APRIN(PDS5B) et PALB2, deux protéines impliquées dans la réparation de l’ADN par recombinaison homologue et l’apparition de cancers

Au Canada, en 2015, il était estimé que 78 000 personnes allaient mourir d’un cancer, représentant 30 % de tous les décès et faisant de celui-ci la première cause de mortalité. De plus, 196 900 nouveaux cas de cancers seraient découverts au cours de cette même année (Canadian Cancer Society’s Advisory Committee on Cancer Statistics. Canadian Cancer Statistics 2015. Toronto, ON : Canadian Cancer Society; 2015). L’intégrité du génome est chaque jour menacée par des conditions environnementales qui endommagent l’ADN (ultraviolets, produits chimiques divers, etc.). Parmi les différents types de lésions, l’un des plus délétères et pouvant mener au cancer est la cassure double-brin (CDB). Celle-ci peut être réparée suivant deux mécanismes majeurs : la jonction des extrémités non homologues (Non-Homologous End-Joining ou NHEJ) ou la Recombinaison Homologue (RH). Cette dernière, prépondérante pendant les phases S/G2, consiste en la réparation d’une CDB grâce à l’utilisation d’une chromatide soeur comme modèle, permettant une réparation fidèle du dommage. La RH est sous la dépendance de diverses protéines, dont RAD51, PALB2 et BRCA2. Ces deux dernières sont connues pour être mutées dans les cancers du sein et des ovaires. Ainsi, la compréhension de l’implication de chaque acteur dans la RH est un objectif fondamental dans la lutte contre le cancer et constitue l’objectif général de cette thèse. En 2012, une étude a montré qu’une nouvelle protéine, APRIN (Androgen-induced PRoliferation INhibitor), appartenant au complexe cohésine, interagissait avec BRCA2 et jouait un rôle dans la RH. Les rôles précis d’APRIN dans ce mécanisme restaient toutefois à être définis. Le projet principal de cette thèse repose sur la caractérisation fonctionnelle d’APRIN dans la réparation par RH. Nous révélons qu’APRIN aurait un rôle spécifique et indépendant de celui de la cohésine dans la RH, et pourrait agir à diverses étapes cruciales de ce mécanisme. De plus, nos données montrent que le niveau d’expression d’APRIN pourrait être un marqueur de prédiction dans le cancer ovarien. Étant donné qu’APRIN interagit aussi avec PALB2, autre partenaire essentiel de BRCA2, nous avons également étudié et caractérisé les fonctions de divers mutants de PALB2. Nous faisons ainsi la découverte inattendue d’un nouveau phénotype induit par une troncation de cette protéine associée à certains cancers agressifs. Ainsi, cette thèse apporte des informations supplémentaires et indispensables à la compréhension de la réparation de l’ADN par RH et de la survenue de certains cancers.

Kokusaika and Internationalisation: Australian and Japanese sister city type relationships

Sister city type relationships at local government level form an important part of Australian-Japanese relations. The original concept of sister cities was to increase international understanding and peace at local level. Over the years, that concept has changed and there is now a robust debate over the inclusion of commercial exchanges into sister city type relationships. This article describes the context of this debate by analysing the different perceptions of sister city type relationships in Australia and Japan. It begins with a discussion of the public policy contexts of sister cities in both Australia and Japan. The second section deals with an analysis of the results of surveys in Australia and Japan. Finally, case studies of two important issues related to SCTRs are discussed: economic and business relations and community involvement. The article concludes by suggesting that sister city type relationships between Australia and Japan are dependent upon the over-arching public policy contexts and sometimes lead to mismatched expectations between the two countries.

A new dimension of sister city relationships in the 21st century : a pilot study in Australia

Sister City agreements have historically provided a goodwill platform for countries 10 undertake activities for the enhancement of peaceful and cooperative relations. They have also become instruments for cities 10 develop their own form of internationalization and to provide for specific activities of cullural,
educational or other similar cooperative exchanges between cities generally in different nations. Sisler City Relationships are broadly-based, officially approved, long-IeI'm partnership between two communities in two countries. Using on-line questionnaires distributed through the membership of Australian Sisler City Association (ASCA), this pilot study confirmed that the existing relationships are mainly focused on cultural exchange, education and council exchange. An overwhelming majority of the local governments, however, are ready for the
extension of the Sister City Relationship by developing business and economic related activities. in fact the pilot study confirms this research is timely and necessaty especially in developing policy guidelines and operation
frameworks.

Revisiting 'how we learn' in academia : practice-based learning exchanges in three Australian universities

Ideas of 'how we learn' in formal academic settings have changed markedly in recent decades. The primary position that universities once held on shaping what constitutes learning has come into question from a range of experience-led and situated learning models. Drawing on findings from a study conducted across three Australian universities, the article focuses on the multifarious learning experiences indicative of practice-based learning exchanges such as student placements. Building on both experiential and situated learning theories, the authors found that students can experience transformative and emotional elucidations of learning, that can challenge tacit assumptions and transform the ways they understand the world. It was found that all participants (hosts, students, academics) both teach and learn in these educative scenarios and that, contrary to common (mis)perceptions that academics live in 'ivory towers', they play a crucial role in contributing to learning that takes place in the so-called 'real world'.

Automated proofs for Diffie–Hellman–based key exchanges

We present an automated verification method for security of Diffie–Hellman–based key exchange protocols. The method includes a Hoare-style logic and syntactic checking. The method is applied to protocols in a simplified version of the Bellare–Rogaway–Pointcheval model (2000). The security of the protocol in the complete model can be established automatically by a modular proof technique of Kudla and Paterson (2005).

Motivations for eWOM exchanges in an online community : self-development, problem solving support, relaxation

Electronic word-of-mouth (eWOM) has gained significant attention from academics and practitioners since it has become an important source of consumers’ product information, which can influence consumer purchase intentions (Cheung & Lee, 2012). eWOM exchanges exist in two types of online communities: online communities of practice and online communities of interest. A few prior studies in online communities of interest have examined members’ motivations for product knowledge exchange (Hung & Li, 2007; Ma & Agarwal, 2007). However, there is a lack of understanding of member motivations for exchanging social bonds and enjoyment in addition to exchanging knowledge pertaining to products in the community. It is important to have an initial comprehension of motivation as an antecedent of these three eWOM exchanges so as to be able to determine the driving factors that lead members to generate eWOM communication. Thus, the research problem "What are the driving factors for members to exchange eWOM in an online community?" was justified for investigation. The purpose of this study was to examine different member motivations for exchanging three types of eWOM. Resource exchange theory and theory on consumer motivation and behavior were applied to develop a conceptual framework for this study. This study focused on an online beauty community since there is an increasing trend of consumers turning to online beauty resources so as to exchange useful beauty product information (SheSpot, 2011). As this study examined consumer motivation in an online beauty community, a web-based survey was the most effective and efficient way to gain responses from beauty community members and these members were appropriate samples from which to draw a conclusion about the whole population. Multiple regression analysis was used to test the relationships between member motivations and eWOM exchanges. It was found that members have different motivations for exchanging knowledge, social bonds, and enjoyment related to products: self-development, problem solving support, and relaxation, respectively. This study makes three theoretical contributions. First, this study identifies the influence of self-development motivation on knowledge exchange in an online community of interest, just as this motivation has previously been found in online communities of practice. This study highlights that members of the two different types of online communities share similar goals of knowledge exchange, despite the two communities evincing different attributes (e.g., member characteristics and tasks’ objectives). Further, this study will assist researchers to understand other motivations identified by prior research in online communities of practice since such motivations may be applicable to online communities of interest. Second, this study offers a new perspective on member motivation for social bonding. This study indicates that in addition to social support from friends and family, consumers are motivated to build social bonds with members in an online community of interest since they are an important source of problem solving support in regard to products. Finally, this study extends the body of knowledge pertaining to member motivation for enjoyment exchange. This study provides a basis for researchers to understand that members in an online community of interest value experiential aspects of enjoyable consumption activities, and thus based on group norms, members have a mutual desire for relaxation from enjoyment exchange. The major practical contribution is that this study provides an important guideline for marketing managers to develop different marketing strategies based on member motivations for exchanging three types of eWOM in an online community of interest, such as an online beauty community. This will potentially help marketing managers increase online traffic and revenue, and thus bring success to the community. Although, this study contributes to the literature by highlighting three distinctive member motivations for eWOM exchanges in an online community of interest, there are some possible research limitations. First, this study was conducted in an online beauty community in Australia. Hence, further research should replicate this study in other industries and nations so as to give the findings greater generalisability. Next, online beauty community members are female skewed. Thus, future research should examine whether similar patterns of motivations would emerge in other online communities that tend to be populated by males (e.g., communities focused on football). Further, a web-based survey has its limitations in terms of self-selection and self-reporting (Bhatnagar & Ghose, 2004). Therefore, further studies should test the framework by employing different research methods in order to overcome these weaknesses.

Freddy Gottschalk making a bridge over his sister Ursula Gottschalk in a reproduction of an illustration for the book "Kinder-Turnen in Haus" by Fritz Strube. Sports

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Portrait of Joseph and his sister Elly Schoenbeck; Cologne, Germany. Portraits family

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Portrait of Ralph and Joan Grahme with Ralph's sister Ilse Schuster nee Gottschalk and her husband James at restaurant "Old Vienna"; London, England.

Left to right: Ralph Grahme, Joan Grahme, Ilse Schuster nee Gottschalk, and James Schuster;

Portrait of Franz Catzenstein and his little sister Ellen. Portraits Children

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Studio portrait of Gretel Heimann (on right) with her sister Anna Portraits Children

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Wladimir Eliasberg with his sister Rose on vacation in upstate New York Portraits Men

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