VictorJuiz/thesis huggingface dataset:
Building an Ecological Civilization across the Rural/Urban Divide and the Politics of Environmental Knowledge Production in Contemporary China
Keywords: China
environmental protection
knowledge production
rural/urban inequalities

Over the past four decades, China’s environment has been transformed markedly, both in terms of pollution and degradation, but also through protection initiatives. This dissertation draws on political ecology, including theories of environmental knowledge production, and uneven development, to examine how China’s ‘green’ turn unfolds onto, and through, rural/urban inequalities, and how it reconfigures this profound divide that organizes society. This dissertation examines how these two ‘crises’ — one environmental and the other socio-economic — are in conversation with each other, and in many ways, build off each other. My analysis is based on first-hand research in the Qinling Mountains (Shaanxi), interviews (including with academics, officials and villagers), participatory observation, as well as on secondary literature on rural-environmental questions. Based on this data, I identify two paradoxical processes transforming rural environments: the ruralization of pollution and the mobilization of rural efforts to ‘green’ the nation. I propose the concept of socio- environmental reproduction as a useful lens to understand this paradox. This concept illustrates how the rural/urban divide is constitutive of the environmental project; it also helps to understand the mechanism by which national greening initiatives further re-assert rural/urban differences. This dynamic appears most clearly when examining the politics and logics of environmental research including limits on fieldwork, pressures to commercialize research and political decisions about what is, or not, acceptable environmental knowledge. This study therefore analyzes institutional, political and discursive frames that regulate rural-environmental research to explore the parameters that shape what is known, or made invisible, about rural-environmental realities. I suggest that the political and economic context shaping environmental research in contemporary China is productive of the invisibility of urgent rural-environmental questions — a process which contributes to reproducing rural/urban inequalities, and illustrates one of the new ways through which uneven development unfolds in contemporary China.
Development of Gold Nanoparticle-based Nanoformulations for Cancer Radiotherapy
Keywords: Gold nanoparticle
Radiotherapy

One of the major clinical challenges in radiotherapy (RT) is dose-limiting toxicity to surrounding normal tissues. Gold nanoparticles (AuNPs) have emerged as a promising approach to overcoming this challenge by combining the radiation dose enhancement effects of Au with the unique features of nanoparticles that enable tumour-selective delivery of AuNPs. Theoretical and experimental studies have demonstrated that AuNPs have the potential to improve radiotherapeutic efficacy. These improvements are the result of physical enhancement of the local radiation dose, and/or sensitization of cells via biological and chemical pathways. To further enhance the radiosensitization effects of AuNPs, this thesis aims to design and develop AuNP-based nano-formulations that (1) combine AuNPs with an agent with anti-cancer properties (pentamidine or cisplatin), or (2) target the nucleus for physical dose enhancement, and evaluate their in vitro radiation enhancement effects. Overall, this work demonstrates the promising potential of the newly developed nano-formulations to improve the radiation enhancement effects of AuNPs. The combination of AuNPs and pentamidine demonstrated enhanced radiosensitization effects relative to AuNPs alone by promoting cellular uptake and via inhibition of post-IR DNA repair. As well, cisplatin prodrug-conjugated AuNPs combined the AuNP-induced production of reactive oxygen species with persistent DNA damage imparted by cisplatin to result in superior radiosensitization in 2D monolayers and growth inhibition in 3D multicellular tumour spheroids. Finally, nuclear-targeted Au-liposomes formed by encapsulation of AuNPs in pH-sensitive liposomes showed significant radiation enhancement effects whereas no significant effects were observed with untargeted Au-liposome, demonstrating the role of nuclear targeting in physical dose enhancement. Based on these findings, future research is warranted to evaluate the in vivo efficacy and safety of these nano-formulations, and to optimize the nuclear-targeted Au-liposomes to fully elucidate the impact of nuclear localization on physical dose enhancement.
Redox Potential Measurements of Aqueous Systems at High Temperature and High Pressure
Keywords: aqueous solution
flow-through electrochemical cell
High temperature / high pressure
Ir electrode
pressure oxidation leaching
Redox potential

Redox potential is an essential variable for characterizing aqueous systems. Its measurement can be beneficial in providing insight into hydrometallurgical processes. An Ir electrode was validated for redox potential measurements at high temperature and high pressure. Measurements were performed using two different flow-through electrochemical cells (FTEC): one with a Ag/AgCl flow-through external pressure balance reference electrode (FTEPBRE), and the second one was a linear FTEC with an Ir quasi-reference electrode. The potential was measured for the H2SO4-FeSO4-Fe2(SO4)3-H2O system for concentrations of 1 M H2SO4, 10-2 M Fe(III), and 10-4–10-2 M Fe(II) at 34 MPa, up to 200 °C, and, for the linear FTEC, at flow rates of 0.2–1.5 mL/min. The change in potential measured with the Ir electrode behaved according to the Nernst equation upon changes in the test solution, and were consistent with the corresponding estimated potential variation predicted by the Aqueous model from the OLI® System software. The Ir working electrode combined with the Ir quasi-reference electrode were fit into a 2 L autoclave to measure the solution potential during pressure oxidation (POX) of two sulfide materials, pyrite and a refractory gold ore, at 200–230 °C, 345–760 kPa O2 overpressure, and, for the refractory ore, 10–30 wt-%, conditions found in the industry. The measured potentials were related to the ratio [Fe(III)]/[Fe(II)], indicating that the mixed potential in solution is dictated by the Nernst potential of the Fe3+/Fe2+ half reaction. An acidic solution is necessary to sustain soluble iron and therefore accomplish meaningful potential measurements; the Ir electrode operated properly at concentrations 0.3–100 mM for Fe(II) and Fe(III). The measured potential, together with the oxygen consumption during POX of the refractory ore, were used to identify the moment when maximum conversion of sulfide material was achieved. Most POX processes operate at conditions that allows the implementation of the developed sensor and the measured potentials could be used to optimize these processes.
The Plot of Attentional Transformation: Literature and History in the Victorian Novel
Keywords: Attention
Genre
Literary History
Narrative form
Plot
Victorian novel

This dissertation tracks the history of a formal phenomenon that is prevalent across nineteenth-century British novels, but which has gone largely overlooked by previous scholars. This is what I call the plot of attentional transformation, and it comprises two chief elements: a narrative agon that arises when the protagonist adopts an abject mode of attention such as inattention, distractibility, or absorption; and a denouement that takes place when the protagonist shakes off this abject condition to assume an antithetical, idealized attentional state. I argue that if nineteenth-century novelists as diverse as Walter Scott, W.M. Thackeray, George Eliot, Wilkie Collins, Robert Louis Stevenson, and William Morris all invoked this plot form, it is because it served a valuable organizing and coordinating function. At the same time as the attentional plot allowed these novelists to organize the fates of their differently classed and gendered characters into single teleological history, it also enabled them coordinate their otherwise independent and unrelated narrative interventions into social and literary politics into one coherent historical narrative. In analyzing how concepts of attention structure the Victorian novel, my project contributes to the area of attentional formalism—a body of research that studies connections between forms of human attention and the form of Victorian literature. But whereas previous scholars have analyzed the Victorian novel’s attentional form primarily in relation to contemporary psychological and technological discourses, and largely by drawing on physiological and temporal models of attention, I take a different tack here. I study how authors such as Scott, Thackeray, Eliot, Collins, Stevenson, and Morris used representations of everyday objects, and engaged with discourses around aesthetics, linguistics, and typography, to imagine attention chiefly as a spatial and object-oriented—as opposed to a psychological, somatic, and temporal—concept. I also intervene in this established research by extending our understanding of what attention is. My dissertation asks us to think of attention not only as a psychological faculty or as a construct of technological modernity but also as a narrative function that has the power to organize and give structure to large and complex master narratives of social and cultural change.
Selection, Constraint, and Adaptation in the Visual Genes of Neotropical Cichlid Fishes and Other Vertebrates
Keywords: fish evolution
molecular evolution
opsins
sensory systems
visual ecology

The visual system serves as a direct interface between an organism and its environment. Studies of the molecular components of the visual transduction cascade, in particular visual pigments, offer an important window into the relationship between genetic variation and organismal fitness. In this thesis, I use molecular evolutionary models as well as protein modeling and experimental characterization to assess the role of variable evolutionary rates on visual protein function. In Chapter 2, I review recent work on the ecological and evolutionary forces giving rise to the impressive variety of adaptations found in visual pigments. In Chapter 3, I use interspecific vertebrate and mammalian datasets of two visual genes (RH1 or rhodopsin, and RPE65, a retinoid isomerase) to assess different methods for estimating evolutionary rate across proteins and the reliability of inferring evolutionary conservation at individual amino acid sites, with a particular emphasis on sites implicated in impaired protein function. In Chapters 4, and 5, I narrow my focus to devote particular attention to visual pigments in Neotropical cichlids, a highly diverse clade of fishes distributed across South and Central America. In Chapter 4, I find accelerated evolutionary rates in RH1 are associated with cichlid colonization of Central America. I experimentally characterize a South American cichlid rhodopsin pigment and assess the functional consequences of a unique amino acid variant. Finally, in Chapter 5, I examine diversity in UV, violet, and blue-sensitive opsins across the Neotropical cichlids. I identify several putative pseudogenization events in the UV opsin, as well as complete loss of this opsin in several South American cichlid species. Conversely, the UV opsin was under strong purifying selection in Central American cichlids. My results also indicate a burst of episodic positive selection in the blue-sensitive opsin at the base of an ancient adaptive radiation in South American cichlids. This thesis combines computational and experimental work investigating visual pigment evolution in Neotropical cichlid fishes. More broadly, this thesis also considers the evolutionary forces governing visual gene loss and inactivation, as well as the molecular mechanisms mediating visual protein function and adaptation.
Transgenerational Effects of Antenatal Synthetic Glucocorticoid Exposure on Transcription and Methylation in the Developing Brain
Keywords: Epigenetics
Neural Development
Prenatal Glucocorticoids
Transgenerational Transmission

The early environment has long term influences on future health that are heritable over multiple generations via maternal and paternal lineages. Antenatal synthetic glucocorticoids (sGC) are administered to women at risk for pre-term delivery because they reduce the morbidity and mortality associated with newborn respiratory distress syndrome. However, the administration of multiple courses of antenatal sGC results in long-term programing of behavioral and physiological responses to stress. In this research, we performed transcriptomic and epigenomic analyses to ascertain the long-term programming effects of antenatal sGC in the brains of first generation (F1) juvenile males and three generations of juvenile female offspring of the paternal lineage. We hypothesized that antenatal sGC exposure results in transgenerational changes in transcription and DNA methylation in the hypothalamic paraventricular nucleus (PVN), prefrontal cortex (PFC) and hippocampus, due to their role in the regulation of the HPA-axis. We observed that antenatal sGC results in generation-, sex-, and brain region-specific changes in gene expression and DNA methylation in three generations juvenile female offspring of the paternal lineage. In the PVN, exposure to sGC programmed large transgenerational changes in gene expression, including type II diabetes, thermoregulation, and collagen formation gene networks. The PFC was the only brain region to show overlap in the significantly differentially expressed genes across all three generations of juvenile females and F1 males. In the PFC, the expression of four genes that were significantly decreased in sGC offspring explained 20-29% of the variability in locomotor behavioral phenotypes. Epigenetic analyses of the hippocampus identified significant changes in CpG methylation in regulatory regions of small non-coding RNAs involved in transcription and splicing. These findings may implicate alternative splicing as a mechanism involved in the transgenerational transmission of the effects of antenatal sGC. This is the first study to show that antenatal sGC exposure, a clinically relevant treatment, results in transgenerational changes in gene expression, and methylation over three generations, via paternal transmission.
Challenging Assumptions: Using Research to Evaluate Child Welfare Worker Qualifications
Keywords: child welfare
child welfare worker
qualifications
workforce

Child welfare workers are the conduit between child welfare systems and children and their families. Required qualifications for practice include certain educational and practice experiences, skills, and knowledge. The overall goal of this dissertation is to increase understanding of the child welfare workforce. To meet this goal, the objectives of this dissertation are: 1) to assess the evidence for the necessary education and training qualifications required for child welfare practice; 2) to examine how worker qualifications have shifted in response to changes in child welfare system mandates and child and family needs; and 3) to contribute to the understanding of the role worker characteristics play in the ongoing services provision. Three studies were undertaken to meet the goal of this dissertation. The first paper is a synthesis of a portion of the child welfare workforce literature and reveals a lack of evidence regarding the specific educational background, skills, and experience that best equip child welfare workers for the demands of practice. Paper two is the first provincial study in Canada to examine how the profile of workers who conduct child maltreatment investigations has changed alongside shifts in child welfare legislation and mandate. Ontario data over the past 20 years illustrate changes in caseload size, training attendance, pre-service education, ethnicity, and years of child welfare worker experience. Paper three, the final study of this dissertation, uses multilevel analyses to examine the decision to transfer a family for ongoing services. Findings reveal that clinical and organizational characteristics predict this service provision, whereas worker characteristics (i.e., education, training attendance, experience, age, position, caseload size) did not. Overall findings suggest that there is little empirical evidence to suggest that valued qualifications actually equip workers with the skills and knowledge for effective child welfare practice and that the efficacy of these qualifications are based primarily on assumptions. Recommendations for future research and practice are provided.
Get to the tumour! Transporting nanoparticles past predatory biological barriers
Keywords: Cancer
Drug delivery
Nanoparticle

Specific delivery of therapeutic and diagnostic agents to the disease tissue is an essential step for their successful translation into the clinic. In the recent years, nanomedicine has become a promising concept for the delivery of therapeutic molecules and contrast agents to the tumour. However, the body is riddled with many intrinsic biological barriers at the systemic, organ, and the cellular level. These barriers can redirect, hinder, and reduce the transport of nanomaterials to the cancer cells, thus limiting the clinical success of nanomedicine. The purpose of this thesis is to investigate the biological barriers that hinders nanoparticle delivery to tumours. To this end, we 1) examined the nanoparticle adsorption of blood serum proteins on reducing the nanoparticle targeting specificity to cancer cells; 2) the hindrance of extracellular matrix and tumour associated macrophages on the transport of nanoparticles in the tumour; and 3) the variability of tumour pathophysiology on the transport of intratumoural nanoparticles. The knowledge presented from this thesis can be used to improve delivery efficiency to the cancer cells via 1) manipulating the biological system, and 2) improve the design of nanomaterials to avoid biological barriers.
Bone Microstructure and Changes in Tissue Mineralization throughout Adulthood
Keywords: Adult body size
Bone histomorphometry
BSE-SEM
Osteoporosis
Skeletal health
South African Apartheid

This research aims to explore the global variability in the structural and material properties of mid-thoracic ribs within a large (n=213) sample of known age, sex, and government “race” designation from apartheid South Africa [DOD 1967-1998]. Most individuals in the study sample were non-white, and inferred to be of poor socioeconomic status. Using linearly polarized light microscopy (LPLM) on the full sample, and back-scattered scanning electron microscopy (BSE-SEM) on a subset (n=143), histomorphometric parameters, and the average tissue mineralization of the cortical and trabecular bone compartments were assessed in photomontages of transverse rib cross-sections. The influence of body size on bone mass and histomorphometry was first considered. Tissue-level changes were then interpreted in a biosocial context, exploring variation associated with adverse apartheid living conditions and adult life history. Body size does not appear to correlate with either bone mass or histomorphometry, suggesting that size-standardization may not be necessary in studies of rib bone microstructure. Compared to the women in the research sample, men exhibited delayed peak bone mass attainment, lower osteocyte densities, and lower average tissue mineralization. Women achieved peak bone mass when anticipated. Relative cortical area, osteon area, bone tissue mineralization, and cortical porosity were the best histological indicators of menopause in women. Poorer bone health indices in males infer greater systematic marginalization under apartheid rule. Men in this sample may have been more susceptible to dietary deficiencies and substance abuse issues, leading to compromised bone mass and quality. This research demonstrates that osteoporosis risk is not just a concern of the aged, white female population in South Africa. It provides novel data on an understudied population, and underscores the importance of skeletal research collections for the study of contemporary epidemiological issues.
Structural Insights into Biosynthesis and Export of the Pseudomonas aeruginosa Pel Biofilm Exopolysaccharide
Keywords: Biofilm
Exopolysaccharide
Pseudomonas aeruginosa
X-ray crystallography

Pseudomonas aeruginosa is an opportunistic pathogen that causes chronic pulmonary infections in cystic fibrosis patients. This bacterium forms biofilms at the infection site, which contributes to increased antibiotic tolerance and promotes immune evasion. Exopolysaccharides are a critical component of P. aeruginosa biofilms. The cationic polysaccharide Pel engages in ionic interactions with extracellular DNA, and provides protection against aminoglycoside antibiotics. Despite the importance of Pel in antibiotic resistance, little is known about its biosynthesis. The process begins in the cytoplasm where nucleotide-sugar precursors are synthesized. Given the monosaccharide analysis, we suspect Pel is synthesized from UDP-N-acetylgalactosamine (UDP-GalNAc) and UDP-N-acetylglucosamine (UDP-GlcNAc). In several proteobacteria a gene adjacent to the pel locus is predicted to encode a nucleotide-sugar epimerase, which we propose is involved in UDP-GalNAc synthesis. We characterized the protein product of this gene from Pseudomonas protegens, PelX. The crystal structure coupled with 1H NMR established that PelX is a UDP-GlcNAc C4-epimerase. We showed that Pel is a major constituent of P. protegens biofilms; however, deletion of pelX does not affect biofilm formation. Because UDP-hexose C4-epimerases are required in other biosynthetic pathways, we conclude that redundant epimerases located elsewhere in the genome may compensate for the absence of PelX. Following precursor polymerization, Pel is transported to the periplasm where it is modified by the bifunctional enzyme PelA. We showed that PelA is recruited to the outer membrane through a direct interaction with the PelB tetratricopeptide repeat domain, and that disrupting this interaction abrogated Pel-dependent biofilm formation. Furthermore, the interaction altered PelA’s enzymatic activities, which may serve to promote the efficient deacetylation of Pel. Once modified, Pel is secreted across the outer membrane. PelC and PelB have each been suggested to form the export channel. We solved the crystal structure of PelC, which revealed a twelve-subunit ring-shaped oligomer, that in vivo disulfide-crosslinking suggests is the physiological arrangement of PelC. We demonstrated that the negative charge within the PelC pore is critical for biofilm formation and proposed that PelC is a molecular funnel that guides the positively charged Pel towards the PelB β-barrel. Together, this work provides insight into a unique polysaccharide secretion pathway.