1,304 research outputs found

    Allele-specific endogenous tagging and quantitative analysis of β-catenin in colorectal cancer cells

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    Wnt signaling plays important roles in development, homeostasis, and tumorigenesis. Mutations in β-catenin that activate Wnt signaling have been found in colorectal and hepatocellular carcinomas. However, the dynamics of wild-type and mutant forms of β-catenin are not fully understood. Here, we genome-engineered fluorescently tagged alleles of endogenous β-catenin in a colorectal cancer cell line. Wild-type and oncogenic mutant alleles were tagged with different fluorescent proteins, enabling the analysis of both variants in the same cell. We analyzed the properties of both β-catenin alleles using immunoprecipitation, immunofluorescence, and fluorescence correlation spectroscopy approaches, revealing distinctly different biophysical properties. In addition, activation of Wnt signaling by treatment with a GSK3β inhibitor or a truncating APC mutation modulated the wild-type allele to mimic the properties of the mutant β-catenin allele. The one-step tagging strategy demonstrates how genome engineering can be employed for the parallel functional analysis of different genetic variants

    Generalized Density-Functional Tight-Binding Repulsive Potentials from Unsupervised Machine Learning

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    We combine the approximate density-functional tight-binding (DFTB) method with unsupervised machine learning. This allows us to improve transferability and accuracy, make use of large quantum chemical data sets for the parametrization, and efficiently automatize the parametrization process of DFTB. For this purpose, generalized pair-potentials are introduced, where the chemical environment is included during the learning process, leading to more specific effective two-body potentials. We train on energies and forces of equilibrium and nonequilibrium structures of 2100 molecules, and test on ∼130 000 organic molecules containing O, N, C, H, and F atoms. Atomization energies of the reference method can be reproduced within an error of ∼2.6 kcal/mol, indicating drastic improvement over standard DFTB

    A search for edge-on galaxy lenses in the CFHT Legacy Survey

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    [ABRIDGED] The new generation of wide field optical imaging like the Canada France Hawaii Telescope Legacy Survey (CFHTLS) enables discoveries of all types of gravitational lenses present in the sky. The Strong Lensing Legacy Survey (SL2S) project has started an inventory, respectively for clusters or groups of galaxies lenses, and for Einstein rings around distant massive ellipticals. Here we attempt to extend this inventory by finding lensing events produced by massive edge-on disk galaxies which remains a poorly documented class of lenses. We implement and test an automated search procedure of edge-on galaxy lenses in the CFHTLS Wide fields with magnitude 18Comment: several major edits, 8 pages, A&A accepte

    Planar and Three-Dimensional Printing of Conductive Inks

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    Printed electronics rely on low-cost, large-area fabrication routes to create flexible or multidimensional electronic, optoelectronic, and biomedical devices1-3. In this paper, we focus on one- (1D), two- (2D), and three-dimensional (3D) printing of conductive metallic inks in the form of flexible, stretchable, and spanning microelectrodes

    Residents\u27 perceptions of smart energy metres

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    Smart metres are a form of expert system with performance features beyond energy‐consumption record keeping, to include monitoring, analysing, and estimating metre readings. Although smart metres have great capabilities, this technology is still in its infancy in many developing countries, and little is known about the kinds of risks associated with smart metres from residents\u27 perspectives. This research therefore aims to fill this gap by examining the influence of four different types of perceived risk on residents\u27 intentions to use smart metres in Jordan. By following a quantitative approach, 242 survey responses were tested by using structural equation modelling–partial least squares. The statistical results indicated that perceived security and technical risks have a significant and negative impact on residents\u27 intentions to use smart metres. However, perceived privacy and health risks, surprisingly, were found to have no significant negative influence on intention to use. Theoretical and practical implications are indicated, and directions of future research are subsequently specified

    The Gas Content in Galactic Disks: Correlation with Kinematics

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    We consider the relationship between the total HI mass in late-type galaxies and the kinematic properties of their disks. The mass MHIM_HI for galaxies with a wide variety of properties, from dwarf dIrr galaxies with active star formation to giant low-brightness galaxies, is shown to correlate with the product VcR0V_c R_0 (VcV_c is the rotational velocity, and R0R_0 is the radial photometric disks scale length), which characterizes the specific angular momentum of the disk. This relationship, along with the anticorrelation between the relative mass of HI in a galaxy and VcV_c, can be explained in terms of the previously made assumption that the gas density in the disks of most galaxies is maintained at a level close to the threshold (marginal) stability of a gaseous layer to local gravitational perturbations. In this case, the regulation mechanism of the star formation rate associated with the growth of local gravitational instability in the gaseous layer must play a crucial role in the evolution of the gas content in the galactic disk.Comment: revised version to appear in Astronomy Letters, 8 pages, 5 EPS figure
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