3,046 research outputs found

    Effects of substrate-induced strain on transport properties of LaMnO[sub 3+δ] and CaMnO₃ thin films using ferroelectric poling and converse piezoelectric effect

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    Author name used in this publication: H. L. W. ChanAuthor name used in this publication: C. L. Choy2009-2010 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

    Principle demonstration of the phase locking based on the electro-optic modulator for Taiji space gravitational wave detection pathfinder mission

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    Weak-light phase locking is a key technology for Taiji space gravitational wave detection and its pathfinder mission. Previously, the phase locking was achieved by a complicated technique, which controls the frequency of the laser via a piezo-electric actuator (kHz range or more) and a temperature actuator (sub-Hz range). We propose an easy phase-locking strategy, which is based on the electro-optic modulator (EOM). Compared with the traditional way, this strategy only needs to modulate the driven voltage of the EOM, and the frequency bandwidth can cover all ranges. An experiment is also established to prove the feasibility of the method. The results show that the noises are &lt;80 mu rad/Hz(1/2) in frequencies from 0.2 to 1 Hz, and the thermal drift is the main noise source in our recent system. (C) 2018 Society of Photo-Optical Instrumentation Engineers (SPIE)</p

    Ferroelectric poling and converse-piezoelectric-effect-induced strain effects in La₀.₇Ba₀.₃MnO₃ thin films grown on ferroelectric single-crystal substrates

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    Author name used in this publication: Y. WangAuthor name used in this publication: H. L. W. ChanAuthor name used in this publication: C. L. Choy2008-2009 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

    Stimulation of Na<sup>+</sup>/H<sup>+</sup> Exchanger Isoform 1 Promotes Microglial Migration

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    Regulation of microglial migration is not well understood. In this study, we proposed that Na+/H+ exchanger isoform 1 (NHE-1) is important in microglial migration. NHE-1 protein was co-localized with cytoskeletal protein ezrin in lamellipodia of microglia and maintained its more alkaline intracellular pH (pHi). Chemoattractant bradykinin (BK) stimulated microglial migration by increasing lamellipodial area and protrusion rate, but reducing lamellipodial persistence time. Interestingly, blocking NHE-1 activity with its potent inhibitor HOE 642 not only acidified microglia, abolished the BK-triggered dynamic changes of lamellipodia, but also reduced microglial motility and microchemotaxis in response to BK. In addition, NHE-1 activation resulted in intracellular Na+ loading as well as intracellular Ca2+ elevation mediated by stimulating reverse mode operation of Na+/Ca2+ exchange (NCXrev). Taken together, our study shows that NHE-1 protein is abundantly expressed in microglial lamellipodia and maintains alkaline pHi in response to BK stimulation. In addition, NHE-1 and NCXrev play a concerted role in BK-induced microglial migration via Na+ and Ca2+ signaling. © 2013 Shi et al

    On dynamic network entropy in cancer

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    The cellular phenotype is described by a complex network of molecular interactions. Elucidating network properties that distinguish disease from the healthy cellular state is therefore of critical importance for gaining systems-level insights into disease mechanisms and ultimately for developing improved therapies. By integrating gene expression data with a protein interaction network to induce a stochastic dynamics on the network, we here demonstrate that cancer cells are characterised by an increase in the dynamic network entropy, compared to cells of normal physiology. Using a fundamental relation between the macroscopic resilience of a dynamical system and the uncertainty (entropy) in the underlying microscopic processes, we argue that cancer cells will be more robust to random gene perturbations. In addition, we formally demonstrate that gene expression differences between normal and cancer tissue are anticorrelated with local dynamic entropy changes, thus providing a systemic link between gene expression changes at the nodes and their local network dynamics. In particular, we also find that genes which drive cell-proliferation in cancer cells and which often encode oncogenes are associated with reductions in the dynamic network entropy. In summary, our results support the view that the observed increased robustness of cancer cells to perturbation and therapy may be due to an increase in the dynamic network entropy that allows cells to adapt to the new cellular stresses. Conversely, genes that exhibit local flux entropy decreases in cancer may render cancer cells more susceptible to targeted intervention and may therefore represent promising drug targets.Comment: 10 pages, 3 figures, 4 tables. Submitte

    Design of an electrochemical micromachining machine

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    Electrochemical micromachining (μECM) is a non-conventional machining process based on the phenomenon of electrolysis. μECM became an attractive area of research due to the fact that this process does not create any defective layer after machining and that there is a growing demand for better surface integrity on different micro applications including microfluidics systems, stress-free drilled holes in automotive and aerospace manufacturing with complex shapes, etc. This work presents the design of a next generation μECM machine for the automotive, aerospace, medical and metrology sectors. It has three axes of motion (X, Y, Z) and a spindle allowing the tool-electrode to rotate during machining. The linear slides for each axis use air bearings with linear DC brushless motors and 2-nm resolution encoders for ultra precise motion. The control system is based on the Power PMAC motion controller from Delta Tau. The electrolyte tank is located at the rear of the machine and allows the electrolyte to be changed quickly. This machine features two process control algorithms: fuzzy logic control and adaptive feed rate. A self-developed pulse generator has been mounted and interfaced with the machine and a wire ECM grinding device has been added. The pulse generator has the possibility to reverse the pulse polarity for on-line tool fabrication.The research reported in this paper is supported by the European Commission within the project “Minimizing Defects in Micro-Manufacturing Applications (MIDEMMA)” (FP7-2011-NMPICT- FoF-285614)

    SIRT1 associates with eIF2-alpha and regulates the cellular stress response

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    SIRT1 is a NAD+ dependent protein deacetylase known to increase longevity in model organisms. SIRT1 regulates cellular response to oxidative and/or genotoxic stress by regulating proteins such as p53 and FOXO. The eukaryotic initiation factor-2, eIF2, plays a critical role in the integrated stress response pathway. Under cellular stress, phosphorylation of the alpha subunit of eIF2 is essential for immediate shut-off of translation and activation of stress response genes. Here we demonstrate that SIRT1 interacts with eIF2α. Loss of SIRT1 results in increased phosphorylation of eIF2α. However, the downstream stress induced signaling pathway is compromised in SIRT1-deficient cells, indicated by delayed expression of the downstream target genes CHOP and GADD34 and a slower post-stress translation recovery. Finally, SIRT1 co-immunoprecipitates with mediators of eIF2α dephosphorylation, GADD34 and CreP, suggesting a role for SIRT1 in the negative feedback regulation of eIF2α phosphorylation

    The catalytic subunit of the system L1 amino acid transporter (S<i>lc7a5</i>) facilitates nutrient signalling in mouse skeletal muscle

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    The System L1-type amino acid transporter mediates transport of large neutral amino acids (LNAA) in many mammalian cell-types. LNAA such as leucine are required for full activation of the mTOR-S6K signalling pathway promoting protein synthesis and cell growth. The SLC7A5 (LAT1) catalytic subunit of high-affinity System L1 functions as a glycoprotein-associated heterodimer with the multifunctional protein SLC3A2 (CD98). We generated a floxed Slc7a5 mouse strain which, when crossed with mice expressing Cre driven by a global promoter, produced Slc7a5 heterozygous knockout (Slc7a5+/-) animals with no overt phenotype, although homozygous global knockout of Slc7a5 was embryonically lethal. Muscle-specific (MCK Cre-mediated) Slc7a5 knockout (MS-Slc7a5-KO) mice were used to study the role of intracellular LNAA delivery by the SLC7A5 transporter for mTOR-S6K pathway activation in skeletal muscle. Activation of muscle mTOR-S6K (Thr389 phosphorylation) in vivo by intraperitoneal leucine injection was blunted in homozygous MS-Slc7a5-KO mice relative to wild-type animals. Dietary intake and growth rate were similar for MS-Slc7a5-KO mice and wild-type littermates fed for 10 weeks (to age 120 days) with diets containing 10%, 20% or 30% of protein. In MS-Slc7a5-KO mice, Leu and Ile concentrations in gastrocnemius muscle were reduced by ∼40% as dietary protein content was reduced from 30 to 10%. These changes were associated with >50% decrease in S6K Thr389 phosphorylation in muscles from MS-Slc7a5-KO mice, indicating reduced mTOR-S6K pathway activation, despite no significant differences in lean tissue mass between groups on the same diet. MS-Slc7a5-KO mice on 30% protein diet exhibited mild insulin resistance (e.g. reduced glucose clearance, larger gonadal adipose depots) relative to control animals. Thus, SLC7A5 modulates LNAA-dependent muscle mTOR-S6K signalling in mice, although it appears non-essential (or is sufficiently compensated by e.g. SLC7A8 (LAT2)) for maintenance of normal muscle mass

    A new rhynchocephalian from the late jurassic of Germany with a dentition that is unique amongst tetrapods.

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    Rhynchocephalians, the sister group of squamates (lizards and snakes), are only represented by the single genus Sphenodon today. This taxon is often considered to represent a very conservative lineage. However, rhynchocephalians were common during the late Triassic to latest Jurassic periods, but rapidly declined afterwards, which is generally attributed to their supposedly adaptive inferiority to squamates and/or Mesozoic mammals, which radiated at that time. New finds of Mesozoic rhynchocephalians can thus provide important new information on the evolutionary history of the group. A new fossil relative of Sphenodon from the latest Jurassic of southern Germany, Oenosaurus muehlheimensis gen. et sp. nov., presents a dentition that is unique amongst tetrapods. The dentition of this taxon consists of massive, continuously growing tooth plates, probably indicating a crushing dentition, thus representing a previously unknown trophic adaptation in rhynchocephalians. The evolution of the extraordinary dentition of Oenosaurus from the already highly specialized Zahnanlage generally present in derived rhynchocephalians demonstrates an unexpected evolutionary plasticity of these animals. Together with other lines of evidence, this seriously casts doubts on the assumption that rhynchocephalians are a conservative and adaptively inferior lineage. Furthermore, the new taxon underlines the high morphological and ecological diversity of rhynchocephalians in the latest Jurassic of Europe, just before the decline of this lineage on this continent. Thus, selection pressure by radiating squamates or Mesozoic mammals alone might not be sufficient to explain the demise of the clade in the Late Mesozoic, and climate change in the course of the fragmentation of the supercontinent of Pangaea might have played a major role
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