Suchergebnisse

This January, the U.S. Memories consortium dissolved when it failed to attract a sufficient initial investment. U.S. Memories would have brought together America's largest computer and semiconductor manufacturers, at a start-up cost of approximately $1 billion, to manufacture 4-megabit dynamic random access memory (DRAM) semiconductor chips with IBM-licensed technology. Some commentators argue that antitrust concerns led to U.S. Memories' demise and could frustrate the rise of additional joint production ventures (JPV s). Should the government intervene and relax the antitrust laws to support JPV s? That was the question posed in hearings before a congressional subcommittee in 1989 on four antitrust reform bills.

Die Zahl der Asylsuchenden ist in der Bundesrepublik Deutschland in den letzten Jahren stark zurückgegangen. Die Anerkennungsquote liegt bei rund einem Prozent. Wo sind die Flüchtlinge geblieben? Gibt es keine Gründe mehr, Asyl zu beantragen? Auf der Suche nach den AsylbewerberInnen wird man in den neueren EU-Mitgliedstaaten an den Außengrenzen und in den EU-Anrainerstaaten fündig: Aufgrund von Zuständigkeitsregelungen stranden immer mehr Flüchtlinge an den Rändern der EU und können andere europäische Zielländer nur noch irregulär erreichen. Die Studie zeigt am Beispiel Deutschlands und Polens, wie sich der Wandel des Asylrechts in den vergangenen 20 Jahren vollzogen hat, wie er erklärt werden kann und in welchem Verhältnis er zu den Strategien von MigrantInnen steht. Sie erschließt damit das Feld der Asylpolitik in dreierlei Hinsicht neu: Zum einen wird die Asylpolitik im Kontext migrationspolitischer Kategorienkonstruktionen analysiert. Auf diese Weise wird die Bedeutung der Kategorisierung und Hierarchisierung von `erwünschten´ und `unerwünschten´ MigrantInnen als zentraler Bestandteil des `Migrationsmanagements´ aufgezeigt. Zum anderen liefern die beiden Länderstudien ein umfängliches Bild der Asylpolitik in Deutschland und Polen. Indem die beiden Fallstudien schließlich in die Entwicklungen auf EU-Ebene eingebettet und aufeinander bezogen werden, eröffnet die Studie einen neuen und umfassenden Einblick in die Dynamiken, die den Wandel des europäischen Asylregimes in den letzten zwei Jahrzehnten bestimmt haben. ; peerReviewed

This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al. ; Targeted treatment of advanced melanoma could benefit from the precise molecular characterization of melanoma samples. Using a melanoma-specific selection of 217 genes, we performed targeted deep sequencing of a series of biopsies, from advanced melanoma cases, with a Breslow index of =4 mm, and/or with a loco-regional infiltration in lymph nodes or presenting distant metastasis, as well of a collection of human cell lines. This approach detected 3-4 mutations per case, constituting unique mutational signatures associated with specific inhibitor sensitivity. Functionally, case-specific combinations of inhibitors that simultaneously targeted MAPK-dependent and MAPK-independent mechanisms were most effective at inhibiting melanoma growth, against each specific mutational background. These observations were challenged by characterizing a freshly resected biopsy from a metastatic lesion located in the skin and soft tissue and by testing its associated therapy ex vivo and in vivo using melanocytes and patient-derived xenografted mice, respectively. The results show that upon mutational characterization of advanced melanoma patients, specific mutational profiles can be used for selecting drugs that simultaneously target several deregulated genes/pathways involved in tumor generation or progression. ; This work was supported by grants from the ISCIII, co-financed by the European Union (FEDER) (PI12/00357) and a Ramón and Cajal research program from MINECO (RYC-2013-14097) to JPV, and from the ISCIII (RTIC; RD06/0020/0107, RD012/0036/0060) and the Asociación Española Contra el Cáncer (AECC) to MAP. The work was also supported by a research award from LUCHAMOS POR LA VIDA to JPV and AGC. I.V. is supported by the Ramón and Cajal research program. ; Peer Reviewed

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide. There is increasing interest in developing specific markers to serve as predictors of response to sorafenib and to guide targeted therapy. Using a sequencing platform designed to study somatic mutations in a selection of 112 genes (HepatoExome), we aimed to characterize lesions from HCC patients and cell lines, and to use the data to study the biological and mechanistic effects of case-specific targeted therapies used alone or in combination with sorafenib. We characterized 331 HCC cases in silico and 32 paired samples obtained prospectively from primary tumors of HCC patients. Each case was analyzed in a time compatible with the requirements of the clinic (within 15 days). In 53% of the discovery cohort cases, we detected unique mutational signatures, with up to 34% of them carrying mutated genes with the potential to guide therapy. In a panel of HCC cell lines, each characterized by a specific mutational signature, sorafenib elicited heterogeneous mechanistic and biological responses, whereas targeted therapy provoked the robust inhibition of cell proliferation and DNA synthesis along with the blockage of AKT/mTOR signaling. The combination of sorafenib with targeted therapies exhibited synergistic anti-HCC biological activity concomitantly with highly effective inhibition of MAPK and AKT/mTOR signaling. Thus, somatic mutations may lead to identify case-specific mechanisms of disease in HCC lesions arising from multiple etiologies. Moreover, targeted therapies guided by molecular characterization, used alone or in combination with sorafenib, can effectively block important HCC disease mechanisms. ; FUNDING: Grants from ISCIII, co-financed by the European Union (FEDER) (PI16/00156), Ramón and Cajal research program from MINECO (RYC-2013-14097) and FUNDACIÓN LUCHAMOS POR LA VIDA to JPV. Grants from ISCIII (RD06/0020/0107-RD012/0036/0060) to MAP. Grant from ISCIII (Ref. PIE15/00079) to JC & JPV. NGD is a recipient of a UC-IDIVAL pre-doctoral fellow. I.V. was also supported by the Ramón and Cajal research program.

Merkel cell carcinoma (MCC) is a highly malignant neuroendocrine tumor of the skin whose molecular pathogenesis is not completely understood, despite the role that Merkel cell polyomavirus can play in 55e90% of cases. To study potential mechanisms driving this disease in clinically characterized cases, we searched for somatic mutations using whole-exome sequencing, and extrapolated our findings to study functional biomarkers reporting on the activity of the mutated pathways. Confirming previous results, Merkel cell polyomavirus-negative tumors had higher mutational loads with UV signatures and more frequent mutations in TP53 and RB compared with their Merkel cell polyomavirus-positive counterparts. Despite important genetic differences, the two Merkel cell carcinoma etiologies both exhibited nuclear accumulation of oncogenic transcription factors such as NFAT or nuclear factor of activated T cells (NFAT), P-CREB, and P-STAT3, indicating commonly deregulated pathogenic mechanisms with the potential to serve as targets for therapy. A multivariable analysis identified phosphorylated CRE-binding protein as an independent survival factor with respect to clinical variables and Merkel cell polyomavirus status in our cohort of Merkel cell carcinoma patients. ; This work was supported by grants from Instituto de Salud-Carlos III (ISCIII); cofinanced by the European Union; (FEDER) (PI12/00357), and a Ramón and Cajal research program (MINECO; RYC-2013-14097) to JPV, Asociación Española Contra el Cáncer and ISCIII grants (RD06/0020/0107, RD012/0036/0060) to MAP, and Coordinated Project of Excellence inter-Institutos de investigación acreditados institutes (ISCIII; PIE15/00081) to MAP. The Ramón and Cajal research program also supports IV. SD was supported by the Torres Quevedo subprogram (MICINN; PTQ-12-05391).

MdC González-Vela et al. ; Merkel cell carcinoma (MCC) is a highly malignant neuroendocrine tumor of the skin whose molecular pathogenesis is not completely understood, despite the role that Merkel cell polyomavirus can play in 55–90% of cases. To study potential mechanisms driving this disease in clinically characterized cases, we searched for somatic mutations using whole-exome sequencing, and extrapolated our findings to study functional biomarkers reporting on the activity of the mutated pathways. Confirming previous results, Merkel cell polyomavirus-negative tumors had higher mutational loads with UV signatures and more frequent mutations in TP53 and RB compared with their Merkel cell polyomavirus-positive counterparts. Despite important genetic differences, the two Merkel cell carcinoma etiologies both exhibited nuclear accumulation of oncogenic transcription factors such as NFAT or nuclear factor of activated T cells (NFAT), P-CREB, and P-STAT3, indicating commonly deregulated pathogenic mechanisms with the potential to serve as targets for therapy. A multivariable analysis identified phosphorylated CRE-binding protein as an independent survival factor with respect to clinical variables and Merkel cell polyomavirus status in our cohort of Merkel cell carcinoma patients. ; This work was supported by grants from Instituto de Salud-Carlos III (ISCIII); cofinanced by the European Union; (FEDER) (PI12/00357), and a Ramón and Cajal research program (MINECO; RYC-2013-14097) to JPV, Asociación Española Contra el Cáncer and ISCIII grants (RD06/0020/0107, RD012/0036/0060) to MAP, and Coordinated Project of Excellence inter-Institutos de investigación acreditados institutes (ISCIII; PIE15/00081) to MAP. The Ramón and Cajal research program also supports IV. SD was supported by the Torres Quevedo subprogram (MICINN; PTQ-12-05391). ; Peer Reviewed

The analysis of institutional innovations for channeling citizen participation allows us to recognize that they can be oriented towards the realization or reinforcement of very diverse and contrasting "societal" projects. In this paper, we propose to address different participatory instances through various theoretical-methodological approaches in order to provide evidence and contribute to the discussion. The selected cases correspond to institutional innovations that encourage individual or collective citizen participation and that are implemented at different levels of government with varied designs. For this purpose, we mainly consider how inclusive each of the instances analyzed are and whether they tend more towards strengthening representative government than towards the progressive installation of a more participatory conception of democracy. The evidence produced allows us to recognize that in the case of the JPV, the PP Barrial, JPC-CB and the application App Ciudadana, the centrality of the management undertaken by the representatives in the government is explicit, strengthening a representative conception of democracy at both levels of government. In the case of community-based cultural policies, the centrality of national and municipal management is not evident, rather it is concealed by the rhetoric of co-management. Plural participation in the framework of these policies has been restricted and depowered by institutional weakness, but also as a result of instrumental and corporate participation. In terms of epistemic diversity, these innovations as a whole fail to guarantee the inclusion of varied, open and accessible channels for people with different life trajectories, in all social positions, to publicly express their dissent. ; El análisis de las innovaciones institucionales para canalizar la participación ciudadana permite reconocer que pueden orientarse a la concreción o reforzamientos de proyectos "societales" muy diversos y contrastantes. En el presente trabajo nos proponemos abordar ...

Die Untersuchung vergleicht die Berichterstattung internationaler Nachrichtensender auf ihren YouTube-Kanälen. Propaganda und "Online-Potenziale" dienen als theoretische Grundlage. Beide werden umfassend operationalisiert, sodass die Beiträge der Sender auf inhaltsanalytischer Basis miteinander verglichen werden können. Die Entwicklung eines Propagandaindex sowie eines Index zur Nutzung von Online-Potenzialen, bündeln die Ergebnisse. Die Erkenntnisse liefern Aufschluss über die Zukunfts- und Gefährdungspotenziale internationaler Nachrichtensender.