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Das Journal für Medienlinguistik (jfml) ist eine medienlinguistische Open-Access-Zeitschrift. Im Sinne einer offenen, interaktiven und unabhängigen Wissenschaftskultur erfolgt die Qualitätssicherung des jfml durch ein Open Peer Review und die medienlinguistische Expertise des Editorial Boards. Das jfml veröffentlicht deutsch- und englischsprachige Artikel, Rezensionen und Tagungsberichte, die fortlaufend erscheinen.
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Trennungen und Scheidungen auf einem hohen Niveau – auch unter Familien mit minderjährigen Kindern – kennzeichnen bereits seit längerer Zeit die Familienentwicklung in Deutschland und anderen europäischen Ländern. Sofern aus einer Beziehung gemeinsame Kinder hervorgegangen sind, impliziert eine Trennung zwar das Ende der Partnerschaft, jedoch nicht das Ende der Elternschaft. Sowohl auf gesellschaftlicher als auch auf individueller Ebene besteht, mit Ausnahme von Sondersituationen, mittlerweile die explizite Erwartung, dass Eltern nach einer Trennung in ökonomischer und sozialer Hinsicht weiterhin gemeinsam Verantwortung für ihre Kinder wahrnehmen. In der gesetzlichen Grundlage wird allerdings weiterhin davon ausgegangen, dass Kinder nach der Trennung bei nur einem Elternteil leben. Für andere Modelle existieren bisher keine oder nur unzureichende Regelungen. Die ökonomischen, sozialen und psychischen Folgen einer Trennung oder Scheidung können nach Geschlecht, sozialer Position und Alter variieren und damit soziale Ungleichheit hervorrufen oder verstärken. Neue Partnerschaften bzw. sogenannte Fortsetzungsfamilien beeinflussen das Leben der betroffenen Erwachsenen und Kinder zusätzlich. Bislang existieren über die Verbreitung und Lebensumstände von Nachtrennungsfamilien in Deutschland nur rudimentäre sozialwissenschaftliche Befunde. Die vorliegende Broschüre stellt einen ersten Versuch dar, bislang vorliegende sozialwissenschaftliche Befunde zur Lebenswirklichkeit von Nachtrennungsfamilien in Deutschland allgemeinverständlich in knapper Form zu bilanzieren. Folgende thematische Schwerpunkte werden behandelt: 1) Allgemeine Trends und rechtliche Rahmenbedingungen, 2) Elternschaft und Partnerschaft nach Trennung und Scheidung, 3) Wohlbefinden und Lebenszufriedenheit nach Trennung und Scheidung sowie 4) Finanzielle Folgen von Trennung und Scheidung. Diese Aspekte werden aus unterschiedlichen Perspektiven beleuchtet und zugrundeliegende empirische Analysen decken ein breites Spektrum der derzeit verfügbaren Datenquellen ab.
Die forensische Entomologie nutzt nekrophage Insekten, hauptsächlich Dipteren und ihre juvenilen Stadien, zur Schätzung der minimalen Leichenliegezeit. Dem liegt zugrunde, dass nekrophage Dipteren binnen Minuten nach dem Todeseintritt potentiell in der Lage sind, einen Leichnam zu detektieren und zu besiedeln. Das anschließende Wachstum und die Entwicklung der juvenilen Stadien erfolgt als Funktion von der Art und der Umgebungstemperatur.
Mit Hilfe von Laborstudien konnten bislang für einige forensisch relevante Fliegenarten Entwicklungsdaten erhoben werden, die eine Altersbestimmung der sich an einem Leichnam entwickelnden Larven und Puppen erlauben und so eine Schätzung der minimalen Leichenliegezeit ermöglichen. Als Nährsubstrat für Laborstudien werden tierische Gewebe verwendet. Eine Übertragbarkeit der Daten auf humanes Gewebe wurde aber bislang nicht verifiziert. In der vorliegenden Arbeit wurde das larvale Wachstum und die juvenile Entwicklungsgeschwindigkeit der forensisch relevanten Schmeißfliege Calliphora vicina (Diptera: Calliphoridae) auf humanem Muskelgewebe untersucht und mit dem Wachstum auf Schweineleber, magerem Schweinemuskelfleisch und Schweinehackfleisch verglichen. Die auf humanem Gewebe heranwachsenden Individuen waren mit bis zu 3,5 mm signifikant länger als die Individuen, die sich auf Leber und dem mageren Schweinemuskelfleisch entwickelten. Bei der Verwendung von Hackfleisch vom Schwein zeigte sich kein Unterschied. Darauf basierend wird die Empfehlung ausgesprochen, für zukünftige Entwicklungsstudien Schweinehackfleisch als Ersatz für humanes Gewebe zu verwenden.
Zahlreiche Anleitungen zur Asservierung forensisch-entomologischer Spuren empfehlen das Sammeln getrennt nach Körperregionen eines Leichnams. Dies soll eine mögliche gewebespezifische Entwicklungsrate berücksichtigen. Das für die vorliegende Arbeit durchgeführte systematische Absammeln von Fliegenlarven von 51 Leichnamen getrennt nach Körperregionen zeigte keine artspezifischen Präferenzen für bestimmte Gewebe oder Körperregionen. Das Artenspektrum entsprach größtenteils dem aufgrund von Studien an Schweinekadavern zu erwartendem Artenspektrum für Deutschland und Mitteleuropa. Insgesamt konnten 15 Schmeißfliegenarten nachgewiesen werden, von denen in der Regel mehrere gleichzeitig an einem Leichnam zu finden waren. Dies zeigt, dass ein Faktor wie interspezifische Konkurrenz in Zukunft mehr Beachtung in der Forschung erhalten sollte.
Bislang wurde in der forensischen Entomologie die minimale Leichenliegezeit durch die Untersuchung juveniler Stadien von Fliegen eingegrenzt. Eine eventuell mögliche Ausweitung dieses Zeitfensters könnte durch eine Altersbestimmung der adulten Fliegen oder der leeren Puparien gelingen. Der Nachweis, dass die dafür untersuchten Fliegen bzw. Puparien tatsächlich von dem fraglichen Leichnam stammen, war bislang nicht möglich. Die forensische relevante Schmeißfliege Lucilia sericata wurde in der vorliegenden Arbeit auf humanem Gewebe und Gewebe von elf weiteren Tierarten großgezogen. Durch die Analyse stabiler Kohlen- und Stickstoffisotope konnte ein von diesen elf Tierarten abgrenzbares humanes Isotopenprofil sowohl für die adulten Fliegen von L. sericata, als auch für ihre leeren Puparien detektiert werden. Dieses Profil spiegelte die Nahrungszusammensetzung der Wirte wider.
Die vorliegende Arbeit erhebt Daten zur Entwicklung einer forensisch relevanten Schmeißfliegenart auf humanem Gewebe, belegt das bislang lediglich am tierischen Modell erhobene Schmeißfliegeninventar als für menschliche Leichen relevant und hinterfragt die gewebespezifische Asservierungsempfehlung als ein akademisches Artefakt. Auf dieser Basis konnten Empfehlungen für die Weiterzucht fallrelevanter entomologischer Spuren ausgesprochen werden, die gerichtsverwertbar sind und die Verwendung von tierischem Gewebe oder Tierkadaver in der forensisch-entomologischen Forschung legitimieren. Die Analyse stabiler Isotope legt darüber hinaus einen neuen, innovativen Grundstein für die routinemäßige Spurenzuordnung älterer Entwicklungsstadien und ist damit Vorreiter auf dem Gebiet der forensischen Entomologie.
In der Zeitschrift Studia Germanistica werden Forschungsergebnisse zu aktuellen Themen auf dem Gebiet der germanistischen Linguistik, Literaturwissenschaft und DaF-Didaktik publiziert, die den Stand der Forschung in Tschechien sowie im Ausland dokumentieren. Bestandteile der Zeitschrift sind kulturwissenschaftliche Studien und Rezensionen. Alle Beiträge werden in Deutsch - mit einer Annotation und Schlüsselwörtern in Englisch - publiziert.
In der Zeitschrift Studia Germanistica werden Forschungsergebnisse zu aktuellen Themen auf dem Gebiet der germanistischen Linguistik, Literaturwissenschaft und DaF-Didaktik publiziert, die den Stand der Forschung in Tschechien sowie im Ausland dokumentieren. Bestandteile der Zeitschrift sind kulturwissenschaftliche Studien und Rezensionen. Alle Beiträge werden in Deutsch - mit einer Annotation und Schlüsselwörtern in Englisch - publiziert.
Beleko
(2018)
Béléko is a small village in the West African state of Mali. In the book's twenty-five chapters we meet Dutch development workers, French missionaries and Malian public service workers, health workers, farmers, village women and their children. All of these characters strive in their different ways to give meaning to their lives as their paths cross in the daily village life of Africa at the end of the 1980s. As each character tells his or her own story, we learn of their backgrounds, their passions and their struggles - and how they influence each other in decisive ways.
Das Meer als Faszinosum und Das Meer als Ort von Katastrophen sind nicht zu trennen. Diese kleine Abhandlung beginnt daher mit einer Hommage an das Meer durch Lichtenberg (1793) und endet mit einer nicht weniger einzigartigen minutiösen protokollartigen Darstellung einer "Sturmspringflut" an der Nordsee mit ihren katastrophalen Folgen durch Ernst Willkomm (1854).
"Erkennt das Recht, das von Gott verliehene Menschenrecht", denn "wir sind in die Rechte freier Menschenwürde vollständig eingetreten". "Des Menschen Recht ist, durch immer höhere Vervollkommnung seiner geistigen, sittlichen und körperlichen Fähigkeiten zum Genusse eines stets wachsenden, reineren Glückes zu gelangen. [---] Bestimmung und Recht sind eins, und das Recht des Menschen ist einfach: seine Bestimmung zu erreichen". "Nur die Not, welche zum Äußersten treibt, ist die wahre Not; nur diese Not ist aber die Kraft des wahren Bedürfnisses; nur ein gemeinsames Bedürfnis ist aber das wahre Bedürfnis; nur wer ein wahres Bedürfnis empfindet, hat aber ein Recht auf Befriedigung desselben." Das erste Zitat stammt aus dem Manuskript eines Vortrages, den Richard Wagner am 14. Juni 1848 abends in der Hauptversammlung des Sächsischen Vaterlandsvereins [...] vor 3000 Menschen im Garten des polnischen Brauhauses hielt und den er am 15. Juni 1848 als Extra-Beilage (zu Nr.191) des Dresdner Anzeigers und Tageblatts veröffentlichte, [...]. Das zweite Zitat findet sich in einem Beitrag in der Nummer 6 der von August Röckel seit dem 26. August 1848 herausgegebenen "Volksblätter" vom 10. Februar 1849 mit dem Titel "Der Mensch und die bestehende Gesellschaft", anonym erschienen, aber heute überwiegend Richard Wagner zugeschrieben. Diese beiden Zitate werden also Arbeiten zugeordnet, die als seine "Revolutionsschriften" bezeichnet werden. Das dritte Zitat stammt aus der von Wagner 1849 unter seinem Namen veröffentlichten Schrift "Das Kunstwerk der Zukunft", die herkömmlich zu den "Reformschriften" (1849 bis 1852) gezählt werden. Im Hauptteil (unter II.) werden diese drei Schriften im Rahmen aller "Revolutions-" und "Reformschriften" vorgestellt; dabei wird auch die Frage der Autorenschaft der anonymen Beiträge in den "Volksblättern" angesprochen. Überdies wird damit das Verhältnis der "Revolutionsschriften" zu den "Reformschriften" kurz angesprochen. Unter I. ist mit einer kurzen Darstellung der historischen Situation in Sachsen zu dieser Zeit zu beginnen. Als Ausblick unter III. wird kurz schließlich der weitere Bogen zu dem eigentlichen Thema der "Reformschriften" gezogen.
Die Versammlungsfreiheit war ein gesuchtes Gut, das erst einmal zu begründen und im Blick auf mögliche Beschränkungen zu untersuchen war. Die Performativität einer Versammlung – das Beieinandersein freier Individuen zu einem Zweck, der sich nicht oder nicht immer einer reglementierenden Norm verdankte – erscheint heute als Teil jener Ethik der Kohabitation, die aus der Kantischen Notwendigkeit der Koordination der Freiheitsräume als Aneinanderstoßen von Willkürgrenzen kommt und im Blick auf Gefährdungsszenarien aktualisiert ist. Doch Aktualisierungen bedürfen der Grundlage, wollen sie nicht geschichtsvergessen sein (niedergelegt in der Geschichte finden wir die Praktiken, die für die damaligen Akteure Sinn verbürgten).
Im Folgenden werden die Freiheit der Person, vornehmlich das Recht auf Habeas Corpus, mithin der Schutz gegen willkürliche Inhaftierungen und die Freiheit des Eigentums, so wie sie in der Paulskirche konzipiert wurden, in Betracht gezogen. Die Vorgehensweise wird vor allem rechtsphilosophisch bzw. analytisch sein: Zunächst werden die jeweiligen Artikel und Paragraphen der Erklärung der Paulskirchenverfassung erörtert, in welchen die respektiven Grundrechte aufgebaut werden. Anschließend werden sie mit den entsprechenden Vorschriften anderer Grund- und Menschenrechtskatalogen verglichen, insbesondere mit den Verfassungen der süddeutschen Staaten, mit der Französischen Erklärung von 1789, mit der Allgemeinen Erklärung der Menschenrechte von 1948 und mit dem heutigen deutschen Grundgesetz. Hie und da wird gelegentlich auch auf relevante historische Ereignisse und prägende Literatur Bezug genommen, wobei dies den eigentlichen Gegenstand der derzeitigen Untersuchung nicht ausmacht.
Guide to active recruiting : attract more female faculty increase diversity – optimize quality
(2018)
Neuropogonoid species in the lichen-forming fungal genus Usnea exhibit great morphological variation that can be misleading for delimitation of species. We specifically focused on the species delimitation of two closely-related, predominantly Antarctic species differing in the reproductive mode and representing a so-called species pair: the asexual U. antarctica and the sexual U. aurantiacoatra. Previous studies have revealed contradicting results. While multi-locus studies based on DNA sequence data provided evidence that these two taxa might be conspecific, microsatellite data suggested they represent distinct lineages. By using RADseq, we generated thousands of homologous markers to build a robust phylogeny of the two species. Furthermore, we successfully implemented these data in fine-scale population genomic analyses such as DAPC and fineRADstructure. Both Usnea species are readily delimited in phylogenetic inferences and, therefore, the hypothesis that both species are conspecific was rejected. Population genomic analyses also strongly confirmed separated genomes and, additionally, showed different levels of co-ancestry and substructure within each species. Lower co-ancestry in the asexual U. antarctica than in the sexual U. aurantiacoatra may be derived from a wider distributional range of the former species. Our results demonstrate the utility of this RADseq method in tracing population dynamics of lichens in future analyses.
Authoritarian regimes and religious institutions in the Muslim majority world see eye-to-eye on the topic of atheism. United by their fear of losing control over their populations and their desire for conformity, consecutive governments have pushed for unfair restrictions on their subjects’ beliefs since their inception. But even in society, non-belief remains a taboo. Should atheists in Muslim majority world become more vocal?
The truth lies in Chemnitz?
(2018)
"Germany to the Germans! Foreigners out" was the central slogan of the racist riots in the city of Rostock in 1992. For around three days, neo-Nazis controlled the streets in the plattenbau district of Lichtenhagen where the central registration for asylum-seekers (as well as a housing block of Vietnamese contract workers) were situated. ...
Die am Wochenende beschlossene Verfassungsänderung gibt Chinas Präsident Xi Jinping die Möglichkeit auf Lebenszeit im Amt zu bleiben. Das wird als Zeichen des wachsenden Autoritarismus und Xis zunehmender Macht gewertet. Doch ein genauerer Blick lässt zweifeln: Die Entscheidung ist eher Ausdruck von Zukunftssorgen und Selbstzweifeln der Regierenden in Peking.
In this research project we aimed to generate genetically modified megakaryocytes and platelets, by targeting protein expression to their secretory alpha-granules to delivery ectopic or therapeutic proteins, to be stored and kept there until an external stimulus triggers platelet activation and platelet secretion takes place. During platelet activation, the therapeutic proteins would then be released to the extracellular space, either as a soluble protein or exposed as a transmembrane protein on the cell surface of platelets. For long-term approaches, genetic modifications must be introduced at the hematopoietic stem cell level.
AIMS: As first approach, we aimed to characterize the lineage-specificity of expression of six different promoter fragments in lentiviral vectors: the murine platelet factor 4 (mPf4) 1222 bp (-1074 to +148), human glycoprotein Ib alpha (hGP1BA) 595 bp (-265 to +330), a short and a longer fragment of the human glycoprotein 6 (hGP6 / hGP6s) 351 bp (-322 to +29) / 726 bp (-697 to +29), as well the human glycoprotein 9 (GP9) promoter 794 bp (-782 to -12). These promoter fragments were included as internal cellular promoters in self-inactivating lentiviral vectors (SIN), using an enhanced green fluorescent protein (eGFP) as gene reporter. GFP detection was evaluated in vitro (in transduced non-megakaryocitc blood cell progenitors and in-vitro differentiated megakaryocytes) and in vivo (Bone marrow cells, blood cells and spleen cells). For targeting of proteins to the secretory alpha granules of megakaryocytes and platelets, we followed two strategies: A) The sorting signal of the cytokine RANTES was fused N-terminally to the destabilized GFP, d2eGFP (RANTES. d2eGFP), to deliver the protein into the granules as soluble cargo. B) The transmembrane granular targeting sequence of P-selectin (the transmembrane domain and cytoplasmic tail (referred as TDCT) was fused to d2eGFP or the B domain deleted codon optimized human coagulation Factor VIII cDNA (referred as BDcohFVIII_TDCT or FVIII_TDCT), to deliver the protein into the membrane of alpha granules. These two strategies were tested in-vitro, from transduced differentiated megakaryocytes in liquid cultures, and in-vivo, by analysis of genetically modified platelets by means of Laser Scanning Confocal Microscopy (LSM) in colocalization analysis (performed at the single cell level) and fluorescence intensity analysis.
RESULTS: GFP expression in blood cells from transplanted mice was significantly higher in platelets, with a smaller background promoter activity in leukocytes and erythrocytes. The highest expression was observed from the mPf4-vector, followed by hGP1BA, hGP6 and hGP6s vectors, identifying the hGP6 vectors as the most restricted to the megakaryocyte and platelet lineage. Analysis in bone marrow cells showed that hGP6-vectors have the lowest activity in the hematopoietic stem and progenitor cells (HSPC) with less than 10% of GFP positive stem cells. Surprisingly, the mPf4 and hGP1BA vectors were both highly active in the HSPC, in a range of 20 to 70% of GFP-positive cells. Polyploidization in later stages of MK-maturation of in-vitro Mks differentiated from Mpl-/- lineage marker negative cells were recovered after gene transfer of the thrombopoietin receptor Mpl, under the control of MK-specific vectors in differentiated into MKs. These results were corroborated in in-vivo analysis, where Mpl-/- mice transplanted with lin-BM cells transduced with the mPf4.Mpl and hGP6.Mpl vectors, showed significantly elevated platelet counts compared to control mice transplanted with a GFP-encoding control vector (PGK-GFP). In the Fluorescent intensity and colocalization analysis of transduced megakaryocytes with the targeting vectors, we observed a significant difference in the GFP targeting compared with those MK transduced with the non-targeting vectors. The median of the WCC values observed from the RANTES.d2eGFP targeting vector was 0.8 (80 % of colocalization) with P-selectin stained granules, and 0.7 (70%) with von Willebrand Factor stained granules. In the case of the non-targeting vector SFFV.d2eGFP the median of the WCC observed were <0.3 (30%) both in P-selectin and von Willebrand Factor stained granules. We observed as well that the GFP signal of MK transduced with the P-selectin.d2eGFP fusion overlapped the signals emitted by P-selectin and von Willebrand factor stained granules, not just in LSM-digitalized images but in the fluorescens intensity analysis as well, indicating a clear signal of GFP colocalization. Likewise, an evident signal overlap between the targeted FVIII (FVIII_TDCT) with the P-selectin / von Willebrand marker was observed. Colocalization and fluorescens intensity analysis performed on activated platelets from transplanted mice with the targeting vectors, corroborated what was previously observed in in-vitro megakaryocytes. The genetic modification of megakaryocyte and platelets will allow in the furture, not just the development of new generation of cells with advanced functions, but it will help us to elucidate new mechanisms and pathways of important cellular processes, by modifying cell function and cell interactions.
Pretubulysin (PT), a biosynthetic precursor of the myxobacterial compound tubulysin D, was recently identified as a novel microtubule-targeting agent (MTA) causing microtubule destabilization. MTAs are the most frequently used chemotherapeutic drugs. They are well studied regarding their direct cytotoxic effects against various tumors as well as for their anti-angiogenic and vascular-disrupting action addressing endothelial cells of the tumor vasculature. However, the impact of MTAs on endothelial cells of the non-tumor vasculature has been largely neglected, although tumor cell interactions with the healthy endothelium play a crucial role in the process of cancer metastasis. Besides their use as potent anti-cancer drugs, some MTAs such as colchicine are traditionally used or recommended for the therapy of inflammatory diseases. Here, too, the role of endothelial cells has been largely neglected, although the endothelium is crucially involved in regulating the process of inflammation.
In the present study, the impact of PT on tumor-endothelial cell interactions was therefore analyzed in vitro to gain insights into the mechanism underlying its anti-metastatic effect that was recently confirmed in vivo. In the second part of this work, the influence of PT and other MTAs, namely the microtubule-destabilizing compounds vincristine (VIN) and colchicine (COL) and the microtubule-stabilizing drug paclitaxel (PAC), on leukocyte-endothelial cell interactions was investigated in vitro and in vivo (only PT). It is important to mention that in all in vitro experiments solely endothelial cells and not tumor cells or leukocytes were treated with the MTAs to strictly focus on the role of the endothelium in the action of these compounds.
The impact of PT on tumor-endothelial cell interactions was analyzed in vitro by cell adhesion and transendothelial migration assays as well as immunocytochemistry using the breast cancer cell line MDA-MB-231 and primary human umbilical vein endothelial cells (HUVECs). The treatment of HUVECs with PT increased the adhesion of MDA cells onto the endothelial monolayer, whereas their transendothelial migration was reduced by the compound. Thereafter, the influence of PT on the endothelial cell adhesion molecules (CAMs) E-selectin, N-cadherin, ICAM-1, VCAM-1 and galectin-3 and on the CXCL12/CXCR4 chemokine system was examined, since they might be involved in the PT-triggered tumor cell adhesion. Interestingly, although PT induced the upregulation of ICAM-1, VCAM-1, N-cadherin and CXCL12, cell adhesion assays using neutralizing antibodies or the CXCL12 inhibitor AMD3100 revealed that all these molecules were dispensable for the PT-evoked tumor cell adhesion. As PT induces the formation of interendothelial gaps and MDA cells might adhere onto components of the underlying extracellular matrix (ECM), the precise location of MDA cells attached to the PT-treated endothelial monolayer was investigated. Instead of a direct interaction between tumor and endothelial cells, this work showed that MDA cells preferred to adhere to the ECM component collagen that was exposed within PT-triggered endothelial gaps. Both the PT-evoked increase in tumor cell adhesion onto and the decrease in trans-endothelial migration were completely abolished when β1-integrins were blocked on MDA cells. Similar results were obtained when endothelial cells were treated with VIN and COL but not PAC, indicating that the observed effects of PT depend on its microtubule-destabilizing activity.
The impact of PT, VIN, COL and PAC on leukocyte-endothelial cell interactions was analyzed in vivo (only PT) by intravital microscopy of the mouse cremaster muscle and in vitro by cell adhesion assays using the monocyte-like cell line THP-1 and TNFα-activated human dermal microvascular endothelial cells (HMEC-1). While PT did not affect the rolling of leukocytes on the endothelium, their firm adhesion onto and transmigration through the activated endothelium was reduced by PT in vivo. In accordance, the treatment of HMEC-1 with PT, VIN and COL decreased the TNFα-induced adhesion of THP-1 cells onto the endothelial monolayer, whereas PAC had no influence on this process. Thereafter, the influence of PT, VIN, COL and PAC on endothelial ICAM-1 and VCAM-1 was examined, since these molecules are substantially involved in the firm adhesion of leukocytes onto the endothelium. The cell surface protein expression of ICAM-1 and VCAM-1 was reduced by PT, VIN and COL in activated endothelial cells, whereas PAC did only slightly affect the TNFα-induced upregulation of VCAM-1. As the pro-inflammatory transcription factor NFκB plays a crucial role in the TNFα-induced expression of these CAMs, the impact of the MTAs on the NFκB promotor activity was investigated. While PT, VIN and COL decreased the activation of NFκB in activated endothelial cells, PAC did not affect this process. However, in contrast to the strong effects regarding the cell surface protein expression of ICAM-1 and VCAM-1, the effects of PT, VIN and COL on the NFκB activity was rather low. Thus, the used MTAs might also affect other relevant signaling pathways and/or the intracellular transport of CAMs might be influenced by the impact of the MTAs on the microtubule network.
Taken together, the current study provides – at least in part – an explanation for the anti-metastatic potential of PT and gives first insights into the use of PT and VIN as anti-inflammatory drugs. Moreover, this work highlights the endothelium as an attractive target for the development of new anti-cancer and anti-inflammatory drugs.
Concepts historiques du capitalisme industriel avancé : « capitalisme organisé » et « corporatisme »
(2018)
Les économistes comme les spécialistes de sciences sociales semblent largement s’accorder sur le fait que le capitalisme industriel est entré à un moment donné dans une phase avancée de son développement, tout particulièrement dans ses variantes que l’on observe en Europe de l’Ouest, en Amérique du Nord et au Japon. Que le capitalisme se situe encore à cette étape, ou qu’il l’ait entre-temps déjà dépassée et laissée à nouveau derrière lui, il se différencie à tout le moins de la phase antérieure (ou bien des phases antérieures), à laquelle on peut rattacher le début d’une première industrialisation et l’avènement de l’industrialisation massive (Hochindustrialisierung). ...
Luftmenschen
(2018)
Wörter können zweifach bewegt werden: wie Erbschaften in der Zeit und wie Güter im Raum. Sie gedeihen nicht nur in ihrer eigenen Sprache, sondern auch in anderen, vor allem dann, wenn dort im Mündlichen oder in der Schriftsprache eine Art Bezeichnungs-"Vakuum" besteht: Wo immer sie dringend benötigt werden, dort haben sie potentiell auch Platz. Die Bewegung selbst erfolgt zuerst mit den Sprechern, und mit diesen bleiben Worte auch im Gebrauch lebendig; gehen sie dann in die Umgangs- oder sogar Hochsprache ein, weitet sich ihr linguistischer Einfluss aus, sie werden beständiger, erscheinen fest verknüpft mit ihrer neuen Umgebung. Mitunter ist dann ihre Herkunft im Rückblick nicht mehr so ohne weiteres zu eruieren. Trotzdem bleiben solche Begriffe Indikatoren für ein Milieu, das zu einer anderen Zeit an einem anderen Ort bestand und das ihnen ihre erste Ursprünglichkeit eingeschrieben hat. Die deutschen Lehnwörter im Hebräischen sind hierfür ein gutes Beispiel.
משל [maschal] - Spruch, Gleichnis, Herrschaft, Prägung ... : über die Faszination einer Wurzel
(2018)
In dem 1792 veröffentlichten Aufsatz "Spruch und Bild, insonderheit bei den Morgenländern" entwickelt Johann Gottfried Herder eine Apologie der Spruchdichtung, die zwischen Poesie und Prosa, zwischen Volksdichtung und Kunstliteratur stehe und vor allem im 'Morgenland' - also bei den Persern, Arabern und Hebräern - in Blüte gestanden habe. [...] Dabei bezeichne jenes 'Wort' משל nicht nur Ursprung und Natur der Sprüche, sondern sogar den expressiven Charakter der menschlichen Sprache überhaupt, wie Herder mit einem Hamann-Zitat fortsetzt: "Poesie ist die Muttersprache des menschlichen Geschlechts [...]. Sinne und Leidenschaften verstehen nichts als Bilder." Sprüche, Bilder, Sinne, Leidenschaften - all das, so legt der Text nahe, bildet einen Zusammenhang, den Herder und auch andere gerne den des 'Ausdrucks' nennen, der hier aber "mit einem einzigen Wort" umrissen wird, eben mit dem Graphem משל, einem Ausdruck von 'Ausdruck'. Was 'bedeutet' dieser Ausdruck und was bedeutet es, diesen Ausdruck so in den Text einzufügen, wie Herder das tut?
Cell-free-synthesized voltage-gated proton channels: Approaches to the study of protein dynamics
(2018)
We often only realize how important health is when diseases manifest themselves through their symptoms and, ultimately, in a diagnosis. Over time, we suffer from many diseases starting with the first childhood disease to colds to gastrointestinal infections. Most diseases pass harmlessly and symptoms fade away. However, not all diseases are so harmless. Alzheimer’s disease, breast cancer, Parkinson’s disease, and colorectal cancer usually cause severe illness with high mortality rates. In pharmaceutical research, efforts are therefore being made to determine the molecular basis of them in order to provide patients with potential relief and, at best, healing. A special group of regulators, involved in the previously mentioned diseases, are voltage-gated proton channels. Thus, the understanding of their structure, function, and potential drug interaction is of great importance for humanity.
Voltage-gated proton channels are localized in the cell membrane. As their name indicates, they are controlled by voltage changes. Depolarization of the cell membrane induces conformational changes that open these channels allowing protons to pass through. Here, the transfer is based on a passive process driven by a concentration gradient between two individual compartments separated by the cell membrane. Voltage-gated proton channels are highly selective for protons and show a temperature- and pH-dependent gating behavior. However, little is known about their channeling mechanism. Previous experimental results are insufficient for understanding the key features of proton channeling.
In this thesis, for the first time, the cell-free production of voltage-sensing domains (VSD) of human voltage-gated proton channels (hHV1) and zebrafish voltage-sensing phosphatases (DrVSP) is described. Utilizing the cell free approach, parameters concerning protein stability, folding and labeling can be easily addressed. Furthermore, the provision of a membrane mimetic in form of detergent micelles, nanodiscs, or liposomes for co-translational incorporations of these membrane proteins is simple and efficient. Both VSDs were successfully produced up to 3 mg/ml. Furthermore, the cell-free synthesis enabled for the first time studies of lipid-dependent co-translational VSD insertions into nanodiscs and liposomes. Cell-free produced VSDs were shown to be active, and to exist mainly as dimers. In addition, also their activation was stated to be lipid-dependent, which has not been described so far. Solution-state NMR experiments were performed with fully and selectively labeled cell-free produced VSDs. With respect to the development of potential drug candidates, I could demonstrate the inhibition of the VSDs by 2-guanidinobenzimidazole (2GBI). Determined KD values were comparable to literature data for the human construct. For the first time, a low affinity for 2GBI of the zebrafish VSD could be described.
In future, the combination of a fast, easy and cheap cell-free production of fully or selectively labeled VSDs and their analysis by solution state NMR will enable structure determinations as well as inhibitor binding studies and protein dynamic investigations of those proteins. The results of these investigations will serve as a basis for example for the development of new drugs. In addition, a detailed description of the lipid-dependent activity might be helpful in controlling the function of voltage-gated proton channels in cancer cells and thereby reducing their growth or disturbing their cell homeostasis in general.
Es ist oft gesagt worden: Das Komische ist das Eigene des Menschen, nur der Mensch - und kein anderes Wesen - lacht. Begründet wurde dies häufig durch die Kennzeichnung des Menschen als Doppelwesen, das sich selbst widersprechen kann. Der Mensch gilt als Wesen, das gleichermaßen über einen Körper und einen Geist verfügt, als Wesen, das vom Zufall heimgesucht wird, aber auch zum Erhabenen fähig ist, oder als Wesen, das durch eine "individuelle[ ]" und eine "soziale[ ] Existenz" ausgezeichnet ist und deshalb "mit irgendeiner Norm" in Konflikt geraten kann. Jeweils ist es die Kollision der beiden Seiten, die nach den verschiedenen theoretischen Ansätzen zur Hervorbringung des komischen Phänomens führt und so - als Reaktion auf die Wahrnehmung des komischen Phänomens - das Lachen verursacht.
It may indeed seem that while the late 1970s and early 1980s were the period when theory was successfully established in western academic discourse, we have now entered an era "after theory" in which not only 'cultural theory' has come to an end but also a specific culture of theory has vanished from our seminars, departments, and universities: a culture of reflection, abstraction, and self-referentiality that had been at the heart of the humanities from the very beginning. And yet, theory is not so easily abolished but rather stored and maintained within each individual reading of a literary text in spite of empirical trends such as DH or pessimistic manifestos. Therefore, in what follows, Nicolas Pethes is interested in an additional aspect of the textual resistance of theory against the institutional resistance to theory: the relation between theory and practice, that is: the question whether acting is also one of the many languages of theory.
In recent years, the interest in theory which has once been a moving force of academic research in the field of literary studies appears to have decreased. The status of theory, its relevance and appropriateness for the understanding of literature have been put into doubt. Faced with this observation, some critics have even suggested that we have now entered into a new era of research which can retrospectively be identified as the era "after theory". Against the background of such pronouncements and to a certain extent in opposition to them, the investigations proposed here wish to uphold the idea of the utility and indeed the need for theoretical approaches to literature. To appreciate the status of theory and its possible contribution to a deepened understanding of literature, it is useful not to focus exclusively on the distinction or supposed divide between literature and theory. Instead we should pay attention to what links and unites them. This common ground or common denominator of literature and theory consists in the dimension of language. Furnishing, so to speak, the intellectual material from which both domains of articulation are formed, language constitutes at once the key element of literature and a principal concern of theory.
Die Bewertung der Nitrataustragsgefährdung (NAG) landwirtschaftlich genutzter Flächen in Wasserschutzgebieten (WSG) erfolgte bislang auf Basis bodenkundlicher Kartierungen und wurde seit 1996 nach einem im Staatsanzeiger für das Land Hessen veröffentlichten Merkblatt des ehemaligen Hessischen Landesamtes für Bodenforschung im Rahmen der Muster-Wasserschutzgebietsverordnung geregelt (HLfB 1996, HMUJFG 1996). Infolge der Verfügbarkeit hochauflösender Bodendaten in Form der „Bodenflächendaten 1: 5.000, landwirtschaftliche Nutzfläche“ (BFD5L) wird die Ermittlung der Nitrataustragsgefährdung landwirtschaftlich genutzter Flächen neu geregelt. Die BFD5L liefert Auswertungen der Bodenschätzungsdaten zur Feldkapazität des Wurzelraums sowie weiterer relevanter Parameter, die zur Bewertung der Nitrataustragsgefährdung herangezogen werden können.
Um die Eignung der BFD5L-Daten zur Ermittlung der Nitrataustragsgefährdung zu überprüfen, wurden in den Jahren 2009 bis 2012 bodenkundliche Vergleichskartierungen im Rahmen eines Pilotvorhabens im Wasserschutzgebiet Eschollbrücken/Pfungstadt in Südhessen, im Wassereinzugsgebiet der Quelle Meineringhausen bei Korbach, im Wasserschutzgebiet des Tiefbrunnens Spieß der Gemeinde Bad Emstal sowie im WSG Quelle Ohmes der Stadt Kirtorf durchgeführt. Ziel war es, die Umsetzungsmöglichkeiten bei der Nutzung der BFD5LDaten in organisatorischer und technischer Hinsicht zu erproben und das bisherige Verfahren zu überarbeiten (PETER & MILLER 2009, PETER & MILLER 2010a und 2010b, PETER & MILLER 2012).
Die Ergebnisse der Vergleichskartierungen zeigen, dass sich die Daten der BFD5L grundsätzlich für die Ermittlung der Nitrataustragsgefährdung in Wasserschutzgebieten eignen. Lediglich für Flächen, für die nach den bislang im System BFD5L enthaltenen Methoden keine Kennwerte abgeleitet werden können sowie für Sonderstandorte, muss die Nitrataustragsgefährdung durch bodenkundliche Geländearbeiten ermittelt werden.
Zielsetzung: Beteiligung von Medizinstudierenden im Rahmen der konzeptionellen Entwicklung eines zielgruppenspezifischen und attraktiven allgemeinmedizinischen Lehrangebots im ländlichen Raum.
Methodik: Es wurde ein Fragebogen entwickelt, der die Bewertung der Studierenden hinsichtlich des aktuellen Ablaufs ihres Studiums, den späteren Berufswunsch sowie die Anforderungen an ein zu entwickelndes allgemeinmedizinisches Schwerpunktprogramm im ländlichen Raum erfasst. Mittels einer Online-Befragung wurden im Sommer 2015 alle Medizinstudierende ab dem vierten vorklinischen Semester (n=2.150) der Goethe-Universität Frankfurt einmalig befragt. Die statistische Auswertung erfolgte primär deskriptiv. Die persönliche Einstellung hinsichtlich der Bereitschaft, als Hausarzt tätig zu werden, wurde auf statistische Signifikanz überprüft. Zudem wurde erhoben, ob ein messbarer Zusammenhang zwischen der eigenen Herkunft und dem späteren Wunscharbeitsort besteht.
Ergebnisse: Von insgesamt 2.150 kontaktierten Studierenden nahmen 617 an der Befragung teil (Rücklaufquote=28,7%). Die Ergebnisse repräsentieren eine große Bandbreite an Ideen und Anregungen, die sowohl die Meinung von Befürwortern als auch eher kritisch gegenüber der Lehre in der Allgemeinmedizin eingestellten Medizinstudierenden widerspiegeln. Von dem geplanten Schwerpunktprogramm erwarten die Studierenden einen starken Praxisbezug ebenso wie das Kennenlernen administrativer sowie wirtschaftlicher Hintergründe zum Führen einer Praxis.
Schlussfolgerungen: Durch die Einbeziehung der Zielgruppe am Entwicklungsprozess bestand die Möglichkeit, das zu entwickelnde Schwerpunktprogramm auf die späteren Teilnehmer passgenauer zuzuschneiden. Zudem ist zu erwarten, dass die Beteiligung der Studierenden zu einer höheren Akzeptanz des Programms führt. Die gewonnenen Ergebnisse zur Gestaltung eines Lehrangebots können als Orientierung für die mögliche Entwicklung ähnlicher Schwerpunktprogramme an anderen medizinischen Fakultäten dienen.
Aim: Participation of medical students in the conceptual development of targeted and attractive teaching content for rural areas.
Method: A questionnaire was developed to gather information on students' views of their current medical studies, career interests, and what requirements should be met by an optional rural health program in general practice. By means of an online survey in summer 2015, all medical students from the fourth preclinical semester onwards (n=2,150) at Goethe University Frankfurt were surveyed on one occasion. Statistical analysis was mainly descriptive. Personal attitudes towards a career as a family practitioner were examined for statistical significance. Further information was gathered on whether a measurable correlation exists between personal background and desired work location.
Results: Of the 2,150 students that were contacted, 617 participated in the survey (response rate=28.7%). The results covered a wide range of ideas and recommendations and were representative both of medical students with a positive attitude toward general practice, as well as those that were rather critical of teaching in general practice. The students expected the planned health program to be of strong practical relevance and to acquaint them with the administrative and economic aspects of running a practice.
Conclusions: By including the target group in the development process, it was possible to tailor the health program to meet the needs of future participants more precisely. Student participation can also be expected to result in greater acceptance of the program. The results on teaching content may also provide other medical faculties with orientation when developing comparable programs.
Wenn hier verhandelt wird, wie Florian Henckel von Donnersmarck im Drehbuch zu "Das Leben der Anderen" (2006) an den Plot eines britisch-französischen Filmklassikers anknüpft und an einen Roman aus der späten DDR, so hat das teils mit der herausgehobenen Stellung seines Erfolgswerks und seinen Selbstkommentaren zu tun, teils mit Überlegungen zur Intertextualitätsforschung. Beginnen wir mit den ersten beiden Aspekten und klären dann bei der Drehbuchanalyse die theoretischen Positionen. Vorausgeschickt sei nur, dass mit einem erweiterten Zitatbegriff gearbeitet wird, wie in der neueren Kulturwissenschaft üblich, und entsprechend einer Entwicklung im Kunstsystem seit den 1980er Jahren. Dort versteht man unter Zitieren längst nicht mehr nur die wörtliche Übernahme einer Textstelle, sondern jede beabsichtigte Bezugnahme eines Kunstwerks auf ein anderes, sei es aus der eigenen Sparte oder aus benachbarten: Akte künstlerischer Selbstreferenz. Mit der Erweiterung des Zitat- geht die des Textbegriffs einher, der hier Zeichensysteme in den Grenzen eines Einzelwerks meint, damit auch Bedeutungsträger eines Films. Als literaturwissenschaftlicher Beitrag zu verstehen ist das Folgende zum einen wegen der faktischen Aufwertung des Drehbuchs durch das konsekrationsfähige Verlagshaus Suhrkamp, zum anderen, wichtiger, weil wir den Film fast ausschließlich auf der Plot-, nicht auf der Bildebene betrachten.
Kann die Kunst dem Krieg etwas entgegensetzen? Lassen sich Kriege und Konflikte mit Kunst bekämpfen? Kann ein Kunstwerk das Denken seiner Betrachter beeinflussen und Frieden stiften? Hätte man die englische Künstlerin Evelyn De Morgan (1855-1919) gefragt, hätte sie diese Fragen sicherlich bejaht. Es sind gleich zwei Kriege, die sich in ihrem Schaffen niederschlugen: der zweite Burenkrieg (1899-1902) als letzter großer Krieg des British Empire und der Erste Weltkrieg (1914-1918), die Urkatastrophe des 20. Jahrhunderts. Auch wenn die Künstlerin weder Mutter noch Ehefrau eines Soldaten war, so war sie dennoch zu tiefst bewegt von den politischen Geschehnissen ihrer Zeit und verarbeitete diese in ihren Werken. ...
Vor rund 25 Jahren bemerkte David Wells in einem Aufsatz, in dem er die mittelalterliche Literatur hinsichtlich allegorischer Verfahren untersuchte, der Löwe in Hartmanns von Aue Iwein brülle geradezu nach seiner Interpretation. Ausführlich verzeichnet er die zuvor versuchten Deutungen, die sich bis zum Erscheinen des Aufsatzes im Jahre 1992 auf knapp 20 belaufen. Seine kleine Anmerkung illustriert die große Unsicherheit im interpretativen Umgang mit Dingen in der mittelalterlichen Literatur, aber ebenso ihr großes interpretatorisches Potential.
Was macht eine höfisch kultivierte Dame oder einen höfischen Ritter aus? Die mittelalterliche, von Frankreich ausgehende Artusepik antwortet auf diese Frage unter Bezug auf drei Komponenten, nämlich eine edle Abkunft (Geburtsadel), eine edle Gesinnung (Tugendadel) und einen gewissen höfischen Lebensstil, zu dem, ganz zentral, auch höfische Luxus- und Repräsentationsobjekte gehören, so etwa ritterliche Bewaffnung und kostbare Kleidung. Was passiert, wenn es an einer Harmonie von innen und außen öffentlich sichtbar mangelt und die Wirkungseinheit von Mensch und Repräsentationsobjekt zu Bruch geht, zeigt uns die mittelalterliche Erzählung vom schlecht geschnittenen Mantel, altfranzösisch: du mantel mautaillé. Sie nimmt in Frankreich des 13. Jahrhunderts (zwischen 1200 und 1210) ihren Anfang, und zwar in Gestalt des Lais (Le lay du cort mantel), einer kurzen Verserzählung keltischer Stoffe (lai narratif ), und verbreitet sich rasch in Europa.
Objektiviertes Begehren : zur Funktion und Bedeutung von Gegenständen in mittelhochdeutschen Mären
(2018)
Die in Mären dargestellten Handlungen konzentrieren sich auf einen spezifischen, außerordentlichen und in sich geschlossenen Fall, der sowohl Vorfall wie auch Zufall oder Rechtsfall sein kann. Didaktisches Substrat, schwankhaftes Erzählen und Exempelliteratur verschmelzen in dieser paargereimten Erzählform.
Dinge, denen besondere Eigenschaften oder Wirkungsweisen zugeschrieben werden, tauchen in der mittelalterlichen Literatur allenthalben auf. Sei es, dass sie einem anderweltlichen Bereich entstammen wie Siegfrieds Tarnkappe im Nibelungenlied oder der Paradiesstein im Alexanderroman, sei es, dass eigentlich 'gewöhnliche' Dinge in den Fokus der Erzählung rücken wie der Schmuck der Jeschute in Wolframs Parzival oder Brünhilds Gürtel - in bestimmten Konstellationen werden Dinge zu 'Mitspielern', deren handlungsdeterminierende Macht derjenigen der menschlichen Protagonisten um nichts nachsteht. Dass Dinge 'handeln', ist in den Texten des Mittelalters keine Seltenheit.
Das Ziel dieses Beitrags ist die Herausstellung von Geschlechterstereotypen der deutschen Jugendlichen, die in Form von semantischen Assoziationen zu Kategorien "Frau/Mann" auftreten, und der mit den Stereotypen verbundenen Asymmetrie. Dafür wurden die empirischen Daten, die infolge der Befragung mit dem Einsatz des psychoassoziativen Experimentes gewonnen wurden, analysiert. Die geschlechtsspezifische Asymmetrie wurde auch insubstantivischen Kollokationen, deren Basen als negativ gefärbte Substereotype eingeschätzt werden können, mit subordinierten Adjektiven verfolgt.
Kultur - Sprache - Gewalt
(2018)
Zum Verständnis der Gewalt dürfte der Versuch beitragen, einen prointuitiven, in der Natur der Sache begründeten Begriff zu konstruieren, dessen Wert in seinem erhöhten Erklärungspotenzial liegt. Im vorliegenden Text wird der Versuch vorgenommen, den Begriff "Gewalt" aus drei fundamentalen menschenkonstitutiven Faktoren abzuleiten, der es ermöglicht, die Gewalt aus der Sicht des Betroffenen systematisch zu beschreiben und erklären. In die Erörterungen werden Kultur und Sprache involviert und innerhalb von drei Subthemen - Interpretation und Gewalt, sprachliche Ordnung und Gewalt, soziale Interaktion und Gewalt - wird ihre Einbeziehung in die "Welt der Gewalt" aus besonderen Perspektiven ins Visier genommen.
By the fabrication of periodically arranged nanomagnetic systems it is possible to engineer novel physical properties by realizing artificial lattice geometries that are not accessible via natural crystallization or chemical synthesis. This has been accomplished with great success in two dimensions in the fields of artificial spin ice and magnetic logic devices, to name just two. Although first proposals have been made to advance into three dimensions (3D), established nanofabrication pathways based on electron beam lithography have not been adapted to obtain free-form 3D nanostructures. Here we demonstrate the direct-write fabrication of freestanding ferromagnetic 3D nano-architectures. By employing micro-Hall sensing, we have determined the magnetic stray field generated by our free-form structures in an externally applied magnetic field and we have performed micromagnetic and macro-spin simulations to deduce the spatial magnetization profiles in the structures and analyze their switching behavior. Furthermore we show that the magnetic 3D elements can be combined with other 3D elements of different chemical composition and intrinsic material properties.
In the current contribution we present a comprehensive study on the heteronuclear carbonyl complex H2FeRu3(CO)13 covering its low energy electron induced fragmentation in the gas phase through dissociative electron attachment (DEA) and dissociative ionization (DI), its decomposition when adsorbed on a surface under controlled ultrahigh vacuum (UHV) conditions and exposed to irradiation with 500 eV electrons, and its performance in focused electron beam induced deposition (FEBID) at room temperature under HV conditions. The performance of this precursor in FEBID is poor, resulting in maximum metal content of 26 atom % under optimized conditions. Furthermore, the Ru/Fe ratio in the FEBID deposit (≈3.5) is higher than the 3:1 ratio predicted. This is somewhat surprising as in recent FEBID studies on a structurally similar bimetallic precursor, HFeCo3(CO)12, metal contents of about 80 atom % is achievable on a routine basis and the deposits are found to maintain the initial Co/Fe ratio. Low temperature (≈213 K) surface science studies on thin films of H2FeRu3(CO)13 demonstrate that electron stimulated decomposition leads to significant CO desorption (average of 8–9 CO groups per molecule) to form partially decarbonylated intermediates. However, once formed these intermediates are largely unaffected by either further electron irradiation or annealing to room temperature, with a predicted metal content similar to what is observed in FEBID. Furthermore, gas phase experiments indicate formation of Fe(CO)4 from H2FeRu3(CO)13 upon low energy electron interaction. This fragment could desorb at room temperature under high vacuum conditions, which may explain the slight increase in the Ru/Fe ratio of deposits in FEBID. With the combination of gas phase experiments, surface science studies and actual FEBID experiments, we can offer new insights into the low energy electron induced decomposition of this precursor and how this is reflected in the relatively poor performance of H2FeRu3(CO)13 as compared to the structurally similar HFeCo3(CO)12.
Fabrication of three-dimensional (3D) nanoarchitectures by focused electron beam induced deposition (FEBID) has matured to a level that highly complex and functional deposits are becoming available for nanomagnetics and plasmonics. However, the generation of suitable pattern files that control the electron beam’s movement, and thereby reliably map the desired target 3D structure from a purely geometrical description to a shape-conforming 3D deposit, is nontrivial. To address this issue we developed several writing strategies and associated algorithms implemented in C++. Our pattern file generator handles different proximity effects and corrects for height-dependent precursor coverage. Several examples of successful 3D nanoarchitectures using different precursors are presented that validate the effectiveness of the implementation.
Three-dimensional (3D) nanomagnetism, where spin configurations extend into the vertical direction of a substrate plane allow for more complex, hierarchical systems and the design of novel magnetic effects. As an important step towards this goal, we have recently demonstrated the direct-write fabrication of freestanding ferromagnetic 3D nano-architectures of ferromagnetic CoFe in shapes of nano-tree and nano-cube structures by means of focused electron beam induced deposition. Here, we present a comprehensive characterization of the magnetic properties of these structures by local stray-field measurements using a high-resolution micro-Hall magnetometer. Measurements in a wide range of temperatures and different angles of the externally applied magnetic field with respect to the surface plane of the sensor are supported by corresponding micromagnetic simulations, which explain the overall switching behavior of in part rather complex magnetization configurations remarkably well. In particular, the simulations yield coercive and switching fields that are in good quantitative correspondence with the measured coercive and switching fields assuming a bulk metal content of 100 at % consisting of bcc Co 3 Fe. We show that thermally-unstable magnetization states can be repetitively prepared and their lifetime controlled at will, a prerequisite to realizing dynamic and thermally-active magnetic configurations if the building blocks are to be used in lattice structures.
Der Band untersucht die Ursachen, Ausprägungen und Reaktionen auf die Entstehung bzw. Erstarkung populistischer Parteien und Bewegungen in Deutschland und Ostmitteleuropa.
Inhaltsverzeichnis:
Arthur Benz: Populismus als Herausforderung für Wissenschaft und Praxis - Einleitung
Dirk Jörke: Populismus – Ursachen und falsche Antworten
Michael Edinger: Mobilisierung gegen das Establishment. Zu einem Wesensmerkmal populistischer Strömungen
Claudia Landwehr und Nils D. Steiner: Populismus – eine Nachfrageperspektive
Joachim Klose: Ein Land, zwei Perspektiven? Zum Populismusin Ost- und Westdeutschland
Petra Guasti und Lenka Buštíková: Populismus in Ostmitteleuropa und der Verzicht auf Politik
Remnants Restante Reste
(2018)
Her poems are as subtle and intimately telling as the differences between the three languages in which she writes and battles to live and dream. These verses touch and tug at one another like the Afrikaans of her childhood, the German of her husband and the South African English of her homeland. They agree to differ in all sorts of nuanced ways.
Im Mittelpunkt Deutsch
(2018)
This paper deals with German 'wobei'-clauses and their Italian counterparts. Based on a corpus study of administrative texts, we identify the type and frequency of the Italian constructions that correspond to 'wobei'-clauses. In particular, we will assess to what extent the Italian converb construction gerundio correlates with 'wobei'-clauses. More specifically, we will focus on the thesis put forward by Haspelmath (1995) and Breindl (2014), according to which comitativity is expressed by converb constructions when it applies to state of affairs.
'Je-desto'-Sätze scheinen in struktureller Hinsicht Einzelgänger zu sein. Das Ungewöhnliche ist, dass sie wie eine obligatorische Verb-dritt-Konstruktion daherkommen: An erster Stelle steht scheinbar der durch je eingeleitete Nebensatz im linken Außenfeld bzw. Vor-vor-Feld, dann folgt die desto-Konstituente, die das Vorfeld einnimmt, und dann an dritter Stelle das finite Verb des Matrixsatzes. Angesichts der Semantik der involvierten Konstituenten ist diese Strukturbeschreibung ungewöhnlich und widerspricht plausiblen Erwartungen. Der Aufsatz bietet eine Analyse, nach der der 'je'-Satz und die 'desto'-Konstituente zusammen eine komplexe Konstituente bilden, die eine einzige, ganz reguläre Einheit konstituiert, was bedeutet, dass der Gesamtsatz eine ziemlich reguläre Verb-zweit-Struktur ist.
Botsotso 18: Poetry
(2018)
Se registra por primera vez el ácaro rojo de las palmas, Raoiella indica Hirst (Acari: Tenuipalpidae), en Guatemala. Este ácaro invasivo se encontró en los departamentos de Petén e Izabal infestando palma de coco (Cocos nucifera), palma de Navidad (Adonidia merrillii) y palmera robeleni (Phoenix roebelenii).
Vorhofflimmern entsteht unter anderem durch ein Ungleichgewicht zwischen sympathischem und parasympathischem autonomen Nervensystem. Sowohl invasive Ansätze via Ablation oder Denervierung als auch minimalinvasive Ansätze via Elektrostimulation liefern erfolgsversprechende Ergebnisse in Bezug auf Beeinflussung eines bestehenden Vorhofflimmerns.
Interessanterweise konnte durch Akupunktur des Tragus eine Reduktion von Vorhofflimmer-Rezidiven nach Kardioversion erreicht werden. Ziel dieser Studie war die Evaluation von Akupunktur-induzierten kardialen (vegetativen) Effekten bei gesunden Probanden.
Herzgesunde männliche Probanden (n=24) wurden im Bereich des Vagus-Innervationsgebietes an der Concha inferior des Ohres (Herzpunkt 100, OHR) sowie an einem klassischen Akupunktur-Punkt des Herzens (ventralen Unterarm, P6/Neiguan, ARM) akupunktiert. Eine „Placebo“-Akupunktur eines Punktes, der gegen Gonarthrose-Schmerzen helfen soll (Magenpunkt 35), diente als Kontrolle. Die Hälfte der Probanden erhielt eine zusätzliche Messung ohne Akupunktur, um Effekte durch das alleinige Platzieren einer Nadel zu untersuchen.
Um eine Aktivierung des ANS zu bewirken und Veränderungen quantifizieren zu können, wurden 12-Kanal Langzeit-EKG Messungen wie folgt durchgeführt: 30 Minuten (min) in liegender Position unter Akupunktur, Entfernung der Akupunkturnadel, 5 min liegend, 5 min sitzend, 5 min stehend, 5 min sitzend.
Es erfolgten Analysen folgender Parameter der Herzfrequenzvariabilität: Herzfrequenz, SDNN, RMSSD, HF, LF, LF/HF. Des Weiteren wurden Periodic Dynamics Repolarization und Deceleration Capacity untersucht.
Verglichen mit Placebo-Akupunktur wurde sowohl durch Akupunktur am OHR als auch am ARM die Herzfrequenz in liegender und sitzender Körperpositionen signifikant gesenkt (Phasen 30L, 5S1, 5S2, ∆5L-5S1, ∆5S1-5ST).
Während die Akupunktur am OHR vor allem die SDNN signifikant erhöhte, führte die Akupunktur am ARM zu einer signifikanten Steigerung von RMSSD und dem parasympathischen Leistungsdichtespektrum-Parameter HF. Der Quotient LF/HF wurde ebenfalls signifikant gesenkt.
Kein Unterschied bestand zwischen Placebo-Akupunktur und Messung ohne Akupunktur, sodass postuliert werden kann, dass das alleinige Platzieren einer Nadel keinen nennenswerten Effekt auf das autonome Nervensystem besitzt.
Die Ergebnisse der Studie zeigen, dass eine Akupunktur an Orten, die mit dem autonomen Nervensystem verschaltet sind, zu einer Modulation des parasympathischen kardialen autonomen Nervensystems führen kann.
Eine Modulation der parasympathisch-sympathischen Balance durch minimalinvasive Zusatzbehandlung, wie in unserer Studie, könnte möglicherweise bei Patienten mit Vorhofflimmern zusätzlich zu medikamentöser oder nach invasiver Behandlung wie der Pulmonalvenenisolation das Therapieresultat verbessern und die Rezidivrate verringern.
This article pinpoints the double being and doing of weapons, warriors and warrior fraternities as quite possibly a characterising trait from the onset of the Corded Ware period well into the mature Bronze Age and beyond. Exquisitely crafted weapons of bronze – many spirited with a life-energy of their own – were used to wage war and sometimes to hack victims into pieces with strong indications that the beautiful warrior with his trained well-groomed body was capable of extreme violence. The companionship of warrior peers in the fraternity was a social construct enabling effective waging of war as well as fulfilling other roles in Bronze Age society, contributing to rituals and social interaction.
Dass Venedig in Hofmannsthals Komödien nicht nur eine beliebte Kulisse, sondern auch einen zentralen sowie ausdrücklich 'literarischen' Themenkomplex darstellt, davon zeugt nicht zuletzt der Umstand, dass Hofmannsthal bestimmende Anregungen zur Komödiendichtung um 1907 gerade vom Venezianer Carlo Goldoni bekommt; Goldonis Komödien hinterlassen auch später im Werk Hofmannsthals deutliche Spuren. Tatsächlich ist die neuzeitliche europäische Komödientradition, die auf die Commedia dell'Arte zurückgeht und sich dann im 18. Jahrhundert in Goldonis Theaterreform weiterentwickelt, für Hofmannsthal neben dem Wiener Volkstheater prägend gewesen.
In den 1980er Jahren ist Roger Bauer zum ersten Mal den Bezügen von Hofmannsthals Komödien zur venezianischen Tradition nachgegangen und hat sich dabei nicht zuletzt mit Goldoni beschäftigt. Doch seitdem hat die Forschung den Themenkomplex Hofmannsthal und Goldoni nur wenig beachtet. An Bauers Studien anknüpfend, nimmt sich dieser Aufsatz vor, das wichtige Thema weiterzuverfolgen, wobei ein besonderes Augenmerk auf "Cristinas Heimreise" liegen soll.
Resilienz
(2018)
Im 'Posthistoire', so kann man wohl feststellen, wird die Aufgabe der Abblendung sozialer Risiken von Begriffen übernommen, die dem weiten Feld ökologischer Debatten entnommen sind. In diesem Sinne hat Norbert Bolz unlängst die inflationäre Rede von 'Nachhaltigkeit' oder 'sustainability' analysiert. [...] Die Übertragung des Begriffs der Nachhaltigkeit aus dem Bereich der Forstwirtschaft in den Bereich gesellschaftspolitischer Debatten hat ihren Grund in der utopischen Aufladung ökologischer Ansätze in den Natur- und Ingenieurswissenschaften seit den sechziger Jahren. Das von Bolz benannte Problem ist also nicht allein eines der politischen Rhetorik, sondern darüber hinaus das einer zunehmend undeutlicher werdenden epistemischen Differenz von Natur und Gesellschaft. Dies schlägt sich in der Verwendung von Begriffen nieder, die gleichermaßen natürliche und soziale Prozesse zu beschreiben vermögen und sich dabei zugleich als wirkmächtige Metaphern für die Programmatiken eines soziotechnisch ausgerichteten Regierens anbieten. Exemplarisch lässt sich dies am Begriff der 'Resilienz' studieren.
Die hier zu besprechende Monographie "Mensch und Landschaft im südwestlichen Latium in der römischen Antike" stellt die leicht überarbeitete Fassung der Dissertation von Michael Teichmann (im Folgenden T.) dar, die er im Winter 2016/17 an der Christian-Albrechts-Universität zu Kiel am Institut für Geoarchäologie eingereicht hat. Der Phoibos Verlag strebt mit der Serie "Phoibos Humanities Series" eine Doppelstrategie an und vertreibt das Werk sowohl als gedrucktes Buch (89 €) wie auch als E-Book (59 €). Möglicherweise erklärt sich so der Verzicht auf einen Index, da das maschinenlesbare E-Book einen solchen theoretisch überflüssig macht. Da der Rezensent mit dem gedruckten Buch gearbeitet hat, fiel das Fehlen eines Indexes doch negativ ins Gewicht. ...
Der hier zu besprechende Sammelband ist das Begleitbuch zu einer Ausstellung der Abguss-Sammlung des Instituts für Klassische Archäologie der Freien Universität Berlin zum Thema "Realismen in der griechischen Plastik", die von Februar bis Juli 2018 dort zu sehen war. Die Ausstellung war aus Lehrveranstaltungen der beiden Herausgeber hervorgegangen und folgte damit bekannten Vorgängern vergangener Jahrzehnte, deren begleitende Kataloge geradezu Handbuchstatus erlangt haben. ...
Neuronal calcium signals propagating by simple diffusion and reaction with mobile and stationary buffers are limited to cellular microdomains. The distance intracellular calcium signals can travel may be significantly increased by means of calcium-induced calcium release from internal calcium stores, notably the endoplasmic reticulum. The organelle, which can be thought of as a cell-within-a-cell, is able to sequester large amounts of cytosolic calcium ions via SERCA pumps and selectively release them into the cytosol through ryanodine receptor channels leading to the formation of calcium waves. In this study, we set out to investigate the basic properties of such dendritic calcium waves and how they depend on the three parameters dendrite radius, ER radius and ryanodine receptor density in the endoplasmic membrane. We demonstrate that there are stable and abortive regimes for calcium waves, depending on the above morphological and physiological parameters. In stable regimes, calcium waves can travel across long dendritic distances, similar to electrical action potentials. We further observe that abortive regimes exist, which could be relevant for spike-timing dependent plasticity, as travel distances and wave velocities vary with changing intracellular architecture. For some of these regimes, analytic functions could be derived that fit the simulation data. In parameter spaces, that are non-trivially influenced by the three-dimensional calcium concentration profile, we were not able to derive such a functional description, demonstrating the mathematical requirement to model and simulate biochemical signaling in three-dimensional space.
Continuous blood glucose monitoring reveals enormous circadian variations in pregnant diabetic rats
(2018)
Aim: Diabetes in pregnancy is a major burden with acute and long-term consequences. Its treatment requires adequate diagnosis and monitoring of therapy. Many experimental research on diabetes during pregnancy has been performed in rats. Recently, continuous blood glucose monitoring of non-pregnant diabetic rats revealed an increased circadian variability of blood glucose that made a single blood glucose measurement per day inappropriate to reflect glycemic status. Continuous blood glucose measurement has never been performed in pregnant rats. We wanted to perform continuous blood glucose monitoring in pregnant rats to decipher the influence of pregnancy on blood glucose in diabetic and normoglycemic status.
Methods: We used the transgenic Tet29 diabetes rat model with an inducible knock down of the insulin receptor via RNA interference upon application of doxycycline (DOX) leading to insulin resistant type II diabetes. All Tet29 rats received a HD-XG telemetry implant (Data Sciences International, USA) that measured blood glucose and activity continuously. Rats were divided into four groups and blood glucose was monitored until end of pregnancy or the corresponding period: Tet29 + DOX (diabetic) non-pregnant, Tet29 + DOX (diabetic) pregnant, Tet29 (normoglycemic) non-pregnant, Tet29 (normoglycemic) pregnant.
Results: All analyzed rats displayed a circadian variation in blood glucose concentration. Circadian variability was much more pronounced in pregnant diabetic rats than in normoglycemic pregnant rats. Pregnancy ameliorated variation in blood glucose in diabetic situation. Pregnancy continuously decreased blood glucose during normoglycemic pregnancy. Diabetic rats were less active than normoglycemic rats. We performed a calculation showing that application of continuous blood glucose measurement reduces animal numbers needed to detect a given effect in experimental setting by decreasing variability and SD.
Interpretation: Continuous blood glucose monitoring via a telemetry device in pregnant rats provides a more informative picture of the glycemic situation in comparison to single measurements. This could improve diagnosis and therapy of diabetes, decrease animal numbers within experimental settings, and add another physiological parameter (activity) to the analysis that could be helpful in testing therapeutic concepts targeting blood glucose levels and peripheral muscle function. We propose continuous glucose monitoring as a new tool for the evaluation of pregnant diabetic rats.
NeoBiota, Volume 38 (2018)
(2018)
NeoBiota, Volume 37 (2018)
(2018)
The genetic mutation of the coagulation factor VIII (fVIII) results in a defective or missing protein, leading to a malfunctioning blood coagulation. The resulting disease is called hemophilia A. Depending on the severity of the mutation, affected patients experience an increased risk of pathologic bleeding after minor trauma or even sudden bleeding events. Substitution therapies with extrinsic fVIII exist using plasmatic or recombinant fVIII products. Due to an insufficient immune tolerance towards substituted fVIII, about 30 % of patients develop allogenic neutralizing antibodies (inhibitors) against substituted fVIII products. The gold standard of treating inhibitors is the immune tolerance induction (ITI), where patients are given frequent, high doses of fVIII to induce an immune tolerance. ITI therapy fails in about 30 % of patients. Mechanisms of action of ITI are part of research, as insufficient knowledge about mechanisms and prognostic factors complicate treatment. For example, the development of anti-idiotypic antibodies, which occur naturally as a regulatory mechanism of the immune system, are being studied. Such anti-idiotypes have been detected in immunoglobuline preparations and in patients after successful ITI.
Inhibitors interfere with fVIII function in coagulation by binding functional epitopes within fVIII domains. Inhibitors against the A2 and C2 domain are predominantly found, however also the C1 domain has been shown to be highly immunogenic in some patients. The polyclonality of inhibitors aggravates the understanding and treatment of these. The present project therefore focusses on the selection of synthetic anti-idiotypic antibodies to target inhibitors in patients. The phage display method was applied to, for one, isolate anti-idiotypic single chain variable fragments (scFvs) specific against human polyclonal anti-fVIII antibodies and second against two C1 domain-specific inhibitory monoclonal antibodies (mAbs).
In the first project, anti-fVIII antibodies were purified from human plasma to serve as target molecules. A previous project showed that using full plasma as a target did not yield anti-idiotypic antibodies from phage display. For the purification, protein A chromatography and fVIII coupled Affi Gel® chromatography were applied. The isolated antibodies were next used as targets for the selection of anti-idiotypic scFvs. Analysis revealed that none of the selected phages solely bound the anti-fVIII antibody target. Consequently, the test protocol was modified, which resulted in a reduction of unspecific binders. Yet, no target-specific binders were isolated from phage pools. Reason for this may have been the high diversity of the polyclonal antibody target and the limited diversity of the phage libraries.
The aim of the second project, was the selection and characterization of scFvs, that target the paratopes of C1 domain-specific mAbs GMA8011 and LE2E9. From a therapeutic viewpoint, the preparation of an anti-idiotypic antibody pool, tailored to each patient’s inhibitor population, could help neutralize inhibitors in patients. Ultimately, one GMA8011-specific scFv-carrying phage clone (H2C1) and two specifics to LE2E9 (H3G7, H3F10) were isolated. In further experiments, only the GMA8011-specific scFv showed competitive behavior in presence of fVIII, pointing towards an anti-idiotypic binding to the inhibitor paratope. The LE2E9-specific scFvs did not prevent binding of the inhibitor to fVIII. Hence, no anti-idiotypic behavior could be determined. For further characterization, selected scFvs were genetically fused to Fc antibody fragments and recombinantly produced. In this antibody format, all three scFvs showed concentration dependent binding to the target and the isotype control. The binding specificity to the target, observed in phage context, could not be reproduced. Competition experiments with fVIII confirmed that none of the scFvs bound the paratope of their target inhibitor.
The selection of anti-idiotypic scFvs from phage display libraries proves to be effortful. Polyclonal anti-fVIII antibodies purified from hemophilic plasma appear to be unsuitable as a target for phage display, likely due to the high diversity of the target molecules. Furthermore, the preparation of an individualized anti-idiotypic pools for patients by selecting scFvs against single inhibitory mAbs proves to be difficult. The selection of scFvs against anti-C1 inhibitors GMA8011 and LE2E9 produced three promising scFv-carrying phages. However, analysis could not detect anti-idiotypic behavior. Further research with inhibitors, monoclonal and polyclonal, and anti-idiotypic antibodies should be performed to bring better insight into the highly complex paratope-epitope interaction.
The Hultschin (Hlučín) region - now part of the Czech Republic - was annexed to the former Czechoslovakia in 1920. Throughout the centuries, its turbulent history has been shaped by various conflicting power interests, which have influenced the co-existence of the Czech and German communities which historically lived alongside each other. The Polish and Jewish communities had a relatively minor influence over the culture of this polylingual region, but the large German minority played a significant role. The influence of German language, culture and customs was not only visible in the political and economic life of the local population; it was also reflected in the various clubs and associations that were active in the region.
Im Grunde begann alles wie im Märchen: Es war einmal ein sehr reicher Mann. Er hieß Eugen Esslinger und war ein gütiger, feingliedrig gebauter Mensch. Zwar empfand er sich als kränklich, war aber äußerst reisefreudig (er bestieg sogar das Matterhorn!) und interessierte sich für Kunst. Eugen Esslinger wurde 1871 als Sohn wohlhabender jüdischer Eltern geboren. Bis zum Ersten Weltkrieg brauchte er keinem Beruf nachzugehen, weil er ein außerordentlich großes Vermögen erbte. Was ihm fehlte, war eine Frau. "Eine brave Frau werde ich haben! Comme tout le monde - nicht ganz. - Hübsch soll sie sein, von den Klügeren und fein musikalisch muß sie sein - Also nicht mehr Künstlerin und Frauenrechtlerin, etc." Eugen Esslinger war homosexuell. Eine Ehe, so glaubte er, würde diesen Makel tilgen. Nach jahrelangem Suchen fand er die passende Frau. Es war Emilie ("Mila") Rauch, geboren 1886 als uneheliches Kind in Linz (ihre Mutter war Witwe, der Vater war ihr unbekannt).
The paper illustrates based on an example the importance of consistency between the empirical measurement and the concept of variables in estimated macroeconomic models. Since standard New Keynesian models do not account for demographic trends and sectoral shifts, the authors proposes adjusting hours worked per capita used to estimate such models accordingly to enhance the consistency between the data and the model. Without this adjustment, low frequency shifts in hours lead to unreasonable trends in the output gap, caused by the close link between hours and the output gap in such models.
The retirement wave of baby boomers, for example, lowers U.S. aggregate hours per capita, which leads to erroneous permanently negative output gap estimates following the Great Recession. After correcting hours for changes in the age composition, the estimated output gap closes gradually instead following the years after the Great Recession.
All lifeforms have to sense changes in their environment and adapt to possibly detrimental conditions. On a cellular level, the highly elaborate proteostasis network (PN) consisting of housekeeping and stress-induced proteins, confers this tolerance against stress and maintains cellular protein homoestasis. This is essential for survival, as an accumulation of stress-induced protein aggregation will eventually affect the functionality of crucial cellular components and ultimately lead to cell death. The guardians of this balance are the molecular chaperones and their activity-regulating co-haperones. They are engaged in all aspects of protein biogenesis, maintenance and degradation, especially during stress.
The heat shock proteins (HSPs) are the major chaperones in mammals and encompass constitutive and stress-induced isoforms. Among them, the HSP70 and the HSP90 family are the most abundant HSPs and their activity is involved in a great variety of homoestasis and stress-induced tasks.
As part of the protein triage the E3 ligase CHIP (C-terminal HSC70-interacting protein) is an essential activity regulating co-chaperone of HSP70 and HSP90 which provides a link between chaperone mediated protein-folding and various degradation pathways. Due to its decisive function, CHIP is involved in a wide array of cellular processes, especially in clearing misfolded HSP70 client proteins that are prone to aggregate. As a consequence, CHIP was reported to confer protection against many aggregation-induced pathologies of the neuronal system. Additionally, CHIP has been identified as a critical factor in various types of cancer and is implied to affect the development and the longevity of mammals.
Despite the significant progress in the understanding of CHIP’s structure and function, many aspects surrounding its chaperone dependency and its substrate recognition remain unclear. Moreover, due to the variety of substrates in diverse cellular pathways, there are yet many connections to elucidate between CHIP and components of the cellular proteostasis network.
The work of this thesis was focused on the role of CHIP in acute stress response and the corresponding status of chaperone association. Moreover, it was investigated if CHIP, as the connecting ligase of folding and degradation systems, might also provide a link between the PN and the reorganisation of the cellular architecture upon stress exposure.
This has become of increasing interest as recent reports highlight the importance of spatial sequestration in protein quality control.
To this end, subcellular distribution of CHIP was analysed by live-cell microscopy during heat stress. It became obvious that during the heat-induced challenge of the chaperone system, CHIP migrated to new cellular sites. Further experiments suggested that the observed migration to the plasma membrane is a chaperone-independent process and in vitro reconstitution of membrane association confirmed the competitive nature of membranes and chaperones for CHIP binding. A detailed in vivo and in vitro analysis of the newly observed membrane association of CHIP revealed a distinct lipid specificity and a novel direct association with lipids. Binding experiments with recombinantly purified deletion mutants of CHIP identified the TPR domain and a positive patch in the coiled-coil domain as main determinants for the lipid association. Through biochemical and biophysical approaches, the structural integrity and functionality of CHIP upon membrane binding was confirmed and further characterised.
Moreover, mass spectrometry analysis provided a high confidence identification of chaperone-free interactors of CHIP at the plasma membrane and other membranous compartments.
In accordance with the lipid specificity, the Golgi apparatus was one of these sites. Only chaperone-free CHIP had a significant effect on the morphology of the organelle, again confirming the competitive role of chaperones and lipids. With respect to the physiological consequences of the changed localisation of CHIP, preliminary results indicated increased cell death when the ligase localises to cellular membranes. The results lead to the conclusion that CHIP acts as an initiator of early stress adaptation and as a sensor for the severity and strength of the stress reaction.
Reactive oxygen species (ROS) are involved in various signalling mechanisms. Redox homeostasis is important in cancer cells, since they are dependent on upregulated antioxidant defence pathways to cope with elevated ROS levels. Therefore, targeting the antioxidant defence system and/ or increasing ROS to a lethal level may be a feasible strategy to counteract cancer cell progression.
Acute lymphoblastic leukaemia (ALL) is the most frequent malignant childhood cancer, displaying on one side resistance to cell death induction and on the other side elevated ROS levels. Therefore, inducing ferroptosis, a ROS- and iron-dependent cell death pathway might be useful to trigger cell death in ALL as a novel treatment strategy. In the first study of this thesis we observed that RSL3, a glutathione (GSH) peroxidase 4 (GPX4) inhibitor, triggered ROS accumulation and lipid peroxidation which contributed to ferroptotic cell death. These observations were based on suppression of RSL3 stimulated cell death using different ferroptosis inhibitors like Ferrostatin-1 (Fer-1), Liproxstatin-1 (Lip-1), as well as iron chelator Deferoxamine (DFO) and the vitamin E derivate α-Tocopherol (α-Toc). RSL3-triggered ROS and lipid peroxide production were also inhibited through Fer-1 and α-Toc. Furthermore, lipoxygenases (LOX) were activated upon RSL3 stimulation and contributed to ferroptotic cell death in ALL as well. Selective inhibition of LOX with the 12/15-LOX inhibitor Baicalein and the pan-LOX inhibitor nordihydroguaiaretic acid (NDGA) abolished RSL3-induced ROS production, lipid peroxidation and cell death. In addition, RSL3 induced lipid peroxide-dependent ferroptotic cell death in FAS-associated Death Domain (FADD)-deficient, death receptor-induced apoptosis resistant cells, demonstrating that ferroptosis might circumvent apoptosis resistance.
The second part of the study revealed that RSL3 and Erastin (Era), a GSH-depleting agent, inhibiting the cystine/glutamate antiporter system xc- and ferroptosis inducer, cooperated with the Smac mimetic BV6 to trigger cell death in ALL cells. RSL3/BV6 and Era/BV6 combination-induced cell death was dependent on ROS accumulation, but independent of caspases and key modulators of necroptosis. RSL3/BV6-treated ALL cells exhibited classical features of ferroptotic cell death with iron-dependency, ROS accumulation and lipid peroxidation which was diminished through either pharmacological inhibition (Fer-1, DFO, α-Toc) or genetic inhibition by overexpressing GPX4. Interestingly, Era/BV6-induced cell death in ALL cells was independent of iron but dependent on ROS accumulation, since α-Toc rescued from Era/BV6-triggered ROS production, lipid peroxidation and cell death. Moreover, inhibition of lipid peroxide formation through the addition of Fer-1 or by overexpressing GPX4 failed to rescue from Era/BV6-triggered cell death, even if Era/BV6-stimulated lipid peroxidation was diminished. Likewise, Fer-1 protected from RSL3/BV6-, but not from Era/BV6-generated ROS production, leading to the assumption that other ROS besides lipid-based ROS contributed to cell death in Era/BV6-treated cells. In summary, while RSL3/BV6 induced ferroptosis in ALL, Era/BV6 stimulated a ROS dependent cell death, which was neither dependent on iron nor caspases or receptor-interacting protein (RIP) kinase 1 nor 3. Additionally, using Erastin alone did not trigger ferroptotic cell death in ALL. Finally, with these two studies we tried to unravel the molecular pathway of ferroptosis by using RSL3 and Erastin as well described ferroptosis stimulators. Here, we demonstrate the possibility of a novel treatment strategy to reactivate programmed cell death by impeding redox homeostasis in ALL.
Since ALL failed to induce ferroptosis upon Erastin treatment, we investigated in the third part of this thesis a new model system to induce ferroptosis upon Erastin and RSL3 exposure. Previous studies revealed that rhabdomyosarcoma (RMS) cells might be susceptible to oxidative stress-induced compounds. To this end, we used Erastin as a prototypic ferroptosis stimulus and GSH-depleting agent and demonstrated that GSH depletion, ROS and lipid ROS accumulation contributed to cell death. Additionally, Fer-1, Lip-1, DFO, lipophilic vitamin E derivate α-Toc and GSH, a cofactor of GPX4, protected from Erastin stimulated ROS accumulation, lipid peroxidation and cell death. Also, the use of a broad spectrum protein kinase C (PKC) inhibitor Bisindolylmaleimide I (Bim1), a PKCα and ß selective inhibitor Gö6976 and siRNA-mediated knockdown of PKCα suppressed Erastin-mediated cell death in RMS. Moreover broad spectrum nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase (NOX) inhibitor Diphenyleneiodonium (DPI) and a more selective NOX1/4 isoform inhibitor GKT137831 abrogated Erastin-generated ROS formation, lipid peroxidation and cell death. With this, we demonstrate that RMS are vulnerable to ferroptotic cell death and investigated the molecular mechanism of ferroptosis by unravelling that PKC and NOX could have a pivotal role in ROS-mediated ferroptosis signalling in RMS. In this regard, ferroptosis inducers may act as a possible novel treatment strategy for RMS, especially those with poor clinical outcome.
The authors relax the standard assumption in the dynamic stochastic general equilibrium (DSGE) literature that exogenous processes are governed by AR(1) processes and estimate ARMA (p,q) orders and parameters of exogenous processes. Methodologically, they contribute to the Bayesian DSGE literature by using Reversible Jump Markov Chain Monte Carlo (RJMCMC) to sample from the unknown ARMA orders and their associated parameter spaces of varying dimensions.
In estimating the technology process in the neoclassical growth model using post war US GDP data, they cast considerable doubt on the standard AR(1) assumption in favor of higher order processes. They find that the posterior concentrates density on hump-shaped impulse responses for all endogenous variables, consistent with alternative empirical estimates and the rigidities behind many richer structural models. Sampling from noninvertible MA representations, a negative response of hours to a positive technology shock is contained within the posterior credible set. While the posterior contains significant uncertainty regarding the exact order, the results are insensitive to the choice of data filter; this contrasts with the authors’ ARMA estimates of GDP itself, which vary significantly depending on the choice of HP or first difference filter.
nzidenz und Mortalität von Gebärmutterhalskrebs (C53 nach ICD-10) müssen signifikant nach oben korrigiert werden, wenn aus der betrachteten Referenzbevölkerung die Frauen ausgeschlossen werden, deren Gebärmutter operativ entfernt wurde. Diese Arbeit stützt sich auf die Studie zur Gesundheit Erwachsener in Deutschland (DEGS1), nach der die Hysterektomie-Prävalenz in Deutschland 2011 bei über 18-jährigen Frauen bei 17,4% lag. Auf Grundlage der Altersverteilung dieser Prävalenz werden die Inzidenz- und Mortalitätsraten von Gebärmutterhalskrebs entsprechend korrigiert. Maximale Korrekturen resultieren bei 70–79-jährigen Frauen mit einer Inzidenzkorrektur von 13,6 auf 22,5, d.h. um 65,4% und einer Mortalitätskorrektur von 7,5 auf 12,4, d.h. um 65,3%. Die mögliche Prävention durch eine HPV-Impfung gewinnt damit an Relevanz.
Proletarier
(2018)
Der These des Begriffshistorikers Werner Conze – enthalten schon im Titel seines Aufsatzes von 1954: "Vom 'Pöbel' zum 'Proletariat'. Sozialgeschichtliche Voraussetzungen für den Sozialismus in Deutschland" - hat der radikale Sozialhistoriker Ahlrich Meyer bescheinigt, im Gewand "neutraler" Begriffsgeschichte im nachhinein bloß ein sozial-eliminatorisches Programm zu sanktionieren, dessen letzte Konsequenzen erst die Nazis endgültig exekutiert hätten - mit tatkräftiger "wissenschaftlicher" Unterstützung von Historikern wie dem Conze-Freund Theodor Schieder oder eben Conze selbst. Die "postnazistische" westdeutsche Geschichtswissenschaft habe letztlich bloß das alte "nazistische Programm der staatlichen Integration der deutschen Kernarbeiterklasse auf die Geschichte projiziert". Wie dem auch sei - auch hier wird einmal mehr deutlich, dass Begriffsgeschichte von Begriffspolitik nicht zu trennen ist. Aber zurück zum Vormärz: Wie immer man die "Conze'sche Integrationsthese" (Meyer) einschätzen mag, mit dem 'Pöbel' und dem 'Proletariat' stehen sich zwei sozialhistorische Protagonisten gegenüber, deren Begriffsgeschichte im Deutschen allemal problematisch ist.
Wie kann die Verkehrswende in Hessen gelingen? Podiumsdiskussion über die Zukunft der Mobilität +++ Mehr als Wohnen: Einladung zur Abschlusstagung im Forschungsprojekt „WohnMobil“ +++ ISOE-Lehrveranstaltungen im Wintersemester +++ Gut gemeint, aber ungeeignet: EU-Verordnung zur Wasserwiederverwendung in der Landwirtschaft +++ Wissenskommunikation für eine nachhaltige Entwicklung +++ Green Talents zu Gast im ISOE +++ Studie „share“: Untersuchung zu free-floating Carsharing abgeschlossen +++ Soziale Aspekte technischer Innovationen: Beispiel SEMIZENTRAL +++ Forschungsprojekt MULTI-ReUse: Interaktive Wissensvermittlung +++ 10 Jahre Senckenberg Biodiversität und Klima Forschungszentrum +++ Frankfurter Wissenschaftsrunde diskutiert Zukunftsthemen „Smart City – Smart Education“ +++ Aus dem ISOE +++ Termine +++ Publikationen
Gedenken an Elmar Altvater +++ Buch zum transdisziplinären Forschungs- und Entwicklungsprojekt CuveWaters erschienen +++ „Brilliant Minds“ für die Nachhaltigkeitsforschung gesucht +++ Frankfurter Forschungsteam untersucht natürliche Bekämpfung exotischer Stechmücken +++ Lösungsstrategien für weniger Plastik in Flüssen und Seen +++ Matthias Bergmann zum Honorarprofessor der Leuphana Universität ernannt +++ Wassermanagement für Millionenstädte – Beispiel Coimbatore in Südindien +++ Behaviour Change für die Verkehrswende +++ Gewässerschutz: Abschlussveranstaltung im Forschungsprojekt NiddaMan +++ Soziale Ökologie an der Uni +++ UN-Weltwassertag: Lösungen für globale Wasserkrise liegen (auch) in der Natur +++ Aus dem ISOE: Neuer Wissenschaftlicher Beirat berufen +++ Termine +++ Publikationen
Wie ist ein nachhaltiger Umgang mit Plastik möglich? +++ Arzneimittelrückstände im Wasser – Fortbildung für Beschäftigte der Pharmazie +++ ISOE-Mobilitätsforschung unterstützt Wissenschaftlichen Beirat des VCD +++ Internationale Summer School für Nachwuchswissenschaftler*innen +++ Savannen-Ökosysteme nachhaltig bewirtschaften +++ Planungssicherheit für Kommunen: Den Wasserbedarf der Zukunft prognostizieren +++ ÖPNV-Forum Stuttgart: Ergebnisse der Studie Mobiles Baden-Württemberg +++ Was Geschlechtergerechtigkeit mit Klimapolitik zu tun hat +++ Mehr Klimaschutz durch "negative Emissionen"? Internationale Konferenz zu Chancen und Risiken neuer Technologien +++ Aus dem ISOE +++ Termine +++ Publikationen
In Carl Barks' 1963 comic strip "The Invisible Intruder", the bed becomes the main theme of the story. We get to know how Uncle Scrooge became a creative and successful entrepreneur. Since his parents were too poor to provide a proper sleeping place for their son, Scrooge had to sleep in a cabinet drawer. Therefore, Scrooge's only aim was to buy himself a bed. His capitalist creativity is, as he himself admits, driven by the "desire for a better bed." With the economic growth of his company, his bed becomes bigger too. But in the end, he throws out his enormous mattress because it is too sensitive to the vibrations caused by the money rammer in the money bin; and moreover, the investigation into the cause of the vibrations became far too expensive. Eventually, Scrooge is returning to his childhood bed: the cabinet drawer. What is striking about this story is not the idea that objects of everyday culture play a leading role within a narrative; it is the fact that the usual cultural function of furniture is altered in a significant way. The misapplication of the drawer draws attention to the object of everyday culture as signifier of the everyday experience in capitalist societies. The function of the bed is no longer defined by criteria of good sleep but of economic calculation. The bed thereby becomes an agency within the narrative that questions the stability of the cultural and linguistic semantics of the everyday. In the following, I will press the point that the representation of the bed in literary texts from Homer to Kafka can be read as an implicit linguistic theory of cultural signification.
Objective: Imaging studies in diffuse low-grade gliomas (DLGG) vary across centers. In order to establish a minimal core of imaging necessary for further investigations and clinical trials in the field of DLGG, we aimed to establish the status quo within specialized European centers.
Methods: An online survey composed of 46 items was sent out to members of the European Low-Grade Glioma Network, the European Association of Neurosurgical Societies, the German Society of Neurosurgery and the Austrian Society of Neurosurgery.
Results: A total of 128 fully completed surveys were received and analyzed. Most centers (n = 96, 75%) were academic and half of the centers (n = 64, 50%) adhered to a dedicated treatment program for DLGG. There were national differences regarding the sequences enclosed in MRI imaging and use of PET, however most included T1 (without and with contrast, 100%), T2 (100%) and TIRM or FLAIR (20, 98%). DWI is performed by 80% of centers and 61% of centers regularly performed PWI.
Conclusion: A minimal core of imaging composed of T1 (w/wo contrast), T2, TIRM/FLAIR, PWI and DWI could be identified. All morphologic images should be obtained in a slice thickness of ≤ 3 mm. No common standard could be obtained regarding advanced MRI protocols and PET.
Importance of the study: We believe that our study makes a significant contribution to the literature because we were able to determine similarities in numerous aspects of LGG imaging. Using the proposed "minimal core of imaging" in clinical routine will facilitate future cooperative studies.
In diesem Beitrag untersuchen wir Entwicklungstendenzen von Infrastrukturen in den Digitalen Geisteswissenschaften. Wir argumentieren, dass infolge (1) der Verfügbarkeit von immer mehr Daten über sozial-semiotische Netzwerke, (2) der Methodeninflation in geisteswissenschaftlichen Disziplinen, (3) der zunehmend hybriden Arbeitsteilung zwischen Mensch und Maschine und (4) der explosionsartigen Vermehrung künstlicher Texte ein erheblicher Anpassungsdruck auf die Weiterentwicklung solcher Infrastrukturen entstanden ist. In diesem Zusammenhang beschreiben wir drei Informationssysteme, die sich unter anderem durch die Interaktionsmöglichkeiten unterscheiden, die sie ihren Nutzern bieten, um solchen Herausforderungen zu begegnen. Dabei skizzieren wir mit VienNA eine neuartige Architektur solcher Systeme, welche aufgrund ihrer Flexibilität die Möglichkeit bieten könnte, letztere Herausforderungen zu bewältigen.
Wenn Literatur über biopolitische und technologische Entwicklungen nachdenkt, kommt sie selten ohne wertende Perspektiven aus. Begeisterten Ausblicken auf angeblich erwartbare oder zumindest möglich scheinende Segnungen technologischen Fortschritts in der Zukunft stehen skeptisch-warnende, dystopische Inszenierungen von Machbarkeitsphantasien und menschlicher Hybris gegenüber. Literarische Zukunftsbilder und die in ihnen zum Ausdruck kommenden Ängste oder Hoffnungen lassen sich daher nicht selten als mehr oder weniger geschickt verkappte Kommentare zu gesellschaftspolitischen Tendenzen der jeweiligen Gegenwart verstehen. Insbesondere das Weiterspinnen von bereits existierenden wissenschaftlichen Erfindungen, deren Potentiale kontrovers diskutiert werden, scheint sich hierfür anzubieten.
Un Jésus postmoderne
(2018)
[Rezension zu:] Thibault, Bruno: Un Jésus postmoderne. Les récritures romanesques contemporaines des Evangiles. - Leiden-Boston: Brill Rodopi 2017 - (Chiasma ; 37)
[Rezension zu:] Ette, Ottmar: WeltFraktale - Wege durch die Literaturen der Welt. - Stuttgart: J.B. Metzler Verlag 2017.
[Rezension zu:] Pillet, Fabien: Vers une esthétique interculturelle de la réception. - Heidelberg: Universitätsverlag Winter 2016.
Am Beispiel von zwei Ausstellungskatalogen historischer Ansichtskarten aus Troppau (Opava) vor 1945 geht der Aufsatz der Frage nach, wie in diesen beiden Medien regionale Kontinuitäten repräsentiert werden können. Die Verwendung deutscher neben tschechischen Ortsbezeichnungen sowohl auf den Karten selbst wie in den Kataloglegenden erweist sich dabei als Indikator für Brüche in der Identität, deren angemessene Repräsentation nicht trivial erscheint. Ansichtskarten als Medium sollen eine lokale oder auch nationale Identität über Räume und Zeiten hinweg vermitteln; sie müssen Sprache und Bild verbinden, welche aber unterschiedlich anfällig für Identitätsbrüche sind. Es wird versucht, die Problematik mit Hilfe von H.U. Gumbrechts Begriffsprägung einer erweiterten Chronotope zu beschreiben. Das erweist sich aber gegenüber der traditionellen historischen Methode bestenfalls partiell als Erkenntnisgewinn.
Die Entscheidung, "Flüchtling" zum Wort des Jahres 2015 zu erklären, bewirkte zweierlei: Sie rief Flucht und Vertreibung in das kulturelle Bewusstsein zurück und rückte ihre medialen Repräsentationsformen in das Blickfeld der Migrationsdiskurse. Der literarische Diskurs der Migration interessiert sich für ästhetische Darstellungsformen von Migrationsformen. Er hinterfragt festgefahrene Vorstellungsmuster und problematisiert die bedeutungskonstruierenden und -konstituierenden Schemata der Migration, zu denen auch die erzwungenen Formen Flucht und Vertreibung zählen. Der literaturwissenschaftliche Diskurs geht der Frage nach Figurationen des Flüchtlings nach und untersucht, in welchen kulturellen Bedeutungszusammenhängen Flüchtlingsfiguren verortet werden, an welchen poetischen Mitteln diese Verortung erprobt wird und welche Erkenntnisse aus dem literarischen Diskurs des Flüchtlings gewonnen werden können. Dieser Diskurs verlöre aber an Wirkung, würde er jene begriffliche Signifikanz nicht auch in ästhetischer Hinsicht begründen. Zugleich gilt es die Wechselwirkung des Literarischen und Gesellschaftlichen im methodischen Vorgehen zu berücksichtigen. Ohne die Wechselwirkung an dieser Stelle historisch vertiefen zu können, sollen die Semantiken, die der öffentlich-politische Diskurs dem Flüchtlingsthema bisher zugeschrieben hat, herangezogen werden, denn in diesen Semantiken lässt sich eine Symbolik erkennen, die Aufschlüsse über das Verständnis des Kulturellen nach einer Definition ex negativo geben kann: Symptomatisch ist die dreifache Annahme, Flüchtlinge betrachteten identitätsstiftende Kriterien der aufnehmenden Gesellschaft nicht als verbindlich, sie teilten deren Geschichte nicht und könnten daher auch nicht an deren Gedächtnishorizont teilhaben; dieses Verständnis erfasst den Flüchtling nicht als Phänomen kultureller und globaler Prozesse, sondern verortet ihn an den Grenzen des Eigenen im Sinne einer Erscheinung außerhalb des eigenkulturellen Raumes.
Vom 20. bis 22. September 2017 fand an der Philologischen Fakultät der Universität des Baskenlandes die nunmehr dritte internationale Fachtagung zu literarischen Repräsentationen von Heimat statt. Unter dem Motto "Unheimliche Heimaträume" widmeten sich die Referentinnen und Referenten mehrheitlich der deutschsprachigen Literatur seit 1918. Dennoch gab es auch dieses Mal eine Sektion zur baskischsprachigen Literatur.