Functional sphere profiling reveals the complexity of neuroblastoma tumor-initiating cell model.

Neuroblastoma (NB) is a neural crest-derived childhood tumor characterized by a remarkable phenotypic diversity, ranging from spontaneous regression to fatal metastatic disease. Although the cancer stem cell (CSC) model provides a trail to characterize the cells responsible for tumor onset, the NB tumor-initiating cell (TIC) has not been identified. In this study, the relevance of the CSC model in NB was investigated by taking advantage of typical functional stem cell characteristics. A predictive association was established between self-renewal, as assessed by serial sphere formation, and clinical aggressiveness in primary tumors. Moreover, cell subsets gradually selected during serial sphere culture harbored increased in vivo tumorigenicity, only highlighted in an orthotopic microenvironment. A microarray time course analysis of serial spheres passages from metastatic cells allowed us to specifically "profile" the NB stem cell-like phenotype and to identify CD133, ABC transporter, and WNT and NOTCH genes as spheres markers. On the basis of combined sphere markers expression, at least two distinct tumorigenic cell subpopulations were identified, also shown to preexist in primary NB. However, sphere markers-mediated cell sorting of parental tumor failed to recapitulate the TIC phenotype in the orthotopic model, highlighting the complexity of the CSC model. Our data support the NB stem-like cells as a dynamic and heterogeneous cell population strongly dependent on microenvironmental signals and add novel candidate genes as potential therapeutic targets in the control of high-risk NB.

New York City: "gilt cage" or "promised land" ? : representations of urban space in Edith Wharton and Anzia Yezierska

This thesis explores the importance of literary New York City in the urban narratives of Edith Wharton and Anzia Yezierska. It specifically looks at the Empire City of the Progressive Period when the concept of the city was not only a new theme but also very much a typical American one which was as central to the American experience as had been the Western frontier. It could be argued, in fact, that the American city had become the new frontier where modern experiences like urbanization, industrialization, immigration, and also women's emancipation and suffrage, caused all kinds of sensations on the human scale from smoothly lived assimilation and acculturation to deeply felt alienation because of the constantly shifting urban landscape. The developing urban space made possible the emergence of new female literary protagonists like the working girl, the reformer, the prostitute, and the upper class lady dedicating her life to 'conspicuous consumption'. Industrialization opened up city space to female exploration: on the one hand, upper and middle class ladies ventured out of the home because of the many novel urban possibilities, and on the other, lower class and immigrant girls also left their domestic sphere to look for paid jobs outside the home. New York City at the time was not only considered the epicenter of the world at large, it was also a city of great extremes. Everything was constantly in flux: small brownstones made way for ever taller skyscrapers and huge waves of immigrants from Europe pushed native New Yorkers further uptown on the island, adding to the crowdedness and intensity of the urban experience. The city became a polarized urban space with Fifth Avenue representing one end of the spectrum and the Lower East Side the other. Questions of space and the urban home greatly mattered. It has been pointed out that the city setting functions as an ideal means for the display of human nature as well as social processes. Narrative representations of urban space, therefore, provide a similar canvas for a protagonist's journey and development. From widely diverging vantage points both Edith Wharton and Anzia Yezierska thus create a polarized city where domesticity is a primal concern. Looking at all of their New York narratives by close readings of exterior and interior city representations, this thesis shows how urban space greatly affects questions of identity, assimilation, and alienation in literary protagonists who cannot escape the influence of their respective urban settings. Edith Wharton's upper class "millionaire" heroines are framed and contained by the city interiors of "old" New York, making it impossible for them to truly participate in the urban landscape in order to develop outside of their 'Gilt Cages'. On the other side are Anzia Yezierska's struggling "immigrant" protagonists who, against all odds, never give up in their urban context of streets, rooftops, and stoops. Their New York City, while always challenging and perpetually changing, at least allows them perspectives of hope for a 'Promised Land' in the making. Central for both urban narrative approaches is the quest for a home as an architectural structure, a spiritual resting place, and a locus for identity forming. But just as the actual city embraces change, urban protagonists must embrace change also if they desire to find fulfillment and success. That this turns out to be much easier for Anzia Yezierska's driven immigrants rather than for Edith Wharton's well established native New Yorkers is a surprising conclusion to this urban theme.

From e-voting to smart-voting : e-Tools in and for elections and direct democracy in Switzerland

To what extent do and could e-tools contribute to a democracy like Switzerland? This paper puts forward experiences and visions concerning the application of e-tools for the most traditional democratic processes- elections and, of special importance in Switzerland, direct-democratic votes.Having the particular voting behaviour of the Swiss electorate in mind (low voter turnout - especially among the youngest age group, low political knowledge, etc.) we believe that e-tools which provide information in the forefront of elections or direct-democratic votes offer an enormous service to the voter. As soon as e-voting will be possible in Switzerland (as planned by the government), those e-tools for gathering information online will become indispensable and will gain power enormously. Therefore political scientists should not only focus on potential effects of e-voting itself but rather on the combination of (connected)e-tools of the pre-voting and the voting sphere. In the case of Switzerland, we argue in this paper, the offer of VAAs such as smartvote for elections and direct-democratic votes can provide the voter with more balanced and qualitatively higher information and thereby make a valuable contribution to the Swiss democracy.

La controverse avant le film : quelle politique pour Good Night, And Good Luck ?

This article aims to explain how newspapers commented on the movie Good Night, and Good Luck before its release. The media coverage anticipated George Clooney's film as a partisan attack launched against George W. Bush's policy since 9/11. Clooney advocates another reading: the historic confrontation between journalist Edward Murrow and Senator Joseph McCarty permits to reflect on the crucial role that the media play for democracy. Such reflection tries to prevent the dividing of the public sphere into antagonistic camps opposing "friends" to "foes," a division that undermines the possibility of a true pluralism. Our socio-semiotic analysis will focus on the critical work accomplished by the media, and on the way that work determines the collective meaning of a cultural object. Simultaneously, we will discuss the necessary conditions for pluralism in a public sphere.