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The 25S rRNA of yeast contains several base modifications in the functionally important regions. The enzymes responsible for most of these base modifications remained unknown. Recently, we identified Rrp8 as a methyltransferase involved in m1A645 modification of 25S rRNA. Here, we discovered a previously uncharacterized gene YBR141C to be responsible for second m1A2142 modification of helix 65 of 25S rRNA. The gene was identified by reversed phase–HPLC screening of all deletion mutants of putative RNA methyltransferase and was confirmed by gene complementation and phenotypic characterization. Because of the function of its encoded protein, YBR141C was named BMT2 (base methyltransferase of 25S RNA). Helix 65 belongs to domain IV, which accounts for most of the intersubunit surface of the large subunit. The 3D structure prediction of Bmt2 supported it to be an Ado Met methyltransferase belonging to Rossmann fold superfamily. In addition, we demonstrated that the substitution of G180R in the S-adenosyl-l-methionine–binding motif drastically reduces the catalytic function of the protein in vivo. Furthermore, we analysed the significance of m1A2142 modification in ribosome synthesis and translation. Intriguingly, the loss of m1A2142 modification confers anisomycin and peroxide sensitivity to the cells. Our results underline the importance of RNA modifications in cellular physiology.
In previous work we have documented the nuclear translocation of endothelial NOS (eNOS) and its participation in combinatorial complexes with Estrogen Receptor Beta (ERβ) and Hypoxia Inducible Factors (HIFs) that determine localized chromatin remodeling in response to estrogen (E2) and hypoxia stimuli, resulting in transcriptional regulation of genes associated with adverse prognosis in prostate cancer (PCa). To explore the role of nuclear eNOS in the acquisition of aggressive phenotype in PCa, we performed ChIP-Sequencing on chromatin-associated eNOS from cells from a primary tumor with poor outcome and from metastatic LNCaP cells. We found that: 1. the eNOS-bound regions (peaks) are widely distributed across the genome encompassing multiple transcription factors binding sites, including Estrogen Response Elements. 2. E2 increased the number of peaks, indicating hormone-dependent eNOS re-localization. 3. Peak distribution was similar with/without E2 with ≈ 55% of them in extragenic DNA regions and an intriguing involvement of the 5′ domain of several miRs deregulated in PCa. Numerous potentially novel eNOS-targeted genes have been identified suggesting that eNOS participates in the regulation of large gene sets. The parallel finding of downregulation of a cluster of miRs, including miR-34a, in PCa cells associated with poor outcome led us to unveil a molecular link between eNOS and SIRT1, an epigenetic regulator of aging and tumorigenicity, negatively regulated by miR-34a and in turn activating eNOS. E2 potentiates miR-34a downregulation thus enhancing SIRT1 expression, depicting a novel eNOS/SIRT1 interplay fine-tuned by E2-activated ER signaling, and suggesting that eNOS may play an important role in aggressive PCa.
Prof. Dr. Kasım Eğit hat 1970 die Abteilung für deutsche Sprache und Literatur an der Atatürk Universität in Erzurum absolviert und hat 1978 den Doktortitel an der Ruhr Universität-Bochum erhalten. Er ist gegenwärtig als Abteilungsleiter für deutsche Sprache und Literatur an der Ege Universität tätig und hat in den Jahren 2003-2009 das Dekanat der philosophischen Fakultät der Ege Universität geleitet. Zwischen den Jahren 1993-2009 war er Abteilungsleiter in der Hochschule für Fremdsprachen. Neben diesen diversen Diensten hat Herr Eğit als Literaturwissenschaftler und auch als Übersetzer viele gewinnbringende Werke für die deutsche und türkische Sprache und Literatur veröffentlicht.
Environmental change impacts on the C- and N-cycle of European forests: a model comparison study
(2013)
Forests are important components of the greenhouse gas balance of Europe. There is considerable uncertainty about how predicted changes to climate and nitrogen deposition will perturb the carbon and nitrogen cycles of European forests and thereby alter forest growth, carbon sequestration and N2O emission. The present study aimed to quantify the carbon and nitrogen balance, including the exchange of greenhouse gases, of European forests over the period 2010–2030, with a particular emphasis on the spatial variability of change. The analysis was carried out for two tree species: European beech and Scots pine. For this purpose, four different dynamic models were used: BASFOR, DailyDayCent, INTEGRATOR and Landscape-DNDC. These models span a range from semi-empirical to complex mechanistic. Comparison of these models allowed assessment of the extent to which model predictions depended on differences in model inputs and structure. We found a European average carbon sink of 0.160 ± 0.020 kgC m−2 yr−1 (pine) and 0.138 ± 0.062 kgC m−2 yr−1 (beech) and N2O source of 0.285 ± 0.125 kgN ha−1 yr−1 (pine) and 0.575 ± 0.105 kgN ha−1 yr−1 (beech). The European average greenhouse gas potential of the carbon sink was 18 (pine) and 8 (beech) times that of the N2O source. Carbon sequestration was larger in the trees than in the soil. Carbon sequestration and forest growth were largest in central Europe and lowest in northern Sweden and Finland, N. Poland and S. Spain. No single driver was found to dominate change across Europe. Forests were found to be most sensitive to change in environmental drivers where the drivers were limiting growth, where changes were particularly large or where changes acted in concert. The models disagreed as to which environmental changes were most significant for the geographical variation in forest growth and as to which tree species showed the largest rate of carbon sequestration. Pine and beech forests were found to have differing sensitivities to environmental change, in particular the response to changes in nitrogen and precipitation, with beech forest more vulnerable to drought. There was considerable uncertainty about the geographical location of N2O emissions. Two of the models BASFOR and LandscapeDNDC had largest emissions in central Europe where nitrogen deposition and soil nitrogen were largest, whereas the two other models identified different regions with large N2O emission. N2O emissions were found to be larger from beech than pine forests and were found to be particularly sensitive to forest growth.
In 'Mein Jenseits', der dritten Novelle innerhalb Walsers umfangreicher literarischer Produktion, werden uns von Walsers früheren Büchern bekannte Themen aus einer neuen, einem "Spätwerk" entsprechenden Perspektive dargeboten, wie im Laufe dieser Analyse gezeigt werden soll. In diesem Zusammenhang soll besonders die zentrale Rolle, die hier einem Bild für das Textganze zukommt, beleuchtet werden.
Wie bekannt, besitzt neben der literarischen Übersetzung auch die fachsprachliche Übertragung einen wichtigen Platz in der übersetzungswissenschaftlichen Forschung. In Rahmen des Themas Übersetzung und Bearbeitung soll in diesem Beitrag festgestellt werden, welche satzstrukturelle Abwandlungen das neue Strafgesetzbuch der Türkei (YTCK) vollzogen hat.
Einen Witz oder eben auch eine Geschichte gut zu erzählen ist ein risikoreiches Unterfangen und verlangt nach bestimmten Kompetenzen. Literaturwissenschaftliche wie auch sprach- und übersetzungswissenschaftliche Beiträge haben sich mit dem Erzählen beschäftigt, und das Fazit scheint berechtigt, Erzähltexte als Schnittstelle fachlicher Entwicklungen anzusehen. Sie erweisen sich als besonders günstige Anschlussstelle für Fragestellungen, die intradisziplinäre Grenzziehungen überschreiten. Dies soll in der folgenden kleinen Skizze aus linguistischer Sicht genauer entfaltet werden.
Ortak ve Suni dil üzerine
(2013)
Ortak ve Suni dilin ayrıştığı nokta bir toplum içerisinde bireylerin sağlıklı iletişim kuramamaları sonucu birbirlerini anlamadıkları ve iletişimin abartılı bir durumda değerlendirilmesidir. Bireyler arasında sağlıklı iletişimin sağlanması, aralarında ihtilafın giderilmesi gibi konular dilbilimcilerin başlıca araştırma alanlarını oluşturmaktadır. Diğer bir ifade ile yapay dil ile ortak bir dilin amaçlanması, geliştirilmesi 16.y.y. dan itibaren günümüze değin sürdürülmüştür. Ne var ki konuyu sadece art zamanlı olarak değerlendirmek yerine, aynı toplum içerisinde eş zamanlı olarak nasıl irdelenebilir? Zira ortak dilin "evrensel" bir dil olduğu varsayımından hareketle aynı toplum içerisinde, iletişimin genellikle "yapay" bir dille gerçekleştiği savını da öne sürebiliriz. Bir toplum içerisinde ortak dile ulaşmanın yolu analiz-sentez yolu ile kavrama kültürünün doğru orantılı olmasıdır.
DEAD box helicases catalyze the ATP-dependent destabilization of RNA duplexes. Whereas duplex separation is mediated by the helicase core shared by all members of the family, flanking domains often contribute to binding of the RNA substrate. The Thermus thermophilus DEAD-box helicase Hera (for “heat-resistant RNA-binding ATPase”) contains a C-terminal RNA-binding domain (RBD). We have analyzed RNA binding to the Hera RBD by a combination of mutational analyses, nuclear magnetic resonance and X-ray crystallography, and identify residues on helix α1 and the C-terminus as the main determinants for high-affinity RNA binding. A crystal structure of the RBD in complex with a single-stranded RNA resolves the RNA–protein interactions in the RBD core region around helix α1. Differences in RNA binding to the Hera RBD and to the structurally similar RBD of the Bacillus subtilis DEAD box helicase YxiN illustrate the versatility of RNA recognition motifs as RNA-binding platforms. Comparison of chemical shift perturbation patterns elicited by different RNAs, and the effect of sequence changes in the RNA on binding and unwinding show that the RBD binds a single-stranded RNA region at the core and simultaneously contacts double-stranded RNA through its C-terminal tail. The helicase core then unwinds an adjacent RNA duplex. Overall, the mode of RNA binding by Hera is consistent with a possible function as a general RNA chaperone.
When studying new particle formation, the uncertainty in determining the "true" nucleation rate is considerably reduced when using Condensation Particle Counters (CPCs) capable of measuring concentrations of aerosol particles at sizes close to or even at the critical cluster size (1–2 nm). Recently CPCs, able to reliably detect particles below 2 nm in size and even close to 1 nm became available. The corrections needed to calculate nucleation rates are substantially reduced compared to scaling the observed formation rate to the nucleation rate at the critical cluster size. However, this improved instrumentation requires a careful characterization of their cut-off size and the shape of the detection efficiency curve because relatively small shifts in the cut-off size can translate into larger relative errors when measuring particles close to the cut-off size.
Here we describe the development of two continuous flow CPCs using diethylene glycol (DEG) as the working fluid. The design is based on two TSI 3776 counters. Several sets of measurements to characterize their performance at different temperature settings were carried out. Furthermore two mixing-type Particle Size Magnifiers (PSM) A09 from Airmodus were characterized in parallel. One PSM was operated at the highest mixing ratio (1 L min−1 saturator flow), and the other was operated in a scanning mode, where the mixing ratios are changed periodically, resulting in a range of cut-off sizes. Different test aerosols were generated using a nano-Differential Mobility Analyzer (nano-DMA) or a high resolution DMA, to obtain detection efficiency curves for all four CPCs. One calibration setup included a high resolution mass spectrometer (APi-TOF) for the determination of the chemical composition of the generated clusters. The lowest cut-off sizes were achieved with negatively charged ammonium sulphate clusters, resulting in cut-offs of 1.4 nm for the laminar flow CPCs and 1.2 and 1.1 nm for the PSMs. A comparison of one of the laminar-flow CPCs and one of the PSMs measuring ambient and laboratory air showed good agreement between the instruments.
The SAWNUC microphysical aerosol nucleation model is used to study the effect of reactor walls on the interpretation of nucleation experiments with respect to nucleation theory. This work shows that loss processes, such as wall losses, influence the interpretation of nucleation experiments, especially at low growth rates and short lifetime of freshly nucleated particles. In these cases the power dependency of the formation rates, determined at a certain particle size, with respect to H2SO4 does not correspond to the approximate number of H2SO4 molecules in the critical cluster as expected by the first nucleation theorem. Observed ∂log(J)/∂log([H2SO4]) therefore can vary widely for identical nucleation conditions but different sink terms.
We investigate the contribution of oceanic methyl iodide (CH3I) to the stratospheric iodine budget. Based on CH3I measurements during three tropical ship campaigns and the Lagrangian transport model FLEXPART we provide a detailed analysis of CH3I transport from the ocean surface to the cold point in the upper tropical tropopause layer (TTL). While average oceanic emissions differ by less than 50% from campaign to campaign, the measurements show much stronger variations within each campaign. A positive correlation between the oceanic CH3I emissions and the efficiency of CH3I troposphere–stratosphere transport has been identified for some cruise sections. The mechanism of strong horizontal surface winds triggering large emissions on the one hand and being associated with tropical convective systems, such as developing typhoons, on the other hand, could explain the identified correlations. As a result of the simultaneous occurrence of large CH3I emissions and strong vertical uplift, localized maximum mixing ratios of 0.6 ppt CH3I at the cold point have been determined for observed peak emissions during the SHIVA-Sonne campaign in the coastal West Pacific. The other two campaigns give considerable smaller maxima of 0.1 ppt CH3I for the TransBrom campaign in the open West Pacific and 0.03 ppt for emissions from the coastal East Atlantic during the DRIVE campaign. In order to assess the representativeness of the large local mixing ratios we use climatological emission scenarios to derive global upper air estimates of CH3I abundances. The model results are compared to available upper air measurements including data from the recent ATTREX and HIPPO2 aircraft campaigns. In the East Pacific region, the location of the available measurement campaigns in the upper TTL, the comparisons give a good agreement indicating that around 0.01 to 0.02 ppt of CH3I enter the stratosphere. However, other tropical regions, which are subject to stronger convective activity show larger CH3I entrainment, e.g., 0.08 ppt in the West Pacific. The strong variations in the geographical distribution of CH3I entrainment suggest that currently available upper air measurements are not representative of global estimates and further campaigns will be necessary in order to better understand the CH3I contribution to stratospheric iodine.
Tropical forest soils are a significant source for the greenhouse gas N2O as well as for NO, a precursor of tropospheric ozone. However, current estimates are uncertain due to the limited number of field measurements. Furthermore, there is considerable spatial and temporal variability of N2O and NO emissions due to the variation of environmental conditions such as soil properties, vegetation characteristics and meteorology. In this study we used a process-based model (ForestDNDC-tropica) to estimate N2O and NO emissions from tropical highland forest (Nyungwe) soils in southwestern Rwanda. To extend the model inputs to regional scale, ForestDNDC-tropica was linked to an exceptionally large legacy soil dataset. There was agreement between N2O and NO measurements and the model predictions though the ForestDNDC-tropica resulted in considerable lower emissions for few sites. Low similarity was specifically found for acidic soil with high clay content and reduced metals, indicating that chemo-denitrification processes on acidic soils might be under-represented in the current ForestDNDC-tropica model. The results showed that soil bulk density and pH are the most influential factors driving spatial variations in soil N2O and NO emissions for tropical forest soils. The area investigated (1113 km2) was estimated to emit ca. 439 ± 50 t N2O-N yr−1 (2.8–5.5 kg N2O-N ha−1 yr−1) and 244 ± 16 t NO-N yr−1 (0.8–5.1 kg N ha−1 yr−1). Consistent with less detailed studies, we confirm that tropical highland rainforest soils are a major source of atmospheric N2O and NO.
Water footprints have been proposed as sustainability indicators, relating the consumption of goods like food to the amount of water necessary for their production and the impacts of that water use in the source regions. We have further developed the existing water footprint methodology by globally resolving virtual water flows and import and source regions at 5 arc minutes spatial resolution, and by assessing local impacts of export production. Applying this method to three exemplary cities, Berlin, Delhi and Lagos, we find major differences in amounts, composition, and origin of green and blue virtual water imports, due to differences in diets, trade integration and crop water productivities in the source regions. While almost all of Delhi's and Lagos' virtual water imports are of domestic origin, Berlin on average imports from more than 4000 km distance, in particular soy (livestock feed), coffee and cocoa. While 42% of Delhi's virtual water imports are blue water based, the fractions for Berlin and Lagos are 2% and 0.5%, respectively, roughly equal to local drinking water abstractions of these cities. Some of the external source regions of Berlin's virtual water imports appear to be critically water scarce and/or food insecure. However for deriving recommendations on sustainable consumption and trade, further analysis of context-specific costs and benefits associated with export production will be required.
Estimates of the recovery time of stratospheric ozone heavily rely on the exact knowledge of the processes that lead to the decomposition of the relevant halogenated source gases. Crucial parameters in this context are fractional release factors (FRFs) as well as stratospheric lifetimes and ozone depletion potentials (ODPs). We here present data from the analysis of air samples collected between 2009 and 2011 on board research aircraft flying in the mid- and high-latitude stratosphere and infer the above-mentioned parameters for ten major source gases: CFCl3 (CFC-11), CF2Cl2 (CFC-12), CF2ClCFCl2 (CFC-113), CCl4 (carbon tetrachloride), CH3CCl3 (methyl chloroform), CHF2Cl (HCFC-22), CH3CFCl2 (HCFC-141b), CH3CF2Cl (HCFC-142b), CF2ClBr (H-1211), and CF3Br (H-1301). The inferred correlations of their FRFs with mean ages of air reveal less decomposition as compared to previous studies for most compounds. When using the calculated set of FRFs to infer equivalent stratospheric chlorine, we find a reduction of more than 20% as compared to the values inferred in the most recent Scientific Assessment of Ozone Depletion by the World Meteorological Organisation (WMO, 2011). We also note that FRFs and their correlations with mean age are not generally time-independent as often assumed. The stratospheric lifetimes were calculated relative to that of CFC-11. Within our uncertainties the ratios between stratospheric lifetimes inferred here agree with the values in recent WMO reports except for CFC-11, CFC-12 and CH3CCl3. Finally, we calculate lower ODPs than recommended by WMO for six out of ten compounds, with changes most pronounced for the three HCFCs. Collectively these newly calculated values may have important implications for the severity and recovery time of stratospheric ozone loss.
Aboveground and belowground biomass compartments of vegetation fulfil different functions and they are coupled by complex interactions. These compartments exchange water, carbon and nutrients and the belowground biomass compartment has the capacity to buffer vegetation dynamics when aboveground biomass is removed by disturbances such as herbivory or fire. However, despite their importance, root-shoot interactions are often ignored in more heuristic vegetation models. Here, we present a simple two-compartment grassland model that couples aboveground and belowground biomass. In this model, the growth of belowground biomass is influenced by aboveground biomass and the growth of aboveground biomass is influenced by belowground biomass. We used the model to explore how the dynamics of a grassland ecosystem are influenced by fire and grazing. We show that the grassland system is most persistent at intermediate levels of aboveground-belowground coupling. In this situation, the system can sustain more extreme fire or grazing regimes than in the case of strong coupling. In contrast, the productivity of the system is maximised at high levels of coupling. Our analysis suggests that the yield of a grassland ecosystem is maximised when coupling is strong, however, the intensity of disturbance that can be sustained increases dramatically when coupling is intermediate. Hence, the model predicts that intermediate coupling should be selected for as it maximises the chances of persistence in disturbance driven ecosystems.
Accurate multidimensional localization of isolated fluorescent emitters is a time consuming process in single-molecule based super-resolution microscopy. We demonstrate a functional method for real-time reconstruction with automatic feedback control, without compromising the localization accuracy. Compatible with high frame rates of EM-CCD cameras, it relies on a wavelet segmentation algorithm, together with a mix of CPU/GPU implementation. A combination with Gaussian fitting allows direct access to 3D localization. Automatic feedback control ensures optimal molecule density throughout the acquisition process. With this method, we significantly improve the efficiency and feasibility of localization-based super-resolution microscopy.
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.
As inhibitor of apoptosis (IAP) proteins can regulate additional signaling pathways beyond apoptosis, we investigated the effect of the second mitochondrial activator of caspases (Smac) mimetic BV6, which antagonizes IAP proteins, on non-apoptotic functions in glioblastoma (GBM). Here, we identify non-canonical nuclear factor-κB (NF-κB) signaling and a tumor necrosis factor-α (TNFα)/TNF receptor 1 (TNFR1) autocrine/paracrine loop as critical mediators of BV6-stimulated migration and invasion of GBM cells. In addition to GBM cell lines, BV6 triggers cell elongation, migration and invasion in primary, patient-derived GBM cells at non-toxic concentrations, which do not affect cell viability or proliferation, and also increases infiltrative tumor growth in vivo underscoring the relevance of these findings. Molecular studies reveal that BV6 causes rapid degradation of cellular IAP proteins, accumulation of NIK, processing of p100 to p52, translocation of p52 into the nucleus, increased NF-κB DNA binding and enhanced NF-κB transcriptional activity. Electrophoretic mobility shift assay supershift shows that the NF-κB DNA-binding subunits consist of p50, p52 and RelB further confirming the activation of the non-canonical NF-κB pathway. BV6-stimulated NF-κB activation leads to elevated mRNA levels of TNFα and additional NF-κB target genes involved in migration (i.e., interleukin 8, monocyte chemoattractant protein 1, CXC chemokine receptor 4) and invasion (i.e., matrix metalloproteinase-9). Importantly, inhibition of NF-κB by overexpression of dominant-negative IκBα superrepressor prevents the BV6-stimulated cell elongation, migration and invasion. Similarly, specific inhibition of non-canonical NF-κB signaling by RNA interference-mediated silencing of NIK suppresses the BV6-induced cell elongation, migration and invasion as well as upregulation of NF-κB target genes. Intriguingly, pharmacological or genetic inhibition of the BV6-stimulated TNFα autocrine/paracrine loop by the TNFα-blocking antibody Enbrel or by knockdown of TNFR1 abrogates BV6-induced cell elongation, migration and invasion. By demonstrating that the Smac mimetic BV6 at non-toxic concentrations promotes migration and invasion of GBM cells via non-canonical NF-κB signaling, our findings have important implications for the use of Smac mimetics as cancer therapeutics.
The efficacy of monetary authority actions depends primarily on the ability of the monetary authority to affect inflation expectations, which ultimately depend on agents' trust. We propose a model embedding trust cycles, as emerging from sequential coordination games between atomistic agents and the policy maker, in a monetary model. Trust affects agents' stochastic discount factor, namely the price of future risk, and their expectation formation process: these effects in turn interact with the monetary transmission mechanism. Using data from the Eurobarometer survey we analyze the link between trust on the one side and the transmission mechanism of shocks and of the policy rate on the other: data show that the two interact significantly and in a way comparable to the obtained in our model.
This paper investigates risk-taking in the liquid portfolios held by a large panel of Swedish twins. We document that the portfolio share invested in risky assets is an increasing and concave function of financial wealth, leading to different risk sensitivities across investors. Human capital, which we estimate directly from individual labor income, also drives risk-taking positively, while internal habit and expenditure commitments tend to reduce it. Our micro findings lend strong support to decreasing relative risk aversion and habit formation preferences. Furthermore, heterogeneous risk sensitivities across investors help reconcile individual preferences with representative-agent models.
We develop a dynamic network model whose links are governed by banks' optmizing decisions and by an endogenous tâtonnement market adjustment. Banks in our model can default and engage in firesales: risk is transmitted through direct and cascading counterparty defaults as well as through indirect pecuniary externalities triggered by firesales. We use the model to assess the evolution of the network configuration under various prudential policy regimes, to measure banks' contribution to systemic risk (through Shapley values) in response to shocks and to analyze the effects of systemic risk charges. We complement the analysis by introducing the possibility of central bank liquidity provision.
This paper analyzes the equilibrium pricing implications of contagion risk in a Lucas-tree economy with recursive preferences and jumps. We introduce a new economic channel allowing for the possibility that endowment shocks simultaneously trigger a regime shift to a bad economic state. We document that these contagious jumps have far-reaching asset pricing implications. The risk premium for such shocks is superadditive, i.e. it is 2.5\% larger than the sum of the risk premia for pure endowment shocks and regime switches. Moreover, contagion risk reduces the risk-free rate by around 0.5\%. We also derive semiclosed-form solutions for the wealth-consumption ratio and the price-dividend ratios in an economy with two Lucas trees and analyze cross-sectional effects of contagion risk qualitatively. We find that heterogeneity among the assets with respect to contagion risk can increase risk premia disproportionately. In particular, big assets with a large exposure to contagious shocks carry significantly higher risk premia.
Seit über 30 Jahren steht der Blaue Engel für besonders umweltfreundliche Produkte und Dienstleistungen. Damit ist er das älteste Umweltschutzzeichen in Deutschland. In den vergangenen Jahren wurden das Produktportfolio des Blauen Engel neu ausgerichtet und die Darstellung des Zeichens modernisiert. Seit 2008 ist der Blaue Engel auch das offizielle Klimaschutzzeichen der Bundesregierung. Regelmäßige empirische Umfragen zeigen, dass der Blaue Engel eine hohe Bekanntheit in der Bevölkerung besitzt. Über ein Drittel der Konsumentinnen und Konsumenten nutzen das Umweltzeichen als Orientierung beim Einkauf. Anders als vor 30 Jahren, muss sich der Blaue Engel heute in der öffentlichen Wahrnehmung in einer Flut von Umwelt- und Nachhaltigkeitszeichen behaupten.
Dieser Studientext präsentiert die Ergebnisse einer empirischen Befragung von Verbraucherinnen und Verbrauchern zu Wahrnehmung und Akzeptanz des Blauen Engel, die das ISOE für das Umweltbundesamt durchgeführt hat. In einer bundesweiten Online-Erhebung wurden 2.034 Personen befragt. Ergänzend erfolgte eine vertiefende qualitative Befragung mit Hilfe von Fokusgruppen. Die Befunde liefern wichtige Erkenntnisse darüber, wofür der Blaue Engel in den Augen der KonsumentInnen steht und wie er im Kontext anderer Label wahrgenommen wird. Darüberhinaus wird deutlich, welche Erwartungen aus Verbrauchersicht mit diesem Zeichen verbunden sind und welche Produkte und Produktgruppen mit ihm assoziiert werden.
Arzneimittelrückstände im Wasser – Lösungen liegen bei den Verursachern +++ Der Blaue Engel – ein Klassiker mit Potenzial +++ ISOE ist Partner von „Hessen schafft Wissen“ +++ Wie gelingt eine erfolgreiche Umsetzung von Forschungsergebnissen in die Praxis? +++ Wasser für das südliche Afrika – Neues Forschungsprojekt des ISOE im Rahmen der internationalen Initiative SASSCAL +++ Kooperation mit der Goethe-Universität Frankfurt am Main – Neue Lehrveranstaltungen zur Sozialen Ökologie im Sommersemester 2013 +++ Weltwassertag – Frankfurt-Premiere des Dokumentarfilms WaterChanges +++ Aus dem ISOE +++ Aktuelle Termine +++ Publikationen
This paper presents a theory that explains why it is beneficial for banks to engage in circular lending activities on the interbank market. Using a simple network structure, it shows that if there is a non-zero bailout probability, banks can significantly increase the expected repayment of uninsured creditors by entering into cyclical liabilities on the interbank market before investing in loan portfolios. Therefore, banks are better able to attract funds from uninsured creditors. Our results show that implicit government guarantees incentivize banks to have large interbank exposures, to be highly interconnected, and to invest in highly correlated, risky portfolios. This can serve as an explanation for the observed high interconnectedness between banks and their investment behavior in the run-up to the subprime mortgage crisis.
Basel III and CEO compensation in banks: pay structures as a regulatory signal : [March 6, 2013]
(2013)
This paper proposes a new regulatory approach that implements capital requirements contingent on managerial compensation. We argue that excessive risk taking in the financial sector originates from the shareholder moral hazard created by government guarantees rather than from corporate governance failures within banks. The idea of the proposed regulation is to utilize the compensation scheme to drive a wedge between the interests of top management and shareholders to counteract shareholder risk-shifting incentives. The decisive advantage of this approach compared to existing regulation is that the regulator does not need to be able to properly measure the bank investment risk, which has been shown to be a difficult task during the 2008-2009 financial crisis.
We assess the effects of monetary policy on bank risk to verify the existence of a risk-taking channel - monetary expansions inducing banks to assume more risk. We first present VAR evidence confirming that this channel exists and tends to concentrate on the bank funding side. Then, to rationalize this evidence we build a macro model where banks subject to runs endogenously choose their funding structure (deposits vs. capital) and risk level. A monetary expansion increases bank leverage and risk. In turn, higher bank risk in steady state increases asset price volatility and reduces equilibrium output.
Euro area data show a positive connection between sovereign and bank risk, which increases with banks’ and sovereign long run fragility. We build a macro model with banks subject to incentive problems and liquidity risk (in the form of liquidity based banks’ runs) which provides a link between endogenous bank capital and macro and policy risk. Our banks also invest in risky government bonds used as capital buffer to self-insure against liquidity risk. The model can replicate the positive connection between sovereign and bank risk observed in the data. Central bank liquidity policy, through full allotment policy, is successful in stabilizing the spiraling feedback loops between bank and sovereign risk.
This paper studies the relation between firm value and a firm's growth options. We find strong empirical evidence that (average) Tobin's Q increases with firm-level volatility. However, the significance mainly comes from R&D firms, which have more growth options than non-R&D firms. By decomposing firm-level volatility into its systematic and unsystematic part, we also document that only idiosyncratic volatility (ivol) has a significant effect on valuation. Second, we analyze the relation of stock returns to realized contemporaneous idiosyncratic volatility and R&D expenses. Single sorting according to the size of idiosyncratic volatility, we only find a significant ivol anomaly for non-R&D portfolios, whereas in a four-factor model the portfolio alphas of R&D portfolios are all positive. Double sorting on idiosyncratic volatility and R&D expenses also reveals these differences between R&D and non-R&D firms. To simultaneously control for several explanatory variables, we also run panel regressions of portfolio alphas which confirm the relative importance of idiosyncratic volatility that is amplified by R&D expenses.
We study whether prices of traded options contain information about future extreme market events. Our option-implied conditional expectation of market loss due to tail events, or tail loss measure, predicts future market returns, magnitude, and probability of the market crashes, beyond and above other option-implied variables. Stock-specific tail loss measure predicts individual expected returns and magnitude of realized stock-specific crashes in the cross-section of stocks. An investor that cares about the left tail of her wealth distribution benefits from using the tail loss measure as an information variable to construct managed portfolios of a risk-free asset and market index.
Recently, we evaluated a fiscal consolidation strategy for the United States that would bring the government budget into balance by gradually reducing government spending relative to GDP to the ratio that prevailed prior to the crisis (Cogan et al, JEDC 2013). Specifically, we published an analysis of the macroeconomic consequences of the 2013 Budget Resolution that was passed by the U.S. House of Representatives in March 2012. In this note, we provide an update of our research that evaluates this year’s budget reform proposal that is to be discussed and voted on in the House of Representative in March 2013. Contrary to the views voiced by critics of fiscal consolidation, we show that such a reduction in government purchases and transfer payments can increase GDP immediately and permanently relative to a policy without spending restraint. Our research makes use of a modern structural model of the economy that incorporates the long-standing essential features of economics: opportunity costs, efficiency, foresight and incentives. GDP rises because households take into account that spending restraint helps avoid future increases in tax rates. Lower taxes imply less distorted incentives for work, investment and production relative to a scenario without fiscal consolidation and lead to higher growth.
Whereas fossil evidence indicates extensive treeless vegetation and diverse grazing megafauna in Europe and northern Asia during the last glacial, experiments combining vegetation models and climate models have to-date simulated widespread persistence of trees. Resolving this conflict is key to understanding both last glacial ecosystems and extinction of most of the mega-herbivores. Using a dynamic vegetation model (DVM) we explored the implications of the differing climatic conditions generated by a general circulation model (GCM) in “normal” and “hosing” experiments. Whilst the former approximate interstadial conditions, the latter, designed to mimic Heinrich Events, approximate stadial conditions. The “hosing” experiments gave simulated European vegetation much closer in composition to that inferred from fossil evidence than did the “normal” experiments. Given the short duration of interstadials, and the rate at which forest cover expanded during the late-glacial and early Holocene, our results demonstrate the importance of millennial variability in determining the character of last glacial ecosystems.
We use unique data from financial advisers’ professional exam scores and combine it with other variables to create an index of financial sophistication. Using this index to explain long-term stock return expectations, we find that more sophisticated financial advisers tend to have lower return expectations. A one standard deviation increase in the sophistication index reduces expected returns by 1.1 percentage points. The effect is stronger for emerging market stocks (2.3 percentage points). The sophistication effect contributes 60% to the model fit, while employer fixed effects combined contribute less than 30%. These results help understand the formation of potentially excessively optimistic expectations.
Den Menschen als vernunftbegabtes Wesen, als animal rationale, zu begreifen heißt, ihn als rechtfertigendes Wesen anzusehen. Die Vernunft ist die Fähigkeit, sich anhand rechtfertigender Gründe in der Welt zu orientieren. Denn „ratio, raison, reason bedeutet“, wie Tugendhat hervorhebt, „ebenso sehr ‚Grund‘ wie ‚Vernunft‘. Das Vermögen der Vernunft ist die Fähigkeit, für seine Meinungen und für seine Handlungen Rede und Antwort stehen zu können; lat. rationem reddere, griech. logon didonai.“ Dieses Rede-und-Antwort-Stehen ist eine soziale Praxis kulturell und historisch situierter Wesen, die einerseits frei sind, ihre Gründe zu wählen und zu prüfen, andererseits aber daran gebunden, welche Gründe ihnen zur Verfügung stehen und welche als gut oder rechtfertigend gelten. Der Raum der Gründe ist ein Raum der Rechtfertigungen, die nicht nur Einzelhandlungen, sondern auch komplexe Handlungsordnungen, also soziale Verhältnisse und politische Institutionen, legitimieren.
Menschen sind aber auch erzählende Wesen. Der Raum der Gründe, in dem sie sich orientieren, ist kein nackter Raum einzelner Sätze oder gar Normen, sondern bevölkert von Narrativen.
A natural experiment in which customer-owned mutual companies converted to publicly listed firms created a plausibly exogenous shock to the stock market participation status of tens of thousands of people. We find the shock changed the way people vote in the affected areas, with a 10% increase in share-ownership rate being followed by a 1.3%–3.1% increase in right-of-center vote share. The institutional details and additional tests suggest that wealth, liquidity, and tax-related incentives cannot fully explain the results. A plausible explanation is that the associated increase in the salience of stock ownership causes a shift in voters’ attention.
The European Commission recently put forward a proposal for a regulation to amend and strengthen the 2009 version of the EU's rules on the regulation of credit rating agencies ("CRA3"). Among other things, Art. 35a of the draft proposal introduces strict liability for rating agencies. This liability proposal is at odds with the aim to strengthen competition in the rating sector and could have a chilling effect on capital markets. The paper analyses existing rules on civil liability of rating agencies under different legal systems. Subsequently, the provision under Art. 35a of the Draft Proposal is examinded more closely. Suggestions on possible improvemts of the proposal are made.
SAFE Newsletter : 2013, Q1
(2013)
SAFE Newsletter
(2013)
The Center of Excellence SAFE – “Sustainable Architecture for Finance in Europe” – is a cooperation of the Center for Financial Studies and Goethe University Frankfurt. It is funded by the LOEWE initiative of the State of Hessen (Landes-Offensive zur Entwicklung wissenschaftlich-ökonomischer Exzellenz). SAFE brings together more than 40 professors and just as many junior researchers who are all dedicated to conducting research in support of a sustainable financial architecture. The Center has two main pillars: excellent research on all important topics related to finance; and policy advice, including the dissemination of relevant research findings to European decision makers from the realms of politics, regulation and administration.
In order to promote a fruitful exchange with interested parties from politics, academia, business and the media, SAFE issues a newsletter on a quarterly basis. This aims to provide an overview of the Center‘s ongoing research and policy activities. The SAFE Newsletter succeeds the House of Finance Newsletter, which was published between 2009 and 2012.
SAFE is based at Goethe University’s House of Finance however extends beyond by drawing on scholars from other parts of Goethe University as well as from fellow research institutions. The Center builds on the reputation of the House of Finance institutions, serving as an interdisciplinary think tank on the issue of finance.
Debt-induced crises, including the subprime, are usually attributed exclusively to supply-side factors. We uncover an additional factor contributing to debt culture, namely social influences emanating from the perceived average income of peers. Using unique information from a representative household survey of the Dutch population that circumvents the need to define the social circle, we consider collateralized, consumer, and informal loans. We find robust social effects on borrowing – especially among those who consider themselves poorer than their peers – and on indebtedness, suggesting a link to financial distress. We check the robustness of our results using several approaches to rule out spurious associations and handle correlated effects.
Planar cell polarity (PCP)–the coordinated polarisation of a whole field of cells within the plane of a tissue–relies on the interaction of three modules: a global module that couples individual cellular polarity to the tissue axis, a local module that aligns the axis of polarisation of neighbouring cells, and a readout module that directs the correct outgrowth of PCP-regulated structures such as hairs and bristles. While much is known about the molecular components that are required for PCP, the functional details of–and interactions between–the modules remain unclear. In this work, we perform a mathematical and computational analysis of two previously proposed computational models of the local module (Amonlirdviman et al., Science, 307, 2005; Le Garrec et al., Dev. Dyn., 235, 2006). Both models can reproduce wild-type and mutant phenotypes of PCP observed in the Drosophila wing under the assumption that a tissue-wide polarity cue from the global module persists throughout the development of PCP. We demonstrate that both models can also generate tissue-level PCP when provided with only a transient initial polarity cue. However, in these models such transient cues are not sufficient to ensure robustness of the resulting cellular polarisation.
Since the 1980s, advances in wastewater treatment technology have led to considerably improved surface water quality in the urban areas of many high income countries. However, trace concentrations of organic wastewater-associated contaminants may still pose a key environmental hazard impairing the ecological quality of surface waters. To identify key impact factors, we analyzed the effects of a wide range of anthropogenic and environmental variables on the aquatic macroinvertebrate community. We assessed ecological water quality at 26 sampling sites in four urban German lowland river systems with a 0–100% load of state-of-the-art biological activated sludge treated wastewater. The chemical analysis suite comprised 12 organic contaminants (five phosphor organic flame retardants, two musk fragrances, bisphenol A, nonylphenol, octylphenol, diethyltoluamide, terbutryn), 16 polycyclic aromatic hydrocarbons, and 12 heavy metals. Non-metric multidimensional scaling identified organic contaminants that are mainly wastewater-associated (i.e., phosphor organic flame retardants, musk fragrances, and diethyltoluamide) as a major impact variable on macroinvertebrate species composition. The structural degradation of streams was also identified as a significant factor. Multiple linear regression models revealed a significant impact of organic contaminants on invertebrate populations, in particular on Ephemeroptera, Plecoptera, and Trichoptera species. Spearman rank correlation analyses confirmed wastewater-associated organic contaminants as the most significant variable negatively impacting the biodiversity of sensitive macroinvertebrate species. In addition to increased aquatic pollution with organic contaminants, a greater wastewater fraction was accompanied by a slight decrease in oxygen concentration and an increase in salinity. This study highlights the importance of reducing the wastewater-associated impact on surface waters. For aquatic ecosystems in urban areas this would lead to: (i) improvement of the ecological integrity, (ii) reduction of biodiversity loss, and (iii) faster achievement of objectives of legislative requirements, e.g., the European Water Framework Directive.
This study indicates that embryonic stem cells [ESCs] cultured with retinoic acid and activin A significantly upregulate the miRNA let-7e. This specific miRNA modulates the Wnt pathway and the expression of early nephrogenic markers under these differentiation conditions. The differentiation markers WT1, Pax2 and Wnt4 were downregulated when miRNA let-7e was silenced, thus indicating the role of miRNA let-7e in the differentiation process. PKCβ, GSK3β phosphorylation (GSK3βP) and β-catenin expression was reduced in differentiated cells and reversed by miRNA let-7e silencing. Addition of a PKCβ inhibitor to the miRNA let-7e silenced cells abolished let-7e-derived effects in differentiation markers, and reversed the increase in GSK3βP and β-catenin, thus indicating that miRNA let-7e is involved in differentiation via the modulation of GSK3β phosphorylation and β-catenin production.
Die Dissertation stellt das Machtgeflecht in der Islamischen Stadt Marawi City (Mindanao, Philippinen) dar, in die die dortigen Gender-Debatten involviert sind. In einer Umgebung, die als Konsequenz des Mindanao Konfliktes als “no war, no peace”-Umgebung definiert werden kann, gibt es drei Hauptdarsteller: die nationale Regierung des mehrheitlich christlichen Staates der Philippinen (GRP), die Autonome Regierung im Muslimischen Mindanao (ARMM), zu der auch Marawi City zählt, und die islamische Rebellengruppe Moro Islamic Liberation Front (MILF), die einen islamischen (unter-)Staat fordert. Die GRP unterstützt Re-Islamisierungs- und Re-Traditionalisierungsbewegungen in der ARMM, um die Opposition zur MILF zu stärken. Die Konsequenz ist jedoch keine Kollaboration zwischen der GRP und der ARMM. Stattdessen nutzen Politiker ihre Privilegien aus, um ihren eigenen Absichten zu folgen. Sei dies, um politische Gegner auszuspielen oder das traditionelle Sultanatssystem zu fördern. Für Gender-Debatten gibt es in diesem Kontext der ungelösten nationalen Frage kaum Spielraum außerhalb einer Islamischen Narrative; dies bedeutet jedoch nicht, dass Gender nicht debattiert wird, sondern, dass die Debatten inner-Islamisch sind, hauptsächlich zwischen Repräsentanten des traditionell synkretistischen Islam und Vertretern Islamischer Revitalisierungsbewegungen. Speziell erstere erscheinen sehr einflussreich bezüglich Gender Strategien in der Region. Dies ist nur teilweise auf die Unterstützung der nationalen Regierung zurückzuführen, sondern ist vor allem eine Frage von Identität. Diese wiederum wird nicht vorranging über Religion, sondern nach ethnischen Maßstäben und im Speziellen im Rahmen von Clanstrukturen definiert.