VictorJuiz/thesis huggingface dataset:
Linking Nuclear Mechanotransduction and Epigenetics in Morphogenesis

Organ primordia shape is important for pattern formation and organ function. Morphogenesis generates forces through cellular rearrangements, proliferation, and shape change. These forces are felt by the cells of each tissue and are transmitted through them via the cytoskeleton. In addition to shaping tissues during development, emerging research suggests that mechanical forces play a role in gene expression. A traditional view of mechanotransduction is that extracellular and intracellular forces elicit a biochemical response, transmitting information to the nucleus. Intriguingly, evidencein vitro shows that nuclear strain can mechanically influence transcription by deforming the chromatin. Forces transmitted from the cytoskeleton to the nuclear lamina via the LINC complex, a direct mechanical connection, have the potential to efficiently couple morphogenesis with gene expression by pulling the genome to activate genome topology sensitive genes like the HoxA/HoxD clusters. To facilitate the investigation of potential nuclear mechanotransduction in vivo, I generated transgenic FRET‐based tension sensors. I utilized these sensors within the LINC complex protein, Nesprin2G, which links actin to SUN proteins, and the inner nuclear membrane protein NEMP1 which joins the nuclear lamina to chromatin to measure nuclear force transmission in living tissues. I tested invivo the responsiveness of each conditionally expressed sensor to physical and chemical manipulation of the mouse embryo. I helped develop software (FLIMvivo) to resolve challenges uniquely abundant with in vivo fluorescence lifetime imaging analysis. I found that force transmission to the nuclear interior indeed varies by tissue in the developing forelimb. Further, I used exogenous force via atomic force microscopy to modulate HoxA expression in live embryo forelimbs and have adapted a recently developed 3D stochastic reconstruction microscopy (3D‐STORM) OligoPaint approach to enable super resolution acquisition of chromatin topology at the single gene locus scale under differing cellular force regimes. These tools will be useful to measure the extent to which the genome and gene expression are influenced directly by the forces felt by cells not only during limb bud development, but also in other developmental processes, cancer, and disease.

Keywords: development
epigenetics
limbbud
mechanotransduction
mouse
nucleus
Advisor: Hopyan, Sevan
Stress Corrosion Cracking and Pitting Corrosion of Carbon Steel in Ethanolic Environments

Several studies have recently claimed that the Stress Corrosion Cracking (SCC) of carbon steel in ethanolic environments occurs by an anodic dissolution mechanism, but the exact mechanism is not well understood. In this research project, potentiostatic slow strain rate testing was conducted on SCC test specimens exposed to ethanolic environments prepared from pure dehydrated ethanol. Cracks of various types—intergranular and transgranular open cracks, and sharp closed transgranular cracks—were found by altering several testing parameters. The presence of chloride was found to be essential for crack initiation. SEM examination indicated that an “anodic” cracking mechanism, not necessarily slip-dissolution, was most likely operating at high elongations. Sharp closed transgranular cracks, with a maximum depth of 4 µm, were detected at elongations below 3% in ethanol solutions containing 2.5 mM LiCl. A focused ion beam was used to extract the tip of such a transgranular crack tip for analytical transmission electron microscopy using electron energy loss spectroscopy, which confirmed that the crack was in a ferrite grain. The sharp closed transgranular cracks seem to ally with the cracks observed in CO-CO2-H2O and anhydrous ammonia environments, which are proposed to grow by unique cleavage mechanisms. The possibility of embrittlement by carbon interstitials produced by ethanol electro-oxidation within the crack is discussed.The similarities of ethanol SCC and CO-CO2-H2O SCC prompted the investigation of the possibility of ethanol electrochemical oxidation into CO on ferrite (Fe) and cementite (Fe3C) surfaces. Density functional theory (DFT) computations on (110) surfaces reveal that the catalytic activity of Fe and Fe3C through the α dehydrogenation pathway can significantly reduce the energy barrier of electro-oxidation of ethanol and production of CO to 0.575 and 0.480 eV vs SHE, respectively. These first principles calculations indicate that at the anodic potentials applied during potentiostatic slow strain rate testing (SSRT), ethanol electro-oxidation to CO is thermodynamically viable on carbon steel, giving further credit to the involvement of cleavage type SCC of carbon steel in ethanolic environments.

Keywords: DFT modelling
Ethanol
Pitting Corrosion
Stress Corrosion Cracking
Advisor: Newman, Roger
Precise Larmor Time Measurements of a Tunneling Bose-Einstein Condensate

This dissertation presents precise tunneling time measurements of ultracold rubidium atoms tunneling through a narrow optical barrier. A pseudo-magnetic field localized to the barrier region causes the spins of the atoms to rotate while inside the barrier and the rotation is used to define a time of interaction. We observe that tunneling atoms spend less time interacting with the barrier as their energy is decreased below the barrier height. Furthermore, we find that atoms spend less time tunneling through higher barriers. Both observations confirm longstanding predictions about tunneling times. We also discover spin waves generated in the reflected cloud of atoms after collision with the barrier. Atomic interactions in the high-density regions of the reflected cloud drive additional spin rotations. We study this effect and find that it becomes the dominant contributor to spin rotations when the measurement of time spent inside the barrier is `strong'.

Keywords: Bose-Einstein Condensate
Cold atoms
Tunneling
Tunneling time
Weak Measurement
Advisor: Steinberg, Aephraim M
The Influence of Aquaculture on Marine Microbiota and Pathogen Communities in a British Columbia Coastal Ecosystem

The productivity of wild-capture fisheries has long plateaued and global dependence on aquaculture is progressively increasing. Despite the perception that substituting wild caught seafood for domestic production benefits the conservation of wild populations through decreased fishing pressure, this is frequently not the case. Aquaculture can challenge the conservation of wild populations via the harvest of wild fish for feed, degradation of wild habitat, and by facilitating the spread of infectious disease. This thesis examines how aquaculture facilities influence microparasite transmission dynamics and the potential consequences for co-occurring wild species. I investigate these topics in coastal British Columbia, Canada, where wild Pacific salmon populations encounter open-net salmon farms along their migration routes. In chapter 2, I use seawater filtration and quantitative PCR (qPCR) to quantify the presence of DNA for 39 viral, bacterial, and eukaryotic microparasite species in the marine environment in relation to active Atlantic salmon farms. I show that the odds of encountering an infectious agent are 2.72 times higher at active salmon farms relative to inactive control sites. In chapter 3, I evaluate Atlantic salmon eDNA dispersal at 2m and 8m depths throughout 55 km of narrow migratory channels, in relation to four Atlantic salmon farms. I show that long distance dispersal (1.5 km – 3.9 km) occurs, and the spatial extent of environmental eDNA dispersal depends primarily on current velocity and depth. In chapter 4, I evaluate environmental microbe communities using deep amplicon sequencing to evaluate variation in community structure among 57 salmon farm tenures in relation to aquaculture activity, temperature, salinity, turbidity, and multiple scales of spatial predictors. The results from chapter 4 show that the effect of salmon farm activity on the marine microbiota was detectable but small relative to environmental variation and spatial structure although three bacterial Orders: Flavobacteriales, Rhodobacterales, and Alteromonadales, stood out as strongly positively correlated with salmon farm activity. The sustainability of aquaculture and the persistence of many wild populations will depend on our understanding of the local and regional influences of domestic reservoirs on microparasite transmission and our ability to develop integrated control measures to limit transmission among wild populations.

Keywords: aquaculture
environmental dispersal
environmental DNA
environmental impacts
infectious disease
Pacific salmon
Advisor: Krkošek, Martin
Short, Steven M
Cluster Structure for Mirkovic-Vilonen Cycles and Polytopes

We look at the Mirkovic-Vilonen (MV) basis for semisimple Lie algebras and compare this to the associated cluster algebra to investigate the question of whether or not the cluster variables are in the MV basis. We begin with finding analogues of the cluster structure among MV cycles and MV polytopes. In particular, we show the exchange relations correspond to an equation involving MV polytopes. We extend a result of Baumann-Kamnitzer in relating valuations of an MV cycle and the dimension of homomorphism spaces of its associated preprojective algebra module. In doing so, we are able to give a partial result for an exchange relation involving MV cycles in low dimensions. In joint work with Dranowski and Kamnitzer, we present a way to calculate the fusion product of MV cycles in type A through a generalization of the Mirkovic-Vybornov isomorphism. Finally, we finish with examining the A3 example and show directly that the cluster variables in this case are in the MV basis.

Keywords: cluster algebras
Mirkovic-Vilonen
Advisor: Kamnitzer, Joel
Sqilxw Educator Rising: Sqilxw Educator Rising: Relationality as Methodology in a Social Work Abolitionist Framework

AbstractWai, iskwis (my name is), Percy Lezard. Sqilxw ways, personal introductions come before any other words. I am outma sqilxw I was born into a family of sexʷwrmin̓ (firekeepers). This research demonstrates how I as a sqilxw stamya? educator have been able to survive and thrive, through my sqilxw identity and Indigenous knowledges, in mainstream post-secondary education institutions. I have used myself as both the subject and researcher within the social context of post-secondary social work settings, with an insider’s vantage point to chronicle my own pedagogical transition, using the qualitative methodology of relationality. Through my interpretations and reflections about two post-secondary programs, I use comparison to highlight the complexities of their strengths and inadequacies. This work includes my account as an Indigenous scholar working within a college program grounded in feminist theory, and a university department grounded in an anti-oppression/anti-racism framework. It explores experiences of anti-Indigenous racism, cis-sexism, pushback for my position of solidarity with Black liberation, and oppressions within a disability justice framework. Using the methodology of relationality, I share the experiences I have encountered and the problems I have faced, to facilitate an understanding of the processes of transition. As the genre of qualitative research brings the reader closer to the subculture studied through the experiences of the author, my work serves to provide an evaluation and insights into the cultures of these two learning environments. Data gathering consisted of a reflexive journal, my personal calendar, faculty agendas, staff memos, and reflective analysis. As well, in each of the institutions, I was able to gather support and insight through ceremony and interactions with Knowledge Keepers and Elders. In this way, I was able to reflect upon teachings and to apply Indigenous knowledges to my work. These research tools were used to capture the experiences of my transition. The results of this study were expressed in a personal narrative that comprises of Section 1: Situation, Owing, Questioning. Section 2: How did I come to formulating an Abolitionist Social Work Framework? Section 3: History of Social Work Harms. Section 4: Alternatives Section 5: Vision and closing remarks.

Keywords: 2 Spirit
Abolition
Harm Reduction
Indigenous Knowledge
Radical Relationality
Transgender
Advisor: Walcott, Rinaldo
Site-specific Antibody-Polymer Conjugates Synthesized by Enzymatic Methods

Antibody conjugates have typically been prepared by random conjugation to lysine amino groups. However, the effects of antibody conjugation remain unclear and are difficult to predict. Site-specific conjugation methods that control the conjugation site have yielded antibody-polymer conjugates with improved properties compared to their analogue prepared by random lysine conjugation. The preparation of site-specific antibody-polymer conjugates is challenging, as few methods are suited for conjugating large payloads with multiple chemical functionalities. My studies focused on developing a method to prepare site-specific antibody-polymer conjugates using microbial transglutaminase (mTG) and characterizing these conjugates. I also applied an existing method, SiteClick™ conjugation, to prepare conjugates for in vivo studies.In Chapter 3, I describe the synthesis and characterization of 11 polyglutamide-based polymers, including metal-chelating polymers (MCPs) for developing a conjugation method based on mTG, and for use with SiteClick™ conjugation. These polymers also included a series of D-enantiomers to examine the enantiopurity of the polyglutamide MCP. In Chapter 4, I describe a method to site-specifically conjugate polymers to proteins using mTG. I describe the conjugation of an H2N-PEG-oligonucleotide and MCP to two antibody fragments, a VHH fragment that binds to programmed death ligand 1, and a Fab fragment that binds to frizzled-2. For the Fab conjugates, the conjugation site was characterized by mass spectrometry experiments which confirmed that the mTG conjugation was site-specific. In Chapter 5, I examined the properties of conjugates prepared by site-specific mTG conjugation and random lysine conjugation. I analyzed for changes to various properties by differential scanning fluorimetry, biolayer interferometry, and cell-binding assays. The site-specific conjugate showed high affinity to the antigen and ca. 4-fold lower non-specific binding to two cell lines compared to the random conjugate. Site-specific conjugation appeared to reduce non-specific binding associated with random lysine conjugation of the polymer. In Chapter 6, I describe experiments that investigated the SiteClick™ method to conjugate an MCP to a therapeutic antibody, Panitumumab, to test whether biodistribution is improved. I optimized the method and overcame purification issues found in previous attempts to conjugate related polymers. I also analyzed the results obtained with our collaborators and compared them to previous results.

Keywords: antibody conjugates
bioconjugation
drug delivery
enzyme
radioimmunotherapy
site-specific conjugation
Advisor: Winnik, Mitchell A.
A Search for the H mm Decay and a Measurement of the Mass of the Higgs Boson using H- 4l Events with 139 fb-1 of Proton-proton Collision Data Collected by the ATLAS Experiment

Using a dataset collected with the ATLAS detector during run-2 of the Large Hadron Collider, a search for the decay of the Higgs boson to two muons and a measurement of its mass are presented. Common to both measurements, an overview of the theoretical background, the Large Hadron Collider, the ATLAS experiment and particle reconstruction algorithms is provided. When the work in this thesis was performed, no evidence for the H ! μμ decay had been observed. The search presented in this thesis uses multivariate classification algorithms to classify events and maximize the expected statistical significance of the result. A signal excess of 2.0 was measured when testing the background-only (no H ! μμ) hypothesis and the signal strength was found to be in agreement with the Standard Model prediction, to within statistical and systematic uncertainties. The measurement of the Higgs boson’s mass was performed using H ! 4l events. Although the measurement of the Higgs boson’s mass has been performed in the same channel by the ATLAS collaboration in the past, the run-2 dataset used in this thesis is approximately four times larger than before, which is expected to reduce the uncertainty by a factor of two. The measurement uses multivariate machine learning techniques to discriminate signal and background events and exploit the inhomogeneous resolution of the ATLAS detector. The measurement is yet to be performed on data, but the expected uncertainty is ± 0.19 (± 0.18 Stat only) GeV.

Keywords: ATLAS Detector
Higgs boson
Large Hadron Collider
Advisor: Savard, Pierre
Colloidal Quantum Dot Surface Modification for Emerging Optoelectronic Applications

Colloidal quantum dots (CQDs) have received attention for their potential in optoelectronic applications. Their solution-processing and tuning beyond silicon offer an alternative to standard crystalline materials and enable integration with numerous substrates, including flexible ones. In this thesis I seek to modify the CQD surface to improve CQD transport and device performance.I begin by studying the limitations in the best prior PbS CQD solar cells, finding that inefficient charge collection limits performance. I found this is caused by a chemical alteration of the active layer following the deposition of the hole transport layer (HTL) using the standard thiol-based ligand exchange. I then develop a new ligand exchange, obtaining a novel HTL material, chemically orthogonal to the underlying active layer, which minimizes interface defects and improves the charge collection probability at the back interface from 50% to ~100%. Improved transport enables increased fill factor and solar cell efficiency (from 12.2% to 13%). Next, I study the effect of the defects in the HTL: the rapid thiol-based HTL ligand exchange causes agglomeration, defects and incomplete passivation. I develop a kinetically-controlled exchange via solvent engineering, improving passivation and order in the final solid, resulting in 13.3% solar cell efficiency (vs. 12.5% for standard device). Finally, I apply the knowledge gained on surface modification to infrared CQD photodetectors. At the time I started my Ph.D., infrared PbS CQD photodetectors failed to combine quantum efficiency, sensitivity and speed and the external quantum efficiency in the IR was limited to 15%. I found that the CQD shape, determined by synthesis thermodynamic, is responsible for weak coupling, detrimental for device performance. I employed colloidal atomic layer deposition to rationally modify the CQD surface and obtain a shape not achievable with synthesis alone, favoring CQD coupling. The resulting CQD solids show one order of magnitude increase in hole mobility, resulting in 70% external quantum efficiency in the IR (vs. 45% for standard device), and record-performing solution-processed short-wavelength infrared photodetectors. The studies in this thesis improve the understanding of CQD surface, surface modification and its effect on transport, offering routes to improve CQD optoelectronic device performance.

Keywords: Materials science
Optoelctronics
Photodetector
Quantum dot
Solar cell
Surface modification
Advisor: Sargent, Edward H.
Exploring STEM in a University Outreach Setting

STEM literature has proliferated in recent decades. However, few studies consider the setting of university-based STEM outreach programs - programs that negotiate the border of informal and formal learning. In this ethnographic case study, I explore a STEM summer camp at a large Canadian university via two cohorts of learners: (15 elementary school age) campers and (14 undergraduate and graduate student) instructors. The research questions ask: What are the motivations for participating in a university STEM outreach program? How do participants perceive or understand STEM, and its purposes, in a university STEM outreach program? How do participants experience teaching and learning in a university STEM outreach program? Data collection methods included semi-structured interviews, questionnaires, reflections, observations, artifacts, and images. Inductive and deductive analysis are used to identify thematic categories. The findings identify similarities in the interests and aspirations of cohorts that underpin common experiential, preparatory, and learning motivations. Both cohorts are motivated to learn about science and engineering; instructors anticipate teaching. Perceptions of STEM prioritize and conflate science and engineering and view STEM as providing an understanding of the world, affecting change, and serving personal goals. STEM is seen as interdisciplinary, with engineering design informing how it is organized, described, and conveyed. STEM is characterized as hands-on, fun, easy, and broadly transferrable. It is positioned as a reciprocal fund of knowledge; a fund of experience that is built, valued, and leveraged. The facilitation of teaching and learning in the outreach program includes tending to the management of the physical camp space, the relational camp space, and leading hands-on, design-oriented activities. Findings suggest that the outreach program is a site of learning shaped for and by its participants. STEM learning is mediated through engineering design and constructionist approaches that prioritize participant funds of knowledge, in a meaningful third space. This offers a reconceptualization of STEM where engineering is present as content, context, and pedagogy; a perspective that broadens and deepens the connections to be made across practices in outreach, engineering, and education so critical to this work. The thesis concludes with implications and recommendations for theory and practice.

Keywords: constructionist
engineering education
funds of knowledge
outreach
STEM education
third space
Advisor: Pedretti, Erminia