Forms of the Postmodern Historical Novel : Christoph Ransmayr, Daniel Kehlmann, Wolfgang Hildesheimer

L’émergence du postmodernisme aux Etats-unis, mouvement esthétique rejetant les dogmes modernistes, date des années 1960. En s’imposant, durant les dernières décennies du 20ème siècle, comme le paradigme esthétique de l’architecture, des arts et de la littérature, le postmodernisme a également créé les conditions propres à une renaissance du roman historique. Cependant, la fiction historique postmoderne constitue maintenant une nouvelle forme du genre basée sur la parodie, l’ironie et le scepticisme envers les discours dominants. Cette nouvelle forme ne se limite plus à la présentation des récits dans un cadre historique réaliste. Elle remet plutôt en question la validité et par conséquent la nature même du discours historique, problématisant et mettant ainsi à l’avant le processus d’interprétation et de reconstruction du passé. Dans cette optique, la fiction historique contemporaine reflète les débats actuels sur les formes de l’historiographie, débats lancés par Hayden White. Dans les années 1980, la fiction historique a de nouveau fleuri dans l'espace culturel allemand tout comme ailleurs. Le présent mémoire analyse des formes postmodernes de la fiction historique en se basant sur trois romans historiques de langue allemande parus entre 1981 et 2005: Die Schrecken des Eises und der Finsternis de Christoph Ransmayr, Die Vermessung der Welt de Daniel Kehlmann et Marbot : Eine Biographie de Wolfgang Hildesheimer. L’analyse s'appuie sur divers modèles de la fiction postmoderne, en particulier sur le schéma de catégorisation du roman historique élaboré par Ansgar Nünning. Le mémoire montre dans quelle mesure ces romans appliquent des moyens stylistiques typiques pour le postmodernisme et portent un regard critique ou comique sur l’histoire et la culture allemande et autrichienne.

The creation and evaluation of novel canine training aids for cocaine using molecularly encapsulated sol-gel polymers and an investigation of canine field accuracy

Biological detectors, such as canines, are valuable tools used for the rapid identification of illicit materials. However, recent increased scrutiny over the reliability, field accuracy, and the capabilities of each detection canine is currently being evaluated in the legal system. For example, the Supreme Court case, State of Florida v. Harris, discussed the need for continuous monitoring of canine abilities, thresholds, and search capabilities. As a result, the fallibility of canines for detection was brought to light, as well as a need for further research and understanding of canine detection. This study is two-fold, as it looks to not only create new training aids for canines that can be manipulated for dissipation control, but also investigates canine field accuracy to objects with similar odors to illicit materials. ^ It was the goal of this research to improve upon current canine training aid mimics. Sol-gel polymer training aids, imprinted with the active odor of cocaine, were developed. This novel training aid improved upon the longevity of currently existing training aids, while also provided a way to manipulate the polymer network to alter the dissipation rate of the imprinted active odors. The manipulation of the polymer network could allow handlers to control the abundance of odors presented to their canines, familiarizing themselves to their canine’s capabilities and thresholds, thereby increasing the canines’ strength in court.^ The field accuracy of detection canines was recently called into question during the Supreme Court case, State of Florida v. Jardines, where it was argued that if cocaine’s active odor, methyl benzoate, was found to be produced by the popular landscaping flower, snapdragons, canines will false alert to said flowers. Therefore, snapdragon flowers were grown and tested both in the laboratory and in the field to determine the odors produced by snapdragon flowers; the persistence of these odors once flowers have been cut; and whether detection canines will alert to both growing and cut flowers during a blind search scenario. Results revealed that although methyl benzoate is produced by snapdragon flowers, certified narcotics detection canines can distinguish cocaine’s odor profile from that of snapdragon flowers and will not alert.^

Exoneration or observation? Examining a novel difference between liars and truth tellers

Individual cues to deception are subtle and often missed by lay people and law enforcement alike. Linguistic statement analysis remains a potentially useful way of overcoming individual diagnostic limitations (e.g. Criteria based Content Analysis; Steller & Köhnken, 1989; Reality monitoring; Johnson & Raye, 1981; Scientific Content Analysis; Sapir, 1996). Unfortunately many of these procedures are time-consuming, require in-depth training, as well as lack empirical support and/or external validity. The current dissertation develops a novel approach to statement veracity analysis that is simple to learn, easy to administer, theoretically sound, and empirically validated. ^ Two strategies were proposed for detecting differences between liars' and truth-tellers' statements. Liars were hypothesized to strategically write statements with the goal of self-exoneration. Liars' statements were predicted to contain more first person pronouns and fewer third person pronouns. Truth-tellers were hypothesized to be motivated toward being informative and thus produce statements with fewer first person pronouns and more third person pronouns. Three studies were conducted to test this hypothesis. The first study explored the verbal patterns of exoneration and informativeness focused statements. The second study used a traditional theft paradigm to examine these verbal patterns in guilty liars and innocent truth tellers. In the third study to better match the context of a criminal investigation a cheating paradigm was used in which spontaneous lying was induced and written statements were taken. Support for the first person pronoun hypothesis was found. Limited support was found for the third person pronoun hypothesis. Results, implications, and future directions for the current research are discussed.^

Forms of the Postmodern Historical Novel : Christoph Ransmayr, Daniel Kehlmann, Wolfgang Hildesheimer

L’émergence du postmodernisme aux Etats-unis, mouvement esthétique rejetant les dogmes modernistes, date des années 1960. En s’imposant, durant les dernières décennies du 20ème siècle, comme le paradigme esthétique de l’architecture, des arts et de la littérature, le postmodernisme a également créé les conditions propres à une renaissance du roman historique. Cependant, la fiction historique postmoderne constitue maintenant une nouvelle forme du genre basée sur la parodie, l’ironie et le scepticisme envers les discours dominants. Cette nouvelle forme ne se limite plus à la présentation des récits dans un cadre historique réaliste. Elle remet plutôt en question la validité et par conséquent la nature même du discours historique, problématisant et mettant ainsi à l’avant le processus d’interprétation et de reconstruction du passé. Dans cette optique, la fiction historique contemporaine reflète les débats actuels sur les formes de l’historiographie, débats lancés par Hayden White. Dans les années 1980, la fiction historique a de nouveau fleuri dans l'espace culturel allemand tout comme ailleurs. Le présent mémoire analyse des formes postmodernes de la fiction historique en se basant sur trois romans historiques de langue allemande parus entre 1981 et 2005: Die Schrecken des Eises und der Finsternis de Christoph Ransmayr, Die Vermessung der Welt de Daniel Kehlmann et Marbot : Eine Biographie de Wolfgang Hildesheimer. L’analyse s'appuie sur divers modèles de la fiction postmoderne, en particulier sur le schéma de catégorisation du roman historique élaboré par Ansgar Nünning. Le mémoire montre dans quelle mesure ces romans appliquent des moyens stylistiques typiques pour le postmodernisme et portent un regard critique ou comique sur l’histoire et la culture allemande et autrichienne.

New weapons to fight old enemies: novel strategies for the (bio)control of bacterial biofilms in the food industry

Biofilms are microbial communities characterized by their adhesion to solid surfaces and the production of a matrix of exopolymeric substances, consisting of polysaccharides, proteins, DNA and lipids, which surround the microorganisms lending structural integrity and a unique biochemical profile to the biofilm. Biofilm formation enhances the ability of the producer/s to persist in a given environment. Pathogenic and spoilage bacterial species capable of forming biofilms are a significant problem for the healthcare and food industries, as their biofilm-forming ability protects them from common cleaning processes and allows them to remain in the environment post-sanitation. In the food industry, persistent bacteria colonize the inside of mixing tanks, vats and tubing, compromising food safety and quality. Strategies to overcome bacterial persistence through inhibition of biofilm formation or removal of mature biofilms are therefore necessary. Current biofilm control strategies employed in the food industry (cleaning and disinfection, material selection and surface preconditioning, plasma treatment, ultrasonication, etc.), although effective to a certain point, fall short of biofilm control. Efforts have been explored, mainly with a view to their application in pharmaceutical and healthcare settings, which focus on targeting molecular determinants regulating biofilm formation. Their application to the food industry would greatly aid efforts to eradicate undesirable bacteria from food processing environments and, ultimately, from food products. These approaches, in contrast to bactericidal approaches, exert less selective pressure which in turn would reduce the likelihood of resistance development. A particularly interesting strategy targets quorum sensing systems, which regulate gene expression in response to fluctuations in cell-population density governing essential cellular processes including biofilm formation. This review article discusses the problems associated with bacterial biofilms in the food industry and summarizes the recent strategies explored to inhibit biofilm formation, with special focus on those targeting quorum sensing.

Étudiants et apprenants de catalan en Catalogne du nord : écho du conflit diglossique espagnol

Dans le département des Pyrénées orientales, nombreux sont ceux qui apprennent le catalan, langue régionale aux côtés du français. Cet espace géographique plurilingue se rattache à l’entité plus vaste de la Catalogne, berceau de conflits diglossique virulents, au coeur de revendications d’autonomie qui secouent le climat politique actuel en Espagne. Cet article rend compte d’une enquête réalisée dans le cadre du projet «Représentations des langues et des identités en Méditerranée en contexte plurilingue» (EA 739 Dipralang). Il s’agit de mettre en évidence les représentations du catalan et du français chez les apprenants de catalan, qu’ils soient locuteurs natifs, étudiants à l’université, dans les filières spécifiques ou comme option, ou encore qu’ils se destinent à l’enseigner dans les classes bilingues. Nous faisons l’hypothèse que ces représentations diffèrent en fonction de l’implication dans la diglossie français-catalan et qu’elles sont un écho au conflit linguistique propre à la Catalogne. Pour la vérifier, nous utilisons la méthode d’analyse combinée mise au point par Bruno Maurer.

Anti-proliferative effects of novel hydroxyamides and triazoles

Chemotherapy is a major cancer treatment option. The synthesis of new compounds with anti-proliferative properties and specificity is a current challenge in drug-discovery today. Our goal was to develop compounds, either hydroxyamides derived from D-glucuronic acid or triazole-cinchone hybrids, and to evaluate their anti-proliferative properties. Anti-proliferative activity of the newly synthesized compounds was examined against human breast adenocarcinoma (MCF-7) and human colon carcinoma (MDST8) cell-lines. Cell growth and viability was analysed by the Cell-Counting Kit-8 method. The 5-fluoroacil was used as a positive control. The compounds were studied between 10-9-10-5M. Fifteen compounds from the hydroxyamide family and two triazole compounds were investigated. Most of the compounds from the hydroxyamide family revealed mild (~20%) to moderate (50%) anti-proliferative effects in both cell-lines, with the exception of Hydroxyamide B1 which did not affect MDST8 proliferation, and hydroxyamide B3 where proliferation of MDST8 was inhibited by 90%. Triazoles (A and B) evoked a strong (~100%) anti-proliferative effect of MDST8 cell-lines. Proliferation of MCF-7 was selectively and effectively (~98%) inhibited by triazole B while triazole A had a mild effect. In conclusion, when compared to hydroxyamides, triazoles evoked a stronger anti-proliferative effect and might be promising anti-tumoral drugs.

Design and Synthesis of Novel Kinase Inhibitors for the Treatment of Chronic Respiratory Diseases

In 2017, Chronic Respiratory Diseases accounted for almost four million deaths worldwide. Unfortunately, current treatments are not definitive for such diseases. This unmet medical need forces the scientific community to increase efforts in the identification of new therapeutic solutions. PI3K delta plays a key role in mechanisms that promote airway chronic inflammation underlying Asthma and COPD. The first part of this project was dedicated to the identification of novel PI3K delta inhibitors. A first SAR expansion of a Hit, previously identified by a HTS campaign, was carried out. A library of 43 analogues was synthesised taking advantage of an efficient synthetic approach. This allowed the identification of an improved Hit of nanomolar enzymatic potency and moderate selectivity for PI3K delta over other PI3K isoforms. However, this compound exhibited low potency in cell-based assays. Low cellular potency was related to sub optimal phys-chem and ADME properties. The analysis of the X-ray crystal structure of this compound in human PI3K delta guided a second tailored SAR expansion that led to improved cellular potency and solubility. The second part of the thesis was focused on the rational design and synthesis of new macrocyclic Rho-associated protein kinases (ROCKs) inhibitors. Inhibition of these kinases has been associated with vasodilating effects. Therefore, ROCKs could represent attractive targets for the treatment of pulmonary arterial hypertension (PAH). Known ROCK inhibitors suffer from low selectivity across the kinome. The design of macrocyclic inhibitors was considered a promising strategy to obtain improved selectivity. Known inhibitors from literature were evaluated for opportunities of macrocyclization using a knowledge-based approach supported by Computer Aided Drug Design (CADD). The identification of a macrocyclic ROCK inhibitor with enzymatic activity in the low micro molar range against ROCK II represented a promising result that validated this innovative approach in the design of new ROCKs inhibitors.

Harnessing the cellular and molecular complexity of high-risk neuroblastoma to investigate novel potential treatment approaches

Neuroblastoma (NB) is the most common type of tumor in infants and the third most common cancer in children. Current clinical practices employ a variety of strategies for NB treatment, ranging from standard chemotherapy to immunotherapy. Due to a lack of knowledge about the molecular mechanisms underlying the disease's onset, aggressive phenotype, and therapeutic resistance, these approaches are ineffective in the majority of instances. MYCN amplification is one of the most well-known genetic alterations associated with high risk in NB. The following work is divided into three sections and aims to provide new insights into the biology of NB and hypothetical new treatment strategies. First, we identified RUNX1T1 as a key gene involved in MYCN-driven NB onset in a transgenic mouse model. Our results suggested that that RUNX1T1 may recruit the Co-REST complex on target genes that regulate the differentiation of NB cells and that the interaction with RCOR3 is essential. Second, we provided insights into the role of MYCN in dysregulating the CDK/RB/E2F pathway controlling the G1/S transition of the cell cycle. We found that RB is dispensable in regulating MYCN amplified NB's cell cycle, providing the rationale for using cyclin/CDK complexes inhibitors in NBs carrying MYCN amplification and relatively high levels of RB1 expression. Third, we generated an M13 bacteriophage platform to target GD2-expressing cells in NB. Here, we generated a recombinant M13 phage capable of binding GD2-expressing cells selectively (M13GD2). Our results showed that M13GD2 chemically conjugated with the photosensitizer ECB04 preserves the retargeting capability, inducing cell death even at picomolar concentrations upon light irradiation. These results provided proof of concept for M13 phage employment in targeted photodynamic therapy for NB, an exciting strategy to overcome resistance to classical immunotherapy.

Design and characterization of wideband Hall current sensors in BCD technology for smart power and metering applications

Power electronic circuits are moving towards higher switching frequencies, exploiting the capabilities of novel devices to shrink the dimension of passive components. This trend demands sensors capable enough to operate at such high frequencies. This thesis aims to demonstrate through experimental characterization, the broadband capability of a fully integrated CMOS X-Hall current sensor in current mode interfaced with a transimpedance amplifier (TIA), chip CH09, realized in CMOS technology for power electronics applications such as power converters. The system exploits a common-mode control system to operate the dual supply system, 5-V for the X-Hall probe and 1.2-V for the readout. The developed prototype achieves a maximum acquisition bandwidth of 12 MHz, a power consumption of 11.46 mW, resolution of 39 mArms, a sensitivity of 8 % /T, and a FoM of 569-MHz/A2mW, significantly higher than current state-of-the-art. Further enhancements were proposed to CH09 as a new chip CH100, aiming for accuracy levels prerequisite for a real-time power electronic application. The TIA was optimized for a wider bandwidth of 26.7 MHz with nearly 30% reduction of the integrated input referred noise of 26.69 nArms at the probe-AFE interface in the frequency band of DC-30 MHz, and a 10% improvement in the dynamic range. The expected input range is 5-A. The chip incorporates a dual sensing chain for differential sensing to overcome common mode interferences. A novel offset cancellation technique is proposed that would require switching of polarity of bias currents. Thermal gain drift was improved by a factor of 8 and will be digitally calibrated utilizing a new built-in temperature sensor with a post calibration measurement accuracy greater than 1%. The estimated power consumption of the entire system is 55.6 mW. Both prototypes have been implemented through a 90-nm microelectronic process from STMicroelectronics and occupy a silicon area of 2.4 mm2.

Study of the tracking performance of a liquid Argon detector based on a novel optical imaging concept

The Deep Underground Neutrino Experiment (DUNE) is a long-baseline accelerator experiment designed to make a significant contribution to the study of neutrino oscillations with unprecedented sensitivity. The main goal of DUNE is the determination of the neutrino mass ordering and the leptonic CP violation phase, key parameters of the three-neutrino flavor mixing that have yet to be determined. An important component of the DUNE Near Detector complex is the System for on-Axis Neutrino Detection (SAND) apparatus, which will include GRAIN (GRanular Argon for Interactions of Neutrinos), a novel liquid Argon detector aimed at imaging neutrino interactions using only scintillation light. For this purpose, an innovative optical readout system based on Coded Aperture Masks is investigated. This dissertation aims to demonstrate the feasibility of reconstructing particle tracks and the topology of CCQE (Charged Current Quasi Elastic) neutrino events in GRAIN with such a technique. To this end, the development and implementation of a reconstruction algorithm based on Maximum Likelihood Expectation Maximization was carried out to directly obtain a three-dimensional distribution proportional to the energy deposited by charged particles crossing the LAr volume. This study includes the evaluation of the design of several camera configurations and the simulation of a multi-camera optical system in GRAIN.

Novel methods of state estimation and parameter identification for high-performance motorcycles

This research activity aims at providing a reliable estimation of particular state variables or parameters concerning the dynamics and performance optimization of a MotoGP-class motorcycle, integrating the classical model-based approach with new methodologies involving artificial intelligence. The first topic of the research focuses on the estimation of the thermal behavior of the MotoGP carbon braking system. Numerical tools are developed to assess the instantaneous surface temperature distribution in the motorcycle's front brake discs. Within this application other important brake parameters are identified using Kalman filters, such as the disc convection coefficient and the power distribution in the disc-pads contact region. Subsequently, a physical model of the brake is built to estimate the instantaneous braking torque. However, the results obtained with this approach are highly limited by the knowledge of the friction coefficient (μ) between the disc rotor and the pads. Since the value of μ is a highly nonlinear function of many variables (namely temperature, pressure and angular velocity of the disc), an analytical model for the friction coefficient estimation appears impractical to establish. To overcome this challenge, an innovative hybrid solution is implemented, combining the benefit of artificial intelligence (AI) with classical model-based approach. Indeed, the disc temperature estimated through the thermal model previously implemented is processed by a machine learning algorithm that outputs the actual value of the friction coefficient thus improving the braking torque computation performed by the physical model of the brake. Finally, the last topic of this research activity regards the development of an AI algorithm to estimate the current sideslip angle of the motorcycle's front tire. While a single-track motorcycle kinematic model and IMU accelerometer signals theoretically enable sideslip calculation, the presence of accelerometer noise leads to a significant drift over time. To address this issue, a long short-term memory (LSTM) network is implemented.

A novel approach to Non-Orthogonal Random Access with application to NB-IoT NTN systems

In the Massive IoT vision, millions of devices need to be connected to the Internet through a wireless access technology. However, current IoT-focused standards are not fully prepared for this future. In this thesis, a novel approach to Non-Orthogonal techniques for Random Access, which is the main bottleneck in high density systems, is proposed. First, the most popular wireless access standards are presented, with a focus on Narrowband-IoT. Then, the Random Access procedure as implemented in NB-IoT is analyzed. The Non-Orthogonal Random Access technique is presented next, along with two potential algorithms for the detection of non-orthogonal preambles. Finally, the performance of the proposed solutions are obtained through numerical simulations.

Otoneurological Evaluation: Current Good Practice.

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Desquamation Is A Novel Phenomenon For Collective Prostate Epithelial Cell Deletion After Castration.

The mechanism underlying castration-induced prostate regression, which is a classical physiological concept translated into the therapeutic treatment of advanced prostate cancer, involves epithelial cell apoptosis. In searching for events and mechanisms contributing to prostate regression in response to androgen modulation, we have frequently observed the collective deletion of epithelial cells. This work was undertaken to characterize this phenomenon hereafter named desquamation and to verify its presence after 17β-estradiol (E2) administration. Electron microscopy revealed that the desquamating cells had preserved cell-cell junctions and collapsed nuclear contents. The TUNEL reaction was negative for these cells, which were also negative for cleaved caspases-8, -9, -3 and nuclear apoptosis-inducing factor. Detailed analyses revealed that the condensed chromatin was first affected detaching from the nuclear lamina, which was observable after lamin A immunohistochemistry, suggesting the lack of lamin A degradation. A search in animals treated with supraphysiological E2 employed as an alternative anti-androgen treatment revealed no desquamation. The combined treatment (Cas + E2 group) caused changes particular to each treatment, including desquamation. In conclusion, desquamation appeared as a novel phenomenon contributing to collective prostate epithelial cell deletion, distinct from the classical castration-induced apoptosis and particular to the androgen deprivation resulting from surgical castration, and should be considered as part of the mechanisms promoting organ regression.