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For many manufacturers, hybridization represents an attractive solution for reducing the energy consumption of their vehicles. However, electrification offers a wide range of possibilities for implementing powertrain concepts. The concepts can differ regarding their mechanical complexity and the required power of the electrical machines. In this article, drive concepts that differ in their functionality and drive train topology are compared. Based on requirements for the C, D, and E segment, the mechanical and electrical effort of the concepts is analyzed. The results show that the mechanical effort in the C segment can be reduced as long as the electrical effort is increased. In case of higher vehicle segments, the electrical effort can increase considerably, making concepts with increased mechanical complexity more suitable. The driving performance and efficiency in hybrid operation are evaluated via simulation. The results show that the difference of acceleration times in hybrid operation between a charged and discharged battery is lower for mechanically complex concepts. At the same time, they achieve lower CO2 emissions. Therefore, these concepts represent a better compromise regarding performance and efficiency. Despite lower transmission efficiencies in hybrid operation, they achieve conversion qualities similar to simpler concepts and lower emissions with lower electrical effort.

Topic modeling is a state-of-the-art technique for analyzing text corpora. It uses a statistical model, most commonly Latent Dirichlet Allocation (LDA), to discover abstract topics that occur in the document collection. However, the LDA-based topic modeling procedure is based on a randomly selected initial configuration as well as a number of parameter values than need to be chosen. This induces uncertainties on the topic modeling results, and visualization methods should convey these uncertainties during the analysis process. We propose a visual uncertainty-aware topic modeling analysis. We capture the uncertainty by computing topic modeling ensembles and propose measures for estimating topic modeling uncertainty from the ensemble. Then, we propose to enhance state-of-the-art topic modeling visualization methods to convey the uncertainty in the topic modeling process. We visualize the entire ensemble of topic modeling results at different levels for topic and document analysis. We apply our visualization methods to a text corpus to document the impact of uncertainty on the analysis.

Das Topic Modeling wird momentan als ein vielversprechendes Verfahren der Digital Humanities diskutiert. Als besonderes geeignetes Korpus fur digitale Erschliesungsmethoden gelten aufgrund der ihnen eigenen Spannung von Singularitat und Exemplaritat Sammlungen von Fallgeschichten. Diese Behauptung soll hier am Magazin zur Erfahrungsseelenkunde uberpruft werden. Der Beitrag fuhrt zudem die Debatte daruber weiter, was in der Analyse von narrativen Texten eigentlich unter ›Topic‹ zu verstehen ist. Vertreten wird die These, dass sich ›Topic‹ in der quantitativen Analyse von Fallgeschichten als ›Motiv‹ fassen lasst. Die Topic Modeling-Analyse der vielen autobiografischen Texte des Magazins verweist auf die dort verwendeten Topoi der Autobiografie.

Bevor ich auf meine eigene Lehre zu sprechen komme, möchte ich eine kleine Akzentverschiebung vornehmen und hoffe, damit vielleicht doch noch einen neuen Punkt in die Diskussion einbringen zu können. Am Anfang meiner Ausführungen steht eine hochschuldidaktische Perspektive, die dazu beitragen soll, nicht vorrangig die technische Umsetzung oder praktische Planung von asynchronen Lernphasen zu beleuchten, sondern die Aufmerksamkeit auf Lernprozesse zu lenken. Als Frage formuliert: Was motiviert die Lernenden zum Lernen? Das betrifft nicht nur die digitale Lehre. Ich schließe damit an die Debatten der Hochschuldidaktik an, die sich in den letzten Dekaden zum Ziel gesetzt haben, die Aktivität von Lernenden zu steigern. Zentral ist dabei die Wende vom Lehren zum Lernen – bzw. vom teaching zum learning, wie es in der international geführten Debatte heißt. Wesentlich für diesen Paradigmawechsel ist das neue Interesse am studentischen Lernprozess: die Studierendenzentrierung. Übernimmt man als Dozierender Verantwortung für den ganzen Lernprozess und nicht nur für den Ablauf des Seminars, dann ergibt sich ein fundamental neues Selbstverständnis für Lehrende.

Background and Purpose: With the emergence of extensively drug-resistant tuberculosis, there is a need for new anti-tubercular drugs that work through novel mechanisms of action. The meta cleavage product hydrolase, HsaD, has been demonstrated to be critical for the survival of Mycobacterium tuberculosis in macrophages and is encoded in an operon involved in cholesterol catabolism, which is identical in M. tuberculosis and M. bovis BCG. Experimental Approach: We generated a mutant strain of M. bovis BCG with a deletion of hsaD and tested its growth on cholesterol. Using a fragment based approach, over 1000 compounds were screened by a combination of differential scanning fluorimetry, NMR spectroscopy and enzymatic assay with pure recombinant HsaD to identify potential inhibitors. We used enzymological and structural studies to investigate derivatives of the inhibitors identified and to test their effects on growth of M. bovis BCG and M. tuberculosis. Key Results: The hsaD deleted strain was unable to grow on cholesterol as sole carbon source but did grow on glucose. Of seven chemically distinct ‘hits’ from the library, two chemical classes of fragments were found to bind in the vicinity of the active site of HsaD by X-ray crystallography. The compounds also inhibited growth of M. tuberculosis on cholesterol. The most potent inhibitor of HsaD was also found to be the best inhibitor of mycobacterial growth on cholesterol-supplemented minimal medium. Conclusions and Implications: We propose that HsaD is a novel therapeutic target, which should be fully exploited in order to design and discover new anti-tubercular drugs.

Item does not contain fulltext Recent utopia research has long since abandoned idealized visions of the future and discusses utopia as 'impulse', 'method', or as a 'state of mind', which is incongruous with the immediate situation. But how should we understand such a self? How does it manifest itself, how does it perform, how does it present itself? At this point, utopia and autobiography research come together and apply the contributions to autofiction as utopia presented with this volume. Wie wird in autofiktionalen Texten die eigene Lebensgeschichte als utopische Erzählung gestaltet? Der Band widmet sich dieser Frage hinsichtlich der gesellschaftlichen, raumzeitlichen und medialen Dimension der utopischen Autofiktion.Die Utopie-Forschung hat sich schon seit längerer Zeit von idealisierten Zukunftsvisionen verabschiedet und diskutiert Utopie unter anderem als ‚Impuls‘, ‚Methode‘ oder als ein ‚Bewusstsein‘, das sich nicht mit dem bestehenden Sein identifiziert. Hier setzt der Band an und fragt speziell nach dem Utopischen in autofiktionalen Lebensentwürfen. 220 p.

Macrodomains are conserved protein interaction modules that can be found in all domains of life as well as in certain viruses. Macrodomains mediate recognition of sequence motifs harbouring adenosine diphosphate ribose (ADPR) modifications, thereby regulating a variety of cellular processes. Due to their role in cancer or viral pathogenesis, macrodomains have emerged as potential therapeutic targets, but the unavailability of small molecule inhibitors has hampered target validation studies so far. Here, we describe an efficient screening strategy for identification of small molecule inhibitors that displace ADPR from macrodomains. We report the discovery and characterisation of a macrodomain inhibitor, GeA-69, selectively targeting macrodomain 2 (MD2) of PARP14 with low micromolar affinity. Co-crystallisation of a GeA-69 analogue with PARP14 MD2 revealed an allosteric binding mechanism explaining its selectivity over other human macrodomains. We show that GeA-69 engages PARP14 MD2 in intact cells and prevents its localisation to sites of DNA damage.

Sieg demonstrates how Ilija Trojanow and Christian Muhrbeck’s collection of stories and photographs, Wo Orpheus begraben liegt [Where Orpheus lies buried] (2013), can be read as a direct response to discourses on European identity and to the question of whether European memory discourses can be integrative, that is, constitutive of a transnational European identity, while still allowing for a plurality of European voices. The ironic title of the book alludes to Bulgaria’s part in Europe’s rich cultural history, and critiques attempts to locate the foundations of European identity in Greek antiquity. But while the texts and images all allude to Bulgaria’s past, they offer no definitive historical narrative that might serve as a new, unifying myth. The complex juxtaposition of texts and images instead raises questions about how we remember and construct the past. Placing emphasis on the politics of remembrance, particularly in Eastern Europe, Trojanow and Muhrbeck’s book casts doubt on the very idea of foundational European myths, arguing instead for a memorial culture that embraces the plurality of European memory.

Alfred Anderschs Landschafts- und Stadtedarstellungen sind schon haufiger zum Gegenstand der Forschung geworden, charakterisieren sie sein Werk doch in hohem Mase. Von den italienischen Weizenfeldern in Die Kirschen der Freiheit (1952) bis zur Darstellung der Eifel in Winterspelt (1974) fokussieren Anderschs Texte wiederholt Landschaften. Untersucht worden sind in dieser Hinsicht insbesondere die asthetischen Darstellungsverfahren von Anderschs Prosa. In der Tat konnen nicht nur einzelne Texte, sondern kann ein Grosteil von Anderschs Werk als Reiseliteratur gelesen werden.1 Nachgewiesen worden ist zudem, dass Andersch Landschaften oftmals in einer Art und Weise beschreibt, als seien sie Kunstwerke.2 Anstatt mich Anderschs asthetischen Darstellungsverfahren erneut zuzuwenden, untersuche ich im Folgenden, wie Anderschs Texte das Asthetische an sich thematisieren. Als Ausgangspunkt fungiert die Beobachtung, dass diese immer wieder asthetische Erlebnisse in den Mittelpunkt stellen. Hier soll daher danach gefragt werden, welche Funktion Anderschs Werke dem Asthetischen zuschreiben. Analysiert werden dabei die metaphysischen Topographien, in denen sich Erlebnisse ereignen, die eine vordiskursive und intuitive Erkenntnis insbesondere der Natur ermoglichen und damit einen Gegenstandsbereich betreffen, der aufgrund seiner Transzendierung des Sinnlichen traditionell der Metaphysik zugehorte. Metaphysische Topographien finden sich, wie gezeigt werden wird, sowohl in Anderschs Prosa als auch in seinem Horspielwerk, das von der Forschung bisher verhaltnismasig wenig beachtet worden ist. Es ist jedoch die Horspielasthetik der 1950er Jahre, die es erlaubt, die Funktion des Asthetischen in Anderschs Werk naher zu bestimmen. Ziel ist es dabei nicht, einen wie auch immer gearteten Einfluss des Horspielschaffens auf das ubrige Werk des Autors zu belegen. Vielmehr lasst sich im zeitgenossischen Horspieldiskurs ein Begriff des Asthetischen aufweisen, der es erlaubt, die zahlreichen metaphysischen Topographien in Anderschs Werk in ihrer Funktion genauer zu bestimmen. Schreibt die zeitgenossische Horspielasthetik dem Horspiel zu, ein »gleichnishafte[s] Erleben«3 zu ermoglichen, so fasst dieser Begriff zugleich das Asthetische, wie es in Anderschs Texten signifiziert und inszeniert wird.

This paper describes how to dimension the electric components of a 48V hybrid system considering real customer use. Furthermore, it provides information about savings in energy and CO2 emissions by a customer-tailored 48V hybrid. Based on measured customer profiles, the electric units such as the electric motor and the energy storage are dimensioned. Furthermore, the CO2 reduction potential in real customer use is determined compared to conventional vehicles. Finally, investigations are carried out to specify the topology design and preliminary considerations in order to hybridize a conventional vehicle with a 48V hybrid system. The emission model results from an empiric approach also taking into account the effects of engine dynamics on emissions. We analyzed transient engine emissions during representative customer driving profiles and created emission meta models. The investigation showed a significant difference in emissions when simulating realistic customer driving profiles using the created verified meta models compared to static approaches which are commonly used for vehicle simulation., {"references":["M. Nalbach, A. Körner, C. Hoff, \"Potential and Components of 48V\nLow Cost Hybrid Vehicles\", Intelligent Transport Systems, 10th\nSymposium Hybrid and Electric Vehicles, Braunschweig, 2013.","T. Dörsam, S. Kehl, A. Klinkig, A. Radon, O. Sirch, \"Die neue\nSpannungsebene 48V im Kraftfahrzeug\", in ATZelektronik, vol. 7, no.\n1, pp. 20-25, 2012.","R. Schmid, W. Hackmann, P. Birke, M. Schiemann, \"Design of a 48VBelt\ndriven Starter Generator-System drawing special system\nrequirements into account\", Intelligent Transport Systems, 10th\nSymposium Hybrid and Electric Vehicles, Braunschweig, 2013.","A.K. Jain, S. Mathapati, V.T. Ranganathan, V. Narayanan, \"Integrated\nStarter Generator for 42-V Powernet Using Induction Machine and\nDirect Torque Control Technique\", IEEE Transactions on Power\nElectronics, vol. 21, no. 3, pp. 701-710, 2006.","U.C. Blessing, J. Meissner, M. Schweiher, T. Hoffmeister, \"Scalable\nHybrid Dual-clutch Transmission\", in ATZ worldwide, vol. 116, no. 12,\npp. 4-9, 2014.","J. Mohrmann, \"Design of a 48V Micro Hybrid System\", master thesis,\nBraunschweig University of Technology, Institute of Automotive\nEngineering, 2014.","J. P. Müller-Kose, \"Representative Load Spectra for Vehicle\nGearboxes\", Shaker Verlag, Aachen, 2002."]}

Fibroblast growth factors (FGFs) orchestrate a variety of cellular functions by binding to their transmembrane tyrosine-kinase receptors (FGFR1-4) and activating downstream signaling pathways. FGF signaling has been demonstrated to be altered in a high proportion of cancers, with activating mutations and/or overexpression of FGFRs frequently observed in lung, gastric, breast and urothelial tumors. Therefore, targeting FGFRs using selective FGFR inhibitors is an attractive therapeutic approach to treat cancer patients. BAY 1163877 is as an orally available, selective and potent inhibitor of FGFR-1, -2 and -3 kinase activity. BAY 1163877 has been advanced through preclinical development and we disclose here the first details of its preclinical profile. BAY 1163877 inhibited FGFR-1, -2, -3 kinase activity in the nanomolar range and demonstrated a kinase selectivity profile for FGFR-1, -2 and -3 over 222 kinases tested. BAY 1163877 inhibited proliferation of various cancer cell lines in vitro and phosphorylation of downstream signaling molecules. BAY 1163877 was also tested in vivo in monotherapy and combination therapy on various human xenografts and syngeneic tumors and inhibited growth of tumors presenting at least one FGFR alteration.Overall, the in vitro and in vivo studies confirm that the FGFR inhibitor BAY 1163877 is a potent and selective inhibitor of altered FGFRs pathways in cancer models. A Phase 1 clinical trial (NCT01976741) has been initiated. Citation Format: Melanie Heroult, Peter Ellinghaus, Christian Sieg, Dirk Brohm, Sylvia Gruenewald, Marie-Pierre Collin, Ulf Boemer, Mario Lobell, Walter Huebsch, Matthias Ocker, Stuart Ince, Andrea Haegebarth, Rolf Jautelat, Holger Hess-Stumpp, Michael Brands, Karl Ziegelbauer. Preclinical profile of BAY 1163877 - a selective pan-FGFR inhibitor in phase 1 clinical trial. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1739. doi:10.1158/1538-7445.AM2014-1739