VictorJuiz/thesis huggingface dataset:
The Functional Characterization of Anti-CRISPR AcrIIC2Nme
Keywords: anti-CRISPR
Bacteria
Cas9
Protein

The CRISPR-Cas system is a prokaryotic adaptive immune system that provides protection against foreign genetic elements, such as bacteriophages. Phages have thus evolved a set of small inhibitors called anti-CRISPRs, which bind and inhibit effector Cas proteins. Among the anti-CRISPRs that target the type II CRISPR system, I characterized the anti-CRISPR AcrIIC2Nme. Through structure-guided mutational analyses, I identified a large electronegative surface that is critical for AcrIIC2Nme activity in vivo. In addition, the anti-CRISPR’s binding site was shown to be the bridge helix of Cas9, a highly electropositive region that stabilizes crRNA binding. Lastly, inactive AcrIIC2Nme mutants were shown to bind Cas9 with lower affinity than WT AcrIIC2Nme. These findings present a structurally novel anti-CRISPR that is the first reported to target the bridge helix of Cas9.
Functional Deficiency of Dicer in Atherosclerosis: A Role for Hemodynamic Shear Stress Regulation of the miRNA Biogenesis Pathway
Keywords: Atheroprone
Atherosclerosis
Dicer
Endothelium
Hemodynamic
microRNA

Endogenous microRNAs act as post-transcriptional gene regulators. miR-145 is significantly reduced in both human and murine atherosclerotic lesions; we have shown that re-expression of miR-145 in an atherosclerotic murine model was associated with a reduction of lesion size. Dicer is an RNase-III enzyme which cleaves pre-miRNA into mature miRNA. The regulation of Dicer and its effects on microRNAs in atherosclerosis remains undefined. Multiple atherosclerotic murine models demonstrate downregulated Dicer expression and is associated with global dysregulation of microRNAs. Investigating the mechanism behind Dicer deficiency is key to understanding atherosclerosis development. Endothelial cells (EC) from specific regions of the aorta in wild-type mice experiencing laminar or disturbed/non-laminar blood flow show differential Dicer expression. Dicer expression and function is regulated by hemodynamic shear stress in vitro. Furthermore, the presence or absence of endothelial Dicer affects expression of flow-responsive genes. We posit that Dicer deficiency can potentially prime atheroprone regions in diseased vasculature.
"Abandoned in every sense”: Dispossession, Depletion, and the Reproduction of Colonial Relations through Transnational Mining in the Peruvian Andes
Keywords: Coloniality
Indigenous rights
Latin America
Mining conflicts
Natural resource extraction
Political ecology

In 2016, the ten indigenous campesino communities of the district of Chamaca, Peru temporarily seized a copper mine owned and operated by a transnational mining company, HudBay Minerals. To understand such mining conflicts in Chamaca, this thesis examines how colonial logics and power relations underpin contemporary development policies of the Peruvian state. In particular, I analyze how the historical entanglements of race, indigenous land tenure and labor, and mining inform contemporary extractivist policies. Drawing on three months of ethnographic research, I argue that the HudBay mining enclosure, justified by such policies, reproduces the colonial power structure in three ways: through 1) dispossessions that deplete indigenous social reproduction; 2) the entrenchment of the colonial gender system; 3) state and corporate legal abandonment that recreates hacienda-indigenous relations. En 2016, las diez comunidades campesinas originarias del distrito de Chamaca, Perú tomaron las instalaciones de la minera transnacional—HudBay Minerals—por cuatro días. Para entender los conflictos mineros en Chamaca, esta tesis examina cómo las lógicas y relaciones de poder coloniales respaldan la política de desarrollo contemporánea del Estado peruano. En particular, analizo cómo las conexiones históricas entre las estructuras raciales, la tenencia de la tierra y la labor de las poblaciones indígenas, y la minería informan la política extractivista del presente. Luego de tres meses de investigación etnográfica, sostengo que el cercamiento minero de HudBay, establecido por tal política, reproduce la estructura colonial en tres maneras: por 1) las desposesiones que agotan la reproducción social de los pueblos originarios; 2) el afianzamiento del sistema de género colonial; 3) el abandonamiento legal por parte del Estado y la empresa, que recrea las relaciones y economía de hacienda.
Prostaglandin E2 and its Receptor Subtype EP4 are Functionally Relevant in Ankylosing Spondylitis Disease Pathogenesis
Keywords: Ankylosing Spondylitis
Arthritis
Rheumatology

Introduction: PGE2/EP4 are good candidates to explore in AS pathogenesis as they have been shown to be involved in all three of these pathways. Methods: ELISA was used to discern PGE2 levels in the serum of AS progressors and nonprogressors.Taqman assays evaluated SNPs in the PTGER4 gene in this group. Flow cytometry was used to evaluate the surface expression of EP4. LEGENDplex analysis was employed to discern cytokine secretion from monocyte subsets in response to PGE2/EP4 agonist. Results: PGE2 serum levels were significantly increased in AS progressors vs. non-progressors and were an independent predictor of disease progression. The CC genotype of the rs6896969 PTGER4 SNP was significantly elevated in disease progressors. PGE2 had a mild effect on cytokine production from AS classical monocytes vs. HCs. Conclusion: PGE2/EP4 are involved in radiographic progression in AS. Further experiments are needed to discern its activity in the IL23/IL17 axis and bone remodelling.
The Regulation of Inclusion: An Exploration of School Culture, Pride Narratives, and the Limits of Queer in the National Imaginary
Keywords: Education
Equity
Inclusion
Pride
Queer
Two-spirit

The following study provides a critical examination of the current landscape of 2SLGBTQ+ (two-spirit, lesbian, gay, bisexual, trans, queer) inclusion for high school students in several major Canadian provinces. In order to locate particular strengths and limitations within the predominant framework of inclusion, this study uses a comparative analysis to highlight the (dis)connections between institutional narratives of inclusion (i.e., school policies; school climate surveys; political discourse; and mainstream Pride narratives) and individual accounts of inclusion in school (i.e., 2SLGBTQ+ perspectives and experiences). Findings highlight the various ways in which the prevailing framework of inclusion remains heavily influenced by heteronormative, colonial, and ableist standards of belonging, which consequently, continues to exclude 2SLGBTQ+ voices and lived experiences. The included perspectives from 2SLGBTQ+ youth, families, and educators offer unique opportunities to both re-examine and reconceptualize how prevalent notions of ‘inclusion’ and ‘well-being’ are being reproduced, operationalized, and experienced by all students in school.
Deep Graph Embeddings in Recommender Systems
Keywords: Deep Learning
Economics
Geometric Deep Learning
Information Retrieval
Machine Learning
Recommender Systems

Recommender Systems are intelligent machine learning systems that help customers discover a ranked set of personalized products from a dynamic pool of diverse choices. We can formally view recommender systems objective as ranking edges in a bipartite graph consisting of user and item nodes. Deep Graph embeddings have shown great success in a variety of applications. In this thesis, we aim to explore the application of deep graph embeddings for recommendation. We first understand the embeddings from numerous recommendation perspectives. Next, we compare graph embeddings against existing seminal recommendation algorithms on standard recommendation tasks. Then, we design a new evaluation metric that we argue is important for the e-commerce setting. Finally, we extend graph embeddings to improve performance on the recommendation tasks. To conclude, our experiments support using deep graph embeddings for recommendation tasks and indicate that it could be useful to bias recommender models towards long-tail items.
Understanding the Impacts of Connected Autonomous Vehicles on Pedestrians with Visual Impairment
Keywords: Communication and Mobility Issues
Connected Autonomous Vehicles
Visually Impaired Pedestrians
Vulnerable Road Users

This thesis develops a policy-framework that can be used for minimizing communication issues between connected autonomous vehicles (CAVs) and visually impaired pedestrians. The existing literature on CAVs is highly focused on different perspectives of the possible users of these technologies. Since, this research uses a dataset collected through a tailor-made stated adaptation survey among visually impaired pedestrians. The dataset includes the current mobility issues of this community, their perceptions about CAVs, and a wide range of socioeconomic attributes. Some evidence-based recommendations are provided on communication techniques, based on the key findings of a series of structural equation models (SEM) and ordered logit models estimated using the survey data. The results reveal that the low-noise issue of electric engines influences visually impaired pedestrians’ safety and security in the contexts of CAVs. It shows that respondents who rely on mobile applications and technology-based devices for navigating purposes tend to trust in CAVs.
Does Age Matter? Mental Health Implications and Determinants of When Youth Present to a Gender Clinic
Keywords: Access to care
Gender-affirming care
Gender incongruent youth
Mental health
Pediatric endocrinology
Transgender youth

Background: Gender-affirming medical care (GAMC) improves the psychological functioning of transgender adolescents and adults. Purpose: 1) To assess the relationship between age at presentation to GAMC and rates of mental health comorbidities. 2) To identify factors influencing when youth present to GAMC. 3) To determine whether older presenting youth face more barriers to care. Methods: 1) Cross-sectional chart review of new patients to a gender clinic. 2) Sequential exploratory mixed methods study involving semi-structured interviews and subsequent questionnaire design and distribution. Results: Older age at presentation was associated with psychoactive medication use. Late pubertal stage was associated with depressive and anxiety disorders. Younger presenting youth recognized gender incongruence earlier and were more likely to have LGBTQ+ family members. More older presenting youth endorsed familial religious affiliations. Conclusions: Later presentation to GAMC is associated with higher rates of mental health comorbidities and may be driven by later recognition of gender incongruence.
Molecular Dynamics Study of the Solvation and Mechanical Properties of Elastin-like Peptides
Keywords: Elastin
Intrinsically Disordered Proteins
Molecular Dynamics Simulations

Elastin is a disordered structural protein that imparts extensibility and elastic recoil to major arteries, lungs, and other elastic human tissues. Elastin-based peptides are biocompatible and able to self-assemble, making them suitable for biomimetic materials. Recent studies have begun to uncover the role of entropic effects, including the hydrophobic effect and conformational entropy, in the structural ensemble of elastin-like peptides. In this study, we use atomistic molecular dynamics simulations of peptides based on the hydrophobic domains of elastin to investigate their solvation and mechanical properties. The modulus of elastin-like domains obtained from equilibrium fluctuations is commensurate with elastic measurements from simulations as they are pulled to full extension and subsequently allowed to collapse. Our findings indicate that the hydrophobic eﬀect is a signiﬁcant driving force for elastic recoil, and suggest that the isolated hydrophobic domains are not responsible for the low resilience of elastin-based materials.
Regulatory Role of Bile Acids in Dietary Fat Absorption and Intestinal Lipoprotein Production
Keywords: bile acid
chylomicron
dyslipidemia
intestinal
lipoprotein
postprandial

Postprandial dyslipidemia is a key feature of insulin resistance that involves the overproduction of chylomicrons from the intestine after a meal, resulting in an excess number of atherogenic lipoprotein remnants. Bile acids have been recognized as signaling molecules with the ability to regulate peripheral lipid metabolism and energy expenditure. Here I examined the utility of intraduodenal bile acid administration for lowering postprandial lipemia and chylomicron production in the Syrian golden hamster model. Bile acid administration was shown to decrease postprandial lipemia by slowing down gastric emptying and decreasing mRNA expression of genes involved in fatty acid absorption and chylomicron assembly. Furthermore, bile acid administration was able to regulate VLDL secretion in the fasting state and decreased postprandial lipemia in insulin resistant hamsters. Altogether, the findings arising from these studies support the potential utility of targeting bile acid receptors in the treatment of postprandial dyslipidemia often seen in insulin resistant states.
"Trying to Figure Out Where We Belong": Narratives of Racialized Sexual Minorities on Community, Identity, Discrimination, and Health
Keywords: intersectionality
LGBTQ
minorities
people of colour
stress

Lesbian, Gay, Bisexual, Transgender, and Queer people of colour are regularly exposed to unique and contextual forms of prejudice and stigma, which have been linked to stress and increased likelihood of mental and physical health problems. In order to better understand the experiences of this multiply marginalized population, we interviewed eleven LGBTQ-POC to examine how they describe their identities, communities, health, and experiences with stigma. This study reveals new information about community intersection and the microaggressions experienced by queer people of colour, and provides theoretical support for previously identified issues concerning identity relationships and wellbeing. Common issues discussed by respondents include disconnect from communities, relationships between identities, coming out, exoticization, and stress and anxiety. Three primary concepts that are introduced and discussed in this study include:
Rethinking Repetition: Selective Scanpath Recapitulation Supports Mnemonic Performance on a Change Detection Task
Keywords: change detection
eyetracking
memory
repetition
scanpath

Stimulus repetition improves processing efficiency and performance on a variety of mnemonic tasks. When images are successfully retrieved from memory, the accompanying pattern of fixations or "scanpath" is highly similar to that elicited during encoding. However, it remains unclear how scanpath repetition promotes efficiency gains on goal-directed tasks. The present study used eye-movement monitoring to test the predictions of scanpath theory against a repeated change detection task. Fixations at repeated-viewing were highly similar to first and final novel- viewing fixations, suggesting that speeded search results from a strategic collapsing of the encoding scanpath based on goal-productivity of novel-viewing fixations. Moreover, older adults repeated more initial encoding fixations than younger adults, designating a specialized role for memory in repetition of the recognition sequence. Results support and extend theories of eye- movement-based repetition effects to account for efficiency gains on change detection as a function of goal-relevance and memory.
Remote Spatial Memory in Major Depressive Disorder (MDD)
Keywords: cognitive neuroscience
hippocampus
internet testing
memory
spatial memory

Spatial memory can be divided into episodic (perceptually detailed) and semantic (coarse, map-like) components. When examining remote spatial memories (routes or environments learned long ago) several previous studies have noted that the episodic component seems to be impaired in patients with hippocampal damage, while the semantic component is preserved. Spatial memory in major depressive disorder (MDD), another group found to have hippocampal defects, has sparsely been studied; any studies that do examine this question tend to focus on new spatial learning. The focus of the current study was to examine remote spatial memory in MDD using a novel online paradigm that is composed of traditionally paper-and-pencil spatial and autobiographical measures. We found no differences between healthy and depressed groups on measures of semantic spatial memory. The depressed group appeared to have alterations on the measure of episodic spatial memory, but the nature of this alternation is unknown.
Global Dysregulation of miRNAs via Dicer Deficiency in Atherosclerosis
Keywords: atherosclerosis
Dicer
hemodynamic
miRNA
post-transcriptional regulation

Molecular and phenotypic changes of vascular smooth muscle cells are key components of atherogenesis. miRNAs control, at least in part, this phenotypic transition via desuppression of pro-inflammatory factors. Although specific miRNAs have been implicated in atherosclerosis, a mechanism for their dysregulation remains unknown. Global expression profiling of miRNAs via microarray in healthy versus atherosclerotic murine aorta displayed an overall 30% reduction of miRNA abundance in atherosclerosis. We observed a decrease in Dicer, a key enzyme for miRNA biogenesis, in atherosclerosis. In accordance with this finding, we observed an accumulation in the Dicer substrate precursor-miRNAs despite a decrease in mature levels. Surprisingly, we found Dicer expression in healthy mice to be basally lower in atheroprone areas of the vasculature. Therefore, we propose that global regulation of miRNAs via Dicer deficiency is an important facet of atherogenesis, and desuppression of atherogenic transcription factors such as Runx2 via downregulation of miR-133 in disease.
Pain Sensitivity is Associated with Moral Judgment
Keywords: Moral Beliefs
Moral Judgements
Pain Sensitivity

Moral psychologists often identify harm perception as a core consideration in moral deliberation. Since pain tends to be a ubiquitous form of harm, pain experiences are likely to activate cognitive harm templates. We examined whether pain sensitivity was associated with individual differences in moral judgement. In Study 1, higher pain sensitivity was positively associated with greater perceived relevance of binding foundations and greater support of all moral foundations. Pain sensitivity predicted greater condemnation of moral transgressions involving binding foundations and greater approval of utilitarian behaviour on moral dilemmas. However, it was unclear whether this effect on moral dilemmas was driven by salience, utilitarian content, or goal-oriented language. Study 2 manipulated question wording in dilemmas without changing details of dilemmas themselves. Participants with higher pain sensitivity indicted higher approval of the behaviours described in moral dilemmas regardless of question wording, suggesting that salience, not utilitarian content, was driving these results.
Automated Localization of Breast Ductal Carcinoma in Situ in Whole Slide Images
Keywords: DCIS
Digital pathology
Machine learning
Segmentation

Duct segmentation in whole slide images (WSIs) is an important step needed to analyze breast ductal carcinoma in-situ (DCIS), an early form of breast cancer. Here, we trained several U-Net architectures – deep convolutional neural networks designed to output probability maps – to segment DCIS in WSIs and validate the optimal patch field of view necessary to achieve superior accuracy at the slide-level. A U-Net trained at 5x achieved the best test results (DSC = 0.771, F1 = 0.601), implying the U-Net benefits from seeing wider contextual information. A custom U-Net based architecture, trained to incorporate patches from all available resolutions, achieved test results of DSC = 0.759 (F1 = 0.682), showing improvement in the model’s duct detecting capabilities. Both architectures showed comparable performance to a second expert annotator on an independent test set. This is preliminary work for a pipeline targeted at predicting recurrence risk in DCIS patients.
When “Good” Beliefs Go Bad: The Upsides and Downsides of Believing Emotions are Controllable
Keywords: Beliefs
Emotion Control
Emotion Regulation
Emotions
Reappraisal

Beliefs we hold about whether emotions are controllable influence how we approach our own emotions – but what about how we approach others’ emotions? I propose that believing someone’s emotions are controllable shapes how we treat them, but the exact nature of this treatment is subject to two competing hypotheses: promoting either more positive responses or more negative responses towards that person’s distress. The present investigation tested these hypotheses in two studies (Ns = 308 and 314) measuring participants’ behavioral intentions towards a person struggling with emotional distress. Across both studies, individuals who believed this person’s emotions were relatively controllable were less positive and more negative towards them. Believing this person’s emotions were relatively controllable also predicted stronger attempts to have her control her emotions using interpersonal emotion regulation strategies likely to backfire. These results suggest beliefs about emotion controllability may powerfully shape our interpersonal interactions, carrying crucial interpersonal downsides.
Automated Blastomere Segmentation for Visual Servo on Early-stage Embryo
Keywords: blastomere
early stage embryo
microrobotics
segmentation
single cell surgery
visual servo

Automation of single biological cell surgery requires the location of organelles and cell structures to be determined to permit automated processing carried out in the cell surgery process. In this work, z-stack images of mouse embryos are used as model to develop image processing algorithms, to determine the centroid position (x,y,z) coordinates of embryo blastomeres. Transparency of embryos allow for a series of images along the vertical cell axis (z) to be obtained. Individual z-stack images are processed using 2D image processing steps to first segment, then estimate the centroid (x,y) coordinates of the blastomeres in the 2D image. Successive processing of all z-stack images then permits the centroid of the blastomeres to be determined in (x,y,z) coordinates. Image processing-based calibration allows PZD micropipette to move to the computed centroid position with PBVS control. These algorithms are experimentally verified with mouse embryos at the 2 blastomere stage of development.
Novel Gene Regulation Mechanisms of Aryl Hydrocarbon Receptor: A ChIP-seq and RNA-seq Study of Ahrdbd/dbd Mice Expressing an Aryl Hydrocarbon Receptor with Mutated DNA-binding Domain
Keywords: 2
3
7
8-tetrachlorodibenzo-p-dioxin (TCDD)
Aryl Hydrocarbon Receptor (AHR)
Aryl Hydrocarbon Response Element (AHRE)
Chromatin Immunoprecipitation Sequencing (ChIP-Seq)
DNA Binding
RNA sequencing (RNA-Seq)

Aryl hydrocarbon receptor (AHR) is a transcription factor known for mediating the toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and regulating many physiological and pathological processes. In its canonical signalling pathway, ligand-activated AHR translocates into nucleus, associates with its heterodimerization partner, and binds the cognate aryl hydrocarbon response element (AHRE) to regulate transcription. Based on recent evidence, we hypothesize that AHR may mediate gene regulation through unrevealed mechanisms, namely indirect DNA binding via tethering to other transcription factors, or direct DNA binding to regions not containing any AHRE. To explore this, Ahrdbd/dbd mice whose AHR is incapable of binding AHRE were used. ChIP-seq showed Ahrdbd/dbd mice indeed had an increased number of AHR-bound regions across the genome upon activation by TCDD. However, RNA-seq found almost no alteration in gene expression. These results support the presence but refute the physiological significance of AHR tethering to other transcription factors or non-AHRE binding to DNA.