Not So Fast: Cultivating miRs as Kinks in the Chain of the Cell Cycle.

In this issue of Cancer Cell, Hydbring and colleagues define a novel class of microRNAs (miRNAs), deemed cell-cycle-targeting miRNAs, that target several cyclins/CDKs, reduce tumor cell growth, and induce apoptosis. These miRNAs effectively suppressed chemoresistant patient-derived xenograft growth in vivo, and efficacy could be prospectively predicted with an expression-based algorithm

Erich Kleinschmidt, Die Entdeckung der Intensität. Geschichte einer Denkfigur im 18. Jahrhundert. 2004

Die Dokumentation der Denkfigur ‚Intensität‘ steht im Zentrum dieser reichen Materialsammlung, die Erich Kleinschmidt für den von ihm bearbeiteten Zeitraum vorgelegt hat. Sie bietet vielfältige Anregungen sowohl für einen methodischen Zugang der quellenorientierten Erschließung dieser Denkfigur als auch im Hinblick auf ihre systematische Weiterentwicklung. Um was geht es hierbei

Sprach- und Literaturwissenschaft in den internationalen ›Wissenskulturen‹. Germanistik an der Schnittstelle neuer Ansätze der Wissens- und Techniksoziologie

This article takes as its point of departure recent developments in the sociologies of knowledge, science, and technology, where a ›cultural‹, ›pragmatic‹ or ›social-constructionist‹ turn is spoken of. Though the individual disciplines strike different keynotes, they are all characterised by the adoption of language- and culture-relative viewpoints, as well as by the integration of subject and discipline-related knowledge in a wider social context. This produces a specific orientation in the sociology of knowledge, which aims at a deliberate counter to the commonplace ›knowledge and technologically determined‹ manner of thinking, in which that which is scientifically, technically, or technologically possible is understood as the driver of social developments. By contrast the social-constructionist approach to knowledge, science, and technology research privileges forms of discussion in which the social actors and their possibilities of action, their wishes, aims, and limitation are included. Against a background of the ever-increasing multicultural and multilingual complexity of many present - and, as seems likely, future - societies, and in connection with the social-constructionist turn, one aspect of inquiry increases in importance, and brings the field of German Studies back to its origins as a linguistic and communication science. That is, it is vital that the developments in the fields of knowledge, science, and technology should be supported by appropriate instruments for the analysis and constitution of socially relevant actor groups with their individual agencies and competencies. In other words: when the constitutive role of social decision-makers in the development of knowledge, science, and technology is considered, then research into the processes by which such decisions are made is also indispensible, as is participation in their development. These key points call for the subject-related skills of German Studies, among other fields, which are examined in this study through the following questions: 1) What interests does (intercultural) German Studies have in filling its place in the constellation of international and multi-disciplinary ›knowledge cultures‹? 2) In what ways has (intercultural) German Studies contributed to the exploration of the language/culture complex? 3) To what extent does the co-operation of language and literary studies open ways of actively influencing the formation of international ›knowledge societies‹ and ›knowledge cultures‹? The starting point is the established sociological assumption that the knowledge produced by academia, and other areas of knowledge generation, will become a key variable in the transformation of the economy and the globalisation of society and the simultaneous redistribution of the production of new knowledge to disparate locations in the national and global system of innovation. Werner Rammert, a sociologist specialising in knowledge and technology, describes this as a ›heterogeneously distributed knowledge-production based regime‹, which is characterised by the heterogeneous nature of the actors involved, such as academics, managers, politicians, as well as those active in other fields, and is therefore accompanied by a so-called ›fragmented differentiation‹. In this type of transdisciplinary academic work, sometimes called ›mode 2‹, various forms of knowledge may be connected through the elimination of strict boundaries between the arts, social sciences and natural sciences, as well as the bringing together of theory and practice. The heterogeneity of the epistemic perspectives involved requires, as Rammert rightly stresses, >>a successful reconciliation of the discrepancies<< (Rammert, Technik - Handeln - Wissen. Zu einer pragmatistischen Technik- und Sozialtheorie, 2007, 192). However, he in no way assumes that this can only be done through a model of scientific exactness oriented on the strict explication and formulation of knowledge, as in the natural sciences. Instead he stresses the relevance of non-explicit or implied knowledge. The questions explored in this article, therefore, focus on the implicit in the ›knowledge societies‹ of the present, always keeping in mind the question as to the role linguistics and literary studies can play in academic and social circles where the social constructive turn (reflected in the sociologies of knowledge and technology) plays a decisive role. Step by step, this article considers: 1) fundamental positions of the cultural turn in knowledge science, academia, and technological studies are briefly sketched out, 2) the significance of the self-understanding of German Studies and intercultural German Studies is developed, 3) the intersections of sociology and linguistics are examined, and finally section 4) on the one hand sketches out the current state of a cultural studies and interculturally oriented linguistics, which concerns itself with the question of the language and culture complex, and on the other hand shows the central role of literary language-use in the communication of implicit knowledge, including an excursus on Goethe's scientific theory, and its reception by the physicists Niels Bohr and Werner Heisenberg. It is shown that it is the co-operation of linguistics and literary studies which allows a language and culture specific study of implicit knowledge, in that the relevance of the interplay between literary and everyday, as well as scientific, language use can first be apprehended and properly investigated. Thus, German Studies, - especially intercultural German Studies, since in the latter special attention is paid to questions of internationalism and intra- and interdisciplinarity - which maintains a presence through institutes and chairs in the German speaking world and beyond, can take an independent and central role in the constellation of the contemporary production of knowledg

Fred Lönker, Poetische Anthropologie. Robert Musils Erzählungen ‚Vereinigungen‘. 2002

Robert Musils Vereinigungen gehören - dies hält Fred Lönker einleitend in der Druckfassung seiner Habilitationsschrift fest - zu den schwierigsten Texten der deutschsprachigen und internationalen Literatur. Der Grund hierfür wurde schon in zeitgenössischen Rezensionen in der sprachlichen Gestaltung dieser Erzählungen gesucht: die Mittel der Satzkonstruktion, der Syntax, seien zu stark differenziert, die Metaphorik extrem. Damit sind nun in der Tat typische Kennzeichen des Musilschen Prosastils akzentuiert. Lönker spricht, wie schon andere Interpreten vor ihm, von dem "hermetischen Charakter", der dieser Schreibweise eigen sei, denn die Fülle an Bildern und Vergleichen verunklare - trotz offenbar zugleich angestrebter Präzision und Genauigkeit der Darstellung - vielfach sogar, wovon überhaupt die Rede ist. Musil selbst macht bezugnehmend auf die Vereinigungen noch in einem Brief vom 5. April 1942 an den Pfarrer und Förderer in seiner Genfer Zeit Robert Lejeune dunkle Andeutungen auf deren "Hermeneutik", "Verschlossenheit" und "künstlerische Geheimlehre

LiLi (CH) : Linguistik und Literaturwissenschaft in der Schweiz

Die Geschichte der Beziehungen zwischen Literaturwissenschaft und Linguistik im Rahmen der Germanistik in den letzten 50 Jahren ist durchaus wechselvoll: einer zunehmenden Abkühlung, ja Entfremdung auf der einen Seite steht auf der anderen das wachsende Interesse an gemeinsam fruchtbar zu beackernden Arbeitsfeldern gegenüber. Ein Streifzug durch die Jahrgänge der Siegener Zeitschrift für Literaturwissenschaft und Linguistik (LiLi) seit den frühen 70er Jahren gibt davon ebenso Zeugnis wie aktuelle Projekte kritischer Kooperation (Kasten/Neuland/Schönert 1997, Hoffmann/Kessler Hrsg. 2003) oder der Versuch einer wissenschaftsgeschichtlichen Aufarbeitung des Verhältnisses der beiden Fächer durch das Marbacher Literaturarchiv (Haß/König Hrsg. 2003). Im folgenden Beitrag wird ein kurzer Blick auf die diesbezügliche Situation in der Schweiz geworfen und ein konzeptueller Zugriff auf mögliche Berührungspunkte exemplarisch skizziert

Detection of activating estrogen receptor gene (ESR1) mutations in single circulating tumor cells

Purpose: Early detection is essential for treatment plans before onset of metastatic disease. Our purpose was to demonstrate feasibility to detect and monitor estrogen receptor 1 (ESR1) gene mutations at the single circulating tumor cell (CTC) level in metastatic breast cancer (MBC). Experimental Design: We used a CTC molecular characterization approach to investigate heterogeneity of 14 hotspot mutations in ESR1 and their correlation with endocrine resistance. Combining the CellSearch and DEPArray technologies allowed recovery of 71 single CTCs and 12 WBC from 3 ER-positive MBC patients. Forty CTCs and 12 WBC were subjected to whole genome amplification by MALBAC and Sanger sequencing. Results: Among 3 selected patients, 2 had an ESR1 mutation (Y537). One showed two different ESR1 variants in a single CTC and another showed loss of heterozygosity. All mutations were detected in matched cell-free DNA (cfDNA). Furthermore, one had 2 serial blood samples analyzed and showed changes in both cfDNA and CTCs with emergence of mutations in ESR1 (Y537S and T570I), which has not been reported previously. Conclusions: CTCs are easily accessible biomarkers to monitor and better personalize management of patients with previously demonstrated ER-MBC who are progressing on endocrine therapy. We showed that single CTC analysis can yield important information on clonal heterogeneity and can be a source of discovery of novel and potential driver mutations. Finally, we also validate a workflow for liquid biopsy that will facilitate early detection of ESR1 mutations, the emergence of endocrine resistance and the choice of further target therapy. ©2017 AACR