VictorJuiz/thesis huggingface dataset:
Towards an Understanding of the Chemical Formation Pathways of Polycyclic Aromatic Hydrocarbons (PAHs) in Sooting Flames
Keywords: combustion
fuel
gas chromatography mass spectroscopy
hydrocarbon
Polycyclic Aromatic Hydrocarbons (PAHs)
soot

Combustion of hydrocarbons inadvertently produces soot which has detrimental effects on both health and environment. Polycyclic Aromatic Hydrocarbons (PAHs) play a central role in soot formation. Several chemical pathways have been predicted to explain the growth of PAH growth during combustion like sequential addition of small species (C1, C2, C3), reactions between aromatic radicals and reactions of Resonantly Stabilised Radicals (RSRs) with another RSR or PAH. These pathways have been developed based on the experimental trends. However, the experimental dataset available in the literature is limited especially for coflow diffusion flames. As a result, a chemical mechanism developed based on the experimental results of one fuel or flame configuration can not explain the PAH growth for other fuels or burner configuration. The uncertainty increases as the PAHs grow larger and depart from the gas-phase. Some studies suggest that this departure starts as PAHs containing 13-16 rings are formed. Other studies suggest that the medium-sized PAHs (containing four or five rings) depart from the gas-phase to form soot. This thesis presents an extensive and comprehensive database comprising of PAHs, soot volume fraction, temperature and soot morphology for aliphatic and aromatic fuels in a coflow diffusion flame. The thesis describes the relationship between the fuel structure and the PAH formation pathways. The potential global chemical pathways for PAH growth discussed here can help in developing more comprehensive and accurate chemical mechanisms. The experimental results show that for aliphatic fuels, PAH growth takes place mainly by sequential addition. For alkylated aromatic, the growth of PAHs take place by the reactions between RSRs, reactions between aromatic radicals and hydrogenation of PAHs followed by addition of methyl radicals. The thesis also discusses the surface chemistry of particulates. The surface composition of the young soot is dominated by medium-sized PAHs and is similar to the gas-phase in its vicinity. With the increase in flame temperature or degree of maturity of the particles, medium-sized PAHs desorb from the surface of the particles into the gas-phase. Large PAHs are dominant only on the surface of the mature particles suggesting that these PAHs might be growing on the surface.
Correction of Cerebrovascular CFTR Expression and Systemic Adrenergic Receptor Blockade Normalize Cerebrovascular Resistance and Mitigate Cardiovascular Dysfunction Following Subarachnoid Hemorrhage
Keywords: catecholamine
cerebral blood flow
mechanosensor
myogenic response
resistance artery
subarachnoid hemorrhage

Subarachnoid hemorrhage (SAH) is a deadly stroke subtype that kills or causes permanent disability in most of its victims. Nimodipine therapy is currently the standard of care for SAH patients. Although nimodipine provides neuroprotective benefits to SAH patients, the resulting rates of morbidity and mortality are still alarmingly high. SAH standard of care has not significantly changed in three decades, highlighting the urgent need to develop better therapeutic strategies. Importantly, SAH also inflicts damage to peripheral tissues, likely due to the surge in circulating catecholamine levels that accompanies SAH. Notably, cardiac dysfunction is a common side effect and detrimental increases in blood pressure are frequently observed in SAH patients. We propose that SAH standard of care can be refined with the addition of two elements: (i) specific targeting of cerebrovascular processes that are altered by SAH and (ii) systemic protection of the cardiovascular system from collateral damage that would otherwise exacerbate the primary cerebral pathology.In an experimental murine model of SAH, we found that lumacaftor, a reagent that increases expression of the cystic fibrosis transmembrane conductance regulator (CFTR), prevents the SAH-induced augmentation of cerebrovascular myogenic responsiveness and the subsequent neuronal injury. In contrast, the current standard of care nimodipine fails to normalize cerebrovascular reactivity and neuronal injury in our SAH model. Importantly, CFTR is not expressed in the peripheral vasculature; lumacaftor therefore exerts high specificity for the cerebral microcirculation and targets only the pathological elevation of cerebrovascular myogenic responsiveness in SAH. Additionally, we investigated the effects of our SAH model on peripheral cardiovascular function. We found evidence of impaired cardiac function and elevated myogenic responsiveness in peripheral arteries; this latter effect is associated with increased total peripheral resistance, a main determinant of blood pressure. Anti-adrenergic therapy with the clinically-available β-blocker bisoprolol and α-blocker terazosin effectively prevents the cardiac dysfunction and restores peripheral artery myogenic responsiveness, respectively. In summary, this investigation provides detailed mechanistic insight into a novel therapeutic approach towards correcting cerebral microvascular dysfunction following SAH and a complementary therapeutic approach towards alleviating peripheral cardiovascular dysfunction that is suited to improve clinical outcome in SAH patients.
Discovery of Novel Circulating Biomarkers in Metastatic Castration Resistant Prostate Cancer to Guide Optimal Treatment Decisions
Keywords: Biomarker
Circulating cell-free DNA
DNA methylation
Epigenetics
Liquid biopsy
Prostate Cancer

Circulating cell free DNA (cfDNA) is emerging as a key tool to identify treatment resistance in metastatic castration resistant prostate cancer (mCRPC). Numerous studies have reported specific genomic aberrations, including androgen receptor mutations and splice variants, associated with resistance to current androgen targeting agents, enzalutamide and abiraterone acetate. While promising, genomic alterations alone do not account for the disease heterogeneity among mCRPC patients. Indeed, global changes in tumor DNA methylation patterns are a major hallmark of prostate cancer. In this study, cfDNA methylation changes in mCRPC patients receiving androgen targeting agents were explored. Firstly, genome-wide methylome alterations were characterized through sequential collection of blood samples from prior to initiating treatment until clinical progression. Patients that sustained methylation changes throughout therapy tended to exhibit a longer time to clinical progression (TTCP). Upon disease progression, alterations in key oncogenic genes involved in proliferation, development and neuronal pathways were demonstrated. In addition, increased detection of cfDNA methylation markers associated with a highly treatment-resistant form of the disease, neuroendocrine prostate cancer, was associated with a faster TTCP. A targeted panel consisting of these methylated regions was developed using droplet digital PCR and independently confirmed correlation with TTCP. This novel cfDNA biomarker panel could potentially serve as a monitoring tool to track the emergence of aggressive disease and could aid with the clinical management of mCRPC. The functional implications of these methylation changes in neuroendocrine disease were also explored using an established pre-clinical cell-line model of mCRPC. Progressive methylation alterations from the castration-sensitive state to castration resistant and neuroendocrine disease were tracked. These epigenetic modifications were integrated with mRNA expression changes and several key genes associated with oncogenic and developmental/lineage reprogramming pathways were identified. Neuroendocrine-related methylation changes from this model were also found in cfDNA from mCRPC patients and correlated with clinical response. Overall, this study highlighted the potential of monitoring the cfDNA methylome during therapy in mCRPC and further revealed novel therapeutic targets for metastatic prostate cancer.
Obesity-driven Immunometabolic Activation of Myeloid Cells
Keywords: Bone Marrow Adipocytes
Glycolytic Shift
Immunometabolism
Ly6Chigh Monocytes
Obesity
Tissue Invasive Monocytes

Background/Rationale: Obesity is a chronic inflammatory disorder and a strong predictor of tissue insulin resistance and Type 2 Diabetes. Accumulation of pro-inflammatory adipose tissue macrophages (ATM) are culprits to tissue insulin resistance. Tissue infiltration and the subsequent differentiation of Ly6Chigh monocytes largely contribute to ATM accumulation during obesity. Interestingly, Ly6Chigh monocytes are elevated in the circulation and in the bone marrow (BM) during obesity. However, the temporal relation of the obesity-driven increase in ATM and BM Ly6Chigh monocytes are unknown. Furthermore, it is also unknown what obesity-induced changes drive the increased production of Ly6Chigh monocytes in the BM. Moreover, it is unknown how monocytes are affected with obesity and whether the metabolic skewing, as observed in ATM, are also induced in BM monocytes. Hypotheses: I hypothesized, that increased BM Ly6Chigh monocytosis occur prior to ATM accumulation with high fat diet (HFD). Additionally, I hypothesized, that local BM adipocyte (BMA) expansion favour increased Ly6Chigh monocyte development. Lastly, I hypothesized, that a glycolytic shift would be induced in BM monocytes with HFD. Methods: A murine HFD feeding model with the durations of 3, 8 and 18 weeks were adopted. Using flow cytometry analysis, the accumulated ATM and BM monocytes were quantified. Furthermore, in vivo correlative analysis between BMA and monocytes were assessed. In vitro models were adopted to assess the direct influence of adipocytes on monocyte development. Lastly, the metabolic status of monocytes were studied using the Seahorse assay, MitoTrackerTM staining and expression analysis of mitochondrial genes via RT qPCR. Results/conclusion: An earlier elevation of the BM monocytes compared to the ATM were detected with HFD. Furthermore, BMA whitening temporally correlated with Ly6Chigh monocyte expansion in the BM during HFD. White adipocytes and HFD-derived BMA directly favoured Ly6Chigh monocytes, in vitro. Interestingly, white adipocytes induced conversion of Ly6Clow to Ly6Chigh monocytes. We further discovered that Ly6Chigh monocytes prefer glycolytic and Ly6Clow monocytes prefer oxidative metabolism. During HFD, the metabolism of Ly6Clow monocytes are skewed to resemble that of Ly6Chigh monocytes. The findings reported here place the BM as a key site for the origin of cellular and metabolic disruptions with obesity.
In the Image of Industry: Indigeneity and Migrant Labor in the Making of Filipino America
Keywords: Archival Theory
Critical Race Studies
Filipino America
Indigeneity
Labor History
Visual Culture

This dissertation presents a cultural and labor history of race in 20th century Filipino America through the political-economic conditions that displaced lowlands peasants and indigenous groups from Northern Luzon in the 19th century. It argues that the constellation of contradictory identities that constitute the “Filipino”—the indigenous “savage” and the industrious migrant worker—across the early 20th century Pacific emerge out of archival productions that decontextualized political economic upheavals, as the island of Luzon became repurposed into a commodity producing colony. Industrial empires, nationalist political elites, rural intellectuals, migrant peasants, and indigenous Cordillerans alike competed over the terms of what the modern “Filipino” would look like as northern resource frontiers produced a global labor force, bringing with it a vibrant transpacific political culture. This dissertation investigates the racial economy of the colonial archive, or the phenomenon of archival production and circulation through which race manifested as ways for empires to manage human resources.
What Does it Mean to be a Solution?: Teachers of Colour Doing Social Justice in the Multicultural School in Canada
Keywords: Black
Indigenous and teachers of colour
Equity and social justice
Race
Racialized teachers
Teacher Education
Teacher subjectivity

This project conceptualizes the racialized teacher subject in the multicultural Canadian school in Toronto, Ontario, by examining what it means for the Black, Indigenous and teacher of colour to be positioned to solve inequity and racial injustice in schools. It asks: What does it mean for the racialized teacher to be a solution? To address this overarching question, the project examines the following issues: how racialized teacher subjectivity becomes constituted prior to and while working in the multicultural school; what kinds of expectations the racialized teacher subject navigates; and the systems that function to produce and constrain the racialized teacher’s social justice goals. Because the project is interested in the complexity of the racialized teacher in a white settler state such as Canada, the space of the racially diverse or “multicultural” Toronto area high school was the site of investigation. The core argument presented is that the racialized teacher subject is restricted through liberal and neoliberal discourses, contending with the position of what I term the multicultural helper – an idealized figure who is expected to facilitate the inclusion of the racialized student into the multicultural school. The types of solutions racialized teachers are typically invited to take up are those that model and facilitate depoliticized and culturally acceptable subjectivities for their students. I argue that racialized teachers do not and cannot actually embody social justice; rather they struggle against and negotiate the position of the multicultural helper. Crucially, they unlearn dominant notions of Canadian multiculturalism in the production of a politically conscious subjectivity. I further argue that the liberal expectations inscribed in multicultural helping require racialized teachers to navigate the contradictions between the benefits and harms of the ways they are positioned in schools. I illustrate that spaces and systems within schooling, in particular those outside the direct influence of the racialized teacher, are governed by discourses of control (Nolan, 2011) and discipline (Foucault, 1995), reproducing injustice and limiting the transformative potential of the racialized teacher’s work.
A Compositional History of Ben Sira in the Context of the Transmission of Instruction Literature in the Ancient Mediterranean
Keywords: Ben Sira
Redaction
Wisdom

The prevailing scholarly opinion is that the Hebrew original of Ben Sira is an irretrievable holy grail or at best very difficult to retrieve. Scholars of Ben Sira are particularly discouraged by the great variation in the extant manuscript traditions in Greek, Hebrew, Syriac, and Latin. Many despair at getting close to a reliable base text in the original Hebrew. The great variability of the manuscript tradition is often given as the implicit and sometimes explicit reason for not doing any redaction-critical studies of Ben Sira. In this dissertation I offer a blueprint for how, in spite of these difficulties, a compositional history of Ben Sira may be approached, and why this is desirable. I will begin by pinpointing the textual categories to which Ben Sira belongs. I shall focus on late biblical literature and the gnomic literature of the ancient Mediterranean in the Hellenistic and Roman periods, and show how the preponderance of evidence suggests and often demonstrates that these works are for the most part the product of multiple authors. In this section I will broadly describe the types of evolutions these texts undergo, focusing on the nature of the material later authors added to earlier versions of the text. Basing my analysis on the likelihood that Ben Sira was the work of multiple authors and on these patterns of textual accretion, I will focus on Ben Sira and show how the manuscript evidence has likely captured different moments in its textual evolution. Next, with the aid of redaction-critical tools and the patterns I have observed, I will extrapolate regarding passages for which there is no manuscript evidence. Finally, on the basis of these findings, I will offer preliminary analyses of the earlier versions of the book, some thoughts on the dates of composition of the versions of this book, and the relevance of this dissertation to the diachronic study of religious texts in general.
Biowire II Platform: High Fidelity Heart-on-a-chip for Drug Screening and Disease Modeling
Keywords: drug testing
heart
maturation
microenvironment
organ-on-a-chip
Tissue engineering

Cardiotoxicity is a major cause of drug failure at the late stages of clinical trials and it is linked to unqualified candidates as early as possible is key for reducing the costs of drug discovery and preventing the patient fatality. Tissue engineering using cardiomyocytes derived from human pluripotent stem cells holds a promise to revolutionize drug discovery, but only if limitations related to tissue maturation, cardiac chamber specification and platform versatility can be overcome. The plastic-based platform developed in this thesis, Biowire II, facilitates the scalable, miniaturized 3D tissue cultivation with multiple cell sources in a low absorption environment. The platform deploys two fluorescent, elastic polymer wires to serve as tissue anchors and force sensors, and enables on-line, non-invasive, recording of passive tension, active force, contractile dynamics, Ca2+ transients, endpoint assessments of action potentials and conduction velocity. The conditions of cardiac tissue formation, including cell seeding density, non-myocyte populations and hydrogels, were characterized in detail to ensure the consistent production of functional tissues with hallmarks of adult myocardium. The temporary electrical pacing and long-term electrical conditioning were incorporated and optimized for the platform to facilitate standardized drug testing and chamber-specific cardiac tissue maturation. By combining directed cell differentiation with electrical field conditioning, we engineered electrophysiologically distinct atrial and ventricular tissues with chamber-specific drug responses and gene expression. This study is the first to report the engineering of the heteropolar cardiac tissues, which contain well-separated atrial and ventricular ends, and demonstrate their spatially confined responses to serotonin and ranolazine. More importantly, Biowire II platform enabled modeling of polygenic left ventricular hypertrophy with induced pluripotent stem cell derived cardiomyocytes from six different patients, using uniquely designed 8-months-long electrical conditioning protocol. The platform was scaled up into a 96 well-plate format with all the key features, such as plastic culture environment, elastic force sensors and embedded carbon electrodes. An innovative fabrication method was developed to rapidly cast suspended force sensors on top of a patterned surface. This advanced version of platform eliminates adhesives, standardizes and further increases the throughput of tissue production and drug testing.
“Freeing” the Chinese Migrant: Diasporic Entanglements of Qing and British Universal Empire
Keywords: British
China
Diaspora
Empire
Free
Qing

This dissertation critically reconstructs the historical emergence of the “free migrant” in China through the encounter of the Qing and British empires across the 18th and 19th centuries. It challenges dominant narratives of the Qing state’s British-guided transition from disdaining Chinese migrants to embracing them as free subjects. Instead, this project traces complex entanglements between the all-encompassing ideologies or “universalisms” of these two imperial powers as they attempted to govern Chinese mobilities in Asia and around the world. While Qing elites did not originally conceive of Chinese circulating overseas as free subjects, I argue that over a long 18th century, the imperial state ultimately chose to enable certain freedoms for migrants within the expanding framework of a centering emperor-focused universalism. In the 19th century, British agents guided by a liberal imperial universalism aggressively sought to “free” Chinese migrants, but chronically subordinated the freedoms of racialized Chinese in the production of freedoms for white liberal subjects. A crisis in human trafficking triggered by British interventions provided an opportunity for British liberal advisors to incorporate and subordinate the Qing within a global order of capitalist nation-states, but also for Qing elites to mobilize liberalism’s terms to contest this subordination. In parallel, jurisdictional contests over the colonial “Anglo-Chinese” in China highlighted the conceptual gap between British legal and liberal subjects, and opened the door for both powers to develop syncretic strategies that appealed to international law. Finally, as Qing thinkers followed diaspora into liberalism’s worlds of racially stratified colonial capitalism, their strategies drew deeper and deeper from its principles, reimagining migrants as political, economic, racial, and ultimately “free” subjects beholden to these regimes. Collectively, this dissertation tells a global history of China, following human and capital flows across a transformative age of mass migration. In doing so it helps us understand not only the emergence of the modern relationship between China and its diaspora, but the broader global order of states and subjects, and the racial inequities built into it.