L’existance de cellules souches leucémiques (CSL) dans la Leucémie Myéloïde Chronique (LMC) prédit que que seule la destruction des CSL conduirait à une guérison. Une proportion importante de patients atteints de LMC développe une résistance aux drogues, environ ~ 30% des cas, Les mécanismes de résistance aux inhibiteurs de tyrosine kinase (TKI) dans la leucémie myéloïde chronique (LMC) restent souvent obscures. Les cellules souches leucémiques de la LMC pourraient rester viables et en repos, malgré la présence de facteurs de croissance ou de médicaments qui semblent les protéger de l'apoptose. Nous avons montré dans la première parti de cette étude que certains transporteurs telles ABCG2, hOCT-1 pourraient jouer un rôle avec le micro environnement dans la résistance des lignées LMC en adhésion au stoma médullaire. De plus, dans deuxième parti nous avons montré que le gène TWIST-1 (est un acteur clé de l'embryogenèse) est déréglementé dans les cellules de LMC innée des résistants à l'imatinib, et que la sur-expression de l’oncogène TWIST-1 pourrait représenter un nouveau facteur clé de pronostiques potentiellement utiles pour améliorer la guérison de LMC aux TKI. De plus, nous avons pu également montrer que le gène TP73 est impliqué dans la résistance des CSL de LMC. Ce gène pourrait être un facteur prédictif pour identifier une résistance potentielle des patients de LMC au moment du diagnostic. Nous avons montré également que ce gène est régulé par le micro-environnement. Nous avons montrés une sur-expression des isoformes tronquées dans les lignées LMC avec l’adhésion au stroma. Les résultats suggèrent que les molécules intrinsèques comme TWIST-1, les transporteurs et les isoformes de p73 sont dérégulées dans les CSL par des mécanismes extrinsèques qui interviennent avec le micro environnement leucémique par le mécanisme d’adhésion dans le phénomène de résistance aux traitements. Ce mécanisme spécial de résistance due à la conservation de ces CSL dans l’état immature en adhésion avec son micro environnement. / The existence of Leukemia stem cells (CSL) in chronic myelogenous leukemia (CML) predicts that only the destruction of CSL lead to a cure. A significant proportion of CML patients develop resistance to drugs, ~ 30% cases, mechanisms of resistance to tyrosine kinase inhibitors (TKI) in chronic myeloid leukemia (CML) often remain obscure. Leukemic stem cells of CML could remain viable and quiet, despite the presence of growth factors or drugs that seem to protect them from apoptosis. We have shown in the first part of this study that some carriers such as ABCG2, hOCT could to be play a role with the microenvironment in the resistance among CML adhesion of stoma Bone marrow. Furthermore, in the second part we showed that the gene TWIST-1 (is a key player of the embryogenesis) is deregulated in cells of CML innately resistant to imatinib, and that overexpression of the oncogene TWIST-1 could represent a new prognostic factor key potentially useful for improving the querison CML to TKI. In addition, we also could show that the TP73 gene is involved in the resistance of CSL CML. This gene could be a predictor to identify potential resistance of CML patients at diagnosis. We have also shown that this gene is regulated by the microenvironment. We have shown an overexpression of truncated isoforms in CML cell lines with the accession to the stroma. The results suggest that intrinsic molecules such as TWIST-1 carriers and p73 isoforms are deregulated in CSL by extrinsic mechanisms involved with the leukemia microenvironment by the mechanism for participation in the phenomenon of drug resistance. This mechanism with its microenvironment.

Cbf11 and Cbf12 proteins, the members of the CSL transcription factors family, are involved in a wide range of cellular processes in the fission yeast Schizosaccharomyces pombe - among other things they regulate cell adhesion and they have also been implicated in maintenance of genome integrity. At the level of the whole genome we previously identified target loci bound by CSL proteins in vivo. Many of them do not contain any consensus CSL-binding element. There are probably different DNA binding modes of the Cbf11/12 proteins and it has not been known what specific biological function is associated with the particular way of DNA binding. For the purpose of studying CSL DNA binding modes we have worked in this project on the implementation of the DNA binding mutation (DBM), which prevents direct DNA binding of CSL proteins to canonical motif in vitro, into the chromosomal locus of the cbf11 and cbf12 genes. Using the "ura4 selection system" we have successfully constructed the scar-less Cbf12-TAP and Cbf12DBM-TAP knock-ins, i.e. the strains without/with DBM in the open reading frame of Cbf12 where Cbf12 is C- terminally TAP-tagged and contains the intact 3'UTR. In our laboratory we have established the CRISPR/Cas9 system by which we have been able to prepare the Cbf11- TAP strain. We have failed to...

Notch pathway plays a critical role during the development and life of metazoan organisms. CSL proteins are the component of the Notch pathway that mediates the regulation of target genes. The discovery of CSL-like proteins in yeast raised the question of their function in unicellular organisms which did not utilize the canonical Notch pathway. CSL-homologues in yeast are conserved in parts that are important for DNA binding and for fission yeast proteins it was shown that they bind to CSL recognition elements in vitro. In fission yeast, CSL paralogues Cbf11 and Cbf12 play antagonistic roles in cell adhesion and the coordination of cell and nuclear division. Yeast CSL proteins have long and intrinsically unstructured N- terminal domains compared to metazoan CSL proteins. In this study, we investigated the functional significance of these extended N-termini of CSL proteins by their complete removal. For newly constructed truncated variants of proteins Cbf11 and Cbf12 in Schizosaccharomyces pombe we observed the lack of ability to bind CSL recognition RBP probe. The removal of N-terminal parts of CSL proteins in fission yeast led to the change in their cellular localization. Once strongly preferred nuclear localization changed by the removal of N-terminal domains to cytoplasmic localization with a...

本研究將繪本運用於成人華語的非正式課程（課外免費教學），旨在透過成人華語學習者對於繪本運用於成人華語文教學的看法及其學習成效，了解成人華語繪本教學的可行性。為達研究目的，本研究採用探索性的研究，以需求分析、課堂觀察記錄與焦點團體訪談為研究工具，蒐集研究資料，作為分析及討論問題的依據。本研究先針對臺灣北部某國立大學之華語文教學中心中級以上之外籍成人學習者發放需求調查問卷，之後以中級程度為限，於該華語中心開設「繪本學華語」免費課，並對修課之學習者進行焦點團體訪談，探討其對成人華語繪本教學的想法與意見。 經過研究實施與資料分析，歸結研究結果如下：（一）有趣又有助於學習者語言能力的繪本教學活動亦適用於成人華語學習者，可見繪本教學不只是兒童的專利；（二）繪本教學能為學習者帶來語言認知、情意上的助益，並彌補正規課程的不足；（三）繪本運用於成人華語教學時，繪本適合與否主要取決於「語言程度」、「繪本題材」與「圖片色彩與畫風」，其中又以「語言程度」最為重要，優先於另外兩者；而就主題而言，與「生活」及「文化」有關的內容最吸引學習者；（四）受限於免費課課程課時短少、分散，且對學習者缺乏約束力與強制力的特性，繪本教學在語言新知與技能提升方面的成效並不明顯，但可作為正規課的複習與輔助教材；（五）繪本運用於中級成人華語免費班教學所遭遇的主要困難為：難以找到與學習者語言程度相符的繪本、過於分散的課型易打斷繪本情節的連續性、免費班學習者語言程度不一。 最後根據調查結果提出華語文教學上的啟發與後續研究建議，以供華語文教學者在成人華語繪本教學方面的參考。 / This study applied picture books to an adult CSL free course, aiming to investigate adult CSL (Chinese as a second language) learners’ perspectives toward using picture books in adult CSL teaching, and the learning efficiency through picture book instruction. The research methods adopted in the study include needs analysis, classroom observations, and focus group interview. The participants of the study are intermediate-level students from a Chinese language center of a university in Northern Taiwan. The results of this study are (1) picture book instruction with interesting and language skill enhancing teaching activities suits adult CSL learners; (2) picture book instruction can benefit adult CSL learners both cognitively and affectively; (3) When using picture books to teach adult CSL learners, the main concerns are language difficulty, topic choice, and the style of pictures; (4) as the instruction time for the adult CSL free course is short and scattered, and it lacks the mandatory and binding force, such picture book instruction does not improve learners’ vocabulary and grammars significantly; however, it may serve as a good supplementary or review course; (5) the three major challenges for picture book adult free CSL course instruction are choices of picture book to suit learners’ needs, short and scattered instruction time, and learners’ various proficiency levels. Pedagogical implications and suggestions for further research are included in the end of the thesis

This paper addresses the issue of design and implementation of syntactic analysis based on the context sensitive languages, respectively, grammars that contains constructs, which isn't possible to analyze with the help of the standard parsers based on the context free grammars. More specifically, this paper deals with the possibility of adding context sensitive support to the classic LL-analysis by replacing the standard pushdown automata (PDA) with deep pushdown automata (DP), which were introduced and published by prof. Alexander Meduna.

I projekteringsfasen utformas en arbetsplatsdispositionsplan (APD-plan), vilket fungerar som en översiktlig illustration av byggarbetsplatsen. Denna ritning visualiserar de byggnader som finns på plats och visar var bland annat upplagsytor för material, transportvägar och bodetablering kan identifieras. För närvarande är 2D-ritningar den dominerande och mest frekvent använda typen av APD-planer. Det finns ytterligare dimensioner som kan adderas på en APD-plan, i denna studie undersöks de nästkommande dimensionerna, volym (3D) samt tidsaspekten (4D). För att analysera de utmaningar, möjligheter och värdet som en APD-plan i 3D och 4D kan medföra samt hur kunskapen och tillgängligheten kan utvecklas för att kontribuera till ett ökande användande av en APD-planering i 3D och 4D. Denna studie har en kvalitativ ansats med sju djupingående intervjuer. Resultatet visar att APD-planering i 3D och 4D ger en tydlig verklighetsbild av byggarbetsplatsens utseende. Vilket möjliggör att risker och fel kan uppmärksammas i ett tidigt skede och genom en simulering kopplat till tidplanen, blir det ett effektivt diskussionsunderlag som kan användas till planering inom det aktuella projektet. För att en implementering och ett fortsatt arbete av 3D och 4D APD-planering ska lyckas, krävs det att organisationerna skapar sig rätt förutsättningar genom att lägga tid och resurser för att etablera en stark kompetens som kan forma ett arbetssätt med APD-planering i 3D och 4D. / During the design phase, a construction site layout plan (CSL-plan) is developed, serving as an overview illustration of the construction site. This plan visualizes the buildings on site and indicates where, among other things such as material storage areas, transport routes, and site offices are located. Currently, 2D drawings are the most frequently used type of CSL-plans. Additional dimensions can be incorporated into an CSL-plan; this study examines the subsequent dimensions: volume (3D) and time (4D). The aim is to analyze the challenges, opportunities, and value that a 3D and 4D APD-plan can offer, and how knowledge and accessibility can be enhanced to encourage greater use of 3D and 4D CSL-planning. This study employs a qualitative approach with seven in-depth interviews. The results suggest that 3D and 4D CSL-planning using various software tools provides a clear, realistic representation of the construction site. This allows risks and errors to be identified at an early stage. Through simulation linked to the schedule, it also becomes an effective discussion framework for project planning. For successful implementation and continued use of 3D and 4D CSL-planning, organizations must create the right conditions by investing time and resources to build strong competencies that can establish an effective workflow with 3D and 4D CSL-planning.

Методом ориентационной микроскопии (EBSD) исследованы структурно-текстурные состояния бесшовных труб из сталей 08ХМФЧА, 25ХМФБ,10Х13Н3МФБ, после горячей прокатки и термических обработок. Установлено, что все структуры (феррит, бейнит, мартенсит) в изделиях как после горячей деформации, так и после термических обработок, характеризуются наличием выраженной кристаллографической текстуры, которую наиболее точно можно определить, как аксиальную, ось которой <111> является параллельной касательной к диаметру трубы. Показано, что процесс формирования текстуры также, как и наблюдающаяся в процессе термической обработки текстурная наследственность, определяются следующими правилами отбора определенных ориентаций α-фазы при γ-α-превращении: 1) наличием стабильных деформационных ориентировок аустенитных зерен; 2) специальными разориентациями (границами) между зернами γ–фазы, на которых начинается превращение; 3) ориентационными соотношениями, реализующимися при превращении; 4) термическими напряжениями, возникающими в изделии при его охлаждении. Последние являются ответственными за формирование специфической кристаллографической текстуры γ-α-превращения в бесшовных стальных трубах. / Microstructure and texture in seamless 0.08C–Cr–Mo–V; 0.25C–Cr–Mo–V–Nb; 0.08–13Cr–3Ni–Mo–V–Nb steel pipes were studied in as rolled and heat treated states using orientation EBSD microscopy. It was found that all types of microstructure (ferrite, martensite, bainite) as well as after hot rolling and after heat treatment have well defined axial crystallographic texture where <111> direction is predominately perpendicular to pipe surface. It was shown that texture formation in heat treated states is inherited due to following factors important for rules of orientation selection during γ to α phase transformation: 1) occurrence of stable orientation of austenite grains resulted from straining; 2) special misorientation (boundaries) of austenite grains where transformation starts; 3) orientation relationships known for phase transformation; 4) thermal stresses in product formed during cooling. The last can be considered as factor defining special texture in steel seamless pipes.

La géométrie à l'école primaire consiste en une familiarisation avec des formes géométriques et leurs propriétés, à travers l'utilisation d'instruments de géométrie. Les objets géométriques reposent sur les représentations graphiques, les relations géométriques sont souvent implicites. L'introduction d'un logiciel de géométrie dynamique (TracenPoche) est vu comme un moyen de les expliciter, conduisant ainsi à voir le dessin comme une figure. Nous avons proposé à des professeurs une série de cinq situations, que nous avons conçues à partir des modes d'intégration de Assude (2007). Nous en proposons une analyse a priori en trois temps (Assude et Mercier, 2007), une analyse a priori du point de vue des savoirs mathématiques, une analyse a priori ascendante du point de vue des actions des élèves modélisée en terme de praxéologie (Chevallard, 1998) et une analyse a priori du point de vue de l'enseignant. Les situations mises en oeuvre dans les classes sont décrites et analysées à l'aide d'éléments de la théorie de l'action conjointe en didactique (TACD, Sensevy, 2011). Nous décrivons l'action conjointe du professeur et des élèves comme un jeu du professeur sur l'élève, permettant ainsi de rendre compte de la dynamique du travail didactique et de l'évolution du « voir un dessin comme une figure ». Les résultats de la thèse, dans le cadre de cette ingénierie exploratoire (Perrin-Glorian, 2009), montrent comment les objets géométriques peuvent être travaillés conjointement dans l'environnement papier-crayon et dans l'environnement tracenpoche, mettant en évidence des caractéristiques de l'action conjointe du professeur et des élèves dans l'explicitation des relations géométriques. / Geometry in primary school is a familiarization with geometric shapes and their properties through the use of geometrical instruments. Geometric objects are based on diagrams and the geometric relationships are often implicit. The introduction of a dynamic geometry software (here TracenPoche) is thus a way to explain how to see « the diagram » as « a figure ». Five situations are given to three teachers. We have built them with « integration modes » from Assude (2007). We proposed an a priori analysis in three stages (Assude and Mercier, 2007), the first a priori analysis - the viewpoint of mathematical knowledge - , the second a priori analysis - students action modelized by the praxeology (Chevallard, 1998) - and the third a priori analysis - the teacher's point of view - . The Situations established in classrooms are described and analyzed using elements of the joint action theory (Sensevy, 2011). We describe the joint action of the teacher and students as a game of the teacher on the student, thereby enabling an analysis of the dynamic of the teaching work and of the evolution of the "seeing a diagram as a figure." The results of this thesis, as part of the exploratory engineering (Perrin-Glorian, 2009), show how geometrical objects can be worked jointly in a paper-and-pencil environment and in a Tracenpoche environment, highlighting the characteristics of the joint action of the teacher and students in the explanation of geometric relationships. The teachers demonstrate initiatives that prove particularly interesting with regard to mathematical issues, and which could be the basis for further research in cooperative engineering (Sensevy & al., 2013).

「溝通」為語言學習的主要目的，如何能使中級華語學習者自然流暢地表達個人觀點並更貼近母語人士的語言習慣是本研究所探討的議題。研究顯示「電影」應用於第二語言教材可以幫助學習者提升溝通能力，更可持續激發語言學習的興趣。然而台灣目前使用電影主要以文化課程輔助進行，尚未規劃專門的電影華語課程，且普遍以成人為主教學對象。 因此本文主要探討如何應用華語電影於青少年華語課程，並分析華語電影教材的學習成效。本研究採用文獻回顧探究電影教學相關研究、中英教學中的電影教學發展、青少年華語教學、教學法與教學模式，以第二章節作為理論架構，依據此架構設計電影華語課程並實際執行。研究結果顯示使用溝通式教學法所延伸的教學活動，同時搭配ADDIE教學模式能有效地將電影教材應用於華語課程中，不僅符合學習者的學習需求，更使教學更具系統性。研究者依電影主題歸納成11種類型，針對青少年學習者選取「愛情類」、「勵志類」類型，以此兩種主題作為框架列舉出20部適合用於華語課程的電影，另外參考電影作為第二語言教材的標準，制定5項華語電影選取原則提供教學者參考。回饋結果顯示，學習者認為電影華語課程能提升聽、說能力，其次為閱讀能力，最後為寫作能力。整體而言，青少年學習者對於電影運用於語言課程中抱持正面的看法，大部分的學習者表示喜愛電影主題和課程中所討論的話題，透過課程中不斷地問答和多元的任務練習活動，學習者溝通時能以自然的表達方式和他人交流想法，並以尊重、包容和分享的情懷欣賞跨文化的議題。最後，研究者於文末提供未來電影華語教學之研究建議。 / Communication is the main purpose of language learning. This research is concerned about how to assist intermediate-level learners in expressing fluently and using the language according to the native speaker's habits. Research shows that using “ Film” can help to improve the communicative ability of the learners, which can also trigger more interest in language learning. However, the use of films for teaching Chinese in Taiwan is limited to culture classes of the adult, not planned for specialized classes. Hence, the main purpose of this research is to analyze how to apply Chinese films in adolescent Chinese courses, and the effect of Chinese film courses. The method of this research is based on the literature review in both teaching Chinese and English by using film, teaching Chinese for adolescent, teaching method and teaching model. Through this framework, the author has planned and implemented the lesson on teaching Chinese through Chinese films. The result has shown that using Communicative Language Teaching and ADDIE teaching model at the same time can incorporate film materials into courses more effectively. According to the film genre, the author has classified 11 types of films, analyzed romance and inspiration topic for adolescent learners, listed 20 films through which are suitable for Chinese courses. Besides, this research has drawn up 5 criteria for selecting Chinese films. The result of the survey has shown that listening and speaking ability can be increased after courses, but not much practice on reading and writing ability. Overall, using film as class material receives a very positive feedback from adolescent learners. Most of the learners show their high interest in themes and topics of the courses, learners can share ideas and express themselves naturally with others through diverse tasks in the class. Meanwhile learning to show respect to different cultures in cross-cultural issues. Pedagogical implications and suggestions for further research are included at the end of this thesis.

The thesis How Do Ordinary Party Members Perceive Themselves? The Case of the KDU-CSL explores both the relation between an ordinary party member and his political party and his role within the party. Therefore, the subject or our research represents the ordinary party member of the KDU-CSL defined as a member without any elected or executive political office. The theoretical framework of the thesis refers to a range authors concerning with political parties and their organisational aspects. The principal empirical part of the thesis is devoted to an analysis of party members in two Czech regions - Prague and the South Moravian region. The thesis is based on the primary qualitative research (semi-structured in-depth interviews and content textual analysis) conducted by the author herself.