230 research outputs found

    RNA-dependent association with myosin IIA promotes F-actin-guided trafficking of the ELAV-like protein HuR to polysomes

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    The role of the mRNA-binding protein human antigen R (HuR) in stabilization and translation of AU-rich elements (ARE) containing mRNAs is well established. However, the trafficking of HuR and bound mRNA cargo, which comprises a fundamental requirement for the aforementioned HuR functions is only poorly understood. By administering different cytoskeletal inhibitors, we found that the protein kinase Cδ (PKCδ)-triggered accumulation of cytoplasmic HuR by Angiotensin II (AngII) is an actin-myosin driven process functionally relevant for stabilization of ARE-bearing mRNAs. Furthermore, we show that the AngII-induced recruitment of HuR and its bound mRNA from ribonucleoprotein particles to free and cytoskeleton bound polysomes strongly depended on an intact actomyosin cytoskeleton. In addition, HuR allocation to free and cytoskeletal bound polysomes is highly sensitive toward RNase and PPtase and structurally depends on serine 318 (S318) located within the C-terminal RNA recognition motif (RRM3). Conversely, the trafficking of the phosphomimetic HuRS318D, mimicking HuR phosphorylation at S318 by the PKCδ remained PPtase resistant. Co-immunoprecipitation experiments with truncated HuR proteins revealed that the stimulus-induced association of HuR with myosin IIA is strictly RNA dependent and mediated via the RRM3. Our data implicate a microfilament dependent transport of HuR, which is relevant for stimulus-induced targeting of ARE-bearing mRNAs from translational inactive ribonucleoprotein particles to polysomes

    Electronic properties of Mn-Phthalocyanine - C60_{60} bulk heterojunctions: combining photoemission and electron energy-loss spectroscopy

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    The electronic properties of co-evaporated mixtures (blends) of manganese phthalocyanine and the fullerene C60_{60} (MnPc:C60_{60}) have been studied as a function of the concentration of the two constituents using two supplementary electron spectroscopic methods, photoemission spectroscopy (PES) as well as electron energy-loss spectroscopy (EELS) in transmission. Our PES measurements provide a detailed picture of the electronic structure measured with different excitation energies as well as different mixing ratios between MnPc and C60_{60}. Besides a relative energy shift, the occupied electronic states of the two materials remain essentially unchanged. The observed energy level alignment is different compared to that of the related CuPc:C60_{60} bulk heterojunction. Moreover, the results from our EELS investigations show that despite of the rather small interface interaction the MnPc related electronic excitation spectrum changes significantly by admixing C60_{60} to MnPc thin films

    Site-specific probing of charge transfer dynamics in organic photovoltaics

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    We report the site-specific probing of charge-transfer dynamics in a prototype system for organic photovoltaics (OPV) by picosecond time-resolved X-ray photoelectron spectroscopy. A layered system consisting of approximately two monolayers of C60_{60} deposited on top of a thin film of Copper-Phthalocyanine (CuPC) is excited by an optical pump pulse and the induced electronic dynamics are probed with 590 eV X-ray pulses. Charge transfer from the electron donor (CuPC) to the acceptor (C60_{60}) and subsequent charge carrier dynamics are monitored by recording the time-dependent C 1ss core level photoemission spectrum of the system. The arrival of electrons in the C60_{60} layer is readily observed as a completely reversible, transient shift of the C60_{60} associated C 1ss core level, while the C 1ss level of the CuPC remains unchanged. The capability to probe charge transfer and recombination dynamics in OPV assemblies directly in the time domain and from the perspective of well-defined domains is expected to open additional pathways to better understand and optimize the performance of this emerging technology

    Statusbericht Bodensystematik

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    Diskussionsstand der AG Bodensystematik bei der Boden- und Substratsystematik sowie Horizontsymbolik für die Bodenkundliche Kartieranleitung, 6. Auflage

    ASP-based Discovery of Semi-Markovian Causal Models under Weaker Assumptions

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    In recent years the possibility of relaxing the so-called Faithfulness assumption in automated causal discovery has been investigated. The investigation showed (1) that the Faithfulness assumption can be weakened in various ways that in an important sense preserve its power, and (2) that weakening of Faithfulness may help to speed up methods based on Answer Set Programming. However, this line of work has so far only considered the discovery of causal models without latent variables. In this paper, we study weakenings of Faithfulness for constraint-based discovery of semi-Markovian causal models, which accommodate the possibility of latent variables, and show that both (1) and (2) remain the case in this more realistic setting

    Bulk sensitive photo emission spectroscopy of C1b compounds

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    This work reports about bulk-sensitive, high energy photoelectron spectroscopy from the valence band of CoTiSb excited by photons from 1.2 to 5 keV energy. The high energy photoelectron spectra were taken at the KMC-1 high energy beamline of BESSY II employing the recently developed Phoibos 225 HV analyser. The measurements show a good agreement to calculations of the electronic structure using the LDA scheme. It is shown that the high energy spectra reveal the bulk electronic structure better compared to low energy XPS spectra.Comment: J. Electron Spectrosc. Relat. Phenom. accepte

    Switching from molecular to bulklike dynamics in electronic relaxation of a small gold cluster

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    We have investigated the ultrafast electronic relaxation of Au−7 using time- resolved photoelectron spectroscopy combined with first-principles simulations of the excited-state dynamics. Unlike previous findings, which have demonstrated molecularlike excited-state relaxation in Au−7 at low excitation energy (1.56 eV), we show here that excitation with 3.12 eV leads to bulklike electronic relaxation without a considerable change of geometry. The experimental findings are fully supported by theoretical simulations, which reveal a bulklike electron-hole relaxation mechanism in a far band-gap cluster. Our findings demonstrate that small gold clusters in the sub-nm size range can exhibit either molecularlike or bulklike properties, depending on the excitation energy

    Ablage, Austausch und Nutzbarkeit von Bodendaten - von der Erfassung bis zur ISO- und INSPIRE-konformen Datenweitergabe

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    Der Austausch von Bodendaten auch zwischen automatisierten Systemen bedarf eines Formats, das strukturelle und inhaltliche Kompatibilität zwischen dem sendenden und dem empfangenden System sicherstellt. Arbeiten an einer KA5-Datenstruktur, einem internationalen Standard zum Bodendatenaustausch und die Erfordernisse der EU-Richtlinie INSPIRE werden vorgestellt bzw. diskutiert

    Treatment decisions, clinical outcomes, and pharmacoeconomics in the treatment of patients with EGFR mutated stage III/IV NSCLC in Germany: an observational study

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    Background: We evaluated treatment decisions and outcomes in a cohort of predominately Caucasian patients with EGFR mutation-positive (EGFR Mut+) non-small-cell lung cancer (NSCLC). Methods: REASON (NCT00997230) was a non-interventional study in German patients with stage IIIB/IV NSCLC. Secondary endpoints for EGFR Mut + NSCLC included progression-free survival (PFS), overall survival (OS), adverse event (AE) management, and pharmacoeconomic outcomes. Results: Among 334 patients with EGFR Mut + NSCLC, tyrosine kinase inhibitors (TKIs) were the most common first-line therapy (56.6%, 53.0% gefitinib). Among patients who received TKIs/gefitinib before first disease progression, PFS was longer compared with those who did not receive a TKI (median 10.1/10.0 vs. 7.0 months; HR 0.67/0.69; log-rank p = 0.012/p = 0.022). OS was longer for those patients who ever received a TKI/gefitinib during their complete therapy course compared with those who never received a TKI (median 18.4/18.1 vs. 13.6 months; HR 0.53/0.55; p = 0.003/p = 0.005). Total mean first-line treatment healthcare costs per person were higher for those receiving TKIs (€46,443) compared with those who received chemotherapy (€27,182). Mean outpatient and inpatient costs were highest with chemotherapy. Rash, diarrhea, and dry skin were the most commonly reported AEs for patients receiving gefitinib. Conclusions: In REASON, TKI therapy was the most common first- and second-line treatment for EGFR Mut + NSCLC, associated with increased drug costs compared with chemotherapy. Patients who received gefitinib or a TKI ever during their complete therapy course had prolonged PFS and OS compared with patients who did not receive a TKI. Trial registration: The trial was registered on October, 2009 with ClinicalTrials.gov : https://clinicaltrials.gov/ct2/show/NCT00997230?term=NCT00997230&rank=
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