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Bencsik, Péter ; Kiss, Krisztina ; Ágg, Bence ; Baán, Júlia A. ; Agoston, Gergely ; Varga, Albert ; Gömöri, Kamilla ; Mendler, Luca ; Faragó, Nóra ; Zvara, Ágnes ; Sántha, Péter ; Puskás, László G. ; Jancsó, Gábor ; Ferdinandy, Peter
Background: Here we examined myocardial microRNA (miRNA) expression profile in a sensory neuropathy model with cardiac diastolic dysfunction and aimed to identify key mRNA molecular targets of the differentially expressed miRNAs that may contribute to cardiac dysfunction. Methods: Male Wistar rats were treated with vehicle or capsaicin for 3 days to induce systemic sensory neuropathy. Seven days later, diastolic dysfunction was detected by echocardiography, and miRNAs were isolated from the whole ventricles. Results: Out of 711 known miRNAs measured by miRNA microarray, the expression of 257 miRNAs was detected in the heart. As compared to vehicle-treated hearts, miR-344b, miR-466b, miR-98, let-7a, miR-1, miR-206, and miR-34b were downregulated, while miR-181a was upregulated as validated also by quantitative real time polymerase chain reaction (qRT-PCR). By an in silico network analysis, we identified common mRNA targets (insulin-like growth factor 1 (IGF-1), solute carrier family 2 facilitated glucose transporter member 12 (SLC2a-12), eukaryotic translation initiation factor 4e (EIF-4e), and Unc-51 like autophagy activating kinase 2 (ULK-2)) targeted by at least three altered miRNAs. Predicted upregulation of these mRNA targets were validated by qRT-PCR. Conclusion: This is the first demonstration that sensory neuropathy affects cardiac miRNA expression network targeting IGF-1, SLC2a-12, EIF-4e, and ULK-2, which may contribute to cardiac diastolic dysfunction. These results further support the need for unbiased omics approach followed by in silico prediction and validation of molecular targets to reveal novel pathomechanisms.
Die Übersetzung der Kashinawa-Mythen in Theodor Koch-Grünbergs "Indianermärchen aus Südamerika"
(2019)
Neben seinen ethnologischen und linguistischen Studien zu indigenen Kulturen der Amazonasregion beschäftigte sich der deutsche Brasilienforscher Theodor Koch-Grünberg auch mit indigenen Mythen und hatte klare Vorstellungen davon, wie diese mündlich überlieferten Erzählungen dokumentiert und übersetzt werden sollten. Modellcharakter hatte für ihn die interlineare Übersetzung des brasilianischen Historikers João Capistrano de Abreu von Texten aus dem Kashinawa, einer Panosprache, die noch heute im brasilianisch-peruanischen Grenzgebiet von Mitgliedern der ethnischen Gruppe gesprochen wird. Capistranos Textsammlung "Rã-txa hu-ni ku-ĩ" wurde 1914 in Brasilien veröffentlicht. Bereits 1920 erfolgte die Publikation der "Indianermärchen aus Südamerika" durch Koch-Grünberg, wobei von den 117 ins Deutsche übertragenen Geschichten 13 aus Capistranos Werk stammten. In diesem Beitrag soll anhand ausgewählter Textbeispiele die Übersetzung Koch-Grünbergs aus dem Kashinawa ins Deutsche diskutiert werden. Grundlage war dabei die transkribierte Textsammlung in Originalsprache mit einer Wort-für-Wort-Übersetzung ins Portugiesische sowie einem angehängten Glossar und einem Grammatiksketch. In Koch-Grünbergs eigenen Aufzeichnungen wird zusätzlich deutlich, dass es sich um einen multiplen Übersetzungsprozess handelt: von einem mündlich präsentierten narrativen Diskurs mit performativen Elementen in Schriftsprache, von einer indigenen Sprache Südamerikas in eine typologisch weit entfernte europäische und von einer vollkommen unbekannten Kultur in eine für den brasilianischen wie den deutschen Leser nachvollziehbare.
Este artigo visa a expor as principais questões envolvidas no processo de tradução do alemão para o português do Brasil do livro "Opium für Ovid: Ein Kopfkissenbuch von 22 Frauen" ("Ópio para Ovídio: um Livro do Travesseiro de 22 mulheres"), de Yoko Tawada. Com vistas ao exercício de traduzir, este trabalho deve ser entendido como um estudo preliminar sobre a escritora e seu livro "Ópio para Ovídio", escrito em uma língua estrangeira. Num contexto de constante migração e, ao mesmo tempo, de negação do Outro e de xenofobia, entende-se como necessária a busca por uma experiência de alteridade. Nesse sentido, este trabalho persegue o deslocamento do olhar para uma perspectiva e uma língua estrangeiras, de modo que o texto traduzido propicie uma experiência com o 'fremd'.
Bu makalenin amacı, Osmanlı Devleti'ne gerçekleştirilen gezilere ilişkin seyahatnamelerin Almancadan Türkçeye yapılmış olan çevirilerini Genette (2016)'in yanmetin kavramı bağlamında irdelemektir. Bu seyahatname çevirileri 1960–2017 yılları arasında yayınlanmıştır. Temel alınan bütünce 16 farklı seyahatnameye ait 34 çeviri sürümü içermektedir. Seyahatname, yanmetin ve çeviri ilişkisine değinildikten sonra sözü edilen seyahatname sürümlerinin yıllara göre dağılımı gösterilmiştir. Seyahatname çevirileri erek kültür dizgesinin bir parçası olduğundan, bu çeviri kitaplardaki iç metinler, erek okurların çeviri metni nasıl okumaları gerektiği ve kendilerini nelerin beklediği konusunda aracılık etmektedir. Böylelikle bu iç metinler, okurların olası ihtiyaçlarını karşılamak üzere ve erek kültürün koşullarına göre üretilmektedir. Örneklerle bu iç metinler aracılığıyla erek okurla nasıl bağ kurulduğu gösterilmiştir. Bu çalışmada ayrıca, belli başlı iç metin türlerinin niceliksel ve niteliksel incelemesiyle çeviri olgusu, çevirinin amacı, çevirmenin görünürlüğü/görünmezliği, yayınevlerinin çeviri politikası, çeviriyi etkileyen etmenler vb. konularda bilgiler sunmak amaçlanmıştır. Toplanan veriler, iç metinlerin bir yandan erek okurların olası ihtiyaçlarına göre şekillenebildiğini gösterirken diğer yandan erek kültür dizgesinin bazı ideolojik dinamiklerine hizmet edebildiğine işaret etmektedir.
A tradução parece trazer dificuldades que exigem soluções diversas que, escolhidas contigencialmente, podem ter implicações históricas e políticas duradouras. A tradução da Bíblia por Lutero é um exemplo marcante da força histórica da tradução e das polêmicas quanto à sua forma. Em "A Tarefa do Tradutor", Benjamin estabelece duas temporalidades distintas para a vida de um texto literário e a de suas traduções, instaurando um debate a respeito dos diferentes tempos históricos que atravessam um texto, em sua relação com as diferentes línguas. A partir dessas considerações, nos propomos a discutir certas dificuldades concretas experienciadas na tradução de citações de uma obra literária dentro de um texto crítico de Benjamin, "Am Kamin", um dos textos em que desenvolve sua teoria do romance. Como traduzir hoje as citações que Benjamin faz do romance "The old wives tale" de Arnold Bennet, citações da tradução para o alemão dos anos 1930, de um texto inglês de 1908 que emula um narrador do início do século XIX, e que não foi ainda traduzido para o português? Por fim, apresento o texto traduzido, "À Lareira".
Im Rahmen der vorliegenden Fallstudie zur Bewusstmachung der Lese- Verstehens- und Recherchekompetenz bei Studierenden des Fachbereichs Übersetzen und Dolmetschen wird der Vorschlag einer didaktischen Progression bei der Strukturalisierung des Unterrichts für literarische Übersetzung erarbeitet. Dies wird am Beispiel der türkischen Übersetzungen von Goethes Briefroman "Genç Werther'in Acıları" versucht darzustellen. Zu unterstreichen ist hier jedoch, dass die Unterrichtseinheit nicht, wie es nach übersetzungstheoretischem Ansatz zu verfolgen ist, mit der Analyse des Ausgangstextes "Die Leiden des jungen Werther" (Goethe, 1774) strukturiert ist. Diese Arbeit hat zum Ziel, den Versuch einer (in Anlehnung an die kognitions- und psychologisch wissenschaftlichen Erkenntnisse) didaktisch modellierten Vorgehensweise mehrerer aufeinanderfolgenden Unterrichtsphasen zu veranschaulichen. Der Fokus liegt jedoch hierbei auf dem Einstieg in die Unterrichtseinheit, wobei der Lese- und Verstehensprozess auf seinen Verlauf hin empirisch zu untersuchen gilt. Dazu wird die Datenerhebungsmethode angesetzt, die in der Kognitionspsychologie und der Übersetzungsprozessforschung fundiert. Die Datenauswertung erfolgt deskriptiv. Dieses Orientierungsmuster, welches zum Ziel hat, die Selbstsicherheit der Studierenden in Bezug zu unterschiedlichen Teilkompetenzen wie Lesen, Verstehen und Recherchieren, zu fördern, soll aus der Grundvorlage selbstkritischer Unterrichtserfahrung zur Durchführung des angegebenen Materials im Übersetzungsunterricht anregen.
Wie können musikalische Emotionen durch die literarische Beschreibung einer fiktiven Musik mobilisiert werden? Man kann vermuten, dass ein Text, der eine existierende Musik beschreibt, versucht, auch etwas über die Emotionen, die sie hervorruft, zu sagen. Wenn er jedoch durch seine eigenen verbalen Mittel Musik erfindet, die niemand je hören kann, dann müssen die mit ihr verknüpften Emotionen, als für den Autor essenziell betrachtet werden. Dies ist die Frage, die wir uns hier stellen, basierend auf einem Vergleich zwischen den imaginären Musikstücken von Vinteuil bei Marcel Proust und von Adrian Leverkühn bei Thomas Mann. In beiden Fällen wird die Musik als analoges Modell verwendet, das dem Autor erlaubt, die Emotionen, die sie mit einer besonderen Klarheit verkörpert, auch durch sie anzusprechen. So bietet die Musik in der proustschen Ästhetik, die immer noch von der romantisch musikalischen Metaphysik durchdrungen ist, eine intime Verbindung zum Gedächtnis. In einem völlig anderen Sinne macht die modernistische Ästhetik, die von Thomas Mann in seinem "Doktor Faustus" hervorgehoben wurde, aus der Musik das Mittel mit einer erschreckenden Auflösungskraft. Symbolik oder Diabolik, so oder so betrachtet, die Musik einigt oder löst, repariert oder trennt - aber in beiden Fällen verdichtet sie den Ausdruck von Lebenskräften.
Pascal Quignard belongs to those contemporary French writers whose work draws on music, while demonstrating ambivalent or even ambiguous feelings towards it. In this article, we explore the reasons, the challenges and the functions of what Quignard himself called the 'hatred of music' in an eponymous and landmark essay in which he reveals the secrets of his relationship to music, a relationship that intertwines his family history with the History of the Second World War.
This article explores the relations between affects and music in George Sand's novel "Adriani" (1853). It examines how the figuration of music highlights the importance of emotions, as they shift from aesthetic (admiration) to moral (compassion), in her protagonists' moral transformations. However, Sand's transposition of an imaginary musical world in the novel is part and parcel of a much more ambitious project, that of social transformations, notably of relations between the sexes. It is through their dialogue in and via music that her heroes discover each other and themselves, while their intimate trajectories enable the reader to imagine interpersonal relations among equals founded on emotional, intellectual and social reciprocity.
Through the example of Mozart, this article studies the role played by music in biographies of composers. By focusing on three different works, all targeting a wide audience, but coming from different centuries and cultures ("Leben des K. K. Kapellmeisters Wolfgang Gottlieb Mozart" by Franz Xaver Niemetschek, "Life of Mozart" by Edward Holmes, and "Mozart" by Jean-Victor Hocquard), it investigates both stylistic matters (how the music is described), and the concrete effect of cultural behaviors (the subordination of the work to the man, or the difficulty of talking about music). The study highlights some essential components of Mozartean mythology, as well as the close relationship between biographies, novels and the evolution of musicology as a discipline.
In poetry, music is often mentioned to express emotions, but it also brings poetry back to its source. Through poems by Eichendorff, Droste-Hülshoff, Baudelaire, Verlaine, Lorca, Rilke and Mandelstam, this article examines a deepening of the relationship between poetry, music and emotion, through which poetry discovers itself by being attentive to what is within itself of the order of the musical or the song.
This paper aims to demonstrate the hidden place of the surrealist poet, Paul Éluard, in Samuel Beckett's writing process. It will show that Beckett not only read and translated Paul Éluard, as is known, but also quoted him extensively. Moving from Beethoven to the short story "Lessness", the place of quotation as a trace of emotion will be examined.
If the poet's song is a 'topos' of Greek and Roman epic literature, the poet Silius Italicus renews it by describing the emotional reaction of his audience in depth and by placing it in a transitional moment of his narrative dedicated to the second Punic war. Tradition from antique historiography relates that Hannibal and his men became "soft" in Capua where feasting, pleasure, inebriation and indolence were common. Yet, Silius Italicus blames Teuthras' two songs for this weakening. This article examines Teuthras' second performance which hides beneath its soft melody a further meaning unintelligible to the audience who cannot escape their emotion. The aim is to reveal how poetical and musical emotion - 'admiratio' - and the weakening of the Carthaginians are structured in term of diegetic, and in the sub- and meta-discourse of Teuthras' second song.
Das Lernen von Fremdsprachen stellt einen komplizierten und langfristigen Prozess dar, der von zahlreichen (internen und externen) Faktoren, die in Wechselwirkung zueinander stehen und den Lernprozess individualisieren, beeinflusst wird. In diesem Zusammenhang befindet sich das Konstrukt Motivation schon mehrere Jahrzehnte im Fokus der angewandten Psycholinguistik. Motivation liefert einerseits den Anreiz zum Sprachenlernen, andererseits ist sie verantwortlich für das Durchhalten innerhalb eines kontinuierlich andauernden, mühsamen Fremdsprachenlernprozesses. Die Aktualität dieser Frage wird dadurch bestätigt, dass mehreren Studien zufolge der Motivationsverlust der Lernenden zu den Alltagsproblemen unseres Schulsystems gehört.
Da Freundschaften eine zentrale Rolle im Leben der Jugendlichen spielen und Schule nicht nur einen Bildungs-, sondern auch einen Erziehungsauftrag hat, ist es naheliegend, das Thema "Freundschaft" auch in den Deutschunterricht zu integrieren. [...] Die im schulischen Unterricht verwendeten Lehrwerke bieten zwar reichlich Material zum Thema "Freundschaft", der Einsatz von einem Spielfilm kann den Unterricht jedoch nicht nur medial bereichern, sondern auch die Schüler und Schülerinnen animieren, auf eine besondere Weise intensiv an ihren Sprachkompetenzen zu arbeiten und zugleich ihre interkulturellen und medialen Kompetenzen zu entwickeln.
Spielfilme stellen für die meisten Lernenden ein attraktives Medium dar, das ein großes Potenzial für sprachliches, interkulturelles, filmästhetisches sowie mediales Lernen besitzt. In der Fremdsprachendidaktik wurden exakte Kriterien für die Filmauswahl sowie vielfältige Methoden zum produktiven Umgang mit Film-werken entwickelt. Trotzdem werden Spielfilme im schulischen Fremdsprachenunterricht relativ selten eingesetzt und noch seltener evaluiert. Das Ziel des vor-liegenden Beitrags ist deshalb, neben einer theoretischen Auseinandersetzung mit der Filmdidaktik, Evaluationsergebnisse eines schulischen Filmprojekts anzwei PASCH-Schulen und zwei deutschen bilingualen Gymnasien in der Slowakei zu präsentieren. Mittels didaktischer Tests wurden Effekte der Filmarbeit auf die Wortschatzerweiterung, den Ausbau des kulturspezifischen Hintergrundwissens sowie den Einfluss auf die "Filmlesefähigkeit" erhoben. Überdies wurden mit je-der Schülergruppe Interviews zu subjektiven Lernerfahrungen durchgeführt. Die Testergebnisse weisen auf positive Effekte hin, die durch die qualitativen Daten noch differenzierter betrachtet werden können.
Baur, Florentin ; Nietzer, Sarah ; Kunz, Meik ; Saal, Fabian ; Jeromin, Julian ; Matschos, Stephanie ; Linnebacher, Michael ; Walles, Heike ; Dandekar, Thomas ; Dandekar, Gudrun
To improve and focus preclinical testing, we combine tumor models based on a decellularized tissue matrix with bioinformatics to stratify tumors according to stage-specific mutations that are linked to central cancer pathways. We generated tissue models with BRAF-mutant colorectal cancer (CRC) cells (HROC24 and HROC87) and compared treatment responses to two-dimensional (2D) cultures and xenografts. As the BRAF inhibitor vemurafenib is—in contrast to melanoma—not effective in CRC, we combined it with the EGFR inhibitor gefitinib. In general, our 3D models showed higher chemoresistance and in contrast to 2D a more active HGFR after gefitinib and combination-therapy. In xenograft models murine HGF could not activate the human HGFR, stressing the importance of the human microenvironment. In order to stratify patient groups for targeted treatment options in CRC, an in silico topology with different stages including mutations and changes in common signaling pathways was developed. We applied the established topology for in silico simulations to predict new therapeutic options for BRAF-mutated CRC patients in advanced stages. Our in silico tool connects genome information with a deeper understanding of tumor engines in clinically relevant signaling networks which goes beyond the consideration of single drivers to improve CRC patient stratification.
Bock, Freia de ; Bosle, Catherin ; Farwick, Christine ; Oepen, Johannes ; Philippi, Heike ; Urschitz, Michael Siegfried
Background: While ICF-CY-based models of care are promising avenues for improving participation of children with chronic health conditions, feasible and valid instruments to assess participation as an outcome in routine are still needed. We aimed to validate a German parent-report version of the Child and Adolescent Scale of Participation (CASP) in children with chronic health conditions of different severity.
Methods: Cross-sectional data were collected in 327 children (mean age 7.8 years, 55% boys) from two paediatric centres (n = 112) and one population-based sample (n = 215). Cronbach’s alpha, factor analyses, face validity assessments, correlation analyses, receiver operating characteristics (ROC) curves, and parent-reported health-related quality of life (HRQoL: KINDL) were used to examine internal consistency, test-retest reliability, and capacity to differentiate between disease severity groups. Disease severity was operationalized according to ICD-diagnosis groups and/or parent-reports on health problems, medical and educational support, and medication. A newly developed item "overall perceived participation" was added to the CASP and evaluated.
Results: We found good to excellent content validity, excellent internal consistency, and good-to-excellent test-retest reliability of the instrument. While children with mild disease had a significantly greater extent of participation (higher CASP scores) than children with severe disease, they did not differ from healthy children. Children with mild compared to severe disease much more differed in participation as measured by the CASP compared to the KINDL (area under the ROC curve: 0.92 vs. 0.75). In addition, the item "overall perceived participation" was highly correlated (r = 0.86) with the CASP total score, indicating the potential value of this specific single item. Finally, we provided preliminary reference values for the CASP obtained in a population-based sample of children without chronic health conditions.
Conclusions: The German version of the CASP and the new item are efficient, valid and reliable measures of social participation in childhood. The CASP-measured participation focuses more on attendance than on involvement into social circumstances of everyday life. To detect children with a high burden of disease on everyday life, the CASP may be more accurate than HRQoL instruments such as the KINDL. As outcome measurement, the CASP may facilitate the implementation of patient-centred paediatric health care.
Der Motivkomplex "Tiere und Tod" gehört zu den Kardinalthemen mit komparatistisch-kulturwissenschaftlichen, phänomenologischen und ethischen Dimensionen. Tiere sterben, auch wenn ihnen von Philosophen wie Heidegger nur ein 'Verenden' zugebilligt wird, weil sie angeblich kein Bewusstsein von Sterben und Tod besitzen. Sie sind entweder die Beute von anderen Tieren (Prädatoren, Carnivoren) oder aber Opfer von Unfällen, Krankheiten oder Altersschwäche. Die Geschichte des Tier-Mensch-Verhältnisses indes ist weniger geprägt "vom natürlichen Tod von Tieren, sondern vor allem vom gewaltsamen Tod." Menschen töten Tiere mit Absicht: Jagd, Opferrituale, Stier- und Hahnenkampf, Tierversuche, Pelztierzucht, Massentötung bei Seuchen, Sadismus, Euthanasie; oder aber eher unbeabsichtigt durch den menschlichen Lebensstil: Krieg, unsachgemäße Tiertransporte, Deprivation von Tieren in Zoo und Zirkus, Massentierhaltung/Käfighaltung, Überfütterung/Mästung. Die massenhafte Tötung jedoch, der als alltäglich und zwangsläufig hingenommene Tod von Tieren, geschieht in Form von Schlachtung durch den 'homo necans'.
Bu çalışmada Almanya'ya işçi olarak giden ilk Türk neslin torunları olan üçüncü ve dördüncü kuşak gençlerin Alman toplumunda yaşadıkları sosyo-kültürel ve psikolojik sorunları saptanmaya çalışılacaktır. Araştırma nesnesi olarak "kurmaca" dalında 2007 Adolf Grimme ödülünü alarak Türk-Alman sinemasında önemli bir başarıya imza atmış bulunan yönetmen Züli Aladağ'ın 2006 yılında çektiği, Almanya'daki Türk gençliğini konu alan "Öfke" adlı filmi incelenecektir. Almanya'da çok kültürlü ortamda yetişen gençlerin, toplumda egemen kültür dışında kendi aralarında oluşturdukları dia-kültür ve bu alt kültürleri oluşturmaya iten sorunlar film çerçevesinde nitel yöntemle gözlemlenecektir. Almanya'daki Türk gençliğin dâhil olduğu dia-kültürleri bağlamında yapılan incelemede gençlerin toplandıkları mekânlar, kullandıkları dil ve ifade biçimleri, dinledikleri müzikler, giyim tarzları ve takıları esas alınacaktır. Belirlenen sorunlar incelenirken nesiller arası çatışmaya, aile içi ilişkilere, iki kültür arasında bocalama ve yaşanan bunalımlara, toplumdan uzaklaşarak özgür olma düşüncelerine ve buna bağlı paradoksal durumlarına, suç ve uyuşturucuya olan eğilimlerine neden-sonuç ilişkisi bağlamında filmden alıntılar yapılarak örnekler verilecektir. İncelemede filmin çekildiği 2006 yılından günümüze kadar yaşanan süreçteki sorunlar ve günümüze yansımaları karşılaştırılarak buna yönelik çözüm yolları önerilecektir.
Personen, die a priori keine Gemeinsamkeiten erkennen lassen, nicht die gleiche Muttersprache haben und sich auch sonst zumindest nicht über eine Sprache verständlich machen können, würden wohl kaum Zeit miteinander verbringen. Was geschieht jedoch, wenn Menschen durch gewisse Umstände dazu gezwungen werden? Drei Filme thematisieren eine durch Krisensituationen hervorgerufene interkulturelle Begegnung und entwickeln divergente Konfliktpotentiale und Lösungsansätze: der 1996 erschienene tschechische Film "Kolya", der 1999 veröffentlichte deutsche Film "Nachtgestalten" und der 2011 ausgestrahlte deutsche Film "Dreiviertelmond". Letzterer soll im Fokus stehen und die deutsch-türkische Verständigung verdeutlichen. Zum einen soll die Filmanalyse bestimmte Motive der interkulturellen Begegnung herausarbeiten und den Umgang mit Fremd und Eigen, Nähe und Distanz erörtern, des Weiteren soll versucht werden, die Filme aus aktueller Perspektive zu besprechen und Antworten darauf zu finden, wie eine Verständigung zwischen den Kulturen, zwischen den Generationen möglich ist. Auffällig ist außerdem, dass die Filme aktuelle Thematiken besprechen, die interessante Debatten anstoßen könnten. Es ließe sich zum Beispiel danach fragen, wie die Kluft zwischen den Generationen, die Unverständlichkeit der Interessen zwischen Jung und Alt, zwischen Menschen, die an ihrem Geburtsort leben und Personen, die aus anderen Ländern zuziehen, verhandelt werden. Ist eine Verständigung trotz festgefahrener Vorstellungen und Wertungen des 'Anderen' überhaupt möglich? Können angelernte und indoktrinierte Urteile und Bilder des 'Anderen' aufgebrochen werden?
Die von Wolfgang Ludwig hinterlassene Pflanzensammlung im Marburger Herbar wurde aufbereitet und dokumentiert. Vorgestellt werden Belege aus der in über 70 Jahren (1938–2010) entstandenen Sammlung, die für die hessische Flora bislang nicht bekannt waren sowie Belege zu inzwischen ausgestorbenen, sehr seltenen oder sonstigen bemerkenswerten Arten.
Im Rahmen der Kartierung der Gefäßpflanzenflora des Vor-, Hochund kammnahen Hintertaunus wurde im Jahre 2004 ein großer Bestand des für Deutschland bislang selten erwähnten Doronicum ×willdenowii entdeckt. Da sich die Art bis heute nicht nur gehalten, sondern vermehrt hat, besteht offensichtlich ein Trend zur lokalen Einbürgerung.
Buchbesprechungen
(2019)
Es werden folgende Publikation rezensiert: Daniel Barthélémy (Hrsg.): Pl@ntNet; Bunzel-Drüke et al.: Naturnahe Beweidung und Natura 2000; Martina D'Ascola: 50 sagenhafte Naturdenkmale in Hessen; Hessisches Landesamt für Naturschutz, Umwelt und Geologie: Guter Heinrich, Pfingst-Nelke, Färber-Scharte & Co. Hessische Verantwortungsarten – Teil 1.
Teufel, Ulrike ; Burgard, Peter ; Meyburg, Jochen ; Lindner, Martin ; Pöschl, Johannes ; Ruef, Peter ; Hoffmann, Georg Friedrich ; Kölker, Stefan
Background: Neonatal manifestation of life-threatening hyperammonemic encephalopathy in urea cycle disorders (UCD) is often misdiagnosed as neonatal sepsis, resulting in significantly delayed start of specific treatment and poor outcome. The major aim of this study was to identify specific initial symptoms or signs to clinically distinguish hyperammonemic encephalopathy in neonates from neonatal sepsis in order to identify affected individuals with UCD and to start metabolic therapy without delay. Furthermore, we evaluated the impact of diagnostic delay, peak plasma ammonium (NH4+) concentration, mode of emergency treatment and transfer to a tertiary referral center on the outcome.
Methods: Detailed information of 17 patients (born between 1994 and 2012) with confirmed diagnosis of UCD and neonatal hyperammonemic encephalopathy were collected from the original medical records.
Results: The initially suspected diagnosis was neonatal sepsis in all patients, but was not confirmed in any of them. Unlike neonatal sepsis and not previously reported blood pressure increased above the 95th percentile in 13 (81%) of UCD patients before emergency treatment was started. Respiratory alkalosis was found in 11 (65%) of UCD patients, and in 14 (81%) plasma NH4+concentrations further increased despite initiation of metabolic therapy.
Conclusion: Detection of high blood pressure could be a valuable parameter for distinguishing neonatal sepsis from neonatal manifestation of UCD. Since high blood pressure is not typical for neonatal sepsis, other reasons such as encephalopathy and especially hyperammonemic encephalopathy (caused by e.g. UCD) should be searched for immediately. However, our result that the majority of newborns with UCD initially present with high blood pressure has to be evaluated in larger patient cohorts.
Das Naturschutzgebiet Kühkopf-Knoblochsaue mit 2 400 ha überflutbarer Aue eignet sich in dem potenziellen Wildreben-Verbreitungsgebiet in Deutschland (Oberrheingebiet zwischen Freiburg und Wiesbaden) aktuell bei weitem am besten zum Wiederaufbau überlebensfähiger, ausreichend heterozygoter Wildrebenbestände. Nach einer ersten Wiederansiedlung 2013 mit 65 Genotypen und 121 ausgebrachten wurzelnackten Pflanzen mit Draht-Verbissschutz wurden 2016 in einer zweiten Wiederansiedlungsmaßnahme 551 Wilde Weinreben (78 Genotypen) an 12 Standorten gepflanzt. Es handelte sich hierbei um zweijährige Topfpflanzen, die ohne Verbissschutz gepflanzt wurden. Ein Jahr nach der Pflanzung war eine durchschnittliche Überlebensrate von 69 % zu konstatieren. Die Überlebensraten variieren an den Standorten zwischen 55 und 87 %. 75 von Wildschweinen herausgewühlte Wilde Weinreben wurden wieder eingepflanzt; die Überlebensrate kann somit noch über 69 % steigen.
Nach einer Eigenzeit des Ästhetischen zu fragen, heißt, sich auf das Problem einzulassen, was für eine Zeit und welche Zeiterfahrung in der Eigenzeit eines Kunstwerks eine besondere Geltung beanspruchen. Die Möglichkeit, dieser Frage nachzugehen, setzt voraus, dass die in der ästhetischen Form verankerten und im Kunstwerk auf Erfahrung drängenden Spannungen einer künstlerischen Eigenzeit auf jeweils begründbare Weise so verstanden werden können, dass sie sich von anderen Formen der Zeit und Zeiterfahrung in bedeutsamer Hinsicht unterscheiden. Ist diese begriffliche Voraussetzung grundsätzlich erfüllt, dann kann von der ästhetischen Eigenzeit als einer Praxis der Zeitgestaltung ausgegangen werden, die bestimmte Modelle und Konstellationen des Zeitlichen auf eine der Kunst eigenen Weise dem Bereich des prinzipiell Erfahrbaren und auf idiomatisch-bestimmte Weise Erkennbaren einschreibt.
Seit Kants Metaphysikkritik, Engels dogmatischer Gegenüberstellung von Dialektik und Metaphysik und Carnaps radikaler Programmatik, Metaphysik "durch logische Analyse der Sprache" zu überwinden, hat der Begriff einen pejorativen Beigeschmack angenommen. Andererseits haben sich unterschiedliche Ansätze zu einer anti- oder nachmetaphysischen Metaphysik entwickelt. Nicht nur im konzeptuellen Rahmen der Kritischen Theorie ist gefragt worden, ob "im Augenblick ihres Sturzes" nicht Solidarität "mit Metaphysik" an der Zeit wäre. Sogar auf dem Terrain der analytischen Philosophie regt sich wieder Interesse an ontologischen Problemen, dem Kernbereich der Metaphysik. Ganz unverächtlich ist heute wieder von einem metaphysischen Bedürfnis, von metaphysischer Unruhe und metaphysischen Gefühlen die Rede; und auch das philosophische Feuilleton nimmt sich metaphysischer Sinnansprüche an. So veranstaltete das "Journal für Philosophie" der "Blaue Reiter" 2009 ein Themenheft "Metaphysik. Wirklichkeiten hinter der Wirklichkeit": Die Beiträge behandelten Gegenstände wie "Marke und Metaphysik. Die Scheinwirklichkeit der Warenwelt", "Die Metaphysik des Geldes", "Viel Lärm um nichts. Im Dschungel der Erklärungsversuche des Unerklärlichen", "Virtuelle Wirklichkeiten. Cyberphilosophie und andere Gespenstergeschichten" oder "Die Metaphysik des Schwebens. Philosophie, Ontologie, Metaphysik. Die Geschichte einer Verirrung". Ist die Metaphysik also wieder im Rennen? Angesichts dieser ein wenig verworrenen Problem- und Diskussionslage, in der es um Sinnansprüche und Orientierungen der Einzelnen geht, meldet sich auch das Bedürfnis nach kritischer Vergewisserung. Hierzu soll der folgende Aufsatz einen Beitrag leisten, der das Verhältnis der Kritischen Theorie zur Metaphysik, verstanden als prinzipiengeleiteter philosophischer Wissensform mit theologischen Residuen, beleuchtet.
Digitales Publizieren umfasst eine Vielfalt von Praktiken, die vom Tweet über den wissenschaftlichen Artikel in einer Online-Zeitschrift bis zum Bloggen reicht. Die online technisch vereinfachte Selbstpublikation hat zur Folge, dass die Strukturierung der wissenschaftlichen Landschaft von anderen medialen Voraussetzungen ausgeht, als es in der Printwelt der Fall ist, in der Qualitätskontrolle zwangsläufig vor der Publikation kommt.
In disem Beitrag möchte ich argumentieren, dass die Germanistik diese neuen medialen Bedingungen nicht als Verlust über die Qualitätskontrolle bzw. als Bedrohung wahrnehmen muss und dass im Gegenteil konkrete Vorschläge angebracht sind, damit die Fachgemeinschaft sich diese medialen Voraussetzungen aneignet und sie für sich fruchtbar macht. Die folgenden Überlegungen basieren auf einer Betrachtung der Publikation an sich, die sich nicht in Selbstpublikation einerseits und evaluierter Publikation andererseits gliedert, sondern die öffentliche Verbereitung von Informationen im digitalen Kontextals Grundlage nimmt. Der erste Teil befasst sich mit digitalen Publikationen und deren Bedeutung für die Germanistik, der zweite Teil mit der Philosophie von Open Access und deren möglicher Umsetzung.
Je mehr Ressourcen in zentralen "virtuellen" Orten zusammengefasst werden, desto mehr stellt sich die Frage nach der Rolle der lokalen Bibliothek und der dort angesiedelten germanistischen Fachreferentinnen und Fachreferenten. Karolin Bubke zeigt in ihrem Beitrag am Beispiel einer mittelgroßen Universitätsbibliothek, wie zum einen die Erwartungen einer mit "Google und Co." aufgewachsenen Studierendengeneration, zum anderen aber auch digitalisierte Rechercheinstrumente wie Online-Fachbibliographien und "Discovery Systeme" den Bedarf an Unterstützung und Beratung vor Ort bei der Literaturrecherche eher erhöhen als vermindern. Deutlich wird aber auch, dass die Anschaffungspolitik lokaler Bibliotheken angesichts der Lizenzierungsmodelle für digitale Literatur vor erheblichen Herausforderungen steht.
Spätestens seit jener Entwicklung, die man heute als "Web 2.0" bezeichnet, verfließen die Grenzen zwischen Publizieren und partizipativem Interagieren im Netz. In unterschiedlicher Weise verstehen sich Blogs und Microblogging-Dienste als Medien der Wissenschaftskommunikation nach außen, als Werkzeuge interaktiver wissenschaftlicher Forschung oder als Möglichkeit der wissenschaftsinternen Vernetzung. Gemeinsam ist diesen verschiedenen Spielarten, dass sie in der traditionellen Anerkennungskultur des Faches bzw. der Geistes- und Kulturwissenschaften allgemein nach wie vor einen ungeklärten oder prekären Staus haben, so dass sich für die Akteure die Frage nach dem symbolischen "Ertrag" des investierten Aufwands stellt. Alexander Lasch problematisiert in seinem einführenden Beitrag zu Blogs in der Wissenschaft insbesondere, dass sich aktive Wissenschaftsblogger häufig einem "Prokrastinationsverdacht" aussetzen; in den auf Prestigeerwerb angelegten wissenschaftlichen Qualifikationswegen kann das Bloggen also sogar negativ wirksam werden.
Im Jahr 2008 wurden im Hochtaunus zwei Vorkommen der für diesen Bereich in der Literatur bisher nicht erwähnten Süßdolde (Myrrhis odorata) entdeckt. Beide haben sich bis heute (2017) in dicht geschlossenen, einmal im Jahr gemähten Pflanzenbeständen gehalten. Die Art besitzt also offensichtlich das Potential zur Einbürgerung, wobei man angesichts der relativ geringen Bestandesgröße noch nicht von einem gesicherten Trend zur Einbürgerung sprechen darf. Beide Pflanzenbestände sind saumartig ausgebildet, wobei der Aspekt auch von typischen Saumarten bestimmt wird. Der für Saumgesellschaften auffallend hohe Anteil an Wiesenarten dürfte darauf zurückzuführen sein, dass beide Säume einmal im Jahr gemäht werden.
In this paper we deal with an implementation as well as numerical experiments for the coupling of interior and exterior problems of the elastodynamic wave equation with transparent boundary conditions in 3D as described in a previous paper by this author. In more detail, the FEM‐BEM‐coupling as well as the time discretization by using leapfrog and convolution quadrature is considered. Our aim is to provide an insight into the necessary steps of the implementation. Based on this, we present numerical experiments for a non‐convex domain and analyze the errors.
Neste artigo, trazemos algumas reflexões a respeito da influência exercida por línguas anteriormente aprendidas no processo de aprendizagem de alemão como L3 por aprendizes brasileiros. Essas influências podem operar tanto por meio de transferências linguísticas intencionais, controladas pelos próprios aprendizes, quanto por transferências não intencionais. Dependendo do referencial teórico adotado, essas transferências intencionais são consideradas estratégias de aprendizagem e/ou de comunicação. Com base em uma pesquisa empírica realizada em 2017 e em alguns debates na área acadêmica em torno do assunto (OXFORD 1990, 2011; BIMMEL e RAMPILLON 2000; SELINKER 1972, 2014; HUFEISEN 2010), este artigo tem como objetivo analisar as estratégias utilizadas por aprendizes de alemão como L3 em um chat online e refletir sobre as influências interlinguais exercidas sobre os aprendizes de forma não intencional. Os resultados obtidos apontam para contrastes (1) quanto ao tipo de estratégias utilizadas por aprendizes em diferentes níveis de aprendizagem e (2) quanto à língua da qual decorreram as influências não intencionais: aprendizes mais proficientes utilizaram estratégias que mobilizaram mais elementos da língua-alvo, como os circunlóquios, e não sofreram nenhuma influência exclusivamente da língua materna (apenas da L1 e da L2 concomitantemente ou apenas da L2), ao contrário de aprendizes menos proficientes.
Samuel Becketts Fernsehspiele zeigen den Autor in ein neues künstlerisches Medium involviert. Die fünf für das Fernsehen konzipierten Stücke ("He, Joe", "Geister-Trio", "... nur noch Gewölk", "Quadrat I+II", "Nacht und Träume") und noch zwei Bearbeitungen von Theaterstücken ("Nicht Ich", "Was Wo") sind kein isoliertes Ereignis im Kontext seines Schaffens, wie man dies von den Hörspielen der 1950er Jahre behaupten könnte. Von "He, Joe" (1965) an bis zu "Was Wo" (1985) hat Beckett sich zwanzig Jahre lang mit dem Fernsehen beschäftigt. Das zwingt uns zu fragen, worin das Spezifische dieses Medium liegt, das dem Werk Becketts besonders entgegenkommt. Adorno hat einmal beobachtet, dass dessen Theaterstücke "dem Medium besonders angemessen sind", was ein Hinweis auf deren künstlerische Reduktion war. Neben dieser Affinität zwischen einer ästhetischen Tendenz seines Werkes zur Reduktion und den technischen Eigenschaften des neuen Mediums gilt es ebenfalls, die Möglichkeit einer noch stärkeren Kontrolle der verschiedenen Produktionsstufen zu berücksichtigen, die Beckett seit seinen frühesten theatralischen Arbeiten suchte. [...] Kontrolle und Reduktion kennzeichnen die späte Phase der Beckett-Produktion, ab Mitte der 1960er Jahre. In diesem Kontext setzen die Fernsehspiele künstlerische Probleme und Verfahren fort, die Beckett in der Prosa, auf der Bühne und im Rundfunk thematisiert hatte; andererseits spürt man die Annäherung an das neue Medium bei der Behandlung von beispielsweise Bildern und Stimmen im späten Theater oder in der späten Prosa. Gilles Deleuze sieht sie als Höhepunkt einer Evolution: sie seien fortgeschrittener als die Theaterstücke oder die Prosa. Dieser Beitrag wiederum beabsichtigt zu zeigen, dass man Becketts Spätwerk vielmehr als eine simultane Entwicklung der unterschiedlichen künstlerischen Mittel begreifen kann, ohne dass aus diesem Grund ein Verdacht auf formale Hybridität aufkommen muss.
After studying the way in which various modern interpretations (political, psychoanalytic, traumatological) of Homer analyze the emotions aroused and/or conveyed by the song of the sirens, we will look at the "self-reflexive" interpretation that Maurice Blanchot ("Le Livre à venir", 1959) proposes of "Odyssey's" "Song XII". We will see that this interpretation can provide an excellent reading grid for modern rewritings of the episode, which overinvest one of the emotional aspects of the sirens' song - that is, the emotion of the language that goes out of itself in order to become music (in Joyce - "Ulysses", 1918-1920) or silence (in Kafka - "Das Schweigen der Sirenen", 1917).
Die Verbindung von Musik und Emotionen in der Geschichte unserer westlichen Kultur ist kongenial und George Sand würde dieser Tatsache sicherlich voll zustimmen. Dennoch sind die Modalitäten dieser Verbindung sehr unterschiedlich und Sand selbst, die sowohl eine große Bewunderin Rousseaus als auch eine Tochter der Romantik ist, hat unterschiedliche Vorstellungen davon verinnerlicht. In ihrem Roman "Consuelo" gefällt sie sich darin, diese in ihren Figuren dargestellt zu versammeln. Nachahmende und didaktische Musik, wie sie Albert prägt, oder erhabene Musik als Ausdruck des Unendlichen, wie diejenige Consuelos: In diesem Artikel soll gezeigt werden, wie es der Hauptfigur des Romans gelingt, diese beiden Musikansätze zu einem Ganzen zu vereinen und eine Kunst zu praktizieren, die sowohl bewegt wie überzeugt, eine kosmopolitische Kunst, die gleichzeitig Ausdruck des kollektiven Gedächtnisses einer leidgeprüften Menschheit als auch Balsam für ihre Seele ist.
Franz Liszt war ein Freund Fryderyk Chopins. Er wurde auch zu seinem ersten Biografen. In 'Chopin' (1852) spricht Liszt natürlich auch von sich selbst und seiner eigenen Musikkonzeption, die für ihn die Möglichkeit eines Austausches, wenn nicht gar einer "Kommunion" zwischen den Menschen darstellt. Chopins Musik besitzt für Liszt auch die Fähigkeit, Menschen ausserhalb physischer Grenzen zu transportieren. Liszt betrachtet die Musik von Chopin nicht nur als eine Emanation seiner Heimat: in Chopins Polonaisen und Mazurkas sieht er Tänze, die ihre Verführungskraft aus den Beziehungen Polens mit dem Osmanischen Reich schöpfen (auch wenn diese vom historischen Standpunkt aus betrachtet konfliktbeladen waren). Im letzten Teil beschäftigt sich dieser Beitrag mit der Sprache der Emotionen. Liszt gelingt es durch sein ausserordentliches Wortschatzraffinement, die Wirkung von Chopins Musik auf die Hörenden zu charakterisieren. Diese Musik beraube sie ihrer selbst.
Au sein de la grande famille des arts, la musique et la littérature ont toujours eu une relation privilégiée, et lorsqu'au XVIIIe siècle, la réflexion sur la relation entre les arts devient un champ d'étude à part entière, elle ne se fait pas faute de la mettre en évidence: arts possédant une origine commune (Rousseau); arts liés au temps alors que les autres arts se déploient dans l'espace (Lessing); arts qui entretiennent une relation de complémentarité esthétique et qui, par ailleurs, ont longtemps été inséparables l'un de l'autre.
Stendhal hat sich immer geweigert, was er "le bête de la musique" (Das Dumme der Musik) nennt, zu studieren, und meinte die technischen Aspekte. Hingegen war er äußerst sensibel für die Schönheit der Opern, insbesondere diejenigen von Mozart, Cimarosa und Rossini. Die musikalische Emotion, die er empfindet, ist ein komplexes Phänomen, dass es zu analysieren gilt, indem mehrere Ebenen unterschieden werden, auch wenn sie sich häufig überschneiden. Musikalische Emotionen können mit den Anfängen der Liebesleidenschaft oder mit deren Erinnerung verbunden sein (siehe 'Lucien Leuwen'), sie kann auch ein Zeichen der Übereinstimmung zwischen zwei Wesen sein. Aber musikalische Emotionen sind manchmal auch auf die Musik allein zurückzuführen, die selbst keinen externen Referenten hat. Die wesentliche Frage für den Schriftsteller bleibt: Wie kann man die musikalische Emotion durch den Text wiedergeben? Diese Schwierigkeit ist bei einer rein musikalisch ausgelösten Emotion größer. Wir werden sehen, wie Stendhal die Schwierigkeit umgeht oder sie löst.
Schmiedl, Sven ; Peters, David ; Schmalz, Oliver ; Mielke, Anke ; Rossmanith, Tanja ; Diop, Shirin ; Piefke, Martina ; Thürmann, Petra ; Schmidtko, Achim
Neuropathic pain is a debilitating and commonly treatment-refractory condition requiring novel therapeutic options. Accumulating preclinical studies indicate that the potassium channel Slack (KNa1.1) contributes to the processing of neuropathic pain, and that Slack activators, when injected into mice, ameliorate pain-related hypersensitivity. However, whether Slack activation might reduce neuropathic pain in humans remains elusive. Here, we evaluated the tolerability and analgesic efficacy of loxapine, a first-generation antipsychotic drug and Slack activator, in neuropathic pain patients. We aimed to treat 12 patients with chronic chemotherapy-induced, treatment-refractory neuropathic pain (pain severity ≥ 4 units on an 11-point numerical rating scale) in a monocentric, open label, proof-of-principle study. Patients received loxapine orally as add-on analgesic in a dose-escalating manner (four treatment episodes for 14 days, daily dose: 20, 30, 40, or 60 mg loxapine) depending on tolerability and analgesic efficacy. Patient-reported outcomes of pain intensity and/or relief were recorded daily. After enrolling four patients, this study was prematurely terminated due to adverse events typically occurring with first-generation antipsychotic drugs that were reported by all patients. In two patients receiving loxapine for at least two treatment episodes, a clinically relevant analgesic effect was found at a daily dose of 20–30 mg of loxapine. Another two patients tolerated loxapine only for a few days. Together, our data further support the hypothesis that Slack activation might be a novel strategy for neuropathic pain therapy. However, loxapine is no valid treatment option for painful polyneuropathy due to profound dopamine and histamine receptor-related side effects.
Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02820519.
Wozu sind Akademiker*innen auf Twitter? Im Unterschied zu Blogs, deren Funktion für die Wissenschaftskommunikation unstrittig ist, werden Aktivitäten auf Twitter und in anderen sozialen Medien immer noch vielfach skeptisch gesehen. Wissenschaft in 280 Zeichen? Abschreckend wirkt neben dem Verdacht extremer und letztendlich unsinniger Komplexitätsreduktion eine pauschale Kritik am Twittern. Zu den Topoi dieses Diskurses, der so verbreitet ist, dass man fast von einem eigenen journalistischen Genre sprechen könnte, gehört die Vorstellung, dass man sich auf Twitter in einem abgeschlossenen Kommunikationsraum, einer ›Bubble‹ oder ›Gemeinde‹, befinde. Diese Pauschalkritik wird, ebenso wie die weniger häufige positive Berichterstattung, auf Twitter intensiv diskutiert. Am häufigsten finden sich zwei Hinweise: erstens, dass es eben nicht die eine Twittererfahrung gibt, sondern individuelle Formen der Präsenz und der Interaktion; zweitens, dass sowohl die Idee der ›Bubble‹ als auch der ›zwei Welten‹, von Twitter auf der einen und ›realem Austausch‹ auf der anderen Seite, nicht erfasst, wie Kommunikation auf Twitter funktioniert und von Wissenschaftler*innen produktiv genutzt wird. Wer verstehen will, dass Twitter für Akademiker*innen attraktiv sein kann, sollte sich bewusst machen, dass Twitter viel Verschiedenes bietet.
Insgesamt ist die mediävistische Germanistik, speziell die Literaturwissenschaft, trotz ›digital turn‹ in der deutschsprachigen Blogosphäre unterrepräsentiert. Linguist*innen sind bei der Gestaltung von Blogs, die nicht an eine Institution angebunden sind, viel aktiver.
Während solche Plattformen und sozialen Medien von Linguist*innen und Historiker*innen häufig zur Fachkommunikation und darüber hinaus genutzt werden, ist für die mediävistische Germanistik eine große Berührungsscheu zu
diagnostizieren. Als Gründe dafür sind eine traditionelle Veröffentlichungsstruktur, Angst vor Prestigeverlust oder Fremdeln mit den Digital Humanities an sich denkbar. Es stellt sich auch die Frage, welchen Wert das Bloggen für die
eigene Publikationsliste haben kann, wenn z.B. ein halb-privat initiiertes Word-Press-Blog keine Qualitätskontrolle der Beiträge außer der die Beiträge verfassenden Person(en) selbst aufweist. Insgesamt ist die Ältere deutsche Literatur
also in diesem ›Limbo‹ so gut wie nicht vertreten. Das interdisziplinäre 'Mittelalterblog' bietet mediävistischen Germanist*innen eine Möglichkeit, diese Bedenken zu reevaluieren. Im Folgenden sollen daher die Entstehung des Projektes, seine Publikationsformate und auch der Bezug zur
Älteren deutschen Literatur- und Sprachwissenschaft beschrieben werden.
The representation of music in literature is often conceived in terms of a 'paragone', a debate over which of the arts ranks highest. In this context, literature is commonly spoken of as imitative or emulative of the music it is trying to represent. This premise informs even the most recent terminologies of literary scholars describing the intermedial relationship of music and literature systematically. Using the narratological concepts of 'showing vs. telling' to describe musical representation in literature, as proposed by the "Handbuch Literatur & Musik", this article argues that such a view is based on a misleading assumption about literary imitation and leads to constrained possibilities of hermeneutical interpretation. After a systematic reconstruction of the proposed terminology and a proposal for its modification, an exemplary analysis of Helmut Krausser's novel "Melodien" ["Melodies", 1993] will serve to demonstrate how a refined conception of the terminology can help to bring about more precise interpretations.
Wissenschaftsnahes Publizieren im digitalen Zeitalter : oder: Machen wir es doch einfach selber!
(2019)
Warum publizieren wir Wissenschaftlerinnen und Wissenschaftler unsere Arbeitsergebnisse nicht einfach selber für jeden frei zugänglich im Netz, zum Beispiel auf der Internetseite unseres Instituts oder in einem zentralen Online-Fachrepositorium (wie z.B. GiNDok des Fachinformationsdienstes Germanistik)? Die Digitalisierung macht's möglich, denn sie befreit den Publikationsvorgang von einer Fessel, in die ihn die Erfindung Gutenbergs - der Buchdruck mit beweglichen Lettern - dereinst gelegt hatte: Jahrhundertelang benötigte jeder, der einen Text veröffentlichen wollte, einen Verleger, der ihm den relativ teuren Publikationsvorgang vorfinanzierte und sich den Kapitaleinsatz dann durch einen erheblichen Anteil am Verkaufserlös der gedruckten Exemplare plus saftiger Gewinne wieder zurückholte. Nun aber kosten Reproduktion und Verbreitung so gut wie nichts mehr, Webspace steht in Hülle und Fülle zur Verfügung.
Klein, Ariane ; Becker, Ingrid ; Minden, Kirsten ; Hospach, Anton ; Schwarz, Tobias ; Foeldvari, Ivan ; Hügle, Boris ; Borte, Michael ; Weller-Heinemann, Frank ; Dressler, Frank ; Kümmerle-Deschner, Jasmin ; Oommen, Prasad Thomas ; Föll, Dirk ; Trauzeddel, Ralf ; Rietschel, Christoph ; Horneff, Gerd
Objective: Biologics have an important role in the treatment of juvenile idiopathic arthritis (JIA). Long‐term safety data are limited. Direct comparison of different agents regarding occurrence of adverse events (AEs), especially of rare events, requires large quantities of patient years. In this analysis, long‐term safety with regard to AE of special interest (AESI) was compared between different biologics.
Methods: Patients with nonsystemic JIA were selected from the German BIKER registry. Safety assessments were based on AE reports. Number of AEs, serious AEs, and 25 predefined AESIs, including medically important infection, uveitis, inflammatory bowel disease, cytopenia, hepatic events, anaphylaxis, depression, pregnancy, malignancy, and death, were analyzed. Event rates and relative risks were calculated using AEs reported after first dose through 70 days after last dose.
Results: A total of 3873 patients entered the analysis with 7467 years of exposure to biologics. The most common AESIs were uveitis (n = 231) and medically important infections (n = 101). Cytopenia and elevation of transaminases were more frequent with tocilizumab (risk ratio [RR] 8.0, 95% confidence interval [CI] 4.2‐15, and RR 4.7, 95% CI 1.8‐12.2, respectively). Anaphylactic events were associated with intravenous route of administration. In patients ever exposed to biologics, eight malignancies were reported. Six pregnancies have been documented in patients with tumor necrosis factor inhibitors. No death occurred in this patient cohort during observation.
Conclusion: Surveillance of pharmacotherapy as provided by the BIKER registry is an import approach, especially for long‐term treatment of children. Overall, tolerance was acceptable. Differences between biologics were noted and should be considered in daily patient care.
The quest for new and improved therapies for glioblastoma (GB) has been mostly unsuccessful in more than a decade despite significant efforts. The few exceptions include the optimization of classical alkylating chemotherapy by including lomustine in the first line regimen for GB with a methylated MGMT promoter and tumor treating fields. The GB signaling network has been well-characterized and genetic alterations resulting in activation of receptor tyrosine kinases and especially epidermal growth factor receptor (EGFR) and downstream mammalian target of rapamycin complex 1 (mTORC1) signaling were found in the majority of GBs. ...
Heinzen, Dennis ; Divé, Iris ; Lorenz, Nadja Irene ; Luger, Anna-Luisa ; Steinbach, Joachim Peter ; Ronellenfitsch, Michael Wilfried
Glioblastomas (GBs) frequently display activation of the epidermal growth factor receptor (EGFR) and mammalian target of rapamycin (mTOR). mTOR exists as part of two multiprotein complexes, mTOR complex 1 (mTORC1) and 2 (mTORC2). In GBs, mTORC1 inhibitors such as rapamycin have performed poorly in clinical trials, and in vitro protect GB cells from nutrient and oxygen deprivation. Next generation ATP-competitive mTOR inhibitors with affinity for both mTOR complexes have been developed, but data exploring their effects on GB metabolism are scarce. In this study, we compared the ATP-competitive mTORC1/2 inhibitors torin2, INK-128 and NVP-Bez235 to the allosteric mTORC1 inhibitor rapamycin under conditions that mimic the glioma microenvironment. In addition to inhibiting mTORC2 signaling, INK-128 and NVP-Bez235 more effectively blocked mTORC1 signaling and prompted a stronger cell growth inhibition, partly by inducing cell cycle arrest. However, under hypoxic and nutrient-poor conditions mTORC1/2 inhibitors displayed even stronger cytoprotective effects than rapamycin by reducing oxygen and glucose consumption. Thus, therapies that arrest proliferation and inhibit anabolic metabolism must be expected to improve energy homeostasis of tumor cells. These results mandate caution when treating physiologically or therapeutically induced hypoxic GBs with mTOR inhibitors.
Olpidiopsis is a genus of obligate holocarpic endobiotic oomycetes. Most of the species classified in the genus are known only from their morphology and life cycle, and a few have been examined for their ultrastructure or molecular phylogeny. However, the taxonomic placement of all sequenced species is provisional, as no sequence data are available for the type species, O. saprolegniae, to consolidate the taxonomy of species currently placed in the genus. Thus, efforts were undertaken to isolate O. saprolegniae from its type host, Saprolegnia parasitica and to infer its phylogenetic placement based on 18S rDNA sequences. As most species of Olpidiopsis for which sequence data are available are from rhodophyte hosts, we have also isolated the type species of the rhodophyte-parasitic genus Pontisma, P. lagenidioides and obtained partial 18S rDNA sequences. Phylogenetic reconstructions in the current study revealed that O. saprolegniae from Saprolegnia parasitica forms a monophyletic group with a morphologically similar isolate from S. ferax, and a morphologically and phylogenetically more divergent species from S. terrestris. However, they were widely separated from a monophyletic, yet unsupported clade containing P. lagenidioides and red algal parasites previously classified in Olpidiopsis. Consequently, all holocarpic parasites in red algae should be considered to be members of the genus Pontisma as previously suggested by some researchers. In addition, a new species of Olpidiopsis, O. parthenogenetica is introduced to accommodate the pathogen of S. terrestris.
Holocarpic oomycetes are poorly known but widespread parasites in freshwater and marine ecosystems. Most of the holocarpic species seem to belong to clades that diverge before the two crown lineages of the oomycetes, the Saprolegniomycetes and the Peronosporomycetes. Recently, the genus Miracula was described to accommodate Miracula helgolandica, a holocarpic parasitoid of Pseudo-nitzschia diatoms, which received varying support for its placement as the earliest-diverging oomycete lineage. In the same phylogenetic reconstruction, Miracula helgolandica was grouped with some somewhat divergent sequences derived from environmental sequencing, indicating that Miracula would not remain monotypic. Here, a second species of Miracula is reported, which was found as a parasitoid in the limnic centric diatom Pleurosira leavis. Its life-cycle stages are described and depicted in this study and its phylogenetic placement in the genus Miracula revealed. As a consequence, the newly discovered species is introduced as Miracula moenusica.
Diatoms are thought to provide about 40% of total global photosynthesis and diatoms of the genus Coscinodiscus are an important, sometimes dominant, cosmopolitan component of the marine diatom community. The oomycete parasitoid Lagenisma coscinodisci is widespread in the northern hemisphere on its hosts in the genus Coscinodiscus. Because of its potential ecological importance, it would be a suitable pathogen model to investigate plankton/parasite interactions, but the species cannot be cultivated on media without its host, so far. Thus, it was the aim of this study to explore the potential of dual culture of host and pathogen in the laboratory and to optimise cultivation to ensure a long-term cultivation of the pathogen. Here, we report successful cultivation of a single spore strain of L. coscinodisci (Isla), on several Coscinodiscus species and strains, as well as the establishment of a cultivation routine with Coscinodiscus granii (CGS1 and CG36), which enabled us to maintain the single spore strain for more than 3 years in 6 cm Petri dishes and 10 ml tissue culture flasks. This opens up the opportunity to study the processes and mechanism in plankton/parasitoid interactions under controlled conditions.
Wali, Vikram B. ; Patwardhan, Gauri A. ; Pelekanou, Vasiliki ; Karn, Thomas ; Cao, Jian ; Ocana, Alberto ; Yan, Qin ; Nelson, Bryce ; Hatzis, Christos ; Pusztai, Lajos
The goal of this study was to identify a novel target for antibody-drug conjugate (ADC) development in triple negative breast cancer (TNBC), which has limited treatment options, using gene expression datasets and in vitro siRNA/CRISPR and in vivo functional assays. We analyzed 4467 breast cancers and identified GABRP as top expressed gene in TNBC with low expression in most normal tissues. GABRP protein was localized to cell membrane with broad range of receptors/cell (815–53,714) and expressed by nearly half of breast cancers tissues. GABRP gene knockdown inhibited TNBC cell growth and colony formation in vitro and growth of MDA-MB-468 xenografts in nude mice. Commercially available anti-GABRP antibody (5–100 μg/ml) or de novo generated Fabs (20 μg/ml) inhibited TNBC cell growth in vitro. The same antibody conjugated to mertansine (DM1) also showed significant anticancer activity at nanomolar concentrations. Our results indicate that GABRP is a potential novel therapeutic target for ADC development.
Edebiyatın sayısız kavramları ve motifleri vardır. Edebiyatı edebiyat kılan da bir bakıma bu temaların, motiflerin ilkin edebi eserlerde görünmesi ve sonra da bunların yeniden ele alınmasıdır. Aşk, ihanet, kardeş katli ve öç alma gibi bir yığın insanlık durumu tarih boyunca edebiyatın teması haline gelmiştir ve gelmeye de devam edecektir. Adem'in cennetten kovulmasından milenyuma kadar eve dönüş motifi de sadece edebiyatın değil, felsefenin, sosyolojinin ve sosyal bilimlerin sıklıkla işlediği temalardan biridir. Hele de Homeros'un "Odysseus" ve Almanların anonim "Nibelungen" destanlarında bu motif bir laytmotiftir. Hatta "Odesa" ismi daha sonraları eve dönüşleri imleyen genel bir kavram haline dönüşmüştür. Bu çalışmada Nibelungen ve Odysseus destanlarında ortak olan eve dönüş miti ele alınmıştır. Kahramanların dünyevi dert nedeniyle, bazen yıllarca süren vatan için kaçınılmaz savaşlardan; bazen ise gönül ilişkilerinde, kendilerine bir yaren, bir eş arama derdinden uzun yolculuklara çıkılır ve sonra da eve dönüşün zorlu yolları bir destansı geri dönüş izleğine dönüşür. Çalışmamızda eve dönüş teması eşliğinde sadece bu destanları ele almadık, eve dönüşün farklı farklı hallerini, bugüne dek edebiyattaki görünümlerini de işledik.
Jung‐König, Mona ; Füllenbach, Christoph ; Murphy, Michael F. ; Manzini, Paola ; Laspina, Stefan ; Pendry, Kate ; Mühling, Jörg ; Wikman, Agneta ; Humbrecht, Catherine ; Rigal, Jean‐Christophe ; Lasocki, Sigismond ; Folléa, Gilles ; Seifried, Erhard ; Müller, Markus M. ; Geisen, Christof ; Aranko, Kari ; Zacharowski, Kai ; Meybohm, Patrick
Background and objectives: Preoperative anaemia is an independent risk factor for a higher morbidity and mortality, a longer hospitalization and increased perioperative transfusion rates. Managing preoperative anaemia is the first of three pillars of Patient Blood Management (PBM), a multidisciplinary concept to improve patient safety. While various studies provide medical information on (successful) anaemia treatment pathways, knowledge of organizational details of diagnosis and management of preoperative anaemia across Europe is scarce.
Materials and methods: To gain information on various aspects of preoperative anaemia management including organization, financing, diagnostics and treatment, we conducted a survey (74 questions) in ten hospitals from seven European nations within the PaBloE (Patient Blood Management in Europe) working group covering the year 2016.
Results: Organization and activity in the field of preoperative anaemia management were heterogeneous in the participating hospitals. Almost all hospitals had pathways for managing preoperative anaemia in place, however, only two nations had national guidelines. In six of the ten participating hospitals, preoperative anaemia management was organized by anaesthetists. Diagnostics and treatment focused on iron deficiency anaemia which, in most hospitals, was corrected with intravenous iron.
Conclusion: Implementation and approaches of preoperative anaemia management vary across Europe with a primary focus on treating iron deficiency anaemia. Findings of this survey motivated the hospitals involved to critically evaluate their practice and may also help other hospitals interested in PBM to develop action plans for diagnosis and management of preoperative anaemia.
Ruesink, Harm ; Reimer, Lasse ; Gregersen, Emil ; Möller, Arne ; Betzer, Cristine ; Jensen, Poul Henning
The group of neurodegenerative diseases, Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA) all exhibit inclusions containing amyloid-type α-synuclein (α-syn) aggregates within degenerating brain cells. α-syn also exists as soluble oligomeric species that are hypothesized to represent intermediates between its native and aggregated states. These oligomers are present in brain extracts from patients suffering from synucleinopathies and hold great potential as biomarkers. Although easily prepared in vitro, oligomers are metastable and dissociate over time, thereby complicating α-syn oligomer research. Using the small amine-reactive cross-linker, formaldehyde (FA), we successfully stabilized α-syn oligomers without affecting their size, overall structure or antigenicity towards aggregate-conformation specific α-syn antibodies FILA and MJFR-14-6-4-2. Further, cross-linked α-syn oligomers show resistance towards denaturant like urea and SDS treatment and remain fully functional as internal standard in an aggregation-specific enzyme-linked immunosorbent assay (ELISA) despite prior incubation with urea. We propose that FA cross-linked α-syn oligomers could serve as important calibrators to facilitate comparative and standardized α-syn biomarker studies going forward.
L’arrêt Lüth – 50 ans après
(2019)
Même 50 ans plus tard, l’arrêt Lüth, rendu par la Cour constitutionnelle fédérale le 15 janvier 1958, n’a rien perdu de son actualité. Il confère durablement à la liberté d’expression un rang primordial pour le débat public démocratique et marque le point de départ du développement d’une dogmatique des droits fondamentaux spécifiquement allemande, à l’origine d’un renforcement des compétences et de la puissance particulières de la Cour constitutionnelle fédérale. Les raisons qui expliquent l’approche particulière de résolution de conflits entre droits suivie dans l’arrêt Lüth ne laissent pas présager un abandon de cette jurisprudence, abandon qui ne serait d’ailleurs ni souhaitable ni réaliste.
The purpose of history education in Austria has changed over at least the last decade. While the focus used to be to give students a master narrative of the national past based on positivist knowledge, the current objective of history education is to foster historical thinking processes that enable students to form transferable skills in the self-reflected handling and creation of history. A key factor in fostering historical thinking is the appropriation of learning tasks. This case study measures the complexity of learning tasks in Austrian history textbooks as one important aspect of their quality. It makes use of three different approaches to complexity to triangulate the notion: general task complexity (GTC), general linguistic complexity (GLC), and domain-specific task complexity (DTC). The question is which findings can be offered by the specific strengths and limitations of the different methodological approaches to give new insights into the study of task complexity in the domain of history education research. By pursuing multidisciplinary approaches in a triangulating way, the case study opens up new prospects for this field. Besides offering new insights on measuring the complexity of learning tasks, the study illustrates the need for further research in this field – not only related to the development of analytical frameworks, but also regarding the notion of complexity in the context of historical learning itself.
This special edition of HERJ (number 16.1) sprang from an international symposium in Salzburg, Austria on 11 and 12 May 2017, called Triangulation in History Education Research (H-Soz-Kult, 2019). It includes 12 articles on mixed-methods research and triangulation in history education research from seven different countries: Australia, Austria, Germany, the Netherlands, Portugal, Switzerland and the United Kingdom.
Faul sein. Den Sonntag gemütlich auf der Couch verbringen. Die To-Do-Liste zur Seite legen. Mal keinem getakteten Tagesablauf folgen. Die Zeit einfach vorbeiziehen lassen. Zur Ruhe kommen und nichts tun geht häufig mit einem negativen Gefühl einher. Von Vorwürfen der Unproduktivität bis hin zu rassistischen Ressentiments, die mit dem Nichtstun verknüpft werden: Faulheit gehört zu den Dingen, die in der kapitalistischen Gesellschaft keinerlei Wertschätzung erfahren. Neu ist die negative Konnotation des Begriffs allerdings nicht. Bereits im vierten Jahrhundert verpönt die christliche Theologie die "Trägheit" als eine der sieben Todsünden. Die abschätzige Bewertung überdauerte den christlichen Glauben, wurde sozusagen profanisiert und ist heute – in Zeiten von Überstunden, Zweit- oder auch gleich Drittjobs und ständiger Verfügbarkeit – ein No-Go. ...
Der Maler und Grafiker Georg Heck (1897-1982) führte ein bewegtes Leben: Seinen unbändigen Schaffensdrang konnten weder zwei Weltkriege noch der Verlust seines rechten Augenlichtes schmälern. Das Museum Giersch der Goethe-Universität präsentiert das Œuvre des Frankfurter Künstlers zwischen "Entartung" und Sezession in einer umfangreichen Retrospektive.
Die Koexistenz von Mensch und Tier und ihre wechselseitigen Beziehungen kristallisieren sich mit besonderer Prägnanz heraus, wenn es um die Darstellung der sogenannten 'companion animals' ('Gefährtentiere') des Menschen, der Haustierspezies wie zum Beispiel Katzen und Hunde, geht. Den Versuch, die Besonderheit dieser Beziehungen und ihre vielfältigen Bedeutungsebenen auszuloten, haben zahlreiche Autoren in unterschiedlichen Epochen unternommen. Eine Gesamtdarstellung literarischer 'companion animals' im globalen Kontext würde den Rahmen eines einzelnen Aufsatzes unweigerlich sprengen. Es ist vielmehr Ziel des folgenden Beitrags, die besondere Relation zwischen Mensch und Katze innerhalb der neueren japanischen Kultur zu beleuchten, wie sie sich in einigen beliebten Erzählungen des 20. und 21. Jahrhunderts beispielhaft manifestiert, die auch im internationalen Raum großen Anklang gefunden haben.
Fährt man in den Urlaub, weiß man eigentlich schon vorab, dass man als Reisende ob der eigenen Unwissenheit mehr bezahlt als die ortskundigen Locals. Man weiß, dass die meisten europäischen Urlaubsorte vom Tourismus leben und drückt im Stillen sein Einverständnis damit aus, indem man überhaupt reist. Gelegentlich aber zahlt man nicht nur etwas mehr, sondern wird beim Rückweg zum Flughafen von einem Taxifahrer, der kein Englisch spricht oder auch nur so tut, um die halbe Insel gefahren, obwohl man vom Beifahrersitz in sein Handy schaut und einem Google Maps einen wesentlich kürzeren Weg angezeigt hat. Man könnte sich aufregen, mit Hand und Fuß mit dem Taxifahrer schimpfen, die Türen des Wagens zuknallen und so dem eigenen Unmut Ausdruck verschaffen. Man kann aber auch ruhig bleiben, dem Taxifahrer thank you for showing us the whole island zurufen, zurückfliegen und eine Ausstellung organisieren, wie Cemile Deniz Alibas, Dominika Bednarsky, Un-Zu Ha-Nul Lee und Lena Stewens es getan haben. ...
Wer im mittelalterlichen Frankfurt von "Hibbdebach" nach "Dribbdebach" wollte, also von Sachsenhausen in die Innenstadt, der war auf die Alte Brücke angewiesen – denn eine andere Möglichkeit den Main zu überqueren gab es bis 1868 nicht. Die Verbindung der Mainufer war bereits seit dem 11. Jahrhundert ein wichtiges Wegkreuz zwischen Nord und Süd und trug wohl dazu bei, dass sich Frankfurt nicht nur zum Krönungsort von Königen und Kaisern entwickelte, sondern auch zur Messestadt; es ist also keinesfalls übertrieben die Alte Brücke Ausgangspunkt der Frankfurter Stadtentwicklung zu nennen. ...
Das Museum Giersch scheint manchmal weit ab vom Schuss, gerät es doch im Schatten der großen Frankfurter Galerien ein ums andere Mal in Vergessenheit. Umso wichtiger ist es, diesem Umstand entgegenzuwirken – denn derzeit präsentiert das Ausstellungshaus am Museumsufer mit der Schau Frobenius – Die Kunst des Forschens ein Stück Frankfurts kultureller Identität. Konträr zum vielbesuchten Städel, erwartet das villenartige Museum den Besucher mit gedimmtem Licht und warmem Holz: Eine ruhige Stimmung breitet sich aus, die nicht nur der Konzentration beim Lesen der ausführlichen Erklärtexte, sondern der Wirkung von mehr als 200 gezeigten Werken zuträglich ist. ...
Im Rahmen der Slowakischen Wissenschaftswoche fand an der Selye J. Universität in Komárno der zweite Jahrgang der internationalen Tagung Komorner Germanistentag am Institut für Deutsche Sprache und Literatur statt. Die Serie dieser Tagung ist für den Lehrstuhl von zweifacher Bedeutung. Einerseits ist es ein Versuch, die Tradition einer internationalen Tagung, die vor etwa zehn Jahren in der Abteilung für moderne Philologie an der Selye J. Universität von Csaba Földes, dem Begründer dieser Abteilung, veranstaltet wurde, wieder ins Leben zu rufen. Andererseits wollte man mit der Konferenz die Gelegenheit ergreifen, das vor zwei Jahren selbstständig gewordene Institut für deutsche Sprache und Literatur vorzustellen. [...] Die Teilnehmer präsentierten ihre Projekte und Forschungsergebnisse in drei thematischen Gruppen, und zwar in Linguistik, Literaturwissenschaft und Sprachdidaktik.
Seit dem 28. Juni 2019 ist in der hessischen Landeshauptstadt eine der größten privaten Jugendstil-Sammlungen Europas in einer Dauerausstellung zu sehen. Mit seiner großzügigen Schenkung hat der Kunstsammler Ferdinand Wolfgang Neess bereits vor zwei Jahren 570 Werke seiner in einem halben Jahrhundert zusammengetragenen Sammlung von Inkunabeln des internationalen Jugendstils dem Landesmuseum Wiesbaden vermacht. Seitdem wurde an der Präsentation dieser einmaligen Objekte im Südflügel des Museums gearbeitet, die nun seit knapp zwei Monaten der Öffentlichkeit zugänglich sind. ...
Lexik und Diskurse rechtspopulistischer Wahlwerbung - Plakate der AfD aus den Jahren 2016 bis 2018
(2019)
Der vorliegende Beitrag widmet sich der politolinguistischen Analyse der Wahlplakate der Alternative für Deutschland (AfD). Zunächst wird das zugrunde gelegte Korpus von Plakaten aus den Jahren 2016 bis 2018 erläutert. Die hierin versammelten Plakate werden dann im Hinblick auf die Lexik statistisch aus-gewertet. Dabei werden als vorherrschende Diskurse Bedrohung, Heimat und Familie identifiziert. Mit Beispielen kann gezeigt werden, dass diese Diskurse in der AfD-Wahlwerbung eng miteinander verknüpft sind. Insbesondere wird dort eine Bedrohung von Heimat und Familie konstruiert und zugleich die Thematik der Migration negativ und als eine wesentliche Ursache dieser Bedrohung dargestellt. Auf diese Weise gelingt es der AfD, thematisch zu polarisieren und zugleich bei den Rezipienten der Plakate, den Wählern, eine Handlungsnotwendigkeit im Sinne einer entsprechenden Stimmabgabe zu erzeugen.
Der Leitfaden "Kein Asylantenheim in meiner Nachbarschaft" als Argumentationsmuster der Neonazis
(2019)
Bei dem im November 2015 online veröffentlichten Leitfaden "Kein Asylantenheim in meiner Nachbarschaft", handelt es sich um eine offizielle Publikation der politischen Partei "Der III. Weg". "Der III. Weg" ist eine Neonazi-Partei, die 2013 durch ehemalige Anhänger der rechtsextremistischen Organisation "Freies Netz Süd" gegründet wurde. Die Partei vertritt eine rechtsextremistische, fremdenfeindliche Einstellung, die sich im auf der offiziellen Webseite der Partei veröffentlichten Zehn-Punkte-Programm ausdrücklich zeigt. Der Leitfaden gehört zum öffentlich-politischen Diskurs der Partei und erfüllt eine appellative Textfunktion, für die die argumentative Themenentfaltung charakteristisch ist. Im vorliegenden Beitrag wird der Leitfaden als ein Argumentationsmuster der Neonazis angesehen, in dem sich vor allem die argumentative Themenentfaltung erkennen lässt.
Plank, Harald ; Winkler, Robert ; Schwalb, Christian H. ; Hütner, Johanna ; Fowlkes, Jason D. ; Rack, Philip D. ; Utke, Ivo ; Huth, Michael
Scanning probe microscopy (SPM) has become an essential surface characterization technique in research and development. By concept, SPM performance crucially depends on the quality of the nano-probe element, in particular, the apex radius. Now, with the development of advanced SPM modes beyond morphology mapping, new challenges have emerged regarding the design, morphology, function, and reliability of nano-probes. To tackle these challenges, versatile fabrication methods for precise nano-fabrication are needed. Aside from well-established technologies for SPM nano-probe fabrication, focused electron beam-induced deposition (FEBID) has become increasingly relevant in recent years, with the demonstration of controlled 3D nanoscale deposition and tailored deposit chemistry. Moreover, FEBID is compatible with practically any given surface morphology. In this review article, we introduce the technology, with a focus on the most relevant demands (shapes, feature size, materials and functionalities, substrate demands, and scalability), discuss the opportunities and challenges, and rationalize how those can be useful for advanced SPM applications. As will be shown, FEBID is an ideal tool for fabrication/modification and rapid prototyping of SPM-tipswith the potential to scale up industrially relevant manufacturing.
Focused electron and ion beam-induced deposition (FEBID/FIBID) are direct-write techniques with particular advantages in three-dimensional (3D) fabrication of ferromagnetic or superconducting nanostructures. Recently, two novel precursors, HCo 3 Fe(CO) 12 and Nb(NMe 3 ) 2 (N-t-Bu), were introduced, resulting in fully metallic CoFe ferromagnetic alloys by FEBID and superconducting NbC by FIBID, respectively. In order to properly define the writing strategy for the fabrication of 3D structures using these precursors, their temperature-dependent average residence time on the substrate and growing deposit needs to be known. This is a prerequisite for employing the simulation-guided 3D computer aided design (CAD) approach to FEBID/FIBID, which was introduced recently. We fabricated a series of rectangular-shaped deposits by FEBID at different substrate temperatures between 5 ∘ C and 24 ∘ C using the precursors and extracted the activation energy for precursor desorption and the pre-exponential factor from the measured heights of the deposits using the continuum growth model of FEBID based on the reaction-diffusion equation for the adsorbed precursor.
Knowledge about the herbaceous layer in relation to environmental factors in West African savannas is still scarce. Early life-cycle events like germination of the herbaceous species are of special interest, as these stages can play critical roles in establishing of the plants and determine population and community dynamics. We aim to assess intraspecific differences in the germinability of herbaceous savanna species with respect to environmental conditions to reveal adaptations in this early life cycle stage. The study was conducted in the Sudanian savanna of Burkina Faso in West Africa. We collected seeds of two annual herbs (Chamaecrista mimosoides, Spermacoce stachydea) along a climatic gradient from different habitats and land use types and conducted germination experiments under equal conditions in climate chambers. For both species several environmental factors showed a significant impact on the germination rates. While higher precipitation caused an increase in the germination rate only for S. stachydea, habitat conditions had a significant influence for both species. Intermediate habitats with balanced soil moisture caused an enhancement of the germination success. Moreover shrub cover had a positive effect on the germinability of C. mimosoides, whereas the germinability of S. stachydea decreased due to an increasing herbaceous cover. The study showed that certain environmental factors are able to modify the intraspecific variability of the germinability trait, which might affect the establishment of the species populations.
Cavagna, Lorenzo ; Trallero-Araguás, Ernesto ; Meloni, Federica ; Cavazzana, Ilaria ; Rojas-Serrano, Jorge ; Feist, Eugen ; Zanframundo, Giovanni ; Morandi, Valentina ; Meyer, Alain ; Silva, José António Pereira da ; Matos Costa, Carlo Jorge ; Molberg, Oyvind ; Andersson, Helena ; Codullo, Veronica ; Mosca, Marta ; Barsotti, Simone ; Neri, Rossella ; Scirè, Carlo Alberto ; Govoni, Marcello ; Furini, Federica ; López-Longo, Francisco Javier ; Martínez-Barrio, Julia ; Schneider, Udo ; Lorenz, Hanns-Martin ; Doria, Andrea ; Ghirardello, Anna ; Ortego-Centeno, Norberto ; Confalonieri, Marco ; Tomietto, Paola ; Pipitone, Nicolò ; Rodriguez Cambron, Ana Belen ; Blázquez Cañamero, María Ángeles ; Voll, Reinhard ; Wendel, Sarah ; Scarpato, Salvatore ; Maurier, Francois ; Limonta, Massimiliano ; Colombelli, Paolo ; Giannini, Margherita ; Geny, Bernard ; Arrigoni, Eugenio ; Bravi, Elena ; Migliorini, Paola ; Mathieu, Alessandro ; Piga, Matteo ; Drott, Ulrich ; Delbrück, Christiane ; Bauhammer, Jutta ; Cagnotto, Giovanni ; Vancheri, Carlo ; Sambataro, Gianluca ; De Langhe, Ellen ; Sainaghi, Pier Paolo ; Monti, Cristina ; Berzolari, Francesca Gigli ; Romano, Mariaeva ; Bonella, Francesco ; Specker, Christof ; Schwarting, Andreas ; Villa Blanco, Ignacio ; Selmi, Carlo ; Ceribelli, Angela ; Nuno, Laura ; Mera-Varela, Antonio ; Gomez, Nair Perez ; Fusaro, Enrico ; Parisi, Simone ; Sinigaglia, Luigi ; Del Papa, Nicoletta ; Benucci, Maurizio ; Cimmino, Marco Amedeo ; Riccieri, Valeria ; Conti, Fabrizio ; Sebastiani, Gian Domenico ; Iuliano, Annamaria ; Emmi, Giacomo ; Cammelli, Daniele ; Sebastiani, Marco ; Manfredi, Andreina ; Bachiller Corral, Javier ; Sifuentes Giraldo, Walter Alberto ; Paolazzi, Giuseppe ; Saketkoo, Lesley Ann ; Giorgi, Roberto ; Salaffi, Fausto ; Cifrian, Jose ; Caporali, Roberto ; Locatelli, Francesco ; Marchioni, Enrico ; Pesci, Alberto ; Dei, Giulia ; Pozzi, Maria Rosa ; Claudia, Lomater ; Distler, Jörg Hans Wilhelm ; Knitza, Johannes ; Schett, George ; Iannone, Florenzo ; Fornaro, Marco ; Franceschini, Franco ; Quartuccio, Luca ; Gerli, Roberto ; Bartoloni, Elena ; Bellando-Randone, Silvia ; Zampogna, Giuseppe ; Gonzalez Perez, Montserrat I. ; Mejia, Mayra ; Vicente, Esther ; Triantafyllias, Konstantinos ; López-Mejias, Raquel ; Matucci-Cerinic, Marco ; Selva-O’Callaghan, Albert ; Castañeda, Santos ; Montecucco, Carlomaurizio ; González-Gay, Miguel Ángel
Antisynthetase syndrome (ASSD) is a rare clinical condition that is characterized by the occurrence of a classic clinical triad, encompassing myositis, arthritis, and interstitial lung disease (ILD), along with specific autoantibodies that are addressed to different aminoacyl tRNA synthetases (ARS). Until now, it has been unknown whether the presence of a different ARS might affect the clinical presentation, evolution, and outcome of ASSD. In this study, we retrospectively recorded the time of onset, characteristics, clustering of triad findings, and survival of 828 ASSD patients (593 anti-Jo1, 95 anti-PL7, 84 anti-PL12, 38 anti-EJ, and 18 anti-OJ), referring to AENEAS (American and European NEtwork of Antisynthetase Syndrome) collaborative group’s cohort. Comparisons were performed first between all ARS cases and then, in the case of significance, while using anti-Jo1 positive patients as the reference group. The characteristics of triad findings were similar and the onset mainly began with a single triad finding in all groups despite some differences in overall prevalence. The “ex-novo” occurrence of triad findings was only reduced in the anti-PL12-positive cohort, however, it occurred in a clinically relevant percentage of patients (30%). Moreover, survival was not influenced by the underlying anti-aminoacyl tRNA synthetase antibodies’ positivity, which confirmed that antisynthetase syndrome is a heterogeneous condition and that antibody specificity only partially influences the clinical presentation and evolution of this condition.
Die nachfolgende Untersuchung hat nicht nur Sabine Schos Farben-Band zum Gegenstand, sondern will Werke acht weiterer deutschsprachiger Autorinnen und Autoren auf den Gebrauch von Farbworten in den Gedichten hin analysieren. Voraussetzung für die Aufnahme in das Korpus war - bis auf Sabine Scho -, dass mindesten drei Gedichtbände vorliegen müssen, damit eine mögliche Entwicklung oder Veränderung deutlich werden kann. Beachtet werden nur Werke, die nach 2000 erschienen sind oder Autoren, deren Publikationstätigkeit erst kurz vor oder nach der Jahrtausendwende begonnen hat. Diese Kriterien erfüllen Nico Bleutge, Björn Kuhligk, Albert Ostermaier, Steffen Popp, Marion Poschmann, Monika Rinck, Jan Wagner und Ron Winkler. Ausgangspunkt bei der Lektüre ihrer Werke ist die Überlegung, dass Farben markante Adjektive sind, die den Anschein erwecken, als könne in einem schwarzweißen Druckerzeugnis bunte Sichtbarkeit hergestellt werden. Wenn es aber stimmt, dass gerade das "Sichtbare nicht zu den Stärken der Dichtung" gehört, dann können Farbworte in den - zumeist kurzen - lyrischen Texten ein besonderer Brennpunkt sein, der nicht nur eine metaphorisch-symbolische Ebene signalisiert, sondern auch Anschaulichkeit und optische Prägnanz anstreben kann. Das mit Farben ebenfalls verbundene heikle Gefühls- und Stimmungsspektrum wird in der Lyrik im 21. Jahrhundert nicht mehr unbedingt angestrebt; deswegen ist von Interesse, wie mit der emotionalen Gefahrenzone umgegangen wird. Entscheidende Fragen in diesem Zusammenhang sind: Wird Gottfried Benns Warnung vor "Wortklischees" berücksichtigt? Wie oft ist der Himmel blau, die Rose rot und der Baum grün? Werden Komposita gebildet und wenn ja, welche, und wie werden bekannte Farbbezeichnungen in unbekannte Zusammenhänge eingeordnet? Spielen synästhetische Effekte und Vergleiche eine größere Rolle? Wie wichtig ist die Stellung der Farbworte im Gedicht oder im Vers, zu Beginn, am Ende oder unauffälliger mitten im Text? Insgesamt soll über den Fokus Farbe eine allgemeinere Diagnostik gegenwartslyrischer Schreibweisen erstellt werden.
Augustin, Albert J. ; Bopp, Silvia ; Fechner, Martin ; Holz, Frank ; Sandner, Dirk ; Winkgen, Andrea ; Khoramnia, Ramin ; Neuhann, Thomas ; Warscher, Marcus ; Spitzer, Martin ; Sekundo, Walter ; Seitz, Berthold ; Duncker, Tobias ; Ksinsik, Christian ; Höh, Helmuth ; Gentsch, Daniela
Introduction: The Retro-IDEAL (ILUVIEN Implant for chronic DiabEtic MAcuLar edema) study is a retrospective study designed to assess real-world outcomes achieved with the ILUVIEN® (0.19 mg fluocinolone acetonide (FAc)) in patients with chronic diabetic macular edema (DME) in clinical practices in Germany.
Methods: This study was conducted across 16 sites in Germany and involved 81 eyes (63 patients) with persistent or recurrent DME and a prior suboptimal response to a first-line intravitreal therapy (primarily anti-VEGF intravitreal therapies).
Results: Patients were followed-up for 30.8 ± 11.3 months (mean ± standard deviation) and had a mean age of 68.0 ± 10.4 years. Best-recorded visual acuity (BRVA) improved by +5.5 letters at month 9 (P ⩽ 0.005, n=56; from a baseline of 49 letters) and this was maintained through to month 30 (P ⩽ 0.05, n = 42). There was a concurrent improvement in central macular thickness with a reduction from 502 µm at baseline to 338 µm at year 1 (P ⩽ 0.0001, n = 43). This effect was sustained to year 3 (i.e. 318 µm; P ⩽ 0.0001, n = 29). Mean intraocular pressure (IOP) remained constant between baseline and year 3 with a peak change of 1.9 mm Hg occurring at year 1. Elevated IOP was observed in a similar percentage of patients prior to (22.2% of cases) and following (27.2%) treatment with the FAc implant. In the majority of cases, these elevations were managed effectively with IOP medications.
Conclusions: Despite substantial amounts of prior intravitreal treatments – primarily with anti–vascular endothelial growth factor (VEGF) drugs – this real-world study showed that sustained structural and functional improvements can last for up to 3 years with a single FAc implant.
Der Begriff Neue Medien nimmt in der Regel Bezug auf neue Technologien. In der Medienwissenschaft wird zwischen digitalen und analogen Medien unterschieden. Digitale Medien resultieren aus der Digitalisierung, die in der zweiten Hälfte des 20. Jahrhunderts entwickelt wurde. Digitalisierung bezeichnet den Prozess der Umwandlung von analogen (stetigen) Informationen in eine digitale (schrittweise, numerische) Form. Als digitale Medien werden meist interaktive Medien auf multimedialer und/oder elektronischer Basis bezeichnet, wie zum Beispiel Internet, CD-Roms, DVDs, MP3-Player, Digitalkameras etc. Mit der rasanten Verbreitung digitaler Technologien entwickelte sich erstmals eine komplexe Vernetzung der Geräte untereinander, die weltweit Daten- und Kommunikationsflüsse ermöglicht. Im Spannungsfeld von Technik, Kultur und Gesellschaft stellen digitale Medien weit mehr als technische Systeme dar und bilden einen untrennbaren Bestandteil einer modernen Gesellschaft. Im Laufe der Zeit wurden neue Medien und v. a. ihre tägliche Nutzung einer starken Kritik unterworfen. Wir möchten feststellen, dass wir es im wirklichen Leben sowie auch im täglichen Unterrichtsprozess für viel wichtiger halten, welche Medien, auf welche Art und Weise, zu welchem Zweck und mit welchem Ziel verwendet werden.
Im Folgenden erörtert Alexander Nebrig den Zusammenhang zwischen der international anschlussfähigen Philosophie Spinozas in Auerbachs Werk einerseits und der internationalen Verbreitung ebendieses Werkes andererseits. Es geht um die ideellen Eigenschaften von Literatur, die ihren Entstehungs- und primären Vertriebsraum überschreitet und in Übersetzungen Erneuerung findet. Bislang wurden Auerbachs Erzählungen vornehmlich mit dem Pantheismus Spinozas in Verbindung gebracht. Die Spinoza-Rezeption lässt sich aber noch stärker präzisieren. Zu zeigen ist, dass die Affektenlehre der spinozistischen Ethik für Auerbachs Figurenpsychologie strukturbildend wurde (I, II). Im Anschluss an die Überprüfung dieser Hypothese wird in einem zweiten Schritt Auerbachs Spinoza-Rezeption in Verbindung mit seiner Einstellung auf internationale Kontrolle des Werkes gebracht (III, IV). Das neue grenzüberschreitende Verwertungsbewusstsein wurde von der Entstehung des übersetzungsrechtlichen Denkens ermöglicht. Auerbach verfolgte aufmerksam die urheberrechtliche Entwicklung und trat selbst als Lobbyist internationaler Urheberübereinkünfte auf, was ihn zu einem Pionier internationaler Werkherrschaft macht. Leitend ist an dieser Zusammenführung von literarischer Hermeneutik und Urheberrechtsgeschichte die bereits an anderen Fällen erörterte These, dass Vertriebs- und Vermittlungslösungen in einem wechselseitigen Verhältnis mit der Werkstruktur stehen können.
In his widely acclaimed book “Das Kalte Herz” (The Cold Heart), economic historian Werner Plumpe tells the story of the history of capitalism, which in his view represents a sober form of economics which has proved itself superior and higher performing than other systems. To this day, the long tradition of capitalism criticism has not understood that in capitalism, great wealth is utilized to produce goods that are usually affordable for people with small incomes.
This contribution aims to describe privacy, publicness and anonymity as essential analytic dimensions for media linguistic research. The dimensions are not inherent in and predetermined by the technical features and forms of communication provided by mobile devices, but are used by the participants as an orientation grid for shaping their online and offline practices in and with mobile media. Considering both mobile device use in the public realm and the dissemination of increasingly private content in social media (which is said to lead to ‘blurred boundaries’ between the private and the public), the paper provides a brief overview of the main developments in mobile media research: Studies adopting various approaches – e. g. sociological-ethnographic, linguistic and media studies – illustrate how publicness, privacy and anonymity are actively shaped and brought about by mobile media users in face-to-face and remote social encounters. As this shows that publicness, privacy and anonymity are still relevant concepts for users, future media linguistics studies should focus on the dynamic multimodal practices by which they are contextualized and accomplished.
Hofmannsthal ist seit seiner Kindheit mit der orientalischen Welt vertraut. Erst nach langjähriger Beschäftigung mit dem Orient hat Hofmannsthal eine Reise in den Orient unternommen. Hofmannsthals "Reise nach Nordafrika" im Jahre 1925 war sein erster und letzter direkter Kontakt mit dem Orient. Er reiste mit der Familie Zifferer nach Marokko, Algerien und Tunesien. Die Städte Fés und Saleh hatten ihn beeindruckt. Er schrieb einen Reisebericht über diese Reise. Der erste Teil seines Reiseberichts Fez berichtet über die Atmosphäre der Stadt und die Einwohner sowie Hofmannsthals Eindrücke und Wahrnehmungen. Er wurde am 12. April 1925 im Berliner Tageblatt publiziert. Im zweiten Teil des Berichts "Das Gespräch in Saleh" handelt es sich um ein Gespräch über das Vorhandensein der Franzosen in Marokko und Reflexionen über die französische und die deutsche Sprache und Kultur. Er wurde am 31. Mai 1925 in der Wiener Freien Presse veröffentlicht. In diesem Aufsatz wird Hofmannsthals Orientbild anhand seines Reiseberichts analysiert.
Immunosuppressive compounds affect the fungal growth and viability of defined aspergillus species
(2019)
Immunosuppressive drugs are administered to a number of patients; e.g., to allogeneic hematopoietic stem cell transplant recipients. Immunosuppressive drugs impair the immune system and thus increase the risk of invasive fungal disease, but may exhibit antifungal activity at the same time. We investigated the impact of various concentrations of three commonly used immunosuppressive compounds—cyclosporin A (CsA), methylprednisolone (mPRED), and mycophenolic acid (MPA)—on the growth and viability of five clinically important Aspergillus species. Methods included disc diffusion, optical density of mycelium, and viability assays such as XTT. MPA and CsA had a species-specific and dose-dependent inhibitory effect on the growth of all Aspergillus spp. tested, although growth inhibition by MPA was highest in A. niger, A. flavus and A. brasiliensis. Both agents exhibited species-specific hyphal damage, which was higher when the immunosuppressants were added to growing conidia than to mycelium. In contrast, mPRED increased the growth of A. niger, but had no major impact on the growth and viability of any of the other Aspergillus species tested. Our findings may help to better understand the interaction of drugs with Aspergillus species and ultimately may have an impact on individualizing immunosuppressive therapy.
Suppression of light nuclei production in collisions of small systems at the Large Hadron Collider
(2019)
We show that the recently observed suppression of the yield ratio of deuteron to proton and of helium-3 to proton in p+p collisions compared to those in p+Pb or Pb+Pb collisions by the ALICE Collaboration at the Large Hadron Collider (LHC) can be explained if light nuclei are produced from the coalescence of nucleons at the kinetic freeze-out of these collisions. This suppression is attributed to the non-negligible sizes of deuteron and helium-3 compared to the size of the nucleon emission source in collisions of small systems, which reduces the overlap of their internal wave functions with those of nucleons. The same model is also used to study the production of triton and hypertriton in heavy-ion collisions at the LHC. Compared to helium-3 in events of low charged particle multiplicity, the triton is less suppressed due to its smaller size and the hypertriton is even more suppressed as a result of its much larger size.
We study how the mass and magnetic moment of the quarks are dynamically generated in nonequilibrium quark matter. We derive the equal-time transport and constraint equations for the quark Wigner function in a magnetized quark model and solve them in the semi-classical expansion. The quark mass and magnetic moment are self-consistently coupled to the Wigner function and controlled by the kinetic equations. While the quark mass is dynamically generated at the classical level, the quark magnetic moment is a pure quantum effect, induced by the quark spin interaction with the external magnetic field.
Ceritinib-induced regression of an insulin-like growth factor-driven neuroepithelial brain tumor
(2019)
Russo, Alexandra ; Paret, Claudia ; Alt, Francesca ; Burhenne, Jürgen ; Fresnais, Margaux ; Wagner, Wolfgang ; Glaser, Martin ; Bender, Hannah ; Huprich, Sabrina ; Harter, Patrick Nikolaus ; Filipski, Katharina Johanna ; Lehmann, Nadine ; Backes, Nora ; Roth, Lea ; Seidmann, Larissa ; Sommer, Clemens ; Brockmann, Marc Alexander ; Pietsch, Torsten ; Neu, Marie Astrid ; Wingerter, Arthur ; Faber, Jörg
The insulin-like growth factor (IGF) pathway plays an important role in several brain tumor entities. However, the lack of inhibitors crossing the blood–brain barrier remains a significant obstacle for clinical translation. Here, we targeted the IGF pathway using ceritinib, an off-target inhibitor of the IGF1 receptor (IGF1R) and insulin receptor (INSR), in a pediatric patient with an unclassified brain tumor and a notch receptor 1 (NOTCH1) germline mutation. Pathway analysis of the tumor revealed activation of the sonic hedgehog (SHH), the wingless and integrated-1 (WNT), the IGF, and the Notch pathway. The proliferation of the patient tumor cells (225ZL) was inhibited by arsenic trioxide (ATO), which is an inhibitor of the SHH pathway, by linsitinib, which is an inhibitor of IGF1R and INSR, and by ceritinib. 225ZL expressed INSR but not IGF1R at the protein level, and ceritinib blocked the phosphorylation of INSR. Our first personalized treatment included ATO, but because of side effects, we switched to ceritinib. After 46 days, we achieved a concentration of 1.70 µM of ceritinib in the plasma, and after 58 days, MRI confirmed that there was a response to the treatment. Ceritinib accumulated in the tumor at a concentration of 2.72 µM. Our data suggest ceritinib as a promising drug for the treatment of IGF-driven brain tumors.
Der betongraue Bunker ist von Zwangsarbeitern der Nationalsozialisten im Zweiten Weltkrieg errichtet worden. Geplant war er als Luftschutzbunker für die Mitarbeiter und Kunden der Reichsbahn, damit sie sich im Ernstfall vom nah gelegenen Bahnhof, dem heutigen Bahnhof Friedrichstrasse, vor dem Bombenhagel retten konnten; bis zu 2.500 Menschen finden darin Platz. Nach dem Ende des Zweiten Weltkrieges wurde der Bunker sehr unterschiedlich genutzt: Zuerst diente er als Kriegsgefängnis der Roten Armee, danach als Lager für Textilien und anschließend für Südfrüchte, was ihm den Namen „Bananenbunker“ einbrachte. Nach dem Mauerfall ging das Gebäude in den Besitz des Bundes über und die Kultur Berlins zog ein: Erst in Form eines Techno-Clubs, in welchem auch Theaterstücke aufgeführt wurden, bis der Bund das Gebäude vorerst schloss. Der Werbeagentur-Inhaber Christian Boros erwarb zusammen mit seiner Frau Karen Boros den Bunker schließlich und baute ihn fünf Jahre lang um: Seit 2008 werden die Kunstwerke aus Boros’ privater Kunstsammlung präsentiert. ...
Groot, Natalia Sánchez de ; Armaos, Alexandros ; Graña-Montes, Ricardo ; Alriquet, Marion ; Calloni, Giulia ; Vabulas, Martin ; Tartaglia, Gian Gaetano
The combination of high-throughput sequencing and in vivo crosslinking approaches leads to the progressive uncovering of the complex interdependence between cellular transcriptome and proteome. Yet, the molecular determinants governing interactions in protein-RNA networks are not well understood. Here we investigated the relationship between the structure of an RNA and its ability to interact with proteins. Analysing in silico, in vitro and in vivo experiments, we find that the amount of double-stranded regions in an RNA correlates with the number of protein contacts. This relationship —which we call structure-driven protein interactivity— allows classification of RNA types, plays a role in gene regulation and could have implications for the formation of phase-separated ribonucleoprotein assemblies. We validate our hypothesis by showing that a highly structured RNA can rearrange the composition of a protein aggregate. We report that the tendency of proteins to phase-separate is reduced by interactions with specific RNAs.
Gatz, Susanne A. ; Aladowicz, Ewa ; Casanova, Michela ; Chisholm, Julia C. ; Kearns, Pamela R. ; Fulda, Simone ; Geörger, Birgit ; Schäfer, Beat Werner ; Shipley, Janet M.
Rhabdomyosarcomas are the most common pediatric soft tissue sarcoma and are a major cause of death from cancer in young patients requiring new treatment options to improve outcomes. High-risk patients include those with metastatic or relapsed disease and tumors with PAX3-FOXO1 fusion genes that encode a potent transcription factor that drives tumourigenesis through transcriptional reprogramming. Polo-Like Kinase-1 (PLK1) is a serine/threonine kinase that phosphorylates a wide range of target substrates and alters their activity. PLK1 functions as a pleiotropic master regulator of mitosis and regulates DNA replication after stress. Taken together with high levels of expression that correlate with poor outcomes in many cancers, including rhabdomyosarcomas, it is an attractive therapeutic target. This is supported in rhabdomyosarcoma models by characterization of molecular and phenotypic effects of reducing and inhibiting PLK1, including changes to the PAX3-FOXO1 fusion protein. However, as tumor re-growth has been observed, combination strategies are required. Here we review preclinical evidence and consider biological rationale for PLK1 inhibition in combination with drugs that promote apoptosis, interfere with activity of PAX3-FOXO1 and are synergistic with microtubule-destabilizing drugs such as vincristine. The preclinical effects of low doses of the PLK1 inhibitor volasertib in combination with vincristine, which is widely used in rhabdomyosarcoma treatment, show particular promise in light of recent clinical data in the pediatric setting that support achievable volasertib doses predicted to be effective. Further development of novel therapeutic strategies including PLK1 inhibition may ultimately benefit young patients with rhabdomyosarcoma and other cancers.
Abhari, Behnaz ; McCarthy, Nicole ; Le Berre, Marie ; Kilcoyne, Michelle ; Joshi, Lokesh ; Agostinis, Patrizia ; Fulda, Simone
Since Inhibitor of Apoptosis (IAP) proteins have been implicated in cellular adaptation to endoplasmic reticulum (ER) stress, we investigated the regulation of ER stress-induced apoptosis by small-molecule second mitochondria-derived activator of caspase (Smac) mimetics that antagonize IAP proteins. Here, we discover that Smac mimetic suppresses tunicamycin (TM)-induced apoptosis via resolution of the unfolded protein response (UPR) and ER stress. Smac mimetics such as BV6 selectively inhibit apoptosis triggered by pharmacological or genetic inhibition of protein N-glycosylation using TM or knockdown of DPAGT1, the enzyme that catalyzes the first step of protein N-glycosylation. In contrast, BV6 does not rescue cell death induced by other typical ER stressors (i.e., thapsigargin (TG), dithiothreitol, brefeldin A, bortezomib, or 2-deoxyglucose). The protection from TM-triggered apoptosis is found for structurally different Smac mimetics and for genetic knockdown of cellular IAP (cIAP) proteins in several cancer types, underlining the broader relevance. Interestingly, lectin microarray profiling reveals that BV6 counteracts TM-imposed inhibition of protein glycosylation. BV6 consistently abolishes TM-stimulated accumulation of ER stress markers such as glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) and reduces protein kinase RNA-like ER kinase (PERK) phosphorylation and X box-binding protein 1 (XBP1) splicing upon TM treatment. BV6-stimulated activation of nuclear factor-κB (NF-κB) contributes to the resolution of ER stress, since NF-κB inhibition by overexpression of dominant-negative IκBα superrepressor counteracts the suppression of TM-stimulated transcriptional activation of CHOP and GRP78 by BV6. Thus, our study is the first to show that Smac mimetic protects from TM-triggered apoptosis by resolving the UPR and ER stress. This provides new insights into the regulation of cellular stress responses by Smac mimetics.
De novo fatty acid biosynthesis in humans is accomplished by a multidomain protein, the Type I fatty acid synthase (FAS). Although ubiquitously expressed in all tissues, fatty acid synthesis is not essential in normal healthy cells due to sufficient supply with fatty acids by the diet. However, FAS is overexpressed in cancer cells and correlates with tumor malignancy, which makes FAS an attractive selective therapeutic target in tumorigenesis. Herein, we present a crystal structure of the condensing part of murine FAS, highly homologous to human FAS, with octanoyl moieties covalently bound to the transferase (MAT—malonyl‐/acetyltransferase) and the condensation (KS—β‐ketoacyl synthase) domain. The MAT domain binds the octanoyl moiety in a novel (unique) conformation, which reflects the pronounced conformational dynamics of the substrate‐binding site responsible for the MAT substrate promiscuity. In contrast, the KS binding pocket just subtly adapts to the octanoyl moiety upon substrate binding. Besides the rigid domain structure, we found a positive cooperative effect in the substrate binding of the KS domain by a comprehensive enzyme kinetic study. These structural and mechanistic findings contribute significantly to our understanding of the mode of action of FAS and may guide future rational inhibitor designs.
Wichers, Robert H. ; Findon, James ; Jelsma, Auke ; Giampietro, Vincent ; Stoencheva, Vladimira ; Robertson, Dene M. ; Murphy, Clodagh M. ; McAlonan, Grainne ; Ecker, Christine ; Rubia, Katya ; Murphy, Declan G. M. ; Daly, Eileen
Adults with autism spectrum disorder (ASD) are frequently prescribed selective serotonin reuptake inhibitors (SSRIs). However, there is limited evidence to support this practice. Therefore, it is crucial to understand the impact of SSRIs on brain function abnormalities in ASD. It has been suggested that some core symptoms in ASD are underpinned by deficits in executive functioning (EF). Hence, we investigated the role of the SSRI citalopram on EF networks in 19 right-handed adult males with ASD and 19 controls who did not differ in gender, age, IQ or handedness. We performed pharmacological functional magnetic resonance imaging to compare brain activity during two EF tasks (of response inhibition and sustained attention) after an acute dose of 20 mg citalopram or placebo using a randomised, double-blind, crossover design. Under placebo condition, individuals with ASD had abnormal brain activation in response inhibition regions, including inferior frontal, precentral and postcentral cortices and cerebellum. During sustained attention, individuals with ASD had abnormal brain activation in middle temporal cortex and (pre)cuneus. After citalopram administration, abnormal brain activation in inferior frontal cortex was ‘normalised’ and most of the other brain functional differences were ‘abolished’. Also, within ASD, the degree of responsivity in inferior frontal and postcentral cortices to SSRI challenge was related to plasma serotonin levels. These findings suggest that citalopram can ‘normalise’ atypical brain activation during EF in ASD. Future trials should investigate whether this shift in the biology of ASD is maintained after prolonged citalopram treatment, and if peripheral measures of serotonin predict treatment response.
Lublinsky, Svetlana ; Major, Sebastian ; Kola, Vasilis ; Horst, Viktor ; Santos, Edgar ; Platz, Johannes ; Sakowitz, Oliver ; Scheel, Michael ; Dohmen, Christian ; Graf, Rudolf ; Vatter, Hartmut ; Wolf, Stefan ; Vajkoczy, Peter ; Shelef, Ilan ; Woitzik, Johannes ; Martus, Peter ; Dreier, Jens P. ; Friedman, Alon
Background: Disease progression and delayed neurological complications are common after aneurysmal subarachnoid hemorrhage (aSAH). We explored the potential of quantitative blood-brain barrier (BBB) imaging to predict disease progression and neurological outcome.
Methods: Data were collected as part of the Co-Operative Studies of Brain Injury Depolarizations (COSBID). We analyzed retrospectively, blinded and semi-automatically magnetic resonance images from 124 aSAH patients scanned at 4 time points (24–48 h, 6–8 days, 12–15 days and 6–12 months) after the initial hemorrhage. Volume of brain with apparent pathology and/or BBB dysfunction (BBBD), subarachnoid space and lateral ventricles were measured. Neurological status on admission was assessed using the World Federation of Neurosurgical Societies and Rosen-Macdonald scores. Outcome at ≥6 months was assessed using the extended Glasgow outcome scale and disease course (progressive or non-progressive based on imaging-detected loss of normal brain tissue in consecutive scans). Logistic regression was used to define biomarkers that best predict outcomes. Receiver operating characteristic analysis was performed to assess accuracy of outcome prediction models.
Findings: In the present cohort, 63% of patients had progressive and 37% non-progressive disease course. Progressive course was associated with worse outcome at ≥6 months (sensitivity of 98% and specificity of 97%). Brain volume with BBBD was significantly larger in patients with progressive course already 24–48 h after admission (2.23 (1.23–3.17) folds, median with 95%CI), and persisted at all time points. The highest probability of a BBB-disrupted voxel to become pathological was found at a distance of ≤1 cm from the brain with apparent pathology (0·284 (0·122–0·594), p < 0·001, median with 95%CI). A multivariate logistic regression model revealed power for BBBD in combination with RMS at 24-48 h in predicting outcome (ROC area under the curve = 0·829, p < 0·001).
Interpretation: We suggest that early identification of BBBD may serve as a key predictive biomarker for neurological outcome in aSAH.
Fund: Dr. Dreier was supported by grants from the Deutsche Forschungsgemeinschaft (DFG) (DFG DR 323/5-1 and DFG DR 323/10–1), the Bundesministerium für Bildung und Forschung (BMBF) Center for Stroke Research Berlin 01 EO 0801 and FP7 no 602150 CENTER-TBI.
Dr. Friedman was supported by grants from Israel Science Foundation and Canada Institute for Health Research (CIHR). Dr. Friedman was supported by grants from European Union's Seventh Framework Program (FP7/2007–2013; grant #602102).
Prescribing practice of pregabalin/gabapentin in pain therapy : an evaluation of German claim data
(2019)
Viniol, Annika ; Ploner, Tina ; Hickstein, Lennart ; Haasenritter, Jörg ; Klein, Karl Martin ; Walker, Jochen ; Donner-Banzhoff, Norbert ; Becker, Annette
Objectives: To analyse the prevalence and incidence of pregabalin and gabapentin (P/G) prescriptions, typical therapeutic uses of P/G with special attention to pain-related diagnoses and discontinuation rates.
Design: Secondary data analysis.
Setting: Primary and secondary care in Germany.
Participants: Four million patients in the years 2009–2015 (anonymous health insurance data).
Intervention: None.
Primary and secondary outcome measures: P/G prescribing rates, P/G prescribing rates associated with pain therapy, analysis of pain-related diagnoses leading to new P/G prescriptions and the discontinuation rate of P/G.
Results: In 2015, 1.6% of insured persons received P/G prescriptions. Among the patients with pain first treated with P/G, as few as 25.7% were diagnosed with a typical neuropathic pain disorder. The remaining 74.3% had either not received a diagnosis of neuropathic pain or showed a neuropathic component that was pathophysiologically conceivable but did not support the prescription of P/G. High discontinuation rates were observed (85%). Among the patients who had discontinued the drug, 61.1% did not receive follow-up prescriptions within 2 years.
Conclusion: The results show that P/G is widely prescribed in cases of chronic pain irrespective of neuropathic pain diagnoses. The high discontinuation rate indicates a lack of therapeutic benefits and/or the occurrence of adverse effects.
In Justice and Reconciliation in World Politics Catherine Lu endorses the idea that those who contribute to the reproduction of structural injustice have responsibilities to address that injustice (Lu, 2017). However, in the book, Lu does not explore the grounds and justification for recognising such a responsibility. In order to address this deficit, this paper proposes that those likely to contribute to the reproduction of structural injustice, in the future, have precautionary duties, in the present, that require them to take action aimed at preventing their future contribution. It is proposed that these ‘collectivization duties’ (Collins, 2013) require them to act responsively with a view to forming a collective that can end the structural injustice in question. This account recommends a collective-action solution alongside recognising that each socially connected agent is obliged to act. However, it does not entail that amorphous groups bear responsibilities and is appropriate in its attribution of blame, thus avoiding both Nussbaum’s (2011) critique of perpetually forward-looking accounts and the ‘agency objection’ (Wringe, 2010).
This article analyzes and criticizes the temporal orientation of Catherine Lu’s theory of colonial redress in Justice and Reconciliation in World Politics. Lu argues that colonial historic injustice can, with few exceptions, justify special reparative measures only if these past injustices still contribute to structural injustice in contemporary social relations. Focusing on Indigenous peoples, I argue that the structural injustice approach can and should incorporate further backward looking elements. First, I examine how Lu’s account has backward-looking elements not present in other structural injustice accounts. Second, I suggest how the structural injustice approach could include additional backward-looking features. I presuppose here, with Lu, that all agents connected to an unjust social structure have a forwardlooking political responsibility to reform this structure, regardless of their relation (or lack thereof) to victims or perpetrators of historic injustice. However, I suggest that agents with connections to historic injustice can occupy a social position that makes them differently situated than other agents within that same structure, leading to differences in how these agents should discharge their forward-looking responsibility and differentiated liability for failure to do so. Third, I argue that Lu obscures the importance of rectifying material dispossession. Reparations, pace Lu, can be justified beyond a minimum threshold of disadvantage. Theorists of settler colonialism and Indigenous scholars show how the dispossession of Indigenous land can be seen as a structure that has not yet ended. I conclude by arguing that rectification can be a precondition for genuine reconciliation.
Structural alienation: Lu's structural approach to reconciliation from within a relational framework
(2019)
In Justice and Reconciliation in World Politics Catherine Lu argues that structural reconciliation, rather than interactional reconciliation, ought to be the primary normative goal for political reconciliation efforts. I suggest that we might have good reason to want to retain relational approaches – such as that of Linda Radzik – as the primary focus of reconciliatory efforts, but that Lu’s approach is invaluable for identifying the parties who ought to bear responsibility for those efforts in cases of structural injustice. First, I outline Lu’s analysis of reconciliation, where she argues for the normative priority of structural approaches within the global political sphere, and propose that it will be useful to identify whether or not a relational account could instead identify underlying structural injustices. Second, I examine one particular relational account of reconciliation (based on Radzik’s account of atonement) and argue that this type of account brings to light underlying structural injustices of the kind Lu is concerned with. Finally, I identify an issue for relational accounts in identifying relevant responsible parties for reconciliation before returning to Lu’s structural account to address this gap.
This paper discusses two possible difficulties with Catherine Lu’s powerful analysis of the moral response to our shared history of colonial evil; both of these difficulties stem from the rightful place of shame in that moral response. The first difficulty focuses on efficacy: existing states may be better motivated by shame at the past than by a shared duty to bring about a just future. The second focuses on equity: it is, at the very least, possible that shame over past misdeeds ought to be brought into the conversation about present duties, in a manner more robust than Lu’s analysis allows.