From logical forms to SPARQL query with GETARUNS

We present a system for Question Answering which computes a prospective answer from Logical Forms produced by a full-fledged NLP for text understanding, and then maps the result onto schemata in SPARQL to be used for accessing the Semantic Web. As an intermediate step, and whenever there are complex concepts to be mapped, the system looks for a corresponding amalgam in YAGO classes. It is just by the internal structure of the Logical Form that we are able to produce a suitable and meaningful context for concept disambiguation. Logical Forms are the final output of a complex system for text understanding - GETARUNS - which can deal with different levels of syntactic and semantic ambiguity in the generation of a final structure, by accessing computational lexical equipped with sub-categorization frames and appropriate selectional restrictions applied to the attachment of complements and adjuncts. The system also produces pronominal binding and instantiates the implicit arguments, if needed, in order to complete the required Predicate Argument structure which is licensed by the semantic component

Model-Based Intelligent Fault Detection and Diagnosis for Mating Electric Connectors in Robotic Wiring Harness Assembly Systems

Mating a pair of electric connectors is one of the most important steps in a robotic wiring harness assembly system. A class of piecewise linear force models is proposed to describe both the successful and the faulty mating processes of connectors via an elaborate analysis of forces during different phases. The corresponding parameter estimation method of this model is also presented by adapting regular least-square estimation methods. A hierarchical fuzzy pattern matching multidensity classifier is proposed to realize fault detection and diagnosis for the mating process. This classifier shows good performance in diagnosis. A typical type of connectors is investigated in this paper. The results can easily be extended to other types. The effectiveness of proposed methods is finally confirmed through experiments.journal articl

オープン・メッシュネットワークの研究開発

This article describes the research project that aims to establish a scalable, efficient wireless L3 mesh network technology, and construct a large-scale mesh network testbed. This project develops software which includes the standardization of the related technology in IETF and IEEE 802, and carries out practical experiments.textapplication/pdfdepartmental bulletin pape

Evidence for Muon Neutrino Oscillation in an Accelerator-Based Experiment

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Molecular modeling of Momordica cochinchinensis asparagine endopeptidase 2 and its interaction with MCoTI-II peptide

Cyclotides are a large family of plant defense peptides, which display a cyclic backbone. The enzymes responsible for the backbone cyclization of these peptides are called asparagine endopeptidases, and the three-dimensional crystallographic structure of one of these cyclization enzyme has recently been described. The group of David Craik has recently discovered another cyclization enzyme, this time from the plant Momordica cochinchinensis, which is selective for cyclotides belonging to the trypsin inhibitor cyclotide family I have carried out molecular dynamics simulations of this new enzyme in an apo state and in an intermediate state when covalently linked with a substrate peptide. This dataset provides the necessary files to reproduce these molecular dynamics simulations carried out with the software pmemd from the Amber 18 simulation package.</p

Delineation of the Unbinding Pathway of α-Conotoxin ImI from the α7 Nicotinic Acetylcholine Receptor

α-Conotoxins potently and specifically inhibit isoforms of nicotinic acetylcholine receptors (nAChRs) and are used as molecular probes and as drugs or drug leads. Interactions occurring during binding and unbinding events are linked to binding kinetics, and knowledge of these interactions could help in the development of α-conotoxins as drugs. Here, the unbinding process for the prototypical α-conotoxin ImI/α7-nAChR system was investigated theoretically, and three exit routes were identified using random accelerated molecular dynamics simulations. The route involving the smallest conformation perturbation was further divided into three subpathways, which were studied using steered molecular dynamics simulations. Of the three subpathways, two had better experimental support and lower potential of mean force, indicating that they might be sampled more frequently. Additionally, these subpathways were supported by previous experimental studies. Several pairwise interactions, including a cation-π interaction and charge and hydrogen bond interactions, were identified as potentially playing important roles in the unbinding event

The [Lys^-2-Arg^-1-des(17−21)]-Endothelin-1 Peptide Retains the Specific Arg^-1−Asp⁸ Salt Bridge but Reveals Discrepancies between NMR Data and Molecular Dynamics Simulations^†

The [des(17−21)]-endothelin-1 (CSH-ET) and [Lys-2-Arg-1-des(17−21)]-endothelin-1 (KR-CSH-ET) peptides, designed by removing the five-residue hydrophobic tail from the endothelin-1 (ET-1) and [Lys-2-Arg-1]-endothelin-1 (KR-ET-1) peptides, respectively, were synthesized. Previous studies on KR-ET-1 showed that, in contrast to ET-1, this engineered compound displays a pH-dependent conformational change related to the formation of a stabilizing salt bridge between the Arg-1 and Asp8 side chains. CD and NMR spectra indicate that CSH-ET and KR-CSH-ET display conformational behavior similar to those of ET-1 and KR-ET-1, respectively. The short salt bridge-stabilized KR-CSH-ET peptide therefore appears to be an attractive elementary scaffold for drug design. The solution structure of the salt-bridged form of KR-CSH-ET was determined by NMR at pH 4.5 and is very similar to the corresponding form of the parent KR-ET-1 peptide. Molecular dynamics simulations of the salt-bridged form of KR-CSH-ET were performed using both the GB/SA implicit solvation scheme or an explicit solvation and the particle-mesh Ewald method for long-range electrostatic calculation. Unexpectedly, the Arg-1−Asp8 salt bridge does not display in the simulation the stability that could be expected from the experimental data. The cooperative involvement of a cation−π interaction in formation of the salt bridge has been hypothesized. Difficulties in accurately simulating cation−π interactions might be responsible for the lack of stability in the simulation. At this time, however, no definitive explanation for the observed discrepancy between experiments and simulations is available, and further experimental studies appear to be necessary to fully understand in atomic detail the pH-dependent conformational change observed in the KR-ET-1 series

Conformational Flexibility Is a Determinant of Permeability for Cyclosporin

Several cyclic peptides have been reported to have unexpectedly high membrane permeability. Of these, cyclosporin A is perhaps the most well-known example, particularly in light of its relatively high molecular weight. Observations that cyclosporin A changes conformation depending on its solvent environment led to the hypothesis that conformational dynamics is a prerequisite for its permeability; however, this hypothesis has been difficult to validate experimentally. Here, we use molecular dynamics simulations to explicitly determine the conformational behavior of cyclosporin A and other related cyclic peptides as they spontaneously transition between different environments, including through a lipid bilayer. These simulations are referenced against simulations in explicit water, chloroform, and cyclohexane and further validated against NMR experiments, measuring conformational exchange, nuclear spin relaxation, and three-dimensional structures in membrane-mimicking environments, such as in dodecylphosphocholine micelles, to build a comprehensive understanding of the role of dynamics. We find that conformational flexibility is a key determinant of the membrane permeability of cyclosporin A and similar membrane-permeable cyclic peptides, as conformationally constrained variants have limited movement into, then through, and finally out of the membrane in silico. We envisage that a better understanding of dynamics might thus provide new opportunities to modulate peptide function and enhance their delivery

Single Amino Acid Substitution in α‑Conotoxin TxID Reveals a Specific α3β4 Nicotinic Acetylcholine Receptor Antagonist

The α3β4 nicotinic acetylcholine receptor (nAChR) is an important target implicated in various disease states. α-Conotoxin TxID (1) is the most potent antagonist of α3β4 nAChR, but it also exhibits inhibition of α6/α3β4 nAChR. The results of alanine scanning of 1 suggested a vital role for Ser9 in the selectivity of the peptide. In this study, Ser9 was substituted with a series of 14 amino acids, including some non-natural amino acids, displaying different physicochemical characteristics to further improve the selectivity of 1 toward α3β4 nAChR. The pharmacological activities of the mutants were evaluated using an electrophysiological approach. The best selectivity was obtained with [S9K]­TxID, 12, which inhibited α3β4 nAChR with an IC50 of 6.9 nM and had no effects on other nAChRs. Molecular modeling suggested a possible explanation for the high selectivity of 12 toward α3β4 nAChR, providing deeper insight into the interaction between α-conotoxins and nAChRs as well as potential treatments for nAChR-related diseases

Single Amino Acid Substitution in α‑Conotoxin TxID Reveals a Specific α3β4 Nicotinic Acetylcholine Receptor Antagonist

The α3β4 nicotinic acetylcholine receptor (nAChR) is an important target implicated in various disease states. α-Conotoxin TxID (1) is the most potent antagonist of α3β4 nAChR, but it also exhibits inhibition of α6/α3β4 nAChR. The results of alanine scanning of 1 suggested a vital role for Ser9 in the selectivity of the peptide. In this study, Ser9 was substituted with a series of 14 amino acids, including some non-natural amino acids, displaying different physicochemical characteristics to further improve the selectivity of 1 toward α3β4 nAChR. The pharmacological activities of the mutants were evaluated using an electrophysiological approach. The best selectivity was obtained with [S9K]­TxID, 12, which inhibited α3β4 nAChR with an IC50 of 6.9 nM and had no effects on other nAChRs. Molecular modeling suggested a possible explanation for the high selectivity of 12 toward α3β4 nAChR, providing deeper insight into the interaction between α-conotoxins and nAChRs as well as potential treatments for nAChR-related diseases