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Chemokines play a key role in the cellular infiltration of inflamed tissue. They are released by a wide variety of cell types during the initial phase of host response to injury, allergens, antigens, or invading microorganisms, and selectively attract leukocytes to inflammatory foci, inducing both migration and activation. Monocyte chemoattractant protein-1 (MCP-1), a member of the CC chemokine superfamily, functions in attracting monocytes, T lymphocytes, and basophils to sites of inflammation. MCP-1 is produced by monocytes, fibroblasts, vascular endothelial cells and smooth muscle cells in response to various stimuli such as tumour necrosis factor-a (TNF-a), interferon-g (IFN-g), and interleukin-1b (IL-1b). It also plays an important role in the pathogenesis of chronic inflammation, and overexpression of MCP-1 has been implicated in diseases including glomerulonephritis and rheumatoid arthritis. Oligonucleotide-directed triple helix formation offers a means to target specific sequences in DNA and interfere with gene expression at the transcriptional level. Triple helix-forming oligonucleotides (TFOs) bind to homopurine/homopyrimidine sequences, forming a stable, sequence-specific complex with the duplex DNA. Purine-rich sequences are frequent in gene regulatory regions and TFOs directed to promoter sequences have been shown to prevent binding of transcription factors and inhibit transcription initiation and elongation. Exogenous TFOs that bind homopurine/ homopyrimidine DNA sequences and form triple-helices can be rationally designed, while the intracellular delivery of single-stranded RNA TFOs has not been studied in detail before. In this study, expression vectors were constructed which directed transcription of either a 19 nt triplex-forming pyrimidine CU-TFO sequence targeting the human MCP-1 or two different 19 nt GU- or CA-control sequences, respectively, together with the vector encoded hygromycin resistance mRNA as one fusion transcript. HEK 293 cells were stable transfected with these vectors and several TFO and control cell lines were generated. Functional relevant triplex formation of a TFO with a corresponding 19 bp GC-rich AP-1/SP-1 site of the human MCP-1 promoter was shown. Binding of synthetic 19 nt CUTFO to the MCP-1 promoter duplex was verified by triplex blotting at pH 6.7. Underlining binding specificity, control sequences, including the GU- and CA-sequence, a TFO containing one single mismatch and a MCP-1 promoter duplex containing two mismatches, did not participate in triplex formation. Establishing a magnetic capture technique with streptavidin microbeads it was verified that at pH 7.0 the 19 nt TFO embedded in a 1.1 kb fusion transcript binds to a plasmid encoded MCP-1 promoter target duplex three times stronger than the controls. Finally, cell culture experiments revealed 76 ± 10.2% inhibition of MCP-1 protein secretion in TNF-a stimulated CU-TFO harboring cell lines and up to 88% after TNF-a and IFN-g costimulation in comparison to controls. Expression of interleukin-8 (IL-8) as one TNF-a inducible control gene was not affected by CU-TFO, demonstrating both highly specific and effective chemokine gene repression. Furthermore, another chemokine target, regulated upon activation normal T cell expressed and secreted (RANTES), which plays an essential role in inflammation by recruiting T lymphocytes, macrophages and eosinophils to inflammatory sites, was analysed using the triplex approach. A 28 nt TFO was designed targeting the murine RANTES gene promoter, and gel mobility shift assays demonstrated that the phosphodiester TFO formed a sequencespecific triplex with the double-stranded target DNA with a Kd of 2.5 x 10-7 M. It was analysed whether RANTES expression could be inhibited at the transcriptional level testing the TFO in two different cell lines, T helper-1 lymphocytes and brain microvascular endothelial cells (bend3 cells). Although there was a sequence-specific binding of the TFO detectable in the gel shift assays, there was no inhibitory effect of the exogenously added and phosphorothioate stabilised TFO on endogenous RANTES gene expression visible. Additionally, the small interfering RNA (siRNA) approach was tested as another strategy to inhibit expression of the pro-inflammatory chemokines MCP-1 and RANTES. Two different methods were pursuit, describing transient transfection with vector derived and synthetic siRNA. The vector pSUPER containing the siRNA coding sequence was used to suppress endogenous MCP-1 in HEK 293 cells. An empty vector without RNA sequence served as a control. Inhibition due to the siRNA was measured in stimulated and unstimulated cells. In TNF-a stimulated cells MCP-1 protein synthesis was decreased by 35 ± 11% after siRNA transfection. Using a synthetic double-stranded siRNA, the TNF-a induced MCP-1 protein secretion could be successfully inhibited about 62.3 ± 10.3% in HEK 293 cells, indicating that the siRNA is functional in these cells to suppress chemokine expression. The siRNA approach targeting murine RANTES in Th1 cells and b-end3 cells revealed no inhibition of endogenous gene expression. Gene therapy approaches rely on efficient transfer of genes to the desired target cells. A wide variety of viral and nonviral vectors have been developed and evaluated for their efficiency of transduction, sustained expression of the transgene, and safety. Among them, lentiviruses have been widely used for gene therapy applications. In order to improve the delivery of TFOs or siRNAs into the target cells, cloning of the lentiviral transfer vector SEW, the production of lentiviral particles by transient transfection were performed with the aim to generate lentiviral vector-derived TFOs in further experiments. Here, Th1 cells were transduced with infectious lentiviral particles and transduction efficacy was measured. Transduction efficacy higher than 82% could be achieved using the lentiviral vector SEW, opening optimal possibilities for the TFO or siRNA approach.
This paper aims to demonstrate the hidden place of the surrealist poet, Paul Éluard, in Samuel Beckett's writing process. It will show that Beckett not only read and translated Paul Éluard, as is known, but also quoted him extensively. Moving from Beethoven to the short story "Lessness", the place of quotation as a trace of emotion will be examined.
Neste artigo, comparamos duas traduções em língua portuguesa do romance "Verstörung" (primeira edição em língua alemã em 1967) do escritor austríaco Thomas Bernhard: a tradução portuguesa (1986, por Leopoldina Almeida) e a brasileira (1999, por Hans Peter Welper e José Laurenio de Melo). Partimos da premissa de que "Verstörung" é um livro com uma dimensão performativa acentuada, ou seja, a perturbação que dá nome ao livro não está representada apenas no enredo e na caracterização dos personagens, mas também – ou sobretudo – no estilo, na linguagem do texto em alemão. Discutimos e comparamos diferentes soluções tradutórias nas referidas versões em português, assim como os paratextos que constam nas duas publicações. Constatamos duas posturas divergentes ao lidar com as especificidades da linguagem da obra, ambas com consequências para o seu efeito performativo. Por fim, sugerimos que essas posturas possam ser reflexos das diferenças da própria crítica literária em relação a Thomas Bernhard em dois momentos diversos.
This article points out facts that help to explain why Franz Kafka was not awarded the Nobel Prize.
"A manager in the minds of doctors" : a comparison of new modes of control in European hospitals
(2013)
Background: Hospital governance increasingly combines management and professional self-governance. This article maps the new emergent modes of control in a comparative perspective and aims to better understand the relationship between medicine and management as hybrid and context-dependent. Theoretically, we critically review approaches into the managerialism-professionalism relationship; methodologically, we expand cross-country comparison towards the meso-level of organisations; and empirically, the focus is on processes and actors in a range of European hospitals.
Methods: The research is explorative and was carried out as part of the FP7 COST action IS0903 Medicine and Management, Working Group 2. Comprising seven European countries, the focus is on doctors and public hospitals. We use a comparative case study design that primarily draws on expert information and document analysis as well as other secondary sources.
Results: The findings reveal that managerial control is not simply an external force but increasingly integrated in medical professionalism. These processes of change are relevant in all countries but shaped by organisational settings, and therefore create different patterns of control: (1) ‘integrated’ control with high levels of coordination and coherent patterns for cost and quality controls; (2) ‘partly integrated’ control with diversity of coordination on hospital and department level and between cost and quality controls; and (3) ‘fragmented’ control with limited coordination and gaps between quality control more strongly dominated by medicine, and cost control by management.
Conclusions: Our comparison highlights how organisations matter and brings the crucial relevance of ‘coordination’ of medicine and management across the levels (hospital/department) and the substance (cost/quality-safety) of control into perspective. Consequently, coordination may serve as a taxonomy of emergent modes of control, thus bringing new directions for cost-efficient and quality-effective hospital governance into perspective.
Rezension zu: E. T. A. Hoffmann, A janela da esquina de meu primo. Tradução: Maria Aparecida Barbosa, Ilustrações: Daniela Bueno, Posfácio: Marcus Mazzari. São Paulo, Cosac Naify, 2010
"A groundbreaking decision"
(2018)
The essay provides a contrapuntal "parallactic" reading of Johann Wolfgang Goethe's "Bildungsroman" Wilhelm Meisters Lehrjahre - with its extensions Wilhelm Meisters theatralische Sendung and Wilhelm Meisters Wanderjahre - and James Joyce's high modernist A Portrait of the Artist as a Young Man (1916) and Ulysses (1922). Derived from astronomy, the term parallax designates, transferred to literary history, a narrative stratagem, a metapoetical rationale, and an interpretive method. Joyce employs it as a key concept and narrative tool in Ulysses to denote a stereoscopic perspective applied to the protagonists’ actions and the world they live in. Leopold Bloom thus refl ects on it and the technique of Ulysses is determined by it. On a higher plane, literary critics, too, engage in literary historical parallax whenever they read texts intertextually — as exemplified in this essay. A parallactic reading of the novels’ protagonists Wilhelm Meister and Stephen Dedalus, as regards not just their identification with Shakespeare’s Hamlet but also the symbolic connotations embedded in their names and mythological pretexts, allows us to shed new light on the roles and significance of narrative irony, chance, and paternity in these novels.
1996 gab es auf dem jährlich in Bologna stattfindenden Festival 'Il Cinema Ritrovato' eine Retrospektive zu Rudolph Valentino. In meinen Aufzeichnungen finde ich den Eindruck von Valentino in 'Camille' notiert. Ich erinnere mich, wie ich hingerissen, ergriffen war von einer Geste des Sich-fallen-Lassens vor der Geliebten, an der Geliebten. Eine Geste, von der ich versuchsweise sagen könnte, dass sich in ihr absolute Verehrung und vollständige physische Hingabe mischen. Doch ist jede Deutung unzureichend, denn die Geste ergreift mich schließlich ganz physisch, wird in der Ergriffenheit unbegreiflich. Ich suchte das damals notierte Phänomen auf einer kümmerlichen DVD-Reproduktion des Films wieder auf. Es ist der Moment, da sich der Held des Films, Armand/Valentino, aus seiner Befangenheit in noch unerwiderter Liebe auf einmal löst - jedoch eben nicht, um zu handeln, vielmehr um sich erschütternd in seiner Ohnmacht zu offenbaren. Wenn er Marguerites/Nazimovas Knie unter dem kostbaren Stoff des Kleides umfasst, den Kopf an diesen Schleier über der Haut lehnt oder schmiegt, dann hat er in der Bewegung zuvor schon auf unerhörte Weise unbedingtes erotisches Verlangen mitgeteilt. Derart ist dieser Körper, diese männliche Person, die wir sehen, dem Begehren ausgeliefert, dass jeder Akt unmöglich wird. Wohin sollte er sich auch richten? Nach außen, auf die Frau, oder auf dies Ungeheure im Innern? Was bleibt, ist das Sich-fallen-Lassen in die Passivität, in ein Niedergleiten an der Oberfläche von Marguerite, das zugleich ein Hineingleiten in das eigene Innerste ist. 'A fallen man' - der Film verweilt bei dem hingegebenen Valentino. Das löst eine Fülle von Assoziationen aus: Ein Geschlechterwechsel scheint auf - nicht die Frau, der Mann gibt sich hin, wird ein Gefallener, prostituiert sich als Schauspieler (etwas, was Fans wie Kritiker an Valentino bemerkt haben) -, ebenso erscheint eine Empathie des Mannes mit der Prostituierten. Im Kino, anders als in Alexandre Dumas' Roman, teilt sich die Anteilnahme nicht durch viele Worte mit, sondern durch Mimesis.
In Franz Hohlers Tschipo (1978), dem ersten Teil einer Trilogie, erlebt ein Schweizer Junge Abenteuer auf seltsamen Inseln. Und in Maggie Stiefvaters Serien The Raven Cycle (2012 – 2016) und The Dreamer Trilogy (2019 – ) bekämpft ein amerikanischer junger Erwachsener mit Namen Ronan Lynch magische Gefahren. Was haben Tschipo und Ronan gemeinsam? Eine seltsame Gabe: Von ihren Träumen bleibt am Morgen etwas zurück...
This paper examines the political-economy and cultural dynamics and discourses underlying the emergence of the Palestinian Hamas and the Algerian Islamic Salvation Front. Both movements emerged in the late 1980s as responses to continuing (neo) colonial conditions in their countries. I explore to what extent the various processes commonly referred to as “globalization,” both the world-wide economic transformations epitomized by post-fordism on the macro/system level and neo-liberal structural adjustment programs within countries, and—perhaps more important—its cultural dynamics contributed to the rise and power of both movements. I examine the socio-economic situation in Algeria and Palestine-Israel during the 1980s and link it to the politics developments in both countries. Next I review the events behind the founding of both movements and the main components of their ideologies and strategies. Finally I explore their arguments to determine whether the political-economic or cultural pressures unleashed by globalization were the determining factor in their emergence and ideological development. I conclude by comparing the two case studies to determine if there are common threads that can serve as the basis for a region-wide investigation of the role of globalization in the emergence and/or rise to social hegemony of Islamist movements in other MENA countries.
Auch wenn in der Nachfolge der Aufklärung sowie mit dem Siegeszug der modernen Naturwissenschaften eine Verlustgeschichte des Transzendenzwunders geschrieben wurde und Max Weber in seinem vielzitierten Diktum von 1917 die moderne Welt als 'entzaubert' deklarierte, entpuppte sich das vermeintlich vormoderne Phänomen des Wunders in der literarischen Moderne als Reflexionsgegenstand verschiedener Fachdisziplinen. Gleichzeitig erlebte das Wunder im Drama und Theater der Moderne eine Renaissance: Jener "clamor for miracles", so George Bernard Shaw in seinem Vorwort zu 'Androcles and the Lion', wird im zweiten Jahrzehnt des 20. Jahrhunderts in England nicht nur diskursiv verhandelt, sondern für das Publikum durchaus bühnenwirksam eingesetzt, wie ich im Folgenden erläutern möchte.
Three-taxon statement analysis (3TA) is a method that may help to formalize the taxonomical intuition of the synapomorphy of the clade as a combination of its diagnostic traits, even if each trait, if taken separately, may be found in one or many other taxa of the same relationship. Using example based on the real morphological data, we are showing that 3TA can recognize clade in case of the complete lack of it synapomorphies, as optimized under the criterion of standard parsimony.
In ihren Arbeiten zu Emily Dickinson und Paul Celan macht Shira Wolosky immer wieder auf die thematischen und linguistischen Gemeinsamkeiten der beiden Autoren aufmerksam. Dabei betont sie beispielsweise die stilistischen Auffälligkeiten in beiden Werken. Zudem beschreibt Wolosky neben den Parallelen eine Art des Austauschprozesses zwischen den Werken, die durch die Übersetzung Celans entstehe. In einer zweiten Arbeit zu Dickinson und Celan führt sie diesen Gedanken weiter aus und sieht in der Übersetzung eine Darstellung von Celans eigener Perspektive auf Dickinsons Werk. Auch in der deutschsprachigen Forschung gibt es Beiträge, die herausgearbeitet haben, dass eine nähere Beschäftigung mit Dickinson und Celan relevant ist, da beide ähnliche Themen in ihren Dichtungen behandeln, darunter "die Beziehung des Ichs innerhalb der Spannungsfelder von Liebe und (zumeist unerfülltem) Begehren, Zeit und Ewigkeit, Schöpfung und Vergänglichkeit, Tod und Unsterblichkeit, Gott und Transzendenz, Offenbarung und verweigerter Theodizee." Trotz dieser vielversprechenden Untersuchungen wurde den Dickinson-Übersetzungen Celans im Allgemeinen in der Forschung wenig Beachtung geschenkt, bzw. wurde der Schwerpunkt vor allem auf linguistische Analysen gelegt (so wie die von Wolosky selbst). Im Folgenden möchte ich daher das Gedicht "Because I could not stop for Death", das in der Übersetzung Celans 1959 im Fischer Almanach erschien, näher betrachten und dabei fragen, auf welche Weise sich Celans Übersetzung von Dickinsons Vorlage unterscheidet. Dabei werde ich an Woloskys These anknüpfen, dass Celan die Gedichte nicht nur übersetzt, sondern auch stark bearbeitet und mit seiner eigenen Dichtung verbindet.
Using the example of the village novel Three Kilometers from the final phase of the Ceaușescu dictatorship, the article follows the discovery of memory, examining the image of the Banat village community, which is dominated by hopelessness, fear and thoughts of flight. The emptiness and the cold motif used at the end point to the dissolution of the Swabian village world. The Banat village is presented at the interface between real life reality and a landscape of memories.
Marie Luise Kaschnitz is not considered to be an experimental author in the usual sense. Her respectful use of traditional forms has been praised, but also criticized, and it was only in her later works that she loosened her strong links with tradition. The beginning of this change is marked by the short story Am Circeo [At Cape Circeo], placed exactly in the centre of her 1960 volume of short stories entitled Long Shadows. The present article examines the experimental elements of this text, attempting to determine what conditioned
them and seeking to reveal their influence on later works.
The study deals with the contacts between Princess Mechtilde Lichnowsky and the Prague German writer Franz Werfel in the years 1913–1914. The author outlines the friendly relationship between Mechtilde and Werfel, sketching the social and biographical background on the eve of World War I. In this context, attention is paid not only to Mechtilde Lichnowsky's drama "Ein Spiel vom Tod", but also to its reception by Werfel, by other authors, and not least by the contemporary press.
Im 'neuen deutschland' nimmt der Kritiker Björn Hayer am 9. Februar 2023 Stellung zur Tatsache, dass die Autorin Judith Zander den mit 15.000 € datierten Huchel-Preis gewonnen hat. Dieser Text hat ein einziges Ziel, auch wenn er behauptet, zwei Anliegen zu verfolgen, wie Hayer bei Twitter schreibt: "Der #Huchel-Preis an #JudithZander wirft nicht nur die Frage auf, warum er nicht an begabtere Stimmen geht. Wie ich in @ndaktuell diskutiere, erklärt die Vergabe auch, warum der #Lyrik unserer Zeit die Leser abhanden gekommen sind. #Gedicht #Poesie #Preis". Hier sei behauptet, dass Hayer nur vorgeblich die Lyrik als solche im Blick hat, wenn er sich am Werk einer einzelnen Autorin abarbeitet. Im Folgenden sollen alle Kriterien untersucht werden, die Hayers Offensiv-Text zugrunde liegen. Auf diese Weise kann sich zeigen, dass es ihm in erster Linie darum geht, Zanders preisgekrönten Gedichtband 'im ländchen sommer im winter zur see' als das Gegenteil von 'starker Lyrik' auszuweisen. Die Auswahl der Kriterien, ihr Passungsverhältnis und ihre argumentative Einbettung entlarven Hayers Text als erstaunlich bodenlos.
Wohl keine andere Zusammenarbeit zwischen einem Theaterpraktiker und einem Bühnenautor ist im deutschsprachigen Theater des 20. Jahrhunderts ähnlich kontinuierlich und fruchtbar verlaufen wie die zwischen Max Reinhardt und Hugo von Hofmannsthal. So eng verbunden ist ihr gemeinsames Wirken gewesen, dass sich kaum sagen lässt, ob Reinhardt die Theaterstücke und Stückbearbeitungen Hofmannsthals auf die Bühne gebracht hat oder ob besser, wie Wolfgang Nehring mit Blick auf "Elektra" und "Ödipus" formuliert, von "Hofmannsthals 'Erneuerung der Antike' für das Theater Max Reinhardts" die Rede sein sollte. Ihren Kulminationspunkt findet die Kooperation zweifellos in der Begründung der Salzburger Festspiele, an der Reinhardt und Hofmannsthal führend beteiligt waren. Wie weitreichend ihre Kooperation konzeptionell gewesen ist, ja wie sehr ihr Zusammenwirken als ein von einem gemeinsamen Leitgedanken durchdrungenes Projekt gesehen werden muss, das sich in seinen Wandlungen über die verschiedenen Werkphasen hinweg durchhält und fortentwickelt, wird vollends indes erst sichtbar, wenn man es in den Epochenzusammenhang einrückt, von dem Hofmannsthals und Reinhardts Projekt nicht nur bestimmt wurde, dessen Rahmen sie im Zuge ihrer Zusammenarbeit vielmehr wesentlich erst aufgespannt haben: denjenigen der Theatermoderne.