VictorJuiz/thesis huggingface dataset:
Characterization of Immune Responses to platelet beta3 Integrin and GPIbalpha Antigens in Murine Models of Fetal and Neonatal Immune Thrombocytopenia
Keywords: Platelets
Immune-mediated thrombocytopenia

Fetal and neonatal alloimmune thrombocytopenia (FNAIT or FNIT) is a life-threatening bleeding disorder caused by maternal antibody-mediated destruction of fetal/neonatal platelets. The incidence of FNIT is estimated at 0.5-1.5/1,000 liveborn neonates, but the frequency and mechanism of FNIT-related miscarriage are unknown. Platelet alphaIIbbeta3 integrin and GPIbalpha are the major target autoantigens in immune thrombocytopenia (ITP), but the reported incidence of anti-GPIbalpha-mediated FNIT is rare. The underlying reasons for this discrepancy have not been explored and maternal immune responses to fetal platelet antigens remain to be elucidated. In Chapter 2, we compared the pathogenesis of anti-GPIbalpha- and anti-beta3 integrin-mediated FNIT using newly developed animal models of FNIT, in which syngeneic GPIbalpha-/- or beta3-/- female mice were pre-immunized with wild-type (WT) platelets. We found, unexpectedly, that miscarriage occurred in most of anti-GPIbalpha-mediated FNIT, which is far more frequent than that mediated by anti-beta3 antibodies. Mothers with anti-GPIbalpha antibodies exhibited extensive fibrin deposition and apoptosis/necrosis in their placentas, which severely impaired placental function. We further demonstrated that anti-GPIbalpha (but not anti-beta3) antisera activated platelets and enhanced fibrin formation on platelets in vitro and thrombus growth in vivo. Finally, we demonstrated that intravenous IgG or anti-neonatal Fc receptor therapy efficiently prevented this life-threatening disease. In Chapter 3, we established naïve murine models of FNIT. Maternal anti-platelet antibody and neonatal thrombocytopenia were observed in beta3-/- mice after the 3rd delivery, but not in GPIbalpha-/- mice even after the 8th delivery. By varying the dosages of WT platelets transfused, it was revealed that platelet GPIbalpha antigen was less immunogenic than beta3 integrin. Interestingly, lipopolysaccharide significantly enhanced the immunogenicity of platelet GPIbalpha antigen, which correlated with more severe FNIT symptoms (e.g. miscarriage). In Chapter 4, we characterized splenocyte-engrafted ITP and FNIT models, in which beta3 integrin- or GPIbalpha-reactive splenocytes were transferred to WT, beta3-/- or GPIbalpha-/- mice, respectively. In summary, my data suggest that platelet GPIbalpha is less immunogenic than beta3 integrin, but infection (e.g. exposure to lipopolysaccharide) can markedly enhance the immunogenicity of platelet GPIbalpha; when anti-GPIbalpha antibody was generated, it frequently caused miscarriage, which may mask the severity and frequency of human anti-GPIbalpha-mediated FNIT.
An Investigation of the Use of Heuristics on Judgment
Keywords: biases
heuristics

How and when are individuals more or less influenced by heuristics when making judgments? The first essay of my dissertation examines whether individuals can reduce their reliance on heuristics that cause them to form biased judgments. According to Kahneman and Frederick (2002, 2005), people have a tendency to commit judgmental biases by basing their judgments on accessible heuristic cues (heuristic attributes) rather than relevant cues (target attributes). This prevalent tendency to substitute an inaccessible (but relevant) attribute with an accessible (but irrelevant) attribute results in a biased judgment. To eliminate people’s tendency to rely on heuristics, the first essay of my dissertation examines whether it is possible to make the target attribute more readily accessible in individuals’ minds by merely exposing individuals to the relevant cue – the target attribute using a non-conscious prime. I demonstrate that brief exposure (20 milliseconds) of the target attribute can increase the accessibility of the target attribute and reduce judgmental biases. The second essay of my dissertation examines the ease-of-retrieval heuristic. Previous research has shown that the ease of retrieving information leads to more favorable judgments, whereas the difficulty of retrieving information leads to less favorable judgments (Menon & Raghubir, 2003; Schwarz et al., 1991; Tormala, Petty, & Briñol, 2002; Tversky & Kahneman, 1973). Contrary to previous research, I find that, when individuals have the opportunity to use a product (i.e., direct product experience), the influence of ease-of-retrieval on their judgments becomes reversed. In particular, after a gustatory product experience with a soft drink or a tactile product experience with a hand lotion, individuals evaluate the product more (less) favorably when listing many reasons why they like (dislike) the product compared to listing a few reasons. I demonstrate that this finding is not a result of alternative explanations such as motivation levels or the reliance of the content of reasons.
Configurations oulipiennes du ludique : le discours de la contrainte dans "Cent mille milliards de poèmes" de Raymond Queneau et "Le château des destins croisés" d'Italo Calvino
Keywords: oulipo
configuration
queneau
ludique
calvino
contrainte
discours
combinatoire
poesie
recit
jeu
ecriture
lecture
litterature experimentale
statistique
sonnet
metalepse
poetique

Parmi le corpus des textes oulipiens, certains textes combinatoires – notamment ceux des origines – s’inscrivent dans une conception interactive de la littérature, bien avant que celle-ci soit théorisée par la cybernétique. Par exemple, "Cent mille milliards de poèmes" de Raymond Queneau (1961) métatextualise le potentiel reconfigurateur du sonnet sur le mode de l’interaction physique du lecteur avec le texte, tout comme "Le château des destins croisés" d’Italo Calvino (1969) métatextualise le potentiel interprétatif du lecteur sur le mode de l’embranchement. Pourtant, les oulipiens ont longtemps été accusés de négliger le rôle du lecteur au profit de la valorisation des jeux d’écriture, alors que les premiers textes oulipiens montrent, en fait, le contraire. Les théoriciens du ludisme littéraire insistent davantage sur l’aspect social du jeu, faisant de la littérature une simple forme de divertissement. Le jeu oulipien, quant à lui, est de l’ordre du construit et de la configuration. En s’appuyant doublement sur un programme d’écriture et une programmation lectorale, le discours de la contrainte prend en charge les modalités de l’interaction, soit sur le mode de l’indifférence – si l’interaction est cryptée – soit sur le mode de la collaboration – si le projet auctorial est de rendre visible la propriété interactive de son texte, comme c’est le cas de "Cent mille milliards de poèmes" et du "Château des destins croisés". Alors que le champ des littératures à contraintes est constitué majoritairement de modèles de lecture cryptanalytique et privilégie les textes qui programment une modalité implicite d'inscription de la contrainte, cette étude montre que l'intégration explicite par le discours de la contrainte exige une interaction qui sert un projet plus vaste de lisibilité en fonction des règles génériques qui sont spécifiques à la poésie et à la fiction. Le cinquantenaire de l’Oulipo valait bien une revalorisation de ce qui constitue pour nous la double spécificité du texte oulipien à contraintes : ses propriétés interactives et l'appui singulier qu'il prend sur la potentialité des formes littéraires.
Fighting Ghosts, Playing Whist, and Fencing with Fire: Three Technologies of Illusion in Performance in Nineteenth-century London
Keywords: John Nevil Maskelyne
Psycho
John Henry Pepper
Pepper's Ghost
Henry Dircks
Sir Henry Irving
Faust
electric duel
Lyceum Theatre
Egyptian Hall
Royal Polytechnic Institute
secular magic
Victorian stage illusion
technologies of illusion

Technologies of illusion are technologies used to evoke an emotional response in an audience by producing an effect that seems to violate the laws of physics; for example, conjuring apparatuses and special effects are technologies of illusion. Traditional histories suggest that audience members value technologies of illusion for their mystery: when they understand the mechanism responsible for an effect, they lose interest in that technology. This view is empirically unsupported. Instead, technologies of illusion should be considered not as apparent violations of nature but as representations of violations of nature. Like all representations, their effectiveness hinges not on the deception of the audience by the performer but on collaboration between both parties to establish the illusion within the socio-cultural contexts that give it meaning. The analysis of three case studies, each of which embodies one of the main fields in which technologies of illusion were used in performance in nineteenth-century London, supports this understanding. The ghost illusion jointly developed by Henry Dircks and John Henry Pepper in 1862 and presented by the latter at the Royal Polytechnic Institution is representative of technologies of illusion used in popular-science demonstrations. Likewise, the card-playing pseudo-automaton Psycho developed by conjuror J. N. Maskelyne in 1875 is representative of technologies of illusion used in performances of secular magic, and the electric sword duel in Sir Henry Irving’s 1885 production of Faust is representative of technologies of illusion used to produce theatrical spectacle. Microhistories of each technology based on primary sources and informed by tacit knowledge gained through performance experiments demonstrate that secrecy of mechanism alone did not guarantee popular acclaim. Despite widespread knowledge of the mechanisms responsible for each illusion, these performers worked with their audiences within the conventions of their respective fields to construct meaning for their effects and achieve success for each technology.
Naughty Nuns and Promiscuous Monks: Monastic Sexual Misconduct in Late Medieval England
Keywords: monasticism
medieval history
nuns
monks
sexuality
social history
medieval England
medieval history
Middle Ages
medieval Church

This dissertation examines monastic sexual misconduct in cloistered religious houses in the dioceses of Lincoln and Norwich between 1430 and 1530. Traditionally, any study of English monasticism during the late Middle Ages entailed the chronicling of a slow decline and decay. Indeed, for nearly 500 years, historiographical discourse surrounding the Dissolution of Monasteries (1536-40) has emphasized its inevitability and presented late medieval monasticism as a lacklustre institution characterized by worsening standards, corruption and even sexual promiscuity. As a result, since the Dissolution, English monks and nuns have been constructed into naughty characters. My study, centred on the sources that led to this claim, episcopal visitation records, will demonstrate that it is an exaggeration due to the distortion in perspective allowed by the same sources, and a disregard for contextualisation and comparison between nuns and monks. In Chapter one, I discuss the development of the monastic ‘decline narrative’ in English historiography and how the theme of monastic lasciviousness came to be so strongly associated with it. Chapter two presents an overview of the historical background of late medieval English monasticism and my methodological approach to the sources. In Chapter three, I survey some of the broad characteristics of monastic sexual misconduct. In particular, I discuss the overall rate of sexual misconduct, the sexual partners of monks and nuns, same-sex relationships, and conventual pregnancies. Chapter four examines the episcopal response to sexual scandal and their use of visitatorial inquisition, compurgation, penance and written injunctions. Finally, in Chapter five, I discuss the connection between the Dissolution and sexual misconduct, and in particular, the sodomy accusations made by Suppression agents in the infamous Compendium Compertorum. The overarching conclusion is that monastic sexual misconduct in the medieval monasteries of Lincoln and Norwich (at the level of individuals) occurred at very low and predictable rates. Nearly half of the monasteries experienced a case of sexual misconduct over the 100 years examined for this study, and certainly a bishop could expect to encounter numerous instances of it during his career. However, although sexual misconduct was clearly considered a sin and corrected by bishops and monastic leaders, in general, it was very much de-emphasized compared to other disciplinary issues. Time and time again, the bishops examined for this study emphasized economic and leadership issues over problems with chastity.
Clues to the Causes of Mass Extinctions in Earth History from U-Pb CA-ID-TIMS Geochronology
Keywords: geochronology
mass extinctions

Mass extinctions in Earth history have repeatedly altered the course of evolution of life on our planet. The extent and rapid rate at which they occurred required processes that were global in scale and catastrophic in nature. Asteroid impacts and volcanic eruptions are cited as triggers of environmental change and subsequent biological turnover. Causal mechanisms remain enigmatic, partly due to a lack of precise and accurate ages to establish the timing and duration of events, and to limitations of interpreting existing ages due to inter-method and inter-laboratory bias. Two of the largest extinction events in the Phanerozoic were triggered by different processes. The Cretaceous-Paleogene (K-Pg) extinctions are widely accepted as due to the consequences of impact, yet the link between the K-Pg boundary layer and Chicxulub impact has been questioned. Shocked zircon from K-Pg ejecta in Spain and Italy are 550 ± 6 Ma (2 and show a correlation between intensity of shock metamorphism and discordance to the time of impact. The data are identical to those from Chicxulub and North American ejecta sites and together support a genetic association. Clarification of this link is essential to understanding the role of impact on end-Cretaceous climate and environment. The end-Permian extinctions are the most profound in the rock record and eruption of the Siberian Flood Volcanic rocks as the trigger is supported by U-Pb ID-TIMS ages. The ages indicate that the marine extinctions in China occurred early in the eruptive sequence prior to 251.99 ± 0.18 Ma (2 synchronous with emission of climate forcing gases. Continued environmental stress from eruption in the Noril’sk and Meymecha-Kotuy areas, may have promoted terrestrial extinctions in the Karoo Basin of South Africa and delayed recovery. The extent of environmental stress is related to the composition of target lithologies, the nature, quantity, and rate of emission of the volatile load, pre-existing oceanic and atmospheric conditions, and global plate configuration.
Isolation of Cellulose Nanofibres: Elucidation of a Novel Approach Utilizing Fungal Pretreatment
Keywords: Cellulose
Nanofibres
Ophiostoma Ulmi
Internal defibrillation
Hydrogen bond
FTIR spectroscopy
NMR spectroscopy
Cellulose nanofibre isolation

In plant cell wall, cellulose chains are organized into perfect stereoregular configuration called microfibrils through a regular network of inter and intramolecular hydrogen bonds. The cellulose microfibril along with hemicellulose chains that tether to the cellulose microfibrils and other polysaccharides through hydrogen bonding forms the cell wall structural framework. Isolation and application of cellulose nanofibres is expanding rapidly due to their environmental benefits and specific strength properties, especially in nano-biocomposite area. Currently, cellulose nanofibres are isolated from natural fibres through a combination of high energy refining and high pressure homogenization or through a combination of biological and mechanical process that involves fibre treatment with hydrolytic enzymes followed by high pressure homogenization and all of these processes are very energy intensive. In this research, a fungal pre-treatment for wood fibres is investigated which can bring about internal defibrillation in the fibres through reduction of hydrogen bonds and cleavage of hemicellulose chains tethering the cellulose microfibrils together. The pre-treatment of wood fibres with Ophiostoma Ulmi, a causative agent of Dutch elm disease in Elm trees, has found to reduce the energy requirement to isolate cellulose nanofibres. The treatment has found to bring about internal defibrillation in the fibres by disrupting the hydrogen bonding that holds the hemicellulose - cellulose microfibril network and the cellulose chain in the cellulose microfibrils together. The effect of bio-treatment on hydrogen bonding density and their nature in the fibre cell wall was investigated using FT-IR and 13C NMR and its effect on cellulose structure using FT-IR and X-ray crystallography. The treated fibres showed a decrease in the intra-molecular hydrogen bonding density and crystallinity and also a decrease in the hemicellulose content. The net energy required to isolate cellulose nanofibres from bio-treated fibres was estimated at 2,000 kWh/T compared to 16,000 kWh/T required for isolating nanofibres from untreated fibres. The isolation of cellulose nanofibres from treated and untreated fibres by refining in disk refiner tends to obey the Rittinger’s law. These observations confirm the fact that Ophiostoma ulmi treatment of fibres can significantly reduce the energy required to isolate cellulose nanofibres from wood pulp fibres.
Using Chemogenomic Screens to Study the Mechanism of Action of an Antifungal Agent and Competitive Fitness in Yeast
Keywords: Chemogenomics
Yeast
Saccharomyces cerevisiae
chitosan oligosaccharide
Chitosan
chitooligosaccharide
antifungal
membrane
Sytox
Fluconazole
Amphotericin B
Terbinafine
haploinsufficiency profiling
homozygous profiling
multicopy suppression profiling
membrane permeabilization
ADP ribosylation factor–like
ARL1
heterozygous deletion strains
suppressor strains
fitness
ergosterol biosynthesis
genome-wide assay
Selection
Competitive fitness
Experimental evolution

Using chemogenomic fitness assays in S cerevisiae, I examined the mechanism of action of an antifungal agent and whether the loss of specific genes confers a competitive fitness advantage during long term culture. Chitosan oligosaccharide (COS), a deacetylated derivative of chitin, is presumed to act by disrupting the cell membranes of microorgansims. Three different chemogenomic fitness assays, haploinsufficiency (HIP), homozygous deletion (HOP) and multicopy suppression (MSP) profiling, were combined with a transcriptomic analysis to gain insight in to the mode of action and mechanisms of resistance to COS. The fitness assays identified deletion strains sensitive to COS and overexpression strains that suppress COS inhibition. The genes associated with these strains are involved in processes such as: transcription, translation, membrane signaling, trafficking and structure, cell division, and proteasome processes. Transcriptome analysis of wild type and 5 suppressors of COS in the presence and absence of COS revealed up-regulated transcripts in the suppressor strains involved in processes such as transcription, cell cycle, and Ras signaling. Down-regulated transcripts included genes related to protein folding and oxidative respiration. Overexpression of the ARL1 gene, a Ras-related protein involved in membrane trafficking, provided protection against COS-induced cell membrane permeability and damage. The ARL1 COS-resistant over-expression strain was as sensitive to Amphotericin B, Fluconazole and Terbinafine as the wild type cells and, when COS and Fluconazole were used in combination they acted in a synergistic fashion. These results indicate that COS’ mechanism of action is different from other commonly studied fungicides that target membranes, suggesting that COS may be an effective fungicide against drug-resistant fungal pathogens. To identify deletion strains that have better competitive fitness when grown in culture, I evaluated the homozygous and heterozygous deletion collections in a long term evolution experiment. After 600 generations, less than 1 % of the strains in each deletion collection were still present. 2-D differential gel electrophoresis protein analysis revealed that the selected populations are enriched for ribosome components. The known functions of the deleted genes in the selected strains provide insight into possible mechanisms that make these strains more fit; further experiments will help confirm these mechanisms.
Regulation of Multidrug Resistance at the Developing Blood-brain Barrier
Keywords: Multidrug Resistance
P-glycoprotein
Breast Cancer Resistance Protein
Glucocorticoid
Cytokine
Brain
Endothelial
Guinea Pig
Development

P-glycopotein (P-gp) plays an important role in the protection of the fetal brain from foreign compounds. The studies described in this thesis have demonstrated that blood-brain barrier (BBB) P-gp protein and activity levels increase in concert with rising levels of fetal plasma glucocorticoids. Brain endothelial cells (which form the primary BBB) become increasingly responsive to the upregulatory effects of glucocorticoids with advancing gestation. These data provide strong evidence that fetal BBB drug resistance likely increases due to rising fetal glucocorticoid levels. The rise in BBB P-gp protection is subsequent to a decline in global fetal protection provided by placental P-gp. The decline in placental P-gp protection suggests that a “window” during development exists in which the fetus and fetal brain are susceptible to teratogens that may be in maternal circulation. Many women take prescription medications during pregnancy, a large number of which are potentially teratogenic with many of these being P-gp substrates. The susceptibility of the developing fetus to circulating teratogens may be further increased in pregnancies complicated by infection. Infections are common during pregnancy and result in the release of pro-inflammatory cytokines - potent inhibitors of P-gp. This thesis describes how pro-inflammatory cytokines released during infection inhibit fetal BBB drug resistance, particularly as the cells become more responsive to cytokines near term. Infection also accounts for ~40% of preterm births. These women often receive synthetic glucocorticoids (a potent modulator of P-gp) to mature the fetal lungs. Prenatal exposure to synthetic glucocorticoids can potentially further enhance the responsiveness of the developing BBB to pro-inflammatory cytokines, widening the “window” in which the fetal brain is susceptible to teratogens - putting the fetal brain at even more risk. The understanding of fetal multidrug resistance regulation and alteration has improved through the studies presented in this thesis. Understanding how events during gestation can negatively affect the drug susceptibility of the offspring will be critical in the development of future therapies to counteract these effects.