165 research outputs found

    Funktionsweise und Replikationstil europÀischer Exchange Traded Funds auf Aktienindices

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    Exchange Traded Funds (ETF) were established in Europe in 2000 and have grown to a size of over 200 bn US$. Some issuers use a full replication strategy while others prefer a swap based approach. The ETF are dealt parallelly in the primary and in the secondary market, as new ETFs can be created at any time. Therefore, the market is very liquid with small ask bid spreads. The fees are considerably lower compared to active managed fonds. For liquid share indices both strategies can replicate the index convincingly. In the EUROSTOXX the ETF can outperform the Index due to dividend and tax optimization. This was not possible for the Dax. For illiquid large indices (MSCI Emerging Markets), there was a considerable difference between the monthly returns of the index compared to the ETFs. Both strategies have counterparty risk. The full replication uses security lending to enhance the performance. The synthetic strategy can have losses up to 10% if the swap partner defaults. --ETF,Exchange Traded Funds,Full Replication,Swap Replication,ETF Performance,ETF Risk

    Regulation of the cytosolic stress response

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    The cytosolic stress response, also known as the heat-shock response (HSR), is one of the major defense mechanisms activated by cells to maintain the integrity of the cellular proteome under proteotoxic environmental conditions. It is characterized by the increased synthesis of heat-shock proteins (Hsps), mainly molecular chaperones and proteases which prevent the aggregation of misfolded proteins and mediate their refolding or degradation. It is generally accepted that the induction of the HSR is coordinated by the heat-shock transcription factor 1 (HSF1). However, many mechanistic aspects of the HSF1 regulation remain unclear. In the present study, a genome-wide RNA interference screen was combined with an extensive biochemical analysis and quantitative proteomics to better understand the regulation of the HSR upon thermal stress. In the screening experiments novel positive and negative modulators of the stress response were identified, including proteins involved in chromatin remodeling, transcription, mRNA splicing, DNA damage repair, and proteolytic degradation. The diversity of the identified regulators suggests that induction and attenuation of the HSR integrate signals from different cellular pathways and are rather multi-factorial processes than single gene/protein events. The modulator proteins are localized in multiple cellular compartments with the majority having their primary location in the nucleus. A protein-protein interaction analysis revealed a HSR regulatory network, with chromatin modifiers and nuclear protein quality control components occupying hub positions. These observations are supported by quantitative proteomics experiments, which showed specific stress-induced reorganizations of the nuclear proteome, including the transient accumulation of chaperones and proteasomal subunits. The histone acetyltransferase EP300 was shown to specifically control the cellular level of HSF1 by stabilizing it against proteasomal turnover under normal conditions. Moreover, the ubiquitin-proteasome system (UPS) was found to participate in the attenuation of the HSR by degrading stress-activated, hyperphosphorylated HSF1. Since HSF1 competes with stress-denatured proteins for access to the proteasome, the extent of cellular protein damage modulates the rate of HSR attenuation. In addition to thermal stress, various other proteotoxic stresses are known to induce the HSR such as the proteasome inhibitor MG132 and the triterpenoid celastrol, which activates HSF1 by an unknown mechanism. Therefore, the networks regulating HSF1 activation upon thermal stress, proteasome inhibition and celastrol treatment were compared in this study. Whereas there is a large overlap between the sets of regulatory factors activated after heat stress and proteasomal impairment, HSF1 activation after celastrol treatment seems to bypass the HSR regulatory network to a large extent. Nevertheless, comparison of the regulatory networks under different proteotoxic conditions revealed a set of HSR core components, including factors involved in chromatin remodeling, DNA damage repair, RNA transport, transcription, and ion transport. The various cellular functions and localizations of these core components reinforce the multifaceted nature of the HSR regulation. The results obtained in this study can help to identify potential targets for the pharmacologic manipulation of the HSR in the treatment of aggregate deposition diseases and cancer

    Rethinking Hybrid Teaching: The Hybrid Rhombus Model as an Approach to Understanding Hybrid Settings

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    [EN] After extended periods of remote-only teaching at university, lecturers tried to come back to lecture halls. Due to restrictions not all students could participate on-site. Therefore, hybrid teaching models proliferated. To reflect the transformative effects on teaching practice, we conducted focus groups with lecturers and found that didactic models aimed at capturing dynamics of the in-situ learning experience do not provide sufficient understanding of the bifurcated nature of hybrid teaching. The hybrid rhombus model is an approach to conceptual understanding of the newly developed situation of teaching in a hybrid way. This paper gives a brief description of the model description and the empirical background, to contribute to the debate of hybrid teaching in relation to digital or on-site teaching.Handle-Pfeiffer, D.; Winter, C.; Löw, C.; Hackl, C. (2022). Rethinking Hybrid Teaching: The Hybrid Rhombus Model as an Approach to Understanding Hybrid Settings. En 8th International Conference on Higher Education Advances (HEAd'22). Editorial Universitat PolitÚcnica de ValÚncia. 1367-1375. https://doi.org/10.4995/HEAd22.2022.146021367137

    A saposin-lipoprotein nanoparticle system for membrane proteins.

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    A limiting factor in membrane protein research is the ability to solubilize and stabilize such proteins. Detergents are used most often for solubilizing membrane proteins, but they are associated with protein instability and poor compatibility with structural and biophysical studies. Here we present a saposin-lipoprotein nanoparticle system, Salipro, which allows for the reconstitution of membrane proteins in a lipid environment that is stabilized by a scaffold of saposin proteins. We demonstrate the applicability of the method on two purified membrane protein complexes as well as by the direct solubilization and nanoparticle incorporation of a viral membrane protein complex from the virus membrane. Our approach facilitated high-resolution structural studies of the bacterial peptide transporter PeptTSo2 by single-particle cryo-electron microscopy (cryo-EM) and allowed us to stabilize the HIV envelope glycoprotein in a functional state

    Impact of asymmetric tethering on outcomes after edge-to-edge mitral valve repair for secondary mitral regurgitation

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    BACKGROUND The impact of postero-anterior and medio-lateral mitral valve (MV) tethering patterns on outcomes in patients undergoing transcatheter edge-to-edge repair (M-TEER) for secondary mitral regurgitation (SMR) is unknown. METHODS The ratio of the posterior to anterior MV leaflet angle (PLA/ALA) in MV segment 2 was defined as postero-anterior tethering asymmetry. Medio-lateral tethering asymmetry was assessed as the ratio of the medial (segment 3) to lateral (segment 1) MV tenting area. We used receiver-operating characteristics and a Cox regression model to identify cut-off values of asymmetric anteroposterior and medio-lateral tethering for prediction of 2~year all-cause mortality after TMVR. RESULTS Among 178 SMR patients, postero-anterior tethering was asymmetric in 67 patients (37.9%, PLA/ALA ratio > 1.54). Asymmetric medio-lateral tethering (tenting area ratio > 1.49) was observed in 49 patients (27.5%). M-TEER reduced MR to ≀ 2 + in 92.1% of patients; MR reduction was less effective in the presence of asymmetric postero-anterior tethering (p = 0.02). A multivariable Cox regression model identified both types of asymmetric MV tethering to be associated with increased all-cause 2-year mortality (postero-anterior tethering asymmetry: HR = 2.77, CI 1.43-5.38; medio-lateral tethering asymmetry: HR = 2.90, CI 1.54-5.45; p < 0.01). CONCLUSIONS Asymmetric postero-anterior and medio-lateral MV tethering patterns are associated with increased 2-year mortality in patients undergoing M-TEER for SMR. A detailed echocardiographic analysis of MV anatomy may help to identify patients who profit most from M-TEER
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