Le projet WA105/ProtoDUνE-DP est une expérience de prototypage qui a pour objectif de tester la technologie de Chambre à Projection Temporelle à Argon Liquide Diphasique (DLArTPC) à grande échelle dans le but de l'utiliser dans la future expérience de physique des neutrinos DUνE. Prévue fin 2026 aux USA, DUνE vise à déterminer l'ordre des masses des neutrinos ainsi que la violation de CP dans le secteur leptonique. Le travail de cette thèse s'oriente dans un premier temps autour des tests et simulations effectués sur les éléments de détection et d'amplification des détecteurs de WA105. Dans un second temps, la thèse s'oriente autour de l'analyse des traces de muons cosmiques vues par un premier prototype de 4t, opéré en 2017 au CERN. La technologie DLArTPC est une variante de la technologie LArTPC permettant une amplification des électrons extraits de la phase liquide à la phase gazeuse. Les amplificateurs d'électrons (LEMs) sont des plaques de PCB de 50x50cm² épais de 1mm, percés de 400k trous de 500 microns de diamètre, recouvertes de chaque côté par une mince couche de cuivre. Une différence de potentiel de l'ordre de 3kv permet d'atteindre un gain supérieur à 10. Une partie du travail de cette thèse a consisté à simuler la dérive des électrons à travers ces LEMs afin d'étudier les efficacités de collection de charge. Une autre partie de cette thèse a consisté à mesurer les caractéristiques importantes (épaisseur, tenue en tension) des amplificateurs destinés au démonstrateur de 300t de WA105, dont la mise en route a été effectuée fin août 2019 au CERN. Le gain est une des caractéristiques principales d'une DLArTPC, et il a été étudié dans le prototype de 4t grâce à la détection de muons cosmiques. Des comparaisons sont effectuées avec les résultats d'un prototype de 3L datant de 2014, et un programme de reconstruction de trace dédié a été développé pour traiter certains événements bruités. Le travail effectué dans cette thèse a permis de mieux comprendre le fonctionnement des DLArTPCs, notamment en ce qui concerne l'aspect multiplication et dérive des électrons. Ces connaissances seront importantes lors de l'opération du démonstrateur de 300t au CERN, ainsi que lors de l'exploitation du module DLArTPC de DUνE. / The WA105/ProtoDUνE-DP project is a prototyping experiment which goal is to test the Double Phase Liquid Argon Time Projection Chamber (DLArTPC) technology at large scale, to use it in the future neutrinos physics experiment DUνE. Scheduled for the end of 2026 in the USA, DUνE aims at measuring the neutrinos mass ordering and the leptonic CP symetry violation. The first part of this thesis is dedicated to tests and simulations of the detection and amplification elements of the WA105 detectors. The second part is focused on the analysis of cosmic muon tracks seen by a first prototype of 4t, operated at CERN in 2017. The DLArTPC technology is a variation of the LArTPC technology allowing for the amplification of the electrons extracted from the liquid phase to the gas phase. The Large Electron Amplifiers (LEMs) are 50x50cm² PCB plates with a thickness of 1mm, pierced by 400k holes of 500 microns diameter, covered on each side by a thin layer of copper giving a gain superior to 10. Part of this thesis work is about the simulation of electrons drifting through those LEMs to study the charge collection efficiencies. Another part of this thesis is about the measurement of important caracteristics (thickness, voltage stability) of the LEMs that are used in the 300t demonstrator of WA105, which commissionning was done in the end of August 2019. The gain is one of the main caracteristics of a DLArTPC, and it has been studied in the 4t prototype by detecting cosmic muons. Comparisons are done with previous results from 2014 from a smaller prototype of 3L, and a dedicated reconstruction program was created to analyse noisy events. The work done in the thesis allowed for a better understanding of DALrTPCs, mainly on the multiplication and drift of electrons. This knowledge will be important during the operation of the 300t demonstrator at CERN, and during the operationg of the DLArTPC module of DUνE.

The purpose of this thesis was to examine two works of science fiction by the Polish writer and satirist, Stanislaw Lem, which exemplify two broad philosophical themes central to his writings; viz., cosmology and personhood. In "The New Cosmogony," Lem focuses on the central problem of the philosophy of scientific cosmology, namely, what kind of explanation is-applicable to that science. Lem synthesizes religious and scientific views of the creation of the universe in his model of the cosmos as a Game of Civilizations with advanced technologies. Central to this work is the philosophical notion of intentionality. In "The Mask," Lem raises questions about personhood, consciousness, freedom, determinism, and responsibility by embedding them in the autobiographical narrative of a conscious, female machine. Lem's views on cosmology and his views on personhood both involve intentionality - the intentions of civilizations, on the one hand, and the intentions of a King and of the machine he created, on the other. Both works challenge all preconceptions about philosophy through the use of paradox, irony, and sometimes ridicule. Lem provides no answers, however. He is interested in setting up futuristic technological situations that are capable of undermining our basic assumptions about the world.

The thesis presents a proposal of production of a molded part from the aluminum alloy of group 2024 (dural). Based on the theoretical study and the requirements of the company was designed a cutting tool with a rounded edge for cutting the unfolded shape of the part on the eccentric press LEN 40 C. A new forming tool from textite material for fluid press Quintus QFC was designed. The parts of the cutting tool were designed primarily from normalized (purchased) parts. Manufactured punch and shearing die are made of commonly available tool steels and processed on the attached drawings. The result of the thesis is a recommendation to invest in a specialized workplace for the production of a unfolded shape and reduction of laboriousness adjusting after forming.

X-Linked Sinus Node Dysfunction and Atrial Fibrillation. Introduction: Atrial fibrillation (AF) is a heritable disorder with male predilection, suggesting a sex chromosome defect in certain patients. Loss-of-function truncation mutations in EMD, encoding the nuclear membrane protein emerin, cause X-linked Emery-Dreifuss muscular dystrophy (EDMD) characterized by localized contractures and skeletal myopathy in adolescence, sinus node dysfunction (SND) in early adulthood, and atrial fibrillation as a variably associated trait. This study sought to identify the genetic basis for male-restricted, nonsyndromic sinus node dysfunction and AF in a multigenerational family. Methods and Results: Genealogical and medical records, and DNA samples, were obtained. Progressive SND and AF occurred in four males related through maternal lineages, consistent with X-linked inheritance. Skeletal myopathy was absent, even at advanced ages. Targeted X chromosome genotyping mapped the disease locus to Xq28, implicating EMD as a positional candidate gene. DNA sequencing revealed hemizygosity for an in-frame 3-bp deletion in EMD (Lys37del) in affected males, disrupting a residue within the LEM binding domain critical for nuclear assembly but leaving the remainder of the protein intact. Buccal epithelial cell staining with emerin antibody demonstrated near-total functional loss of emerin. Female relatives underwent prospective electrocardiographic and genetic testing. Those heterozygous for Lys37del had ∼50-70% emerin-positive nuclei and variable degrees of paroxysmal supraventricular arrhythmia. Conclusions: Mutation of EMD can underlie X-linked familial AF. Lys37del is associated with epithelial cell emerin deficiency, as in EDMD, yet it causes electrical atriomyopathy in the absence of skeletal muscle disease. Targeted genetic testing of EMD should be considered in patients with SND-associated AF and/or family history suggesting X-linked inheritance.

Lamina Emergent Mechanisms (LEMs) are a class of compliant mechanisms that can be manufactured from sheet goods and possess motion out of the plane of fabrication. LEMs can be designed to perform sophisticated motions. This thesis expands LEM understanding and increases the ability to utilize them in applications by introducing the fundamentals of spherical LEMs, creating joints suitable for LEMs, and providing an example of a LEM application. In this thesis, the fundamentals of spherical LEMs are developed. This includes classification of all possible spherical 4R LEMs and a discussion of the motion characteristics of the various mechanisms. The motion characteristics associated with spherical 4R LEMs are then used to predict the motion of spherical 6R LEMs and arrays of spherical LEMs. Multiple spherical LEM prototypes are shown and discussed. A common difficulty of working with compliant mechanisms, especially LEMs, is creating suitable joints. There is often a trade off between flexibility in the desired direction of deflection, and stiffness in directions of undesired deflection. For this thesis, LEM joints that possess higher off-axis stiffness, especially in tension and compression, than previous designs were developed: the I-LET, the T-LET, and the IT-LET. Joint geometries were optimized and then modeled in commercial finite element analysis (FEA) software capable of nonlinear analysis. These models were used to predict the bending of tensile/compressive stiffnesses of the joints. As a benchmark, lamina emergent torsional (LET) joints were modeled and optimized for maximum tension and compression loading while maintaining the same bending stiffness as the joint being compared. Mechanisms that utilized the new joints were created and are briefly discussed. The use of these joints allows for minimized parasitic motion under tension and compression loads and expands the capability of LEM joints. The Lens Lift™ was developed to demonstrate an application of LEMs. The Lens Lift™ is a LEM device that allows for easier and more sterile use of disposable contact lenses. It possesses a monolithic structure and can be fabricated using simple manufacturing processes. As the contact lens user opens the blister pack used to store the lens, the lens is lifted out of the pack and presented to the user. The user can then lift the lens with one touch and place it in the eye. A provisional patent has been filed for the device and the device currently being evaluated by a major contact lens manufacturer for further development.

This work is linked to the line of research Education and Arts in the Post Graduation Program in Education, in the Federal University of Santa Maria and the group FAPEM: Training, Action and Research in Music Education. The objective of the present research was to investigate the impact of the Program LEM: Playing and Singing "for the training and teacher development, from the perspective of student teachers in music/workshop organizers. According to this objective, it is intended to know the aims of undergraduate students to participate as workshop participants of the workshops of the program LEM to analyze the relationships established between the music workshops, its training and development staff, understanding the assumptions that underlie the development of education in the workshops and also place the "Program LEM: Play and Sing" in the context of academic and professional training. The qualitative methodological approach was chosen to analyze the perspectives of seven workshop participants as the subjects of the present research. For data collection it was used the semi-structured interview, which took place in two stages: the first session on Individual (EI) and the second group (EG). Thus, data analysis was established by qualitative analysis, performed from the relationship between the perspectives of workshop participants, workshops in music, education and the development of education. From the interpretation of the background and the references about teacher training and professional development, the conception of the process of training student teachers in music workshops in the Laboratory for Music Education was developed, researching this area as a place of training and academic and professional performance. As a result, we present the "LEM Program: Play and Sing" by addressing its significance for the undergraduates, the relationship between the experiences in music workshops and training, and setting out the objectives of the workshop participants to participate in the program according to assumptions that underlie their teaching in music workshops. Still, we highlight the LEM program as a place of training and academic and professional performance. / Esta dissertação está vinculada à linha de pesquisa Educação e Artes do Programa de Pós Graduação em Educação da Universidade Federal de Santa Maria e ao grupo FAPEM: Formação, Ação e Pesquisa em Educação Musical. O objetivo da pesquisa foi investigar as repercussões do Programa LEM: Tocar e Cantar para a formação inicial e desenvolvimento docente, sob a perspectiva dos licenciandos em música/oficineiros. Para tanto, buscou-se conhecer os objetivos dos licenciandos ao participarem como oficineiros das oficinas do Programa LEM, analisar as relações que estabelecem entre as oficinas de música, sua formação inicial e seu desenvolvimento docente, compreender pressupostos que fundamentam o desenvolvimento da docência nas oficinas e, ainda, situar o Programa LEM: Tocar e Cantar no contexto da formação acadêmico-profissional. Como abordagem metodológica optou-se pela pesquisa qualitativa para analisar as perspectivas de sete oficineiros, sujeitos da pesquisa. Para a coleta dos dados o instrumento utilizado foi a entrevista semi-estruturada, que ocorreu em duas etapas: a primeira em sessão Individual (EI) e a segunda em grupo (EG). A análise dos dados foi constituída pela análise qualitativa de conteúdo, realizada a partir da relação entre as perspectivas dos oficineiros, as oficinas de música, a formação inicial e o desenvolvimento da docência. A partir da interpretação e do embasamento nos referenciais sobre a formação docente e desenvolvimento profissional, foi possível compreender acerca do processo formativo dos licenciandos em música nas oficinas do Laboratório de Educação Musical, analisando esse espaço como um lugar de formação e atuação acadêmico-profissional. Como considerações finais, apresentam-se o Programa LEM: Tocar e Cantar , abordando sua significação para os licenciandos, as relações entre as vivências nas oficinas de música e a formação profissional, e expondo os objetivos dos oficineiros ao participarem do Programa e os pressupostos que fundamentam a sua docência nas oficinas de música. Ainda, destaca-se o Programa LEM como lugar de formação e atuação acadêmicoprofissional.

La radiothérapie externe est un traitement anticancéreux locorégional efficace et curatif. Néanmoins, il y a toujours des malades qui meurent de tumeurs locales non-contrôlées. Les nouvelles techniques en radiothérapie visent toujours à trouver un moyen d'augmenter la dose à la tumeur tout en réduisant au minimum la dose aux tissus sains adjacents. Une des dernières techniques innovantes est l'hadronthérapie par ions carbone. Ces dix dernières années ont vu augmenter le nombre de nouveaux centres d hadronthérapie dans le monde avec des faisceaux d'ions carbone, forts des résultats promettant des projets pilotes Berkeley (USA), Chiba (Japon) et Darmstadt (Allemagne). Les avantages théoriques des ions carbone sont: une meilleure balistique et une meilleure efficacité dans la destruction des cellules tumorales. Ainsi cette technique a le potentiel d'augmenter le contrôle des tumeurs, particulièrement pour celles inopérables et radiorésistantes. Les effets biologiques varient le long de la trajectoire des ions de haut TEL (Transfert d'´Énergie Linéique) comme les ions carbone. Ainsi des modèles radiobiologiques sont nécessaires pour quantifier les effets biologiques. Il existe plusieurs modèles radiobiologiques qui reposent sur des approches et des approximations théoriques différentes. Ces modèles ont été développés au sein de chacune des institutions où se déroulaient les projets pilotes. Au stade actuel des connaissances, il semble peu probable d'atteindre une rapide convergence des résultats produits par ces différents modèles. Parmi les modèles radiobiologiques utilisés en clinique, il y a le Local Effect Model (LEM), développé en Allemagne et implémenté dans les systèmes de planification de traitement certifiés CE, le modèle de la National Institute of Radiological Science (NIRS), employé dans les centres japonais d'hadronthérapie possédant un système d'irradiation passif, et le Microdosimetric Kinetic Model (MKM) employé dans les centres japonais d'hadronthérapie possédant un système d'irradiation actif en mode pencil beam scanning / External beam radiotherapy (EBRT) is a therapy technique aiming at treating locoregional tumors with high efficiency. However, many tumors remain uncontrolled. Newest EBRT techniques always aim at increasing the dose to the tumor while sparing the surrounding healthy tissues. Carbon-ion beam therapy is one of these promising techniques. The number of clinical centres offering carbon-ion beam radiotherapy has been increasing over the world for the last decade. This keen interest spread after very promising results from pilot projects at Berkeley (USA), Chiba (Japan) and Darmstadt (Germany). The theoretical advantages of carbon-ionsare better spatial selectivity in dose deposition and better efficiency in cell killing. They have thus the potential to increase the control of tumors, particularly for unresectable radioresistant tumors. In high linear-energy-transfer (LET) radiations, such as carbon-ion beams, biological effects vary along the ion track, hence, to quantify them, specific radiobiological models are needed. There exist several radiobiological models based on very different theoretical approaches and approximations. They were created and improved in each of the pilot institutions. At the current state of knowledge, no convergence between the model results seems to be possible in the very near future. Clinically employed radiobiological models are the Local Effect Model (LEM) developed in Germany and implemented in CE-certified treatment planning systems, the National Institute of Radiological Science (NIRS) model employed in Japanese centres with passive beam delivery systems and the microdosimetric kinetic model (MKM) in Japanese centres with active scanning beam delivery systems

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / This dissertation is linked to the research line Education the Arts from the PPGE/UFSM and the group of studies and research in Training, Action and Research in Musical Education - FAPEM. Aimed to investigate the "Program LEM: Playing and Singing", in the form of music workshops, seeking to emphasize its contributions in the formation of musical training and teaching-musical by students and former students of Pedagogy/UFSM, which are called up workshopers . Specifically, it is sought to know their ideas about the workshops for the musical and pedagogicmusical development of unidocent teachers, identify the contributions of workshops for the musical and pedagogic-musical development of unidocent teachers, and also map the musical and teaching-music training some needs raised to unidocency. As a methodological approach, the qualitative research was chosen mainly on the basis of the analysis of contexts and realities experienced by eight workshopers subjects of the research. A semi-structured interview was the main tool for collecting data, being divided into two stages: the first, a semi-structured individual interview (EI) and the second, with the completion of an interview in a group (EG). The theoretical reference was built from two subjects: the training of teachers, and the relationship between music education and unidocency, and workshops on music, which presents a brief history of its existence in the country as well as the formation of the "Program LEM: Playing and Singing" at UFSM. Data analysis was divided into crossing between the relationship of workshops with the Program, the workshops and training in Pedagogy, and following, it was sought to make up relations between the unidocent training, the musical education, and the educational practice developed by the workshopers. As a conclusion of this research, there is the "Program LEM: Playing and Singing" as a musical training space-relevant in the initial training of teachers, contributing to the unidocents have more alternatives of work and assurance when working with music in school. Still, it is pointed out that initiatives like this should be encouraged in unidocent forming. / A presente dissertação está vinculada à linha de pesquisa Educação e Artes do PPGE/UFSM e ao grupo de estudos e pesquisas em Formação, Ação e Pesquisa em Educação Musical FAPEM. Teve como objetivo investigar acerca do Programa LEM: Tocar e Cantar , no formato de oficinas de música, buscando verificar suas contribuições na constituição da formação musical e pedagógico-musical de alunas e ex-alunas da Pedagogia/UFSM, denominadas oficinandas. Especificamente, buscou-se conhecer suas concepções sobre as oficinas de música para o desenvolvimento musical e pedagógico-musical de professoras unidocentes, identificar as contribuições das oficinas de música para o desenvolvimento musical e pedagógico-musical de professoras unidocentes, e ainda, mapear algumas necessidades formativas musicais e pedagógico-musicais levantadas para a unidocência. Como abordagem metodológica, optou-se pela pesquisa qualitativa principalmente em função da análise de contextos e realidades vivenciadas pelas oito oficinandas sujeitas da pesquisa. A entrevista semi-estruturada foi o principal instrumento de coleta dos dados, sendo dividida em duas etapas, a primeira em entrevista semi-estruturada individual (EI) e a segunda na realização de uma entrevista em grupo (EG). O referencial teórico foi construído a partir de dois temas: a formação de professores; e a relação entre a unidocência e a educação musical, e oficinas de música, do qual se apresenta um breve relato histórico de sua existência no país bem como a constituição do Programa LEM: Tocar e Cantar , na UFSM. A análise dos dados foi dividida primeiramente num cruzamento entre a relação das oficinas com o Programa, as respectivas oficinas e a formação inicial na Pedagogia e, em seguida, buscou-se tecer relações entre a formação unidocente, a educação musical e a prática educativa escolar desenvolvida pelas oficinandas. Como conclusão dessa investigação, apresenta-se o Programa LEM: Tocar e Cantar como espaço músico-formativo relevante na formação inicial de professores, contribuindo para que as unidocentes possuam mais alternativas de trabalho e segurança no momento da prática com música na escola. Ainda, aponta-se que iniciativas como essas devem ser incentivadas na formação de unidocente.

The contents of nuclei are highly organized. Nuclear organization is facilitated by a dense protein network, called the nuclear lamina, which underlies the nuclear envelope. The nuclear lamina is composed of filamentous lamins and more than eighty lamin-associated proteins (LAPs). Among the first LAPs identified are LEM Domain (LEM-D) proteins, named after LAP2, emerin and MAN1. LEM-D proteins have many shared and unique functions that include providing structural support to the nucleus, regulating signal transduction pathways and gene expression, facilitating proper progression through the cell cycle and maintaining chromatin attachments at the nuclear periphery. Despite requirements for these processes in all cell types, loss of globally expressed LEM-D proteins causes tissue-restricted defects. Identification of the primary function in tissues susceptible to LEM-D protein loss is a persistent challenge in the nuclear lamina field. Research described here uses Drosophila as a model to understand LEM-D protein function. Loss of the Drosophila emerin homologue Otefin (Ote) causes a complex phenotype in the ovary wherein both somatic and germline cells are compromised. Using tissue-restricted expression experiments, it was determined that Ote function is only required in germline stem cells (GSCs) to maintain all cells in the ovary. Developmental, molecular and genetic analyses revealed that the primary defect in ote mutant ovaries is an early block in germline differentiation, followed by GSC death. Genetic rescue experiments revealed that both of these GSC defects are due to the activation of the DNA Damage Response (DDR) proteins ATR and Chk2. Interestingly, activation of ATR and Chk2 occurs independent of detectable canonical DDR triggers, including DNA damage. Immunohistochemical analyses suggest that Ote might be regulating chromatin condensation and/or heterochromatin organization in GSCs. Through studies of Ote, a rescue method was discovered that involves culturing animals at elevated temperatures. This novel rescue strategy, termed hyperthermia, acts independent of ATR or Chk2 inhibition. Interestingly, elevated temperatures leads to chromatin decondensation in Drosophila, suggesting that hyperthermia may rescue oogenesis by alleviating chromatin defects observed in ote mutant germ cells. Together, results from experiments discussed herein dissect a complex ovary phenotype to reveal the critical requirement for a nuclear lamina LEM-D protein. Investigations into Ote function have revealed several aspects of GSC biology. The ATR/Chk2 checkpoint activated in the absence of Ote uncovered a previously unidentified cause of female GSC death. Further, findings that ATR and Chk2 are activated in the absence of canonical triggers suggest that GSCs possess a system to monitor defects or changes in the nucleus that do not involve DNA damage. Therefore, studies of Ote function and ote mutant phenotypes have uncovered valuable insights into LEM-D protein function and revealed the existence of novel conditions required for GSC maintenance.

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