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Introduction: Vasospastic brain infarction is a devastating complication of aneurysmal subarachnoid hemorrhage (SAH). Using a probe for invasive monitoring of brain tissue oxygenation or blood flow is highly focal and may miss the site of cerebral vasospasm (CVS). Probe placement is based on the assumption that the spasm will occur either at the dependent vessel territory of the parent artery of the ruptured aneurysm or at the artery exposed to the focal thick blood clot. We investigated the likelihood of a focal monitoring sensor being placed in vasospasm or infarction territory on a hypothetical basis.
Methods: From our database we retrospectively selected consecutive SAH patients with angiographically proven (day 7–14) severe CVS (narrowing of vessel lumen >50%). Depending on the aneurysm location we applied a standard protocol of probe placement to detect the most probable site of severe CVS or infarction. We analyzed whether the placement was congruent with existing CVS/infarction.
Results: We analyzed 100 patients after SAH caused by aneurysms located in the following locations: MCA (n = 14), ICA (n = 30), A1CA (n = 4), AcoA or A2CA (n = 33), and VBA (n = 19). Sensor location corresponded with CVS territory in 93% of MCA, 87% of ICA, 76% of AcoA or A2CA, but only 50% of A1CA and 42% of VBA aneurysms. The focal probe was located inside the infarction territory in 95% of ICA, 89% of MCA, 78% of ACoA or A2CA, 50% of A1CA and 23% of VBA aneurysms.
Conclusion: The probability that a single focal probe will be situated in the territory of severe CVS and infarction varies. It seems to be reasonably accurate for MCA and ICA aneurysms, but not for ACA or VBA aneurysms.
Recent clinical data support the clinical use of oral lavender oil in patients suffering from subsyndromal anxiety. We identified the molecular mechanism of action that will alter the perception of lavender oil as a nonspecific ingredient of aromatherapy to a potent anxiolytic inhibiting voltage dependent calcium channels (VOCCs) as highly selective drug target. In contrast to previous publications where exorbitant high concentrations were used, the effects of lavender oil in behavioral, biochemical, and electrophysiological experiments were investigated in physiological concentrations in the nanomolar range, which correlate to a single dosage of 80 mg/d in humans that was used in clinical trials. We show for the first time that lavender oil bears some similarities with the established anxiolytic pregabalin. Lavender oil inhibits VOCCs in synaptosomes, primary hippocampal neurons and stably overexpressing cell lines in the same range such as pregabalin. Interestingly, Silexan does not primarily bind to P/Q type calcium channels such as pregabalin and does not interact with the binding site of pregabalin, the α2δ subunit of VOCCs. Lavender oil reduces non-selectively the calcium influx through several different types of VOCCs such as the N-type, P/Q-type and T-type VOCCs. In the hippocampus, one brain region important for anxiety disorders, we show that inhibition by lavender oil is mainly mediated via N-type and P/Q-type VOCCs. Taken together, we provide a pharmacological and molecular rationale for the clinical use of the oral application of lavender oil in patients suffering from anxiety.
Im Rahmen des Vortrags wird zunächst ein Überblick über die aktuell angewandten Linsensysteme in der (refraktiven) Kataraktchirurgie sowie im Rahmen des RLA gesprochen. Hierzu zählen die monofokalen sphärischen Standardlinsen, aber auch asphärische, torische und multifokale Implantate.
Speziell wird auf die Ergebnisse einer Studie zu einem neuen multifokalen-torischen Implantat eingegangen. Der Schwerpunkt des Vortrages liegt dann weiterhin auf den trifokalen Korrektionsmöglichkeiten. Zum einen wird die sog. binokulare Trifokalität, bei der zwei multifokale Intraokularlinsen unterschiedlicher Addition implantiert werden, besprochen. Durch die Anpassung jeweils eines Auges an den Intermediär- bzw. Nahbereich soll so bei verringerten optischen Phänomenen ein deutliches Sehen in drei Hauptdistanzen ermöglicht werden. Weiterhin befasst sich der Vortrag aber auch mit den neuen echten trifokalen Optiksystemen, welche ebenfalls deutliches Sehen in verschiedenen Entfernungen gewährleisten können.
Im dritten Teil des Vortrages werden aktuelle Langzeitergebnisse aus einer FDA Studie zur Evaluation einer kammerwinkelgestützten phaken Intraokularlinse, mit speziellem Augenmerk auf den cornealen Endothelzellverlust, sowie eine neuartige sulcusgestütze phake Intraokularlinse mit zentralem Loch zur Glaukomvermeidung vorgestellt.
Dual-processing altruism
(2013)
Altruism refers to an other-benefiting behavior that is costly but bears no direct profit to oneself. At least three different forms can be distinguished: help giving, altruistic punishment, and moral courage. We investigated the differential impact of two thinking modes, intuitive (System 1) and rational (System 2), on these three altruistic behaviors. Situational (state-related) thinking style was manipulated via experimental instructions and generally preferred thinking style (trait-related) was assessed via questionnaires. We found that of the subjectively preferred thinking styles (trait), faith in intuition (System 1) promoted sharing and altruistic punishment, whereas need for cognition (System 2) promoted volunteering in a situation that required moral courage. By contrast, we did not find a significant effect of situational thinking style (state) on any of the altruistic behaviors, although manipulation checks were positive. Results elucidate the affective-motivational underpinnings of different types of altruistic behaviors.
Years of endemic infections with highly pathogenic avian influenza (HPAI) A subtype H5N1 virus in poultry and high numbers of infections in humans provide ample opportunity in Egypt for H5N1-HPAIV to develop pandemic potential. In an effort to better understand the viral determinants that facilitate human infections of the Egyptian H5N1-HPAIVvirus, we developed a new phylogenetic algorithm based on a new distance measure derived from the informational spectrum method (ISM). This new approach, which describes functional aspects of the evolution of the hemagglutinin subunit 1 (HA1), revealed a growing group G2 of H5N1-HPAIV in Egypt after 2009 that acquired new informational spectrum (IS) properties suggestive of an increased human tropism and pandemic potential. While in 2006 all viruses in Egypt belonged to the G1 group, by 2011 these viruses were virtually replaced by G2 viruses. All of the G2 viruses displayed four characteristic mutations (D43N, S120(D,N), (S,L)129Δ and I151T), three of which were previously reported to increase binding to the human receptor. Already in 2006–2008 G2 viruses were significantly (p<0.02) more often found in humans than expected from their overall prevalence and this further increased in 2009–2011 (p<0.007). Our approach also identified viruses that acquired additional mutations that we predict to further enhance their human tropism. The extensive evolution of Egyptian H5N1-HPAIV towards a preferential human tropism underlines an urgent need to closely monitor these viruses with respect to molecular determinants of virulence.
Introduction: Gastropoda are guided by several sensory organs in the head region, referred to as cephalic sensory organs (CSOs). These CSOs are innervated by distinct nerves. This study proposes a unified terminology for the cerebral nerves and the categories of CSOs and then investigates the neuroanatomy and cellular innervation patterns of these cerebral nerves, in order to homologise them. The homologisation of the cerebral nerves in conjunction with other data, e.g. ontogenetic development or functional morphology, may then provide insights into the homology of the CSOs themselves.
Results: Nickel-lysine axonal tracing (“backfilling”) was used to stain the somata projecting into specific nerves in representatives of opisthobranch Gastropoda. Tracing patterns revealed the occurrence, size and relative position of somata and their axons and enabled these somata to be mapped to specific cell clusters. Assignment of cells to clusters followed a conservative approach based primarily on relative location of the cells. Each of the four investigated cerebral nerves could be uniquely identified due to a characteristic set of soma clusters projecting into the respective nerves via their axonal pathways.
Conclusions: As the described tracing patterns are highly conserved morphological characters, they can be used to homologise nerves within the investigated group of gastropods. The combination of adequate number of replicates and a comparative approach allows us to provide preliminary hypotheses on homologies for the cerebral nerves. Based on the hypotheses regarding cerebral nerve homology together with further data on ultrastructure and immunohistochemistry of CSOs published elsewhere, we can propose preliminary hypotheses regarding homology for the CSOs of the Opisthobranchia themselves.
Introduction: Recent data suggest that benefit from trastuzumab and chemotherapy might be related to expression of HER2 and estrogen receptor (ESR1). Therefore, we investigated HER2 and ESR1 mRNA levels in core biopsies of HER2-positive breast carcinomas from patients treated within the neoadjuvant GeparQuattro trial.
Methods: HER2 levels were centrally analyzed by immunohistochemistry (IHC), silver in-situ hybridization (SISH) and qRT-PCR in 217 pretherapeutic formalin-fixed, paraffin-embedded (FFPE) core biopsies. All tumors had been HER2-positive by local pathology and had been treated with neoadjuvant trastuzumab/ chemotherapy in GeparQuattro.
Results: Only 73% of the tumors (158 of 217) were centrally HER2-positive (cHER2-positive) by IHC/SISH, with cHER2-positive tumors showing a significantly higher pCR rate (46.8% vs. 20.3%, p<0.0005). HER2 status by qRT-PCR showed a concordance of 88.5% with the central IHC/SISH status, with a low pCR rate in those tumors that were HER2-negative by mRNA analysis (21.1% vs. 49.6%, p<0.0005). The level of HER2 mRNA expression was linked to response rate in ESR1-positive tumors, but not in ESR1-negative tumors. HER2 mRNA expression was significantly associated with pCR in the HER2-positive/ESR1-positive tumors (p=0.004), but not in HER2-positive/ESR1-negative tumors.
Conclusions: Only patients with cHER2-positive tumors - irrespective of the method used - have an increased pCR rate with trastuzumab plus chemotherapy. In patients with cHER2-negative tumors the pCR rate is comparable to the pCR rate in the non-trastuzumab treated HER-negative population. Response to trastuzumab is correlated to HER2 mRNA levels only in ESR1-positive tumors. This study adds further evidence to the different biology of both subsets within the HER2-positive group.
Der "Beratungs-Wegweiser, Beratungsstellen und Adressverzeichnis" wird vom Studien-Service-Center (SSC) als ergänzendes Angebot zum „Wegweiser für Erstsemester“ sowie der Internetseite der Goethe-Universität herausgegeben und enthält studiengangbezogene Informationen und Kontaktdaten. Vertiefende Informationen zu diversitätsunterstützenden Angeboten der zentralen sowie fachübergreifenden Einrichtungen und der Fachbereiche können in der Broschüre "Diversity kompakt. Angebote für Studierende in unterschiedlichen Lebens und Studiensituationen" - herausgegeben von Di3 - nachgeschlagen werden.
Die Wissenschaft steht unter Druck. In Zeiten, in denen es um nichts Geringeres geht als um die Transformation hin zu einer nachhaltigen Entwicklung, fordern Gesellschaft und Politik von ihr nicht nur gesichertes, sondern vor allem anwendbares Wissen. Um solches Wissen erzeugen zu können, muss die Wissenschaft ihre Strukturen und Arbeitsformen verändern. Ein erneuertes Verständnis von Kritik kann Orientierung in diesem von der Wissenschaft aktiv zu gestaltenden Veränderungsprozess bieten.
Background: Critical organ shortage results in the utilization of extended donor criteria (EDC) liver grafts. These marginal liver grafts are prone to increased ischemia reperfusion injury (IRI) which may contribute to deteriorated graft function and survival. Experimental data have shown that the calcineurin inhibitor tacrolimus exerts protective effects on hepatic IRI when applied intravenously or directly as a hepatic rinse. Therefore, the aim of the present study is to examine the effects of an ex vivo tacrolimus perfusion on IRI in transplantation of EDC liver grafts.
Methods/Design: The TOP-Study (tacrolimus organ perfusion) is a randomized multicenter trial comparing the ex vivo tacrolimus perfusion of marginal liver grafts with placebo. We hypothesize that a tacrolimus rinse reduces IRI, potentially improving organ survival following transplantation of EDC livers. The study includes livers with two or more EDC, according to Eurotransplant International Foundation’s definition of EDC livers. Prior to implantation, livers randomized to the treatment group are rinsed with tacrolimus at a concentration of 20 ng/ml in 1000 ml Custodiol solution and in the placebo group with Custodiol alone. The primary endpoint is the maximum serum alanine transamninase (ALT) level within the first 48 hours after surgery; however, the study design also includes a 1-year observation period following transplantation. The TOP-Study is an investigator-initiated trial sponsored by the University of Munich Hospital. Seven other German transplant centers are participating (Berlin, Frankfurt, Heidelberg, Mainz, Münster, Regensburg, Tübingen) and aim to include a total of 86 patients.
Discussion: Tacrolimus organ perfusion represents a promising strategy to reduce hepatic IRI following the transplantation of marginal liver grafts. This treatment may help to improve the function of EDC grafts and therefore safely expand the donor pool in light of critical organ shortage.
Trial register: EudraCT number: 2010-021333-31, ClinicalTrials.gov identifier: NCT01564095
Aufgrund von § 84 Abs. 3 Nr. 1 des Hessischen Hochschulgesetzes vom 14. Dezember 2009 (GVBl. I, S. 666), zuletzt geändert durch Gesetz vom 26. Juni 2012 (GVBl. I, S. 227), und von § 10 Abs. 6 der Ordnung der Aka-demie für Bildungsforschung und Lehrerbildung an der Johann Wolfgang Goethe-Universität vom 19. April 2011 (UniReport Satzungen und Ordnungen vom 19. April 2011) haben das Direktorium der Akademie für Bildungsforschung und Lehrerbildung am 7. Februar 2013 sowie der Fachbereichsrat des Fachbereichs 4 am 12. Februar 2013 nachstehenden Änderungen beschlossen: ...
Für das Studium des Studienanteils Bildungswissenschaften in den Studiengängen Lehramt an Grundschulen (L 1), Lehramt an Haupt- und Realschulen (L 2), Lehramt an Gymnasien (L 3) und Lehramt an Förderschulen (L 5) hat die Akademie für Bildungsforschung und Lehrerbildung (ABL) der Goethe-Universität im Benehmen mit den Fachbereichen Gesellschaftswissenschaften (03), Erziehungswissenschaften (04), sowie Psychologie und Sportwissenschaften (05) der Goethe-Universität auf der Grundlage von § 48 Abs. 2 Ziff. 1 HHG, §§ 10, 12 der Ordnung der ABL i.V. mit § 28 Abs. 2 SPoL folgende Regelungen (fachspezifischer Anhang zur SPoL gemäß § 2 Abs. 2 SPoL) erlassen: ...
Aufgrund des Beschlusses des Fachbereichsrats des Fachbereichs Sprach- und Kulturwissenschaften der Johann Wolfgang Goethe-Universität vom 21.12.2012 wird die Ordnung für den Bachelorstudiengang Islamische Studien vom 14.07.2010 in der Fassung vom 06.10.211 nachfolgend geändert beziehungsweise ergänzt: ...
Background: After induction of DNA double strand breaks (DSBs), the DNA damage response (DDR) is activated. One of the earliest events in DDR is the phosphorylation of serine 139 on the histone variant H2AX (gH2AX) catalyzed by phosphatidylinositol 3-kinases-related kinases. Despite being extensively studied, H2AX distribution[1] across the genome and gH2AX spreading around DSBs sites[2] in the context of different chromatin compaction states or transcription are yet to be fully elucidated.
Materials and methods: gH2AX was induced in human hepatocellular carcinoma cells (HepG2) by exposure to 10 Gy X-rays (250 kV, 16 mA). Samples were incubated 0.5, 3 or 24 hours post irradiation to investigate early, intermediate and late stages of DDR, respectively. Chromatin immunoprecipitation was performed to select H2AX, H3 and gH2AX-enriched chromatin fractions. Chromatin-associated DNA was then sequenced by Illumina ChIP-Seq platform. HepG2 gene expression and histone modification (H3K36me3, H3K9me3) ChIP-Seq profiles were retrieved from Gene Expression Omnibus (accession numbers GSE30240 and GSE26386, respectively).
Results: First, we combined G/C usage, gene content, gene expression or histone modification profiles (H3K36me3, H3K9me3) to define genomic compartments characterized by different chromatin compaction states or transcriptional activity. Next, we investigated H3, H2AX and gH2AX distributions in such defined compartments before and after exposure to ionizing radiation (IR) to study DNA repair kinetics during DDR. Our sequencing results indicate that H2AX distribution followed H3 occupancy and, thus, the nucleosome pattern. The highest H2AX and H3 enrichment was observed in transcriptionally active compartments (euchromatin) while the lowest was found in low G/C and gene-poor compartments (heterochromatin). Under physiological conditions, the body of highly and moderately transcribed genes was devoid of gH2AX, despite presenting high H2AX levels. gH2AX accumulation was observed in 5’ or 3’ flanking regions, instead. The same genes showed a prompt gH2AX accumulation during the early stage of DDR which then decreased over time as DDR proceeded.
Finally, during the late stage of DDR the residual gH2AX signal was entirely retained in heterochromatic compartments. At this stage, euchromatic compartments were completely devoid of gH2AX despite presenting high levels of non-phosphorylated H2AX.
Conclusions: We show that gH2AX distribution ultimately depends on H2AX occupancy, the latter following H3 occupancy and, thus, nucleosome pattern. Both H2AX and H3 levels were higher in actively transcribed compartments. However, gH2AX levels were remarkably low over the body of actively transcribed genes suggesting that transcription levels antagonize gH2AX spreading. Moreover, repair processes did not take place uniformly across the genome; rather, DNA repair was affected by genomic location and transcriptional activity. We propose that higher H2AX density in euchromaticcompartments results in high relative gH2AXconcentration soon after the activation of DDR, thus favoring the recruitment of the DNA repair machinery to those compartments. When the damage is repaired and gH2AX is removed, its residual fraction is retained in the heterochromatic compartments which are then targeted and repaired at later times.
Background: Castleman’s disease is a rare lymphoproliferative disorder. It typically presents as mediastinal masses and causes a wide range of clinical symptoms. Histologically, Castleman’s disease is classified as either a hyalinic vascular or plasma cell variant. The prognosis mainly depends on the histological type and broadly varies. We herein report our sonographic findings in a patient with Castleman’s disease, including gray-scale ultrasonography, color Doppler ultrasonography, and sonoelastography ultrasonography, which have not been previously reported in the literature. These findings allowed for a preoperative diagnosis and avoidance of overly aggressive therapy.
Case presentation: A 28-year-old European female patient with unicentric Castleman’s disease of hyalinic vascular type (HV) restricted to the axilla was referred to us because of a 4-month history of a painless, solitary mass located in the left axilla. The patient’s medical history was unremarkable.
Conclusion: Castleman’s disease is a pathologic entity of unknown etiology and pathogenesis. In this case report of unicentric HV-type CD, we demonstrate that typical sonographic findings can lead to a preoperative diagnosis of Castleman’s disease. Core needle biopsy usually allows for a final diagnosis and helps to avoid unnecessary operations and overtreatment.
Background: The introduction of fast-track treatment procedures following cardiac surgery has significantly shortened hospitalisation times in intensive care units (ICU). Readmission to intensive care units is generally considered a negative quality criterion. The aim of this retrospective study is to statistically analyse risk factors and predictors for re-admission to the ICU after a fast-track patient management program.
Methods: 229 operated patients (67 ± 11 years, 75% male, BMI 27 ± 3, 6/2010-5/2011) with use of extracorporeal circulation (70 ± 31 min aortic crossclamping, CABG 62%) were selected for a preoperative fast-track procedure (transfer on the day of surgery to an intermediate care (IMC) unit, stable circulatory conditions, extubated). A uni- and multivariate analysis were performed to identify independent predictors for re-admission to the ICU.
Results: Over the 11-month study period, 36% of all preoperatively declared fast-track patients could not be transferred to an IMC unit on the day of surgery (n = 77) or had to be readmitted to the ICU after the first postoperative day (n = 4). Readmission or ICU stay signifies a dramatic worsening of the patient outcome (mortality 0/10%, mean hospital stay 10.3 ± 2.5/16.5 ± 16.3, mean transfusion rate 1.4 ± 1,7/5.3 ± 9.1). Predicators for failure of the fast-track procedure are a preoperative ASA class > 3, NYHA class > III and an operation time >267 min ± 74. The significant risk factors for a major postoperative event (= low cardiac output and/or mortality and/or renal failure and/or re-thoracotomy and/or septic shock and/or wound healing disturbances and/or stroke) are a poor EF (OR 2.7 CI 95% 0.98-7.6) and the described ICU readmission (OR 0.14 CI95% 0.05-0.36).
Conclusion: Re-admission to the ICU or failure to transfer patients to the IMC is associated with a high loss of patient outcome. The ASA > 3, NYHA class > 3 and operation time >267 minutes are independent predictors of fast track protocol failure.
Aufgrund des Beschlusses des Fachbereichsrats des Fachbereichs Sprach- und Kulturwissenschaften der Johann Wolfgang Goethe-Universität vom 21.11.2012 wird die Ordnung für die Masterstudiengänge des Fachbereichs Sprach- und Kulturwissenschaften vom 21.05.2008, geändert am 11.05.2011, nachfolgend ergänzt: ...
Die folgende Grundordnung ist gemäß §§ 36 Abs. 2, 84 Abs. 2 S. 2 des Hessischen Hochschulgesetzes (HHG) vom 23. Dezember 2009 (GVBl. I 2009, S. 666), zuletzt geändert durch Artikel 1 des Gesetzes vom 26. Juni 2012 (GVBl. I S. 227), im Einvernehmen mit dem Präsidium vom Senat der Johann Wolfgang Goethe-Universität Frankfurt am Main in seiner Sitzung am 30. Januar 2013 beschlossen und vom Hochschulrat am 14. Februar 2013 genehmigt worden.
Over the last century, humans from industrialized societies have witnessed a radical increase in some dental diseases. A severe problem concerns the loss of dental materials (enamel and dentine) at the buccal cervical region of the tooth. This “modern-day” pathology, called non-carious cervical lesions (NCCLs), is ubiquitous and worldwide spread, but is very sporadic in modern humans from pre-industrialized societies. Scholars believe that several factors are involved, but the real dynamics behind this pathology are far from being understood. Here we use an engineering approach, finite element analysis (FEA), to suggest that the lack of dental wear, characteristic of industrialized societies, might be a major factor leading to NCCLs. Occlusal loads were applied to high resolution finite element models of lower second premolars (P2) to demonstrate that slightly worn P2s envisage high tensile stresses in the buccal cervical region, but when worn down artificially in the laboratory the pattern of stress distribution changes and the tensile stresses decrease, matching the results obtained in naturally worn P2s. In the modern industrialized world, individuals at advanced ages show very moderate dental wear when compared to past societies, and teeth are exposed to high tensile stresses at the buccal cervical region for decades longer. This is the most likely mechanism explaining enamel loss in the cervical region, and may favor the activity of other disruptive processes such as biocorrosion. Because of the lack of dental abrasion, our masticatory apparatus faces new challenges that can only be understood in an evolutionary perspective.
Blood levels of Glial Fibrillary Acidic Protein (GFAP) in patients with neurological diseases
(2013)
Background and Purpose: The brain-specific astroglial protein GFAP is a blood biomarker candidate indicative of intracerebral hemorrhage in patients with symptoms suspicious of acute stroke. Comparably little, however, is known about GFAP release in other neurological disorders. In order to identify potential “specificity gaps” of a future GFAP test used to diagnose intracerebral hemorrhage, we measured GFAP in the blood of a large and rather unselected collective of patients with neurological diseases.
Methods: Within a one-year period, we randomly selected in-patients of our university hospital for study inclusion. Patients with ischemic stroke, transient ischemic attack and intracerebral hemorrhage were excluded. Primary endpoint was the ICD-10 coded diagnosis reached at discharge. During hospital stay, blood was collected, and GFAP plasma levels were determined using an advanced prototype immunoassay at Roche Diagnostics.
Results: A total of 331 patients were included, covering a broad spectrum of neurological diseases. GFAP levels were low in the vast majority of patients, with 98.5% of cases lying below the cut-off that was previously defined for the differentiation of intracerebral hemorrhage and ischemic stroke. No diagnosis or group of diagnoses was identified that showed consistently increased GFAP values. No association with age and sex was found.
Conclusion: Most acute and chronic neurological diseases, including typical stroke mimics, are not associated with detectable GFAP levels in the bloodstream. Our findings underline the hypothesis that rapid astroglial destruction as in acute intracerebral hemorrhage is mandatory for GFAP increase. A future GFAP blood test applied to identify patients with intracerebral hemorrhage is likely to have a high specificity.
Mit den sich wandelnden Anforderungen an den Fremdsprachenunterricht, die jeweilige Fremdsprache so zu unterrichten, dass sie schriftlich wie mündlich auch außerhalb schulischer Aufgabenstellungen verwendet werden kann, wandeln sich auch dementsprechend die Methoden. Diese variierenden Methoden nehmen häufig auf, was zuvor vielleicht von den vorausgegangenen Methoden vernachlässigt wurde und gehen auf aktuelle Bedürfnisse der Gesellschaft ein. Zudem berücksichtigen diese Methoden neueste Ergebnissen der unterschiedlichen Bezugswissenschaften. Deutsch als Fremdsprache/Zweitsprache ist von dieser Entwicklung der Methoden des Fremdsprachenunterrichts nicht auszunehmen. Ausgehend von diesen Festlegungen soll im Folgenden die Methode der Dramapädagogik und deren Bedeutung für den Erwerb der Fremdsprache kurz besprochen werden.
Ein besonders geeignetes Werk für die exemplarische Darstellung der stormschen Novellistik und Erzählkunst in seinen Ich-Erzählungen stellt die 78-seitige historische und gattungsgetreu geschlossene Novelle "Aquis Submersus" aus dem Jahre 1876 dar, die seiner "mittleren Schaffensperiode angehört, und damit zwischen seiner Früh- und Spätphase" (Kunze 1978: 283) angesiedelt ist. Sie weist eine prägnante Struktur und einen strengen Aufbau auf, der in insgesamt vier Teile mit zwei Hauptteilen untergliedert ist und eine Rahmenstruktur enthält. Dies zeigt sich auch darin, daß Storm die eigentliche Novellenhandlung in eine Rahmenerzählung einbettet, die eine weitere Rahmenkonstruktion umschliesst. Bevor jedoch auf die erzähltechnischen Besonderheiten eingegangen werden soll, ist es an dieser Stelle unumgänglich, zunächst einen kurzen Überblick über die Novelle folgen zu lassen, die die erzähltechnische Analyse unterstützen wird.
Else Lasker-Schüler, Tino und Jussuf, viele Namen, die sie sich selber gab, führen zu einer einzigartigen, starken Frau, die ihr Leben in Literatur umgesetzt hat. Zu einer Frau, die einer der führenden expressionistischen Persönlichkeiten wurde, ihr Leben literarisierend vermarktete und doch im wahrsten Sinne des Wortes nie mit sich und der Umwelt zufrieden werden konnte und auch werden wollte.
Background: Protein translocation across membranes is a central process in all cells. In the past decades the molecular composition of the translocation systems in the membranes of the endoplasmic reticulum, peroxisomes, mitochondria and chloroplasts have been established based on the analysis of model organisms. Today, these results have to be transferred to other plant species. We bioinformatically determined the inventory of putative translocation factors in tomato (Solanum lycopersicum) by orthologue search and domain architecture analyses. In addition, we investigated the diversity of such systems by comparing our findings to the model organisms Saccharomyces cerevisiae, Arabidopsis thaliana and 12 other plant species.
Results: The literature search end up in a total of 130 translocation components in yeast and A. thaliana, which are either experimentally confirmed or homologous to experimentally confirmed factors. From our bioinformatic analysis (PGAP and OrthoMCL), we identified (co-)orthologues in plants, which in combination yielded 148 and 143 orthologues in A. thaliana and S. lycopersicum, respectively. Interestingly, we traced 82% overlap in findings from both approaches though we did not find any orthologues for 27% of the factors by either procedure. In turn, 29% of the factors displayed the presence of more than one (co-)orthologue in tomato. Moreover, our analysis revealed that the genomic composition of the translocation machineries in the bryophyte Physcomitrella patens resemble more to higher plants than to single celled green algae. The monocots (Z. mays and O. sativa) follow more or less a similar conservation pattern for encoding the translocon components. In contrast, a diverse pattern was observed in different eudicots.
Conclusions: The orthologue search shows in most cases a clear conservation of components of the translocation pathways/machineries. Only the Get-dependent integration of tail-anchored proteins seems to be distinct. Further, the complexity of the translocation pathway in terms of existing orthologues seems to vary among plant species. This might be the consequence of palaeoploidisation during evolution in plants; lineage specific whole genome duplications in Arabidopsis thaliana and triplications in Solanum lycopersicum.
Background: In a previous analysis (Int J Radiat Oncol Biol Phys 70:828-835,2010), we assessed whether an adjuvant supplementation with selenium (Se) improves Se status and reduces the radiation-induced side-effects of patients treated by adjuvant radiotherapy (RT) for cervical and uterine cancer. Now, a potential relation between the planning target volume (PTV) of the RT and the Se effect concerning radiation induced diarrhoea was evaluated in detail.
Methods: Whole blood Se concentrations had been measured in patients with cervical (n=11) and uterine cancer (n=70) after surgical treatment, during, and at the end of RT. Patients with initial Se concentrations of less than 84 μg/l were categorized as Se-deficient and randomized before RT to receive Se (as sodium selenite) per os on the days of RT, or to receive no supplement during RT. Diarrhoea was graded according to the Common Toxicity Criteria system (CTC, Version 2a). The evaluation of the PTV of the RT was ascertained with the help of a specialised computer-assisted treatment planning software used for radiation planning procedure.
Results: A total of 81 patients had been randomized for the initial supplementation study, 39 of which received Se [selenium group, SeG] and 42 serving as controls [control group, CG]. Mean Se levels did not differ between SeG and CG upon study initiation, but were significantly higher in the SeG compared to the CG at the end of RT. The actuarial incidence of at least CTC 2 radiation induced diarrhoea in the SeG was 20.5% compared to 44.5% in the CG (p=0.04). The median PTV in both groups was 1302 ml (916–4608). With a PTV of <= 1302 ml (n=41) the actuarial incidence of at least CTC 2 diarrhoea in the SeG was 22.3% (4 of 18 patients) compared to 34.8% (8 of 23 patients) in the CG (p=0.50). In patients with a PTV of > 1302 ml (n=40) the actuarial incidence of at least CTC 2 diarrhoea in the SeG was 19.1% (4 of 21 patients) versus 52.6% (10 of 19 patients) in the CG (p=0.046).
Conclusions: Se supplementation during RT was effective to improve blood Se status in Se-deficient cervical and uterine cancer patients, and reduces episodes and severity of RT-induced diarrhoea. This effect was most pronounced and significant in patients with large PTV (> 1302 ml).
Der Gemeinsame Vertreter kann in das Fadenkreuz der Anleihegläubiger geraten und in das des Emittenten. Er hat daher das rechte Maß zu finden zwischen Engagement, Sorgfalt und Konfliktbewältigung bei der Erfüllung seiner Aufgaben. Das gilt insbesondere dann, wenn der Schuldner in die Krise geraten ist und im Kreis der Anleihegläubiger der Ruf nach einem „aktiven“ und engagierten Vertreter laut wird.
Um einen „Hilferuf“ handelt es sich dabei nicht immer. Vielmehr haben sich einzelne Investoren darauf spezialisiert, Anleihebedingungen zu durchforsten, um etwaige – und sei es auch nur „technische“ - Verstöße gegen dort enthaltene rechtliche Vorgaben zu entdecken. Sind sie fündig geworden, aber durch „no-action“-Klauseln daran gehindert, selbst tätig zu werden, schauen sie auf den Gemeinsamen Vertreter und erwarten von ihm die aggressive Wahrnehmung ihrer Rechte. Dazu kann gehören, aktiv die Fälligstellung zu fordern und so Drohpotential gegen den Emittenten aufzubauen;2 freilich, das muss nicht jedem Gläubiger recht sein, z.B. solchen, die bei zunächst eintretenden Kursverfall aus anlagerechtlichen Gründen gehalten ist, sich kostspielig vom Engagement zu trennen.
Konflikte innerhalb derselben Anleihegläubigerklasse sind damit programmiert. Und sie übertragen und bündeln sich dann in der Person des Gemeinsamen Vertreters – jedenfalls dann, wenn er exklusiv damit betraut ist, über die Ausübung von Gläubigerrechten zu befinden. Der gemeinsame Vertreter steht dann vor der Frage, ob er den Erwartungen aggressiver Obligationäre nachgeben soll oder nicht.3 Er muss deshalb wissen, was seine Rolle ist. Dazu ist die Reichweite seiner Interventionsmöglichkeiten und –pflichten im Spannungsfeld zwischen gesetzlicher und rechtsgeschäftlicher Aufgabenzuweisung, business judgment rule, Haftungsbeschränkung und der Beschlusskontrolle näher zu bestimmen; ansonsten wird es nicht zur gewünschten Koordinierung des Gläubigerverhaltens durch den Gemeinsamen Vertreter kommen.
Im Folgenden soll eine Diskussion über die dabei entstehenden Rückkoppelungseffekte angestoßen werden, welche sich mit dem gesetzgeberischen Idealbild nicht so recht zu vertragen scheinen.
Seit Erlass des Schuldverschreibungsgesetzes von 2009 (SchVG) zeichnet sich ab, dass die Emissionspraxis der deutschen Staatsanleihen im Hinblick auf kollektive Gläubigermechanismen („Collective Action Clauses“ – CACs), wie sie das SchVG erstmals rechtssicher ermöglicht, substantiellen Änderungen unterliegen wird. Während die Haltung inländischer öffentliche Emittenten noch bei Verabschiedung des SchVG reserviert war, hat sich die Situation seit Mai 2010 grundlegend geändert: Verschiedene Mitgliedstaaten der Eurozone sind mit Verbindlichkeiten in ihrer Währung in Schwierigkeiten geraten und mussten um internationale Hilfe nachsuchen. Vor dem Hintergrund der politischen Forderung nach einer Beteiligung der bestehenden Gläubigerschaft („private sector involvement“, „PSI“) musste schließlich Griechenland im Frühjahr 2012 eine Umschuldung (mithilfe entsprechender Klauseln) bemühen. Politische und rechtliche Festlegungen der Eurogruppe über die künftige Dokumentation der (verbrieften) Staatenschuld im Hinblick auf eine potentiell erforderlich werdende Umschuldung folgten. Bei den nationalen Umsetzungsarbeiten sind auch gewisse „Unzulänglichkeiten“ des durch das SchVG geschaffenen gesetzlichen Gestaltungsrahmens aufgegriffen worden.
Die nachfolgende Abhandlung zeichnet im Einzelnen die verschiedenen Entwicklungslinien nach, beginnend (i) mit dem SchVG und der darin zum Ausdruck gekommenen traditionellen Haltung der öffentlichen Hand zu CACs, leitet über (ii) zur GriechenlandUmschuldung („PSI“) und deren rechtlichen Besonderheiten und Ergebnisse unter dem (neuen) Blickwinkel einer Beteiligung privater Gläubiger, soll (iii) die von der Eurogruppe gezogenen Konsequenzen in Gestalt der Empfehlungen des Wirtschafts- und Finanzausschusses für „Umschuldungsklauseln“ der Mitgliedsstaaten der Eurozone im Hinblick auf Art. 12 Abs. 3 des ESM-Vertrags erläutern und schließlich (iv) einen Überblick über die gesetzgeberischen Schritte in Deutschland zur Umsetzung der Empfehlungen liefern.
Thesen
1. Um die Anerkennung einer Beschlussnichtigkeit in extremen Situationen wird man kaum umhin kommen. Der Gesetzgeber sollte die Nichtigkeitsgründe und ihre Geltendmachung wie im Aktienrecht klarstellend einschränken.
2. Gläubigerbeschlüsse unterliegen einer (begrenzten) materiellen Beschlusskontrolle anhand des Maßstabs der „gemeinsamen Interessen“ der Gläubigergesamtheit. Ohne ein derartiges materielles Kriterium wird man nicht auskommen. Wie es letztendlich benannt wird, ist dann nichts weiter als eine Frage der Begrifflichkeit. Eine gesetzliche Klarstellung erscheint nicht zwingend. Inhaltlich muss sich die materielle Beschlusskontrolle beschränken auf den Ausschluss sachfremder Erwägungen als Grundlage eines Eingriffs der Mehrheit in Rechte und Ansprüche der Minderheit.
3. Die Gestaltungswirkung des der Anfechtungsklage stattgebenden Urteils folgt bereits aus der kollektiven Bindung des § 4 SchVG. Eine – wenngleich nicht zwingende – gesetzliche Klarstellung könnte in Gestalt eines Hinweises in § 20 SchVG erfolgen, dass ein der Anfechtungs- (und Nichtigkeits-) Klage stattgebendes Urteil der kollektiven Bindung des § 4 SchVG unterliegt.
Der gesetzlichen Korrektur und Präzisierung bedürfen, nicht zuletzt im Interesse der Beschleunigung, Vollzugssperre und Freigabeverfahren.
Die vorstehenden Überlegungen führen zu folgenden Ergebnissen:
1. Das SchVG erlaubt den Gläubigern sämtlicher vor Inkrafttreten des Gesetzes begebenen Anleihen, einschließlich solcher die nicht dem SchVG 1899 unterliegen, einen Beschluss über die Anwendbarkeit des SchVG zu fassen (Opt-in).
2. Der Anwendbarkeit des SchVG und damit insbesondere auch der Opt-in-Regelung steht eine Teilrechtswahl ausländischen Rechts in den Anleihebedingungen nicht entgegen, solange die Substanz der verbrieften Forderung deutschem Recht unterliegt.
Dies ergibt sich bereits aus dem gültigen Gesetz. Aufgrund entgegenstehender instanzgerichtlicher Rechtsprechung besteht allerdings Klarstellungsbedarf. Dies insbesondere auch deshalb, weil hiermit Fragen angesprochen sind, welche die Funktionsfähigkeit und Marktakzeptanz des neuen Gesetzes in wesentlichen Anwendungsbereichen berühren. Im Rahmen der Reform des Schuldverschreibungsrechts hat die Bundesregierung angekündigt, laufend zu prüfen, ob beabsichtigten Wirkungen dieses Gesetzes erreicht worden sind, und, soweit erforderlich, rechtzeitig die hieraus resultierenden erforderlichen Maßnahmen zu ergreifen.48 Nachdem unlängst bereits die Straffung des Freigabeverfahrens erfolgte49 ist zu hoffen, dass auch der hier identifizierte gesetzliche Klarstellungsbedarf zügig in Angriff genommen wird.
Ribosome biogenesis is best understood in the yeast Saccharomyces cerevisiae. In human or mammalian ribosome biogenesis, it has been shown that basic principles are conserved to yeast, but additional features have been reported. Our understanding about the interplay between proteins and RNA in human ribosome biogenesis is far from complete.
The present study focused on the analysis of the human ribosome biogenesis co-factors PWP2, EMG1 and Exportin 5 (XPO5) to understand the degree of conservation of ribosome biogenesis. The proteins were characterized in respect to their localization and interaction partners. For the early 90S co-factor, PWP2, it was possible to pull down and identify the human UTP-B complex with MALDI mass spectrometry. Besides the orthologues of the members of this complex known in yeast (TBL3, WDR3, WDR36, UTP6, UTP18), the human UTP-B complex is not only conserved from yeast to humans, but contains also additional components, like the DEAD-box RNA helicase DDX21, which lacks a yeast orthologue. DDX21 was localized to the nucleus, assembled to the native UTP-B complex and co-precipitated also with other UTP-B complex members, presumably extending the functions of this complex in ribosome biogenesis.
This phenomenon was also observed for the 90S co-factor EMG1, an RNA methyltransferase, whose mutant form causes the Bowen-Conradi syndrome, if aspartic acid is mutated to glycine at position 86. This study revealed that the mutant, EMG1-D86G, clearly lost its nucleolar localization and co-precipitated to histones for unknown reasons.
A participation of the nuclear export receptor XPO5 in human ribosome biogenesis was shown in this study. Pulldown analysis, sucrose density gradients and UV crosslinking and analysis of cDNAs of XPO5 revealed the involvement of XPO5 in pre-60S subunit maturation. Moreover, besides the known pre-miRNAs and tRNAs as substrates for nuclear export, XPO5 crosslinked to snoRNAs. XPO5 was further demonstrated to interact with the miRNA Let-7a, which has an important regulatory function for MYC, a transcription factor required for ribosome biogenesis.
All results support a role of these proteins in human ribosome biogenesis and therefore it seems that the biogenesis of ribosomes in human cells requires additional components, like DDX21 and XPO5.
Are books different? : Die Auswirkungen des Falls der Buchpreisbindung in Großbritannien 1995 - 2006
(2013)
Sicherlich gibt es im Buchhandel wie in jeder anderen Branche Zeiten der Krise und des Umsatzrückgangs, aber grundsätzlich legen die Zahlen nicht nah, dass das Ende bevorsteht. Es stellt sich also die Frage, ob zutrifft, was Richter Buckley in seinem zum geflügelten Wort gewordenen Urteil feststellte: Sind Bücher wirklich anders, oder anders gefragt, braucht der Buchhandel den Schutz des Staates, um seine Funktion erfüllen zu können?
Um eine Antwort auf diese Fragen zu finden, soll in dieser Arbeit das Hauptaugenmerk auf die Entwicklung des britischen Buchhandels im Zeitraum von 1995 (dem Jahr der faktischen Abschaffung des Net Book Agreement bis 2006 gelegt werden. Nach dem beinahe hundertjährigen Bestehen der Buchpreisbindung waren diese Jahre richtungweisend für die Neuorientierung des britischen Buchhandels auf die Bedingungen eines freien Marktes, und es soll untersucht werden, welche Umwälzungen sich daraus für die Branche ergeben haben.
Current theories of the pathophysiology of schizophrenia have focused on abnormal temporal coordination of neural activity. Oscillations in the gamma-band range (>25 Hz) are of particular interest as they establish synchronization with great precision in local cortical networks. However, the contribution of high gamma (>60 Hz) oscillations toward the pathophysiology is less established. To address this issue, we recorded magnetoencephalographic (MEG) data from 16 medicated patients with chronic schizophrenia and 16 controls during the perception of Mooney faces. MEG data were analysed in the 25–150 Hz frequency range. Patients showed elevated reaction times and reduced detection rates during the perception of upright Mooney faces while responses to inverted stimuli were intact. Impaired processing of Mooney faces in schizophrenia patients was accompanied by a pronounced reduction in spectral power between 60–120 Hz (effect size: d = 1.26) which was correlated with disorganized symptoms (r = −0.72). Our findings demonstrate that deficits in high gamma-band oscillations as measured by MEG are a sensitive marker for aberrant cortical functioning in schizophrenia, suggesting an important aspect of the pathophysiology of the disorder.