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Reproducibility is a defining feature of science, but the extent to which it characterizes current research is unknown. We conducted replications of 100 experimental and correlational studies published in three psychology journals using high-powered designs and original materials when available. Replication effects were half the magnitude of original effects, representing a substantial decline. Ninety-seven percent of original studies had statistically significant results. Thirty-six percent of replications had statistically significant results; 47% of original effect sizes were in the 95% confidence interval of the replication effect size; 39% of effects were subjectively rated to have replicated the original result; and if no bias in original results is assumed, combining original and replication results left 68% with statistically significant effects. Correlational tests suggest that replication success was better predicted by the strength of original evidence than by characteristics of the original and replication teams.
Tight junctions seal intercellular clefts via membrane-related strands, hence, maintaining important organ functions. We investigated the self-association of strand-forming transmembrane tight junction proteins. The regulatory tight junction protein occludin was differently tagged and cotransfected in eucaryotic cells. These occludins colocalized within the plasma membrane of the same cell, coprecipitated and exhibited fluorescence resonance energy transfer. Differently tagged strand-forming claudin-5 also colocalized in the plasma membrane of the same cell and showed fluorescence resonance energy transfer. This demonstrates self-association in intact cells both of occludin and claudin-5 in one plasma membrane. In search of dimerizing regions of occludin, dimerization of its cytosolic C-terminal coiled-coil domain was identified. In claudin-5, the second extracellular loop was detected as a dimer. Since the transmembrane junctional adhesion molecule also is known to dimerize, the assumption that homodimerization of transmembrane tight junction proteins may serve as a common structural feature in tight junction assembly is supported
The hormone calcitonin (CT) is primarily known for its pharmacologic action as an inhibitor of bone resorption, yet CT-deficient mice display increased bone formation. These findings raised the question about the underlying cellular and molecular mechanism of CT action. Here we show that either ubiquitous or osteoclast-specific inactivation of the murine CT receptor (CTR) causes increased bone formation. CT negatively regulates the osteoclast expression of Spns2 gene, which encodes a transporter for the signalling lipid sphingosine 1-phosphate (S1P). CTR-deficient mice show increased S1P levels, and their skeletal phenotype is normalized by deletion of the S1P receptor S1P(3). Finally, pharmacologic treatment with the nonselective S1P receptor agonist FTY720 causes increased bone formation in wild-type, but not in S1P(3)-deficient mice. This study redefines the role of CT in skeletal biology, confirms that S1P acts as an osteoanabolic molecule in vivo and provides evidence for a pharmacologically exploitable crosstalk between osteoclasts and osteoblasts.
Fontanes Medien
(2023)
Theodor Fontane war, im durchaus modernen Sinne, ein Medienarbeiter: Als Presse-Agent in London lernte er die innovativste Presselandschaft seiner Zeit kennen; als Redakteur in Berlin leistete er journalistische Kärrnerarbeit; er schrieb Kritiken über das Theater, die bildende Kunst und die Literatur – und auch seine Romane wie seine Reisebücher sind stets Medienprodukte, als Serien in in Zeitungen und Zeitschriften platziert, bevor sie auf dem Buchmarkt erschienen.
Der vorliegende Band dokumentiert die Ergebnisse eines internationalen Kongresses, veranstaltet 2019 vom Theodor-Fontane-Archiv in Potsdam. Die ebenso rasante wie umfassende Medialisierung und Vernetzung der Gesellschaft im Laufe des 19. Jahrhunderts wird dabei als produktive Voraussetzung der schriftstellerischen Tätigkeit Fontanes begriffen. Eingebettet in ein weit verzweigtes Netz der Korrespondenz und der postalischen Textzirkulation, vertraut mit den Routinen und Publika der periodischen Massenpresse, für die er sein Leben lang schrieb, und auf vielfältige Weise geprägt von der visuellen Kultur seiner Zeit wird Theodor Fontane als gleichermaßen journalistisch versierter wie ästhetisch sensibler Grenzgänger erkennbar.
Fontanes Medien
(2022)
Theodor Fontane war, im durchaus modernen Sinne, ein Medienarbeiter: Als Presse-Agent in London lernte er die innovativste Presselandschaft seiner Zeit kennen; als Redakteur in Berlin leistete er journalistische Kärrnerarbeit; er schrieb Kritiken über das Theater, die bildende Kunst und die Literatur – und auch seine Romane wie seine Reisebücher sind stets Medienprodukte, als Serien in in Zeitungen und Zeitschriften platziert, bevor sie auf dem Buchmarkt erschienen.
Der vorliegende Band dokumentiert die Ergebnisse eines internationalen Kongresses, veranstaltet 2019 vom Theodor-Fontane-Archiv in Potsdam. Die ebenso rasante wie umfassende Medialisierung und Vernetzung der Gesellschaft im Laufe des 19. Jahrhunderts wird dabei als produktive Voraussetzung der schriftstellerischen Tätigkeit Fontanes begriffen. Eingebettet in ein weit verzweigtes Netz der Korrespondenz und der postalischen Textzirkulation, vertraut mit den Routinen und Publika der periodischen Massenpresse, für die er sein Leben lang schrieb, und auf vielfältige Weise geprägt von der visuellen Kultur seiner Zeit wird Theodor Fontane als gleichermaßen journalistisch versierter wie ästhetisch sensibler Grenzgänger erkennbar.
We report on the gamma-ray activity of the blazar Mrk 501 during the first 480 days of Fermi operation. We find that the average Large Area Telescope (LAT) gamma-ray spectrum of Mrk 501 can be well described by a single power-law function with a photon index of 1.78 +/- 0.03. While we observe relatively mild flux variations with the Fermi-LAT (within less than a factor of two), we detect remarkable spectral variability where the hardest observed spectral index within the LAT energy range is 1.52 +/- 0.14, and the softest one is 2.51 +/- 0.20. These unexpected spectral changes do not correlate with the measured flux variations above 0.3 GeV. In this paper, we also present the first results from the 4.5 month long multifrequency campaign (2009 March 15-August 1) on Mrk 501, which included the Very Long Baseline Array (VLBA), Swift, RXTE, MAGIC, and VERITAS, the F-GAMMA, GASP-WEBT, and other collaborations and instruments which provided excellent temporal and energy coverage of the source throughout the entire campaign. The extensive radio to TeV data set from this campaign provides us with the most detailed spectral energy distribution yet collected for this source during its relatively low activity. The average spectral energy distribution of Mrk 501 is well described by the standard one-zone synchrotron self-Compton (SSC) model. In the framework of this model, we find that the dominant emission region is characterized by a size less than or similar to 0.1 pc (comparable within a factor of few to the size of the partially resolved VLBA core at 15-43 GHz), and that the total jet power (similar or equal to 10(44) erg s(-1)) constitutes only a small fraction (similar to 10(-3)) of the Eddington luminosity. The energy distribution of the freshly accelerated radiating electrons required to fit the time-averaged data has a broken power-law form in the energy range 0.3 GeV-10 TeV, with spectral indices 2.2 and 2.7 below and above the break energy of 20 GeV. We argue that such a form is consistent with a scenario in which the bulk of the energy dissipation within the dominant emission zone of Mrk 501 is due to relativistic, proton-mediated shocks. We find that the ultrarelativistic electrons and mildly relativistic protons within the blazar zone, if comparable in number, are in approximate energy equipartition, with their energy dominating the jet magnetic field energy by about two orders of magnitude.
Objectives: Chronic back pain (CBP) can lead to disability and burden. In addition to its medical causes, its development is influenced by psychosocial risk factors, the so-called flag factors, which are categorized and integrated into many treatment guidelines. Currently, most studies investigate single flag factors, which limit the estimation of individual factor significance in the development of chronic pain. Furthermore, factors concerning patients’ lifestyle, biography and treatment history are often neglected. Therefore, the objectives of the present study are to identify commonly neglected factors of CBP and integrate them into an analysis model comparing their significance with established flag factors.
Methods: A total of 24 patients and therapists were cross-sectionally interviewed to identify commonly neglected factors of CBP. Subsequently, the impact of these factors was surveyed in a longitudinal study. In two rehabilitation clinics, CBP patients (n = 145) were examined before and 6 months after a 3-week inpatient rehabilitation. Outcome variables, chronification factor pain experience (CF-PE) and chronification factor disability (CF-D), were ascertained with confirmatory factor analysis (CFA) of standardized questionnaires. Predictors were evaluated using stepwise calculations of simple and multiple regression models.
Results: Through interviews, medical history, iatrogenic factors, poor compliance, critical life events (LEs), social support (SS) type and effort–reward were identified as commonly neglected factors. However, only the final three held significance in comparison to established factors such as depression and pain-related cognitions. Longitudinally, lifestyle factors found to influence future pain were initial pain, physically demanding work, nicotine consumption, gender and rehabilitation clinic. LEs were unexpectedly found to be a strong predictor of future pain, as were the protective factors, reward at work and perceived SS.
Discussion: These findings shed insight regarding often overlooked factors in the development of CBP, suggesting that more detailed operationalization and superordinate frameworks would be beneficial to further research.
Conclusion: In particular, LEs should be taken into account in future research. Protective factors should be integrated in therapeutic settings.
Objectives: Chronic back pain (CBP) can lead to disability and burden. In addition to its medical causes, its development is influenced by psychosocial risk factors, the so-called flag factors, which are categorized and integrated into many treatment guidelines. Currently, most studies investigate single flag factors, which limit the estimation of individual factor significance in the development of chronic pain. Furthermore, factors concerning patients’ lifestyle, biography and treatment history are often neglected. Therefore, the objectives of the present study are to identify commonly neglected factors of CBP and integrate them into an analysis model comparing their significance with established flag factors.
Methods: A total of 24 patients and therapists were cross-sectionally interviewed to identify commonly neglected factors of CBP. Subsequently, the impact of these factors was surveyed in a longitudinal study. In two rehabilitation clinics, CBP patients (n = 145) were examined before and 6 months after a 3-week inpatient rehabilitation. Outcome variables, chronification factor pain experience (CF-PE) and chronification factor disability (CF-D), were ascertained with confirmatory factor analysis (CFA) of standardized questionnaires. Predictors were evaluated using stepwise calculations of simple and multiple regression models.
Results: Through interviews, medical history, iatrogenic factors, poor compliance, critical life events (LEs), social support (SS) type and effort–reward were identified as commonly neglected factors. However, only the final three held significance in comparison to established factors such as depression and pain-related cognitions. Longitudinally, lifestyle factors found to influence future pain were initial pain, physically demanding work, nicotine consumption, gender and rehabilitation clinic. LEs were unexpectedly found to be a strong predictor of future pain, as were the protective factors, reward at work and perceived SS.
Discussion: These findings shed insight regarding often overlooked factors in the development of CBP, suggesting that more detailed operationalization and superordinate frameworks would be beneficial to further research.
Conclusion: In particular, LEs should be taken into account in future research. Protective factors should be integrated in therapeutic settings.
Triaxial high temperature (900 °C) deformation experiments were conducted at constant strain rate in a Paterson-type deformation apparatus on cylinders of Carrara marble with two right or left stepping, non-overlapping weak inclusions of Solnhofen limestone, oriented at 45° to the cylinders’ longitudinal axes. Applying different values of confinement (30, 50, 100 and 300 MPa) we induced various amounts of brittle deformation in the marble matrix and investigated the effect of brittle precursors on the initiation and development of heterogeneity-induced high temperature shear zones.
Viscosity contrast between the matrix and the inclusions induces local stress concentration at the tips of these latter. The initial arrangement of the inclusions results in either an overpressured (contractional) or underpressured (extensional) domain in the step-over region of the sample. At low confinement (30 and 50 MPa) abundant brittle deformation is observed, but the spatial distribution of microfractures is dependent on the kinematics of the step-over region: microcracks occur either along the shearing plane between inclusions (in extensional bridge samples), or broadly distributed outside the step-over region (contractional bridge samples). Accordingly, ductile deformation localizes along the inclusions plane in the extensional bridge samples as opposed to distributing over large areas of the matrix in the contractional bridge samples. If microcracking is suppressed (high confinement), strain is accommodated by viscous creep and strain progressively de-localizes in extensional bridge samples. Our experiments demonstrate that brittle precursors enhance the degree of localization in the ductile deformation regime, but only if the interaction of pre-existing heterogeneities induces an extensional mean stress regime in between.
In this study, the apparent relationship between the transport process and the surface chemistry of the Calcium-Silicate Hydrate (CSH) phases was investigated. For this purpose, a method was developed to synthesize ultrathin CSH phases to be used as a model substrate with the specific modification of their structure by introducing europium (Eu(III)). The structural and chemical changes during this Eu(III)-doping were observed by means of infrared spectroscopy (IR), X-ray photoelectron spectroscopy (XPS), and time-resolved laser fluorescence spectroscopy (TRLFS). These alterations of the CSH phases led to significant changes in the surface chemistry and consequently to considerable variations in the interaction with water, as evidenced by measurements of the contact angles on the modified model substrates. Our results provide the basis for a more profound molecular understanding of reactive transport processes in cement-based systems. Furthermore, these results broaden the perspective of improving the stability of cement-based materials, which are subjected to the impact of aggressive aqueous environments through targeted modifications of the CSH phases.