VictorJuiz/thesis huggingface dataset:
Participatory Action Research for Environmental Health among Senegalese Peri-urban Farmers
Keywords: participatory action research
environmental health
Senegal
pesticides
wastewater
risk perception

Participatory action research (PAR) oriented by an eco-system health framework is one approach to involving marginalised peoples in their own problem solving. A PAR project during 2005-06 that engaged peri-urban farmers in Senegal using popular education documented change on environment and health perceptions and behaviour. Health as a theme took on greater importance, as farmers related good health to their ability to work and their overall productivity. Farmers came to better recognize the symptoms of pesticide poisoning and to establish more clearly the link between pesticide-related work practices and health effects. Less clear remained their recognition of symptoms and links with wastewater use practices, though malaria and parasitic infection were linked to urban agriculture. African worldviews, including notions of locus of power, were important determinants of perceived vulnerability to risks. Farmers cited fatigue as an important clue to the work-health interface and indicator of overall wellbeing. Farmers’ understanding evolved to become more dynamic, describing the complex web of environmentally-related health risk. By 2006, farmers experimented more with less toxic pest control methods, adjusted their clothing to protect their skin and mouth, and reduced some exposure pathways through improved hygiene behaviour. However, toxic pesticides continued to be used and exposure to wastewater with limited protection remained widespread. Change was dependent upon: the researcher’s deep understanding of how farmers learned; farmers’ trust in the purveyors of new information; and the clarity, consistency and relevance of messages devised. Change varied with farmers’ literacy; the language used; and the way in which tools and media were interpreted culturally and technically. The health belief model provided a partial explanation for changes in perceptions and behaviour. Social, political and economic barriers preventing change included: leaving the onus for change on farmers, diminishing the responsibility of pesticide manufacturers and governments; land tenure arrangements which reduced investment in health and environment protection; urban poverty and illiteracy; and eco-system constraints. Examination of the PAR process, its leadership, owners, tools and ideas developed, and knowledge created provided useful insight into issues of power and control.
Mechanism of Mismatch Repair Induced Mutagenesis in Somatic Hypermutation
Keywords: Immunology
DNA Repair
Mutagenesis
B Cell
Mismatch Repair
Somatic Hypermutation

B cells produce a diverse array of antibody specificities that are of low affinity during the initial phase of a humoral immune response. However, somatic hypermutation of the rearranged V region in the immunoglobulin locus generates new antibody affinities, accompanied by the selection of B cells that produce superior antibody affinities. Somatic hypermutation is initiated by the conversion of G:C base pairs to G:U lesions by the enzyme activation induced cytosine deaminase. Left unrepaired, G:U lesions will give rise to transition mutations at G:C base pairs, but are converted to transition and transversion mutations at G:C and A:T base pairs by the paradoxical participation of the base excision repair and mismatch repair pathways. The mismatch repair pathway, which evolved to correct errors produced during DNA replication, is co-opted by hypermutating B cells to produce A:T mutations via the processing of G:U lesions. This process requires the mismatch repair components Msh2, Msh6, and Exo1, but is additionally dependent upon the translesional DNA polymerase eta, a known A:T mutator, and on ubiquitinated PCNA, an initiator of translesion synthesis. The presence of certain types of lesions in the template strand during DNA replication leads to the activation of translesion synthesis. I propose that a similar mechanism operates during somatic hypermutation to activate translesion synthesis and recruit DNA polymerase eta. Our model suggests that mismatch repair-generated single-stranded DNA tracts contain abasic sites produced as a result of uracil excision by uracil-N-glycosylase. Synthesis opposite abasic sites activates translesion synthesis and results in the recruitment of polymerase eta and the subsequent production of A:T mutations. In this thesis, I present data from hypermutating murine B cells and the B cell line Ramos to support this model, demonstrating that the base excision repair and mismatch repair pathways cooperate during somatic hypermutation to generate A:T mutations. In addition, I explore the role of the Mre11-Rad50-Nbs1 complex in its contribution to A:T mutations in Ramos cells. Taken together, these studies demonstrate that conversion of classical DNA repair pathways into mutation-generating processes is driven by the unique environment of the V region in hypermutating B cells.
Electronic Excitations in Lanthanum Cuprates Measured by Resonant Inelastic X-ray Scattering
Keywords: x-ray
cuprate
RIXS

Excitations of the valence electrons in the high-temperature superconducting cuprate La2−xSrxCuO4 were measured by Resonant Inelastic X-ray Scattering (RIXS). Several types of electronic excitations resonant at the Cu 1s →4p transition were studied over a wide range of dopings 0<x<0.35. A 500 meV excitation was observed at a reduced momentum transfer q=(π 0) corresponding to the zone boundary, whose temperature and doping dependence was the same as the two-magnon Raman scattering mode. The momentum dependence of this 2-magnon excitation agrees with recent theoretical calculations. Momentum resolved measurements of the x=0 sample revealed a broad range of excitations above and below the main charge transfer peak, and their dispersions were measured across the Brillouin zone. These include a dispersionless ∼1.8 eV peak, which is either a local crystal field (d-d excitation) or dipole-forbidden charge transfer excitation, and a dispersive 2.2 eV peak identified as a Zhang-Ng type charge-transfer exciton. The 2.2 eV peak was less dispersive than predicted from the theoretical models, due to electron-phonon coupling, as illustrated by the temperature dependent shift in the peak position. With increased hole doping, the RIXS spectral weight transfers from higher to lower energies, analogous to earlier optical conductivity studies. At the finite momentum of q=(π 0), however, the changes are most systematic: an isosbestic point was observed at 2.2 eV where the spectra of all dopings cross, and spectral weight is transferred from high to low energies, with near-linear dependence on x, in a manner suggesting that the integrated RIXS intensity is preserved. The intensity and energy variations of the spectral peaks, as well as the isosbestic point and possible sum rule, could be explained qualitatively by a rigid three-band model which includes the non-bonding oxygen, upper Hubbard, and Zhang-Rice singlet bands. The estimated properties of the bands, such as width and energy separation, are in reasonably quantitative agreement with current theoretical models and angle-resolved photoemission measurements. Moreover, anomalies in the doping dependence are similar to those observed in other types of spectroscopies. These results underscore the relevance of the RIXS method in understanding the electronic behavior of the Lanthanum cuprates.
Evolutionary Ecology of Growth in Insects: What Maintains Variation in Growth Trajectories at the Phenotypic and Genotypic Levels?
Keywords: Evolutionary ecology
Growth
Phenotypic plasticity
Insects
Condition

Growth rates are highly variable, both within and among genotypes and populations. The resolution of the trade-off between size and age at maturity has been the study of extensive research by life historians. The fitness advantages of large body size and rapid development time are well supported, leading to two predictions. First, realized growth rates should be maximized. Second, growth rate will be subject to strong stabilizing or directional selection, and consequently, low genetic variability. In real populations, despite the advantages of rapid growth, animals often, in fact, grow at rates lower than the maximum rate that is physiologically possible, even in the absence of external constraints on growth rate (e.g. resource restriction or risk of predation while foraging). This implies that growth may have direct fitness consequences that are independent of the size and age of maturity, thereby lowering the optimal rate of growth. In addition to inducing plastic declines in growth rate, such costs may also select for lower intrinsic rates of growth. Despite the strong fitness effects arising from attaining a large body size quickly, variation in growth rate persists at both the phenotypic and genetic levels. The evolutionary and ecological factors contributing to this variation in growth rate are the focus of this thesis. Growth rate variation in insect model species was produced by the manipulation of resource levels during development. By comparing fitness-associated traits and body composition of adults from different treatment groups, I identify direct costs of rapid growth that could explain why animals benefit from growth at submaximal rates. In the second part of the thesis, the relationship between environmental variation and genetic variance in growth rate is investigated by quantitative genetic analysis of body size at different ages and in different growth environments. The results of this analysis suggest that environmental stress can lead to increased genetic variance via decanalization. This has consequences for the evolvability of growth rates in changing environments.
The Role of Von Hippel-Lindau Protein in the Glomerulus
Keywords: von Hippel-Lindau gene/protein
Rapidly progressive glomerular nephritis
Podocytes
Hypoxia inducible factors

Rapidly progressive glomerulonephritis (RPGN) is a clinical syndrome characterized by loss of renal function within days to weeks and by glomerular crescents on biopsy. The pathogenesis of this disease is unclear, but circulating factors such as antineutrophil cytoplasmic antibodies (ANCA) are believed to play a major role. In this thesis, we show that deletion of the Von Hippel-Lindau gene (Vhlh) from intrinsic glomerular cells of mice is sufficient to initiate a necrotizing crescentic glomerulonephritis and the clinical features that accompany RPGN. Loss of Vhlh leads to stabilization of hypoxia-inducible factor alpha subunits (HIFαs). Using gene expression profiling, we identified de novo expression of the HIFα target gene Cxcr4. In glomeruli from mice with RPGN, the course of RPGN is markedly improved in mice treated with a blocking antibody to Cxcr4, whereas overexpression of Cxcr4 alone in podocytes of transgenic mice is sufficient to cause glomerular disease. Despite the development of glomerular disease in mice that overexpress Cxcr4, their disease was milder and lacked features of full-blown RPGN. The Vhlh gene encodes VHL protein (pVHL, product of the Von Hippel-Lindau gene) that functions as the substrate recognition component of an E3 ubiquitin ligase. Although HIFα subunits are the best characterized substrates for pVHL, additional non-HIF mediated targets have been identified. To determine the role of HIF stabilization in this RPGN model, we generated double mutants that lack aryl hydrocarbon receptor nuclear translocator gene (Arnt, also called HIF1beta), an obligate dimerization partner for HIFα subunit function. Podocyte-selective deletion of Arnt in Vhlh mutant mice completely rescued the RPGN phenotype and mice survived longer than 8 months of age. Furthermore, stabilization of HIF2α alone led to glomerular disease characterized by crescentic transformation. Collectively, these results indicate an alternative mechanism for the pathogenesis of RPGN and glomerular disease in an animal model and suggest novel molecular pathways for intervention in this disease. In addition, we demonstrate a key role for VHL-HIF-Cxcr4 molecular pathway for the integrity of the glomerular barrier.
Rousseau and Plato on the Legislator and the Limits of Law
Keywords: Rousseau
Plato
Legislator
Positive Law
Civil Religion
Mores

Both Jean-Jacques Rousseau and Plato offer doctrines of the great legislator, that highly virtuous figure who designs foundational laws for a political community, in order to shed light on the problem of legislation. This problem is that positive law is incapable of achieving the ends in political life that are expected of it, even though it is understood to be the chief tool at the disposal of the lawgiver. Close consideration of Rousseau’s and Plato’s political texts reveals that both philosophers are in agreement about the limited function of positive law, insofar as its exclusive purpose is to forestall the ills of human life. But they also agree that the effectiveness of legislation requires something more: the condition of effective laws is a comprehensive system of civic education, directed primarily at the passions, through which individual human beings are turned into good citizens. Taking into account the extreme difficulty of establishing such educational institutions, both Rousseau and Plato put forward doctrines of the legislator to indicate what sort of figure could possibly accomplish this task with success. The study finds that the two philosophers’ conceptions of the legislator are by and large similar, and finally, that they both express pessimism on the capacity of laws to promote the good life.
Andrea Riccio's Della Torre Tomb Monument: Humanism and Antiquarianism in Padua and Verona
Keywords: Riccio, Andrea
Funerary art
Renaissance
bronze
humanism

An important masterpiece by the Paduan sculptor Andrea Riccio, the Della Torre tomb monument broke with contemporary funerary monuments in both its form and content. Understanding what enabled this break with tradition is the central issue in the study of this monument—one that has not been sufficiently addressed in previous scholarship. Despite the lack of overt references to the Christian faith on the Della Torre monument, the narrative programme is concerned with two very important Christian concerns—the necessity of a life of virtue and the health and afterlife of the soul. I argue that the narrative on the tomb, influenced by contemporary funerary oratory and poetry, presents a model of virtue for the viewer. Moreover, I argue that Riccio has illustrated the presence of this exemplar by the very structure of the monument itself. This dissertation focuses on the artistic and intellectual community surrounding the creation of this monument and, in particular, on the reconciliation of this strictly all’antica monument with Christian thought in this period. Upon a thorough contextual examination, this unprecedented monument becomes less of an anomaly. It reflects the ideas of an important circle of humanists from both Padua and Verona, thus illustrating the breadth of their interests and their involvement in contemporary debates over religion, the nature and potential immortality of the soul, and the necessity of virtue. Analysing this monument within the context of humanist ideas prevalent among the individuals within the Della Torre circle, those who had, or likely had, a great influence on the significance of the monument’s narrative, gives this monument what has been long denied to it—a proper understanding of its Christian programme and didactic function. The fulfillment of this task, which promises to shed additional light on the adaptation of pagan elements to Christian purposes, is the overall aim of this work.
1H NMR Metabolomics of Earthworm Responses to Sub-lethal Polycyclic Aromatic Hydrocarbon Exposure
Keywords: Metabolomics
1H NMR

1H nuclear magnetic resonance (NMR) metabolomics was used to determine the response of earthworm exposure to polycyclic aromatic hydrocarbons (PAHs) in contact and soil tests. Eisenia fetida is recommended for toxicology testing, but to date this species has not frequently been used in environmental metabolomic studies. The metabolic profile of E. fetida was characterized with the goal of using this species in metabolomic studies. Testing several individual solvents for earthworm tissue extraction indicated that D2O buffer extracted the highest concentration of the widest variety of earthworm metabolites. Sample preparation methods were evaluated to reduce variability and achieve reproducible control groups for use in metabolomic studies. 96h depuration and intact lyophilization of earthworms before homogenization resulted in the least variation between sample extracts. This sample preparation method was used to compare E. fetida and two other earthworm species (Lumbricus rubellus and Lumbricus terrestris) and E. fetida had the most reproducible 1H NMR spectra. E. fetida was then used to identify the metabolic response after exposure to several concentrations of the polycyclic aromatic hydrocarbons (PAHs) naphthalene, phenanthrene and pyrene, individually and in mixtures. With exposure to individual PAHs in contact tests, earthworm responses were both PAH- and concentration- dependent. In earthworms exposed to PAH mixtures in contact tests, an increase in amino acids was measured. Furthermore, an increase in specific amino acids and a decrease in maltose were identified as potential indicators of sub-lethal phenanthrene exposure in soil. Lastly, the relationship between earthworm response and contaminant bioavailability in soil was tested. Contaminant bioavailability is typically assessed using indirect methods [e.g., ‘soft’ extraction techniques like hydroxypropyl cyclodextrin (HPCD) extraction]. However, it was found that the directly measured response of earthworm exposure to sub-lethal concentrations of phenanthrene in soil is related to both the total and bioavailable phenanthrene. This suggests there is potential for the use of 1H NMR metabolomics for the assessment of contaminant bioavailability. This thesis has demonstrated that E. fetida are suitable for metabolomic studies and has indicated that 1H NMR metabolomics may have potential for measuring and monitoring earthworm exposure to sub-lethal concentrations of PAHs.
Patient Preferences, Referral Practices, and Surgeon Enthusiasm for Degenerative Lumbar Spinal Surgery
Keywords: spinal surgery
patient preferences
physician preferences
regional variation

Degenerative disease of the lumbar spine (DDLS) is a common condition for which surgery is beneficial in selected patients. Wide variation in surgical referral and rates of surgery has been observed contributing to unequal access to care. Our objectives were to examine (1) the variation in preferences for referral and surgery among surgeons, family physicians (FPs) and patients, (2) how FP referral practices compare with preferences and guideline recommendations, and (3) how the ‘enthusiasm’ of patients and physicians influence regional variation in surgical rates. We used conjoint analysis in a mailed survey to elicit preferences based on clinical vignettes from surgeons, FPs and patients. A Delphi expert panel provided consensus guideline recommendations for surgical referral to compare with actual FP referral practices. Rates of surgery for DDLS, obtained from Ontario hospital discharge data, were used to quantify regional variation and regression models assessed the relationship with patient and physician enthusiasm. We identified significant differences in preferences for referral and surgery between patients, FPs and surgeons. Surgeons placed high importance on leg-dominant symptoms while patients had high importance for quality of life symptoms (i.e. severity, duration, walking tolerance). Surgical referral practices were poorly predicted by individual FP preferences and guideline recommendations based on clinical factors alone. Variation in Ontario surgical rates was higher than that of hip or knee replacements and was highly associated with the enthusiasm of surgeons (p<0.008), rather than FPs or patients. By appreciating the variation in preferences between patients and physicians, and exploring other non-clinical factors that influence referrals, we may be able to improve the efficiency of referrals and enhance the shared decision making process. With an understanding of the influence that surgeons have in driving variation in surgical rates, further research may allow us to direct strategies to improve access and allow for a more equitable delivery of care for patients suffering from DDLS.
Effective Search Techniques for Non-classical Planning via Reformulation
Keywords: artificial intelligence
automated planning
temporally extended goals
preferences
golog

Automated planning is a branch of AI that addresses the problem of generating a course of action to achieve a specified objective, given an initial state of the world. It is an area that is central to the development of intelligent agents and autonomous robots. In the last decade, automated planning has seen significant progress in terms of scalability, much of it achieved by the development of heuristic search approaches. Many of these advances, are only immediately applicable to so-called classical planning tasks. However, there are compelling applications of planning that are non-classical. An example is the problem of web service composition, in which the objective is to automatically compose web artifacts to achieve the objective of a human user. In doing so, not only the hard goals but also the \emph{preferences} of the user---which are usually not considered in the classical model---must be considered. % Also, the automated composition %should deal with abstract representations of the web %artifacts---which may also not adjust to the classical model. In this thesis we show that many of the most successful advances in classical planning can be leveraged for solving compelling non-classical problems. In particular, we focus on the following non-classical planning problems: planning with temporally extended goals; planning with rich, temporally extended preferences; planning with procedural control, and planning with procedural programs that can sense the environment. We show that to efficiently solve these problems we can use a common approach: reformulation. For each of these planning tasks, we propose a reformulation algorithm that generates another, arguably simpler instance. Then, if necessary, we adapt existing techniques to make the reformulated instance solvable efficiently. In particular, we show that both the problems of planning with temporally extended goals and with procedural control can be mapped into classical planning. Planning with rich user preferences, even after reformulation, cannot be mapped into classical planning and thus we develop specialized heuristics, based on existing heuristics, together with a branch-and-bound algorithm. Finally, for the problem of planning with programs that sense, we show that under certain conditions programs can be reduced to simple operators, enabling the use of a variety of existing planners. In all cases, we show experimentally that the reformulated problems can be solved effectively by either existing planners or by our adapted planners, outperforming previous approaches.