151 research outputs found

    Study on Dynamic Characteristics of a Pile Group Foundation

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    The earthquake response of a structure on group of piles is investigated. The test model, which is employed in this study, is a foundation on four piles. Three conditions are prepared for examination of the contact effects of the foundation bottom and the backfilling effects on dynamic characteristics of the foundation on the piles. Forced vibration tests are carried out for ascertaining the impedance functions as the inertial interaction, and earthquake observations for the earthquake input motion as the kinematic interaction. On the basis of the test and the observation results, the correlation analyses are executed for examining the applicability of the analytical method based on the substructure method in which the three-dimensional wave propagation theory is applied for calculation of the Green\u27s functions. The analytical method is concluded to have sufficient applicability for the practical design procedure of a structure on pile group

    Acute inhibition of AMPA receptors by perampanel reduces amyloid β-protein levels by suppressing β-cleavage of APP in Alzheimer's disease models

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    Hippocampal hyperexcitability is a promising therapeutic target to prevent Aβ deposition in AD since enhanced neuronal activity promotes presynaptic Aβ production and release. This article highlights the potential application of perampanel (PER), an AMPA receptor (AMPAR) antagonist approved for partial seizures, as a therapeutic agent for AD. Using transgenic AD mice combined with in vivo brain microdialysis and primary neurons under oligomeric Aβ-evoked neuronal hyperexcitability, the acute effects of PER on Aβ metabolism were investigated. A single oral administration of PER rapidly decreased ISF Aβ40 and Aβ42 levels in the hippocampus of J20, APP transgenic mice, without affecting the Aβ40 /Aβ42 ratio; 5 mg/kg PER resulted in declines of 20% and 31%, respectively. Moreover, PER-treated J20 manifested a marked decrease in hippocampal APP βCTF levels with increased FL-APP levels. Consistently, acute treatment of PER reduced sAPPβ levels, a direct byproduct of β-cleavage of APP, released to the medium in primary neuronal cultures under oligomeric Aβ-induced neuronal hyperexcitability. To further evaluate the effect of PER on ISF Aβ clearance, a γ-secretase inhibitor was administered to J20 1 h after PER treatment. PER did not influence the elimination of ISF Aβ, indicating that the acute effect of PER is predominantly on Aβ production. In conclusion, acute treatment of PER reduces Aβ production by suppressing β-cleavage of amyloid-β precursor protein effectively, indicating a potential effect of PER against Aβ pathology in AD

    Phobos Regolith Simulant for MMX Mission: Spectral Measurement for Remote Target Identification and Deconvolution System Training

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    The two natural satellites of Mars, Phobos and Deimos are both important targets for scientific investigation. The JAXA mission Martian Moons eXplorer (MMX) is designed to explore Phobos and Deimos, with a launch date scheduled for 2024. The MMX spacecraft will observe both Martian moons and will land on one of them (Phobos, most likely), to collect a sample and bring it back to Earth. The designs of both the landing and sampling devices depend largely on the surface properties of the target body and on how its surface is reacting to an external action in the low gravity conditions of the target. The Landing Operation Working Team (LOWT) of MMX started analyzing previous observations and theoretical/experimental considerations to better understand the nature of Phobos surface material, developing a Phobos regolith simulant material for the MMX mission [1]. At the Institute for Planetary Research of the German aerospace Center (DLR) in Berlin we performed a spectral characterization of the Phobos regolith simulant. Those data will be used to train an Artificial Neural Network (NN) to produce a system that could rapidly classify data during the mission and for endmember decomposition

    Involvement of NMDAR2A tyrosine phosphorylation in depression‐related behaviour

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102200/1/embj2009300-sup-0001.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102200/2/embj2009300.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102200/3/embj2009300-sup-0003.pd

    Mieap, a p53-Inducible Protein, Controls Mitochondrial Quality by Repairing or Eliminating Unhealthy Mitochondria

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    Maintenance of healthy mitochondria prevents aging, cancer, and a variety of degenerative diseases that are due to the result of defective mitochondrial quality control (MQC). Recently, we discovered a novel mechanism for MQC, in which Mieap induces intramitochondrial lysosome-like organella that plays a critical role in the elimination of oxidized mitochondrial proteins (designated MALM for Mieap-induced accumulation of lysosome-like organelles within mitochondria). However, a large part of the mechanisms for MQC remains unknown. Here, we report additional mechanisms for Mieap-regulated MQC. Reactive oxygen species (ROS) scavengers completely inhibited MALM. A mitochondrial outer membrane protein NIX interacted with Mieap in a ROS-dependent manner via the BH3 domain of NIX and the coiled-coil domain of Mieap. Deficiency of NIX also completely impaired MALM. When MALM was inhibited, Mieap induced vacuole-like structures (designated as MIV for Mieap-induced vacuole), which engulfed and degraded the unhealthy mitochondria by accumulating lysosomes. The inactivation of p53 severely impaired both MALM and MIV generation, leading to accumulation of unhealthy mitochondria. These results suggest that (1) mitochondrial ROS and NIX are essential factors for MALM, (2) MIV is a novel mechanism for lysosomal degradation of mitochondria, and (3) the p53-Mieap pathway plays a pivotal role in MQC by repairing or eliminating unhealthy mitochondria via MALM or MIV generation, respectively

    Possible Existence of Lysosome-Like Organella within Mitochondria and Its Role in Mitochondrial Quality Control

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    The accumulation of unhealthy mitochondria results in mitochondrial dysfunction, which has been implicated in aging, cancer, and a variety of degenerative diseases. However, the mechanism by which mitochondrial quality is regulated remains unclear. Here, we show that Mieap, a novel p53-inducible protein, induces intramitochondrial lysosome-like organella that plays a critical role in mitochondrial quality control. Mieap expression is directly regulated by p53 and is frequently lost in human cancer as result of DNA methylation. Mieap dramatically induces the accumulation of lysosomal proteins within mitochondria and mitochondrial acidic condition without destroying the mitochondrial structure (designated MALM, for Mieap-induced accumulation of lysosome-like organelles within mitochondria) in response to mitochondrial damage. MALM was not related to canonical autophagy. MALM is involved in the degradation of oxidized mitochondrial proteins, leading to increased ATP synthesis and decreased reactive oxygen species generation. These results suggest that Mieap induces intramitochondrial lysosome-like organella that plays a critical role in mitochondrial quality control by eliminating oxidized mitochondrial proteins. Cancer cells might accumulate unhealthy mitochondria due to p53 mutations and/or Mieap methylation, representing a potential cause of the Warburg effect

    First demonstration of single-mode MCF transport network with crosstalk-aware in-service optical channel control

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    Multicore fiber (MCF) transmission is considered as one of the promising technologies for breaking the capacity limit of traditional single mode fibers (SMFs). Managing the XT and configuring optical paths adaptively based on the XT are important as well as achieving longer-distance and larger-capacity transmission, because inter-core crosstalk (XT) could be the main limiting factor for MCF transmission. In a real MCF network, the inter-core XT in a particular core is likely to change continuously as the optical paths in the adjacent cores are dynamically assigned to match the dynamic nature of the data traffic. If we configure the optical paths while ignoring the inter-core XT value, the Q-factors may become excessive. Therefore, monitoring the inter-core XT value continuously and configuring optical path parameters adaptively and flexibly are essential. To address these challenges, we develop an MCF transport network testbed and demonstrate an XT-aware traffic engineering scenario. With the help of a software-defined network (SDN) controller, the modulation format and optical path route are adaptively changed based on the monitored XT values by using programmable devices such as a real-time transponder and a reconfigurable optical add-drop multiplexer (ROADM)
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