Property-preserving subnet reductions for designing manufacturing systems with shared resources

AbstractThis paper handles two problems in manufacturing system design: resource sharing and system abstraction. In a manufacturing system, resources such as robots, machines, etc. are shared by several processes. When the resources are switched from one process to another, they may need some modifications such as cleaning oil, adding equipments and so on. Previous designing methods assume that the resources have no intermediate modifications. Hence, they need to be extended to handle such kinds of resource-sharing problems. As for abstraction, modeling operations with single places in manufacturing system design is very popular. From the viewpoint of verification, the objective is to verify whether the reduced model has the same desirable properties as the original one. This paper presents three kinds of property-preserving subnet reduction methods. For each reduction method, conditions are presented for ensuring that the properties liveness, boundedness and reversibility are preserved. Applications of these reduction methods to handling the above resource sharing and system abstraction problems are illustrated with an example from the manufacturing system

SNX27 and SORLA interact to reduce amyloidogenic subcellular distribution and processing of amyloid precursor protein

Proteolytic generation of amyloidogenic amyloid {beta} (A{beta}) fragments from the amyloid precursor protein (APP) significantly contributes to Alzheimer's disease (AD). Although amyloidogenic APP proteolysis can be affected by trafficking through genetically associated AD components such as SORLA, how SORLA functionally interacts with other trafficking components is yet unclear. Here, we report that SNX27, an endosomal trafficking/recycling factor and a negative regulator of the {gamma}-secretase complex, binds to the SORLA cytosolic tail to form a ternary complex with APP. SNX27 enhances cell surface SORLA and APP levels in human cell lines and mouse primary neurons, and depletion of SNX27 or SORLA reduces APP endosome-to-cell surface recycling kinetics. SNX27 overexpression enhances the generation of cell surface APP cleavage products such as soluble alpha-APP C-terminal fragment (CTF{alpha}) in a SORLA-dependent manner. SORLA-mediated A{beta} reduction is attenuated by downregulation of SNX27. This indicates that an SNX27/SORLA complex functionally interacts to limit APP distribution to amyloidogenic compartments, forming a non-amyloidogenic shunt to promote APP recycling to the cell surface

Characterization of the monoclonal antibody against classical swine fever virus glycoprotein E-rns and its application to an indirect sandwich ELISA

Classical swine fever virus (CSFV) E-rns is an envelope glycoprotein possessing RNase activity. The E-rns-based enzyme-linked immunosorbent assay (ELISA) has been considered a discriminating diagnostic test for differentiating infected from vaccinated animals. The purpose of this study was to produce a specific monoclonal antibody (MAb) to E-rns for further developing an indirect sandwich ELISA. The MAb CW813 was shown to specifically recognize both the monomer and dimer forms of Pichia pastoris yeast-expressed E-rns (yE(rns)). The antigenic site recognized by MAb CW813 was mapped to the region of amino acid residues 101-160 of E-rns where it was neither a neutralizing epitope nor essential to RNase activity. Furthermore, MAb CW813 was utilized as a capture antibody to develop a yE(rns)-based indirect sandwich ELISA for detecting swine antibody to E-rns. The assay demonstrated a high sensitivity and specificity that may provide an alternative method for developing a diagnostic kit with easy manipulation and low cost

SORLA attenuates EphA4 signaling and amyloid, β-induced neurodegeneration

Sortilin-related receptor with LDLR class A repeats (SORLA, SORL1, or LR11) is a genetic risk factor associated with Alzheimer's disease (AD). Although SORLA is known to regulate trafficking of the amyloid {beta} (A{beta}) precursor protein to decrease levels of proteotoxic A{beta} oligomers, whether SORLA can counteract synaptic dysfunction induced by A{beta} oligomers remains unclear. Here, we show that SORLA interacts with the EphA4 receptor tyrosine kinase and attenuates ephrinA1 ligand-induced EphA4 clustering and activation to limit downstream effects of EphA4 signaling in neurons. Consistent with these findings, SORLA transgenic mice, compared with WT mice, exhibit decreased EphA4 activation and redistribution to postsynaptic densities, with milder deficits in long-term potentiation and memory induced by A{beta} oligomers. Importantly, we detected elevated levels of active EphA4 in human AD brains, where EphA4 activation is inversely correlated with SORLA/EphA4 association. These results demonstrate a novel role for SORLA as a physiological and pathological EphA4 modulator, which attenuates synaptotoxic EphA4 activation and cognitive impairment associated with A{beta}-induced neurodegeneration in AD

Acid-sensing ion channel 3 mediates peripheral anti-hyperalgesia effects of acupuncture in mice inflammatory pain

Background: Peripheral tissue inflammation initiates hyperalgesia accompanied by tissue acidosis, nociceptor activation, and inflammation mediators. Recent studies have suggested a significantly increased expression of acid-sensing ion channel 3 (ASIC3) in both carrageenan- and complete Freund's adjuvant (CFA)-induced inflammation. This study tested the hypothesis that acupuncture is curative for mechanical hyperalgesia induced by peripheral inflammation. Methods: Here we used mechanical stimuli to assess behavioral responses in paw and muscle inflammation induced by carrageenan or CFA. We also used immunohistochemistry staining and western blot methodology to evaluate the expression of ASIC3 in dorsal root ganglion (DRG) neurons. Results: In comparison with the control, the inflammation group showed significant mechanical hyperalgesia with both intraplantar carrageenan and CFA-induced inflammation. Interestingly, both carrageenan- and CFA-induced hyperalgesia were accompanied by ASIC3 up-regulation in DRG neurons. Furthermore, electroacupuncture (EA) at the ST36 rescued mechanical hyperalgesia through down-regulation of ASIC3 overexpression in both carrageenan- and CFA-induced inflammation. Conclusions: In addition, electrical stimulation at the ST36 acupoint can relieve mechanical hyperalgesia by attenuating ASIC3 overexpression

Determination of steroid estrogens in wastewater by high performance liquid chromatography-tandem mass spectrometry

This paper discusses the requirement for, and presents an analytical procedure for, the determination of four unconjugated steroid hormones and a conjugated steroid (estrone-3-sulfate) in wastewaters. The method quantifies the steroids by LC/MS/MS following solid phase extraction and a two stage clean-up procedure. Samples were extracted using C18 cartridges and eluates were then purified by gel permeation chromatography, followed by a further clean-up step on an aminopropyl cartridge. The limits of detection achieved were 0.2 ng l-1 for estriol, 17β-estradiol and 17α-ethinylestradiol, and 0.1 ng l-1 for estrone and the conjugate. The robustness of the method was demonstrated by achieving recoveries of >83% for all steroids in settled sewage and final effluent samples with relative standard deviations of 0.5 - 12%. The method was used to analyse a range of samples from a wastewater treatment works in south east England which demonstrated a >80% removal for estrone, estradiol and estriol with little impact on concentrations of ethinylestradiol or the conjugate

Average Lattice Symmetry and Nanoscale Structural Correlations in Magnetoresistive Manganites

We report x-ray scattering studies of nanoscale structural correlations in the paramagnetic phases of the perovskite manganites La$_{0.75}$(Ca$_{0.45}$Sr$_{0.55}$)$_{0.25}$MnO$_3$, La$_{0.625}$Sr$_{0.375}$MnO$_3$, and Nd$_{0.45}$Sr$_{0.55}$MnO$_3$. We find that these correlations are present in the orthorhombic $O$ phase in La$_{0.75}$(Ca$_{0.45}$Sr$_{0.55}$)$_{0.25}$MnO$_3$, but they disappear abruptly at the orthorhombic-to-rhombohedral transition in this compound. The orthorhombic phase exhibits increased electrical resistivity and reduced ferromagnetic coupling, in agreement with the association of the nanoscale correlations with insulating regions. In contrast, the correlations were not detected in the two other compounds, which exhibit rhombohedral and tetragonal phases. Based on these results, as well as on previously published work, we propose that the local structure of the paramagnetic phase correlates strongly with the average lattice symmetry, and that the nanoscale correlations are an important factor distinguishing the insulating and the metallic phases in these compounds.Comment: a note on recent experimental work, and a new reference adde

The energy spectrum of all-particle cosmic rays around the knee region observed with the Tibet-III air-shower array

We have already reported the first result on the all-particle spectrum around the knee region based on data from 2000 November to 2001 October observed by the Tibet-III air-shower array. In this paper, we present an updated result using data set collected in the period from 2000 November through 2004 October in a wide range over 3 decades between $10^{14}$ eV and $10^{17}$ eV, in which the position of the knee is clearly seen at around 4 PeV. The spectral index is -2.68 $\pm$ 0.02(stat.) below 1PeV, while it is -3.12 $\pm$ 0.01(stat.) above 4 PeV in the case of QGSJET+HD model, and various systematic errors are under study now.Comment: 12 pages, 7 figures, accepted by Advances in space researc

Moon Shadow by Cosmic Rays under the Influence of Geomagnetic Field and Search for Antiprotons at Multi-TeV Energies

We have observed the shadowing of galactic cosmic ray flux in the direction of the moon, the so-called moon shadow, using the Tibet-III air shower array operating at Yangbajing (4300 m a.s.l.) in Tibet since 1999. Almost all cosmic rays are positively charged; for that reason, they are bent by the geomagnetic field, thereby shifting the moon shadow westward. The cosmic rays will also produce an additional shadow in the eastward direction of the moon if cosmic rays contain negatively charged particles, such as antiprotons, with some fraction. We selected 1.5 x10^{10} air shower events with energy beyond about 3 TeV from the dataset observed by the Tibet-III air shower array and detected the moon shadow at $\sim 40 \sigma$ level. The center of the moon was detected in the direction away from the apparent center of the moon by 0.23$^\circ$ to the west. Based on these data and a full Monte Carlo simulation, we searched for the existence of the shadow produced by antiprotons at the multi-TeV energy region. No evidence of the existence of antiprotons was found in this energy region. We obtained the 90% confidence level upper limit of the flux ratio of antiprotons to protons as 7% at multi-TeV energies.Comment: 13pages,4figures; Accepted for publication in Astroparticle Physic

Entropy-Corrected New Agegraphic Dark Energy Model in Horava-Lifshitz Gravity

In this work, we have considered the entropy-corrected new agegraphic dark energy (ECNADE) model in Horava-Lifshitz gravity in FRW universe. We have discussed the correspondence between ECNADE and other dark energy models such as DBI-essence,Yang-Mills dark energy, Chameleon field, Non-linear electrodynamics field and hessence dark energy in the context of Horava-Lifshitz gravity and reconstructed the potentials and the dynamics of the scalar field theory which describe the ECNADE.Comment: 12 page