Transcription factor (TF) binding to DNA is fundamental for gene regulation. However, it remains unknown how the dynamics of TF-DNA interactions change during cell-fate determination in vivo. Here, ...we use photo-activatable FCS to quantify TF-DNA binding in single cells of developing mouse embryos. In blastocysts, the TFs Oct4 and Sox2, which control pluripotency, bind DNA more stably in pluripotent than in extraembryonic cells. By contrast, in the four-cell embryo, Sox2 engages in more long-lived interactions than does Oct4. Sox2 long-lived binding varies between blastomeres and is regulated by H3R26 methylation. Live-cell tracking demonstrates that those blastomeres with more long-lived binding contribute more pluripotent progeny, and reducing H3R26 methylation decreases long-lived binding, Sox2 target expression, and pluripotent cell numbers. Therefore, Sox2-DNA binding predicts mammalian cell fate as early as the four-cell stage. More generally, we reveal the dynamic repartitioning of TFs between DNA sites driven by physiological epigenetic changes.
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•Transcription factors display temporally distinct DNA binding in live mouse embryos•Sox2-DNA binding is heterogeneous between four-cell blastomeres within the embryo•Histone 3 arginine 26 methylation regulates Sox2-DNA binding•More Sox2 engaged in long-lived DNA binding predicts inner cell allocation
Quantification of the dynamics of Sox2-DNA binding in single cells of live mouse embryos shows that its heterogeneities in four-cell blastomeres are regulated by histone methylation and predict a bias in the contribution of cells to the inner mass.
This research investigates the extent to which organizational change initiatives may lead to divergent patterns of sensemaking among organizational members. Drawing on the symbolic convergence ...theory, we performed an in-depth fantasy theme analysis of organization members’ rhetoric around an organizational change at a private university. Our analysis uncovers six fantasy themes and two corresponding fantasy types, which lead to no rhetorical vision. The lack of cognitive convergence between change initiators and change recipients suggests the inherent incompatibility between managerial and employee fantasies around organizational change, barring the exceptions of dual-responsibility change recipients (e.g., faculty members who also assume administrative responsibilities), who tend to adopt the change initiator rhetoric. Overall, this study informs our extant knowledge of change sensemaking with novel theoretical and methodological insights and bears implications for organizational change researchers and practitioners alike.
The Tubridge flow diverter is a novel device developed in China and aimed at reconstructing the parent artery and occluding the aneurysm. We conducted this study to evaluate its feasibility, safety, ...and efficacy for the treatment of large or giant internal carotid artery aneurysms, which are still challenging with conventional therapy.
The clinical and angiographic data of 28 patients with 28 large or giant internal carotid artery aneurysms treated with Tubridge flow diverters were prospectively collected and analyzed.
Thirty-three Tubridge flow diverters were successfully implanted except for 1 poor midstent opening; the result was a technical success rate of 97.0% (32/33). Follow-up angiographies were available for 25 aneurysms; the mean follow-up was 9.9 months (5-24 months). Of the 25 aneurysms, 18 (72.0%) were completely occluded, 6 (24.0%) were improved, and 1 (4.0%) was unchanged. All of the visible covered branches and parent arteries were patent, with no stenosis or obliteration. During a follow-up of 6-30 months (mean, 19 months), symptoms were resolved in 13 patients, improved in 6 patients, and unchanged in 4 patients. Five patients experienced transient clinical deterioration due to a postoperative increased mass effect. Procedure-related morbidity and mortality were both zero.
Our preliminary experience shows that the Tubridge flow diverter is a safe and effective tool for treating large and giant internal carotid artery aneurysms. However, multicenter randomized trials and studies involving a long-term follow-up are necessary.
The multilayer one-class classification (OCC) frameworks have gained great traction in research on anomaly and outlier detection. However, most multilayer OCC algorithms suffer from loosely connected ...feature coding, affecting the ability of generated latent space to properly generate a highly discriminative representation between object classes. To alleviate this deficiency, two novel OCC frameworks, namely: 1) OCC structure using the subnetwork neural network (OC-SNN) and 2) maximum correntropy-based OC-SNN (MCOC-SNN), are proposed in this article. The novelties of this article are as follows: 1) the subnetwork is used to build the discriminative latent space; 2) the proposed models are one-step learning networks, instead of stacking feature learning blocks and final classification layer to recognize the input pattern; 3) unlike existing works which utilize mean square error (MSE) to learn low-dimensional features, the MCOC-SNN uses maximum correntropy criterion (MCC) for discriminative feature encoding; and 4) a brand-new OCC dataset, called CO-Mask, is built for this research. Experimental results on the visual classification domain with a varying number of training samples from 6131 to 513 061 demonstrate that the proposed OC-SNN and MCOC-SNN achieve superior performance compared to the existing multilayer OCC models. For reproducibility, the source codes are available at https://github.com/W1AE/OCC .
ABSTRACT As part of the Megamaser Cosmology Project, here we present a new geometric distance measurement to the megamaser galaxy NGC 5765b. Through a series of very long baseline interferometry ...observations, we have confirmed the water masers trace a thin, sub-parsec Keplerian disk around the nucleus, implying an enclosed mass of 4.55 0.40 × 107 M . Meanwhile, from single-dish monitoring of the maser spectra over two years, we measured the secular drifts of maser features near the systemic velocity of the galaxy with rates between 0.5 and 1.2 km s−1 yr−1. Fitting a warped, thin-disk model to these measurements, we determine a Hubble Constant H0 of 66.0 6.0 km s−1 Mpc−1 with an angular-diameter distance to NGC 5765b of 126.3 11.6 Mpc. Apart from the distance measurement, we also investigate some physical properties related to the maser disk in NGC 5765b. The high-velocity features are spatially distributed into several clumps, which may indicate the existence of a spiral density wave associated with the accretion disk. For the redshifted features, the envelope defined by the peak maser intensities increases with radius. The profile of the systemic masers in NGC 5765b is smooth and shows almost no structural changes over the two years of monitoring time, which differs from the more variable case of NGC 4258.
Among older patients with untreated chronic lymphocytic leukemia, treatment with ibrutinib, either alone or in combination with rituximab, was superior to treatment with bendamustine plus rituximab ...with regard to progression-free survival. The two regimens that contained ibrutinib were equally effective.
The paper presents a novel approach for multi-frequency acoustic topology optimization of sound-absorption materials. In this work, the isogeometric boundary element method based on subdivision ...surfaces is used to solve Helmholtz equations. To avoid time-consuming frequency sweep, we adopt a series expansion method to decouple the frequency-dependent terms from the integrand in the boundary element method, including the terms associated with the impedance boundary conditions that were introduced to model the absorption materials. Moreover, the second-order Arnoldi (SOAR) approach is employed to reduce the order of the systems. Three dimensional numerical examples were given to demonstrate the effectiveness of the proposed algorithm.
•Series expansions are utilized for frequency decoupling of acoustic BEM.•The model order is reduced by the second-order Arnoldi (SOAR) algorithm.•The isogeometric BEM is employed to integrate CAD and numerical analysis.•Multi-frequency topology optimization is performed with the isogeometric BEM.
ABSTRACT We use new precision measurements of black hole (BH) masses from water megamaser disks to investigate scaling relations between macroscopic galaxy properties and supermassive BH mass. The ...megamaser-derived BH masses span 106-108 M , while all the galaxy properties that we examine (including total stellar mass, central mass density, and central velocity dispersion) lie within a narrower range. Thus, no galaxy property correlates tightly with M BH in ∼L* spiral galaxies as traced by megamaser disks. Of them all, stellar velocity dispersion provides the tightest relation, but at fixed * the mean megamaser M BH are offset by −0.6 0.1 dex relative to early-type galaxies. Spiral galaxies with non-maser dynamical BH masses do not appear to show this offset. At low mass, we do not yet know the full distribution of BH mass at fixed galaxy property; the non-maser dynamical measurements may miss the low-mass end of the BH distribution due to an inability to resolve their spheres of influence and/or megamasers may preferentially occur in lower-mass BHs.
Flaw-free bulk Cu specimens with a high density of nano-scale mechanical twins were produced by means of dynamic plastic deformation at liquid nitrogen temperature. The nano-twinned Cu exhibits a ...tensile yield strength of 600
MPa and an elongation-to-failure of 11%. The significant strengthening originates from the effective blockage of glide dislocations by numerous twin boundaries and dislocations.
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