172,626 research outputs found

    Ligand-Specific Regulation of the Endogenous Mu-Opioid Receptor by Chronic Treatment with Mu-Opioid Peptide Agonist

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    Since the discovery of the endomorphins (EM), the postulated endogenous peptide agonists of the mu-opioid receptors, several analogues have been synthesized to improve their binding and pharmacological profiles. We have shown previously that a new analogue, cis-1S,2R-aminocyclohexanecarboxylic acid2-endomorphin-2 (ACHC-EM2), had elevated mu-receptor affinity, selectivity, and proteolytic stability over the parent compound. In the present work, we have studied its antinociceptive effects and receptor regulatory processes. ACHC-EM2 displayed a somewhat higher (60%) acute antinociceptive response than the parent peptide, EM2 (45%), which peaked at 10 min after intracerebroventricular (icv) administration in the rat tail-flick test. Analgesic tolerance developed to the antinociceptive effect of ACHC-EM2 upon its repeated icv injection that was complete by a 10-day treatment. This was accompanied by attenuated coupling of mu-sites to G-proteins in subcellular fractions of rat brain. Also, the density of mu-receptors was upregulated by about 40% in the light membrane fraction, with no detectable changes in surface binding. Distinct receptor regulatory processes were noted in subcellular fractions of rat brains made tolerant by the prototypic full mu-agonist peptide, DAMGO, and its chloromethyl ketone derivative, DAMCK. These results are discussed in light of the recently discovered phenomenon, that is, the “so-called biased agonism” or “functional selectivity

    EXPTIME Tableaux for the Coalgebraic Mu-Calculus

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    The coalgebraic approach to modal logic provides a uniform framework that captures the semantics of a large class of structurally different modal logics, including e.g. graded and probabilistic modal logics and coalition logic. In this paper, we introduce the coalgebraic mu-calculus, an extension of the general (coalgebraic) framework with fixpoint operators. Our main results are completeness of the associated tableau calculus and EXPTIME decidability. Technically, this is achieved by reducing satisfiability to the existence of non-wellfounded tableaux, which is in turn equivalent to the existence of winning strategies in parity games. Our results are parametric in the underlying class of models and yield, as concrete applications, previously unknown complexity bounds for the probabilistic mu-calculus and for an extension of coalition logic with fixpoints

    Estimation of evapotranspiration in the Mu Us Sandland of China

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    Evapotranspiration (ET) was estimated from 1981–2005 over Wushen County located in the Mu Us Sandland, China, by applying the Advection-Aridity model, which is based on the complementary relationship hypothesis. We used National Oceanic and Atmospheric Administration (NOAA) Advanced Very High Resolution Radiometer (AVHRR), Moderate Resolution Imaging Spectroradiometer (MODIS), and meteorological data. Our results show that the estimated daily ET was about 4.5% higher than measurements using an Eddy Covariance (EC) system after forcing energy balance closure over an alfalfa field from 22 July 2004 to 23 August 2004. At a regional scale, the estimated monthly ET was about 8.7% lower than measurements using the EC system after forcing energy balance closure over an alfalfa field in August 2004. These results were about 3.0% higher than ET measurements by microlysimeter over sand dunes during June 1988. From 1981 to 2005, the average annual ET and precipitation levels were 287 mm and 336 mm, respectively, in Wushen County. The average annual ET varied from 230 mm in western parts of Wushen County to 350 mm in eastern parts of the county. Both inter-annual and seasonal variations in ET were substantial in Wushen County. The annual ET was 200–400 mm from 1981–2005, and the seasonal pattern of ET showed a single peak distribution. The cumulative ET during the June–September 2004 period was 250 mm, which was 87% of the total annual ET. The annual ET, precipitation, and the maximum Normalized Difference Vegetation Index (NDVI<sub>max</sub>) showed positive correlations temporally and spatially

    Social trauma and the mu-opioid system in depression

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    The overarching thesis under investigation is that the endogenous opioid system plays a key role in depression subsequent to traumatic childhood social experiences. This is suggested by the fact that animal work indicates that mu-opioids robustly mediate separation-distress, and that early social stressors lead to long term dysregulation in key related circuitries and neuroanatomical structures

    Measurements of the branching fractions for the semileptonic decays D-s(+) -> phi e(+)v(e), phi mu(+)v(mu), eta mu(+)v(mu) and eta 'mu(+)v(mu)

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    By analyzing 482 pb(-1) of e(+) e(-) collision data collected at the center-of-mass energy root s = 4.009 GeV with the BESIII detector, we measure the branching fractions for the semi-leptonic decays D-s(+) -> phi e(+)v(e), phi mu(+)v(mu), eta mu(+)v(mu) and eta'mu(+)v(mu) to be B(D-s(+) -> phi e(+)v(e)) = (2.26 +/- 0.45 +/- 0.09)%, B(D-s(+) -> phi mu+v(mu)) = (1.94 +/- 0.53 +/- 0.09)%, B(D-s(+) -> eta mu(+)v(mu)) = (2.42 +/- 0.46 +/- 011)% and B(D-s(+) -> eta'mu(+)v(mu)) = (1.06 +/- 0.54 +/- 0.07)%, where the first and second uncertainties are statistical and systematic, respectively. The branching fractions for the three semi-muonic decays D-s(+) -> phi mu(+)v(mu), eta mu(+)v(mu) and eta'mu(+)v(mu) are determined for the first time and that of D-s(+) -> phi e(+)v(e) is consistent with the world average value within uncertainties

    Improved precision and mechanical properties of 3D-printed silica ceramics via sintering temperature optimization

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    Ceramic cores are the key components of precision casting hollow turbine blades, and 3D-printed silica-based ceramic cores are crucial to the development of the aerospace industry. However, silica-based ceramic cores have problems in terms of mechanical properties and friction properties. In this paper, silica ceramics were prepared by stereolithography-based 3D printing technology and processed at different sintering temperatures. The effect of sintering temperature on the microstructure, physical–mechanical properties, and friction and wear properties of the silica ceramics was investigated. The results show that, with the increase of sintering temperature, the average particle size and bulk density of the samples increased, while the open porosity and layer thickness decreased. The surface of ceramics became more and more flat with the increase in temperature. The flexural strength first increased with increasing temperature, and then suddenly decreased at 1350°C. The average surface roughness decreased with increasing temperature. The wear of the material decreased with increasing sintering temperature and increased at 1350°C. The optimum sintering temperatures were 1250°C and 1300°C, giving a flexural strength of 23.18 and 23.25 MPa, bulk density of 1.72 and 1.78 g/cm3, and open porosity of 24.49% and 23.66%, respectively

    Improving wear resistance of 3D printed alumina-based ceramics via sintering temperature

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    Ceramic materials with intricate structures can be efficiently fabricated using stereolithography (SLA) based 3D printing technology, offering advantages over traditional methods. Sintering temperature has primary effect on properties of ceramics. This study investigated the crucial sintering temperature for 3D printed ceramics to ensure the desired properties. The results indicate that all samples exhibit a consistent layered structure across the experimental sintering temperatures. When the sintering temperature is increased from 1,250 °C to 1,350 °C, the grain’s morphology changes from spherical to plate-like. Surface morphology analysis reveals a decrease in surface roughness at sintering temperatures above 1,350 °C. Mechanical tests show improved flexural strength and stiffness as the sintering temperature rises. Friction and wear experiments demonstrate that as the sintering temperature increases from 1,450 °C to 1,550 °C, the wear pattern on ceramic surfaces transitions from deep pits to shallow grooves. The increase in sintering temperature effectively enhances the wear resistance of 3D printed alumina ceramics. This improvement plays a significant role in expanding the application field of these ceramics, prolonging the lifespan of parts, reducing production costs, enhancing performance, and promoting environmental protection. In this study, ceramics achieve the highest strength and best wear resistance when sintered at 1,600 °C, resulting in the best overall performance

    Opioid mediated activity and expression of mu and delta opioid receptors in isolated human term non-laboring myometrium

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    The existence of opioid receptors in mammalian myometrial tissue is now widely accepted. Previously enkephalin degrading enzymes have been shown to be elevated in pregnant rat uterus and a met-enkephalin analogue has been shown to alter spontaneous contractility of rat myometrium. Here we have undertaken studies to determine the effects of met-enkephalin on in vitro human myometrial contractility and investigate the expression of opioid receptors in pregnant myometrium. Myometrial biopsies were taken from women undergoing elective caesarean delivery at term. Organ bath experiments were used to investigate the effect of the met-enkephalin analogue [d-Ala 2, d-met 5] enkephalin (DAMEA) on spontaneous contractility. A confocal immunofluorescent technique and real time PCR were used to determine the expression of protein and mRNA, respectively for two opioid receptor subtypes, mu and delta. DAMEA had a concentration dependent inhibitory effect on contractile activity (1×10−7 M–1×10−4 M; 54% reduction in contractile activity, P<0.001 at 1×10−4 M concentration). Mu and delta opioid receptor protein sub-types and their respective mRNA were identified in all tissues sampled. This is the first report of opioid receptor expression and of an opioid mediated uterorelaxant action in term human non-labouring myometrium in vitroSB. 21/03/201
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