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We synthesized two green-light activatable 5’-caps for oligonucleotides based on the BODIPY and coumarin scaffold. Both bear an alkyne functionality allowing their use in numerous biological applications. They were successfully incorporated in oligonucleotides via solid-phase synthesis. Copper-catalyzed alkyne-azide cycloaddition (CuAAC) using a bisazide photo-tether gave cyclic oligonucleotides that could be relinearized by activation with green light and were shown to exhibit high stability against exonucleases. Chemical ligation as another example for bioconjugation yielded oligonucleotides with an internal strand break site. Irradiation at 530 nm or 565 nm resulted in complete photolysis of both caging groups.
Gene therapy on the move
(2013)
The first gene therapy clinical trials were initiated more than two decades ago. In the early days, gene therapy shared the fate of many experimental medicine approaches and was impeded by the occurrence of severe side effects in a few treated patients. The understanding of the molecular and cellular mechanisms leading to treatment- and/or vector-associated setbacks has resulted in the development of highly sophisticated gene transfer tools with improved safety and therapeutic efficacy. Employing these advanced tools, a series of Phase I/II trials were started in the past few years with excellent clinical results and no side effects reported so far. Moreover, highly efficient gene targeting strategies and site-directed gene editing technologies have been developed and applied clinically. With more than 1900 clinical trials to date, gene therapy has moved from a vision to clinical reality. This review focuses on the application of gene therapy for the correction of inherited diseases, the limitations and drawbacks encountered in some of the early clinical trials and the revival of gene therapy as a powerful treatment option for the correction of monogenic disorders.
The three-dimensional quantification of small-scale processes in the upper troposphere and lower stratosphere is one of the challenges of current atmospheric research and requires the development of new measurement strategies. This work presents the first results from the newly developed Gimballed Limb Observer for Radiance Imaging of the Atmosphere (GLORIA) obtained during the ESSenCe (ESa Sounder Campaign) and TACTS/ESMVal (TACTS: Transport and composition in the upper troposphere/lowermost stratosphere, ESMVal: Earth System Model Validation) aircraft campaigns. The focus of this work is on the so-called dynamics-mode data characterized by a medium-spectral and a very-high-spatial resolution. The retrieval strategy for the derivation of two- and three-dimensional constituent fields in the upper troposphere and lower stratosphere is presented. Uncertainties of the main retrieval targets (temperature, O3, HNO3, and CFC-12) and their spatial resolution are discussed. During ESSenCe, high-resolution two-dimensional cross-sections have been obtained. Comparisons to collocated remote-sensing and in situ data indicate a good agreement between the data sets. During TACTS/ESMVal, a tomographic flight pattern to sense an intrusion of stratospheric air deep into the troposphere was performed. It was possible to reconstruct this filament at an unprecedented spatial resolution of better than 500 m vertically and 20 × 20 km horizontally.
The three-dimensional quantification of small scale processes in the upper troposphere and lower stratosphere is one of the challenges of current atmospheric research and requires the development of new measurement strategies. This work presents first results from the newly developed Gimballed Limb Observer for Radiance Imaging of the Atmosphere (GLORIA) obtained during the ESSenCe and TACTS/ESMVal aircraft campaigns. The focus of this work is on the so-called dynamics mode data characterized by a medium spectral and a very high spatial resolution. The retrieval strategy for the derivation of two- and three-dimensional constituent fields in the upper troposphere and lower stratosphere is presented. Uncertainties of the main retrieval targets (temperature, O3, HNO3 and CFC-12) and their spatial resolution are discussed. During ESSenCe, high resolution two-dimensional cross-sections have been obtained. Comparisons to collocated remote-sensing and in-situ data indicate a good agreement between the data sets. During TACTS/ESMVal a tomographic flight pattern to sense an intrusion of stratospheric air deep into the troposphere has been performed. This filament could be reconstructed with an unprecedented spatial resolution of better than 500 m vertically and 20 km × 20 km horizontally.
Die Frankfurter Universitätsklinik hat mit der Eröffnung des interdisziplinären Brustkrebszentrums 1997 im Rhein-Main-Gebiet neue Maßstäbe bei der Behandlung von Brustkrebs gesetzt. Ziel ist es, die diagnostischen und therapeutischen Abläufe in der Brustkrebsbehandlung zu optimieren sowie die ökonomischen und fachlichen Ressourcen besser zu nutzen. Doch eine gute Therapie ist nur ein Werkzeug bei der Bekämpfung der seit Jahren zunehmenden Brustkrebserkrankungen. Nach Kaufmanns Ansicht ist es wichtig, "zweigleisig zu fahren: Früherkennungsmaßnahmen tragen dazu bei, Tumoren früh zu erkennen. Darüber hinaus gilt es, durch mehr Information mehr Körper- und Gesundheitsbewusstsein zu entwickeln. Denn wer gut informiert ist, hat die besseren Chancen."
Editionen separieren Texte von den Kontexten, in denen sie bei ihrem Entstehungsprozess mit der Hand und technischen Schreibwerkzeugen unterschiedlichster Art geschrieben, als Erstdruck publiziert und von den Zeitgenossen ursprünglich rezipiert worden sind. Zugleich generieren sie, je nach ihren editorischen Prämissen, für die späteren Leser durch die von ihnen vollzogene Selektion, die Anordnung nach Textsorten oder die Anwendung anderer Strukturierungsregeln sowie durch die dabei vorgenommene Hierarchisierung, Kommentierung oder auch Nicht-Kommentierung ihrerseits neue Kontexte und konstruieren so ein bestimmtes, die Rezeption lenkendes Profil von Autor und Werk. Das ist, wie bei anderen prominenten Autoren, auch in der Wirkungsgeschichte Walter Benjamins der Fall. Ich möchte diesem Spannungsverhältnis von Dekontextualisierung und Rekontextualisierung im Folgenden am Beispiel der sogenannten 'kleineren' literaturkritischen Arbeiten - schon das Epitheton ist ein Beispiel für den erwähnten Selektions- und Hierarchisierungsprozess - nachgehen, also anhand der 'Kritiken und Rezensionen', die Benjamin seit der zweiten Hälfte der 1920er Jahre in der 'Frankfurter Zeitung', der 'Literarischen Welt' und an anderer Stelle veröffentlicht hat und deren Korpus im Wesentlichen in dem 1972 publizierten dritten Band der 'Gesammelten Schriften' publiziert worden ist. Ich werde mich dabei, in Blick auf den für diesen Beitrag zur Verfügung stehenden Raum, auf die Skizze zentraler Grundprobleme, auf pointierte Thesen und exemplarische Beispiele beschränken – in der Hoffnung, gerade durch solche Verknappung und Pointierung Impulse für eine weiterführende Diskussion der angesprochenen Probleme zu liefern. Einleitend werde ich zunächst einige grundsätzliche Fragen der Benjamin-Edition skizzieren. Im Anschluss daran werde ich die aktuelle Editionslage von Benjamins Arbeiten zur Literaturkritik im Hinblick auf die Leitfrage meines Beitrags, also auf das Spannungsverhältnis von Text(en) und Kontext(en), kritisch analysieren. Schließlich soll anhand einiger ausgewählter Rezensionen exemplarisch gezeigt werden, welche Bedeutung die in der bisherigen Editionspraxis meist ausgeblendeten Kontexte (z.B. Publikations-, Medien-, Wissenschaftskontexte, biografisch-soziale Kontexte, historische und politische Kontexte etc.) für ein Verständnis des Literaturkritikers Benjamin gewinnen können, sofern man ihnen editorisch die gebührende Beachtung schenkt. Dabei werden Umrisse eines neuen und anderen Benjamin-Bildes sichtbar, das sich von dem bisher verbreiteten nicht nur in Nuancen unterscheidet.
In seiner Rezension zur Kritischen Ausgabe der 'Einbahnstraße' schreibt Lorenz Jäger in der 'Frankfurter Allgemeinen Zeitung' vom 11.3.2010: "Zwischen Moskau und Paris liegt der geographische Raum dieses Buches, auch nach Süden hin ist er offen." Tatsächlich spielt der Süden Europas im Leben und Werk Benjamins eine wichtige Rolle. In Italien und Spanien hat er nicht nur längere Phasen seines Lebens verbracht, sondern bekanntlich auch zentrale, seine intellektuelle Entwicklung prägende Zäsuren erlebt. Seine autobiographischen Texte, Reisebilder und die Besprechungen einschlägiger Werke zur Kultur und Landschaft Südeuropas geben davon ein eindrucksvolles Zeugnis. Hinsichtlich der Rezeption der romanischen Literatur im engeren Sinn wird man aber von einer eher schmalen Tür nach Süden sprechen müssen, jedenfalls gemessen an den breiten Toren, die nach Westen in Richtung Frankreich bzw. nach Osten zur russischen Literatur führen. Gewiss, Benjamin kannte die italienischen Klassiker Dante, Petrarca, Boccaccio, Aretino oder Marsilio Ficino, aber sehr tiefe Spuren haben sie in seinem Werk nicht hinterlassen. Etwas anders sieht es bei den großen Autoren des spanischen 'Siglo de Oro' aus. Mit Cervantes als Erzähler, vor allem aber mit dem "Handorakel" von Baltasar Gracián und den Trauerspielen Calderons hat er sich seit den 1920er Jahren wiederholt und intensiv auseinandergesetzt. Aber auch hier fehlt, sieht man von der kurzen Rezension des spanischen Surrealisten Ramón Gómez de la Serna ab, jede nähere Beschäftigung mit bedeutenden Autoren des 19. und 20. Jahrhunderts. Umso auffälliger ist vor diesem Hintergrund das Interesse, das Benjamin dem italienischen Dichter, Philologen, Essayisten und großen Aphoristiker Giacomo Leopardi (1798–1837) entgegengebracht hat. Es findet seinen deutlichsten Niederschlag in der Rezension einer deutschen Übersetzung von Leopardis 'Pensieri', die im Frühjahr 1928 geschrieben wurde und in der 'Literarischen Welt' vom 18.3.1928 erschienen ist. Größere Aufmerksamkeit hat diese Besprechung nicht gefunden. Bekannter ist der sich daran anschließende, zwei Monate später an gleicher Stelle publizierte Disput mit dem Übersetzer Richard Peters, der dem Kritiker Gelegenheit gab, zu grundsätzlichen Fragen der Übersetzungstheorie Stellung zu nehmen (WuN XIII, 144–147). Dagegen wurde die Verbindung zwischen Benjamin und Leopardi bislang in der Forschung von keiner Seite thematisiert.
Gen- und Stammzelltherapie stehen für das, wovon die Medizin schon immer geträumt hat: geschädigtes Gewebe durch gesundes ersetzen und die Wirkung defekter Gene durch intakte Kopien korrigieren. Wie ist der Stand der weltweiten Forschung? Welche Hindernisse sind zu überwinden, damit mehr Patienten von der regenerativen Medizin profi tieren werden?
During early G1 phase, Rb is exclusively mono-phosphorylated by cyclin D:Cdk4/6, generating 14 different isoforms with specific binding patterns to E2Fs and other cellular protein targets. While mono-phosphorylated Rb is dispensable for early G1 phase progression, interfering with cyclin D:Cdk4/6 kinase activity prevents G1 phase progression, questioning the role of cyclin D:Cdk4/6 in Rb inactivation. To dissect the molecular functions of cyclin D:Cdk4/6 during cell cycle entry, we generated a single cell reporter for Cdk2 activation, RB inactivation and cell cycle entry by CRISPR/Cas9 tagging endogenous p27 with mCherry. Through single cell tracing of Cdk4i cells, we identified a time-sensitive early G1 phase specific Cdk4/6-dependent phosphorylation gradient that regulates cell cycle entry timing and resides between serum-sensing and cyclin E:Cdk2 activation. To reveal the substrate identity of the Cdk4/6 phosphorylation gradient, we performed whole proteomic and phospho-proteomic mass spectrometry, and identified 147 proteins and 82 phospho-peptides that significantly changed due to Cdk4 inhibition in early G1 phase. In summary, we identified novel (non-Rb) cyclin D:Cdk4/6 substrates that connects early G1 phase functions with cyclin E:Cdk2 activation and Rb inactivation by hyper-phosphorylation.
Background: Computed tomography (CT) low-dose (LD) imaging is used to lower radiation exposure, especially in vascular imaging; in current literature, this is mostly on latest generation high-end CT systems.
Purpose: To evaluate the effects of reduced tube current on objective and subjective image quality of a 15-year-old 16-slice CT system for pulmonary angiography (CTPA).
Material and Methods: CTPA scans from 60 prospectively randomized patients (28 men, 32 women) were examined in this study on a 15-year-old 16-slice CT scanner system. Standard CT (SD) settings were 100 kV and 150 mAs, LD settings were 100 kV and 50 mAs. Attenuation of the pulmonary trunk, various anatomic landmarks, and image noise were quantitatively measured; contrast-to-noise ratios (CNR) and signal-to-noise ratios (SNR) were calculated. Three independent blinded radiologists subjectively rated each image series using a 5-point grading scale.
Results: CT dose index (CTDI) in the LD series was 66.46% lower compared to the SD settings (2.49 ± 0.55 mGy versus 7.42 ± 1.17 mGy). Attenuation of the pulmonary trunk showed similar results for both series (SD 409.55 ± 91.04 HU; LD 380.43 HU ± 93.11 HU; P = 0.768). Subjective image analysis showed no significant differences between SD and LD settings regarding the suitability for detection of central and peripheral PE (central SD/LD, 4.88; intra-class correlation coefficients [ICC], 0.894/4.83; ICC, 0.745; peripheral SD/LD, 4.70; ICC, 0.943/4.57; ICC, 0.919; all P > 0.4).
Conclusion: The LD protocol, on a 15-year-old CT scanner system without current high-end hardware or post-processing tools, led to a dose reduction of approximately 67% with similar subjective image quality and delineation of central and peripheral pulmonary arteries.
The re-emergence of tuberculosis in its present-day manifestations - single, multiple and extensive drug-resistant forms and as HIV-TB coinfections - has resulted in renewed research on fundamental questions such as the nature of the organism itself, Mycobacterium tuberculosis, the molecular basis of its pathogenesis, definition of the immunological response in animal models and humans, and development of new intervention strategies such as vaccines and drugs. Foremost among these developments has been the precise chemical definition of the complex and distinctive cell wall of M. tuberculosis, elucidation of the relevant pathways and underlying genetics responsible for the synthesis of the hallmark moieties of the tubercle bacillus such as the mycolic acid-arabinogalactan-peptidoglycan complex, the phthiocerol- and trehalose-containing effector lipids, the phosphatidylinositol-containing mannosides, lipomannosides and lipoarabinomannosides, major immunomodulators, and others. In this review, the laboratory personnel who have been the focal point of some to these developments review recent progress towards a comprehensive understanding of the basic physiology and functions of the cell wall of M. tuberculosis.
G-protein-coupled receptor (GPCR) expression is extensively studied in bulk cDNA, but heterogeneity and functional patterning of GPCR expression in individual vascular cells is poorly understood. Here, we perform a microfluidic-based single-cell GPCR expression analysis in primary smooth muscle cells (SMC) and endothelial cells (EC). GPCR expression is highly heterogeneous in all cell types, which is confirmed in reporter mice, on the protein level and in human cells. Inflammatory activation in murine models of sepsis or atherosclerosis results in characteristic changes in the GPCR repertoire, and we identify functionally relevant subgroups of cells that are characterized by specific GPCR patterns. We further show that dedifferentiating SMC upregulate GPCRs such as Gpr39, Gprc5b, Gprc5c or Gpr124, and that selective targeting of Gprc5b modulates their differentiation state. Taken together, single-cell profiling identifies receptors expressed on pathologically relevant subpopulations and provides a basis for the development of new therapeutic strategies in vascular diseases.
ATP-binding cassette (ABC) transporters, a superfamily of integral membrane proteins, catalyse the translocation of substrates across the cellular membrane by ATP hydrolysis. Here we demonstrate by nucleotide turnover and binding studies based on 31P solid-state NMR spectroscopy that the ABC exporter and lipid A flippase MsbA can couple ATP hydrolysis to an adenylate kinase activity, where ADP is converted into AMP and ATP. Single-point mutations reveal that both ATPase and adenylate kinase mechanisms are associated with the same conserved motifs of the nucleotide-binding domain. Based on these results, we propose a model for the coupled ATPase-adenylate kinase mechanism, involving the canonical and an additional nucleotide-binding site. We extend these findings to other prokaryotic ABC exporters, namely LmrA and TmrAB, suggesting that the coupled activities are a general feature of ABC exporters.
The title compound, C22H18N2O2, was derived from 1-(2-hydroxyphenyl)-3-(4-methoxyphenyl)propane-1,3-dione. The central pyrazole ring forms dihedral angles of 16.83 (5), 48.97 (4) and 51.68 (4)°, respectively, with the methoxyphenyl, phenyl and hydroxyphenyl rings. The crystal packing is stabilized by O-H...N hydrogen bonding. Key indicators: single-crystal X-ray study; T = 173 K; mean σ(C–C) = 0.002 Å; R factor = 0.037; wR factor = 0.096; data-to-parameter ratio = 17.0.
Der Drömling ist mit einer Fläche von ca. 320 km2 das größte Feucht- und Niedermoorgebiet im deutschen Altpleistozän, das noch große geschlossene Niedermoorkomplexe aufweist. Das Gebiet ist Lebensraum zahlreicher seltener und vom Aussterben bedrohter Tier- und Pflanzenarten. Mit dem im Zuge der Kultivierung entstandenen umfangreichen Graben- und Stauanlagensystem und den historisch bedeutsamen Rimpau’schen Moordammkulturen ist die Drömlingsniederung zugleich eine einmalige Kulturlandschaft.
We investigate complexes of two paramagnetic metal ions Gd3+ and Mn2+ to serve as polarizing agents for solid-state dynamic nuclear polarization (DNP) of 1H, 13C, and 15N at magnetic fields of 5, 9.4, and 14.1 T. Both ions are half-integer high-spin systems with a zero-field splitting and therefore exhibit a broadening of the mS = −1/2 ↔ +1/2 central transition which scales inversely with the external field strength. We investigate experimentally the influence of the chelator molecule, strong hyperfine coupling to the metal nucleus, and deuteration of the bulk matrix on DNP properties. At small Gd-DOTA concentrations the narrow central transition allows us to polarize nuclei with small gyromagnetic ratio such as 13C and even 15N via the solid effect. We demonstrate that enhancements observed are limited by the available microwave power and that large enhancement factors of >100 (for 1H) and on the order of 1000 (for 13C) can be achieved in the saturation limit even at 80 K. At larger Gd(III) concentrations (≥10 mM) where dipolar couplings between two neighboring Gd3+ complexes become substantial a transition towards cross effect as dominating DNP mechanism is observed. Furthermore, the slow spin-diffusion between 13C and 15N, respectively, allows for temporally resolved observation of enhanced polarization spreading from nuclei close to the paramagnetic ion towards nuclei further removed. Subsequently, we present preliminary DNP experiments on ubiquitin by site-directed spin-labeling with Gd3+ chelator tags. The results hold promise towards applications of such paramagnetically labeled proteins for DNP applications in biophysical chemistry and/or structural biology.
It’s intuitively plausible to suppose that there are many things that we can be rationally certain of, at least in many contexts. The present paper argues that, given this principle of Abundancy, there is a Preface Paradox for (rational) credence. Section 1 gives a statement of the paradox, discusses its relation to its familiar counterpart for (rational) belief, and points out the congeniality between Abundancy and broadly contextualist trends in epistemology. This leads to the question whether considerations of context-sensitivity might lend themselves to solving the Preface for credence. Sections 2 and 3 scrutinize two approaches in this spirit—one mimicking Hawthorne’s (2002) Semantic Contextualist approach to an epistemic version of the Preface, the other one analogous to Clarke’s (2015) Sensitivist approach to the doxastic version—arguing that neither approach succeeds as it stands.
Protective ant-plant mutualisms that are exploited by non-defending parasitic ants represent prominent model systems for ecology and evolutionary biology. The mutualist Pseudomyrmex ferrugineus is an obligate plant-ant and fully depends on acacias for nesting space and food. The parasite Pseudomyrmex gracilis facultatively nests on acacias and uses host-derived food rewards but also external food sources. Integrative analyses of genetic microsatellite data, cuticular hydrocarbons and behavioral assays showed that an individual acacia might be inhabited by the workers of several P. gracilis queens, whereas one P. ferrugineus colony monopolizes one or more host trees. Despite these differences in social organization, neither of the species exhibited aggressive behavior among conspecific workers sharing a tree regardless of their relatedness. This lack of aggression corresponds to the high similarity of cuticular hydrocarbon profiles among ants living on the same tree. Host sharing by unrelated colonies, or the presence of several queens in a single colony are discussed as strategies by which parasite colonies could achieve the observed social organization. We argue that in ecological terms, the non-aggressive behavior of non-sibling P. gracilis workers — regardless of the route to achieve this social structure — enables this species to efficiently occupy and exploit a host plant. By contrast, single large and long-lived colonies of the mutualist P. ferrugineus monopolize individual host plants and defend them aggressively against invaders from other trees. Our findings highlight the necessity for using several methods in combination to fully understand how differing life history strategies affect social organization in ants.
Previous investigation of seismic anisotropy indicates the presence of a simple mantle flow regime beneath the Turkish-Anatolian Plateau and Arabian Plate. Numerical modeling suggests that this simple flow is a component of a large-scale global mantle flow associated with the African superplume, which plays a key role in the geodynamic framework of the Arabia-Eurasia continental collision zone. However, the extent and impact of the flow pattern farther east beneath the Iranian Plateau and Zagros remains unclear. While the relatively smoothly varying lithospheric thickness beneath the Anatolian Plateau and Arabian Plate allows progress of the simple mantle flow, the variable lithospheric thickness across the Iranian Plateau is expected to impose additional boundary conditions on the mantle flow field. In this study, for the first time, we use an unprecedented data set of seismic waveforms from a network of 245 seismic stations to examine the mantle flow pattern and lithospheric deformation over the entire region of the Iranian Plateau and Zagros by investigation of seismic anisotropy. We also examine the correlation between the pattern of seismic anisotropy, plate motion using GPS velocities and surface strain fields. Our study reveals a complex pattern of seismic anisotropy that implies a similarly complex mantle flow field. The pattern of seismic anisotropy suggests that the regional simple mantle flow beneath the Arabian Platform and eastern Turkey deflects as a circular flow around the thick Zagros lithosphere. This circular flow merges into a toroidal component beneath the NW Zagros that is likely an indicator of a lateral discontinuity in the lithosphere. Our examination also suggests that the main lithospheric deformation in the Zagros occurs as an axial shortening across the belt, whereas in the eastern Alborz and Kopeh-Dagh a belt-parallel horizontal lithospheric deformation plays a major role.
In order to elucidate what species among so many kind of marine organisms are likely to be consmed Iargely by the balaenopterid whales, the existing evidence on the food habits of baleen whales is reviewed. To meet with this primary purpose the report was mainly focussed on to describe qualitative aspects of food species having been known to date from the notable whaling grounds over the world rather than documenting quantitative subjects. One of interesting facts noticed throughout the contribution was that there exists fairly intense diversity in the assembly of food species composition by regions such as; northern hemisphere vs. southern hemisphere, Pacific region vs. Atlantic region, inshore waters vs. offshore waters, embayed waters vs. open waters, where the former usually shows more diversed complexity than the latter. The fact however suggests that although the composition of food species locally varies over the various whaling grounds, the food organisms as taxonomical groups are very similar one another even in locally isolated whaIing grounds when the food organisms and their assemblies are considered by the family or genus basis. In this connection many evidences given in the text may suggest that the balaenopterid whales as a whole may substantially live on quite simply compositioned forage assembly in comparison with tremendous variety of organisms existing in the marine ecosystems. One of important aspects of the baleen whales food must be found in their characteristics of forming dense swarms, schools, and/or aggregations in the shallower enough layers to be fed by the whales. The present and past status of larger baleen whales as the mighty monarch through their evolutional pathways may entirely depend upon the spatial distribution pattern of possible food organisms, i.e. the animal aggregations.
Objective: We sought to evaluate the efficacy and tolerability of intranasal midazolam (in‐MDZ) as first‐line inhospital therapy in patients with status epilepticus (SE) during continuous EEG recording.
Methods: Data on medical history, etiology and semiology of SE, anticonvulsive medication usage, efficacy and safety of in‐MDZ were retrospectively reviewed between 2015 and 2018. Time to end of SE regarding the administration of in‐MDZ and ß‐band effects were analyzed on EEG and with frequency analysis.
Results: In total, 42 patients (mean age: 52.7 ± 22.7 years; 23 females) were treated with a median dose of 5 mg of in‐MDZ (range: 2.5–15 mg, mean: 6.4 mg, SD: 2.6) for SE. The majority of the patients suffered from nonconvulsive SE (n = 24; 55.8%). In total, 24 (57.1%) patients were responders, as SE stopped following the administration of in‐MDZ without any other drugs being given. On average, SE ceased on EEG at 05:05 (minutes:seconds) after the application of in‐MDZ (median: 04:56; range: 00:29–14:53; SD:03:13). Frequency analysis showed an increased ß‐band on EEG after the application of in‐MDZ at 04:07 on average (median: 03:50; range: 02:20–05:40; SD: 01:09). Adverse events were recorded in six patients (14.3%), with nasal irritations present in five (11.9%) and prolonged sedation occurring in one (2.6%) patient.
Conclusions: This pharmaco‐EEG–based study showed that in‐MDZ is effective and well‐tolerated for the acute treatment of SE. EEG and clinical effects of in‐MDZ administration occurred within 04:07 and 5:05 on average. Intranasal midazolam appears to be an easily applicable and rapidly effective alternative to buccal or intramuscular application as first‐line treatment if an intravenous route is not available.
Her yeni edebî metnin kendinden öncekilerden ya ilham aldığı ya da yeniden üretilerek ortaya çıktığı gerçeği bugün edebiyat çevreleri tarafından kabul edilen bir görüştür. Sinema sanatı edebiyat ile her zaman yakın ilişki içerisinde olmuştur. Senaryolar ise edebî metinlerden beslenerek onlardan ilham almıştır ya da özgün senaryo ile edebî metin benzeşmiştir. Edebiyattan beslenen sinema böylece kendi türünü de oluşturmaya başlamıştır. Özellikle melodram türü sinema filmleri 1960 - 1975 yılları arasında Yeşilçam sinemasına hâkim olmuştur. Hamdi Değirmencioğlu'nun 1973 yılında 10. Antalya Altın Portakal Film Festivalinde kendisine ödül kazandıran "Hayat mı Bu?" adlı melodram türündeki senaryosu Grimm Kardeşlerin Halk efsanesi olan "Die zwei gleichen Söhne" ile benzerlikler taşımaktadır. Grimm Kardeşlerin 1816–1818 yılları arasında yayınlanmış olan "Deutsche Sagen" (Alman Efsaneleri) eserinde toplam 585 halk efsanesi yer almaktadır. Halk efsanesine konu olan Genç Kral Pepin / III. Pepin (714-768) tarihsel gerçek bir kişidir ve hikâyesi Alman efsaneleri arasında 441. sırada yer almaktadır. Onun hayatından yola çıkarak anne kompleksinin negatif özellikli arketipi olan üvey anne figürüne farklı bir yorum katan bu Alman halk efsanesi, Değirmencioğlu'nun senaryosunu yazdığı 1972 yapımlı Yeşilçam Sinema filmindeki üvey anne figürü ile benzeşmektedir. Bu çalışmada, Grimm Kardeşlerin "Die zwei gleichen Söhne" adlı efsanesi ile Hamdi Değirmencioğlu'nun "Hayat mı Bu?" adlı film senaryosu metinlerarasılık kuramı ile incelenmeye çalışılmıştır.
Günter Grass'ın 'Yengeç Yürüyüşü" Romanında 'Konrad' Karakterini Dijital Kuşak Olarak Çözümleme
(2021)
"Yengeç Yürüyüşü" romanında, 1945 yılında Nasyonal Sosyalist dönemde torpillenen "Wilhelm Gustloff" gemisinin batırılış öyküsüyle birlikte Pokriefke ailesinin üç kuşak üyelerinin de aile öyküsüne yer verilmiştir."Y kuşağı" teknolojiye olan yatkınlığı ile bilinirken, günümüzde "Z kuşağı", iletişim araçları olarak internet ve akıllı telefonları daha etkin bir şekilde kullanmaktadır. Bu durumda her iki dijital kuşak da iletişim teknolojilerini iyi derecede kullanan teknoloji gurusu olarak kabul edilmektedir. Dijital temelli teknolojik gelişmelerin yaşamı değiştirmeye başladığı iki binli yıllar bu bağlamda dönüm noktası olarak ele alınabilir. Romanın olay örgüsünde 1995'lere gelindiğinde genç Konrad'ın dijital iletişim aracı olarak bilgisayar kullanması sonucunda internetten beslenen antisemitizmle yollarının kesişmesinin de öyküsü anlatılır. Romanda, ben-anlatıcı Paul'un başarısız gazetecilik kariyeri, ironik bir şekilde, yetenekli bir bilgisayar kullanıcısı olan oğlu Konrad'ın Neo-Nazilerin www.blutzeuge.de sayfasını düzenli olarak ziyaret etmesi gerçeği ile bir paradox oluşturur. Baba Paul'un başarısızlığının aksine Konrad, büyükanne Tulla'nın yardımıyla bir bilgisayar edinerek ihtiyacı olan bilgiyi elde etmekte başarılı olacaktır. Ancak, istediği bilgiye kavuşan Konrad, internet aracılığıyla bir yandan başarılı araştırmalara imza atarken öte yandan da internet üzerinden tanıştığı bir genci öldürme eylemine karışır. Bu olayla Nasyonal Sosyalist döneminin ideolojik propaganda çalışmalarının Neonazizm aracılığıyla yürütülmeye devam edildiğine bir göndermede bulunulduğu söylenebilir. Bu çalışmada üçüncü kuşak aile üyesi olan Konrad'ın dijital ortamı kullanarak kendisinden önceki kuşakların hatalarını yinelediği kesitler, metin odaklı bir yaklaşımla irdelenerek örnek ve alıntılarla çözümlenmeye çalışılacaktır.
Die Anzahl der Werke zum Thema Antikriegsliteratur, vor allem im Zusammenhang mit dem Ersten Weltkrieg, ist im literarischen Bereich reichlich vorhanden. Die deutsche Literatur bietet durch ihre umfangreiche Anzahl Möglichkeiten diese Werke zu untersuchen. Die Darstellung des Krieges in dem Roman "Im Westen nichts Neues" ist deshalb bemerkenswert, weil es viele Beispiele zum Thema Kriegstrauma enthält. Wie wird Kriegstrauma im Roman "Im Westen nichts Neues" in der Gegenwartsliteratur geschildert bzw. thematisiert? Um diese Frage zu beantworten, soll das Motiv, "Kriegstrauma" und dessen Darstellungen, die im Roman vorkommen, gelöst werden. Der Ausdruck auf der ersten Seite der Einführung des Romans "Die Schrecken des Ersten Weltkrieges sind die Schrecken aller Kriege", deutet auf das Hauptthema im Roman. Dieser Roman wird auch heute 100 Jahre nach dem Ersten Weltkrieg als ein Zeitzeugen-Dokument angesehen. Der Roman schildert die Erfahrungen eines einfachen Frontsoldaten im Ersten Weltkrieg, den Erich Maria Remarque im Jahre 1927 als er an der Westfront Dienst war geschrieben hat. Im Roman "Im Westen nichts Neues" wird die Geschichte des deutschen Soldaten Paul Bäumer und seiner Kameraden im Ersten Weltkrieg erzählt. Traumata / Kriegstraumata / Kriegserlebnisse der Soldaten an der Front sind ein zentrales Thema des Romans.
We simultaneously considered morphology and molecular phylogeny to modify the generic classification of the ‘pyropterine clade’ (Lycidae, Erotinae, Dictyopterini). To place species previously included in Benibotarus Kôno, 1932 in reciprocally monophyletic genera, we propose Gomezzuritus gen. nov. with the type-species Dictyopterus alternatus Fairmaire, 1856. Further, we transfer Gomezzuritus alternatus (Fairmaire, 1856) comb. nov., G. longicornis (Reiche, 1878) comb. nov., and G. rubripes (Pic, 1897) comb. nov. from Benibotarus to Gomezzuritus gen. nov. The pyropterine clade contains five genera in the Palaearctic region: Pyropterus Mulsant, 1838, Gomezzuritus gen. nov., Helcophorus Fairmaire, 1891, Greenarus Kazantsev, 1995, and Benibotarus Kôno, 1932. The arrangement of longitudinal elytral costae proved misleading for consideration of relationships. Two genera in distant positions share only four primary costae (Pyropterus and Helcophorus), and three similarly distant genera share the shortened primary costa 3, resulting in three primary and four secondary longitudinal costae (Gomezzuritus, Greenarus, and Benibotarus). The larva of Gomezzuritus alternatus is described in detail, and it is compared with the larvae of other Dictyopterini, including the presumed larva of G. longicornis.
The recently developed stereospecific sodium salt glycosylation procedure has been successfully applied to the synthesis of the β-ᴅ-2′-deoxyribofuranosides of benzimidazole, 5,6-dihalogeno benzimidazoles, and some 2-substituted analogues in high yield. The 5,6-dibromo analogue was obtained by bromination of the parent nucleoside. These have all been characterized by spectroscopic methods, including 1H NMR, which permitted analyses of their solution conformations and comparison with those of the corresponding ribofuranosides. Some biological aspects, including preliminary results on cytotoxicity and antiviral activity, are briefly considered.
This paper describes the effect of the "Boleslaw" mining and metallurgic complex in Bukowno near Olkusz on the vegetation of the fresh coniferous forest association Vaccinia myrtilli-Pineitum. The increase in concentration of zinc, lead and cadmium in selected plant species under the influence of industrial emission, and the dependence of this increase upon the magnitude of dust fall and site conditions, are analized. The extent of accumulation of heavy metals in plants was assumed to be an indicator of the degree of pressure exerted by the industrial complex. The degradation of fresh coniferous forest was. increasing along with an increase in this pressure. The species composition of the association, and the quantitative relations among species representing various site types underwent considerable changes. In patches extremely degraded, the plant species characteristic of poor sandy grass-lands gained predominance over forest plants.
Almanca dilbilgisinde tümcenin temel öğeleri genellikle eylem temel alınarak yapılır. Türkçe dilbilgisi için bu durum sözde kalmaktadır. Çünkü öğeler genellikle eylemin birleşim değeri göz önünde bulundurulmadan, o anda tümcede rastlantısal olarak bulunan öğeler olarak değerlendirilmektedir. Dolayısıyla, nitel araştırma yöntemiyle internetten ve basılı dokümanlardan elde edilen verilerin yorumlanmasıyla oluşan bu makalede, birleşim değeri çerçevesinde değerlendirme yapılmış olup eylemin gerektirdiği öğeler buna göre ele alınmalıdır. Diğer bir sorun da, Almanca dilbilgisi bağlamında üzerinde genel anlamda uzlaşılan, ancak Türkçede tartışmalı olan nesne terimi ve kavramıdır. Dolayısıyla bu çalışmada genel anlamda nesne kavramından yola çıkılarak sonilgeçli nesne kavramına gelinecektir. Amaç, Türkçe - Almanca nesne türlerini karşılaştırmak değil, Türk dili bağlamında “nesne”nin daha iyi anlaşılmasını sağlamak için Almancadan da örnekler vermektir. Nesne teriminin Türkçede Akkusativobjekt ile sınırlı tutulmasının yanlış olduğu ve çıkma durumu nesnesi, bulunma durumu nesnesi, sonilgeçli nesne gibi terimlerin dilbilgisel bir gerçek olduğu sonucuna varılmıştır. Bu bağlamda Türkçede eyleyen (Aktant) olarak sonilgeçli nesne (Postpositionalobjekt) gerektiren eylemler olduğu saptanmıştır.
Zu ausgewählten Aspekten der Selbstdarstellung von Ärzten auf deutschen Arztbewertungsportalen
(2019)
Doctors, like other professional groups, are subject to competition rules on the market. As a result, the issue of marketing in the field of medical services is becoming increasingly important. In recent years, the growing importance of doctor evaluation websites can be viewed from this perspective, as these websites give doctors opportunities for online self-presentation. The subject of this analysis is the profiles of doctors on one of the leading German doctor evaluation websites. The starting point for the analysis is the assumption that these websites not only contain information, but also appeal to readers, attempt to influence readers' attitudes, and consequently also contribute to the creation of a positive image of the doctor. Profiles are analyzed starting from a division into thematic blocks, with the help of which specific functions of these texts are implemented.
The current state of German studies is driving certain changes in degree programmes at Polish universities. Above all, students expect training in practical subjects. It is often noted that a change should take place in the field of German studies, in order to improve skills in the field of technical language and specialist communication. On the one hand, this would mean turning away from classic, canonical German studies. On the other hand, it would meet the expectations of future students. In this article we provide a critical overview of the curricular requirements regarding the technical language component of degree programmes at Polish universities. Degree programmes are analyzed in terms of the occurrence and content of the technical language component, and future developments are forecasted.
Die seit Jahren allmählich aber sukzessive ansteigende Digitalisierung bleibt nicht ohne Einfluss auf die Veränderungen in der Forschung, darunter auch in der Phraseologie. Den Möglichkeiten, die einem in diesem Kontext angeboten werden, scheinen keine Grenzen gesetzt zu werden. Das betrifft auch die Lexikographie - hier Phraseographie, die sich von der traditionellen Arbeitsweise und den Arbeitsmethoden immer mehr entfernt und Vorteile der digitalisierten Welt in zunehmendem Maße nutzt. Vor diesem Hintergrund wird zum einen das Potential der phraseologischen Online-Wörterbücher geprüft, das zum anderen mit den Möglichkeiten der Printwörterbücher verglichen wird. Das Ziel ist dabei, die Funktionalitäten der beiden Typen von phraseologischen Wörterbüchern miteinander zu vergleichen, um feststellen zu können, ob alle Vorteile der Digitalisierung von den Autoren der Online-Wörterbücher genutzt werden, um verschiedenen Erwartungen der Benutzer gerecht zu werden und ihre Bedürfnisse zu befriedigen. Die Grundlage der Analyse bilden auf der einen Seite sechs repräsentative phraseologische Printwörterbücher für Deutsch, vier für Polnisch, vier phraseologische deutsch-polnische Wörterbücher und zwei polnisch-deutsche und auf der anderen Seite drei Online-Wörterbücher für Deutsch, ein Online-Wörterbuch für Polnisch und zwei deutsch-polnische Online-Wörterbücher. Aus dem Vergleich der Mikrostruktur in den analysierten Wörterbüchern ergeben sich Schlussfolgerungen in Bezug auf die Empfehlungen und fertige Lösungen mancher Probleme lexikographischer Natur, die ihre Anwendung in der digitalen Phraseographie finden können.
Schriftsteller im Spagat : zur deutschsprachigen Gegenwartsliteratur von Autoren polnischer Herkunft
(2012)
Im Beitrag wird das Schaffen von drei Autoren polnischer Herkunft – Artur Becker, Dariusz Muszer und Leszek Oświęcimski – skizzenhaft präsentiert, die in den späten 1980er Jahren nach Deutschland migrierten. In ihren Romanen und Erzählungen thematisieren sie die Unmöglichkeit der Rückkehr (Becker), die Erfahrung totaler Fremdheit (Muszer) und Dekonstruktion der nationalen Stereotype (Oświęcimski). Der geschärfte Blick auf das Fremde und das Eigene aus der Perspektive der Migranten im (mentalen, kulturellen, künstlerischen) Spagat zwischen Polen und Deutschland sowie ihre erzählerischen Strategien bilden den Gegenstand des Beitrags.
Der Beitrag präsentiert die Ergebnisse einer Untersuchung, in der 120 verbale Phrasembelege aus 17 Leitartikeln des Mährischen Tagblatts (MT) vom August 1880 mit den Einträgen in ausgewählten Wörterbüchern der Gegenwartssprache verglichen wurden, um Informationen über die Entwicklung dieser Phraseme zu gewinnen. Die formalen und semantischen Unterschiede wurden nach dem Vergleich mit den Belegen im Deutschen Wörterbuch der Brüder Grimm und ggf. im Deutschen Referenzkorpus in 20 Fällen als ältere Varianten bestimmt, siebenmal ging es um kontextbedingte Modifikationen und dreimal wahrscheinlich um unbeabsichtigte Kontaminationen mehrerer Phraseme. Bei 23 Belegen kann man erst nach einem Vergleich mit weiteren MT- bzw. anderen zeitgenössischen Texten ihre Konnotationen bestimmen und entscheiden, ob es sich um ältere Varianten handelt oder ob ihre Verwendung schon der heutigen Kodifizierung entspricht. Mehr als die Hälfte der Phraseme (67 Tokens) wurden in der heutigen Form und Bedeutung verwendet.
Článek seznamuje s výsledky analýzy nadpisů na úvodnì stránce 16 rakouských internetových novin. Analýza se zaměřila na rozsah pouņitì frazémů v nadpisech, na typy pouņitých frazémů a na způsob jejich pouņitì (normálnì nebo modifikované) v souvislosti s tìm, zda se dané frazémy vyskytujì jen v nadpise nebo i v textu. Výsledky jsou porovnány se závěry dřìvějńìho obdobného výzkumu týkajìcìho se internetové verze rakouského denìku 'Die Presse'.
Výzkumy ukazují, že v novinových nadpisech se s oblibou používají frazémy. Otázkouje, zda to platí i pro internetové texty, jejichž nadpisy by měly obsahovat klíčová slova z textu a být tedy spíše informativní. Článek seznamuje s výsledky analýzy nadpisů v internetové verzi rakouského deníku Die Presse, která se zaměřila na rozsah použití frazémů v nadpisech textů jednotlivých rubrik, na typy použitých frazémů a na způsob jejich použití (normální nebo modifikované).
The paper is an analysis of the literal and the idiomatic use of the German word group '(jm.) (die/seine) Zähne zeigen' and of its Czech counterpart 'ukázat (někomu) (své) zoubky/zuby' (cf. 'to show (sb) one's teeth') in German and Czech electronic text corpora. Its aim is to find possible reasons for the translation of the German idiom in a novel by a single Czech word paraphrasing its meaning. Examples from the parallel corpora seem to support the assumption the reason could be the effort of the translator to prevent misinterpretation due to the difference in the frequency of the literal and the idiomatic use of the particular word group in the given languages.
The paper presents an analysis and a comparison of the meanings and functions of proverbs in two editorials by the lawyer and journalist Dr Jakob Eben. The texts comment on the situation and the relations between nationalities in the Habsburg Monarchy in July 1880. One proverb is used in its normal form by the author (directly), while the other appears in a modified form, in a quotation (indirectly). In both cases the proverbs are used as part of a persuasive strategy in the text type of the editorial, for the purpose of provoking antipathy against the "others", i.e. the Czech politicians as political rivals, by means of their negative characteristics. In their specific co-text and context, the proverbs acquire additional semantic-pragmatic components of meaning, enabling them to participate in various isotopic chains and to contribute significantly to textual coherence. Additionally, their positioning marks important points in the argumentative structure of the text. The analysis also indicates some possibilities for the specification of semantic and pragmatic information in dictionaries.
Příspěvek zkoumá, v jakém rozsahu je kontaktová funkce titulkŧ jedněch německých, jedněch rakouských a dvou ĉeských internetových novin realizována pomocí lexikálních prostředkŧ popisujících nebo vyjadřujících emoce.
Streamer chamber data for collisions of Ar + KCl and Ar + BaI2 at 1.2 GeV/nucleon are compared with microscopic model predictions based on the Vlasov-Uehling-Uhlenbeck equation, for various density-dependent nuclear equations of state. Multiplicity distributions and inclusive rapidity and transverse momentum spectra are in good agreement. Rapidity spectra show evidence of being useful in determining whether the model uses the correct cross sections for binary collisions in the nuclear medium, and whether momentum-dependent interactions are correctly incorporated. Sideward flow results do not favor the same nuclear stiffness parameter at all multiplicities.
Oscillating magnetic field disrupts magnetic orientation in Zebra finches, Taeniopygia guttata
(2009)
Background Zebra finches can be trained to use the geomagnetic field as a directional cue for short distance orientation. The physical mechanisms underlying the primary processes of magnetoreception are, however, largely unknown. Two hypotheses of how birds perceive magnetic information are mainly discussed, one dealing with modulation of radical pair processes in retinal structures, the other assuming that iron deposits in the upper beak of the birds are involved. Oscillating magnetic fields in the MHz range disturb radical pair mechanisms but do not affect magnetic particles. Thus, application of such oscillating fields in behavioral experiments can be used as a diagnostic tool to decide between the two alternatives. Methods In a setup that eliminates all directional cues except the geomagnetic field zebra finches were trained to search for food in the magnetic north/south axis. The birds were then tested for orientation performance in two magnetic conditions. In condition 1 the horizontal component of the geomagnetic field was shifted by 90 degrees using a helmholtz coil. In condition 2 a high frequently oscillating field (1.156 MHz) was applied in addition to the shifted field. Another group of birds was trained to solve the orientation task, but with visual landmarks as directional cue. The birds were then tested for their orientation performance in the same magnetic conditions as applied for the first experiment. Results The zebra finches could be trained successfully to orient in the geomagnetic field for food search in the north/south axis. They were also well oriented in test condition 1, with the magnetic field shifted horizontally by 90 degrees. In contrast, when the oscillating field was added the directional choices during food search were randomly distributed. Birds that were trained to visually guided orientation showed no difference of orientation performance in the two magnetic conditions.
Spätwerk, Alterswerk, Altersstil – an der Schwelle zur Ewigkeit streift der alte, der uralte Künstler die Fesseln des Materiellen und der Zeitlichkeit ab«, fasste der Kunsthistoriker Hans Ost 1992 die gängigen Vorstellungen zusammen, die bis heute gerne bemüht werden, wenn die Rede auf die späten und insbesondere die letzten Werke eines schöpferisch Tätigen kommt: Frei von jeglichen Verbindlichkeiten folgt der alte Meister anscheinend nur noch seinem Genius und schafft so das Unvergleichliche. Ost wies darauf hin, dass zwar bereits Goethe 1831 im Gespräch mit seinem Sekretär Friedrich Wilhelm Riemer den Eindruck äußerte, der Venezianer Tizian habe im hohen Alter in seinen Gemälden nur noch die abstrakte Idee der zuvor so täuschend echt nachgeahmten Stoffe geliefert – allerdings wies Goethe diesen Bildern, anders als ab dem 19. Jahrhundert bis zum Teil heute geschehend, nicht unweigerlich einen höheren künstlerischen Rang zu.
Gute Musikvideoclips weisen bei aller Ästhetisierung zuweilen ein durchaus kritisches Potenzial auf: das 1993 von Regisseur Marcus Nispel zu George Michaels Stück »Killer/Papa was a rolling stone« gedrehte Video greift überwiegend auf Haushaltsartikel, deren Firmenlogos und Werbespots zurück, die uns aus dem Alltag bekannt sind, ersetzt die Namen der Artikel jedoch durch einzelne Worte, die dem Liedtext entstammen. So ergibt sich eine den Glücksversprechen der Konsumindustrie gegenüber provokante Aussage, denn die zu Logos und Produktnamen umfunktionierten Begriffe bezeichnen gerade menschliche Grunderfahrungen und Tugenden wie »Freiheit«, »Leben«, »Wahrheit« und »Sterben«, die somit als dem Ausverkauf anheim gegeben dargestellt werden.