La leucémie lymphoïde aiguë (ALL) est le cancer pédiatrique le plus fréquent. Une proportion importante de ces cas sont des leucémies lymphoïdes aiguës à cellules T (T-ALL). Présentement, le traitement implique l’utilisation d’une chimiothérapie hautement toxique pour une durée s’échelonnant sur plusieurs années. Bien que la rémission soit possible, les séquelles physiques et psychologiques peuvent être dévastatrices, particulièrement dans un contexte pédiatrique. Des rechutes sont également possibles à long terme. Des approches génétiques, cellulaires et moléculaires ont permis d’identifier le thymocyte au stade DN3 comme étant la cellule à l’origine de la leucémie. En effet, dans les cas où la leucémie est induite par l’expression aberrante de SCL/TAL1, des données ont démontré que les thymocytes au stade DN3 sont reprogrammés en cellules souches pré-leucémiques (pré-LSCs) par l’action du complexe SCL-LMO1. Ces cellules acquièrent par la suite une mutation activatrice de NOTCH1, qui accélère le développement de la leucémie. Le stade DN3 est le point de convergence de signaux collaborant pour favoriser survie, différentiation et prolifération cellulaire. Les deux voies de signalisation principales sont celles de NOTCH1 et du pré-TCR. Ces deux signaux sont connus pour jouer un rôle tant au stade pré-leucémique qu’en progression au stade leucémique. Alors qu’il était connu que NOTCH1 était en mesure d’augmenter la fréquence des pré-LSCs, nos travaux révèlent que le pré-TCR favorise leur expansion clonale. Nous démontrons également que les effecteurs de NOTCH1 et du pré-TCR dans les pré-LSCs sont la voie mTOR et la voie de ERK, respectivement. Ces voies de signalisation peuvent être ciblées pharmacologiquement par le Trametinib (inhibiteur MEK1) et le Dactolisib (inhibiteur PI3K/mTOR), menant à un effet additif avec la chimiothérapie (VXL : Vincristine, Dexaméthasone et L-asparaginase) sur les pré-LSCs en essais ex vivo. Nous démontrons également que le Trametinib est synergique avec VXL contre des blastes humains de T-ALL en essais ex vivo. Les résultats de cette même association sont encourageants en essais in vivo de xénogreffe de blastes humains de T-ALL chez des souris immunosupprimées. / Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. T-cell acute lymphoblastic leukemia (T-ALL) accounts for a significant portion of these cases. The current standard of care unfortunately involves the use of highly toxic chemotherapy over multiple years. In spite achievement of high remission rate, the life-long physical and psychological sequalae are devastating and cannot be overlooked, especially in the pediatric setting. Genetic, cellular, and molecular approaches have identified thymocyte at the DN3 stage of differentiation as the cell of origin of leukemia. When leukemia is induced by aberrant expression of SCL/TAL1, data show that DN3 cells are reprogrammed into self-renewing pre-leukemic stem cells (pre-LSCs) by the action of the SCL-LMO1 complex. Then, reprogrammed cells gain a NOTCH1 gain-of-function mutation that speeds up development of leukemia. Interestingly, the DN3 stage is a point at which multiple collaborating signals converge to drive cell survival, differentiation, and proliferation. The two main signaling pathways operating at the DN3 stage are NOTCH1 and the pre-TCR. Both signals are recognized for playing a role in leukemogenesis, both at the pre-leukemic stage and in the transition to acute leukemia. While it was known that NOTCH1 increases pre-LSC frequency, we demonstrate herein that pre-TCR promotes pre-LSC clonal expansion. Additionally, we provide evidence that the mTOR pathway and the ERK pathway are effectors of NOTCH1 and pre-TCR signaling, respectively. These pathways can be targeted pharmacologically with Trametinib (MEK1 inhibitor) and Dactolisib (PI3K/mTOR inhibitor), leading to additive effects on pre-LSC viability when combined with chemotherapy (VXL: Vincristine, Dexamethasone and L-asparaginase) in ex vivo assays. We also demonstrate that association of VXL with Trametinib is synergistic against primary human leukemic blasts in ex vivo assays. Results from in vivo testing of this association through patient-derived xenografts (PDX) conducted on immunocompromised mice look promising.

數位行動浪潮襲捲全球，智慧型手機的普及讓行動行銷成為一股趨勢，如何善用行動媒體的特性來提高整合行銷傳播的綜效亦是近年來數位行銷領域相當關注的話題。APP是行動媒體中最能直接與消費者接觸的工具，而社群APP因為內容具備即時性、社群性等特徵，成為各大品牌搶奪消費者眼球的必爭之地。 　　在眾多社群APP中，Facebook的廣告服務已行之有年，後起之秀Instagram亦於2015年9月對台灣企業開放廣告功能，讓廣告主能以付費的方式觸及更多的使用者。此二平台的廣告運作機制非常相似，消費者都會先接收貼文廣告，再從貼文廣告連接到品牌帳號的主要頁面，兩個品牌訊息加總將有機會產生跨訊息綜效。不過，這兩個平台在內容表現形式上卻不盡相同，且Instagram強大的濾鏡功能能讓照片更具美感，進而影響使用者對品牌的解讀及反應，所呈現的綜效也可能有所不同。 　　因此本研究選定Facebook與Instagram為研究對象，以社群APP平台為自變項，廣告態度及品牌態度為依變項，來驗證跨訊息綜效是否產生，並比較此二平台在廣告資訊處理歷程及效果上的差異。本研究採用實驗法，招募100名政治大學非傳播學院之大學生及研究生進行實驗，所得結果如下： 一、 單一媒體的跨訊息綜效並不顯著，但不同媒體（Facebook與Instagram）的資訊處理歷程、態度形成及跨訊息效果卻不盡相同。 二、 與說服知識相比，美感反應才是影響操弄意圖推論高低的主要變項，接收Facebook廣告的消費者會因為較低美感反應產生較高操弄意圖推論，接收Instagram廣告的消費者則會因為美感反應較高而使操弄意圖推論較低。 三、 操弄意圖推論對訊息涉入度具顯著負向影響，操弄意圖愈高，訊息涉入度愈低，反之亦然。Facebook的操弄意圖推論較高，因此訊息涉入度較低，消費者較缺乏訊息處理動機，而Instagram的操弄意圖推論較低使得訊息涉入度較高，亦即消費者具備較高的訊息處理動機。

The thesis deals with possibilities of an application of system dynamics methodics for an understanding and teaching the project management. A dynamic simulation model has been created for this purpose by using Vensim. A web simulator for the project management, which is based on the simulation model, has been created in the next part of the thesis. The benefit of the simulator over the model is its user- friendliness and its self-explanatory graphic interface, which makes it possible to use the simulation model for purposes of teaching and further reaserch in the field of project management. Powered by TCPDF (www.tcpdf.org)

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Estudos de literatura científica mostram que desenvolver produtos confortáveis não é algo trivial. No entanto, o conforto é um aspecto importante a ser considerado para valorizar e diferenciar linhas aéreas e produtos do setor automotivo. O objetivo inicial desta pesquisa era verificar a influência de acessórios e dispositivos de ajustes nos níveis de conforto e desconforto de passageiros em cabines de aviões. No entanto, com o amadurecimento dos métodos, dos protocolos e das ferramentas desta pesquisa, verificou-se que a metodologia proposta, além de ter utilidade para levantar as necessidades dos usuários, no design de cabines para passageiros, pode ser útil para a sensibilização de projetistas, ao integrar o Processo de Desenvolvimento de Produtos (PDP). Desta forma, o método criado a partir de conhecimentos das Ciências Sociais e Etnografia, com técnicas da Observação Participante e da Análise Ergonômica da Atividade, mostrou-se uma poderosa ferramenta para capacitação e sensibilização de projetistas, arquitetos, engenheiros e designers, para promover a inovação no projeto de ambientes e objetos. Portanto, esta tese discute a importância das atividades dos usuários no desenvolvimento de projetos, para permitir que projetistas possam criar soluções que vão mais além do que é sugerido e estabelecido por parâmetros apresentados em normas técnicas e legislação. Assim, apresenta-se aqui uma nova proposta metodológica para o Design de Produtos e Ambientes dedicados a Passageiros e Viajantes, de uma forma mais ampla, que favoreça a experiência em mobilidade. / Scientific studies show that the development of comfortable products is not trivial. However, comfort is an important aspect to be considered to enhance and distinguish airlines and automotive products and services. The initial objective of this research was to verify the influence of accessories and adjustable devices in passengers comfort and discomfort in aircraft cabins. However, with the maturation of the methods, protocols and tools from this research, it become clear that the proposed methodology, besides being useful to assess users\' needs for designing passengers cabins, may be also useful for sensitization designers by integrating the Product Development Process (PDP). Thus, the method created from Social Sciences and Ethnography knowledge, with participant observations\' techniques and Ergonomics\' Activity Analysis, proved to be a powerful tool for training and sensitization designers, architects, engineers and designers, to promote innovation in interiors and objects design. Therefore, this thesis discusses the importance of users\' activities on the development of projects, to empower designers in creating of solutions that go beyond what is suggested and established by parameters of technical legislation and standards. Thus, we present here a new methodological proposal for products and interiors design for passengers and travelers, in a wide focus, that favors experience in mobility.

有鑒於全球半導體產業已趨成熟，全球半導體通路商之間的競爭也越來越白熱化，越來越多家半導體通路商藉由企業併購，進行所代理產品線的互補、技術整合與併購後的企業資源整合，進而產生併購綜效(Synergy)，以達半導體通路商的經濟規模，才足以持續保有競爭力。 本研究藉由大聯大控股公司的併購策略，持續保持競爭力，以及併購後所產生綜效作為研究對象，針對未來半導體通路商產業的全球佈局之策略參考，在面對全球景氣循環不佳環境下，半導體通路商毛利率越來越低情況下，如何思考通路商的營運策略、通路商的價值與市場定位，尋求全球戰略佈局，發揮企業的核心價值與核心競爭力。在其併購前之充分準備、規劃與決定併購方式，併購後如何持續做好經營管理，組織設計與調整組織..等做完整分析，從中找出『半導體通路商之核心能力、併購戰略與整合佈局』等交互關係。 研究說明併購前應有的考慮事項如：環境評估、競爭策略方向、白地策略、價值鏈加值、併購後之系統整合、資源整合、組織的設計創新、經營管理制度創新..等因素，供相關企業於併購前後可採取之策略參考，圓滿達成併購績效目標，並達到預期併購綜效，符合股東期望。 本案例研究結果歸納出下列重點： 1.併購前首重交易前之準備階段(即評估併購目標公司和制定整併計畫)。 2.挑選併購對象時，相關併購所創造的價值比無相關併購要來得高。 3.周詳的整合計畫與管理機制，是實現併購綜效的主要關鍵。 4.留住關鍵人才是確保企業併購成功的重要基石。 5.併購後，如何消彌兩家企業間文化差異，是合併後經營成敗的關鍵因素。 6.併購後保留雙方的優良企業文化，再循序漸進轉化成新的企業願景、文化。 7.藉由不斷的溝通協調，建立共識，設定目標，資源整合等，才可以提升綜效。 8.設計新組織架構、新的營運與管理模式，讓併購綜效延續，持續保有競爭力。 9.階段性組織調整與經營策略調整，並配合上游供應商策略，是半導體通路商重要成功關鍵因素。 10.依併購對象規模條件決定，小公司由子集團併購，大公司由控股公司併購。 / In view of the mature global semiconductor industry, more and more intense competition between the global semiconductor distributor, a growing number of semiconductor distributors through mergers and acquisitions, product line agent complementary, technology integration, mergers and acquisitions, enterprise resource integration, and thus produce a net synergistic effect (synergy), to achieve the economies of scale of the semiconductor distributor, enough to sustain their competitiveness. By WPG Holdings company's acquisition strategy, the study continued to remain competitive and generate synergies after the acquisition as an object of study for future semiconductor distributors industry's and global distribution strategy reference, the poor in the face of the global business cycle environment, getting lower and lower gross profit margin in the semiconductor distributors, how to think about the operating strategy of the distributor, distributor’s value and market positioning, seeking global strategic layout, play to the company's core values and core competitiveness. Fully prepared in the pre-merger planning and decision mergers and acquisitions, post-merger continued good business management, organizational design and adjust the organization. Do a complete analysis, to find out the core competencies of the semiconductor distributors, M & A strategy and integration layout and other interactive relationship. Study shows that pre-merger due considerations such as: environmental assessment, direction of competitive strategy, Seizing the white space strategy, value chain, value-added, M & A system integration, integration of resources, organization design innovation, management system innovation. And other factors, for related enterprises can be taken before and after the M & A strategy reference, the successful completion of the merger and acquisition performance objectives, and achieve the expected synergistic gains, in line with the expectations of shareholders. This case study results are summarized to the following priorities: 1. Preparation phase before the first heavy trading in the pre-merger (ie, assessment of the M & A target company and the development of the whole and plans). 2. Selection of acquisition targets, the value of mergers and acquisitions are creating related to mergers and acquisitions to come. 3. Comprehensive integration planning and management mechanism, which is the key to achieve synergistic gains. 4. Retain key personnel to ensure that the cornerstone of success of mergers and acquisitions. 5. After the merger, and how to eliminate a key factor in business success of the cultural differences between the two companies merged. 6. After the merger, to retain both excellent corporate culture, and then step-by-step into the new corporate vision, culture. 7. By continuous communication and coordination, consensus-building, goal setting, resource integration, can enhance the synergy. 8. The design of the new organizational structure, the new operation and management mode, make a merger synergy continuation, continued to stay competitive. 9. Phased organizational restructuring and business strategy adjustment, and in line with the strategy of vendor suppliers are the semiconductor distributor important critical success factors. 10. Conditions in accordance with the scale of acquisition targets decided, a small company by the sub-group mergers and acquisitions, and large companies by the holding company mergers and acquisitions.

Darbo aktualumas. 2000 m. Europos Taryba patvirtino Lisabonos strategiją, kuria nustatė Europos Sąjungos strateginius tikslus, siekiant žiniomis grindžiamoje ekonomikoje padidinti užimtumą, stiprinti ekonomines reformas ir socialinę sanglaudą. Per pirmuosius penkerius Lisabonos strategijos įgyvendinimo metus ES mastu norimų rezultatų nebuvo pasiekta, todėl buvo priimtas sprendimas orientuotis į nacionalinių Lisabonos strategijos įgyvendinimo programų kūrimą. Šiame darbe analizuojamos Lisabonos strategijos ir 4 pagrindinių Lietuvos ilgalaikių strategijų sąsajos. Šios strategijos dėl bendros kilmės, panašių vizijų ir siekių, Lisabonos procese turėtų būti įgyvendinamos kartu su Nacionaline Lisabonos strategijos įgyvendinimo programa, atsižvelgiant į bendrus prioritetus, koordinuojant veiksmus ir planuojant tikslingą projektų bei reformų finansavimą. Darbo objektas – Lisabonos strategija. Darbo tikslas – sukurti Nacionalinės Lisabonos strategijos įgyvendinimo sinergetinį modelį, kuris užtikrintų efektyvesnį Lisabonos strategijos įgyvendinimą atsižvelgiant į Lietuvos strateginius prioritetus. Praktinė darbo reikšmė grindžiama Lisabonos strategijos įgyvendinimo Lietuvoje sinergetinio modelio sukūrimu bei jo analize. Teorinė darbo reikšmė orientuota į tinkamą Lisabonos strategijos ir 4 pagrindinių Lietuvos ilgalaikių strategijų įgyvendinimo koordinavimą bei makroekonominės politikos suderinamumą siekiant sinergijos efekto. / The relevance of the study. European Council has confirmed Lisbon strategy in year 2000, according to this strategy European‘s Council strategical aims were set, by way of increasing business in economy, grounded by knowledge, consolidate economical reforms and social cohesion. There wasn‘t obtained desirable results in the degree of EU during the first five years of realization of Lisbon strategy, thus there was accepted a decision oriented around creation of programs of nacional Lisbon strategy realization. There are analized connections between Lisbon strategies and 4 general permanent Lithuania‘s strategies in this issue. In Lisbon process these strategies should be realized together with Nacional Lisbon‘s strategy realization program, because of their common origin, similar visions and objects. This should be realized considering to common priorities, cordinating actions and planning purposeful sponsorship to projects and reforms. The object of the study – Lisbon strategy. The aim of the study – to create a synergy model of realization of Nacional Lisbon strategy, whick will make the realization of Lisbon strategy more effetive, considering to Lithuania‘s strategical priorities. Practical import of this issue is going entirely by realization of Lisbon strategy in Lithuania, creation of synergy model and it‘s analyse. Theorical import of this issue is oriented to suitable cordination of Lisbon‘s strategy and 4 general permanent Lithuania‘s strategies realization and... [to full text]

Ces travaux ont pour objectif l'identification et la compréhension de l'effet de la corrosion aqueuse sur la durée de vie en fatigue à grand nombre de cycles (HCF) d'un acier inoxydable martensitique utilisé dans des applications aéronautiques. Tout d'abord, l'effet géométrique des défauts de corrosion sur la limite de fatigue à 10^7 cycles à l'air a été étudié avec quatre tailles différentes de piqûres de corrosion. A partir de ces résultats, une nouvelle approche volumique non locale de modélisation numérique a été proposée pour prendre en compte une géométrie réelle d'un défaut de corrosion issu des analyses en microtomographie X. Ensuite, les phénomènes de couplage chargement cyclique/corrosion ont été identifiés par des essais de fatigue à grande durée de vie (entre 10^5 et 10^7 cycles) dans une solution aqueuse à 0,1 M NaCl (à pH = 6) pour deux rapports de charge (R = -1 et 0,1). Le comportement électrochimique du film passif a été étudié in situ au cours des essais de fatigue-corrosion par le suivi du potentiel libre de corrosion et des mesures d'impédance électrochimique. Les observations des mécanismes d'amorçage de fissures et des mesures électrochimiques in-situ ont permis d'identifier un scénario d'amorçage de fissures de fatigue. Ce scénario implique des processus de rupture locale du film passif (induite par le chargement cyclique) et de corrosion assistée par le chargement cyclique. Finalement un modèle analytiquede prévision de la durée de vie en fatigue dans un milieu aqueux corrosif a été proposé à partir des résultats expérimentaux. / This study addresses the effects of corrosion on the high cycle fatigue (HCF)strength of a martensitic stainless steel used in aeronautic applications. First, the geometry of corrosion pits on the fatigue strength in air at 10^7 cycles were studied with four different pit sizes. A new non-local fatigue criterion was proposed to simulate real shapes of pits as identified by X-ray microtomography. Corrosion fatigue synergy phenomena was studied by HCF tests (between 10^5 and 10^7 cycles) in a 0.1 M NaCl aqueous solution (pH = 6) with two load ratios (R = -1 and 0.1). Next, the electrochemical behavior of the passive film was investigated during in situ corrosion fatigue tests by free potential measurements and electrochemical impedance spectroscopy (EIS). Based on fractography analysis and electrochemical test results, corrosion fatigue crack initiation mechanisms were investigated. A scenario of fatigue crack initiation was proposed based on physical evidence. This scenario implied combined processes of local passive film rupture (induced by the cyclic loading), stress-assisted corrosion and enhanced pitting development. Local passive film ruptures were the main cause of the corrosion fatigue crack initiation. Finally, a analytical model for corrosion fatigue crack initiation was proposed based.

Estudos de literatura científica mostram que desenvolver produtos confortáveis não é algo trivial. No entanto, o conforto é um aspecto importante a ser considerado para valorizar e diferenciar linhas aéreas e produtos do setor automotivo. O objetivo inicial desta pesquisa era verificar a influência de acessórios e dispositivos de ajustes nos níveis de conforto e desconforto de passageiros em cabines de aviões. No entanto, com o amadurecimento dos métodos, dos protocolos e das ferramentas desta pesquisa, verificou-se que a metodologia proposta, além de ter utilidade para levantar as necessidades dos usuários, no design de cabines para passageiros, pode ser útil para a sensibilização de projetistas, ao integrar o Processo de Desenvolvimento de Produtos (PDP). Desta forma, o método criado a partir de conhecimentos das Ciências Sociais e Etnografia, com técnicas da Observação Participante e da Análise Ergonômica da Atividade, mostrou-se uma poderosa ferramenta para capacitação e sensibilização de projetistas, arquitetos, engenheiros e designers, para promover a inovação no projeto de ambientes e objetos. Portanto, esta tese discute a importância das atividades dos usuários no desenvolvimento de projetos, para permitir que projetistas possam criar soluções que vão mais além do que é sugerido e estabelecido por parâmetros apresentados em normas técnicas e legislação. Assim, apresenta-se aqui uma nova proposta metodológica para o Design de Produtos e Ambientes dedicados a Passageiros e Viajantes, de uma forma mais ampla, que favoreça a experiência em mobilidade. / Scientific studies show that the development of comfortable products is not trivial. However, comfort is an important aspect to be considered to enhance and distinguish airlines and automotive products and services. The initial objective of this research was to verify the influence of accessories and adjustable devices in passengers comfort and discomfort in aircraft cabins. However, with the maturation of the methods, protocols and tools from this research, it become clear that the proposed methodology, besides being useful to assess users\' needs for designing passengers cabins, may be also useful for sensitization designers by integrating the Product Development Process (PDP). Thus, the method created from Social Sciences and Ethnography knowledge, with participant observations\' techniques and Ergonomics\' Activity Analysis, proved to be a powerful tool for training and sensitization designers, architects, engineers and designers, to promote innovation in interiors and objects design. Therefore, this thesis discusses the importance of users\' activities on the development of projects, to empower designers in creating of solutions that go beyond what is suggested and established by parameters of technical legislation and standards. Thus, we present here a new methodological proposal for products and interiors design for passengers and travelers, in a wide focus, that favors experience in mobility.

綜觀國內外探討金融產業經營效率之相關文獻，多數針對銀行、證券、保險中其一產業進行獨立實證研究，較無法將金融控股之綜效表現加以捕捉並體現在估計效率值中，也因此在本文中，將同時涵蓋銀行業務與證券業務，並以納入金控體制與否加以區分為不同子集合進行探討，透過數理方法聯結金控體制下銀行與證券業務部門兩者間因多角化經營所產生之綜效，以修正傳統方法上表現綜效法上之不足，使估計效率值具有更高的參考依據。 此外，研究產業效率所參考之研究方法，在相關文獻中無參數法乃以資料包絡分析法(Data envelopement analysis, DEA)為多數研究者所採用；參數法則以隨機邊界模型(stochastic frontier approach, SFA)為主要研究方法，進一步在不同群組技術效率之比較中，Battese et al. (2004) 與 O’Donnell et al. (2008)提出為多數研究者所接受之共同邊界模型(Metafrontier)，而Huang et al. (2013)所提出之修正模型使共同邊界模型在效率研究上更加完備，本文則希望以此修正模型作為主要研究模型，並同時引用Battese et al. (2004)傳統模型加以比較：(1)考慮綜效前後 (2)傳統模型與修正模型間效率值的差異，期待為後續相關研究者在方法論上提供參考依據。 關鍵字：經營效率、技術效率、共同邊界、計量方法、關聯結構法、金融控股銀行 / This study aims to discuss the evidence suggested that synergy improve the operating performance of Taiwan’s commerical banks and securites firms. Furthermore, efficiency comparisons amongst two basis metafrontier models, Haung et al.(2013) and Battese et al.(2004), and copula-adjusted metafrontier. The empirical results suggest that copula-adjusted metafrontier could significantly improve the efficiency of financial holding companies based on the data of sample period 2001-2012. On the framework of copula-adjusted metafrontier, the evidence also imply that financial holging companysubsidiary technical efficiency is better than non-financial holding company compared to the framework of Haung et al.(2013) and Battese et al.(2004), the conclusion emphasis that synergy is perhaps one crucial key factor influenced the efficiency estimation. Otherwise, this study appears to support the copula-adjusted metafrontier model is also well-adjusted compared to programming techniques because not only it enables the statistical inferences to be drawn, but also provides more efficiency estimations.