Le Mélanome Uvéal (MU) est la tumeur de l’œil la plus fréquente dans les adultes. Aucune thérapie pour la prévention ou le soins des métastases a donné preuve d’efficacité. Nous avons établi 7 lignées cellulaires de MU à partir soit de la tumeur du patient soit du matériel tumorale provenant de xénogreffes dérivées de patients (Patient-derived Xenografts, PDXs). Ces lignées cellulaires présentent les altérations cytogénétiques et les mutations « drivers » qui ont été jusqu’au présent identifiées dans la maladie; quatre d’entre elles présentent une déficience de la protéine BAP1 (BRCA1 associated protein-1), l’ altération qui caractérise la progression tumorale dans le MU. Cette collection de lignées a été utilisée pour identifier des nouvelles stratégies thérapeutiques. Une analyse in vitro avec une série d’inhibiteurs specifiques des vois de signalisation MEK/ERK, PKC, et PI3K/mTOR a montré l’efficacité de l’inhibiteur de mTOR Everolimus sur la prolifération cellulaire, effet qui a été confirmé dans 4 PDXs ou le composé a ralenti significativement la croissance cellulaire. Nous avons ensuite effectué une analyse systématique de la synergie en combinant les inhibiteurs. La synergie la plus importante est produite par l’association d’ Everolimus et de l’inhibiteur de PI3K GDC0941, résultat confirmé par une forte augmentation de l’apoptose quand les 2 drogues sont utilisées en combinaison. Pour conclure nous avons établi un instrument utile pour l’étude préclinique du MU . Nos résultats montrent que Everolimus est efficace dans l’inhibition de la croissance de MU in vitro et in vivo et que la combinaison d’un inhibiteur de mTOR et d’un inhibiteur de PI3K est très efficace dans l’induction de l’apoptose des cellules de MU. Enfin, des dérivées de la vitamine D pourraient exercer un effet antiprolifératif spécifique sur les MU avec mutation de BAP1. / Uveal melanoma (UM) is the most common primary tumor of the eye in adults. There is no standard adjuvant treatment to prevent metastasis and no effective therapy in the metastatic setting. We have established a unique panel of 7 UM cell lines from either patient’s tumors or patient-derived tumor xenografts (PDXs). These cell lines bear the cytogenetic alterations and driver mutations associated with UM so far. Importantly four of them display BAP1 (BRCA1 associated protein-1) deficiency, the hallmark of tumor progression in UM. We used this panel of cell lines to identify novel therapeutic strategies for UM patients. In vitro analysis of a series of specific inhibitors of the MEK/ERK, PKC and PI3K/mTOR pathways showed the efficacy of mTOR inhibitor Everolimus in reducing the viability of UM cell lines, a finding confirmed by significantly delayed tumor growth in 4 PDXs. We then preformed a systematic analysis of drug synergy examining the effect of combinations of the selected inhibitors. The best synergy was found with PI3K inhibitor GDC0941 and Everolimus. This was confirmed by a strong increase in apoptosis with this drug combination. In conclusion we have established an useful tool for performing preclinical studies in UM . Our results show that Everolimus efficiently inhbits UM growth in vitro and in vivo, and that mTOR inhibition coupled with PI3K inhibition is a highly effective in inducing apoptosis in UM cells. Finally Vitamin D derivatives might possibly exert a specific anti proliferative effect on BAP1 mutated UM cell lines.

INTRODUCTION: Cerebral Palsy (CP) is a sensorimotor disorder characterized by dysfunctional motor coordination, balance problems, and loss of selective motor control. Motor coordination exhibited as co-contraction, has been subjectively quantified using gait analysis, but recent studies have begun to objectively analyze the amount of co-contraction by collecting electromyography (EMG) data. Center of pressure excursion (COPE) measurements collected during a single leg standing test (SLST) have shown to be more valid measurements of balance in populations with motor disabilities than a SLST alone. A recent study has correlated increased COPE velocity with a lower fall risk as determined by reported fall frequency, suggesting a more objective measure of fall risk. The current study aimed to determine if the fall risk calculated by COPE velocity in children with CP is correlated with co-contraction index value in various muscle synergy groups. It was hypothesized that i) co-contraction index values will differ between high and low fall risk groups, ii) there will be preferential activation of different synergy groups within the high and low fall risk groups, and iii) there will be a negative and direct correlation between COPE velocity and co-contraction index values for all synergy groups. METHODS: Fall risk grouping was determined by average COPE velocity values calculated from previously reported fall frequency groups. Balance ability was determined by COPE measurements during a SLST on a force plate. Muscle synergy groups were determined by common muscle pairings at the hip, knee and ankle. Co-contraction indices were determined from linear envelopes plotted from muscle group EMG data. An independent t-test was run on muscle synergy groups between high and low fall risk groups. Nonparametric Analysis of Variance (ANOVA) and Tukey post-hoc tests were run on the high and low fall risk groups separately to determine differences in co-contraction index value within high and low fall risk groups. A Pearson correlation analyzed COPE velocity and co-contraction index value. RESULTS: No significant differences in muscle synergy between the high and low fall risk groups were found (p = 0.476, 0.076, 0.064, 0.364). The ANOVA and Tukey post-hoc tests for high fall risk group found significant differences in co-activation index value between the sagittal hip and frontal hip groups (p = 0.022) and sagittal hip and ankle groups (p = 0.016). Low fall risk group was found to have significant differences between the sagittal hip and frontal hip groups (p = 0.038) and frontal hip and knee groups (p = 0.012). Weak and negative correlations were found between COPE velocity and both knee and ankle groups (r = -0.309, -0.323, p = 0.059, 0.050). Negligible and insignificant correlations were found between frontal hip and sagittal hip synergies and COPE velocity ((r = 0.013, -0.068, p = 0.475, 0.367). CONCLUSION: There is insufficient evidence to claim that muscle group activations are different depending on fall risk grouped by COPE velocity. It is not currently possible to correlate COPE velocity to a specific synergy group recruitment. However, data do suggest that sagittal hip and knee strategies are recruited more than ankle and frontal hip strategies during SLST.

1980年代以降，「產業群聚現象」為各國在發展高科技產業的歷程中，極重要的趨勢與特色，美國的矽谷模式可謂其濫觴並成為仿效的成功典範。透過在特定的地理區域中，結合產業界（私人部門）、學術機構、研究機構、中央與地方政府（公共部門），建構有利於高科技產業長期發展與繁榮地區經濟的「科學城」。 　　產業群聚的優勢在於群居成員可分攤基礎建設成本、共享所需的生存資源；更易因地理上的便利性，形成上下游或關聯性產業的合作網路，使產品、技術、資訊與情感的交流更密切，演化為利害與共、共存共榮的「命運共同體」。本研究以產業環境、研究環境與居住環境所組成的共生環境作為形成高科技產業群聚的中心假設，採用組織生態學、資源依賴與合作網路的觀點，以「環境資源共享」與「產業網路互補」為經緯，剖析不同群聚的共生型態與綜效利益，釐清不同的產業特性對群聚利益的呼應，與對整體產業與企業競爭力的影響。 　　本研究發現共生環境資源的多寡，決定高科技產業群聚的形成與長期發展。產業環境的優勢反映在生產效率與利益的增強，研究環境的優勢反映在技術與研發實力的提昇，居住環境的優勢有助吸引高科技人才加入。而高科技產業專業分工明顯、產品生命週期短、時效性要求高的產業特性，使得合作廠商需要頻繁的溝通與協調，而這些工作卻必須透過面對面的互動才能達成，這也是形成高科技產業群聚的主因。 　　產業群聚的利益在於地理上的接近性，使群聚成員共享生存環境資源，便於建構合作網路關係。「環境資源共享之經濟性」與「產業網路合作之互補性」兩構面，決定高科技產業群聚的共生綜效利益。共生綜效利益高低，會決定群聚的長期發展與演化。共生綜效利益越高，則產業群聚會趨於成長、擴張；反之，將逐漸萎縮、解散。而合作機制的建立，是提高群聚共生綜效的關鍵。合作網路體系中的核心廠商，則負有建立合作機制的責任，政府（公共部門）也可主導合作機制的建立。 　　不同的高科技產業特性，搭配「適合的」共生綜效利益，可提高產業與企業的競爭力。環境依賴程度高的產業特性，對環境資源共享之經濟性的需求就會較高；專業分工程度高的產業特性，對產業網路合作之互補性的需求就會較高。

國內大多數之公司皆為中小企業，其相較於大公司資源有限，並無一套有系統的策略形成與管理工具。此工具一直是管理階層重視之議題，然而從過去之文獻發現，策略形成的方法紛呈，最為著名的是Porter(1980)競爭策略，但此類文獻大部分皆為國外學者所著，因而本研究針對國內吳思華(2000)的策略九說，以個案實作之方式，闡明其亦能有效協助公司形成策略。 依據過往文獻發現，策略形成工具協助公司形成策略後，往往就不了了之，並無明確說明如何執行已形成之策略。本研究依據Kaplan and Norton(1992)提出之平衡計分卡概念，以吳安妮(2002)(2003)提出策略執行系統4.7.4為架構與策略診斷性系統分析，協助公司執行已形成之策略及分析公司有無水平或垂直缺口，以免導致公司擁有策略後，卻因執行的後繼無力，而無法展現成效。 最後，以免公司內部單位各自為政，造成資源浪費，因而依據Niven(2002)與吳安妮(2002)提供之觀念，使總公司、SBU與SSU三者之策略能有效連結，形成綜效。 關鍵字：中小企業、策略九說、策略形成與執行系統、策略診斷性分析、綜效。 / Most domestic companies are all small and medium enterprises. The limitations in resources for small and medium enterprises are much greater, causing them to not have a systematic strategy formation and management tools. These management tools have been important management issues, however, the literature only found ways to form strategies, the most famous being the Porter (1980) competitive strategy, but most of these documents were all written by foreign scholars. One famous document written by domestic scholars by Wu Se-hwa (2000) strategy nine, wrote a case by case implementation of management tools can also effectively help companies clarify their strategy. Based on previous literature found about the formation of strategic tools to assist companies to form policy, there is often no clear description of how the strategy has been formed. The study, based on Kaplan and Norton (1992) proposed the concept of the Balanced Scorecard, to Miss Anne (2002) (2003) proposed strategies for the implementation of the system 4.7.4 system architecture and analysis of diagnostic strategies to help companies execute strategy and has formed the analysis of the company to see whether they have horizontal or vertical gaps, so as not to cause the company to have a strategy, with the inability to perform follow-ups, and can not show results. Finally, in order to avoid fragmented units within the company, resulting in waste of resources, which according to Niven (2002) and Anne Wu (2002) provided, thus allowing the head office, SBU and SSU's strategy to effectively link the three to form a synergy. Keywords: SMEs, strategy nine, strategic formulation and implementation, analysis of diagnostic strategies, synergy.

生存、獲利以及成長是企業的目標。第二次世界大戰之後，國際性的商業活動快速的成長，隨著全球商業活動自由化、國際化，加上資訊科技的興起，市場全球化與生產全球化為企業創造了機會，也使得企業面臨的競爭環境日趨嚴峻，企業面臨來自全球的挑戰，威脅其生存與獲利。在競爭環境的迅速變動下，企業為了追求永續經營，不斷的成長成為企業生存之必要條件。購併是企業追求快速成長的捷徑之一。 雖然購併能夠幫助企業迅速取得所需要的關鍵資源，但是從所收集的資料顯示，失敗的購併案例還是佔了七成之多，可見成功的購併是一件相當不容易的事。 本研究所描述的個案企業是目前世界上歷史最悠久的化學與製藥公司，公司成立的日期可以回溯到西元1668年。以購併取得所需要的關鍵資源在該企業是常見的作法，所以該企業透過經驗的累積發展出購併相關活動的標準作業程序（SOP）。但是即使已經有豐富的購併經驗，並不是每一件購併案都能夠達成原先所設定的目標。 本研究希望透過研究實際購併案例的啟動購併動機與後續整合行動以印證相關購併理論，並且整理歸納出成功的購併案例中值得學習的作法以及失敗的購併案例中為何失敗的地方以供未來想要採取購併方式的企業作為參考。 歸納個案企業的購併案例得到以下結論。企業選擇購併作為成長方式的動機是為了達成綜效理論中所提及的啟動綜效、營運綜效和市場綜效。至於後續整合行動，在事前必須要有清楚的整合計畫、工作小組、組織架構與人事布局；然後透過即時且透明的溝通管道傳達給每一位員工；並且強化人力資源管理系統讓不管原本是屬於購併公司的員工還是被購併進來的員工都能夠清楚的瞭解自己在購併後的新組織中可能的職涯發展，協助所有員工穩定下來以渡過整合變動期。 / Survive, gain and grow are the targets for all companies. Business environment has been changed and globalization is the mainstream for all business activities after World War II. This change creates opportunities but also bring threats to companies. Companies now have to face challenges from all over the world. Keep growing is the means for companies to keep survival from these challenges. Merger and acquisition（M&A）is one of the shortcuts for companies to pursue fast growth. M&A can help companies to get key resources quickly. However, the chance to get fail is extremely high up to 70% from collected research data. Apparently it is not easy to have a success M&A case. This paper is describing a more than 300 years old pharmaceutical company whom accumulates a lot of experiences in M&A cases from company history. These M&A cases will be analyzed to prove related theories. Key successful factors will also be concluded for companies who will choose M&A as their growth alternative for reference. To sum up illustrated M&A cases, the motivation of a company to trigger M&A is aiming for starting synergy, operating synergy and market synergy. To ensure post-merger integration can proceed smoothly, it requires clear integration plan which contains dedicated task forces for execution, well-thought-out organization structure and important position appointment. Reinforce personnel system to ensure its function can provide necessary and sufficient assistance to all employees timely. Transparent and open communication channels shall be established in order to eliminate insecure atmosphere.

<p>Through a harmonization of IT-tools among intraorganizational units synergies can be attained through economies of scale and homogenous interfaces towards supply chain partners. In this thesis the possibilities for such synergies at Siemens Medical Solutions in Germany are investigated. By evaluating performance of IT-tools and the cost impact of different scenarios recommendations for harmonization at Siemens Medical Solutions are given.</p>

Through a harmonization of IT-tools among intraorganizational units synergies can be attained through economies of scale and homogenous interfaces towards supply chain partners. In this thesis the possibilities for such synergies at Siemens Medical Solutions in Germany are investigated. By evaluating performance of IT-tools and the cost impact of different scenarios recommendations for harmonization at Siemens Medical Solutions are given.

Three UBC researchers have been awarded the 2007 NSERC Synergy Award for Innovation. A development of advanced pulp screen rotors that employ innovative energy-saving technology has garnered a 2007 NSERC Synergy Award. The 2007 Leo Derikx Award from the NSERC Synergy Awards has been awarded to UBC's Mineral Deposit Research Unit. A UBC collaboration with Weyerhaeuser, an international forest products company, and Paprican, the Pulp and Paper Research Insittute of Canada, is among the recipients of a 2007 NSERC Synergy Award for Innovation.

Chronic neck-shoulder pain is associated with impairments of proprioception and motor control. Thus, assessment of proprioceptive and motor function may be powerful tools both for research and clinical practice. However, insufficient knowledge of certain features of human sensorimotor control hampers both development and interpretation of results of clinically relevant tests. For example, evidence is lacking which proprioception submodalities are reflected in common tests of proprioception. For testing motor function, a better understanding of the control of goal directed arm movements is needed. The purpose of the thesis was to gain further insights into the sensorimotor control of the upper limb in healthy subjects, with implications for clinical testing. The main aims were: (1) to study relationships of outcomes of different tests of shoulder proprioception and (2) to study control strategies in bimanual pointing tasks by analysis of the structure of joint angle variability with the Uncontrolled Manifold (UCM) method. Correlations between proprioceptive acuity in different variants of ipsilateral position-matching and velocity-discrimination were studied. The main finding was that two uncorrelated mechanisms based either on perception of position or movement might underlie perception of limb location in ipsilateral position-matching. The results provided important information for interpretation of common and development of novel tests of shoulder proprioception. The structure of joint angle variance was computed with respect to several task variables during bimanual pointing. Joint angle variability was decomposed in variance affecting and not affecting a task variable. The results showed that the variance in joint space was structured according to the predictions of the UCM hypothesis. It was also shown that the arms were united into one synergy to significantly larger degree than joints within each arm were united into single-arm synergies. It was concluded that the UCM approach might quantify components of motor variability during repetitive motor tasks.

Mit Hilfe eines variabel einsetzbaren Reaktornetzwerkmodells (RNM) wird in der vorliegenden Dissertation der Prozess der Vergasung von Brennstoffmischungen in der Fließbildsimulation beschrieben. Neben der Untersuchung von gestuften Prozessketten zur Veredelung von kohlenstoffhaltigen Energieträgern ist damit auch die differenzierte Analyse von Effekten während der Vergasung von binären und ternären Brennstoffmischungen möglich. Die Erstellung sowie Validierung des RNM wird anhand des PEFR-Vergasers, des SFGT-Vergasers und des Hybridwandvergaser vorgenommen. Die anschließende Analyse der Vergasung von Brennstoffmischungen zeigt, dass in ihren Eigenschaften sehr heterogene Brenn¬stoffmischungen Synergieeffekte bei der Vergasung hervorrufen. Diese sind in der Literatur schon oft beschrieben worden, eine systematische Analyse wird jedoch erst in der vorliegenden Dissertation durchgeführt. / Within this document the modeling and simulation of fuel blend gasification is investigated based on a variably applicable Reduced Order Model (ROM) developed for the flowsheet simulation of entrained-flow gasification reactors and processes. On one hand this enables the investigation of cascaded solid fuel conversion technologies and on the other hand effects during gasification of binary and ternary fuel blends are describable. The development as well as the validation of the ROM has been carried out for the SFGT gasifier, the PEFR gasifier and the hybrid-wall gasifier. The subsequent analysis of binary and ternary fuel blend gasification shows that fuel blends with very heterogeneous component properties induce synergy effects which have been reported in various peer review publications.