Docking through democracy re-ranking protein-protein decoys with a voting system

We have develop a machine learning framework to enhance protein-protein docking results, using Schulze voting method applied to several models from Support Vector machines

Strange Bedfellows and Their Grandchildren: German Literature as Evidence and Confession of Reunification

From Hegel to Merkel, from Bismarck to BMW, German culture has defined and re-defined itself through a cycle of reaction; thesis, antithesis, synthesis. Modern Germany has certainly not escaped this pattern, existing in a very deep and surprisingly present way in reaction to the collapse of the East German state and the formation of a unified Germany. This paper examines the ways in which contemporary German authors evidence this reaction in their work. As a nation at the heart of the East/West divide throughout the Cold War, Germany provides an ideal lens through which to view the shifting cultural, economic, artistic and societal trends of the last three decades. Feelings of powerlessness, loss and nostalgia are evidenced within these trends. Even a small sampling of contemporary German sources sheds light on the ways in which national and personal trauma are internalized and digested—both in the individual and in society as a whole. Using the novels Simple Stories (Schultze, 2002), Berlin Blues (Regener, 2001), and the short stories Ubuville (1998) and German Lesson (Wondratschek, 1998) among others, this paper examines the ways in which contemporary German authors manifest this reaction in their work. This paper demonstrates that although the works vary in form and tone, they all display the feelings of disaffection and the omnipresence of the reunification as the great ,“elephant in the room” of modern Germany. The forceful merging of two nations, two political systems and two peoples, left behind a great and living trauma, one which is made manifest daily in the thoughts and actions of Germans (especially in the East) and in their creative output. As attention in the global West was focused unilaterally on the West Germans and the financial burden they bore as a result of reunification, the real plight of reunification and the true force of the trauma (that is, the trauma endured by East Germans) was largely ignored. This paper is thus useful in not only sounding the depths of modern German literature, but also in defining the effects of reunification on those that faced regionalist discrimination and financial pillaging at the hands of the global West. This paper demonstrates how, in the ever shifting maelstrom of an increasingly globalized world, post-unification Germans and particularly former East Germans are an ideal subject of study to increase our understanding of inter- and pan-generational trauma and the resultant processes of personal identification in which we all, to some degree, take part

Forschung@H-BRS

Die Hochschule präsentiert mit ihrer neuen Broschüre "Forschung@H-BRS" ausgewählte Projekte von Wissenschaftlerinnen und Wissenschaftlern aus den Instituten und Fachbereichen in einem ansprechenden Format. Hochschulpräsident Harmtut Ihne blickt zu Anfang der Broschüre auf den Stand der anwendungsorientierten Forschung an der Hochschule und in Deutschland

Three Failed Attempts of Joint Rankings of Research in Economics and Business

The attempts by Schulze, Warning, and Wiermann (2008) and Ritzberger (2008) to develop a joint ranking list of journals for economics and business research are critically evaluated. The results show a lack of sufficient knowledge of the quality of business journals. Based on these obscure journal rankings, Fabel, Hein, and Hofmeister (2008) derive a ranking of universities and departments. While Diamantopoulos and Wagner (2008) already show a lack of face-validity of these results, this article explains that the reason for this lies not only in the obscure weighting of the journals but, even more importantly, in a remarkable incompleteness of the data base.Journal ranking, university ranking

Effects of latent membrane protein 2A expression and constitutive nuclear factor-κB activity on B cell development in mice

Deckblatt-Impressum persönlicher Dank Inhaltsverzeichnis Abkürzungsverzeichnis Einleitung Literatur Material und Methoden Ergebnisse Diskussion Zusammenfassung Summary Literaturverzeichnis Anhang Danksagung Lebenslauf SelbständigkeitserklärungHodgkin Lymphome gehören zu den häufigsten malignen Erkrankungen des Immunsystems. Es konnte gezeigt werden, dass Hodgkin/Reed Sternberg (H/RS) Zellen, die malignen Zellen des Hodgkin Lymphoms, von B-Zellen abstammen. Die molekulare Pathogenese der H/RS Zellen ist bis heute ungeklärt. Wichtige Faktoren, die in der Pathogenese dieser Zellen eine Rolle spielen, sind die permanente Aktivität des Transkriptionsfaktors Nuclear Factor (NF)-kB und das in mehr als 50 % der H/RS Zellen exprimierte Latente Membranprotein 2A (LMP2A) des Epstein-Barr Virus. Ziel dieser Arbeit war es, erstmals ein Mausmodell zu entwickeln, in dem NF-kB permanent aktiv ist und LMP2A-exprimiert wird. Die Auswirkungen der beiden Faktoren auf die B-Zellen der Mäuse sollten untersucht werden. Zur Etablierung des Mausmodells wurden modifizierte fötale hämatopoietische Stammzellen in B-Zell-defiziente Rezipienten transplantiert. Auf diese Weise konnte man Untersuchungen an Mäusen mit definiert veränderten B-Zellen durchführen. Die Spender-Stammzellen stammten aus Föten mit einem knockout des NF-kB-Inhibitors IkB(alpha). Sie wurden vor der Transplantation mit einem LMP2A-kodierenden Retrovirus infiziert. Als Kontrolle dienten mit dem LMP2A-Retrovirus infizierte Stammzellen aus Wildtyp-IkB(alpha)-Föten. Die permanente Aktivität von NF-kB und die Expression von LMP2A konnten bereits fünf Wochen nach der Transplantation in den hämatopoietischen Zellen der Rezipienten nachgewiesen werden. So ermöglichte das Modell erstmals in vivo die Expression von LMP2A und die permanenten Aktivität von NF-kB in Kombination zu untersuchen. Durchflusszytometrische Analysen belegten einen verringerten Anteil an B-Zellen in Zellfraktionen mit LMP2A Expression. Hervorzuheben ist, dass der Anteil an B-Zellen, die B-Zell-Rezeptoren in hoher Dichte exprimierten (IgM high), innerhalb dieser Zellfraktion niedriger war als in Fraktionen ohne LMP2A Expression. Als Ursache hierfür kommt die - im Rahmen dieser Arbeit nachgewiesene - durch LMP2A und permanente NF-kB Aktivität verminderte Expression der B-zellspezifischen Transkriptionsfaktoren EBF und Pax5 in Betracht. Deren Verlust führt in knockout Mausmodellen zur Unterbrechung der B-Zell-Entwicklung im pro-B-Zell-Stadium. Proliferationsversuche bewiesen eine Hemmung der Proliferation der B-Zellen durch LMP2A. Diese Hemmung und die mittels RT-PCR Analysen gezeigte Herunterregulierung von B-Zell-Differenzierungsfaktoren (EBF und Pax5) spiegeln wider, dass die B-Zellen in ihrer normalen Differenzierung und Proliferation gestört sind. Die permanente Aktivität von NF-kB forcierte die Proliferation der B-Zellen nach Stimulation mit B-zellspezifischen Stimulantien. Diese Zellen profitierten also von Überlebensvorteilen, die sie gegenüber Zellen mit physiologischer NF-kB Aktivität hatten. Sowohl NF-kB als auch LMP2A steigerten die Transkription des Rezeptors und Transkriptionsfaktors Notch1. Es ist bereits belegt, dass dieser Faktor in H/RS Zellen aktiv ist und proliferative und anti-apoptotische Effekte aufweist. NF-kB und LMP2A könnten also den Notch1 Signalweg nutzen, um das Überleben der B-Zellen zu sichern. Im Rahmen dieses Mausmodells konnte gezeigt werden, dass die permanente Aktivität des Transkriptionsfaktors NF-kB und die Expression des Epstein-Barr Virus Proteins LMP2A nicht ausreichend sind für die maligne Transformation von B-Zellen in Milz und Knochenmark. Die Untersuchungen konnten allerdings demonstrieren, dass beide Faktoren auf B-Zellen und deren Transformation Auswirkungen haben. NF-kB verstärkt dabei das Tumorpotential der B-Zellen durch forcierte Proliferation. Beide Faktoren verringern die Transkription der B-Zell-Differenzierungsfaktoren EBF und Pax5.Hodgkin lymphoma are among the most frequent malignant lymphoid disorders. The Hodgkin/Reed Sternberg (H/RS) cells, the malignant cells of the lymphoma, are B cell derived. The molecular pathogenesis of these cells is unknown to date. Common features of more than 50 % of H/RS cells are the constitutive activity of the transcription factor Nuclear Factor (NF) -kB und the expression of the Epstein-Barr virus latent membrane protein 2A (LMP2A). Aim of this study was to establish a mouse model with constitutively active NF-kB und LMP2A expression. The effects of these factors on B-cells in mice were investigated.To establish the model modified fetal haematopoietic stem cells were transplanted into B cell deficient recipients. The donor haematopoietic stem cells were extracted from foetuses with a knockout of the NF-kB-inhibitor IkB(alpha). Before transplantation they were transfected with a retrovirus encoding for LMP2A. Haematopoietic stem cells that were infected with the LMP2A retrovirus from wildtype IkB(alpha) foetuses served as controls. Mice with defined genetic changes in their B cell population were analysed. Five weeks after transplantation the recipients showed constitutive NF-kB activity und LMP2A expression in haematopoietic cells. This model enabled us to analyse effects of permanent NF-kB activity und expression of LMP2A in combination in vivo. Flowcytometric analysis showed lower fractions of B cells when LMP2A was expressed. Additionally the fraction of high IgM expressing B cells decreased. Transcriptional downregulations of B cell specific differentiation factors EBF und Pax5 could be the reasons for this. In EBF und Pax5 knockout mice B cell development is blocked in the pro-B cell stage. Additionally, proliferation assays demonstrated decreased proliferative responses of LMP2A expressing B-cells to B cell specific stimuli. The inhibition of proliferation und the down regulation of the transcription of B-cell specific transcription factors (EBF und Pax5, shown in RT-PCR analysis) revealed deregulated differentiation und proliferation of the B-cells. Permanent NF-kB activity increased B-cell proliferation after stimulation. That means it lead to advantages in survival compared to cells with physiological NF-kB activity. NF-kB as well as LMP2A increased transcription of the receptor und transcription factor Notch1. It was already shown that Notch1 is active in H/RS cells und provides proliferative und antiapoptotic effects. NF-kB und LMP2A might use the Notch1 signalling pathway to protect B-cells from cell death. This mouse model enabled us to show that permanent NF-kB activity und LMP2A expression are not sufficient to turn B-cells malignant like H/RS cells. Nevertheless, analysis demonstrated strong effects on B-cells und their transformation. NF-kB increases the tumor potentials of B-cells by increasing proliferation. Both factors decrease transcription of the transcription factors EBF und Pax5

Interview with Axel Schulze

In German

Editorial

It is with great pleasure that the Editorial Committee presents the second edition of 2010. The articles in this edition cover a wide range of topics. As always, emphasis is placed on an integrated lifeview foundation that offers new insights into relevant philosophical, moral and ethical issues in the variety of disciplines

Discriminating Rankings of Research in Business

The attempts by Schulze, Warning, and Wiermann (2008) and Ritzberger (2008) to develop a joint ranking list of journals for economics and business research are critically evaluated. Their lists suggest that the quality of top business journals is substantially lower than that of many economics journals. If, however, the authors of these lists do not want to claim a general superiority of one discipline (economics) over another one (business), they should give a clear indication that these lists are only applicable for economists. This warning appears necessary because Fabel, Hein, and Hofmeister (2008) derive a ranking of universities and departments with respect to research productivity in business from the business research discriminating list RbR_IMP by Schulze et al. While Diamantopoulos and Wagner (2008) already show a lack of face-validity of these results, this article explains that the reason for this lies not only in the degrading and also biased weighting of the business journals across subfields, but even more importantly, in a remarkable incompleteness of the data base