VictorJuiz/thesis huggingface dataset:
Fast and Flexible CAD for FPGAs and Timing Analysis
Keywords: CAD
FPGA
Placement
Reinforcement Learning
Routing
Timing Analysis

Field Programmable Gate Arrays (FPGAs) are a widely used platform for hardware acceleration and digital systems design, which offer high performance and power efficiency while remaining reprogrammable. However a major challenge to using FPGAs is the complex Computer Aided Design (CAD) flow required to program them, which makes FPGAs difficult and time-consuming to use. This thesis investigates techniques to address these challenges. A key component of the CAD flow is timing analysis, which is used to verify correctness and drive optimizations. Since the dominant form of timing analysis, Static Timing Analysis (STA), is time consuming to perform, we investigate methods to efficiently perform STA in parallel. We then develop Extended Static Timing Analysis (ESTA), which performs a more detailed and less pessimistic form of timing analysis by accounting for the probability of signal transitions. We next study a variety of enhancements to the FPGA physical design flow, including to key optimization stages like packing, placement and routing. These techniques are combined in the open-source VTR 8 design flow, and significantly outperform previous methods. We also develop advanced architecture modelling capabilities which allow VTR 8 to target a wider range of FPGA architectures. These enhancements allow FPGA architects more fine grained control of the targeted FPGA architecture, enabling more in depth study of key architectural features such as the routing network. Additionally, we show how these enhancements enable the VPR placement and routing tool within VTR to target commercial FPGAs as part of a fully open-source design flow. Finally, we study how Reinforcement Learning (RL) can be used to learn new effective heuristics for use in CAD algorithms, and show how this can be used to improve the run-time quality trade-off of an FPGA placement algorithm.
Dimensions of Perceived Reality
Keywords: Composition
Orchestra
Soprano
String Ensemble
Wind Ensemble

Dimensions of Perceived Reality is a multi-dimensional, modular composition for solo soprano and full orchestra which can be performed by the entire ensemble or by subsets of the full orchestration. These subsets are a wind ensemble (woodwinds and brass plus percussion), and string ensemble (strings plus piano and harp). All of this material is notated in a single conductor’s score. The goal of composing in this manner is to make it possible for both ensembles to function independently and uniquely on their own, but also in combination as a full orchestral whole. Adding a further dimension to this modularity, Dimensions of Perceived Reality may also be further parsed by using the full string ensemble version plus any of the winds and/or percussion added as desired. The implied philosophical allegory is that alone we can only perceive a small segment of reality, but we can paint a greater picture of our own existence by mindfully observing our surroundings and engaging with others. The first movement, which begins in introspection of our own humanity, becomes increasingly fragmented in its tonality and content between the two ensembles, as if gazing at oneself in a broken mirror. From our innermost sense of humanity, we move outwards in the second movement to the immediate environment we inhabit, the Earth and its complexity, with the wind ensemble representing the serenity of nature and the string ensemble providing turbulent energy. Space and time are explored in the third movement, where the string ensemble features material that is an inconsistent time-dilation of the motifs presented in the wind ensemble. The final movement meditates on existence itself, maintaining almost consistent unity between the two ensembles. Consequently, this movement is consistently similar in all its possible configurations. This composition is written in a way that also takes into consideration the digital evolution of the 21st century, allowing for presentation of the parts in all of their combinations as an adaptive recording through a sound installation, phone app, or virtual reality experience. The text of the composition is sourced from eight different poems by the English romantic period poet William Wordsworth.
Towards Understanding how Lymph Nodes Process Nanoparticle Vaccines for Humoral Immunity
Keywords: Adjuvant
Drug delivery
Humoral immunity
Lymph node
Nanomedicine
Vaccines

Vaccines are essential to induce the pathogen specific immune responses against infectious disease. Antigens derived from pathogens needs to be delivered to and retained in the immune organs (especially lymph nodes) for efficient immune responses and production of neutralized antibodies. A strategy is to use engineered nanoparticles as delivery carriers to help antigen delivery inside lymph nodes. We do not know how lymph nodes process nanoparticle-based vaccines for immune responses. In this thesis, we first found that follicular dendritic cell (FDC) networks determine the intra-lymph node follicle fate of nanoparticles based on nanoparticle size. The FDCs clear smaller nanoparticles (5-15 nm) and retain larger nanoparticles (50-100 nm) on their dendrites. These retained larger nanoparticles are then presented to B cells to induce humoral immune responses. Next, we assessed the role of immune cell population on nanoparticle delivery inside lymph nodes and found subcapsular sinus macrophage prevent the nanoparticle delivery to FDCs. Suppressing the subcapsular sinus macrophage results in enhancement of nanoparticle delivery to lymph node follicles and up to 60 times more antigen specific antibody production. Lastly, removal of liver macrophages promotes nanoparticle delivery to lymph nodes and tumours after systemic administration. These studies reveal the mechanism of how our immune system process nanoparticles. This knowledge enables us to rationally engineer nanoparticle vaccines and develop strategies of altering immune cell populations to generate effective immune responses.
Remembering as Praxis: Reconceptualizing Structural and State-sanctioned Violence, Oppression, and Trauma through Radical Survival Narrative Pedagogy
Keywords: Dialectical historical materialism
Life Narratives
Pedagogy
State-sanctioned violence
Structural Violence
Trauma

This study looks at women’s narratives as entry points to understanding the gendered and racialized nature of the experiences of violence, oppression, trauma, resistance, and survival, and their connections to patriarchal capitalist relations of imperialism and colonialism across national and cultural boundaries. The first section establishes the theoretical and epistemological framework of transnational feminist theory and Dialectical Historical Materialism, forming a praxis that posits the need to examine macro structures such as imperialism and colonialism, in ways that forefront the material realities of women’s lives and the historical, material conditions that have produced their experiences and stories. The second section presents a narrative analysis within this theoretical framework. The data include narratives by Indigenous survivors of Residential Schools in settler colonial Canada, testimonios of revolutionary struggle from Central America, and political prisoner memoirs from the Middle East. The analysis traces threads of violence, trauma, resistance, and survival which emphasize the connections between the personal and the political, and between private and public memory, and call us to consider how we may challenge, decolonize, and confront dominant ideologies and collective post-trauma/survival subjectivities and solidarities. From this analysis and a critique of mainstream conceptualizations of trauma and the concept of ‘trauma texts,’ I offer the concept of ‘radical survival narratives,’ informed by the narratives themselves, as well as by the concept of ‘radical vulnerability’ from Social Justice and Critical Disability Studies, and the Indigenous literary theory concept of ‘survivance.’ The third section is the development of an arts-based pedagogic framework for community-based and formal education settings. Through both its content and process, this pedagogy of the radical survival narratives is aimed at developing learners’ understanding of the social relations of colonialism and imperialism within patriarchal capitalism and reframing our understanding of violence and trauma through a pedagogy of these narratives. The pedagogy further highlights resistance and survival, pushing back against capitalist, colonialist, imperialist structures and agendas, and building strength and solidarity.
Non-canonical Hedgehog Activity Initiates Ciliogenesis via LKB1-AMPK and Gαi-LGN-NuMA-Dynein Axes
Keywords: Autophgay
Hedgehog pathway
primary cilia

Primary cilia function as critical signaling hubs whose absence leads to severe disorders collectively known as ciliopathies, yet our knowledge of ciliogenesis remains limited. Here I show that Smo induces ciliogenesis through two distinct yet essential non-canonical Hh pathways in several cell types including primary neurons. Surprisingly, Sonic Hh ligand (Shh) activation of Smo can induce autophagy via an LKB1-AMPK axis to remove the satellite pool of OFD1. This is required, but not sufficient, to induce ciliogenesis. Additionally, Smo activates the Gαi-LGN-NuMA-Dynein axis, which results in accumulation of a portion of OFD1 at centrioles at early stages of ciliogenesis. Both pathways are critical for redistribution of BBS4 from satellites to centrioles, and this also relies on centriolar translocation of OFD1. Notably, different Smo agonists, which activate Smo distinctly, activate one or the other of these pathways and only recapitulate the activity of Shh in combination. These studies provide new insights into physiological stimuli (Hh) that activate autophagy and promote ciliogenesis and introduce a novel role for the Gαi-LGN-NuMA-Dynein complex in this process.
New Strategies for C–O and C–C Functionalization in the Contexts of Cyclopropanol Chemistry, Transnitrilation, and Ni Catalysis
Keywords: catalysis
cross-coupling
cyclopropanol
homoenolate
nickel
nitrile

This thesis describes new methods for C–O and C–C functionalization in the contexts of cyclopropanol and homoenolate chemistry, transnitrilation, and Ni catalysis. These strategies represent novel approaches to synthetic problems and may be of interest to chemists tasked with reaction design in these areas. Chapter 1 provides an overview of the chemistry in this thesis and highlights its common themes and synthetic strategies. Chapter 2 describes a new method for the Ni-catalyzed β-functionalization of cyclopropanol-derived homoenolates with redox-active N-hydroxyphthalimide esters, which are derived from carboxylic acids and act as alkylating reagents. Chapter 3 describes new methods for the conversion of cyclopropanols and α-chloroaldehydes to trans-2-substituted cyclopropylamines, which products are valuable from a pharmaceutical perspective. Key intermediates that enable the success of these reactions are electrophilic Zn homoenolates. Chapter 4 outlines the rational design of a new redox-active leaving group to enable Ni-catalyzed carbon–oxygen bond arylation of cyclopropanols, leading to arylcyclopropane products. Chapter 5 describes a new protocol for synthesizing malononitriles from benzyl cyanides. This protocol follows a transnitrilation mechanism involving anion relay. Chapter 6 describes a new protocol for Ni-catalyzed reductive cyanation of aryl (pseudo)halides, using a malononitrile derivative as a new, electrophilic cyanating reagent. This malononitrile reagent enables access to valuable benzonitrile products without the use of cyanide.
Perceptions of Individuals in Mixed-race Relationships
Keywords: Intergroup Relations
Mixed-Race/Interracial
Person Perception
Relationships
Stereotyping

Although the number of mixed-race couples is increasing at an exponential rate in North America, these couples continue to experience stigma and discrimination, which can have deleterious effects on the physical and mental health of the individuals in these relationships. Given that first impressions of individuals can be formed instantaneously and that these first impressions can greatly influence subsequent attitudes and behaviours, in three studies I examined perceivers’ first impressions of targets in mixed-race romantic relationships when viewed on their own versus with their romantic partners. In three studies, I examined perceivers’ first impressions of targets in mixed-race relations when viewed on their own versus with their romantic partners, including perceptions of targets’ warmth and competence (Study 1), global morality (Study 2), and sub facets of morality (i.e., likelihood to betray, to conform, and prejudice level; Study 3). I found that perceptions of warmth and competence did not differ based on whether targets were viewed alone or with their partners, however, perceptions of morality did. In particular, all targets viewed with their partners were perceived as more moral and less likely to betray close others than when viewed alone, however, individuals with same-race partners were perceived as most moral and least likely to betray. Furthermore, individuals in mixed-race couples were rated as less conforming and less prejudiced than individuals in same-race couples when viewed with their partners. In sum, when viewed with their romantic partners, individuals in mixed-race dyads were perceived less favourably than those in same-race dyads in terms of morality, betrayal likelihood, and conformity. However, individuals in mixed-race dyads were perceived more favourably than those in same-race dyads in terms of prejudice. These results were largely driven by the presence of romantic partners given that perceptions of global morality, betrayal, conformity, and prejudice were similar across targets viewed alone. Together, these studies suggest that evaluations of targets’ morality are affected by whether their romantic partner is same- or other-race. These studies lay the foundation for understanding the unique challenges faced by members of mixed-race couples.
Core Values: Cider Production, Agrarian Livelihoods and Tuning Tastes in the Pacific Northwest
Keywords: Agrarian
Craft Cider
Farmworkers
Food and Agriculture
Pacific Northwest
Rural Sociology

This dissertation draws on a case study of emerging craft cider production in the U.S. and Canadian Pacific Northwest. It is guided by the overarching question: To what extent has the contemporary craft cider industry in the Pacific Northwest constrained or enabled agrarian change in land, labour, livelihoods and consumer embodiment? Through a regional analysis encompassing British Columbia, Washington State and Oregon, I draw on ethnographic data from participant observation and in-depth interviews with actors across the craft cider industry from 2017-2019. This dissertation is organized into three distinct analytic chapters. First, I find that while craft cider has helped buffer some farm producers against the volatility of selling raw fruit to large commodity markets, the benefits of this value-added niche market do not widely support continued primary production or farm succession. Some young cidermakers wish to maintain a connection to agrarianism but are shifting away from full-time farming due to lifestyle preferences and political-economic constraints, as exemplified by token forms of on-site production that carry great symbolic weight. Given the craft industry’s emphasis on elevating performances of manual labour intensity and ethical ingredient sourcing, a second analytic chapter focuses on how cidermakers account for the labour of predominantly racialized (im)migrant farmworkers. I find that actors in the craft cider industry engage with inequalities affecting farmworkers through structural obfuscation, ideological justification, and ambivalence or critique. This analysis illuminates both barriers and opportunities to strengthen equity for farmworkers as part of movements to advance food system sustainability. Third, I investigate how actors who are attempting to “tune” people’s tastes away from industrial-scale production navigate the contradictions of their simultaneous dependence on an industrial food system. I find that cidermakers attempt to re-tune consumers’ tastes by appeasing consumers, whose bodies reflect the influence of food system industrialization in the form of taste preferences. Simultaneously, cidermakers endeavour to ease consumers into more diverse possibilities for taste and ecologically resilient farming. Taken as a whole, this dissertation advances scholarly understandings of rural livelihoods, labour in alternative food initiatives, and embodied social change.
The Effect of Hypoxia Mimetic and Laminar Flow on Islet of Langerhans Beta-Cell Function and Endothelial Cell Morphology
Keywords: Angiogenesis
Endothelial cells
Hypoxia
Islets
Microfluidic

Pancreatic islets are highly vascularized in vivo, ensuring proper blood glucose sensing and insulin secretion directly into the blood stream. Islet vascularity is determined by several factors including blood flow, endocrine tissue, and endothelial cells (ECs). However, once islets are isolated and cultured under static conditions (petri dish), their microenvironment is disrupted, and vascularity is quickly lost. Therefore, we designed and manufactured a microfluidic device to mimic nutrient flow in ex vivo islet culture for short- and long-term (Chapter 2). We found that culturing islets in the device resulted in twice the maintained EC-density and -connected length compared to static culture. This positive effect was due to the penetration of serum albumin, an anti-apoptotic signal for ECs, into the tissue. We then observed maintained function of islet beta-cells via two-photon NAD(P)H response and insulin secretion. In chapter 3, we investigated the combined effect of the hypoxia mimetic, cobalt chloride (CoCl2) and microfluidic flow. We found that CoCl2 induced hypoxia did not affect beta cell metabolism, insulin secretion, or survival. CoCl2 stimulated HIF-1α, PDK-1, and LDHA mRNA and also stimulated VEGF expression and secretion. We observed a modest switch to the less oxidative isoform of COX4 (isoform 1 to 2); which was mirrored in the glucose-stimulated cytoplasmic NAD(P)H response. EC morphology and survival were greater in CoCl2 treated islets compared to exogenous VEGF-A in both static and microfluidic flow culture. The EC response appeared to be mechanistically independent from survival induced by the penetration of serum albumin. Lastly, in chapter 4, we conducted preliminary experiments to investigate the role of CoCl2 induced angiogenic factors regulation of VE-cadherin, as a possible mechanism in islet EC maintenance. We found several angiogenic factors and their receptor mRNA present in islets and focused on VEGF-A and FGFs as possible candidates. However, results around their regulation of VE-cadherin were inconclusive. Future studies are required to determine the mechanism of the CoCl2 induced EC maintenance. Taken altogether, these studies are important for long-term ex vivo studies to understand the function of islets and they are also important for the clinical implications of islet transplantation.
Neural Correlates of Self-regulatory Fatigue and the Role of High Affinity Striatal Dopaminergic Receptors in Tourette Syndrome and Healthy Subjects
Keywords: functional magnetic resonance imaging
positron emission tomography Imaging
prefrontal cortex
self-regulatory fatigability
striatum
Tourette syndrome

Tourette syndrome (TS) is a developmental neuropsychiatric condition characterized by motor and vocal tics. Tics are semi-voluntary movements or vocalizations that are stereotyped, repetitive and non-rhythmic. They usually occur in response to a premonitory urge, and can be suppressed temporarily. TS typically involves multiple comorbidities, in particular obsessive-compulsive disorder, attention deficit/hyperactivity disorder, and emotional dysregulation. Given the clinical phenomenology, TS has been conceptualized as a syndrome of inhibitory deficits involving motor, cognitive, emotional and behavioral domains. Neuroimaging studies have implicated the cortico-striato-thalamo-cortical circuitry, in particular the striatal dopamine system, and cortical control areas. However, despite numerous studies, findings have been mixed, and a definitive explanation of the neurobiology underlying TS has remained elusive. The objective of this body of work was to utilize novel neuroimaging approaches in an attempt to identify neural mechanisms that could contribute to the manifestation of TS. In a positron emission tomography (PET) imaging study of the striatum, I investigated striatal D2/3 dopamine receptors in TS using the radioligands [11C]raclopride and [11C]-(+)-PHNO, an agonist that binds preferentially to D3 receptors, thus allowing higher sensitivity and measurement of receptors in a high affinity state. Eleven adults with TS and 11 matched healthy control (HC) participants underwent [11C]raclopride and [11C]-(+)-PHNO PET scans. There were no significant group differences between TS and HC participant binding potentials (BPND) in ventral, motor and associative striatum. In a functional magnetic resonance imaging (fMRI) study of self-regulatory fatigability using an eye blink inhibition paradigm, high-performing HC participants had relatively higher activation in known prefrontal cortex (PFC) control areas – inferior frontal gyrus (IFG), dorsolateral prefrontal cortex (DLPFC), and supplemental motor area (SMA) – whereas self-regulatory fatigability was associated with relatively higher activation in ventromedial PFC, rostroventral anterior cingulate cortex (ACC), and orbitofrontal cortex (OFC). Based on these findings, I carried out a region of interest (ROI) analysis comparing 19 HC and 12 TS participants. There was substantially less percent signal change in the DLPFC/IFG and SMA ROIs in the TS group in comparison to the HC group. These findings suggests that self-regulatory deficits in TS arise from fatigability in cortical control.
A Theory of Nanoparticle Dosing
Keywords: Biodistribution
Cancer
Dose
Nanotechnology
Pharmacokinetics

Cancer nanomedicine has been impeded by poor delivery to target tumours. Many efforts have been made to modify nanoparticles to increase tumour delivery, including their sizes, shapes, and surface chemistries. These efforts have had minor payoffs. At the root of this problem is poor pharmacokinetics mediated by preferential nanoparticle accumulation in the liver. In Aim 1, I determined the reason for preferential accumulation of nanoparticles in livers away from tumours. Liver macrophages were intravascular and had direct access to nanoparticles, while tumour macrophages were extravascular and could only access nanoparticles that penetrated through cellular and stromal barriers. In Aim 2, I leveraged this preferential accumulation to develop a theory of nanoparticle dosing. There was a fundamental dose threshold of one trillion nanoparticles that overwhelmed the liver to enable prolonged circulation times and enhance tumour delivery. In Aim 3, I explored the therapeutic potential of this dose threshold concept. Caelyx’s antitumour efficacy could be improved by simply increasing the dose of nanoparticles without increasing the dose of doxorubicin. The work in this thesis overcomes a major part of the liver barrier and achieves meaningful nanoparticle delivery to tumours for cancer nanomedicine.