ignored the inter-agent forces by simply assuming their robots were far apart or treated these forces as disturbances without verifying the stability in close proximity. I solved for the first time this problem for a pair of magnetic agents in close proximity in 2D (and later in 3D) by making full use of inter-agent forces to control the motion of agents. In my approach, the positions of microrobots were controlled independently. As a practical demonstration, I showed for the first time that the motion of two functional magnetic microrobots as microgrippers can be controlled in 3D to run a task. Subsequently, to generalize the inter-agent force control to more agents, I introduced two solutions: 1) via optimization-based control (as a control technique), and 2) via motion planning and tracking (as a robotics technique). My PhD research enabled for the first time the collision-free autonomous navigation of a team of magnetic microrobots in close proximity. This solution allows magnetic microrobots to potentially act in a cluttered environment, such as the human body or microfluidic channels. To this end, I employed rapidly-exploring random tree (RRT) motion planning. I further incorporated the idea to run two practical demos that could be applied to cell testing/manipulation. The results of this PhD work can be applied to actuation and sensing, especially in the design of field-activated medical devices and for localized targeted drug delivery.

Keywords: 3D micromanipulation
Medical robotics
Microrobotics
Multi-agent control
Targeted cargo delivery
Underactuated robotics
Advisor: Diller, Eric
Binding and Uptake of Single and Dual-opsonized Target Particles by Macrophages

Phagocytosis is an evolutionarily conserved mechanism that serves as the first line of host defense in multicellular organisms. Phagocytes are exposed to a variety of ligands on heterogeneous target particles in vivo, and this recognition is driven by an extensive repertoire of receptors with distinct ligand specificity. However, our current view of phagocytosis has been shaped by studying individual receptor-ligand interactions and their downstream signaling pathways. This makes it physiologically relevant to observe the simultaneous engagement of multiple phagocytic receptors and the underlying coordination of downstream signaling pathways for efficient phagocytosis. Potential crosstalk between the two well-characterized opsonic receptors, FcγR and CR3, was briefly explored in the early 1970s, where macrophages were challenged with dual-opsonized target particles. However, subsequent studies on receptor crosstalk have been primarily restricted to the use of single opsonin on different target particles and typically presented at relatively high opsonin concentrations to induce maximal receptor engagement and signaling. Beyond validating these initial explorations on receptor crosstalk, we attempted to identify the early signaling mechanisms that underlie the binding and phagocytosis of dual-opsonized target particles (IgG and IgM/C3bi) during the simultaneous activation of both opsonic receptors, compared to single receptor activation. For this purpose, we used signaling protein inhibitor studies as well as live-cell brightfield and fluorescence imaging to fully understand the role of cytoskeletal elements and tyrosine kinases, F-actin dynamics, internalization kinetics and phagosome maturation rates for FcγRs and CR3. Importantly, opsonic receptors were studied together and in isolation, in the context of relatively low opsonin concentrations on target particles deemed optimal through flow cytometry analysis and particle binding assays. We saw enhanced particle binding and a synergistic effect on particle internalization when FcγRs and CR3 were simultaneously engaged with relatively low opsonin concentrations on target particles. Next, we investigated the early signaling requirements for the binding and uptake of single and dual-opsonized particles. Inhibition of early signaling and cytoskeletal molecules revealed a differential involvement of Src kinase for FcγRs- versus CR3- and dual receptor-mediated phagocytosis. Src activity recruits Syk kinase, and we observed intermediate levels of Syk phosphorylation in dual-opsonized particles compared to those opsonized with IgG or IgM/C3bi alone. These results likely correlate to the intermediate levels of F-actin that is recruited to sites of dual-opsonized particle uptake and underlie the notoriously delayed internalization of IgM/C3bi-opsonized target particles by macrophages.

Keywords: C3bi
crosstalk
IgG
macrophages
opsonin
phagocytosis
Advisor: Harrison, Rene
An Examination of Instagram Use and Body Image in a Sociocultural Model of Disordered Eating

Instagram has been identified as a particularly problematic social media site for emerging adults and has been linked to body image concerns (Fardouly, Willburger, Vartanian, 2018) and disordered eating (Holland Tiggemann, 2017; Turner Lefevre, 2017). There is limited research on the mechanisms that underlie the relationship between the use of image-based social networking sites, such as Instagram, and disordered eating. Phase I of the present study assessed thin-ideal internalization, appearance comparison, and body dissatisfaction as mediators of the relationship between frequency of overall Instagram use and disordered eating. One hundred and sixty women (ages 18-24) completed questionnaires regarding frequency of Instagram use, thin-ideal internalization, trait appearance comparison, body dissatisfaction, and disordered eating. Frequency of Instagram use and thin-ideal internalization were directly and separately associated with body dissatisfaction and disordered eating. The proposed mediators were not found to underlie the relationship between Instagram use and disordered eating. To date, there is limited research on how Instagram use impacts daily experiences of mood and body dissatisfaction, which has important implications for capturing potential negative effects of Instagram use on women’s lives. Daily changes in mood and body dissatisfaction might influence decisions to engage in weight control behaviours and cannot be fully captured through retrospective assessment. In order to make research-based recommendations regarding Instagram use, we need to know more about how it impacts users daily. In Phase II of the present study, ninety-two women (ages 18-24) who completed Phase I were randomly assigned to an experimental (Instagram) or control (Reddit) condition and completed daily measures of mood and body dissatisfaction pre- and post-Instagram (or Reddit) use. Body dissatisfaction increased significantly post-Instagram use. In addition, participants low on trait appearance comparison experienced greater positive affect post-social media exposure. Findings from the current study reveal the potentially harmful impact of brief exposures to Instagram use, specifically on how women feel about their bodies and, more broadly, how they feel in general. Policy implications include social media companies ensuring safer online platforms and educational initiatives aimed at increasing young women’s body satisfaction and reducing tendencies to engage in appearance comparisons while online.

Keywords: body image
disordered eating
emerging adulthood
Instagram
social media
thin-ideal internalization
Advisor: Goldstein, Abby L
Teachers Navigating Their Experiences of "Going Gradeless" in Ontario, Canada

The purpose of this qualitative study was to explore the experiences of Ontario secondary school teachers, navigating conceptual, pedagogical, cultural and political challenges as they shifted their practice from marks to "gradeless". Twenty-eight teachers from fifteen schools in seven school districts in the province of Ontario in Canada participated in semi-structured, face-to-face interviews. The 28 teachers in this study shared complex journeys of growth and innovation, providing feedback and supporting student learning through use of clear goals, and explicit communication of success criteria. The study provides models of gradeless classroom assessment that range from hidden or deferred marks to four-level rubrics to single-point rubrics to rich descriptive feedback, and from task criteria to curriculum expectations to overarching learning goals. The interviewees described concepts of assessment that centre on the learner, and pedagogical approaches that support student voice and choice. They experienced challenges from the cultural expectations of students, parents and colleagues, but none of the interviewees were restricted by policy requirements from making the changes in assessment practice that they identified as "gradeless", and which serve to support the learning of their students. This study suggests that teachers' conceptual understanding begins with their personal experiences of assessment, is developed through the pedagogy they employ, the cultural influences on their professional and school community, and the policy that underpins their practice. The study demonstrates that when teachers discover processes that improve the achievement of their students, they will persist with the new process even if faced with strong cultural pressure. It suggests that greater communication to, and education of, the school community, parents and students is needed to shift cultural expectations of assessment. The study reveals that given clear policy, grounded in research, teachers can develop stronger conceptual understanding of assessment, and are empowered to move forward, even in the face of strong cultural pressures. Implications for future research in classroom assessment, teacher change, and 21st century learning are further discussed.

Keywords: assessment
competency
feedback
gradeless
Growing Success
teacher
Advisor: Campbell, Carol
Change for Orchestra and Soprano

“Change” is a 16-minute composition for soprano soloist and orchestra. It uses shifting timbres, colours and the cyclic use of motives and harmonic ideas to evoke notions of the resiliency of human spirit. “Change” sets Raymond Knister’s poem of the same title, which is in the public domain. The orchestral instrumentation comprises of: piccolo, two flutes, two oboe, three clarinets (third double bass clarinet), three bassoons; four horns, two trumpets in B flat, two tenor trombones, bass trombone, tuba; timpani, three percussion (bowed vibraphone, bass drum, tubular bells, bowed crotales, glockenspiel, marimba, handbells); harp, and strings (suggested 16 14 10 10 6). “Change” uses a linear form in seven sections (relating to the structure of the text). The work in some sense is one large blossoming and decaying musical gesture; the composition slowly develops into a full tutti musical gesture which then gradually decays away into similar music to that which opened the work. “Change” explores various changes in orchestration and colour with most sections of the work exploring a variation in timbre or instrumentation. The music moves from hushed delicate gestures to a darker rich harp and marimba colour, and then to a full shimmering brass hue. The music shifts away from the brass texture to a more sparse colour; glissandi trombones, delicate string writing on harmonics with fleeting flute flutterings and lip bends above. Then the music beings to combine instrumental families as it builds to tutti writing for the orchestra. A chorale melody begins to drive the music to the climactic phrases. The piece ends in a similar style as it began, with delicate, hushed gestures, though developed through inversion and slight variations in retrograde: motifs are re-interpolated and transformed as if upon reflection they have grown and evolved, akin to how humans grow and reflect at certain stages in our lives; we may continue to live a similar life as we did years ago, but we change and reorientate ourselves. The music is left open-ended, peacefully evaporating into nothing, it’s as if moments of our life pass us by and are now only a memory.

Keywords: Orchestra
Orchestra and Voice
Voice
Advisor: Hatzis, Christos
Palej, Norbert
Manganese-based Positive-contrast MRI for Non-invasive Monitoring of Biomaterials and Cells in Tissue Engineering

Cells and scaffolds are the pillars of tissue engineering and regenerative medicine. They have the potential to regenerate any tissue or organ; however, a major unmet challenge limiting their clinical translation is the absence of non-invasive technologies for spatial and temporal tracking of implant fate in deep tissue and with high spatial resolution. Contrast-enhanced magnetic resonance imaging (CE-MRI) is highly suited for this task; however, current methods suffer from contrast agent toxicity or fail to provide longitudinal monitoring with high sensitivity and specificity. To address this need, this thesis aims to further develop positive-contrast MRI with manganese (Mn), an essential micronutrient, for in vivo imaging and tracking of cells and scaffolds. To image scaffolds and track their fate, biomaterials were labelled with manganese porphyrin (MnP) contrast agents, which exhibit anomalously high T1 relaxivity and form stable Mn-chelates. Atypical conjugation approaches were explored to achieve facile, biocompatible and efficient labelling of a variety of decellularized extracellular matrix and collagen-based scaffolds including injectable hydrogels, tissue grafts and whole organ constructs. This thesis demonstrates the first report to track these materials in vivo with CE-MRI and the potential for quantitative tracking of degradation over time. For non-invasive cellular MRI, both direct and indirect labelling techniques with Mn-based agents were designed to guide cell injection in real-time and probe cell fate longitudinally. Firstly, the utility of a commercially scalable MnP agent for safe and highly efficient labelling of human embryonic stem cells was demonstrated ex vivo. MR imaging of the labelled cells permitted detection of early cell fate and injection success in vivo. Secondly, to track cells longitudinally with high sensitivity and specificity, a reporter gene platform, bright-ferritin, was designed to produce endogenous T1-cellular contrast by the formation of manganese-ferritin nanoparticles intracellularly. The bright-ferritin system exhibited superior relaxivity and contrast generation in vitro and in vivo over conventional T2 iron-ferritin systems and T1 manganese-transporter systems. This bright-ferritin platform has the potential for on-demand, longitudinal, and sensitive, quantitative cell-tracking in vivo. Overall, this body of work demonstrates the utility of Mn-based bright-MRI for the assessment of scaffold and cell implantations.

Keywords: Cell Tracking
Magnetic Resonance Imaging
Manganese
Porphyrin
Scaffold Monitoring
Tissue Engineering
Advisor: Cheng, Hai-Ling Margaret
Agrarian Social Structures, Insurgent Embeddedness, and State Expansion: Evidence from Colombia

In the context of civil war, the efficacy of counterinsurgency strategies varies dramatically across space and time. While this process of state expansion produces different outcomes between different national level cases, it also engenders diverging results at the sub-national level. Counterinsurgent responses can lead to notable reductions in violence, an achievement mirrored by improved stability and order in contested zones. Quite frequently, however, violence will increase as stability and order worsen. The fact that state expansion into contested spaces produces such different results across areas of extremely close proximity begs the following questions: How is the state able to establish control, and by extension order, in some contested spaces more easily than in others? Conversely, what enables armed non-state actors to withstand and survive this massive onslaught in some cases, while failing elsewhere? Since 2002, the Colombian state has embarked upon a massive state expansion project in many volatile areas of the country that were previously controlled and governed by armed non-state actors. This projection of military, bureaucratic, and economic power into these contested spaces has not always brought peace and stability with it, casting into doubt the efficacy of the central government’s larger attempt at state expansion. This dissertation explores the above research puzzle through a comparative historical analysis of two sub-national counterinsurgency laboratories in rural Colombia which demonstrate enormous variation in counterinsurgent outcomes: Montes de María and Arauca. I provide a longitudinal qualitative model that highlights the importance of pre-existing agrarian social structures on the process of insurgent institutionalization in these spaces, or the ability of these armed non-state actors to embed themselves in rural civilian communities. I find that those actors that are better able to appropriate local cleavages in favor of specific constituencies will achieve a higher level of embeddedness in these spaces and thus possess a higher level of populational control over civilians. These advantages are crucial for insurgents during periods of state expansion, as they are better equipped to protect civilian populations from counterinsurgent violence and to prevent potential defection to their rivals.

Keywords: Civil War
Colombia
Counterinsurgency
Advisor: Handley, Antoinette
Sarcomere Structure in Drosophila Musculature Studied with Polarimetric Second Harmonic Generation Microscopy

Nonlinear optical microscopy is a powerful imaging modality that enables label-free imaging with endogenous signal generated from the protein arrays that constitute biological structures and can be used to reveal structural and functional information in a system. Second Harmonic Generation (SHG) Microscopy does not require photon absorption for signal generation, providing the added benefit of having a significantly reduced photo-bleaching effect. SHG signal is observed in non-centrosymmetric molecules like myosin and can be used to directly visualize muscle structure. Additionally, polarimetric SHG imaging allows for the quantification of the sample’s microstructure. Muscle function depends on highly ordered protein complexes. UNC45 is a USC chaperone necessary for myosin incorporation into thick filaments. UNC45 is expressed throughout the entire Drosophila life cycle and has been shown to be important during late embryogenesis when initial muscle development occurs. However, the effects of UNC45 manipulation at later developmental times have not yet been studied. The focus of my thesis is to utilize both traditional and nonlinear optical microscopy to investigate changes in myosin filament organization and interactions between protein complexes and how it relates to muscle function. UNC45 was knocked down with RNAi in a way that permitted survival to the pupal stage. Immunofluorescence and electron microscopy imaging showed diminished expression of UNC45 and disorganized myosin filaments and Z-disk proteins. Changes in synaptic physiology and impaired locomotor behavior were also observed. These observations were confirmed and further analyzed on a whole-larval scale using the newly developed wide-field SHG microscopy, revealing changes in the striated pattern of somatic muscles and a reduced signal intensity. Polarimetric parameters were used to study chiral and achiral properties of larval muscles. R- and C-ratios were determined using scanning SHG microscopy. R-ratio values were higher in the mutant compared to control, suggesting that a second protein structure was producing a second harmonic response. CD image and C-ratio revealed the bimodal distribution of myosin filaments and changes in chiral structure in UNC45 knockdown larva. Overall, this technique provides insight on how second harmonic properties changes with myosin filament structure. This opens new perspective to study the dynamic properties of muscle structure.

Keywords: Drosophila Melanogaster
Microscopy
Muscle
Myosin
SHG
Advisor: Stewart, Bryan A
Barzda, Virginijus
Investigating the Association between Iron and Breast Cancer Risk and Factors Associated with Iron Status among Canadian Women

Iron is an essential nutrient but also a potent contributor to oxidative stress. Changes in iron status across reproductive stages may have important implications for women’s health. This dissertation investigates the role of iron as a potential risk factor for breast cancer and assesses determinants of body iron status among Canadian women. First, a systematic review and meta-analysis was conducted to evaluate associations between iron and breast cancer risk. When comparing the highest vs. lowest category, heme iron intake and serum iron, but not other measures of iron intake or body iron status, were positively associated with breast cancer risk, with pooled relative risks of 1.12 (95% CI: 1.04–1.22) and 1.22 (95% CI: 1.01–1.47), respectively. Nonlinear dose-response was also observed. Second, in a population-based case-control study of Ontario women (3030 cases, 3402 controls), iron intake was not associated with overall breast cancer risk. Among premenopausal women, higher intakes of total, dietary, and dietary nonheme iron were associated with increased risk of hormone receptor-negative breast cancer. Among postmenopausal women, heme iron and supplemental iron were positively and inversely associated with breast cancer risk, respectively. Among women providing DNA (1696 cases, 1761 controls), those with genotypes resulting in reduced antioxidant capacity, particularly glutathione S-transferase deletions, were most susceptible to the effects of higher dietary iron intake. Third, based on nationally representative data from the Canadian Health Measures Survey, iron deficiency affects 16% and 4% of pre- and postmenopausal women, respectively, whereas 21% of postmenopausal women have elevated iron stores as defined by serum ferritin levels. Age, East/Southeast Asian (vs. White) race/ethnicity, alcohol consumption, and red meat (main source of heme iron) consumption were positively associated with serum ferritin in both pre- and postmenopausal women; aspirin use and dairy consumption were inversely associated with serum ferritin in postmenopausal women. Overall, these results suggest that heme iron may be a major contributor to body iron stores and a potential risk factor for breast cancer, especially among postmenopausal women. This dissertation provides additional insights into iron’s role in breast cancer etiology and highlights the importance of considering elevated iron stores in addition to iron deficiency.

Keywords: breast cancer
heme iron
iron intake
iron status
serum ferritin
Advisor: Cotterchio, Michelle