Aims Protein Phosphatase Inhibitor 1 (I-1) functions as an amplifier of the β-adrenergic cascade in cardiomyocytes. Once activated via PKA, I-1 specifically blocks PP-1-mediated dephosphorylation of phospholamban and the ryanodine receptor-1. In heart failure I-1 activity as well as its expression is significantly reduced. It is still unclear whether this adaptation is protective or detrimental. This work aims at examining the impact of I-1 depletion on the course of pressure-induced heart failure, more precisely on acute and long-term mortality, on cardiac morphology and function and on expression levels of hypertrophy markers. Results may help evaluating the benefit of putative I-1 inhibiting substances in the therapy of heart failure. Methods and Results 25 I-1KO and 28 WT mice (C57Bl/6J, age- and sex-matched) underwent transverse aortic constriction (TAC). Cardiac function was assessed via transthoracic echocardiography prior to the intervention and weekly afterwards. Additionally, mice were exposed to β-adrenergic stimulation by injection of dobutamine once prior to TAC and two times afterwards, each controlled by echocardiography. For male mice acute survival was significantly increased in WT compared to I-1KO, whereas the mortality of surviving animals did not differ during the investigation period. For female mice no difference was seen in acute mortality after TAC, but during heart failure progression I-1KO revealed a significantly better survival. Prior to TAC contractility in I-1KO after application of dobutamine was significantly lower than in WT. This effect was mainly induced by female mice. Overall female mice of both WT and I-1KO showed smaller increases in heart rate (HR) and stroke volume (SV) when stimulated. In contrast, following TAC neither line- nor sex-dependent differences were found according to β-adrenergic stimulation. The comparison of hypertrophy markers in control groups revealed clearly decreased levels for I-1KO compared to WT. Conclusion In pressure-induced heart failure, I-1 knockout alters cardiac contractility and modulates mortality in a phase- and sex-dependent way. The depletion is detrimental for male mice in the acute phase of cardiac stress, whereas it is protective for female mice during heart failure progression. The increased mortality in the acute phase might result from the loss of I-1 as an amplifier of β-adrenergic signaling as this leads to a restriction of contractile adaptation. The increased survival in heart failure progression might be caused by a reduced transmission of pathologically increased sympathetic activity on the SR due to the depletion of I-1. Additionally, hypertrophy marker analyses point to differences in expression levels even under non-pathological conditions. / Ziel Der Proteinphosphatase-Inhibitor I-1 wirkt als ein Verstärker der β-adrenergen Kaskade in Kardiomyozyten. Nach PKA-abhängiger Phosphorylierung hemmt er spezifisch die Dephosphorylierung von PLB und RYR-2 durch die Proteinphosphatase-1. Im Rahmen einer Herzinsuffizienz sind sowohl Aktivität als auch Expression von I-1 deutlich reduziert. Hierbei ist unklar, ob dies eine protektive oder eine schädliche Adaption der β-adrenergen Kaskade darstellt. Diese Arbeit untersucht den Einfluss einer Depletion des I-1 (I-1KO) im Rahmen der druckinduzierten Herzinsuffizienz auf die akute bzw. auf die langfristige Mortalität, auf die kardiale Morphologie und Funktion sowie auf die Expression typischer Hypertrophiemarker. Hieraus sollen Erkenntnisse über den Nutzen der Verwendung putativ I-1 inhibierender Substanzen in der Behandlung der Herzinsuffizienz gewonnen werden. Methoden und Resultate 25 I-1KO- sowie 28 WT-Mäuse (C57Bl/6J, age and sex matched) erhielten eine Transverse Aortic Constriction (TAC). Die kardiale Funktion wurde einmalig vor der Intervention sowie danach wöchentlich mittels TTE untersucht. Zusätzlich wurden die Tiere einmalig vor TAC und zweimalig danach unter echokardiographischer Kontrolle mittels Dobutamin β-adrenerg stimuliert. Für die männlichen Tiere zeigte sich in den ersten Tagen nach TAC eine signifikant erhöhte Überlebensrate des WT gegenüber I-1KO. Die Mortalität der überlebenden männlichen Tiere unterschied sich hingegen nicht über den Versuchszeitraum. Für die weiblichen Tiere bestand kein Unterschied in der akuten Sterblichkeit nach TAC, während sich im Verlauf eine signifikant bessere Überlebensrate der weiblichen I-1KO gegenüber WT zeigte. Vor TAC wurde eine signifikant herabgesetzte Kontraktilität (FAS) des I-1KO unter Dobutamin festgestellt, der im Wesentlichen durch die weiblichen Tiere bewirkt wird. Insgesamt zeigten die weiblichen Tiere beider Linien unter β-adrenerger Stimulation eine geringere Zunahme von Herzfrequenz (HR) und Schlagvolumen (SV). Hingegen waren nach TAC keine linien- oder geschlechtsabhängigen Unterschiede unter Dobutamingabe feststellbar. Ein Vergleich der Hypertrophiemarker in der Kontrollgruppe zeigte für I-1KO ein deutlich vermindertes Niveau der Marker gegenüber WT. Ergebnis Der I-1-Knockout verändert die kardiale Kontraktilität und wirkt sowohl in phasen- als auch in geschlechtsabhängiger Weise auf die Mortalität infolge druckinduzierter Herzinsuffizienz. Er ist nachteilig für männliche Tiere in der akuten Phase kardialer Belastung, während er für weibliche Tiere im weiteren Verlauf protektive Wirkung entfaltet. Eine erhöhte Mortalität in der akuten Phase kann durch den Ausfall der Verstärkerfunktion des I-1 erklärt werden, da hiermit eine Einschränkung der akut notwendigen kontraktilen Adaptionsfähigkeit einhergeht. Ein Überlebensvorteil bei chronischer kardialer Belastung könnte darauf zurückzuführen sein, dass die pathologisch erhöhte sympathische Aktivierung der β-adrenergen Kaskade infolge der I-1-Depletion eine geringere Auswirkung auf die Zielstrukturen des aktivierten I-1 am Sarkoplasmatischen Retikulum hat. Darüber hinaus lassen die Analysen der Hypertrophiemarker eine veränderte Genexpression zwischen I-1KO und WT auch unter nicht-pathologischen Bedingungen vermuten.

Aims Protein Phosphatase Inhibitor 1 (I-1) functions as an amplifier of the β-adrenergic cascade in cardiomyocytes. Once activated via PKA, I-1 specifically blocks PP-1-mediated dephosphorylation of phospholamban and the ryanodine receptor-1. In heart failure I-1 activity as well as its expression is significantly reduced. It is still unclear whether this adaptation is protective or detrimental. This work aims at examining the impact of I-1 depletion on the course of pressure-induced heart failure, more precisely on acute and long-term mortality, on cardiac morphology and function and on expression levels of hypertrophy markers. Results may help evaluating the benefit of putative I-1 inhibiting substances in the therapy of heart failure. Methods and Results 25 I-1KO and 28 WT mice (C57Bl/6J, age- and sex-matched) underwent transverse aortic constriction (TAC). Cardiac function was assessed via transthoracic echocardiography prior to the intervention and weekly afterwards. Additionally, mice were exposed to β-adrenergic stimulation by injection of dobutamine once prior to TAC and two times afterwards, each controlled by echocardiography. For male mice acute survival was significantly increased in WT compared to I-1KO, whereas the mortality of surviving animals did not differ during the investigation period. For female mice no difference was seen in acute mortality after TAC, but during heart failure progression I-1KO revealed a significantly better survival. Prior to TAC contractility in I-1KO after application of dobutamine was significantly lower than in WT. This effect was mainly induced by female mice. Overall female mice of both WT and I-1KO showed smaller increases in heart rate (HR) and stroke volume (SV) when stimulated. In contrast, following TAC neither line- nor sex-dependent differences were found according to β-adrenergic stimulation. The comparison of hypertrophy markers in control groups revealed clearly decreased levels for I-1KO compared to WT. Conclusion In pressure-induced heart failure, I-1 knockout alters cardiac contractility and modulates mortality in a phase- and sex-dependent way. The depletion is detrimental for male mice in the acute phase of cardiac stress, whereas it is protective for female mice during heart failure progression. The increased mortality in the acute phase might result from the loss of I-1 as an amplifier of β-adrenergic signaling as this leads to a restriction of contractile adaptation. The increased survival in heart failure progression might be caused by a reduced transmission of pathologically increased sympathetic activity on the SR due to the depletion of I-1. Additionally, hypertrophy marker analyses point to differences in expression levels even under non-pathological conditions. / Ziel Der Proteinphosphatase-Inhibitor I-1 wirkt als ein Verstärker der β-adrenergen Kaskade in Kardiomyozyten. Nach PKA-abhängiger Phosphorylierung hemmt er spezifisch die Dephosphorylierung von PLB und RYR-2 durch die Proteinphosphatase-1. Im Rahmen einer Herzinsuffizienz sind sowohl Aktivität als auch Expression von I-1 deutlich reduziert. Hierbei ist unklar, ob dies eine protektive oder eine schädliche Adaption der β-adrenergen Kaskade darstellt. Diese Arbeit untersucht den Einfluss einer Depletion des I-1 (I-1KO) im Rahmen der druckinduzierten Herzinsuffizienz auf die akute bzw. auf die langfristige Mortalität, auf die kardiale Morphologie und Funktion sowie auf die Expression typischer Hypertrophiemarker. Hieraus sollen Erkenntnisse über den Nutzen der Verwendung putativ I-1 inhibierender Substanzen in der Behandlung der Herzinsuffizienz gewonnen werden. Methoden und Resultate 25 I-1KO- sowie 28 WT-Mäuse (C57Bl/6J, age and sex matched) erhielten eine Transverse Aortic Constriction (TAC). Die kardiale Funktion wurde einmalig vor der Intervention sowie danach wöchentlich mittels TTE untersucht. Zusätzlich wurden die Tiere einmalig vor TAC und zweimalig danach unter echokardiographischer Kontrolle mittels Dobutamin β-adrenerg stimuliert. Für die männlichen Tiere zeigte sich in den ersten Tagen nach TAC eine signifikant erhöhte Überlebensrate des WT gegenüber I-1KO. Die Mortalität der überlebenden männlichen Tiere unterschied sich hingegen nicht über den Versuchszeitraum. Für die weiblichen Tiere bestand kein Unterschied in der akuten Sterblichkeit nach TAC, während sich im Verlauf eine signifikant bessere Überlebensrate der weiblichen I-1KO gegenüber WT zeigte. Vor TAC wurde eine signifikant herabgesetzte Kontraktilität (FAS) des I-1KO unter Dobutamin festgestellt, der im Wesentlichen durch die weiblichen Tiere bewirkt wird. Insgesamt zeigten die weiblichen Tiere beider Linien unter β-adrenerger Stimulation eine geringere Zunahme von Herzfrequenz (HR) und Schlagvolumen (SV). Hingegen waren nach TAC keine linien- oder geschlechtsabhängigen Unterschiede unter Dobutamingabe feststellbar. Ein Vergleich der Hypertrophiemarker in der Kontrollgruppe zeigte für I-1KO ein deutlich vermindertes Niveau der Marker gegenüber WT. Ergebnis Der I-1-Knockout verändert die kardiale Kontraktilität und wirkt sowohl in phasen- als auch in geschlechtsabhängiger Weise auf die Mortalität infolge druckinduzierter Herzinsuffizienz. Er ist nachteilig für männliche Tiere in der akuten Phase kardialer Belastung, während er für weibliche Tiere im weiteren Verlauf protektive Wirkung entfaltet. Eine erhöhte Mortalität in der akuten Phase kann durch den Ausfall der Verstärkerfunktion des I-1 erklärt werden, da hiermit eine Einschränkung der akut notwendigen kontraktilen Adaptionsfähigkeit einhergeht. Ein Überlebensvorteil bei chronischer kardialer Belastung könnte darauf zurückzuführen sein, dass die pathologisch erhöhte sympathische Aktivierung der β-adrenergen Kaskade infolge der I-1-Depletion eine geringere Auswirkung auf die Zielstrukturen des aktivierten I-1 am Sarkoplasmatischen Retikulum hat. Darüber hinaus lassen die Analysen der Hypertrophiemarker eine veränderte Genexpression zwischen I-1KO und WT auch unter nicht-pathologischen Bedingungen vermuten.

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O nucléolo é uma organela subnuclear formada pela atividade transcricional dos genes ribossomais 18S-5.8S-26S (rDNA 45S) e consequente biogênese dos ribossomos. A atividade destes genes resulta na região organizadora do nucléolo (NOR), na forma de uma constrição secundária em cromossomos metafásicos. As constrições secundárias se condensam progressivamente durante a mitose e se descondensam ao final da telófase quando a reestruturação do nucléolo se inicia. Genomas que apresentam mais de um locus de rDNA 45S deve apresentar, obrigatoriamente, pelo menos um par de NORs, enquanto os demais loci poderão ou não serem expressos. O controle da expressão dos genes ribossomais e a formação da cromatina nucleolar são modulados por eventos epigenéticos. Embora alguns pontos sobre o funcionamento dos genes ribossomais e a formação do nucléolo estejam bem estabelecidos, questões como o padrão de condensação da cromatina nucleolar durante a mitose, o padrão de funcionamento de sítios adicionais de genes ribossomais, o papel das modificações epigenéticas na dinâmica da cromatina nucleolar e na expressão do rDNA 45S e o mecanismo de herança dos genes ativos, permanecem abertas. A espécie Crotalaria juncea (Leguminosae-Papilionoideae), com 2n=2x=16 cromossomos, que possui um locus de rDNA 45S no braço curto do cromossomo 1, que sempre forma constrição secundária, e um sítio adicional com atividade facultativa no braço curto do cromossomo 4, é um excelente modelo para o estudo destas questões. No contexto apresentado, foram estudadas a dinâmica de condensação das NORs durante o ciclo celular e sua correlação com a atividade dos genes ribossomais, incluindo o locus adicional, e ainda o papel da metilação da citosina do DNA durante estes processos. Os resultados demonstram que a cromatina da região organizadora do nucléolo segrega em um estado descondensado durante a mitose, na forma de constrição secundária, ou seja, tal estrutura não se condensa durante a metáfase e não volta a se distender no início da telófase. Aparentemente, o que causa correlações equivocadas entre a atividade nucleolar e a observação morfológica da constrição secundária na metáfase é a contração forçada da cromatina da NOR causada por agentes antimitogênicos. Este modelo de segregação em um estado aberto pode ser explicado pela descrição de diversas proteínas que permanecem diretamente ligadas ou indiretamente associadas à região da NOR durante a mitose, funcionando como uma barreira física para a compactação. Ambos os sítios, principais e adicionais, do rDNA 45S presentes em Crotalaria juncea apresentam atividade transcricional, embora o locus do cromossomo 4 mostre atividade facultativa. Ao contrário do que foi anteriormente proposto, uma vez ativo, o locus adicional permanece descondensado durante todo o ciclo mitótico, seguindo o mesmo comportamento dos sítios principais. As constrições secundárias e a cromatina nucleolar são hipermetiladas em nível citológico, independentemente de sua atividade. A aparente hipometilação observada no rDNA 45S em cromossomos mitóticos e núcleos interfásicos se deve ao menor grau de compactação da região organizadora do nucléolo e, consequentemente, à baixa densidade de cromatina. / The nucleolus is a subnuclear organelle formed as a result of transcriptional activity of ribosomal RNA genes 18S-5.8S-26S (45S rDNA) and subsequent ribosome biogenesis. This activity forms the nucleolar organizing region (NOR) as a secondary constriction in metaphase chromosomes. The secondary constrictions progressively condense during mitosis and decondense at the end of telophase, when nucleoli start to reassemble. Genomes presenting more than one 45S rDNA locus must have at least one pair of NOR bearing chromosomes, while other loci may be expressed or not. Ribosomal gene expression and nucleolar chromatin assembly are modulated by specific epigenetic events. Although some topics related to rDNA gene activity and nucleolus formation are well understood, questions such as the behavior of nucleolar chromatin condensation during mitosis, standard functions associated with rDNA additional sites, role of epigenetic modifications in nucleolar chromatin and 45S rDNA expression processes, and inheritance mechanism of active genes, remain to be solved. Crotalaria juncea (Leguminosae - Papilionoideae) has 2n=2x=16 chromosomes and carries a 45S rDNA locus at the short arm of chromosome 1, always presenting a secondary constriction, and an additional site with facultative activity at the short arm of chromosome 4, being an excellent model to resolve these questions. Thus, this study aimed to study NOR condensation dynamics during the cell cycle and its correlation with ribosomal gene activity, including the additional locus, while analyzing the role of rDNA cytosine methylation during this process. The results show that NOR chromatin segregate in a decondensed way throughout mitosis, as a secondary constriction. In other words, this structure does not condense during metaphase and the NOR is not reassembled at the beginning of telophase. Misinterpretations relating nucleolar activity with morphological observations of secondary constrictions, appear to be induced by the artificial contraction of NOR chromatin caused by antimitotic drugs. This segregation model in an open state may be supported by strong diversity of proteins that are maintained attached to NORs during mitosis, serving as a physic barrier for condensation. Both principal and additional 45S rDNA sites of C. juncea are transcriptionally active, although the additional locus in chromosome 4 presented facultative activity depending upon ribosomal request. Unlike what was previously proposed, once the additional site is activated, it remains in an open configuration throughout the cell cycle, similarly to principal site behavior. Secondary constrictions and nucleolar chromatin are hypermethylated at cytological level, regardless of their activity. The seeming hipomethylated state of 45S rDNA in interphase nucleus and mitotic chromosomes is due to a lower compaction level of nucleolar organizing regions and subsequent low chromatin density.

Racial differences in the distribution of cerebrovascular occlusive disease are well documented. Extracranial stenosis is more common in Caucasian while intracranial stenosis is more common in Asian, Hispanic and African-American. The prevalence of asymptomatic intracranial stenosis in middle age and elderly general population in China was about 7%. The frequency of intracranial atherosclerosis among patients with stroke and TIA is 40 to 50% in Chinese populations. Concurrent extracranial and intracranial stenoses is common in Asian, the incidence range from 10 to 39% in patients with stroke. The current population of China is 1.3 billion and it was estimated that 30% of the population will be aged 60 and above by 2050 in China. The incidence of stroke in China is 215 per 100000 which is one of the highest among the world and this burden is expected to escalate in the coming decades. However, studies of concurrent stenoses among Chinese are scarce. The aim of this precis is to present my studies that were conducted mainly among Chinese stroke patients on this particular field. The scope of the studies covers the following 4 areas: (1) Identification of Long-term prognosis of patients with concurrent stenoses; (2) Long-term prognosis of patients with concurrent stenoses and ischemic heart disease; (3) Lesion pattern and stroke mechanisms in concurrent stenoses; and (4) genetic polymorphisms of ischemic stroke patients with concurrent stenoses. The background, objectives, subjects, methods, results, and conclusions of these studies will be presented in this precis. / Man, Bik Ling. / Adviser: Lawrence K.S. Wong. / Source: Dissertation Abstracts International, Volume: 73-06, Section: B, page: . / Thesis (M.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 144-184). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web.

Este trabalho teve como objetivo avaliar a influência da espessura de dentina radicular apical, da constrição apical e do diâmetro do forame apical na precisão de leituras realizadas com os localizadores foraminais eletrônicos Mini Apex Locator e Root ZX II®. Foram utilizados 30 incisivos inferiores permanentes unirradiculados de humanos, extraídos, com raízes íntegras e ápices completamente formados e portadores de um único canal. Por meio de um paquímetro, as espessuras radiculares dos dentes foram medidas, no sentido mésio-distal a 1,0 e a 4,0mm aquém do forame apical. Após a abertura coronária, uma lima tipo K no 10, munida de limitador de penetração, foi introduzida no canal radicular até que sua extremidade pudesse ser visualizada na altura do forame, com o auxílio de um microscópio óptico com aumento de 7,8X. Dessa medida, subtraiu-se 1,0mm, estabelecendo-se o comprimento de trabalho. A dilatação do canal radicular foi feita, inicialmente, com brocas de Gates Glidden, em ordem numérica decrescente, da número 5 até a número1, até 4,0mm aquém do forame apical. Os dentes foram fixados em um modelo experimental especialmente desenvolvido para permitir a medição com os localizadores foraminais eletrônicos. Tal modelo era constituído por dois segmentos de PVC: um de menor calibre, com diâmetro correspondente a meia polegada por 2,0cm de comprimento, com as duas extremidades abertas e outro, de maior calibre, com uma das extremidades fechada e com diâmetro interno equivalente ao diâmetro externo do primeiro segmento (3/4 de polegada). No segmento de maior diâmetro, foi feito um orifício lateral que permitiu o posicionamento do eletrodo labial do localizador foraminal eletrônico e, para a medição, no seu interior, foi colocado alginato e, então, encaixado o componente de menor diâmetro, fazendo com que o ápice radicular ficasse imerso no alginato. Foram realizadas as leituras com os localizadores, iniciando-se com a lima tipo K no 10 e seguindo-se a seqüência de instrumentação e medida até a lima tipo K no 130; a lima tipo K no 10 foi utilizada em todos os diâmetros. Terminada essa fase, os dentes tiveram os canais sobreinstrumentados, isto é, a ponta da lima ultrapassou o forame apical em 1,0mm, a partir da lima tipo K no 25 e seguindo até a lima tipo K no 130; novas medidas foram obtidas com cada lima que sobreinstrumentou o forame e a lima no 10 foi utilizada em todos os diâmetros. Em todos os casos o canal radicular estava preenchido com hipoclorito de sódio a 1%. Para a análise estatística foram empregados os testes de Análise de Variância a dois critérios e de Tukey. Os resultados indicaram que as variáveis capazes de influenciar a recisão das leituras com os localizadores foraminais eletrônicos foram a eliminação da constrição apical com o consequente aumento do diâmetro do forame apical, ao contrário da espessura da parede dentinária do canal radicular, que não interferiu significativamente na precisão das leituras. / This study evaluated the influence of the apical root dentin thickness, apical constriction and diameter of the apical foramen in the accuracy of readings obtained using the electronic apex locators Mini Apex Locator and Root ZX II ®. The study was conducted on 30 extracted human single-rooted permanent mandibular incisors, with intact and completely formed roots and presenting a single canal. The root thickness of the teeth was measured with a pachymeter in mesiodistal direction, at 1.0 and 4.0mm from the apical foramen. After coronal opening, a 10 K file with a stop was introduced in the root canal until its end could be observed at the level of the apical foramen, with aid of a light microscope with 7.8X magnification. One millimeter was subtracted from this measurement for establishment of the working length. Enlargement of the root canal was initially performed using Gates Glidden burs, in decreasing order, from number 5 to number 1, up to 4.0mm beyond the apical foramen. The teeth were fixated in an experimental model especially designed to allow the measurement with the electronic apex locators. This model was composed of two PVC segments: one smaller, with diameter corresponding to half inch with 2.0cm length, with both ends open; and the other, with larger diameter, with one end closed and internal diameter similar to the external diameter of the first segment (3/4 inch). In the segment with greater diameter, a lateral orifice was made to allow positioning of the lip electrode of the electronic apex locator. For the measurement, alginate was poured and the component with smaller diameter was fitted, so as the root apex was immersed in alginate. Readings were performed using the electronic apex locators, initiating with a 10 K file and following the sequence of instrumentation and measurement up to 130 K file. The 10 K file was used in all diameters. After this stage, the root canals were overinstrumented, i.e. the file tip was introduced until 1.0mm beyond the apical foramen, beginning with 25 K file up to 130 K file; new measurements were obtained with each file overinstrumenting the apical foramen, and the 10 K file was used in all diameters. In all cases, the root canal was irrigated with 1% sodium hypochlorite. Statistical analysis was performed by two-way analysis of variance and the Tukey test. The results indicated that the variables that may influence the accuracy of readings with the electronic apex locators were the elimination of apical constriction with consequent increase in the diameter of the apical foramen, different from the thickness of the root canal dentinal wall, which did not significantly influence the accuracy of readings.

Le procédé de soudage TIG met en jeu un arc électrique entre une électrode réfractaire de tungstène et les pièces à souder. L'électrode et la zone fondue sont protégées contre la pollution ambiante par une atmosphère neutre d'argon. Ainsi, de est un procédé de prédilection dans les secteurs aussi variés que le nucléaire, l'aéronautique, les industries chimiques et agro-alimentaires.<br />Nonobstant ces qualités, ce procédé souffre d'un lourd handicap : sa faible productivité, particulièrement dans le cas des pièces de forte épaisseur. En effet, au-delà de 3mm d'épaisseur, il est nécessaire d'usiner les bords à souder et de faire des passes multiples avec du métal d'apport. L'accroissement du nombre de passes multiplie les risques de défauts et augmente les déformations et accroît la zone thermiquement affectée.<br />Il parait alors intéressant de disposer d'un procédé simple permettant de s'affranchir des faibles pénétrations inhérentes aux soudures TIG.<br />Il nous a semblé opportun de développer une technique permettant d'étendre les domaines d'utilisation du soudage TIG de 3 à 7mm d'épaisseur soudable maximale sans préparations. Cette technique appelée ATIG consiste à déposer, en endroit du joint à souder un flux activant qui va, au passage de l'arc électrique, modifier les courants de convection dans le bain de fusion, ainsi que l'équilibre électrochimique du plasma.<br />Ce document traite du développement de ces produits, ainsi que de la mise en évidence des mécanismes d'activation opérant au cours du soudage.<br />Ce travail, mené en collaboration avec la société B.S.L.i a conduit à la formulation de deux compositions (appliquées respectivement aux aciers inoxydables et aux alliages de titane) en phase de commercialisation par la société CASTOLIN S.A., ainsi qu'à la réalisation industrielle d'une colonne chimique avec plus de 2200 soudures ATIG orbitales.

To study transport properties in single InAs nanowires (NW) with etched constrictions, a bunch of back-gated single InAs NW devices were made. The standard device contained a NW section with an etched constriction, placed between two pre-patterned side-gates. For comparison, devices either without etched constriction or without side-gates were also fabricated. Transport measurement results of three devices were presented and discussed. The device without side-gates exhibited Coulomb blockade due to electron tunneling through double quantum dots (QDs). The device without the etched constriction displayed conductance quantization. The standard device showed both Coulomb blockade (due to electron tunneling through either multiple QDs or single QD) and Fabry-Perot conductance oscillation at different gate bias regime. A 3-D electrostatic and 2-D eigenvalue coupled simulation was conducted to explain the observed conductance quantization. This model suggests that the nonuniform potential distribution in a thick NW dramatically modifies the confinement energies in the NW.

To study transport properties in single InAs nanowires (NW) with etched constrictions, a bunch of back-gated single InAs NW devices were made. The standard device contained a NW section with an etched constriction, placed between two pre-patterned side-gates. For comparison, devices either without etched constriction or without side-gates were also fabricated. Transport measurement results of three devices were presented and discussed. The device without side-gates exhibited Coulomb blockade due to electron tunneling through double quantum dots (QDs). The device without the etched constriction displayed conductance quantization. The standard device showed both Coulomb blockade (due to electron tunneling through either multiple QDs or single QD) and Fabry-Perot conductance oscillation at different gate bias regime. A 3-D electrostatic and 2-D eigenvalue coupled simulation was conducted to explain the observed conductance quantization. This model suggests that the nonuniform potential distribution in a thick NW dramatically modifies the confinement energies in the NW.

This study examines the production and perception of laryngeal constriction in the early vocalizations of Bai and English infants. The first part of the study documents the development of laryngeal voice quality features in the non-syllabic and syllabic utterances of Bai and English infants. The second part of the study focuses on the perception of laryngeal constriction in infant vocalizations by adult Bai and English listeners. The study is grounded in Esling’s (2005) model of the vocal tract, which characterizes the laryngeal vocal tract as a separate articulator, distinct from the oral vocal tract. The study of Bai and English infants’ production identifies universal and language-specific patterns in infants’ development of laryngeal constriction. In the first months of life, most sounds produced by Bai and English infants are constricted. As the year progresses, all infants explore degrees of constriction in dynamic utterances that feature alternations between constricted and unconstricted laryngeal voice quality settings. As well, throughout the year, infants produce an increasing proportion of unconstricted vocalizations. By the end of the first year, when infants have developed increasing control of the laryngeal and oral vocal tracts, they produce syllabic utterances that begin to reflect the use of laryngeal voice quality features in their ambient language. English syllabic utterances are mostly unconstricted, mirroring the prevalence of unconstricted settings in the target language. By contrast, Bai syllabic utterances are mostly constricted or dynamic, reflecting the use of laryngeal voice quality in Bai, a register tone language that employs laryngeal voice quality features distinctively at the syllabic level. The second part of the study highlights universal and language-particular patterns in Bai and English adults’ perception of laryngeal voice quality in infants’ utterances. In evaluating the importance of a range of infant sounds in learning the target language (Bai or English), adults from both language groups assign lower ratings to infant utterances that occur earlier in development, such as constricted non-syllabic utterances, and higher ratings to sounds that occur later, such as syllabic utterances with rapidly articulated syllables. Bai and English adults’ perceptions also reflect some language-specific patterns that correspond to language-particular characteristics identified in infants’ use of laryngeal voice quality in syllabic and non-syllabic utterances. These correspondences suggest that adults are attuned to laryngeal voice quality in infants, and that, in turn, infants become attuned to the use of laryngeal voice quality features in their ambient language early in development. The production study demonstrates the fruitfulness of Esling’s (2005) model of the vocal tract in revealing previously undocumented patterns in the development of laryngeal constriction in the first year of life and in highlighting the importance of emergent laryngeal control as a stimulator of phonetic development. The perception study shows that adults whose native languages differ markedly in their use of laryngeal constriction can systematically evaluate laryngeal voice quality features in the full range of non-distress vocalizations produced by infants in the first year of life.