VictorJuiz/thesis huggingface dataset:
Ligand-based Reactions of Metal Bis- and Trisdithiolenes: Fresh Insights into Old Reactions and New Frontiers

Metal dithiolenes [M(S2C2R2)n] have been studied for decades because of their interesting chemical and spectroscopic properties, which are related to the unusual electronic properties of the dithiolene ligand. The ligand-based reactivity of metal bisdithiolenes [M(S2C2R2)2] toward alkenes has been proposed for use in alkene purification schemes. According to the proposal, compounds Ni(S2C2R2)2 (R=CF3,CN) react with simple alkenes to form stable S,S-interligand adducts and the alkene can be released from the adduct by reduction. We showed that Ni(S2C2(CF3)2)2 reacts with ethylene and 1-hexene to form, preferentially, S,S-intraligand adducts, which rapidly decompose to inactive metal-containing materials and dihydrodithiins. However, the product selectivity can be significantly modified so that stable S,S-interligand adducts are obtained as dominant products by adding [Ni(S2C2(CF3)2)2]- to Ni(S2C2(CF3)2)2/alkene reaction mixtures. Mechanistic implications are discussed. Next, the reactions of Pt(S2C2(CF3)2)2 with 2,3-dimethyl-1,3-butadiene are addressed. Prior to our report, only symmetry-allowed S,S-interligand adducts had been observed as products in the reactions between conjugated dienes and metal bisdithiolenes. We discovered a novel mode of diene binding, where two dienes bind to one dithiolene ligand of Pt(S2C2(CF3)2)2, in an C,S-intraligand fashion, forming a new chiral bisthioether ligand. From bisdithiolenes, the focus shifts to new mixed-ligand molybdenum trisdithiolenes [Mo(S2C2(CF3)2)2(S2C6H4) and Mo(S2C6H4)2(S2C2(CF3)2)]. These complexes rapidly and cleanly bind ethylene, in an S,S-intraligand fashion, as predicted by MO arguments. The resulting intraligand adducts are sufficiently stable to be characterized, in contrast to the nickel bisdithiolene case. The metal-chelated dihydrobenzodithiin, formed upon ethylene addition, can be substituted with a variety of donor ligands, allowing access to new types of molybdenum dithiolenes. We have recently extended these studies to catalytic reactions: Mo(S2C2(CF3)2)2(S2C6H4) was used as a catalyst to form dihydrobenzodithiins from (S2C6H4)2 and a variety of alkenes, in the first example of dithiolene-based reactivity being exploited for carbon-heteroatom bond-forming catalysis. Finally, the synthesis, characterization and redox reactivity of a new Fe2Ni bis-double-decker complex is described, demonstrating for the first time a sandwich complex of a metal bisdithiolene with both NiS2C2 rings in an η5 π-donating mode. For the radical cation, experimental and computation evidence indicates that the lone electron is delocalized over the entire molecule.

Keywords: dithiolene
transition metal
nickel
iron
platinum
coordination
ligand
noninnocent
Advisor: Fekl, Ulrich
Remote, Non-contact Gaze Estimation with Minimal Subject Cooperation

This thesis presents a novel system that estimates the point-of-gaze (where a person is looking at) remotely while allowing for free head movements and minimizing personal calibration requirements. The point-of-gaze is estimated from the pupil and corneal reflections (virtual images of infrared light sources that are formed by reflection on the front corneal surface, which acts as a convex mirror) extracted from eye images captured by video cameras. Based on the laws of geometrical optics, a detailed general mathematical model for point-of-gaze estimation using the pupil and corneal reflections is developed. Using this model, the full range of possible system configurations (from one camera and one light source to multiple cameras and light sources) is analyzed. This analysis shows that two cameras and two light sources is the simplest system configuration that can be used to reconstruct the optic axis of the eye in 3-D space, and therefore measure eye movements, without the need for personal calibration. To estimate the point-of-gaze, a simple single-point personal calibration procedure is needed. The performance of the point-of-gaze estimation depends on the geometrical arrangement of the cameras and light sources and the method used to reconstruct the optic axis of the eye. Using a comprehensive simulation framework developed from the mathematical model, the performance of several gaze estimation methods of varied complexity is investigated for different geometrical system setups in the presence of noise in the extracted eye features, deviation of the corneal shape from the ideal spherical shape and errors in system parameters. The results of this investigation indicate the method(s) and geometrical setup(s) that are optimal for different sets of conditions, thereby providing guidelines for system implementation. Experimental results with adults, obtained with a system that follows those guidelines, exhibit RMS point-of-gaze estimation errors of 0.4-0.6º of visual angle (comparable to the best commercially available systems, which require multiple-point personal calibration procedures). Preliminary results with infants demonstrate the ability of the proposed system to record infants' visual scanning patterns, enabling applications that are very difficult or impossible to carry out with previously existing technologies (e.g., study of infants' visual and oculomotor systems).

Keywords: Gaze
Point-of-gaze
Point-of-regard
Eye-gaze
Eye-tracking
Remote
Non-contact
Minimal subject cooperation
Single-point calibration
Minimal calibration
Pupil
Corneal reflection
Advisor: Eizenman, Moshe
Investigating Sources of Variability in Pharmacological Response to Nausea and Vomiting of Pregnancy

Nausea and vomiting of pregnancy (NVP) is the most common medical condition in pregnancy, and, unfortunately, variability exists among pregnant women in the therapeutic effect of anti-emetics as well as in factors that can exacerbate NVP. Identifying and managing these sources of variability will result in significant improvements in the quality of life of pregnant woman. This dissertation addressed clinical pharmacology strategies in managing NVP by focusing on three predominant areas of variability. The first challenge addressed in this dissertation was women with pre-existing gastrointestinal (GI) conditions and adherence and tolerability to prenatal multivitamin supplementation. To identify the role of iron in reducing adherence and increasing NVP and GI symptoms, two separate studies were conducted. In the first study, women randomized to a prenatal multivitamin supplementation with higher iron content experienced more adverse GI effects and increased severity of NVP symptoms. In the second study, after discontinuing iron-containing prenatal multivitamins, two-thirds of women in a prospective cohort reported improvement in their NVP symptoms which was corroborated with validated scales to quantify NVP severity. The second challenge addressed in this dissertation was the effect of heartburn and acid reflux on the severity of NVP. In a controlled, prospective study, women experiencing heartburn and acid reflux experienced greater severity of NVP compared to women with no GI symptoms. Furthermore, treatment of heartburn and acid reflux with acid-reducing pharmacotherapy with associated with a reduction in GI symptoms and NVP severity. Therefore, histamine 2 blockers or proton pump inhibitors, which do not appear to be associated with increased fetal risks, should be administered when required. The third clinical pharmacology challenge addressed in this dissertation was to determine the pharmacokinetic variability of the active ingredients of Diclectin®, first-line pharmacotherapy for the treatment of NVP. Large variability was observed in the area under the curve for both active metabolites: a 6.5-fold difference for pyridoxal-5’-phosphate and a 2.1-fold difference for doxylamine. Whether these pharmacokinetic differences contribute to suboptimal efficacy remains to be determined. In conclusion, based on the results presented in this dissertation, several improvements in clinical pharmacology strategies can be made to enhance management of NVP.

Keywords: nausea and vomiting of pregnancy
pregnancy
Advisor: Koren, Gideon
Participatory Action Research for Environmental Health among Senegalese Peri-urban Farmers

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.

Keywords: participatory action research
environmental health
Senegal
pesticides
wastewater
risk perception
Advisor: Cole, Donald
Mechanism of Mismatch Repair Induced Mutagenesis in 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.

Keywords: Immunology
DNA Repair
Mutagenesis
B Cell
Mismatch Repair
Somatic Hypermutation
Advisor: Martin, Alberto
Electronic Excitations in Lanthanum Cuprates Measured by Resonant Inelastic X-ray Scattering

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.

Keywords: x-ray
cuprate
RIXS
Advisor: Kim, Young-June
Evolutionary Ecology of Growth in Insects: What Maintains Variation in Growth Trajectories at the Phenotypic and Genotypic Levels?

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.

Keywords: Evolutionary ecology
Growth
Phenotypic plasticity
Insects
Condition
Advisor: Rowe, Locke
The Role of Von Hippel-Lindau Protein in the Glomerulus

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.

Keywords: von Hippel-Lindau gene/protein
Rapidly progressive glomerular nephritis
Podocytes
Hypoxia inducible factors
Advisor: Quaggin, Susan E.
Rousseau and Plato on the Legislator and the Limits of Law

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.

Keywords: Rousseau
Plato
Legislator
Positive Law
Civil Religion
Mores
Advisor: Orwin, Clifford
Andrea Riccio's Della Torre Tomb Monument: Humanism and Antiquarianism in Padua and Verona

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.

Keywords: Riccio, Andrea
Funerary art
Renaissance
bronze
humanism
Advisor: Nagel, Alexander