Following by the signing of ECFA recently, the industrial environment is changed rapidly forcing many small and medium enterprises to face various kinds of internal and external challenges. They encounter the obstacles to advance their technical and producing system which is their weakness as well. In the earlier year, these enterprises was founded basing on the trusting relationship between the owner and the employees, and the working regulations, salary, and bounces were created according to their cooperating consensus. However, when their original mode of production could not catch up in time along with the growth of capacity, advance of the industry and expansion of market, the relationship has started to change. Hence, they tried to change the original structure by looking for transforming or through the organizational improvement in response to the upcoming crisis and challenges. Among these changes, the establishment and import of systematization has become the major pattern in present. This research is focused on a traditional machinery factory which produces non-standard products internationally hoping to create new experience inspired by the success in the past including introducing the new management mode and new strategy from the stage of contract signing, design to post service making the company on the invincible position. During the process of transforming, many relationship-oriented enterprises including the one discussed in this research are facing several different factors among clients vs. company, agency vs. company, company vs. suppliers, and company vs. employees and what influence will be caused due to the establishment of the new system is the main discussion in this research. Furthermore, whether the customized production is suitable for the new system? What kind of obsolete will the company encounter? Will there be any problem caused? Also, the research will discuss how to locate the most suitable method within all kinds of possible limiting factors through hard facts, dangerous half-truths & total nonsense and convert these knowhow into power to decrease all the impacts brought by the changes.

Für das Rett Syndrom, eine der häufigsten genetischen Ursachen für mentale Retardie-rung bei Frauen, gibt es bisher keine kausale Therapie, obwohl gentherapeutische Studi-en mit konditionellen knockout Mäusen gezeigt haben, dass es sich um eine therapierbare Erkrankung handelt. Um neue Therapien entwickeln zu können, werden Mausmodelle benötigt, die auf den beim Menschen am häufigsten gefundenen Mutation beruhen. In der vorliegenden Arbeit wurde ein Mausmodell mit der häufigsten humanen Nonsense-Mutation R168X im Mecp2 Gen charakterisiert. Mit Hilfe dieses Mausmodells wurden dann die Therapieansätze der „Stop-Codon Readthrough-Therapie“ und einer Knochenmarktransplantation auf ihre Wirksamkeit in vitro und in vivo untersucht. Die Charakterisierung der Mauslinie zeigte, dass männliche MeCP2R168X-Mäuse im Gegensatz zu anderen MeCP2-Mausmodellen kein verkürztes MeCP2 Protein exprimieren. Desweiteren weisen männliche MeCP2R168X-Mäuse einen Phänotyp, inklu-sive der drastisch verkürzten Lebenspanne, auf, wie er bei bereits etablierten Mausmo-dellen für das Rett Syndrom beschrieben wurde. Dagegen zeigten weibliche, heterozy-gote MeCP2R168X-Mäuse nur einen sehr mild ausgeprägten Phänotyp verglichen mit bereits etablierten MeCP2-Mauslinien. Für die „Stop-Codon Readthrough-Therapie“ wurde die Effizienz der Aminoglykoside Geniticin, Gentamicin und Neomycin, der Komponenten NB54, NB84 und NB124, sowie der niedermolekularen Substanz PTC124 auf ihre Wirksamkeit bei der Induktion eines Readthroughs mit transfizierten HeLa-Zellen und MeCP2R168X/y-Mausohrfibroblasten in vitro untersucht. Dabei zeigte sich eine deutliche Steigerung der Readthrough-Effizienz der NB-Komponenten, gemessen an der detektierbaren Menge an MeCP2, mit zunehmender Generation (NB54 --> NB84 --> NB124) und gegenüber dem klinisch angewandten Gentamicin. Während die Behandlung mit Neomycin zu einem minimalen Readthrough-Produkt führte, zeigte die Behandlung mit PTC124 kei-nen messbaren Readthrough. Anschließend wurden männliche MeCP2R168X-Mäuse mit den in vitro getesteten Sub-stanzen, mit Ausnahme von Geniticin, behandelt. Die Expression eines MeCP2-Proteins voller Länge konnte durch keine der applizierten Substanzen induziert werden. Auch bei Behandlungen über einen längeren Zeitraum mit hohen Dosierungen, im Fall von Gentamicin nahe der LD50-Dosis und nachweisbarer intrazellulärer Aufnahme, konnte in den behandelten Tieren weder ein verkürztes noch ein MeCP2 Protein nativer Länge detektiert werden. Die Ergebnisse dieser Arbeit zeigen, dass für die „Stop-Codon Readthrough-Therapie“ für das Rett Syndrom neue Komponenten entwickelt werden oder andere Applikationswege gewählt werden müssen, da mit den derzeit verfügbaren Substanzen kein therapeutischer Erfolg erzielt werden kann. Im letzten Teil dieser Arbeit wurde die Theorie einer gestörten Phagozytose MeCP2-defizienter Mikroglia, sowie die Therapie von MeCP2-defizienten Mäusen durch eine Knochenmarktransplantation überprüft. Dabei konnte weder in vitro noch in vivo eine Veränderung der Phagozytoseaktivität der MeCP2-defizienten Mikroglia nachgewiesen werden, wie sie von Derecki und Kollegen publiziert wurde. Die Transplantation von gesundem Knochenmark führte bei männlichen MeCP2R168X-Tieren zu keiner Verlängerung der Überlebensspanne oder einer allgemeinen Abmilde-rung der Symptomatik, wie sie ebenfalls von Derecki und Kollegen publiziert wurde. Bei weiblichen Tieren führte die Transplantation gesunden Knochenmarks zu einer Verschlechterung der motorischen Fähigkeiten. Diese Ergebnisse sind im Einklang mit denen Ergebnissen der Arbeitsgruppen von An-drew Pieper, Antonio Bedalov und Jeffrey Neul, die in anderen Mausmodellen die Wir-kung der Knochenmarktransplantation untersuchten. Die Ergebnisse aller beteiligten Arbeitsgruppen legen daher nahe, dass eine Knochen-marktransplantation nach einer Ganzkörperbestrahlung keine geeignete Therapie für das Rett Syndroms darstellt.

This thesis analyses the difficulties in reading modern poetry that arise out of not the references but the unconventional use of language, and presents them in a theoretical framework based on Julia Kristeva&rsquo / s semanalytic theory and Melanie Parsons&rsquo / s application of it to a comparison of Nonsense literature and twentieth century poetry. Then aspects of the works of G. M. Hopkins, Dylan Thomas and Edith Sitwell are discussed and poems by these poets are analysed within this framework.

Thesis (Ph.D.)--McMaster University (Canada), 1995. / Source: Dissertation Abstracts International, Volume: 56-12, Section: B, page: 6730. Adviser: J. P. Capone.

Thesis (Ph.D.)--Cornell University, 2000. / Includes bibliographical references.

Environ un tiers des maladies humaines, héréditaires ou acquises, sont dues à la génération d’un codon stop prématuré (PTC). Le système de contrôle appelé dégradation des ARNm non-sens (NMD) permet de détecter puis de dégrader des ARNm contenant un PTC. Les facteurs principaux de la NMD : UPF1, UPF2 et UPF3 reconnaissent les PTCs en interagissant avec le complexe de terminaison de traduction contenant les ribosomes, les facteurs de terminaison eRF1, eRF3 et la protéine poly(A) binding (Pab1p en levure). Nous avons pu résoudre la structure d'un tel complexe en levure comprenant un ribosome en cours de traduction en présence d’un ARNt dans le site P et de facteurs de terminaisons dans le site A. Aucune densité n’a pu être observée pour Pab1p indiquant la flexibilité de l’interaction avec ce complexe. Nous avons aussi évalué l’impact des facteurs de la NMD sur la terminaison dans un système de traduction in vitro humain. UPF3B retarde la reconnaissance du codon stop et favorise la dissociation des sous-unités ribosomales. UPF2 abolit l’effet de UPF3B tandis que l’addition de UPF1 n’a pas d’influence dans la terminaison. Par in vivo et in vitro pulldowns, nous avons montré que UPF3B interagit avec eRF3a et UPF1 et pourrait constituer le lien manquant entre la terminaison et la NMD. Nos résultats illustrent la complexité des mécanismes de la terminaison et de la NMD. / Premature termination codons (PTCs) account for approximately one third of inherited and acquired diseases. A surveillance pathway called nonsense-mediated mRNA decay (NMD) detects and degrades PTC-containing transcripts. NMD core factors UPF1, UPF2 and UPF3 mediate the recognition of PTCs by associating with the terminating translation machinery composed of the ribosome, the release factors eRF1 and eRF3 and the poly(A) binding protein (Pab1p in yeast). Using electron cryo-microscopy, we solved such a complex in yeast and observed the translating ribosome, containing a P-site tRNA and an A-site density for the release factors but not for Pab1p indicating that Pab1p is flexibly bound. We also probed the function of NMD factors in mammalian termination using a reconstituted human in vitro translation system. Surprisingly, we found that UPF3B delayed stop codon recognition and promoted ribosomal dissociation. The addition of UPF2 could abolish UPF3B’s effect on translation termination. UPF1 had no influence in the termination process alone or in combination with UPF2. Using in vitro and in vivo pulldowns we found that UPF3B interacts with eRF3a and UPF1, indicating that UPF3B could be the missing link between termination and NMD. Our results point to a complex interplay between the NMD factors and the termination apparatus.

A presente tese se ocupa de uma vertente da literatura e do cinema contemporâneos, especialmente do escritor Julio Cortázar e do cineasta David Lynch, que: busca um novo tratamento para a realidade, não esconde os artifícios discursivos das obras, joga com estratégias ilusionistas e antiilusionistas, debate a própria ficção por meio de recursos metaficcionais, que se utiliza da metáfora do teatro como espaço diferenciado e como palco de ilusões e que trabalha com a questão do fantástico (ou absurdo). Grande parte do trabalho é dedicada ao estudo da obra do escritor argentino Julio Cortázar. Estudo esse que se constrói a partir das correspondências entre as produções ficcionais e teóricas de Cortázar, além de suas próprias entrevistas. Cortázar é nosso foco principal e dele, acreditamos, brotou um veio dos mais significativos na narrativa contemporânea, que estabelece novos modos de se lidar com a representação e com as referências. É devido a esses aspectos, apontados anteriormente, que estabelecemos relações com outros autores, inclusive do cinema, como é o caso de David Lynch / This thesis deals with one aspect of literature and contemporary cinema, especially the writer Julio Cortázar and filmmaker David Lynch, that: a search for new treatment really does not hide the artifice of the discursive works, plays with illusionist and anti-illusionist strategies, debate the fiction itself through metaficcionais resources, which uses the metaphor of the theater as a space variable and to stage illusions and working with the issue of the fantastic (or nonsense). Much of the work is devoted to the study of the work of Argentine writer Julio Cortázar. Study which is constructed from the correspondence between the fictional and theoretical productions of Cortázar, and his own interviews. Cortázar is our main focus and goals, we came a shaft of the most significant in contemporary novels, establishing new ways of dealing with the representation and referrals. It is because of these issues, previously mentioned, we have established relationships with other authors, including the cinema, as is the case of David Lynch

Murilo Rubião é visto como um caso raro na literatura brasileira: poucos autores produziram como ele uma ficção tão decididamente marcada por situações insólitas, eventos estranhos, cenas inusitadas. Não à toa, sua literatura é estudada a partir de discussões em torno do chamado fantástico contemporâneo (ou neofantástico, ou realismo fantástico, ou realismo mágico, ou realismo maravilhoso). Por agora, no entanto, a questão é outra: alguns engenhos em Rubião potencializam um horizonte de pensamento que promove reflexões sobre a noção de não-senso (não-significado). O não-senso é uma possibilidade, por assim dizer, transgenérica - ainda que por vezes possa ser decidido em melhores circunstâncias no que se convencionou chamar, genericamente, literatura nonsense, literatura do absurdo e mesmo literatura fantástica. A fim de fazer jus a este horizonte, esta dissertação cruza os contos, animada por uma lógica do acontecimento, buscada fora das tradições platônicas e aristotélicas, criando ao longo dos capítulos cenários e instâncias associativas que, por sua vez, solicitam algumas distinções: explicação laboratorial e experiência lógica, senso-significado e senso-sentido, imagem e imagem pura, ser e extra-ser. A discussão aqui travada visa contribuir para a prática de uma experiência na literatura de Rubião. / Murilo Rubião is seen as a rare case in Brazilian literature: few authors have produced a fiction so strongly marked by unusual situations, strange events, and unusual scenes. Not for nothing, his literature is studied starting by discussions on the so-called contemporary fantastic (or neo-fantastic, or fantastic realism, or magic realism, or marvelous realism). For now, however, the question is another one: some of Rubiãos pyrotechnics empower a horizon of thought that promotes reflections on the notion of nonsense (non-meaning). The nonsense is, so to speak, a transgender possibility - though sometimes it can be determined, in the best circumstances, in what is generically called nonsense literature, literature of the absurd, and even fantastic literature. In order to make justice to this horizon, this dissertation travels the tales, it animated by a logic of the event, outside of the Platonic and Aristotelian traditions, creating, throughout the chapters, sceneries and associative instances which, in turn, ask for some distinctions: laboratorial explanation and logic experience, sense-meaning and sense-sense, image and pure image, being and extra-being. The discussion promoted here aims to contribute to the practice of an experience in the literature of Rubião.

The development and acquisition of English pronunciation in learners of English is a much neglected area of linguistic study. Research predominantly focuses on the pronunciation skills in adult English learners. However, there is no relevant data pertaining to the pronunciation skills in young English learners. Studies pertaining to pronunciation and oral proficiency are needed in order to fully assess the development and promotion of English language pronunciation in educational settings. It is necessary to encourage the active learning of pronunciation skills in young learners, in order for them to under pin the phonetical and phonological structures of the English language at the earliest stages of their language acquisition. The natural curiosity that young children display for sounds, rhymes and words is a resource that should be exploited by teachers in order to promote and encourage proficient pronunciation at the earliest stage of a child’s Second Language Acquisition (SLA). The current study focuses on the use of nonsense language in Second Language educational settings in order to introduce phonology and phonetics at the earliest stage of English language acquisition to encourage correct pronunciation in young L2 learners of English. The materials chosen for the study are selected verses from Edward Lear’s nonsense ABC. The nonsense ABC is introduced as a teaching/learning tool to help young primary school children in Sweden develop their pronunciation skills and avoid fossilized language patterns at a later stage of Second Language Acquisition. Young language learners need a solid foundation on which to build their language skills in order to develop as mature Second Language learners. The findings of this investigation showed that the introduction of nonsense language as a practical and didactical tool for the development of pronunciation had a positive effect on the development of pronunciation skills in the beginner English Language Learners (ELL) who actively participated in the study.

Le système de contrôle appelé dégradation des ARNm non-sens (NMD) permet de détecter puis de dégrader des ARNm contenant un codon de terminaison prématuré (PTC). Les facteurs principaux de la NMD : UPF1, UPF2 et UPF3 reconnaissent les PTCs en interagissant avec les facteurs de terminaison eRF1, eRF3 et la protéine Poly(A) binding (PABP). La reconstitution d’un système de traduction in vitro a permis d’étudier la terminaison de la traduction en présence des facteurs PABP et UPF1, à l’aide de méthodes de biochimie et de cryo-microscopie électronique. L’étude du rôle du facteur de NMD UPF3B dans la terminaison de la traduction a mis en évidence une double action de cette protéine ; tout d’abord, un retardement de la reconnaissance du codon stop et également la promotion de la dissociation du ribosome. Ce travail a également permis de mettre en évidence une nouvelle interaction entre UPF3B et la kinase SMG1-8-9 et de montrer comment cette interaction affecte l’état de phosphorylation de UPF1. Les résultats de cette étude montrent une interaction complexe entre les différents facteurs de NMD et la kinase SMG1. / Nonsense-mediated mRNA decay (NMD) is an important eukaryotic quality control mechanism that recognizes and degrades mRNA containing a premature termination codon (PTC). Up-frameshift proteins constitute the conserved core NMD factors (UPF1, UPF2 and UPF3). They mediate the recognition of a NMD substrate, i.e. a ribosome stalled at a PTC. UPF proteins were shown to associate with eukaryotic release factors (eRF1 and eRF3) and were suggested to impede translation termination. We showed that, at a normal termination codon, Poly(A)-binding protein (PABP) stimulates translation termination by directly interacting with eRF3a. Using a reconstituted in vitro translation system, we studied translation termination in the presence of the factors PABP and UPF1 using biochemistry and single particle electron cryo-microscopy (Cryo-EM). Additionally, we analysed the role of the other NMD factors UPF2 and UPF3B in translation termination in vitro. We discovered a novel role for UPF3B in translation termination. Moreover, we observed a novel interaction between UPF3B and the SMG1-8-9 kinase complex. The presence of UPF3B affects the kinase activity of SMG1 and thus the phosphorylation state of UPF1. Our results highlight a much more complex interplay of the NMD factors with the translation termination machinery and SMG1 kinase than anticipated.