VictorJuiz/thesis huggingface dataset:
Rare Stellar Populations in the Magellanic Clouds: Identification of Super-Asymptotic Giant Branch Star and Yellow Supergiant Binary Candidates

In this thesis, I present a series of observational studies in which I identify and characterize multiple new populations of massive stars in rare or elusive phases of stellar evolution---thereby demonstrating the power of large surveys and systematic observation campaigns to constrain models of massive star evolution. First, I investigate the true nature of the peculiar star HV2112. Previous studies have identified HV2112 as the first Thorne-Zytkow object (TZO) candidate --- supergiants with with neutron star cores. However, others have argued its properties are more consistent with that of a super asymptotic giant branch star (sAGB), which are the most massive stars that do not undergo iron core collapse. I characterized the extreme variability of HV2112 and identified a population of 11 stars that possessed the same photometric and variability properties as HV2112. I derived physical properties and rates to uncover the true identity of this population. I find that all analyses are consistent with predictions for sAGB stars, while HV2112 itself remains ambiguous. This increases the population of sAGB star candidates by an order of magnitude, providing important information on the transition between low and high mass stellar evolution. I also demonstrate the feasibility of identifying yellow supergiant (YSG) binary systems using photometric data. Binarity plays a vital role in the evolution of massive stars: ~70% of massive stars should interact with a companion. Observational constraints on massive star binary populations in therefore crucial, but the binary fraction of YSGs is poorly-constrained. I demonstrate that optical photometry can be effective at discriminating between single YSGs and YSG+B-star binaries cooler YSG temperatures, while UV photometry can be effectively used to probe systems with hotter YSGs. I use these methods to identify hundreds of YSGs in the Magellanic Clouds that show signs of a blue/UV photometric excess. This demonstrates that optical/UV photometry can be a robust way to obtain better constraints on YSG binarity using large photometric surveys. Spectroscopic follow-up will still be necessary to understand the true nature of these systems, thus I also present some predictions and a pilot study of optical spectroscopy.

Keywords: binary stars
massive stars
peculiar stars
stellar astrophysics
stellar populations
Advisor: Drout, Maria R
Gaensler, Bryan M
A Combined Cell and Gene Therapy to Treat Retinitis Pigmentosa

Retinitis pigmentosa (RP) is an inherited retinal degenerative disease that causes severe vision loss or blindness. It is a genetically heterogeneous disease that is driven by any single deleterious mutation in over 70 identified genes. Gene therapy to prevent vision loss is showing promise in the clinic, but this therapeutic strategy poses risks of oncogenicity and genotoxicity. Moreover, developing new treatments to address each mutation is an infeasible approach. Cell therapy to restore vision, such as photoreceptor transplantation to replace those that have been lost, is hindered by poor cell survival. Also, the inadequate integration of cells into the neural retina severely diminishes its therapeutic potential. Alternatively, recombinant proteins can be used to prevent photoreceptor degeneration, but their short half-lives demand frequent redosing which may lead to complications of the eye. To address these limitations, I developed a combined cell and gene therapy that is expected to protect photoreceptors independent of the genetic cause. Human embryonic stem cells were genetically engineered to secrete soluble CX3CL1, a ligand that has been shown to preserve photoreceptors and their function in mouse models of RP by inhibiting microglia activation – a non-cell autonomous mechanism of photoreceptor degeneration. These cells were differentiated into eye-resident retinal pigment epithelium cells, which have been shown to be quiescent, long-lived, and safe in the human subretinal space. After the subretinal delivery of these cells into a mouse model of RP, I show that rod photoreceptors are protected in a local-acting manner within a two-week interval post-treatment. Finally, this thesis explores how genome editing can be used to ensure stable transgene expression in therapeutic cells, improve cell therapy safety, and prevent allogeneic cell rejection without systemic immunosuppression of the host. This novel therapeutic strategy could pave the way for the treatment of other neurodegenerative diseases, as exogenous CX3CL1 has been demonstrated to be an effective therapeutic in animal models of cerebral ischemia, Parkinson’s disease, and Alzheimer’s disease.

Keywords: Allogeneic Cell Tolerance
Cell Therapy
Genome Engineering
Retinitis Pigmentosa
Vision Loss
Advisor: Nagy, Andras
Geometry of Leaf Spaces of Singular Foliations

This thesis has three parts. First, we survey Stefan and Sussmann's work on singular foliations, highlighting diffeological objects that arise. We then propose a transverse equivalence of singular foliations, and show: equivalent foliations have diffeomorphic leaf spaces; the converse need not hold; and regular foliations with Hausdorff holonomy groupoid are transverse equivalent if and only if they are Morita equivalent. Second, we show that for a singular foliation (M,F), the quotient π : M → M/F induces an isomorphism π* : Ω*(M/F) → Ω*(M,F; b), where Ω*(M,F; b) denotes the complex of F-basic forms on M, when: F is regular; when the union of k-leaves is a diffeological submanifold, for all k; and when π* is an isomorphism if we excise the 0-leaves. Finally, we introduce diffeological quasifolds and quasifold groupoids. A quasifold is locally modelled by the affine action of countable groups Γ on ℝⁿ. When the Γ are finite, we recover orbifolds. We show that the categories of diffeological quasifolds and quasifold groupoids are equivalent, when we restrict the arrows to local diffeomorphisms and locally invertible bibundles, respectively.

Keywords: Basic cohomology
Diffeology
Lie Groupoids
Quasifolds
Singular foliations
Advisor: Karshon, Yael
Synthesis and Characterization of Electrodeposited Nanocrystalline Medium- and High-Entropy Alloys

This thesis outlines the first systematic study on the feasibility of using electrodeposition to synthesize nanocrystalline medium- and high-entropy alloys (M/HEAs, alloys made up of 3–4 and 5+ elements, respectively), towards producing stronger and more thermally stable materials. A graduated three-stage experimental approach was employed to incrementally study and assess electroplating systems of increasing complexity, building from ternary (NiFeCo) to quaternary (NiFeCoW and NiFeCoMo), and finally quinary (NiFeCoMoW) systems. These candidate systems were identified from a novel set of material selection guidelines developed for the electrodeposition of M/HEAs. To this end, an ease of codeposition parameter and grading scheme was employed to examine alloy bases in existing literature. Fully dense, high-quality, near-equimolar deposits with nanocrystalline and/or amorphous structures were successfully synthesized in each system from aqueous electrolytes. Evaluating their thermal stability revealed incremental improvements with increasing alloy complexity, as compared to their binary and pure metal counterparts: from ~100°C in Ni and ~250°C in NiCo, to ~300°C in NiFeCo and ~500°C in NiFeCo(W/Mo). Heightened stability was also reflected by improvements in the activation energy for grain growth, measuring up to 3.1 eV in NiFeCoW, compared to 1.3 eV in nanocrystalline Ni. However, the theory of improved stability with increasing number of elements was not observed, as NiFeCoMoW displayed near identical performance to its quaternary subsets. Mechanical testing via nanoindentation revealed a regular-to-inverse Hall-Petch transition in each of the annealed M/HEAs, coupled with grain-boundary relaxation processes at low annealing temperatures (≤400°C). Again, improved performance with increasing alloy complexity was not observed, as the as-deposited hardness and elastic modulus of each electrodeposited M/HEA was comparable to those of less compositionally complex counterparts. However, the advantage of these M/HEAs was showcased in their post-processed performance, whereupon nanograin nucleation in the NiFeCo(W/Mo) alloys resulted in a ~60% improvement in hardness. From these results, it was concluded that electrodeposition is indeed an effective means to fabricate nanostructured HEAs with improved thermal stability and mechanical properties. In its first documented use, the graduated experimental approach that was employed herein proved valuable in providing a better understanding of the increasingly complex electroplating systems that were studied.

Keywords: Electrodeposited
High-Entropy Alloys
Nanostructured
Advisor: Erb, Uwe
Zou, Yu
Metabolic and Signaling Interactions between Mitochondria and Chloroplasts in Nicotiana tabacum Leaf

Plant cells contain two organelles directly involved in energy metabolism, the chloroplast and the mitochondrion. Optimal cell function likely depends upon specific metabolic and signaling interactions between these two organelles. I used a combination of i. transgenic plant lines with modified mitochondrial electron transport chain (mETC) capacity, ii. chemical inhibitors of specific organelle ETC activities, and iii. specific treatment conditions; to generate unique metabolic and signaling states of the two organelles. This novel approach revealed that: 1. The mitochondrion is a necessary electron sink for photo-generated reductant, contributing to the “P700 oxidation capacity” of Photosystem I. 2. When the capacity of the mitochondrion to consume photo-generated reductant is limiting, the induction of non-photochemical quenching at Photosystem II depends upon PGR5/PGRL1-dependent cyclic electron transport (CET). 3. In the light, the plant cell is able to acclimate to a restriction in oxidative phosphorylation by increasing the capacity for photophosphorylation (through increased chloroplast ATP synthase amount) combined with an increase in mitochondrial electron sink capacity (through increased uncoupling protein amount). 4. CET provides an important means to optimize chloroplast ETC activities in response to changes in mitochondrial electron sink capacity. 5. The expression response of previously identified “mitochondrial dysfunction genes” is highly dependent upon the specific lesions in mitochondrial function that are applied, as well as the specific treatment conditions (e.g. light vs. dark). In part, this relates to differential effects of these lesions on chloroplast function and/or cell fate (acclimation or cell death), as well as the interconnected nature of signal transduction pathways. 6. The status of the mitochondrial ETC may be communicated to the cell, at least in part, through the generation of nitric oxide. Evidence is provided that nitric oxide can be produced in a nitrite-dependent manner at mitochondrial Complex III when the ETC is over-reduced. The results presented in this thesis provide new insight into the metabolic and signaling interactions that occur between the plant chloroplast and mitochondrion.

Advisor: Vanlerberghe, Greg C
Setting the PACE for Learners: A Theory-Informed Approach for Supporting Learners’ Motivation, Self-Regulated Learning, and Achievement in Web-Based Environments

Online instruction has the potential to add incredible value to health professions education (HPE). To achieve this potential, it must be designed and delivered in a manner that facilitates constructive learning interactions between learners and content, educators, and peers. A key determinant of such interactions in online environments is learners’ motivation. This dissertation focuses on the motivational design of online instruction: how it is designed and delivered to support, rather than thwart, learners’ motivation. We propose a novel, theoretically informed approach for designing motivating instruction in HPE, which we call the PACE model after its four key conditions: purpose, adaptability, confidence, and engrossment. The PACE model proposes that instruction can be designed to harness the motivational potential of the life goals that learners pursue through their career. The model predicts that, when learners frame their learning in terms of the life goal(s) it serves, when they can adapt an activity to best align with their life goals, when they are confident that they can attain their learning goal(s), and when they become engrossed with instruction because it affords interest-enhancing actions, instruction will best support learners’ deep engagement toward long-term retention and knowledge transfer. In an initial experimental study, we provide support for a predicted interaction between life goal framing and learners’ confidence. However, we fail to generate evidence that a life goal framing prompt is an effective motivational design strategy when embedded in an online module delivered to medical students. Then, we review the experimental literature on motivational design strategies for online instruction in HPE. We find that studies have overwhelmingly targeted the engrossment condition of the PACE model, relative to the other conditions, and thus the other conditions should receive future attention. Taken together, this dissertation provides the basis for a program of research to advance a theoretically informed and empirically substantiated approach for designing motivating instruction in HPE, including in online environments. When the PACE model is supported by additional evidence, it can provide educators with a source of needed knowledge to design motivating, engaging, and ultimately effective online instruction in HPE.

Keywords: Educational technology
Health professions education
Motivation
Self-regulation
Advisor: Brydges, Ryan
Non-vanishing and 1-level Density for Artin L-functions of D4 Fields

We study families of Artin L-functions associated to the 2-dimensional irreducible representations of the Galois group of D4 number fields, ordered by their conductors. We compute the first moment of the central values of these L-functions, and as a consequence prove that infinitely many L-functions in each family are non-vanishing at 1/2. In order to obtain these results, we prove asymptotic formulas with power saving error-terms for these families. As a consequence, we are also able to study the 1-level density of the low-lying zeros of the L-functions in these families and verify the Katz-Sarnak conjecture.

Keywords: 1-level density
Artin L-functions
Central values
Non-vanishing
Quartic dihedral fields
Advisor: Shankar, Arul
Stress and Reward Function in Concurrent Depression and Chronic Cannabis Use

The co-occurrence of major depressive disorder (MDD) and cannabis use is a common clinical presentation. Chronic cannabis use is associated with poor depression symptom course and functional outcomes in MDD. The endocannabinoid system through which cannabis acts is implicated in the regulation of stress responses and reward processing underlying anhedonia, which may be putative processes through which depression outcomes are worsened with chronic cannabis use. This investigation utilized a prospective design to examine differences in depression, functioning, perceived stress, and facets underlying anhedonia (consummatory and anticipatory pleasure, motivation, and reward sensitivity/responsiveness) between the following groups: individuals with MDD and chronic cannabis (DEP x CAN) versus MDD alone (DEP). Aims in this investigation included: to examine whether chronic cannabis in those with MDD is associated with (i) greater levels of anhedonia, (ii) greater levels of depression severity and poorer ability to function at work and socially, (iii) stronger relations between anhedonia and poor depression outcomes, and (iv) greater levels of perceived stress, as well as stronger relations between stress and poor depression outcomes. Assessments were completed biweekly for two months. Results did not support group differences in self-reported anhedonia, perceived stress, or associations between stress and depression severity and functioning over the study period. Group differences in depression severity and in the associations between facets underlying anhedonia and outcomes were demonstrated. Higher consummatory pleasure was associated with future lower depression in the DEP group, whereas higher consummatory pleasure and higher reward sensitivity/responsiveness was associated with worse functioning at a later week in the DEP x CAN group. Theoretically, while deficits in appetitive behaviour and sensitivity to stress are both posited to be central to the maintenance of depression as well as later stages of substance misuse, results do not support an additive effect of cannabis use on these two processes beyond that which is a function of major depression. While results highlight the importance of attending to the various facets of reward processing dysfunction underlying anhedonia, replication in larger samples with greater power, as well as incorporation of behavioural measures alongside self-report will be important to strengthen present findings.

Advisor: Quilty, Lena C
Bagby, R. Michael
The Role of Cell Size Regulation in Embryonic Wound Repair

Coordinated cell behaviours drive embryonic development and tissue repair, and also contribute to the spread of tumours. Therefore, understanding the mechanisms of collective cell behaviour in living animals will have important implications for the treatment of congenital disorders, chronic wounds or cancer metastasis. To investigate the cellular and molecular mechanisms of cell coordination in living embryos I took advantage of the embryonic wound healing response. Embryos repair wounds rapidly, with no inflammation or scarring, in a process driven by the collective movement of the cells around the wound. Using embryos of the fruit fly, Drosophila melanogaster, combined with genetic and pharmacological manipulations, five-dimensional time-lapse microscopy and image analysis, I demonstrated that contrary to the prevalent dogma, cytoskeletal rearrangements are not sufficient for rapid embryonic wound repair. Instead, I showed that for wounds to close fast, the cells adjacent to the wound must increase their volume. The swelling of the cells adjacent to the wound is driven by the damage-induced activation of the serine/threonine kinase p38 mitogen-activated protein kinase (MAPK). My results indicated that p38 activates the sodium/potassium/chloride cotransporter NKCC1 to promote an increase in volume in the cells adjacent to the wound that enables rapid coordinated cell movements. In addition, I demonstrated that another regulator of cell size, the mechanistic target of rapamycin complex 1 (mTORC1), is necessary for rapid wound healing. mTORC1 inhibition prevented cell swelling around embryonic wounds and slowed wound healing down. Catabolic processes, such as autophagy, can disrupt cell swelling. I demonstrate that the number of autophagosomes around wounds decreases as wound closure progresses, in a process that requires mTORC1 signalling. Inhibiting autophagy rescues the wound healing response in embryos with defective mTORC1 signalling, further indicating that mTORC1 suppresses autophagy to facilitate cell swelling and rapid wound repair. Together, my results show that p38-induced osmoregulation and mTORC1-controlled reduction of catabolic activity promote cell swelling to drive collective cell behaviours in vivo.

Keywords: cell volume
coordinated cell behaviours
epithelial morphogenesis
wound healing
Advisor: Fernandez-Gonzalez, Rodrigo
Determining the Significance of BORF2 Interaction with A3B and p53 in EBV Infection

Epstein-Barr virus (EBV) is a human herpesvirus that infects over 90% of the world's population and is a causative agent of several types of cancers. EBV establishes lifelong infection in the host by alternating between latent and lytic infection. During the lytic phase of infection, the virus produces a cascade of ~70 proteins, many of which function to manipulate cellular processes to enable efficient production of virions. However, the functions of many of these proteins are poorly understood. In this study, I identified novel functions of the EBV lytic protein BORF2, that interacts with the cellular proteins APOBEC3B (A3B) and p53. A3B is a member of the APOBEC3 family of cytidine deaminases, which play a critical role in innate immune defense against viral infections by inducing hypermutation of viral genomes. p53 is a tumor suppressor protein that regulates the cell cycle and plays a critical role in G1/S arrest. Using affinity purification mass spectrometry (AP-MS), our lab discovered that BORF2 interacts with A3B and p53. I confirmed this interaction through proteomic and fluorescent microscopy experiments. My results also showed that BORF2 protects the viral genome by sequestering A3B away from the EBV replication compartment. Furthermore, we collaborated with the Harris lab at the University of Minnesota to perform infection assays which showed that BORF2 protects the EBV genome from A3B mutations. We also found that the interaction between BORF2 and A3B is conserved in KSHV with its viral protein ORF61, homologue of BORF2. In addition to its interaction with A3B, I showed that BORF2 induces p53 independently of A3B binding. My immunofluorescence microscopy experiments revealed that p53 bodies were juxtaposed to and not co-localized with BORF2-A3B bodies. However, in the absence of A3B, p53 co-localized with BORF2. My results suggest that A3B outcompetes p53 for the interaction with BORF2, leading us to propose a competition model where BORF2 can only induce G1/S through a p53-dependent manner in cells that express A3B. Therefore, my research has provided new insights into the mechanisms by which EBV protects its genome from A3B mutagenesis and contributes to G1/S arrest. The discovery of the mechanism by which EBV neutralizes A3B may provide opportunities for the development of therapeutic approaches against EBV as well as A3B-induced cancers.

Keywords: APOBEC3B
BORF2
Cell Cycle
EBV
Herpesvirus
p53
Advisor: Frappier, Lori L