3,742 research outputs found

    Multiagent simple temporal problem: The arc-consistency approach

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    Copyright © 2018, Association for the Advancement of Artificial Intelligence (www.aaai.org). All rights reserved. The Simple Temporal Problem (STP) is a fundamental temporal reasoning problem and has recently been extended to the Multiagent Simple Temporal Problem (MaSTP). In this paper we present a novel approach that is based on enforcing arc-consistency (AC) on the input (multiagent) simple temporal network. We show that the AC-based approach is sufficient for solving both the STP and MaSTP and provide efficient algorithms for them. As our AC-based approach does not impose new constraints between agents, it does not violate the privacy of the agents and is superior to the state-of-the-art approach to MaSTP. Empirical evaluations on diverse benchmark datasets also show that our AC-based algorithms for STP and MaSTP are significantly more efficient than existing approaches

    Comparison of three topologies for VRM fast transient application

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    This paper compares three topologies for voltage regulator module VRM for fast transient application. The topologies are the most popular multi-phase converter, a synchronous rectifier buck converter topology and a recently introduced new stepping inductor converter. Analysis and simulation show that the stepping inductor topology gives the fastest response with minimal amount of output filter capacitance.published_or_final_versio

    The nature of hydrogen-bonding interaction in the prototypic hybrid halide perovskite, tetragonal CH3NH3PbI3

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    In spite of the key role of hydrogen bonding in the structural stabilization of the prototypic hybrid halide perovskite, CH3NH3PbI3 (MAPbI(3)), little progress has been made in our in-depth understanding of the hydrogen-bonding interaction between the MA(+)-ion and the iodide ions in the PbI6-octahedron network. Herein, we show that there exist two distinct types of the hydrogen-bonding interaction, naming alpha-and beta-modes, in the tetragonal MAPbI(3) on the basis of symmetry argument and density-functional theory calculations. The computed Kohn-Sham (K-S) energy difference between these two interaction modes is 45.14 meV per MA-site with the alpha-interaction mode being responsible for the stable hydrogen-bonding network. The computed bandgap (E-g) is also affected by the hydrogen-bonding mode, with E-g of the alpha-interaction mode (1.73 eV) being significantly narrower than that of the beta-interaction mode (2.03 eV). We have further estimated the individual bonding strength for the ten relevant hydrogen bonds having a bond critical point.open113728sciescopu

    Tai Chi for Chronic Pain Conditions: A Systematic Review and Meta-analysis of Randomized Controlled Trials

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    Several studies reported that Tai Chi showed potential effects for chronic pain, but its role remains controversial. This review assessed the evidence regarding the effects of Tai Chi for chronic pain conditions. 18 randomized controlled trials were included in our review. The aggregated results have indicated that Tai Chi showed positive evidence on immediate relief of chronic pain from osteoarthritis (standardized mean difference [SMD],-0.54; 95% confidence intervals [CI],-0.77 to-0.30; P < 0.05). The valid duration of Tai Chi practice for osteoarthritis may be more than 5 weeks. And there were some beneficial evidences regarding the effects of Tai Chi on immediate relief of chronic pain from low back pain (SMD,-0.81; 95% CI,-1.11 to-0.52; P < 0.05) and osteoporosis (SMD,-0.83; 95% CI,-1.37 to-0.28; P = 0.003). Therefore, clinicians may consider Tai Chi as a viable complementary and alternative medicine for chronic pain conditions

    Interleukin-1β sequesters hypoxia inducible factor 2α to the primary cilium.

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    BACKGROUND: The primary cilium coordinates signalling in development, health and disease. Previously we have shown that the cilium is essential for the anabolic response to loading and the inflammatory response to interleukin-1β (IL-1β). We have also shown the primary cilium elongates in response to IL-1β exposure. Both anabolic phenotype and inflammatory pathology are proposed to be dependent on hypoxia-inducible factor 2 alpha (HIF-2α). The present study tests the hypothesis that an association exists between the primary cilium and HIFs in inflammatory signalling. RESULTS: Here we show, in articular chondrocytes, that IL-1β-induces primary cilia elongation with alterations to cilia trafficking of arl13b. This elongation is associated with a transient increase in HIF-2α expression and accumulation in the primary cilium. Prolyl hydroxylase inhibition results in primary cilia elongation also associated with accumulation of HIF-2α in the ciliary base and axoneme. This recruitment and the associated cilia elongation is not inhibited by blockade of HIFα transcription activity or rescue of basal HIF-2α expression. Hypomorphic mutation to intraflagellar transport protein IFT88 results in limited ciliogenesis. This is associated with increased HIF-2α expression and inhibited response to prolyl hydroxylase inhibition. CONCLUSIONS: These findings suggest that ciliary sequestration of HIF-2α provides negative regulation of HIF-2α expression and potentially activity. This study indicates, for the first time, that the primary cilium regulates HIF signalling during inflammation

    Early Elevation of Matrix Metalloproteinase-8 and -9 in Pediatric ARDS Is Associated with an Increased Risk of Prolonged Mechanical Ventilation

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    BACKGROUND: Matrix metalloproteinases (MMP) -8 and -9 may play key roles in the modulation of neutrophilic lung inflammation seen in pediatric Acute Respiratory Distress Syndrome (ARDS). We aimed to perform a comprehensive analysis of MMP-8 and MMP-9 activity in tracheal aspirates of pediatric ARDS patients compared with non-ARDS controls, testing whether increased MMP-8 and -9 activities were associated with clinical outcomes. METHODS: Tracheal aspirates were collected from 33 pediatric ARDS patients and 21 non-ARDS controls at 48 hours of intubation, and serially for those who remained intubated greater than five days. MMPs, tissue inhibitor of metalloproteinases (TIMPs), human neutrophil elastase (HNE) and myeloperoxidase (MPO) activity were measured by ELISA, and correlated with clinical indicators of disease severity such as PRISM (Pediatric Risk of Mortality) scores, oxygen index (OI), multi-organ system failure (MOSF) and clinical outcome measures including length of intubation, ventilator-free days (VFDs) and mortality in the Pediatric Intensive Care Unit (PICU). RESULTS: Active MMP-9 was elevated early in pediatric ARDS subjects compared to non-ARDS controls. Higher MMP-8 and active MMP-9 levels at 48 hours correlated with a longer course of mechanical ventilation (r = 0.41, p = 0.018 and r = 0.75, p<0.001; respectively) and fewer number of VFDs (r = -0.43, p = 0.013 and r = -0.76, p<0.001; respectively), independent of age, gender and severity of illness. Patients with the highest number of ventilator days had the highest levels of active MMP-9. MMP-9 and to a lesser extent MMP-8 activities in tracheal aspirates from ARDS subjects were sensitive to blockade by small molecule inhibitors. CONCLUSIONS: Higher MMP-8 and active MMP-9 levels at 48 hours of disease onset are associated with a longer duration of mechanical ventilation and fewer ventilator-free days among pediatric patients with ARDS. Together, these results identify early biomarkers predictive of disease course and potential therapeutic targets for this life threatening disease

    ADAM10 mediates trastuzumab resistance and is correlated with survival in HER2 positive breast cancer.

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    Trastuzumab prolongs survival in HER2 positive breast cancer patients. However, resistance remains a challenge. We have previously shown that ADAM17 plays a key role in maintaining HER2 phosphorylation during trastuzumab treatment. Beside ADAM17, ADAM10 is the other well characterized ADAM protease responsible for HER ligand shedding. Therefore, we studied the role of ADAM10 in relation to trastuzumab treatment and resistance in HER2 positive breast cancer. ADAM10 expression was assessed in HER2 positive breast cancer cell lines and xenograft mice treated with trastuzumab. Trastuzumab treatment increased ADAM10 levels in HER2 positive breast cancer cells (p ≤ 0.001 in BT474; p ≤ 0.01 in SKBR3) and in vivo (p ≤ 0.0001) compared to control, correlating with a decrease in PKB phosphorylation. ADAM10 inhibition or knockdown enhanced trastuzumab response in naïve and trastuzumab resistant breast cancer cells. Trastuzumab monotherapy upregulated ADAM10 (p ≤ 0.05); and higher pre-treatment ADAM10 levels correlated with decreased clinical response (p ≤ 0.05) at day 21 in HER2 positive breast cancer patients undergoing a trastuzumab treatment window study. Higher ADAM10 levels correlated with poorer relapse-free survival (p ≤ 0.01) in a cohort of HER2 positive breast cancer patients. Our studies implicate a role of ADAM10 in acquired resistance to trastuzumab and establish ADAM10 as a therapeutic target and a potential biomarker for HER2 positive breast cancer patients
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