3,627 research outputs found

    Differential subcellular localization and activity of kelch repeat proteins KLHDC1 and KLHDC2.

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    We have previously identified and characterized human KLHDC2/HCLP-1, a kelch repeat protein that interacts with and inhibits transcription factor LZIP. In this study, we identified and characterized a paralog of KLHDC2 called KLHDC1. KLHDC1 and KLHDC2 share about 50% identity at the level of amino acid sequence and both gene loci localize to human chromosome 14q21.3. This cluster of KLHDC1 and KLHDC2 genes is highly conserved in vertebrates ranging from pufferfish to human. Both genes are expressed highly in skeletal muscle, but weakly in various other tissues. While KLHDC2 was predominantly found in the nucleus, KLHDC1 is a cytoplasmic protein. Neither KLHDC1 nor KLHDC2 binds to actin. In addition, KLHDC1 was unable to inhibit LZIP/CREB3-mediated transcriptional activation. Thus, KLHDC1 and KLHDC2 have differential localization and activity in cultured mammalian cells.postprin

    Structure of the large terminase from a hyperthermophilic virus reveals a unique mechanism for oligomerization and ATP hydrolysis

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    The crystal structure of the large terminase from the Geobacillus stearothermophilus bacteriophage D6E shows a unique relative orientation of the N-terminal adenosine triphosphatase (ATPase) and C-terminal nuclease domains. This monomeric ‘initiation’ state with the two domains ‘locked’ together is stabilized via a conserved C-terminal arm, which may interact with the portal protein during motor assembly, as predicted for several bacteriophages. Further work supports the formation of an active oligomeric state: (i) AUC data demonstrate the presence of oligomers; (ii) mutational analysis reveals a trans-arginine finger, R158, indispensable for ATP hydrolysis; (iii) the location of this arginine is conserved with the HerA/FtsK ATPase superfamily; (iv) a molecular docking model of the pentamer is compatible with the location of the identified arginine finger. However, this pentameric model is structurally incompatible with the monomeric ‘initiation’ state and is supported by the observed increase in kcat of ATP hydrolysis, from 7.8 ± 0.1 min−1 to 457.7 ± 9.2 min−1 upon removal of the C-terminal nuclease domain. Taken together, these structural, biophysical and biochemical data suggest a model where transition from the ‘initiation’ state into a catalytically competent pentameric state, is accompanied by substantial domain rearrangements, triggered by the removal of the C-terminal arm from the ATPase active site

    Excitation Spectra And Hard-core Thermodynamics Of Bosonic Atoms In Optical Superlattices

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    A generalized double-well-basis coupled representation is proposed to investigate excitation spectra and thermodynamics of bosonic atoms in double-well optical superlattices. In the hard-core limit and with a filling factor of one, excitations describing the creation of pairs of a doubly occupied state and a simultaneous empty state, and those from a symmetric singly occupied state to an antisymmetric state are carefully analyzed and their excitation spectra are calculated within mean-field theory. Based on the hard-core statistics, the equilibrium properties such as heat capacity and particle populations are studied in detail. The cases with other filling factors are also briefly discussed.published_or_final_versio

    PAK4 phosphorylates p53 at serine 215 to promote liver cancer metastasis

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    PAK4 kinase contributes to signaling pathways controlling cancer cell transformation, invasion and survival, but its clinicopathological impact has begun to emerge only recently. Here we report that PAK4 overexpression in hepatocellular carcinoma (HCC) conveys aggressive metastatic properties. A novel nuclear splice isoform of PAK4 lacking exon 2 sequences was isolated as part of our studies. By stably overexpressing or silencing PAK4 in HCC cells we showed that it was critical for their migration. Mechanistic investigations in this setting revealed that PAK4 directly phosphorylated p53 at S215, which not only attenuated transcriptional transactivation activity but also inhibited p53-mediated suppression of HCC cell invasion. Taken together, our results showed how PAK4 overexpression in HCC promotes metastatic invasion by regulating p53 phosphorylation.postprin

    Automating Vehicles by Deep Reinforcement Learning using Task Separation with Hill Climbing

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    Within the context of autonomous driving a model-based reinforcement learning algorithm is proposed for the design of neural network-parameterized controllers. Classical model-based control methods, which include sampling- and lattice-based algorithms and model predictive control, suffer from the trade-off between model complexity and computational burden required for the online solution of expensive optimization or search problems at every short sampling time. To circumvent this trade-off, a 2-step procedure is motivated: first learning of a controller during offline training based on an arbitrarily complicated mathematical system model, before online fast feedforward evaluation of the trained controller. The contribution of this paper is the proposition of a simple gradient-free and model-based algorithm for deep reinforcement learning using task separation with hill climbing (TSHC). In particular, (i) simultaneous training on separate deterministic tasks with the purpose of encoding many motion primitives in a neural network, and (ii) the employment of maximally sparse rewards in combination with virtual velocity constraints (VVCs) in setpoint proximity are advocated.Comment: 10 pages, 6 figures, 1 tabl

    Artificial interspecific hybridization between Macrobrachium species

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    Viable F-1 hybrids were obtained from crosses of female Macrobrachium nipponense and male Macrobrachium hainanense involving spermatophore transfer and artificial insemination. This represents the first successful known case of hybridization of two Macrobrachium species by means of artificial insemination. The hatching rate was over 90%. About 20-60% of newly hatched larvae metamorphosed to postlarvae. The morphological characteristics of the hybrids resembled a combination of features of both parents. Malate dehydrogenase (MDH) and esterase (EST) isozyme electrophoresis indicated parents and F-1 hybrids showed co-dominant expression of the paternal and maternal alleles controlling the isozymes and confirmed the hybridization. (C) 2004 Elsevier B.V. All rights reserved.Viable F-1 hybrids were obtained from crosses of female Macrobrachium nipponense and male Macrobrachium hainanense involving spermatophore transfer and artificial insemination. This represents the first successful known case of hybridization of two Macrobrachium species by means of artificial insemination. The hatching rate was over 90%. About 20-60% of newly hatched larvae metamorphosed to postlarvae. The morphological characteristics of the hybrids resembled a combination of features of both parents. Malate dehydrogenase (MDH) and esterase (EST) isozyme electrophoresis indicated parents and F-1 hybrids showed co-dominant expression of the paternal and maternal alleles controlling the isozymes and confirmed the hybridization. (C) 2004 Elsevier B.V. All rights reserved

    A Novel Load Shedding Strategy Combining Undervoltage and Underfrequency with Considering of High Penetration of Wind Energy

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    Low carbon emission is one of the main targets for smart grid planning. To achieve this goal, intermittent energies such as wind and solar are integrated to the power systems increasingly. However, this may create huge challenges to the power system operators for balancing the generation and demand at all times and guaranteeing the system reliability at the same time. With high penetration of renewable energies, power system operators are compelled to curtail the loads when the power system cannot rely on power from renewable energies continuously due to strong dependence on the environment. As an important defense to protect the power network from collapsing and to keep the system integrating, load shedding has been designed and proposed for decades. However, most of the shedding schemes consider the load increasing instead of lack of generation. This paper applies a load shedding scheme with considering both voltage and frequency changes when the generation is inadequate since the power system cannot obtain the expected renewable generation and renewable energies are highly penetrated into the grid.State Grid Corporation of Chin
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