Cannabinoid Receptor Subtype 2 (Cb2R) Agonist Gw405833 Reduces Agonist-Induced Ca2+ Oscillations In Mouse Pancreatic Acinar Cells

Emerging evidence demonstrates that the blockade of intracellular Ca 2+ signals may protect pancreatic acinar cells against Ca 2+ overload, intracellular protease activation, and necrosis. The activation of cannabinoid receptor subtype 2 (CB 2 R) prevents acinar cell pathogenesis in animal models of acute pancreatitis. However, whether CB 2 Rs modulate intracellular Ca 2+ signals in pancreatic acinar cells is largely unknown. We evaluated the roles of CB 2 R agonist, GW405833 (GW) in agonist-induced Ca 2+ oscillations in pancreatic acinar cells using multiple experimental approaches with acute dissociated pancreatic acinar cells prepared from wild type, CB 1 R-knockout (KO), and CB 2 R-KO mice. Immunohistochemical labeling revealed that CB 2 R protein was expressed in mouse pancreatic acinar cells. Electrophysiological experiments showed that activation of CB 2 Rs by GW reduced acetylcholine (ACh)-, but not cholecystokinin (CCK)-induced Ca 2+ oscillations in a concentration-dependent manner; this inhibition was prevented by a selective CB 2 R antagonist, AM630, or was absent in CB 2 R-KO but not CB 1 R-KO mice. In addition, GW eliminated L-arginine-induced enhancement of Ca 2+ oscillations, pancreatic amylase, and pulmonary myeloperoxidase. Collectively, we provide novel evidence that activation of CB 2 Rs eliminates ACh-induced Ca 2+ oscillations and L-arginine-induced enhancement of Ca 2+ signaling in mouse pancreatic acinar cells, which suggests a potential cellular mechanism of CB 2 R-mediated protection in acute pancreatitis

Determining the deflection of the vertical of VLBI stations using radio telescope axis information

The complete expression of pointing calibration model (PCM) for the axis related errors (ARE) of the radio telescope is derived directly. The definition of the common axis related parameters in both pointing correction model of ARE and Lösler's indirect model (IM) is unified, then the relationship between PCM and IM of the radio telescope is established. Thus, the deflection of the vertical (DOV) determination of VLBI stations is realized by using radio telescope azimuth axis information. As a direct surveying approach, this method does not rely on special DOV surveying equipment. It could only depend on pointing calibration surveying data for telescope aperiodic maintenance and the local surveying data including leveling. Verified by a variety of DOV surveying methods, the DOV obtained by our method shows a good agreement with real surveyed DOV in west-east component. Owing to the non-uniform distribution of the radio sources sky coverage of the station during its pointing calibration, the north-south component of DOV has the same direction as the surveyed DOV, but has a difference in value. In the future, further providing an optimized telescope pointing calibration, the high precision surveying of DOV will be obtained by using VLBI telescope azimuth axis

Influences of the Ag content on microstructures and properties of Zn–3Mg–xAg alloy by spark plasma sintering

In order to improve the comprehensive mechanical properties of Zn–3Mg alloy to meet application requirements of medical metal implants, spark plasma sintering (SPS) was adopted to prepare Zn–3Mg–xAg alloy (x = 0, 1, 1.5, 2, 2.5). Electron backscatter diffraction (EBSD)observation was adopted to investigate the growth twins in Zn–3Mg–xAg alloy, and then influences of Ag element on compactness, microstructure, tensile and compression properties of the zinc-based alloy were studied. Results showed that the length of growth twins first increased, then decreased with the increase of Ag element. Growth twins improved the ductility of alloy by turning the hard oriented grains into soft ones. The Zn–3Mg–1.5Ag alloy showed the best comprehensive mechanical properties due to the joint effect of solid solution strengthening, precipitation phase strengthening, fine grain strengthening and defect weakening. The tensile strength of Zn–3Mg–1.5Ag was 273.8 ± 16.9 MPa, which was 2.5 and 1.6 times that of Zn and Zn–3Mg respectively; the elongation was 10.67 ± 0.77%, which was 3.6 and 2.6 times that of Zn and Zn–3Mg respectively. Compressive strength of Zn–3Mg–1.5Ag was 543.7 ± 38.1 MPa, which was 3.8 times that of Zn; fracture strain of Zn–3Mg–1.5Ag was 20.49 ± 1.21%, which was 2 and 1.5 times of pure Zn and Zn–3Mg alloy

A 41-mW 30-Gb/s CMOS optical receiver with digitally-tunable cascaded equalization

This paper presents a 65-nm CMOS, 1-V, 1.37-pJ/bit optical receiver with embedded equalizer, enabling adaptability to overcome channel losses and component variations. The digitally-controlled continuous-time linear equalizer (CTLE) consists of three cascaded tunable peaking stages offering 16-dB of adjustable low-frequency gain. Optical measurement results with a 30-Gb/s photodetector (PD) show that the receiver achieves 10-12 BER at 30 Gb/s for a 215-1 PRBS input with a -5.6-dBm input sensitivity. Using a lower bandwidth 14-Gb/s PD, the receiver can still reach 30 Gb/s at 10-12 BER with only a 0.6-dB degradation in input sensitivity. These measurement results demonstrate the effectiveness of the proposed receiver and the programmable cascaded CTLE.[Chiang, Patrick]Oregon State University, Corvallis, OR, United State

Cannabinoid receptor subtype 2 (CB2R) agonist, GW405833 reduces agonist-induced Ca2+ oscillations in mouse pancreatic acinar cells

Emerging evidence demonstrates that the blockade of intracellular Ca2+ signals may protect pancreatic acinar cells against Ca2+ overload, intracellular protease activation, and necrosis. The activation of cannabinoid receptor subtype 2 (CB2R) prevents acinar cell pathogenesis in animal models of acute pancreatitis. However, whether CB(2)Rs modulate intracellular Ca2+ signals in pancreatic acinar cells is largely unknown. We evaluated the roles of CB2R agonist, GW405833 (GW) in agonist-induced Ca2+ oscillations in pancreatic acinar cells using multiple experimental approaches with acute dissociated pancreatic acinar cells prepared from wild type, CB1R-knockout (KO), and CB2R-KO mice. Immunohistochemical labeling revealed that CB2R protein was expressed in mouse pancreatic acinar cells. Electrophysiological experiments showed that activation of CB(2)Rs by GW reduced acetylcholine (ACh)-, but not cholecystokinin (CCK)-induced Ca2+ oscillations in a concentration-dependent manner; this inhibition was prevented by a selective CB2R antagonist, AM630, or was absent in CB2R-KO but not CB1R-KO mice. In addition, GW eliminated L-arginine-induced enhancement of Ca2+ oscillations, pancreatic amylase, and pulmonary myeloperoxidase. Collectively, we provide novel evidence that activation of CB(2)Rs eliminates ACh-induced Ca2+ oscillations and L-arginine-induced enhancement of Ca2+ signaling in mouse pancreatic acinar cells, which suggests a potential cellular mechanism of CB2R-mediated protection in acute pancreatitis.Seed Fund of Shangtou University Medical College; Guangdong Science and Technology FoundationOpen Access JournalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Spatial inhomogeneity of point defect properties in refractory multi principal element alloy with short range order: A first principles study

Short range order can be developed in multi principal element alloys and influences the point defect behavior due to the large variation of the local chemical environment. The effect of short range order on vacancy and interstitial formation energy and migration behavior was studied in body centered cubic multi principal element alloy NbZrTi by first principles calculations. Two short range order structures created by density functional theory and Monte Carlo method at 500 and 800 K were compared with the structure of random solid solution. Both vacancy and interstitial formation energies increase with the degree of short range order. Point defect formation energies tend to be higher in regions enriched in Nb and lower in regions enriched in Zr and Ti. Both vacancies and interstitials prefer to migrate toward Zr,Ti rich regions and away from Nb rich regions, suggesting that Zr,Ti rich regions can potentially act as recombination centers for point defect annihilation. Compared to an ideal random solid solution, the short range order increases the spatial inhomogeneity of point defect energy landscape. Tuning the degree of short range order by different processing techniques can be a viable strategy to optimize the point defect behavior to achieve enhanced radiation resistance in multi principal element alloys