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Sample records for 8mo sd 2y

  1. Gaseous hydrogen embrittlement of PH 13-8 Mo steel

    NASA Astrophysics Data System (ADS)

    Ding, Y. S.; Tsay, L. W.; Chiang, M. F.; Chen, C.

    2009-04-01

    In this study, notched tensile and fatigue crack growth tests in gaseous hydrogen were performed on PH 13-8 Mo stainless steel specimens at room temperature. These specimens were susceptible to hydrogen embrittlement (HE), but at different degrees, depending on the aging conditions or the microstructures of the alloys. In hydrogen, the accelerated fatigue crack growth rate (FCGR) usually accompanied a reduced notched tensile strength (NTS) of the specimens, i.e., the faster the FCGR the lower the NTS. It was proposed that the same fracture mechanism could be applied to these two different types of specimens, regardless of the loading conditions. Rapid fatigue crack growth and high NTS loss were found in the H800 (426 °C under-aged) and H900 (482 °C peak-aged) specimens. The HE susceptibility of the steel was reduced by increasing the aging temperature above 593 °C, which was attributed to the increased amount of austenite in the structure. Extensive quasi-cleavage fracture was observed for the specimens that were deteriorated severely by HE.

  2. Evaluation of Spherical Bearings with PH13-8 Mo Ball Material.

    DTIC Science & Technology

    1982-05-01

    The objective of this program was to demonstrate that passive PH13 - 8 Mo is a viable alternate to 440C as ball material for MS spherical bearings...Sixty spherical bearings with passivated PH13 - 8 Mo balls from two suppliers, were tested at room temperature and 325 F, both dry and with liquid

  3. Transition states and modeling for Co9S8/MoS 2 catalysis

    NASA Astrophysics Data System (ADS)

    Gonzalez, Gabriel Angel

    Transition state computational studies of the sulfur removal from dibenzothiophene (DBT) molecule have herein been performed considering the Co9S8/MoS2 interface existing on unsupported Co/MoS2 catalysts. The linear synchronous transit (LST) and quadratic synchronous transit (QST) methods integrated in a density functional theory (DFT) program such as Dmol3 were used for the calculations of energy barriers of the transition states. Three different configurations present on the Co9S8/MoS2 interface have been envisaged as possible catalytic sites: sulfur-sulfur (S, S) sites, and molybdenum-sulfur (Mo, S) and molybdenum-molybdenum (Mo, Mo) edge sites. This study revealed that the (Mo, Mo) edge site is the most catalytically active site for the hydrodesulfurization (HDS) reaction followed by the (Mo, S) edge site while the (S, S) site shows almost inertness for the HDS reaction. This information allows us to propose clues to design new catalysts based on bulk Co9S8/MoS2 phases with higher efficiency by increasing the proportion of (Mo, Mo) edge sites.

  4. Stress corrosion study of PH13-8Mo stainless steel using the Slow Strain Rate Technique

    NASA Technical Reports Server (NTRS)

    Torres, Pablo D.

    1989-01-01

    The need for a fast and reliable method to study stress corrosion in metals has caused increased interest in the Slow Strain Rate Technique (SSRT) during the last few decades. PH13-8MoH950 and H1000 round tensile specimens were studied by this method. Percent reduction-in-area, time-to-failure, elongation at fracture, and fracture energy were used to express the loss in ductility, which has been used to indicate susceptibility to stress corrosion cracking (SCC). Results from a 3.5 percent salt solution (corrosive medium) were compared to those in air (inert medium). A tendency to early failure was found when testing in the vicinity of 1.0 x 10(-6) mm/mm/sec in the 3.5 percent salt solution. PH13-8Mo H1000 was found to be less likely to suffer SCC than PH13-8Mo H950. This program showed that the SSRT is promising for the SCC characterization of metals and results can be obtained in much shorter times (18 hr for PH steels) than those required using conventional techniques.

  5. Low Temperature Creep of a Titanium Alloy Ti-6Al-2Cb-1Ta-0.8Mo

    NASA Technical Reports Server (NTRS)

    Chu, H. P.

    1997-01-01

    This paper presents a methodology for the analysis of low temperature creep of titanium alloys in order to establish design limitations due to the effect of creep. The creep data on a titanium Ti-6Al-2Cb-1Ta-0.8Mo are used in the analysis. A creep equation is formulated to determine the allowable stresses so that creep at ambient temperatures can be kept within an acceptable limit during the service life of engineering structures or instruments. Microcreep which is important to design of precision instruments is included in the discussion also.

  6. The partitioning of alloying elements in vacuum arc remelted, Pd-modified PH 13-8 Mo alloys

    NASA Astrophysics Data System (ADS)

    Cieslak, M. J.; Vandenavyle, J. A.; Carr, M. J.; Hills, C. R.; Semarge, R. E.

    1988-12-01

    The partitioning of alloying elements in as-solidified PH 13-8 Mo stainless steel containing up to 1.02 wt pct Pd has been investigated. The as-solidified structure is composed of two major phases, martensite and ferrite. Electron probe microanalysis reveals that Mo, Cr, and Al partition to the ferrite phase while Fe, Ni, Mn, and Pd partition to the martensite (prior austenite) during solidification and cooling from the solidus. In addition to bulk segregation between phases, precipitation of the intermetallic, PdAI, in the retained ferrite is observed. Precipitation of the normal hardening phase, β-NiAl, is also observed in the retained ferrite. Partition ratios of the various alloying elements are determined and are compared with those observed previously in duplex Fe-Cr-Ni stainless steel solidification structures. The martensite start temperature (Ms) was observed to decrease with increasing Pd concentration.

  7. Carbide precipitates in solution-quenched PH13-8 Mo stainless steel: A small-angle neutron scattering investigation

    NASA Astrophysics Data System (ADS)

    Sen, D.; Patra, A. K.; Mazumder, S.; Mittra, J.; Dey, G. K.; de, P. K.

    2004-08-01

    This paper deals with the small-angle neutron scattering (SANS) investigation on solution-quenched PH13-8 Mo stainless steel. From the nature of the variation of the functionality of the profiles for varying specimen thickness and also from the transmission electron microscopy (TEM), it has been established that the small-angle scattering signal predominantly originates from the block-like metallic carbide precipitates in the specimen. The contribution due to double Bragg reflection is not significant in the present case. The single scattering profile has been extracted from the experimental profiles corresponding to different values of specimen thickness. In order to avoid complexity and non-uniqueness of the multi-parameter minimization for randomly oriented polydisperse block-like precipitate model, the data have been analyzed assuming randomly oriented polydisperse cylindrical particle model with a locked aspect ratio.

  8. The influence of palladium on the hydrogen-assisted cracking resistance of PH 13-8 Mo stainless steel

    NASA Astrophysics Data System (ADS)

    Scully, J. R.; van den Avyle, J. A.; Cieslak, M. J.; Romig, A. D.; Hills, C. R.

    1991-10-01

    We compare the hydrogen-assisted cracking resistance of wrought PH 13-8 Mo stainless steel alloyed with 0.4 to 1.0 wt pct palladium to the conventional alloy when aged to yield strengths of 1170 to 1250 MPa. Intergranular hydrogen cracking is suppressed with Pd in both static load and constant extension rate tests conducted with electrochemical hydrogen charging. These results are analyzed to elucidate the role of Pd in suppressing intergranular cracking. Palladium is found both in substitutional solid solution in the martensitic phase and also in the form of randomly distributed PdAl precipitates in all Pd-modified alloys. Interfacial segregation of Pd to grain boundaries and lath boundaries is not observed at any levels above a detection limit of approximately 0.5 monolayers. Hydrogen permeation analyses indicate that hydrogen ingress is not inhibited by Pd but that apparent diffusion coefficients are lowered relative to the conventional alloy. Lower diffusion coefficients are consistent with the creation of a strong but reversible hydrogen trap, identified as the uniformly distributed PdAl phase. We hypothesize that PdAl trap sites force a redistribution of trapped hydrogen, which lowers the amount of interfacially segregated hydrogen at prior austenite grain boundaries for the electrochemical conditions applied. These assertions are supported by a simplistic trapping model for PH 13-8 Mo which shows that both the hydrogen trap binding energy and the trap density for the PdAl trapping site are greater than the hydrogen trap binding energy and density for prior austenite grain boundaries.

  9. Heat treatment of investment cast PH 13-8 Mo stainless steel: Part II. Isothermal aging kinetics

    NASA Astrophysics Data System (ADS)

    Robino, C. V.; Cieslak, M. J.; Hochanadel, P. W.; Edwards, G. R.

    1994-04-01

    The hardening response of investment cast PH 13-8 Mo stainless steel has been evaluated by hardness measurements following aging in the temperature range normally specified for this alloy (510 °C to 593 °C). A new relationship between fraction transformed and hardness was developed, and analysis of the data in terms of the kinetics of precipitation, in a manner similar to that frequently applied to other precipitation-hardenable martensitic steels, yielded low time exponents and a low value for the apparent activation energy. The values of the time exponents were 0.49, 0.37, 0.56, and 0.53 at 510 °C, 538 °C, 566 °C, and 593 °C, respectively, and that for the apparent activation energy was 139 kJ/mole. As has been proposed for other maraging type steels, these estimates suggest that Β-NiAl precipitates along or near dislocations and that growth of the precipitates is dominated by dislocation pipe diffusion. However, these predictions were neither supported nor refuted by transmission electron microscopy (TEM) because of difficulties in imaging the Β-NiAl precipitates at the aging times and temperatures used. Further, analysis of the data using the formalism of Wert and Zener for the growth of precipitates with interfering diffusion fields indicated that the estimates of fraction transformed from hardness data are not fully appropriate for maraging type steels. Consideration of the nature of the Avrami analysis and the electron microscopy results suggests that other phenomena, including dislocation recovery and reversion of martensite to austenite, occur at rates sufficient to convolute the Avrami analysis. It is further suggested that these results cast doubt on the fundamental implications of previous analyses of precipitation kinetics in age-hardening martensitic steels. Although the Avrami analysis was found not to provide a tenable description of the precipitation kinetics, it does provide a reasonable methodology for portrayal of the hardening response

  10. Heat treatment of investment cast PH 13-8 Mo stainless steel: Part I. Mechanical properties and microstructure

    NASA Astrophysics Data System (ADS)

    Hochanadel, P. W.; Edwards, G. R.; Robino, C. V.; Cieslak, M. J.

    1994-04-01

    The microstructure of investment cast PH 13-8 Mo stainless steel heat-treated to various conditions was studied using light and electron microscopy, electron probe microanalysis, and Mössbauer spectroscopy. The mechanical properties were investigated by using uniaxial tensile testing, hardness testing, and Charpy impact testing. The Β-NiAl strengthening precipitates, though detectable by electron diffraction, were difficult to resolve by transmission electron microscopy (TEM) in specimens aged at low temperatures (566 °C and below). A high dislocation density was observed in the lath martensitic structure. The higher strength and lower ductility observed at low aging temperatures was attributed to both the high dislocation density and the precipitation of Β-NiAl. When samples were aged at high temperatures (> 566 °C), a lower dislocation density and a reverted austenite fraction on the order of 15 pct were observed. Spherical Β-NiAl precipitates were observed in the overaged condition. The decrease in strength and corresponding increase in ductility observed in samples aged at temperatures above 566 °C were attributed to the reverted austenite and recovery. Mechanical properties were improved when the homogenizing temperature and time were increased. Electron probe microanalysis quantified the increased homogeneity realized by increasing homogenizing temperature and time. Elimination of the refrigeration step, which normally follows the solution treatment, did not degrade the mechanical properties. Mössbauer spectroscopy showed only minor decreases in the fraction of retained austenite when refrigeration followed the solution treatment.

  11. Heat treatment of investment cast PH 13-8 Mo stainless steel; Part 2: Isothermal aging kinetics

    SciTech Connect

    Robino, C.V.; Cieslak, M.J. . Physical and Joining Metallurgy Dept.); Hochanadel, P.W.; Edwards, G.R. . Dept. of Metallurgical and Materials Engineering)

    1994-04-01

    The hardening response of investment cast PH 13-8 Mo stainless steel has been evaluated by hardness measurements following aging in the temperature range normally specified for this alloy (510 C to 593 C). A new relationship between fraction transformed and hardness was developed, and analysis of the data in terms of the kinetics of precipitation, in a manner similar to that frequently applied to other precipitation-hardenable martensitic steels, yielded low time exponents and a low value for the apparent activation energy. The values of the time exponents were 0.49, 0.37, 0.56, and 0.53 at 510 C, 538 C, 566 C, and 593 C, respectively, and that for the apparent activation energy was 139 kJ/mole. As has been proposed for other maraging type steels, these estimates suggest that [beta]-NiAl precipitates along or near dislocations and that growth of the precipitates is dominated by dislocation pipe diffusion. However, these predictions were neither supported nor refuted by transmission electron microscopy (TEM) because of difficulties in imaging the [beta]-NiAl precipitates at the aging times and temperatures used. Further, analysis of the data using the formalism of Wert and Zener for the growth of precipitates with interfering diffusion fields indicated that the estimates of fraction transformed from hardness data are not fully appropriate for maraging type steels. Consideration of the nature of the Avrami analysis and the electron microscopy results suggests that other phenomena, including dislocation recovery and reversion of martensite to austenite, occur at rates sufficient to convolute the Avrami analysis. It is further suggested that these results cast doubt on the fundamental implications of previous analyses of precipitation kinetics in age-hardening martensitic steels.

  12. An investigation of the high-temperature and solidification microstructures of PH 13-8 Mo stainless steel

    NASA Astrophysics Data System (ADS)

    Cieslak, M. J.; Hills, C. R.; Hlava, P. F.; David, S. A.

    1990-09-01

    Differential thermal analysis (DTA), high-temperature water-quench (WQ) experiments, and optical and electron microscopy were used to establish the near-solidus and solidification microstructures in PH 13-8 Mo. On heating at a rate of 0. 33 °C/s, this alloy begins to transform from austenite to δ-ferrite at ≈1350 °C. Transformation is complete by ≈1435 °C. The solidus is reached at ≈1447 °C, and the liquidus is ≈1493 °C. On cooling from the liquid state at a rate of 0. 33 °C/s, solidification is completed as δ-ferrite with subsequent transformation to austenite beginning in the solid state at ≈1364 °C. Insufficient time at temperature is available for complete transformation and the resulting room-temperature microstructure consists of matrix martensite (derived from the shear decomposition of the austenite) and residual δ-ferrite. The residual δ-ferrite in the DTA sample is enriched in Cr (≈16 wt pct), Mo (≈4 wt pct), and Al (≈1. 5 wt pct) and depleted in Ni (≈4 wt pct) relative to the martensite (≈12. 5 wt pct Cr, ≈2 wt pct Mo, ≈1 wt pct Al, ≈9 wt pct Ni). Solid-state transformation of δ σ γ was found to be quench-rate sensitive with large grain, fully ferritic microstructures undergoing a massive transformation as a result of water quenching, while a diffusionally controlled Widmanstätten structure was produced in air-cooled samples.

  13. Microstructural evolution and response to double-loop reactivation testing of heat-treated pH 13-8 Mo martensitic stainless steel

    SciTech Connect

    Cieslak, W.R.; Cieslak, M.J.; Hills, C.R.

    1987-01-01

    The double loop electrochemical potentiokinetic reactivation (DL-EPR) test was used to investigate the intergranular and interlath corrosion susceptibility of pH 13-8 Mo as a function of heat treatment. Degree of sensitization was measured to the ratio of the peak current on a reverse (reactivation) scan to that on the forward anodic scan. Corrosion morphology was characterized by SEM, and microstructure by AEM. PH 13-8 Mo in the as-received condition was not sensitized. Precipitation-strengthening to the H925 temper caused susceptibility to intergranular corrosion, and averaging at H1150 caused susceptibility to interlath corrosion. Corrosion susceptibility was most likely caused by a classic Cr-depletion mechanism. 4 refs., 3 figs. (CS)

  14. The dimensional stability analysis of seventeen stepped specimens of 18Ni 200 grade, PH13-8Mo and A-286

    NASA Technical Reports Server (NTRS)

    Wigley, D. A.

    1983-01-01

    This report documents the results of a dimensional stability analysis of seventeen stepped specimens that were used in the evaluation of factors influencing warpage in metallic alloys being used for cryogenic wind tunnel models. Specimens used in the analysis were manufactured from 18Ni 200 Grade Maaraging steel, PH13-8Mo, and A-286 stainless steel. Quantitative data are provided on the behavior of the specimens due to the effects of both machining and cryogenic cycling effects.

  15. Positron annihilation study of structural relaxation and crystallization in a metallic glass Al80Fe8Mo7Ni5 alloy

    NASA Astrophysics Data System (ADS)

    Abo-Elsoud, M.

    2013-04-01

    Kinetic transformations induced in the metallic glass Al80Fe8Mo7Ni5 by thermal treatments from the amorphous to the crystallized state, following the variation of the Doppler broadening of the positron annihilation line-shaped S-and W-parameters were reported. The behavior of the annihilation line-shape shows reversible and non-reversible contributions. Crystallization of the sample appears as a three-stage process. The corresponding crystallization process consists of only one activation enthalpy, Eai. The mean value obtained for Eai is: Eam=(3.65±0.14) eV. In-situ high-temperature X-ray diffraction showed that the crystallization was a complex involving growth of the Al7Fe8Mo crystalline phase along with crystallization of the amorphous matrix Al phase at T ≈500 °C. Electron micrograph with image analysis of the scanning electron microscopy pictures confirmed the presence of fcc-Al and Al7Fe8Mo crystalline phase.

  16. Consolidated Fleet N2Y-1

    NASA Technical Reports Server (NTRS)

    1930-01-01

    Consolidated Fleet N2Y-1: The Consolidated Fleet N2Y-1 aircraft were used as trainers for the pilots who would fly the 'parasite' fighters attached to the airships Akron and Macon. This N2Y-1 was turned over to the NACA for research work. Note that the vertical surfaces are instrumented for NACA work. This N2Y was used for landing gear tests.

  17. The Consolidated Fleet XN2Y-1

    NASA Technical Reports Server (NTRS)

    1935-01-01

    The Consolidated Fleet XN2Y-1 was a Fleet 1 trainer purchased by the Navy for evaluation. The purchase of several N2Y-1 aircraft followed, for use as trainers for the pilots who would fly the 'parasite' fighters attached to the airships Akron and Macon. The XN2Y-1 was turned over to the NACA for research work. Note the that vertical surfaces are instrumented for NACA spin work.

  18. Use of the double-loop reactivation test to measure sensitization in aged and welded pH 13-8 Mo martensitic stainless steel

    SciTech Connect

    Cieslak, W.R.; Cieslak, M.J.; Hills, C.R.

    1987-01-08

    Electrochemical potentiokinetic reactivation (EPR) testing provides quantitative detection of small degrees of sensitization. We have used double-loop (DL-EPR) testing, a method which has been characterized for use on austenitic stainless steels, to measure sensitization resulting from aging or from welding of PH 13-8 Mo martensitic stainless steel. Aging at either 500/sup 0/C or 620/sup 0/C results in an increase of the reactivation current density. The 500/sup 0/C treatment promotes preferential susceptibility to corrosion along prior austenite grain boundaries, and the 620/sup 0/C treatment promotes preferential susceptibility along martensite interlath boundaries. A narrow band in the heat-affected zone of autogenous weldments also undergoes localized corrosion during the reactivation scan. Increased reactivation current density is likely caused by classic Cr-depletion resulting from carbide precipitation.

  19. Elevated temperature flow strength, creep resistance and diffusion welding characteristics of Ti-6Al-2Nb-1Ta-0.8Mo

    NASA Technical Reports Server (NTRS)

    Whittenberger, J. D.; Moore, T. J.

    1979-01-01

    A study of the flow strength, creep resistance and diffusion welding characteristics of the titanium alloy Ti-6Al-2Nb-1Ta-0.8Mo has been conducted. Two mill-processed forms of this alloy were examined. The forged material had been processed above the beta transus (approximately 1275 K) while the rolled form had been subjected to work below the beta transus. Between 1150 and 1250 K, the forged material was stronger and more creep resistant than the rolled alloy. Both forms exhibit superplastic characteristics in this temperature range. Strain measurements during diffusion welding experiments at 1200 K reveal that weld interfaces have no measurable effect on the overall creep deformation. Significant deformation appears to be necessary to produce a quality diffusion weld between superplastic materials. A 'soft' interlayer inserted between faying surfaces would seemingly allow manufacture of quality diffusion welds with little overall deformation.

  20. Plane shock generator explosive lens: Shock characterization of 4340 and PH13-8Mo steels, C360 brass and PZT 65/35 ferro-electric ceramic

    NASA Astrophysics Data System (ADS)

    Weirick, L. J.

    1994-03-01

    Sandia National Laboratories is currently involved in the optimization of a Plane Shock Generator Explosive Lens (PSGEL). The PSGEL component consists of a detonator, explosive, brass cone and tamper housing. The purpose of the PSGEL component is to transmit a plane shock wave through the 4340 steel bulkhead (wave separator) which has a ferro-electric (PZT)ceramic disk attached to the opposite surface of the steel bulkhead. The planar shock wave depolarizes the PZT 65/35 ferro-electric ceramic to produce an electrical output. One aspect of the optimization program involves the possible replacement of 4340 steel with PH13-8Mo steel for the bulkhead. These materials, as well as the PZT 65/35 ferro-electric ceramic and the brass for the cone, required the stock characterization with respect to Hugoniot parameters. The work presented here gives the shock Hugoniot values for these four materials and documents their measurements.

  1. Elevated-temperature flow strength, creep resistance and diffusion welding characteristics of Ti-gAl-2Nb-1Ta-0.8Mo

    NASA Technical Reports Server (NTRS)

    Whittenberger, J. D.; Moore, T. J.

    1977-01-01

    A study of the flow strength, creep resistance and diffusion welding characteristics of the titanium alloy Ti-6Al-2Nb-1Ta-0.8Mo was conducted. Two mill-processed forms of this alloy were examined. The forged material was essentially processed above the beta transus while the rolled form was subjected to considerable work below the beta transus. Between 1150 and 1250 K, the forged material was stronger and more creep resistant than the rolled alloy. Both forms exhibit superplastic characteristics in this temperature range. Strain measurements during diffusion welding experiments at 1200 K reveal that weld interfaces have no measurable effect on the overall creep deformation. Significant deformation appears to be necessary to produce a quality diffusion weld between superplastic materials. A 'soft' interlayer inserted between faying surfaces would seemingly allow manufacture of quality diffusion welds with little overall deformation.

  2. Detection of Rsp and modifier variation in the meiotic drive system Segregation distorter (SD) of Drosophila melanogaster.

    PubMed

    Lyttle, T W; Brittnacher, J G; Ganetzky, B

    1986-09-01

    Identification of allelic variability at the two major loci (Sd and Rsp) that interact to cause sperm dysfunction in Segregation distorter (SD) males of D. melanogaster has been hampered by the difficulty in separating the elements recombinationally. In addition, small differences in the strength of Sd alleles or sensitivities of Rsp alleles to Sd are difficult to measure against background genetic or environmental variation. Viability effects of the markers used to score progeny classes may also introduce a bias. Removal of Sd and E(SD) from their second chromosome location to create a Dp(2;Y)Sd E(SD) chromosome eliminates these problems, since any combination of Rsp alleles can be easily tested without resorting to recombinational techniques. Further, since these pairs of Rsp alleles are compared in their response to Dp Sd E(SD) in the same individual males, background variation and viability effects can be easily removed to allow fine-scale resolution of Rsp differences. Tests of all possible pairwise combination of six laboratory chromosomes in this way revealed at least three and possibly four different Rsp allelic classes. In addition, the hierarchical nature of the tests further allowed for determination of the presence of linked suppressors or enhancers of Sd activity. A sample of 11 second chromosomes selected from a group recently isolated from a natural population was also unambiguously ordered as to Rsp allelic status using this approach. The resultant pattern was similar to that obtained for the laboratory chromosomes, except for the not unexpected observation that the natural population apparently harbored more drive suppressors. The pattern of results obtained from these pairwise combinations of Rsp alleles supports the notion that there are no dominance interactions within the group, but that each responds more or less independently to Sd in giving sperm dysfunction.

  3. Experimental study of upper sd shell nuclei and evolution of sd-fp shell gap

    SciTech Connect

    Sarkar, M. Saha

    2012-06-27

    The intruder orbitals from the fp shell play important role in the structure of nuclei around the line of stability in the upper sd shell. Experimentally we have studied {sup 35}Cl, {sup 30}P, {sup 36}Cl, {sup 37}Ar and {sup 34}Cl in this mass region using the INGA setup. Large basis cross-shell shell model calculations have indicated the need for change of the sd-fp energy gap for reliable reproduction of negative parity and high spin positive parity states. Indication of population of states of large deformation has been found in our data. Theoretical interpretation of these states has been discussed.

  4. Machining-induced deformation in stepped specimens of PH 13-8 Mo, 18 nickel maraging steel grade 200T1 and grain-refined HP 9-4-20

    NASA Technical Reports Server (NTRS)

    Wigley, D. A.

    1985-01-01

    The results of a study to evaluate the dimensional changes created during machining and subsequent cycling to cryogenic temperatures for three different metallic alloys are presented. Experimental techniques are described and results presented for 18 Ni Grade 200 maraging steel, PH-13-8 Mo stainless steel, and Grain-refined HP 9-4-20.

  5. Microstructural Evolution and Mechanical Properties of Simulated Heat-Affected Zones in Cast Precipitation-Hardened Stainless Steels 17-4 and 13-8+Mo

    NASA Astrophysics Data System (ADS)

    Hamlin, Robert J.; DuPont, John N.

    2017-01-01

    Cast precipitation-hardened (PH) stainless steels 17-4 and 13-8+Mo are used in applications that require a combination of high strength and moderate corrosion resistance. Many such applications require fabrication and/or casting repair by fusion welding. The purpose of this work is to develop an understanding of microstructural evolution and resultant mechanical properties of these materials when subjected to weld thermal cycles. Samples of each material were subjected to heat-affected zone (HAZ) thermal cycles in the solution-treated and aged condition (S-A-W condition) and solution-treated condition with a postweld thermal cycle age (S-W-A condition). Dilatometry was used to establish the onset of various phase transformation temperatures. Light optical microscopy (LOM), scanning electron microscopy (SEM), and energy dispersive spectrometry (EDS) were used to characterize the microstructures, and comparisons were made to gas metal arc welds that were heat treated in the same conditions. Tensile testing was also performed. MatCalc thermodynamic and kinetic modeling software was used to predict the evolution of copper (Cu)-rich body center cubic precipitates in 17-4 and β-NiAl precipitates in 13-8+Mo. The yield strength was lower in the simulated HAZ samples of both materials prepared in the S-A-W condition when compared to their respective base metals. Samples prepared in the S-W-A condition had higher and more uniform yield strengths for both materials. Significant changes were observed in the matrix microstructure of various HAZ regions depending on the peak temperature, and these microstructural changes were interpreted with the aid of dilatometry results, LOM, SEM, and EDS. Despite these significant changes to the matrix microstructure, the changes in mechanical properties appear to be governed primarily by the precipitation behavior. The decrease in strength in the HAZ samples prepared in the S-A-W condition was attributed to the dissolution of precipitates

  6. Participation of peripheral P2Y1, P2Y6 and P2Y11 receptors in formalin-induced inflammatory pain in rats.

    PubMed

    Barragán-Iglesias, Paulino; Mendoza-Garcés, Luis; Pineda-Farias, Jorge Baruch; Solano-Olivares, Verónica; Rodríguez-Silverio, Juan; Flores-Murrieta, Francisco Javier; Granados-Soto, Vinicio; Rocha-González, Héctor Isaac

    2015-01-01

    Metabotropic P2Y receptors subfamily consists of eight functional mammalian receptors. Specifically, P2Y1, P2Y6 and P2Y11 receptors have been described in the sensory nervous system, but their participation, at peripheral level, in behavioral pain models is scarcely understood. This study assessed the role of peripheral P2Y1, P2Y6 and P2Y11 receptors in formalin-induced inflammatory pain. Ipsilateral, but not contralateral peripheral pre-treatment with the endogenous P2Y1 (ADP, 100-1000nmol/paw), P2Y6 (UDP, 180-300nmol/paw) and P2Y11 (ATP, 100-1000nmol/paw), or selective P2Y1 (MRS2365, 0.1-10nmol/paw), P2Y6 (PSB0474, 0.1-0.10pmol/paw) and P2Y11 (NF546, 0.3-3nmol/paw) receptor agonists increased 0.5% formalin-induced flinching behavior. Concordantly, peripheral pre-treatment with the selective P2Y1 (MRS2500, 0.01-10pmol/paw), P2Y6 (MRS2578, 3-30nmol/paw) and P2Y11 (NF340, 1-10nmol/paw) receptor antagonists significantly decreased 1% formalin-induced flinching behavior. Furthermore, the pronociceptive effect of ADP (100nmol/paw) or MRS2365 (10nmol/paw), UDP (300nmol/paw) or PSB0474 (10pmol/paw) and ATP (1000nmol/paw) or NF546 (3nmol/paw) was blocked by the selective P2Y1 (MRS2500, 0.01nmol/paw), P2Y6 (MRS2578, 3nmol/paw), and P2Y11 (NF340, 1nmol/paw) receptor antagonists, respectively. Western blot analysis confirmed the presence of P2Y1 (66kDa), P2Y6 (36kDa) and P2Y11 (75kDa) receptors in dorsal root ganglia (DRG) and sciatic nerve. Results suggest that peripheral activation of P2Y1, P2Y6 and P2Y11 receptors plays a pronociceptive role in formalin-induced pain.

  7. Final report of the safety assessment of Alcohol Denat., including SD Alcohol 3-A, SD Alcohol 30, SD Alcohol 39, SD Alcohol 39-B, SD Alcohol 39-C, SD Alcohol 40, SD Alcohol 40-B, and SD Alcohol 40-C, and the denaturants, Quassin, Brucine Sulfate/Brucine, and Denatonium Benzoate.

    PubMed

    2008-01-01

    Alcohol Denat. is the generic term used by the cosmetics industry to describe denatured alcohol. Alcohol Denat. and various specially denatured (SD) alcohols are used as cosmetic ingredients in a wide variety of products. Many denaturants have been previously considered, on an individual basis, as cosmetic ingredients by the Cosmetic Ingredient Review (CIR) Expert Panel, whereas others, including Brucine and Brucine Sulfate, Denatonium Benzoate, and Quassin, have not previously been evaluated. Quassin is a bitter alkaloid obtained from the wood of Quassia amara. Quassin has been used as an insect antifeedant and insecticide and several studies demonstrate its effectiveness. At oral doses up to 1000 mg/kg using rats, Quassin was not toxic in acute and short-term tests, but some reversible piloerection, decrease in motor activity, and a partial loss of righting reflex were found in mice at 500 mg/kg. At 1000 mg/kg given intraperitoneally (i.p.), all mice died within 24 h of receiving treatment. In a cytotoxicity test with brine shrimp, 1 mg/ml of Quassin did not possess any cytotoxic or antiplasmodial activity. Quassin administered to rat Leydig cells in vitro at concentrations of 5-25 ng/ml inhibited both the basal and luteinizing hormone (LH)-stimulated testosterone secretion in a dose-related fashion. Quassin at doses up to 2.0 g/kg in drinking water using rats produced no significant effect on the body weights, but the mean weights of the testes, seminal vesicles, and epididymides were significantly reduced, and the weights of the anterior pituitary glands were significantly increased. The sperm counts and levels of LH, follicle-stimulating hormone (FSH), and testosterone were significantly lower in groups treated with Quassin. Brucine is a derivative of 2-hydroxystrychnine. Swiss-Webster mice given Brucine base, 30 ml/kg, had an acute oral LD(50) of 150 mg/kg, with central nervous system depression followed by convulsions and seizures in some cases. In those

  8. Comparative analysis of P2Y4 and P2Y6 receptor architecture in native and transfected neuronal systems.

    PubMed

    D'Ambrosi, Nadia; Iafrate, Monia; Saba, Elena; Rosa, Patrizia; Volonté, Cinzia

    2007-06-01

    Although extensive studies provided molecular and pharmacological characterization of metabotropic P2Y receptors for extracellular nucleotides, little is still known about their quaternary structure. By the use of transfected cellular systems and SDS-PAGE, in our previous work we established the propensity of P2Y(4) receptor to form dimeric interactions. Here we focused on endogenously expressed P2Y(4) and P2Y(6) subtypes, comparing their oligomeric complexes under Blue Native (BN) gel electrophoresis. We provided evidence that P2Y(4) and P2Y(6) receptors form high order complexes in native neuronal phenotypes and that the oligomers can be disaggregated down to the dimeric P2Y(4) or to the dimeric and monomeric P2Y(6) receptor. Moreover, dimeric P2Y(4) and monomeric P2Y(6) proteins display selective microdomain partitioning in lipid rafts from specialized subcellular compartments such as synaptosomes. Ligand activation by UTP shifted the oligomerization of P2Y(6) but not of P2Y(4) receptor, as analysed by BN electrophoresis. Finally, whereas transfected P2Y(4) and P2Y(6) proteins homo-interact and posses the appropriate domains to associate with all P2Y(1,2,4,6,11) subtypes, in naive PC12 cells the endogenous P2Y(4) forms hetero-oligomers only with the P2Y(6) subunit. In conclusion, our results indicate that quaternary structure distinguishing P2Y(4) from P2Y(6) receptors might be crucial for specific ligand activation, membrane partitioning and consequent functional regulation.

  9. 77 FR 46284 - Amendment of Class E Airspace; Lemmon, SD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-03

    ... Federal Aviation Administration 14 CFR Part 71 Amendment of Class E Airspace; Lemmon, SD AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: This action amends Class E airspace at... proposed rulemaking (NPRM) to amend Class E airspace for the Lemmon, SD, area, creating...

  10. Credit WCT. Original 2Y4" x 2Y4" color negative is housed ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Credit WCT. Original 2-Y4" x 2-Y4" color negative is housed in the JPL Photography Laboratory, Pasadena, California. JPL staff members Harold Anderson and John Morrow cast grain from the 1-gallon BakerPerkins model 4-PU mixer. A 1-pint Baker-Perkins model 2-PX mixer stands to the left in this view (JPL negative no. JPL-10295BC, 27 January 1989) - Jet Propulsion Laboratory Edwards Facility, Mixer & Casting Building, Edwards Air Force Base, Boron, Kern County, CA

  11. User's Manual for Space Debris Surfaces (SD_SURF)

    NASA Technical Reports Server (NTRS)

    Elfer, N. C.

    1996-01-01

    A unique collection of computer codes, Space Debris Surfaces (SD_SURF), have been developed to assist in the design and analysis of space debris protection systems. SD_SURF calculates and summarizes a vehicle's vulnerability to space debris as a function of impact velocity and obliquity. An SD_SURF analysis will show which velocities and obliquities are the most probable to cause a penetration. This determination can help the analyst select a shield design which is best suited to the predominant penetration mechanism. The analysis also indicates the most suitable parameters for development or verification testing. The SD_SURF programs offer the option of either FORTRAN programs and Microsoft EXCEL spreadsheets and macros. The FORTRAN programs work with BUMPERII version 1.2a or 1.3 (Cosmic released). The EXCEL spreadsheets and macros can be used independently or with selected output from the SD_SURF FORTRAN programs.

  12. SdAb heterodimer formation using leucine zippers

    NASA Astrophysics Data System (ADS)

    Goldman, Ellen R.; Anderson, George P.; Brozozog-Lee, P. Audrey; Zabetakis, Dan

    2013-05-01

    Single domain antibodies (sdAb) are variable domains cloned from camel, llama, or shark heavy chain only antibodies, and are among the smallest known naturally derived antigen binding fragments. SdAb derived from immunized llamas are able to bind antigens with high affinity, and most are capable of refolding after heat or chemical denaturation to bind antigen again. We hypothesized that the ability to produce heterodimeric sdAb would enable reagents with the robust characteristics of component sdAb, but with dramatically improved overall affinity through increased avidity. Previously we had constructed multimeric sdAb by genetically linking sdAb that bind non-overlapping epitopes on the toxin, ricin. In this work we explored a more flexible approach; the construction of multivalent binding reagents using multimerization domains. We expressed anti-ricin sdAb that recognize different epitopes on the toxin as fusions with differently charged leucine zippers. When the initially produced homodimers are mixed the leucine zipper domains will pair to produce heterodimers. We used fluorescence resonance energy transfer to confirm heterodimer formation. Surface plasmon resonance, circular dichroism, enzyme linked immunosorbent assays, and fluid array assays were used to characterize the multimer constructs, and evaluate their utility in toxin detection.

  13. 76 FR 34286 - South Dakota Disaster Number SD-00041

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-13

    ... From the Federal Register Online via the Government Publishing Office SMALL BUSINESS ADMINISTRATION South Dakota Disaster Number SD-00041 AGENCY: U.S. Small Business Administration. ACTION... the following areas as adversely affected by the disaster. Primary Counties: Stanley. All...

  14. RadNet Air Data From Rapid City, SD

    EPA Pesticide Factsheets

    This page presents radiation air monitoring and air filter analysis data for Rapid City, SD from EPA's RadNet system. RadNet is a nationwide network of monitoring stations that measure radiation in air, drinking water and precipitation.

  15. RadNet Air Data From Pierre, SD

    EPA Pesticide Factsheets

    This page presents radiation air monitoring and air filter analysis data for Pierre, SD from EPA's RadNet system. RadNet is a nationwide network of monitoring stations that measure radiation in air, drinking water and precipitation.

  16. Head-Torso-Hand Coordination in Children with and without Developmental Coordination Disorder

    ERIC Educational Resources Information Center

    Elders, Vera; Sheehan, Sinead; Wilson, Andrew D.; Levesley, Martin; Bhakta, Bipin; Mon-Williams, Mark

    2010-01-01

    Aim: This study investigated the nature of coordination and control problems in children with developmental coordination disorder (DCD). Method: Seven adults (two males, five females, age range 20-28y; mean 23y, SD 2y 8mo) and eight children with DCD (six males, two females, age range 7-9y; mean 8y, SD 8mo), and 10 without DCD (seven males, three…

  17. Serotonin and Dopamine Transporter Binding in Children with Autism Determined by SPECT

    ERIC Educational Resources Information Center

    Makkonen, Ismo; Riikonen, Raili; Kokki, Hannu; Airaksinen, Mauno M.; Kuikka, Jyrki T.

    2008-01-01

    Disturbances in the serotonergic system have been recognized in autism. To investigate the association between serotonin and dopamine transporters and autism, we studied 15 children (14 males, one female; mean age 8y 8mo [SD 3y 10mo]) with autism and 10 non-autistic comparison children (five males, five females; mean age 9y 10mo [SD 2y 8mo]) using…

  18. P2Y Receptors Sensitize Mouse and Human Colonic Nociceptors

    PubMed Central

    Hockley, James R. F.; Tranter, Michael M.; McGuire, Cian; Boundouki, George; Cibert-Goton, Vincent; Thaha, Mohamed A.; Blackshaw, L. Ashley; Michael, Gregory J.; Baker, Mark D.; Knowles, Charles H.; Winchester, Wendy J.

    2016-01-01

    Activation of visceral nociceptors by inflammatory mediators contributes to visceral hypersensitivity and abdominal pain associated with many gastrointestinal disorders. Purine and pyrimidine nucleotides (e.g., ATP and UTP) are strongly implicated in this process following their release from epithelial cells during mechanical stimulation of the gut, and from immune cells during inflammation. Actions of ATP are mediated through both ionotropic P2X receptors and metabotropic P2Y receptors. P2X receptor activation causes excitation of visceral afferents; however, the impact of P2Y receptor activation on visceral afferents innervating the gut is unclear. Here we investigate the effects of stimulating P2Y receptors in isolated mouse colonic sensory neurons, and visceral nociceptor fibers in mouse and human nerve-gut preparations. Additionally, we investigate the role of Nav1.9 in mediating murine responses. The application of UTP (P2Y2 and P2Y4 agonist) sensitized colonic sensory neurons by increasing action potential firing to current injection and depolarizing the membrane potential. The application of ADP (P2Y1, P2Y12, and P2Y13 agonist) also increased action potential firing, an effect blocked by the selective P2Y1 receptor antagonist MRS2500. UTP or ADP stimulated afferents, including mouse and human visceral nociceptors, in nerve-gut preparations. P2Y1 and P2Y2 transcripts were detected in 80% and 56% of retrogradely labeled colonic neurons, respectively. Nav1.9 transcripts colocalized in 86% of P2Y1-positive and 100% of P2Y2-positive colonic neurons, consistent with reduced afferent fiber responses to UTP and ADP in Nav1.9−/− mice. These data demonstrate that P2Y receptor activation stimulates mouse and human visceral nociceptors, highlighting P2Y-dependent mechanisms in the generation of visceral pain during gastrointestinal disease. SIGNIFICANCE STATEMENT Chronic visceral pain is a debilitating symptom of many gastrointestinal disorders. The activation of

  19. Decay out of SD Band in ^192Pb

    NASA Astrophysics Data System (ADS)

    McNabb, D. P.; Cizewski, J. A.; Ding, K. Y.; Fotiades, N.; Archer, D. E.; Becker, J. A.; Bernstein, L. A.; Hauschild, K.; Younes, W.; Clark, R. M.; Fallon, P.; Lee, I. Y.; Macchiavelli, A. O.; MacLeod, R. W.

    1997-04-01

    Gamma-ray transitions linking the yrast SD bands to the known (ND) levels have been found in ^194Pb(M. J. Brinkman, et al., Phys. Rev. C53), R1461 (1996), A. Lopez-Martens, et al., Phys. Lett. B380, 18 (1996) and K. Hauschild, et al., submitted to Phys. Rev. C (1996). and ^194Hg.(T. L. Khoo, et al., Phys. Rev. Lett. 76), 1583 (1996). The spin, parity and excitation energy of these SD bands were established. Linking transitions are understood as arising from ND states nearby in excitation energy which are admixed with the SD states.(E. Vigezzi, et al., Phys. Lett. B249), 163 (1990). We anticipate a smaller phase space for quasicontinuous decay of the SD band in ^192Pb because it is predicted to lie lower in excitation than the SD band in ^194Pb.footnote S. J. Krieger, et al. Nucl. Phys. A542, 43 (1992). To search for linking transitions in ^192Pb we used the Gammasphere array at LBNL and the ^24Mg(^173Yb,5n) reaction at 134 MeV. Candidates for linking transitions and general features of the decay will be discussed.

  20. SD-CAS: Spin Dynamics by Computer Algebra System.

    PubMed

    Filip, Xenia; Filip, Claudiu

    2010-11-01

    A computer algebra tool for describing the Liouville-space quantum evolution of nuclear 1/2-spins is introduced and implemented within a computational framework named Spin Dynamics by Computer Algebra System (SD-CAS). A distinctive feature compared with numerical and previous computer algebra approaches to solving spin dynamics problems results from the fact that no matrix representation for spin operators is used in SD-CAS, which determines a full symbolic character to the performed computations. Spin correlations are stored in SD-CAS as four-entry nested lists of which size increases linearly with the number of spins into the system and are easily mapped into analytical expressions in terms of spin operator products. For the so defined SD-CAS spin correlations a set of specialized functions and procedures is introduced that are essential for implementing basic spin algebra operations, such as the spin operator products, commutators, and scalar products. They provide results in an abstract algebraic form: specific procedures to quantitatively evaluate such symbolic expressions with respect to the involved spin interaction parameters and experimental conditions are also discussed. Although the main focus in the present work is on laying the foundation for spin dynamics symbolic computation in NMR based on a non-matrix formalism, practical aspects are also considered throughout the theoretical development process. In particular, specific SD-CAS routines have been implemented using the YACAS computer algebra package (http://yacas.sourceforge.net), and their functionality was demonstrated on a few illustrative examples.

  1. P2Y receptors in health and disease.

    PubMed

    Erlinge, David

    2011-01-01

    The purine- and pyrimidine-sensitive P2Y receptors belong to the large group of G-protein-coupled receptors that are the target of approximately one-third of the pharmaceutical drugs used in the clinic today. It is therefore not unexpected that the P2Y receptors could be useful targets for drug development. This chapter will discuss P2Y receptor-based therapies currently used, in development and possible future developments. The platelet inhibitors blocking the ADP-receptor P2Y(12) reduce myocardial infarction, stroke, and mortality in patients with cardiovascular disease. Clopidogrel (Plavix) was for many years the second most selling drug in the world. The improved P2Y(12) inhibitors prasugrel, ticagrelor, and elinogrel are now entering the clinic with even more pronounced protective effects. The UTP-activated P2Y(2) receptor stimulates ciliary movement and secretion from epithelial cells. Cystic fibrosis is a monogenetic disease where reduced chloride ion secretion results in a severe lung disease and early death. No specific treatment has been available, but the P2Y(2) agonist Denufosol has been shown to improve lung function and is expected to be introduced as treatment for cystic fibrosis soon. In preclinical studies, there are indications that P2Y receptors can be important for diabetes, osteoporosis, cardiovascular, and atherosclerotic disease. In conclusion, P2Y receptors are important for the health of humans for many diseases, and we can expect even more beneficial drugs targeting P2Y receptors in the future.

  2. 78 FR 39820 - Standing Rock Sioux Tribe Disaster #SD-00058

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-02

    ... ADMINISTRATION Standing Rock Sioux Tribe Disaster SD-00058 AGENCY: U.S. Small Business Administration. ACTION... Assistance Only for the Standing Rock Indian Reservation (FEMA-4123-DR), dated 06/25/2013. Incident: Severe... adversely affected by the disaster: Primary Area: Standing Rock Indian Reservation. The Interest Rates...

  3. 75 FR 4417 - Wind Cave National Park, Custer County, SD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-27

    ... Wind Cave National Park, Custer County, SD AGENCY: National Park Service. ACTION: Notice of... Statement, Wind Cave National Park, Custer County, South Dakota. SUMMARY: Pursuant to Section 102(2)(C) of... Environmental Impact Statement (Plan), Wind Cave National Park, Custer County, South Dakota. On December 3,...

  4. 76 FR 67596 - Amendment of Class E Airspace; Spearfish, SD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-02

    ... Procedures at Black Hills Airport--Clyde Ice Field, and updates the geographic coordinates of the airport... additional controlled airspace at Black Hills Airport--Clyde Ice Field (76 FR 43610) Docket No. FAA-2011-0431... procedures at Black Hills Airport--Clyde Ice Field, Spearfish, SD. This action is necessary for the...

  5. 76 FR 35935 - South Dakota Disaster Number SD-00041

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-20

    ... Doc No: 2011-15140] U.S. SMALL BUSINESS ADMINISTRATION [Disaster Declaration 12590 and 12591] South Dakota Disaster Number SD-00041 AGENCY: U.S. Small Business Administration. ACTION: Amendment 2. SUMMARY... completed loan applications to: U.S. Small Business Administration, Processing and Disbursement...

  6. 76 FR 35936 - South Dakota Disaster Number SD-00041

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-20

    ...: 2011-15124] U.S. SMALL BUSINESS ADMINISTRATION [Disaster Declaration 12590 and 12591] South Dakota Disaster Number SD-00041 AGENCY: U.S. Small Business Administration. ACTION: Amendment 3. SUMMARY: This is... applications to: U.S. Small Business Administration, Processing and Disbursement Center, 14925 Kingsport...

  7. 78 FR 48764 - South Dakota Disaster # SD-00061

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-09

    ... From the Federal Register Online via the Government Publishing Office SMALL BUSINESS ADMINISTRATION South Dakota Disaster SD-00061 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY...: Submit completed loan applications to: U.S. Small Business Administration, Processing and...

  8. 78 FR 48302 - Establishment of Class E Airspace; Wagner, SD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-08

    ... Federal Aviation Administration 14 CFR Part 71 Establishment of Class E Airspace; Wagner, SD AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: This action establishes Class E... Federal Register a notice of proposed rulemaking (NPRM) to establish Class E airspace for the Wagner,...

  9. Role of P2Y12 Receptor in Thrombosis.

    PubMed

    Zhang, Yaqi; Zhang, Si; Ding, Zhongren

    2017-01-01

    P2Y12 receptor is a 342 amino acid Gi-coupled receptor predominantly expressed on platelets. P2Y12 receptor is physiologically activated by ADP and inhibits adenyl cyclase (AC) to decrease cyclic AMP (cAMP) level, resulting in platelet aggregation. It also activates PI3 kinase (PI3K) pathway leading to fibrinogen receptor activation, and may protect platelets from apoptosis. Abnormalities of P2Y12 receptor include congenital deficiencies or high activity in diseases like diabetes mellitus (DM) and chronic kidney disease (CKD), exposing such patients to a prothrombotic condition. A series of clinical antiplatelet drugs, such as clopidogrel and ticagrelor, are designed as indirect or direct antagonists of P2Y12 receptor to reduce incidence of thrombosis mainly for patients of acute coronary syndrome (ACS) who are at high risk of thrombotic events. Studies on novel dual-/multi-target antiplatelet agents consider P2Y12 receptor as a promising part in combined targets. However, the clinical practical phenomena, such as "clopidogrel resistance" due to gene variations of cytochrome P450 or P2Y12 receptor constitutive activation, call for better antiplatelet agents. Researches also showed inverse agonist of P2Y12 receptor could play a better role over neutral antagonists. Personalized antiplatelet therapy is the most ideal destination for antiplatelet therapy in ACS patients with or without other underlying diseases like DM or CKD, however, there is still a long way to go.

  10. How Changes in Anti-SD Sequences Would Affect SD Sequences in Escherichia coli and Bacillus subtilis.

    PubMed

    Abolbaghaei, Akram; Silke, Jordan R; Xia, Xuhua

    2017-03-31

    The 3' end of the small ribosomal RNAs (ssu rRNA) in bacteria is directly involved in the selection and binding of mRNA transcripts during translation initiation via well-documented interactions between a Shine-Dalgarno (SD) sequence located upstream of the initiation codon and an anti-SD (aSD) sequence at the 3' end of the ssu rRNA. Consequently, the 3' end of ssu rRNA (3'TAIL) is strongly conserved among bacterial species because a change in the region may impact the translation of many protein-coding genes. Escherichia coli and Bacillus subtilis differ in their 3' ends of ssu rRNA, being GAUCACCUCCUUA3' in E. coli and GAUCACCUCCUUUCU3' or GAUCACCUCCUUUCUA3' in B. subtilis Such differences in 3'TAIL lead to species-specific SDs (designated SDEc for E. coli and SDBs for B. subtilis) that can form strong and well-positioned SD/aSD pairing in one species but not in the other. Selection mediated by the species-specific 3'TAIL is expected to favour SDBs against SDEc in B. subtilis but favour SDEc against SDBs in E. coli Among well-positioned SDs, SDEc is used more in E. coli than in B. subtilis, and SDBs more in B. subtilis than in E. coli Highly expressed genes and genes of high translation efficiency tend to have longer SDs than lowly expressed genes and genes with low translation efficiency in both species, but more so in B. subtilis than in E. coli Both species overuse SDs matching the bolded part of 3'TAIL shown above. The 3'TAIL difference contributes to host-specificity of phages.

  11. The Independent Distorting Ability of the Enhancer of Segregation Distortion, E(sd), in Drosophila Melanogaster

    PubMed Central

    Temin, R. G.

    1991-01-01

    Segregation distortion is a meiotic drive system, discovered in wild populations, in which males heterozygous for an SD chromosome and a sensitive SD(+) homolog transmit the SD chromosome almost exclusively. SD represents a complex of three closely linked loci in the centromeric region of chromosome 2: Sd, the Segregation distorter gene; E(SD), the Enhancer of Segregation Distortion, required for full expression of drive; and Rsp, the target for the action of Sd, existing in a continuum of states classifiable into sensitive (Rsp(s)) and insensitive (Rsp(i)). In an SD/SD(+) male which is Sd E(SD) Rsp(i)/Sd(+) E(SD)(+) Rsp(s), the Sd and E(SD) elements act jointly to induce the dysfunction of those spermatids receiving the Rsp(s) chromosome. By manipulating the number of copies and the position of the Enhancer region, I demonstrated that: (1) E(SD), whether in its normal position or translocated to the Y chromosome, is able to enhance the degree of Sd-caused distortion in a dosage-dependent manner; (2) even in the absence of Sd, the E(SD) allele in two doses can cause significant distortion, in Sd(+) or Df(Sd)-bearing genotypes; (3) quantitative differences among Enhancers of different sources suggest allelic variation at E(SD), which could account at least in part for differences among wild SD chromosomes in strength of distortion; (4) E(SD)/E(SD)-mediated distortion, like that of Sd, is directed at the Rsp target, whether Rsp is on the second or the Y chromosome; (5) E(SD), like Sd, is suppressed by an unlinked dominant suppressor of SD action. These results show that E(SD) is independently capable of acting on Rsp and is not a simple modifier of the action of Sd. E(SD) provides an example of a trans-acting gene embedded in heterochromatin that can interact with another heterochromatic gene, Rsp, as well as parallel the effect of a euchromatic gene, Sd. PMID:1906417

  12. Microscopic Shell Model Calculations for sd-Shell Nuclei

    NASA Astrophysics Data System (ADS)

    Barrett, Bruce R.; Dikmen, Erdal; Maris, Pieter; Shirokov, Andrey M.; Smirnova, Nadya A.; Vary, James P.

    Several techniques now exist for performing detailed and accurate calculations of the structure of light nuclei, i.e., A ≤ 16. Going to heavier nuclei requires new techniques or extensions of old ones. One of these is the so-called No Core Shell Model (NCSM) with a Core approach, which involves an Okubo-Lee-Suzuki (OLS) transformation of a converged NCSM result into a single major shell, such as the sd-shell. The obtained effective two-body matrix elements can be separated into core and single-particle (s.p.) energies plus residual two-body interactions, which can be used for performing standard shell-model (SSM) calculations. As an example, an application of this procedure will be given for nuclei at the beginning ofthe sd-shell.

  13. What's the Nature of sdA Stars?

    NASA Astrophysics Data System (ADS)

    Pelisoli, I.; Kepler, S. O.; Koester, D.; Romero, A. D.

    2017-03-01

    White dwarfs with log g lower than 7.0 are called Extremely Low Mass white dwarfs (ELMs). They were first found as companions to pulsars, then to other white dwarfs and main sequence stars (The ELM Survey: 2010 to 2016), and can only be formed in interacting binaries in the age of the Universe. In our SDSS DR12 white dwarf catalog (Kepler et al. 2016), we found a few thousand stars in the effective temperature and surface gravity ranges attributed to ELMs. We have called these objects sdAs, alluding to their narrow hydrogen line spectra showing sub-main sequence log g. One possible explanation for the sdAs is that they are ELMs. Increasing the ELMs sample would help constrain the number of close binaries in the Galaxy. Interestingly, if they turn out to be A stars with an overestimated log g, the distance modulus would put these young stars in the Galaxy's halo.

  14. Stochastic Dynamic Mixed-Integer Programming (SD-MIP)

    DTIC Science & Technology

    2015-05-05

    door to stochastic optimization models, which are typically dynamic in nature. This project lays the foundation for stochastic dynamic mixed...project lays the foundation for stochastic dynamic mixed-integer and linear programming (SD-MIP). This project has produced several new ideas in...models. Recent research has opened the door to stochastic optimization models, which are typically dynamic in nature. This project lays the foundation for

  15. Evaluation of microvision SD2500 scanning laser display

    NASA Astrophysics Data System (ADS)

    Harding, Thomas H.; Rash, Clarence E.; Dennis, Scott J.

    2006-05-01

    Microvision's Spectrum TM SD2500 is a candidate technology for the Modular Integrated Helmet Display System (MIHDS)program. This HMD design is intended to provide a full-color, see-through, daylight and night-readable, moderate-resolution (800X600 pixels) display. The employed technology is that of scanning lasers. This paper presents the testing results for the latest version of this prototype system.

  16. Shell Model Depiction of Isospin Mixing in sd Shell

    SciTech Connect

    Lam, Yi Hua; Smirnova, Nadya A.; Caurier, Etienne

    2011-11-30

    We constructed a new empirical isospin-symmetry breaking (ISB) Hamiltonian in the sd(1s{sub 1/2}, 0d{sub 5/2} and 0d{sub 3/2}) shell-model space. In this contribution, we present its application to two important case studies: (i){beta}-delayed proton emission from {sup 22}Al and (ii) isospin-mixing correction to superallowed 0{sup +}{yields}0{sup +}{beta}-decay ft-values.

  17. sd(2) Graphene: Kagome band in a hexagonal lattice.

    PubMed

    Zhou, Miao; Liu, Zheng; Ming, Wenmei; Wang, Zhengfei; Liu, Feng

    2014-12-05

    Graphene, made of sp^{2} hybridized carbon, is characterized with a Dirac band, representative of its underlying 2D hexagonal lattice. The fundamental understanding of graphene has recently spurred a surge in the search for 2D topological quantum phases in solid-state materials. Here, we propose a new form of 2D material, consisting of sd^{2} hybridized transition metal atoms in hexagonal lattice, called sd^{2} "graphene." The sd^{2} graphene is characterized by bond-centered electronic hopping, which transforms the apparent atomic hexagonal lattice into the physics of a kagome lattice that may exhibit a wide range of topological quantum phases. Based on first-principles calculations, room-temperature quantum anomalous Hall states with an energy gap of ∼0.1  eV are demonstrated for one such lattice made of W, which can be epitaxially grown on a semiconductor surface of 1/3 monolayer Cl-covered Si(111), with high thermodynamic and kinetic stability.

  18. On the Components of Segregation Distortion in Drosophila Melanogaster. V. Molecular Analysis of the Sd Locus

    PubMed Central

    Powers, P. A.; Ganetzky, B.

    1991-01-01

    Segregation Distorter (SD) is a naturally occurring meiotic drive system comprising at least three distinct loci: Sd, Rsp and E(SD). Heterozygous SD/SD(+) males transmit the SD chromosome in vast excess over the normal homolog. The distorted transmission involves the induced dysfunction of the spermatids that receive the SD(+) chromosome. In the 220-kb region of DNA that contains the Sd gene, we identified a 5-kb tandem duplication that is uniquely associated with all SD chromosomes, absent in SD(+) chromosomes, and detectably altered in Sd revertants. On northern blots, genomic probes from the tandem duplication detect an SD-specific 4-kb transcript in addition to several smaller transcripts present in both SD and SD(+). Seven classes of cDNAs derived from these transcripts have been isolated. All of these cDNAs share extensive sequence identity at their 3' ends but differ at their 5' ends. Sequence analysis indicates that these cDNAs potentially encode four distinct, but related, polypeptides. Introduction of the tandem duplication into SD(+) flies by germline transformation did not confer the dominant gain-of-function Sd phenotype. This result, taken together with our analysis of the Sd cDNAs, suggests that the duplication is part of a much larger gene that encodes several different polypeptides. PMID:1936954

  19. Confinement orientation effects in S/D tunneling

    NASA Astrophysics Data System (ADS)

    Medina-Bailon, C.; Sampedro, C.; Gámiz, F.; Godoy, A.; Donetti, L.

    2017-02-01

    The most extensive research of scaled electronic devices involves the inclusion of quantum effects in the transport direction as transistor dimensions approach nanometer scales. Moreover, it is necessary to study how these mechanisms affect different transistor architectures to determine which one can be the best candidate to implement future nodes. This work implements Source-to-Drain Tunneling mechanism (S/D tunneling) in a Multi-Subband Ensemble Monte Carlo (MS-EMC) simulator showing the modification in the distribution of the electrons in the subbands, and, consequently, in the potential profile due to different confinement direction between DGSOIs and FinFETs.

  20. Development of selective agonists and antagonists of P2Y receptors

    PubMed Central

    Ivanov, Andrei A.; de Castro, Sonia; Harden, T. Kendall; Ko, Hyojin

    2008-01-01

    Although elucidation of the medicinal chemistry of agonists and antagonists of the P2Y receptors has lagged behind that of many other members of group A G protein-coupled receptors, detailed qualitative and quantitative structure–activity relationships (SARs) were recently constructed for several of the subtypes. Agonists selective for P2Y1, P2Y2, and P2Y6 receptors and nucleotide antagonists selective for P2Y1 and P2Y12 receptors are now known. Selective nonnucleotide antagonists were reported for P2Y1, P2Y2, P2Y6, P2Y11, P2Y12, and P2Y13 receptors. At the P2Y1 and P2Y12 receptors, nucleotide agonists (5′-diphosphate derivatives) were converted into antagonists of nanomolar affinity by altering the phosphate moieties, with a focus particularly on the ribose conformation and substitution pattern. Nucleotide analogues with conformationally constrained ribose-like rings were introduced as selective receptor probes for P2Y1 and P2Y6 receptors. Screening chemically diverse compound libraries has begun to yield new lead compounds for the development of P2Y receptor antagonists, such as competitive P2Y12 receptor antagonists with antithrombotic activity. Selective agonists for the P2Y4, P2Y11, and P2Y13 receptors and selective antagonists for P2Y4 and P2Y14 receptors have not yet been identified. The P2Y14 receptor appears to be the most restrictive of the class with respect to modification of the nucleobase, ribose, and phosphate moieties. The continuing process of ligand design for the P2Y receptors will aid in the identification of new clinical targets. PMID:18600475

  1. P2Y nucleotide receptors: Promise of therapeutic applications

    PubMed Central

    Jacobson, Kenneth A.; Boeynaems, Jean-Marie

    2010-01-01

    Extracellular nucleotides, such as ATP and UTP, have distinct signaling roles through a class of G protein-coupled receptors, termed P2Y. However, the receptor ligands are typically charged molecules of low bioavailability and stability in vivo. Recent progress in the development of selective agonists and antagonists for P2Y receptors and study of knockout mice have led to new drug concepts based on these receptors. The rapidly accelerating progress in this field has already resulted in drug candidates for cystic fibrosis, dry eye disease, and thrombosis. On the horizon are novel treatments of cardiovascular diseases, inflammatory diseases, and neurodegeneration. PMID:20594935

  2. Open sd-shell nuclei from first principles

    SciTech Connect

    Jansen, Gustav R.; Signoracci, Angelo J.; Hagen, Gaute; Navratil, Petr

    2016-07-05

    We extend the ab initio coupled-cluster effective interaction (CCEI) method to open-shell nuclei with protons and neutrons in the valence space, and compute binding energies and excited states of isotopes of neon and magnesium. We employ a nucleon-nucleon and three-nucleon interaction from chiral effective field theory evolved to a lower cutoff via a similarity renormalization group transformation. We find good agreement with experiment for binding energies and spectra, while charge radii of neon isotopes are underestimated. For the deformed nuclei 20Ne and 24Mg we reproduce rotational bands and electric quadrupole transitions within uncertainties estimated from an effective field theory for deformed nuclei, thereby demonstrating that collective phenomena in sd-shell nuclei emerge from complex ab initio calculations.

  3. Open sd-shell nuclei from first principles

    DOE PAGES

    Jansen, Gustav R.; Signoracci, Angelo J.; Hagen, Gaute; ...

    2016-07-05

    We extend the ab initio coupled-cluster effective interaction (CCEI) method to open-shell nuclei with protons and neutrons in the valence space, and compute binding energies and excited states of isotopes of neon and magnesium. We employ a nucleon-nucleon and three-nucleon interaction from chiral effective field theory evolved to a lower cutoff via a similarity renormalization group transformation. We find good agreement with experiment for binding energies and spectra, while charge radii of neon isotopes are underestimated. For the deformed nuclei 20Ne and 24Mg we reproduce rotational bands and electric quadrupole transitions within uncertainties estimated from an effective field theory formore » deformed nuclei, thereby demonstrating that collective phenomena in sd-shell nuclei emerge from complex ab initio calculations.« less

  4. Charge radii of neon isotopes across the sd neutron shell

    SciTech Connect

    Marinova, K.; Geithner, W.; Kappertz, S.; Kloos, S.; Kotrotsios, G.; Neugart, R.; Wilbert, S.; Kowalska, M.; Keim, M.; Blaum, K.; Lievens, P.; Simon, H.

    2011-09-15

    We report on the changes in mean square charge radii of unstable neon nuclei relative to the stable {sup 20}Ne, based on the measurement of optical isotope shifts. The studies were carried out using collinear laser spectroscopy on a fast beam of neutral neon atoms. High sensitivity on short-lived isotopes was achieved thanks to nonoptical detection based on optical pumping and state-selective collisional ionization, which was complemented by an accurate determination of the beam kinetic energy. The new results provide information on the structural changes in the sequence of neon isotopes all across the neutron sd shell, ranging from the proton drip line nucleus and halo candidate {sup 17}Ne up to the neutron-rich {sup 28}Ne in the vicinity of the ''island of inversion.'' Within this range the charge radius is smallest for {sup 24}Ne with N=14 corresponding to the closure of the neutron d{sub 5/2} shell, while it increases toward both neutron shell closures, N=8 and N=20. The general trend of the charge radii correlates well with the deformation effects which are known to be large for several neon isotopes. In the neutron-deficient isotopes, structural changes arise from the onset of proton-halo formation for {sup 17}Ne, shell closure in {sup 18}Ne, and clustering effects in {sup 20,21}Ne. On the neutron-rich side the transition to the island of inversion plays an important role, with the radii in the upper part of the sd shell confirming the weakening of the N=20 magic number. The results add new information to the radii systematics of light nuclei where data are scarce because of the small contribution of nuclear-size effects to the isotope shifts which are dominated by the finite-mass effect.

  5. Functionalized Congeners of P2Y1 Receptor Antagonists:

    SciTech Connect

    de Castro, Sonia; Maruoka, Hiroshi; Hong, Kunlun; Kilbey, II, S Michael; Costanzi, Stefano; Hechler, Béatrice; Gachet, Christian; Harden, T. Kendall; Jacobson, Kenneth A.

    2010-01-01

    The P2Y{sub 1} receptor is a prothrombotic G protein-coupled receptor (GPCR) activated by ADP. Preference for the North (N) ring conformation of the ribose moiety of adenine nucleotide 3',5'-bisphosphate antagonists of the P2Y{sub 1} receptor was established by using a ring-constrained methanocarba (a bicyclo[3.1.0]hexane) ring as a ribose substitute. A series of covalently linkable N{sup 6}-methyl-(N)-methanocarba-2'-deoxyadenosine-3',5'-bisphosphates containing extended 2-alkynyl chains was designed, and binding affinity at the human (h) P2Y{sub 1} receptor determined. The chain of these functionalized congeners contained hydrophilic moieties, a reactive substituent, or biotin, linked via an amide. Variation of the chain length and position of an intermediate amide group revealed high affinity of carboxylic congener 8 (K{sub i} 23 nM) and extended amine congener 15 (K{sub i} 132 nM), both having a 2-(1-pentynoyl) group. A biotin conjugate 18 containing an extended {epsilon}-aminocaproyl spacer chain exhibited higher affinity than a shorter biotinylated analogue. Alternatively, click coupling of terminal alkynes of homologous 2-dialkynyl nucleotide derivatives to alkyl azido groups produced triazole derivatives that bound to the P2Y{sub 1} receptor following deprotection of the bisphosphate groups. The preservation of receptor affinity of the functionalized congeners was consistent with new P2Y{sub 1} receptor modeling and ligand docking. Attempted P2Y{sub 1} antagonist conjugation to PAMAM dendrimer carriers by amide formation or palladium-catalyzed reaction between an alkyne on the dendrimer and a 2-iodopurine-derivatized nucleotide was unsuccessful. A dialkynyl intermediate containing the chain length favored in receptor binding was conjugated to an azide-derivatized dendrimer, and the conjugate inhibited ADP-promoted human platelet aggregation. This is the first example of attaching a strategically functionalized P2Y receptor antagonist to a PAMAM dendrimer to

  6. P2Y Purinergic Regulation of the Glycine Neurotransmitter Transporters*

    PubMed Central

    Jiménez, Esperanza; Zafra, Francisco; Pérez-Sen, Raquel; Delicado, Esmerilda G.; Miras-Portugal, Maria Teresa; Aragón, Carmen; López-Corcuera, Beatriz

    2011-01-01

    The sodium- and chloride-coupled glycine neurotransmitter transporters (GLYTs) control the availability of glycine at glycine-mediated synapses. The mainly glial GLYT1 is the key regulator of the glycine levels in glycinergic and glutamatergic pathways, whereas the neuronal GLYT2 is involved in the recycling of synaptic glycine from the inhibitory synaptic cleft. In this study, we report that stimulation of P2Y purinergic receptors with 2-methylthioadenosine 5′-diphosphate in rat brainstem/spinal cord primary neuronal cultures and adult rat synaptosomes leads to the inhibition of GLYT2 and the stimulation of GLYT1 by a paracrine regulation. These effects are mainly mediated by the ADP-preferring subtypes P2Y1 and P2Y13 because the effects are partially reversed by the specific antagonists N6-methyl-2′-deoxyadenosine-3′,5′-bisphosphate and pyridoxal-5′-phosphate-6-azo(2-chloro-5-nitrophenyl)-2,4-disulfonate and are totally blocked by suramin. P2Y12 receptor is additionally involved in GLYT1 stimulation. Using pharmacological approaches and siRNA-mediated protein knockdown methodology, we elucidate the molecular mechanisms of GLYT regulation. Modulation takes place through a signaling cascade involving phospholipase C activation, inositol 1,4,5-trisphosphate production, intracellular Ca2+ mobilization, protein kinase C stimulation, nitric oxide formation, cyclic guanosine monophosphate production, and protein kinase G-I (PKG-I) activation. GLYT1 and GLYT2 are differentially sensitive to NO/cGMP/PKG-I both in brain-derived preparations and in heterologous systems expressing the recombinant transporters and P2Y1 receptor. Sensitivity to 2-methylthioadenosine 5′-diphosphate by GLYT1 and GLYT2 was abolished by small interfering RNA (siRNA)-mediated knockdown of nitric-oxide synthase. Our data may help define the role of GLYTs in nociception and pain sensitization. PMID:21245148

  7. Product of the SNPP VIIRS SD screen transmittance and the SD BRDF from both yaw maneuver and regular on-orbit data

    NASA Astrophysics Data System (ADS)

    Lei, Ning; Xiong, Xiaoxiong

    2016-09-01

    To assure data quality, the Earth-observing Visible Infrared Imaging Radiometer Suite (VIIRS) regularly performs on orbit radiometric calibrations of its 22 spectral bands. The primary calibration radiance source for the reflective solar bands (RSBs) is a sunlit solar diffuser (SD). During the calibration process, sunlight goes through a perforated plate (the SD screen) and then strikes the SD. The SD scattered sunlight is used for the calibration, with the spectral radiance proportional to the product of the SD screen transmittance and the SD bidirectional reflectance distribution function (BRDF). The BRDF is decomposed to the product of its value at launch and a numerical factor quantifying its change since launch. Therefore, the RSB calibration requires accurate knowledge of the product of the SD screen transmittance and the BRDF (RSB; launch time). Previously, we calculated the product with yaw maneuver data and found that the product had improved accuracy over the prelaunch one. With both yaw maneuver and regular on orbit data, we were able to improve the accuracy of the SDSM screen transmittance and the product for the solar diffuser stability monitor SD view. In this study, we use both yaw maneuver and a small portion of regular on-orbit data to determine the product for the RSB SD view.

  8. Warping, extra dimensions, and a slice of AdSd

    NASA Astrophysics Data System (ADS)

    McDonald, Kristian L.

    2010-01-01

    Inspired by the Randall-Sundrum framework we consider a number of phenomenologically relevant model-building questions on a slice of compactified AdSd for d>5. Such spaces are interesting as they enable one to realize the weak scale via warping. We perform the Kaluza-Klein (KK) reduction for gravitons and bulk vectors in these spaces, and for the case of AdS6 consider the KK spectrum of gauge scalars. We further obtain the KK towers for bulk fermions on a slice of AdS7 and AdS9 and show that the Randall-Sundrum approach to flavor generalizes to these spaces with the localization of chiral zero-mode fermions controlled by their bulk Dirac mass parameters. However, for the phenomenologically interesting case where the transverse radius is R-1˜TeV, we show that bulk standard model fields are not viable due to a resulting volume suppression of the gauge-coupling constants. A similar suppression occurs for the case of UV localization. Thus it seems that the standard model fields should be confined to the infrared brane in such spaces. Sterile fields and extended gauge sectors may propagate in the bulk, with the gauge-coupling volume suppression experienced by the latter motivating a weak coupling to standard model fields. We also discuss some issues regarding the effective 4D theory description in these spaces.

  9. Cangrelor: a novel P2Y12 receptor antagonist.

    PubMed

    Norgard, Nicholas B

    2009-08-01

    Antiplatelet therapy is critical in the prevention of thrombotic complications of acute coronary syndrome and percutaneous coronary interventions. Current antiplatelet agents (aspirin, clopidogrel and glycoprotein IIb/IIIa antagonists) have demonstrated the capacity to reduce major adverse cardiac events. However, these agents have limitations that compromise their clinical utility. The platelet P2Y12 receptor plays a central role in platelet function and is a focus in the development of antiplatelet therapies. Cangrelor is a potent, competitive inhibitor of the P2Y12 receptor that is administered by intravenous infusion and rapidly achieves near complete inhibition of ADP-induced platelet aggregation. This investigational drug has been studied for use during coronary procedures and the management of patients experiencing acute coronary syndrome and is undergoing evaluation for use in the prevention of perioperative stent thrombosis.

  10. UV photolysis for relieved inhibition of sulfadiazine (SD) to biomass growth.

    PubMed

    Pan, Shihui; Yan, Ning; Zhang, Yongming; Rittmann, Bruce E

    2015-05-01

    UV photolysis was used to relieve inhibition of biomass growth by sulfadiazine (SD), a broad-spectrum anti-microbial. To investigate the effects of SD on biomass growth, three substrates-glucose alone (G), glucose plus sulfadiazine (G+SD), and glucose plus photolyzed SD (G+PSD)-were used to culture the bacteria acclimated to glucose. The biomass was strongly inhibited when SD was added into the glucose solution, but inhibition was relieved to a significant degree when the SD was treated with UV irradiation as a pretreatment. The biomass growth kinetics were described well by the Monod model when glucose was used as a substrate alone, but the kinetics followed a hybrid Aiba model for non-competitive inhibition when SD was added to the solution. When photolyzed SD was added to glucose solution to replace original SD, the growth still followed Aiba inhibition, but inhibition was significantly relieved: the maximum specific growth rate (μ max) increased by 17 %, and the Aiba inhibition concentration increased by 60 %. Aniline, a major product of UV photolysis, supported the growth of the glucose-biodegrading bacteria. Thus, UV photolysis of SD significantly relieved inhibition by lowering the SD concentration and by generating a biodegradable product.

  11. Distribution of P2Y6 and P2Y12 receptor: their colocalization with calbindin, calretinin and nitric oxide synthase in the guinea pig enteric nervous system.

    PubMed

    Xiang, Zhenghua; Burnstock, Geoffrey

    2006-04-01

    The distribution of P2Y(6) and P2Y(12) receptor-immunoreactive (ir) neurons and fibers and their coexistence with calbindin, calretinin and nitric oxide synthase (NOS) has been investigated with single and double labeling immunostaining methods. The results showed that 30-36% of the ganglion cells in the myenteric plexus are strongly P2Y(6) receptor-ir neurons; they are distributed widely in the myenteric plexus of stomach, jejunum, ileum and colon, but not in the submucosal plexus, with a typical morphology of multipolar neurons with a long axon-like process. About 42-46% of ganglion cells in both the myenteric and submucosal plexuses show P2Y(12) receptor-ir. About 28-35% of P2Y(6) receptor-ir neurons were found to coexist with NOS and 41-47% of them coexist with calretinin, but there was no coexistence of P2Y(6) receptor-ir with calbindin. In contrast, all P2Y(12) receptor-ir neurons were immunopositive for calbindin, although occasionally P2Y(12) receptor-ir neurons without calbindin immunoreactivity were found, while none of the P2Y(12) receptor-ir neurons were found to coexist with calretinin or NOS in the gastrointestinal system of guinea pig. The P2Y(12) receptor-ir neurons coexpressing calbindin-ir in the small intestine are Dogiel type II/AH, intrinsic primary afferent neurons.

  12. Nucleotides Acting at P2Y Receptors: Connecting Structure and Function.

    PubMed

    Jacobson, Kenneth A; Paoletta, Silvia; Katritch, Vsevolod; Wu, Beili; Gao, Zhan-Guo; Zhao, Qiang; Stevens, Raymond C; Kiselev, Evgeny

    2015-08-01

    Eight G protein-coupled P2Y receptor (P2YR) subtypes are important physiologic mediators. The human P2YRs are fully activated by ATP (P2Y2 and P2Y11), ADP (P2Y1, P2Y12, and P2Y13), UTP (P2Y2 and P2Y4), UDP (P2Y6 and P2Y14), and UDP glucose (P2Y14). Their structural elucidation is progressing rapidly. The X-ray structures of three ligand complexes of the Gi-coupled P2Y12R and two of the Gq-coupled P2Y1Rs were recently determined and will be especially useful in structure-based ligand design at two P2YR subfamilies. These high-resolution structures, which display unusual binding site features, complement mutagenesis studies for probing ligand recognition and activation. The structural requirements for nucleotide agonist recognition at P2YRs are relatively permissive with respect to the length of the phosphate moiety, but less so with respect to base recognition. Nucleotide-like antagonists and partial agonists are also known for P2Y1, P2Y2, P2Y4, and P2Y12Rs. Each P2YR subtype has the ability to be activated by structurally bifunctional agonists, such as dinucleotides, typically, dinucleoside triphosphates or tetraphosphates, and nucleoside polyphosphate sugars (e.g., UDP glucose) as well as the more conventional mononucleotide agonists. A range of dinucleoside polyphosphates, from triphosphates to higher homologs, occurs naturally. Earlier modeling predictions of the P2YRs were not very accurate, but recent findings have provided much detailed structural insight into this receptor family to aid in the rational design of new drugs.

  13. Nucleotides Acting at P2Y Receptors: Connecting Structure and Function

    PubMed Central

    Paoletta, Silvia; Katritch, Vsevolod; Wu, Beili; Gao, Zhan-Guo; Zhao, Qiang; Stevens, Raymond C.; Kiselev, Evgeny

    2015-01-01

    Eight G protein–coupled P2Y receptor (P2YR) subtypes are important physiologic mediators. The human P2YRs are fully activated by ATP (P2Y2 and P2Y11), ADP (P2Y1, P2Y12, and P2Y13), UTP (P2Y2 and P2Y4), UDP (P2Y6 and P2Y14), and UDP glucose (P2Y14). Their structural elucidation is progressing rapidly. The X-ray structures of three ligand complexes of the Gi-coupled P2Y12R and two of the Gq-coupled P2Y1Rs were recently determined and will be especially useful in structure-based ligand design at two P2YR subfamilies. These high-resolution structures, which display unusual binding site features, complement mutagenesis studies for probing ligand recognition and activation. The structural requirements for nucleotide agonist recognition at P2YRs are relatively permissive with respect to the length of the phosphate moiety, but less so with respect to base recognition. Nucleotide-like antagonists and partial agonists are also known for P2Y1, P2Y2, P2Y4, and P2Y12Rs. Each P2YR subtype has the ability to be activated by structurally bifunctional agonists, such as dinucleotides, typically, dinucleoside triphosphates or tetraphosphates, and nucleoside polyphosphate sugars (e.g., UDP glucose) as well as the more conventional mononucleotide agonists. A range of dinucleoside polyphosphates, from triphosphates to higher homologs, occurs naturally. Earlier modeling predictions of the P2YRs were not very accurate, but recent findings have provided much detailed structural insight into this receptor family to aid in the rational design of new drugs. PMID:25837834

  14. MODELLING THE P2Y PURINOCEPTOR USING RHODOPSIN AS TEMPLATE

    PubMed Central

    Van Rhee, A. Michiel; Fischer, Bilha; Van Galen, Philip J. M.; Jacobson, Kenneth A.

    2012-01-01

    The P2Y1 purinoceptor cloned from chick brain (Webb, T. et al. (1993) FEBS Lett., 324, 219–225) is a 362 amino acid, 41 kDa protein. To locate residues tentatively involved in ligand recognition a molecular model of the P2Y purinoceptor has been constructed. The model was based on the primary sequence and structural homology with the G-protein coupled photoreceptor rhodopsin, in analogy to the method proposed by Ballesteros and Weinstein ((1995) Meth. Neurosci. 25, 366–428). Transmembrane helices were constructed from the amino acid sequence, minimized individually, and positioned in a helical bundle. The helical bundle was then minimized using the Amber forcefield in Discover (BIOSYM Technologies) to obtain the final model. Several residues that have been shown to be critical in ligand binding in other GPCRs are conserved in the P2Y1 purinoceptor. According to our model the side chains of these conserved residues are facing the internal cleft in which ligand binding likely occurs. The model also suggests four basic residues (H121 in TM3, H266 and K269 in TM6 and R299 in TM7) near the extracellular surface that might be involved in ligand binding. These basic residues might be essential in coordinating the triphosphate chain of the endogenous ligand adenosine 5′-triphosphate (ATP). Potential binding sites for agonists have been explored by docking several derivatives (including newly synthesized N6-derivatives) into the model. The N6-phenylethyl substituent is tolerated pharmacologically, and in our model this substituent occupies a region predominantly defined by aromatic residues such as F51 (TM1), Y100 (TM2) and F120 (TM3). The dimethylated analogue of ATP, N6,N6-dimethyl-adenosine 5′-triphosphate, is less well tolerated pharmacologically, and our model predicts that the attenuated activity is due to interference with hydrogen bonding capacity to Q296 (TM7). PMID:8872457

  15. 5 7 Fe Mössbauer spectroscopic studies of single-crystalline K x Fe2- y S 2 and K x Fe2- y Se 2

    NASA Astrophysics Data System (ADS)

    Tsuchiya, Yuu; Ikeda, Shugo; Kobayashi, Hisao

    2016-12-01

    We have investigated the physical properties of single-crystalline K x Fe2- y S 2 and K x Fe2- y Se2 samples using 57Fe Mössbauer spectroscopy. The observed 57Fe Mössbauer spectra were reconstructed using a major antiferromagnetic ordered K2Fe4Se5 phase and a minor paramagnetic phase down to 5 K, despite being superconducting below 32.2 K in K x Fe2- y Se2. The analysis of 57Fe Mössbauer spectrum for K x Fe2- y S 2 at 290 K confirms the presence of a major antiferromagnetic ordered K2Fe4 S 5 phase and a minor paramagnetic phase in the K x Fe2- y S 2 single crystal. The derived hyperfine interaction parameters of the paramagnetic phase in K x Fe2- y S 2 suggest that the microstructure of this phase in K x Fe2- y S 2 is similar to that of the superconducting phase in K x Fe2- y Se2 although the K x Fe2- y S 2 single crystals exhibit no superconductivity down to 5 K.

  16. P2Y2R Deficiency Attenuates Experimental Autoimmune Uveitis Development

    PubMed Central

    Relvas, Lia Judice M.; Makhoul, Maya; Dewispelaere, Remi; Caspers, Laure; Communi, Didier; Boeynaems, Jean-Marie; Robaye, Bernard; Bruyns, Catherine; Willermain, François

    2015-01-01

    We aimed to study the role of the nucleotide receptor P2Y2R in the development of experimental autoimmune uveitis (EAU). EAU was induced in P2Y2+/+ and P2Y2-/- mice by immunization with IRBP peptide or by adoptive transfer of in vitro restimulated semi-purified IRBP-specific enriched T lymphocytes from spleens and lymph nodes isolated from native C57Bl/6 or P2Y2+/+ and P2Y2-/- immunized mice. Clinical and histological scores were used to grade disease severity. Splenocytes and lymph node cell phenotypes were analyzed using flow cytometry. Semi-purified lymphocytes and MACS-purified CD4+ T lymphocytes from P2Y2+/+ and P2Y2-/- immunized mice were tested for proliferation and cytokine secretion. Our data show that clinical and histological scores were significantly decreased in IRBP-immunized P2Y2-/- mice as in P2Y2-/- mice adoptively transfered with enriched T lymphocytes from C57Bl/6 IRBP-immunized mice. In parallel, naïve C57Bl/6 mice adoptively transferred with T lymphocytes from P2Y2-/- IRBP-immunized mice also showed significantly less disease. No differences in term of spleen and lymph node cell recruitment or phenotype appeared between P2Y2-/- and P2Y2+/+ immunized mice. However, once restimulated in vitro with IRBP, P2Y2-/- T cells proliferate less and secrete less cytokines than the P2Y2+/+ one. We further found that antigen-presenting cells of P2Y2-/- immunized mice were responsible for this proliferation defect. Together our data show that P2Y2-/- mice are less susceptible to mount an autoimmune response against IRBP. Those results are in accordance with the danger model, which makes a link between autoreactive lymphocyte activation, cell migration and the release of danger signals such as extracellular nucleotides. PMID:25692550

  17. Expression of P2Y receptors in cell lines derived from the human lung.

    PubMed

    Communi, D; Paindavoine, P; Place, G A; Parmentier, M; Boeynaems, J M

    1999-05-01

    1. Northern blotting experiments have been performed with RNA extracted from several cell lines derived from the human lung in order to detect P2Y1, P2Y2, P2Y4 and P2Y6 mRNA. We have investigated the 1HAEo- and 16HBE14o- epithelial cell lines derived from the airway epithelium, the A549 cell line displaying properties of type II alveolar epithelial cells, the CALU-3 serous cells, the 6CFSMEo- submucosal cells and the HASMSC1 airway smooth muscle cells. We have also evaluated one pancreatic epithelial cell line called CFPAC-1. These experiments revealed that P2Y2 and P2Y6 mRNA are co-expressed in the IHAEo-, 16HBE14o- and A549 epithelial cell lines. The CFPAC-1 pancreatic cell line was strongly positive for the P2Y2 receptor. No signal was obtained for the P2Y1 and P2Y4 receptors. 2. We have then performed RT-PCR experiments with specific oligonucleotides of these last two P2Y receptors with the RNA used for the Northern blotting experiments. P2Y4 mRNA was detected in five cell lines: 1HAEo-, 16HBE14o-, 6CFSMEo-, HASMSC1 and CFPAC-1. P2Y1 mRNA was only detected in the CALU-3 cell line. 3. Inositol trisphosphates assays have identified a response typical of the P2Y2 receptor in the 1HAEo- and the 16HBE14o- airway epithelial cell lines which co-express P2Y2 and P2Y6 mRNA. By contrast, the 6CFSMEo- submucosal cells expressed a UTP-specific response which displayed pharmacological characteristics compatible with the human P2Y4 receptor: in particular, there was no response to UDP or ATP and the UTP effect was totally inhibited by pertussis toxin.

  18. Elastic-plastic deformations of a beam with the SD-effect

    SciTech Connect

    Pavilaynen, Galina V.

    2015-03-10

    The results for the bending of a cantilever beam with the SD-effect under a concentrated load are discussed. To solve this problem, the standard Bernoulli-Euler hypotheses for beams and the Ilyushin model of perfect plasticity are used. The problem is solved analytically for structural steel A40X. The SD-effect for elastic-plastic deformations is studied. The solutions for beam made of isotropic material and material with the SD-effect are compared.

  19. Self-Concept of Children with Cerebral Palsy Compared with that of Children without Impairment

    ERIC Educational Resources Information Center

    Shields, Nora; Loy, Yijun; Murdoch, Alison; Taylor, Nicholas F.; Dodd, Karen J

    2007-01-01

    This study examined whether the self-concept of children with cerebral palsy (CP) differed from that of children without impairment. Forty-seven children (24 males, 23 females; mean age 11y 8mo [SD 2y 6mo]) with spastic diplegia or hemiplegia were matched with children without impairment. The level of disability of the children with CP was…

  20. Determinants of Intensity of Participation in Leisure and Recreational Activities by Children with Cerebral Palsy

    ERIC Educational Resources Information Center

    Palisano, Robert J.; Chiarello, Lisa A.; Orlin, Margo; Oeffinger, Donna; Polansky, Marcy; Maggs, Jill; Bagley, Anita; Gorton, George

    2011-01-01

    Aim: To test a model of child, family, and service determinants of intensity of participation in leisure and recreational activities by children with cerebral palsy (CP). Method: Participants were 288 children with CP, age range 6 to 12 years (mean 9y 8mo, SD 2y), and their parents from seven children's hospitals. The sample comprised 166 (57.6%)…

  1. How UV photolysis accelerates the biodegradation and mineralization of sulfadiazine (SD).

    PubMed

    Pan, Shihui; Yan, Ning; Liu, Xinyue; Wang, Wenbing; Zhang, Yongming; Liu, Rui; Rittmann, Bruce E

    2014-11-01

    Sulfadiazine (SD), one of broad-spectrum antibiotics, exhibits limited biodegradation in wastewater treatment due to its chemical structure, which requires initial mono-oxygenation reactions to initiate its biodegradation. Intimately coupling UV photolysis with biodegradation, realized with the internal loop photobiodegradation reactor, accelerated SD biodegradation and mineralization by 35 and 71 %, respectively. The main organic products from photolysis were 2-aminopyrimidine (2-AP), p-aminobenzenesulfonic acid (ABS), and aniline (An), and an SD-photolysis pathway could be identified using C, N, and S balances. Adding An or ABS (but not 2-AP) into the SD solution during biodegradation experiments (no UV photolysis) gave SD removal and mineralization rates similar to intimately coupled photolysis and biodegradation. An SD biodegradation pathway, based on a diverse set of the experimental results, explains how the mineralization of ABS and An (but not 2-AP) provided internal electron carriers that accelerated the initial mono-oxygenation reactions of SD biodegradation. Thus, multiple lines of evidence support that the mechanism by which intimately coupled photolysis and biodegradation accelerated SD removal and mineralization was through producing co-substrates whose oxidation produced electron equivalents that stimulated the initial mono-oxygenation reactions for SD biodegradation.

  2. Cytokeratin 8 in Association with sdLDL and ELISA Development

    PubMed Central

    Ashmaig, Mohmed

    2015-01-01

    Background: Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide. Cytokeratins (CKs) which may also be expressed in vascular smooth muscle cells (SMCs) are generally considered to be markers for the differentiation of epithelial cells. Small, dense, low-density lipoprotein (sdLDL) particles, also termed LDL-IV, independently predict risk of CVD. Aims: The aims of this study were to develop an analytical method, apart from ultracentrifugation capable of isolating sdLDL in order to study any associated proteins. Materials and Methods: Using modified gradient gel electrophoresis (GGE), de-identified sdLDL-enriched plasma was used to physically elute and isolate sdLDL particles. To validate the finding, additional plasma from 77 normal and 48 higher risk subjects were used to measure sdLDL particles and CK8. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting method were used to identify the characteristics of proteins associated with sdLDL. An enzyme-linked immunosorbent assay (ELISA) method was developed and validated for the measurement of CK8 in plasma. Results: The validation of the CK8 ELISA method showed good analytical performance. The isolated sdLDL particles were verified with nondenaturing GGE with the apolipoprotein B component confirmed by Western immunoblotting. Confirmed by SDS-PAGE and Western immunoblotting, CK8 was associated with sdLDL. Two-tailed statistical analysis showed that CK8 and sdLDL particles were significantly higher in the high-risk CVD group compared to control group (P < 0.01 and P < 0.01, respectively). Conclusion: This study reports a novel association between CK8 and sdLDL in individuals with CVD who have a predominance of sdLDL. PMID:26713292

  3. Synthesis and Potency of Novel Uracil Nucleotides and Derivatives as P2Y2 and P2Y6 Receptor Agonists

    PubMed Central

    Ko, Hyojin; Carter, Rhonda L.; Cosyn, Liesbet; Petrelli, Riccardo; de Castro, Sonia; Besada, Pedro; Zhou, Yixing; Cappellacci, Loredana; Franchetti, Palmarisa; Grifantini, Mario; Van Calenbergh, Serge; Harden, T. Kendall; Jacobson, Kenneth A.

    2008-01-01

    The phosphate, uracil, and ribose moieties of uracil nucleotides were varied structurally for evaluation of agonist activity at the human P2Y2, P2Y4, and P2Y6 receptors. The 2-thio modification, found previously to enhance P2Y2 receptor potency, could be combined with other favorable modifications to produce novel molecules that exhibit high potencies and receptor selectivities. Phosphonomethylene bridges introduced for stability in analogues of UDP, UTP and uracil dinucleotides markedly reduced potency. Truncation of dinucleotide agonists of the P2Y2 receptor, in the form of Up4-sugars, indicated that a terminal uracil ring is not essential for moderate potency at this receptor and that specific SAR patterns are observed at this distal end of the molecule. Key compounds reported in this study include: 9, α,β-methylene-UDP, a P2Y6 receptor agonist; 30, Up4-phenyl ester and 34, Up4-[1]glucose, selective P2Y2 receptor agonists; 43, the 2-thio analogue of INS37217 (P1-(uridine 5′)-P4- (2′-deoxycytidine 5′) tetraphosphate), a potent and selective P2Y2 receptor agonist. PMID:18514530

  4. MEGARA Optics: stain removal in PBM2Y prisms

    NASA Astrophysics Data System (ADS)

    Aguirre-Aguirre, D.; Izazaga-Pérez, R.; Villalobos-Mendoza, B.; Carrasco, E.; Gil de Paz, A.; Gallego, J.; Iglesias, J.

    2017-01-01

    MEGARA is the new integral-field and multi-object optical spectrograph for the GTC. For medium and high resolution, the dispersive elements are volume phase holographic gratings, sandwiched between two flat windows and two prisms of high optical precision. The prisms are made of Ohara PBM2Y optical glass. After the prisms polishing process, some stains appeared on the surfaces. For this, in this work is shown the comparative study of five different products (muriatic acid, paint remover, sodium hydroxide, aqua regia and rare earth liquid polish) used for trying to eliminate the stains of the HR MEGARA prisms. It was found that by polishing with the hands the affected area, and using a towel like a kind of pad, and polish during five minutes using rare earth, the stains disappear completely affecting only a 5% the rms of the surface quality. Not so the use of the other products that did not show any apparent result.

  5. P2Y1 and P2Y2 receptor distribution varies along the human placental vascular tree: role of nucleotides in vascular tone regulation

    PubMed Central

    Buvinic, Sonja; Poblete, M Inés; Donoso, M Verónica; Delpiano, Ana María; Briones, René; Miranda, Ramiro; Huidobro-Toro, J Pablo

    2006-01-01

    The expression of purinergic P2Y receptors (P2YRs) along the cord, superficial chorionic vessels and cotyledons of the human placenta was analysed and functional assays were performed to determine their vasomotor activity. Immunoblots for the P2Y1R and P2Y2R revealed a 6- to 8-fold increase in receptor expression from the cord to the chorionic or cotyledon vessels. In the cord and chorionic vessels the receptor distribution was mainly in the smooth muscle, whereas in the cotyledon vessels these receptors were equally distributed between the endothelium and smooth muscle cells. An exception was the P2Y2R at the umbilical artery, which was distributed as in the cotyledon. mRNA coding for the P2Y1R and P2Y2R were detected by RT-PCR and the mRNA coding for the P2Y4R, P2Y6R and P2Y11R was also identified. Application of 2-MeSADP and uridine triphosphate (UTP), preferential P2Y1R and P2Y2R ligands, respectively, resulted in contraction of isolated rings from umbilical and chorionic vessels. The vasoconstriction was blocked in a concentration-dependent manner by 10–100 nm indomethacin or 10 nm GR32191, suggesting the involvement of thromboxane receptors. MRS 2179, a selective P2Y1R antagonist, reduced the 2-MeSADP- but not the UTP-evoked contractions. Perfusion of cotyledons with 2-MeSADP or UTP evoked concentration-dependent reductions in perfusion pressure mediated by the NO–cGMP pathway. Blockade of NO synthase abolished the vasodilatation and the rise in luminal NO elicited by either agonist. MRS 2179 antagonized the dilatation and rise in luminal NO evoked by 2-MeSADP but not by UTP. In summary, P2Y1R and P2Y2R are unevenly distributed along the human placental vascular tree; both receptors are coupled to different signalling pathways in the cord/chorionic vessels versus the cotyledon leading to opposing vasomotor responses. PMID:16543271

  6. 77 FR 68716 - Proposed Amendment of Class E Airspace; Hot Springs, SD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-16

    ... Federal Aviation Administration 14 CFR Part 71 Proposed Amendment of Class E Airspace; Hot Springs, SD...: This action proposes to amend Class E airspace at Hot Springs, SD. Additional controlled airspace is necessary to accommodate new Standard Instrument Approach Procedures (SIAPs) at Hot Springs...

  7. 78 FR 14911 - Amendment of Class E Airspace; Hot Springs, SD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-08

    ... Federal Aviation Administration 14 CFR Part 71 Amendment of Class E Airspace; Hot Springs, SD AGENCY... airspace at Hot Springs, SD. Additional controlled airspace is necessary to accommodate new Area Navigation (RNAV) Standard Instrument Approach Procedures at Hot Springs Municipal Airport. The FAA is taking...

  8. 32. DETAIL OF WALL SHOWN IN SD231. BEHIND WALL FRAMING ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    32. DETAIL OF WALL SHOWN IN SD-2-31. BEHIND WALL FRAMING IS SAMPLING ROOM WITH WOOD SAMPLING ELEVATOR. CRUSHED OXIDIZED ORE BIN ON LEFT (SOUTH). - Bald Mountain Gold Mill, Nevada Gulch at head of False Bottom Creek, Lead, Lawrence County, SD

  9. 76 FR 43610 - Proposed Amendment of Class E Airspace; Spearfish, SD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-21

    ... Ice Field. The geographic coordinates of the airport also would be updated. The FAA is taking this... instrument approach procedures at Black Hills Airport-Clyde Ice Field, Spearfish, SD. Controlled airspace is... authority as it would amend controlled airspace at Black Hills Airport-Clyde Ice Field, Spearfish, SD....

  10. How to Make a Singleton sdB Star via Accelerated Stellar Evolution

    NASA Astrophysics Data System (ADS)

    Clausen, Drew; Wade, Richard A.

    2011-06-01

    Many hot subdwarf B stars (sdBs) are in close binaries, and the favored formation channels for subdwarfs rely on mass transfer in a binary system to strip a core He-burning star of its envelope. However, these channels cannot account for sdBs that have been observed in long-period binaries nor the narrow mass distribution of isolated (or "singleton") sdBs. We propose a new formation channel involving the merger of a helium white dwarf and a low-mass, hydrogen-burning star, which addresses these issues. Hierarchical triples whose inner binaries merge and form sdBs by this process could explain the observed long-period subdwarf+main-sequence binaries. This process would also naturally explain the observed slow rotational speeds of singleton sdBs. We also briefly discuss the implications of this formation channel for extreme horizontal branch morphology in globular clusters and the UV upturn in elliptical galaxies.

  11. Mineralogic variation in drill holes USW NRG-6, NRG-7/7a, SD-7, SD-9, SD-12, and UZ{number_sign}14: New data from 1996--1997 analyses

    SciTech Connect

    Chipera, S.J.; Vaniman, D.T.; Bish, D.L.; Carey, J.W.

    1997-05-30

    New quantitative X-ray diffraction (QXRD) mineralogic data have been obtained for samples from drill holes NRG-6, NRG-7/7A, SD-7, SD-9, SD- 12, and UZ{number_sign}14. In addition, new QXRD analyses were obtained on samples located in a strategic portion of drill hole USW H-3. These data improve our understanding of the mineral stratigraphy at Yucca Mountain, and they further constrain the 3-D Mineralogic Model of Yucca Mountain. Some of the unexpected findings include the occurrence of the zeolite chabazite in the vitric zone of USW SD-7, broad overlap of vitric and zeolitic horizons (over vertical ranges up to 70 m), and the previously unrecognized importance of the bedded tuft beneath the Calico Hills Formation as a subunit with generally more extensive zeolitization than the Calico Hills Formation in the southern part of the potential repository area. Reassessment of data from drill hole USW H-5 suggests that the zeolitization of this bedded unit occurs in the northwestern part of the repository exploration block as well. Further analyses of the same interval in USW H-3, however, have not permitted the same conclusion to be reached for the southwestern part of the repository block because of the much poorer quality of the cuttings in H-3 compared with those from H-5. X-ray fluorescence (XRF) chemical data for drill holes USW SD-7, 9, and 12 show that the zeolitic horizons provide a >10 million year record of retardation of Sr transport, although the data also show that simplistic models of one-dimensional downward flow in the unsaturated zone (UZ) are inadequate. Complex interstratification of zeolites and glass, with highly variable profiles between drill cores, point to remaining problems in constructing detailed mineral stratigraphies. However, the new data in this report provide important information for constructing bounding models of zeolite stratigraphy for transport calculations.

  12. 4-Alkyloxyimino Derivatives of Uridine-5′-triphosphate: Distal Modification of Potent Agonists as a Strategy for Molecular Probes of P2Y2, P2Y4, and P2Y6 Receptors

    PubMed Central

    2015-01-01

    Extended N4-(3-arylpropyl)oxy derivatives of uridine-5′-triphosphate were synthesized and potently stimulated phospholipase C stimulation in astrocytoma cells expressing G protein-coupled human (h) P2Y receptors (P2YRs) activated by UTP (P2Y2/4R) or UDP (P2Y6R). The potent P2Y4R-selective N4-(3-phenylpropyl)oxy agonist was phenyl ring-substituted or replaced with terminal heterocyclic or naphthyl rings with retention of P2YR potency. This broad tolerance for steric bulk in a distal region was not observed for dinucleoside tetraphosphate agonists with both nucleobases substituted. The potent N4-(3-(4-methoxyphenyl)-propyl)oxy analogue 19 (EC50: P2Y2R, 47 nM; P2Y4R, 23 nM) was functionalized for chain extension using click tethering of fluorophores as prosthetic groups. The BODIPY 630/650 conjugate 28 (MRS4162) exhibited EC50 values of 70, 66, and 23 nM at the hP2Y2/4/6Rs, respectively, and specifically labeled cells expressing the P2Y6R. Thus, an extended N4-(3-arylpropyl)oxy group accessed a structurally permissive region on three Gq-coupled P2YRs, and potency and selectivity were modulated by distal structural changes. This freedom of substitution was utilized to design of a pan-agonist fluorescent probe of a subset of uracil nucleotide-activated hP2YRs. PMID:24712832

  13. Weight-loss diets and 2-y changes in circulating amino acids in 2 randomized intervention trials123

    PubMed Central

    Zheng, Yan; Ceglarek, Uta; Huang, Tao; Li, Lerong; Rood, Jennifer; Ryan, Donna H; Bray, George A; Sacks, Frank M; Schwarzfuchs, Dan; Thiery, Joachim; Shai, Iris; Qi, Lu

    2016-01-01

    Background: Circulating amino acids, such as branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs), have been associated with diabetes risk; however, little is known about how a long-term dietary intervention for weight loss affects circulating amino acids. Objectives: We examined the effects of weight-loss diets on long-term changes in plasma amino acids and the associations of these changes with weight loss and the improvement of insulin resistance. Design: We repeatedly measured plasma amino acid profiles over 2 y in overweight or obese participants from 2 randomized, dietary intervention, weight-loss trials [774 subjects from the POUNDS LOST (Preventing Overweight Using Novel Dietary Strategies Trial) and 318 subjects from the DIRECT (Dietary Intervention Randomized Controlled Trial)]. Results: Intervention diets consistently lowered most of the amino acid concentrations, including BCAAs and AAAs, in both trials. In the POUNDS LOST, average-protein diets (15% of daily energy) showed stronger effects than did high-protein diets (25% of daily energy) on reducing concentrations of the diabetes-associated BCAA valine at 6 mo independent of the weight change. In both trials, weight loss was directly related to the concurrent reduction of the BCAAs leucine and isoleucine, the AAAs tyrosine and phenylalanine, and 4 other amino acids. For example, per kilogram of weight loss, there was a 0.04-SD decrease in log tyrosine (∼0.6 μmol/L) in both trials. In addition, we showed that reductions in alanine and the AAA tyrosine were significantly related to improved insulin resistance (measured with the use of the homeostasis model assessment of insulin resistance), independent of weight loss, in both trials (both P < 0.05). For example, per 1-SD decrease in log tyrosine (∼17 μmol/L), there was a 0.04-SD (∼3%) improvement in insulin resistance in the POUNDS LOST and a 0.13-SD (∼8%) improvement in insulin resistance in the DIRECT. Conclusion: Our findings

  14. 78 FR 73751 - Proposed Amendment of Class E Airspace; Philip, SD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-09

    ... Federal holidays. An informal docket may also be examined during normal business hours at the office of... areas extending upward from 700 feet or more above the surface of the earth. * * * * * AGL SD E5...

  15. P2Y Receptors in the Mammalian Nervous System: Pharmacology, Ligands and Therapeutic Potential

    PubMed Central

    Weisman, Gary A.; Woods, Lucas T.; Erb, Laurie; Seye, Cheikh I.

    2015-01-01

    P2Y receptors for extracellular nucleotides are coupled to activation of a variety of G proteins and stimulate diverse intracellular signaling pathways that regulate functions of cell types that comprise the central nervous system (CNS). There are 8 different subtypes of P2Y receptor expressed in cells of the CNS that are activated by a select group of nucleotide agonists. Here, the agonist selectivity of these 8 P2Y receptor subtypes is reviewed with an emphasis on synthetic agonists with high potency and resistance to degradation by extracellular nucleotidases that have potential applications as therapeutic agents. In addition, the recent identification of a wide variety of subtype-selective antagonists is discussed, since these compounds are critical for discerning cellular responses mediated by activation of individual P2Y receptor subtypes. The functional expression of P2Y receptor subtypes in cells that comprise the CNS is also reviewed and the role of each subtype in the regulation of physiological and pathophysiological responses is considered. Other topics include the role of P2Y receptors in the regulation of blood-brain barrier integrity and potential interactions between different P2Y receptor subtypes that likely impact tissue responses to extracellular nucleotides in the CNS. Overall, current research suggests that P2Y receptors in the CNS regulate repair mechanisms that are triggered by tissue damage, inflammation and disease and thus P2Y receptors represent promising targets for the treatment of neurodegenerative diseases. PMID:22963441

  16. Molecular Characterization of a Novel Bovine Viral Diarrhea Virus Isolate SD-15

    PubMed Central

    Zhu, Lisai; Lu, Haibing; Cao, Yufeng; Gai, Xiaochun; Guo, Changming; Liu, Yajing; Liu, Jiaxu; Wang, Xinping

    2016-01-01

    As one of the major pathogens, bovine viral diarrhea virus caused a significant economic loss to the livestock industry worldwide. Although BVDV infections have increasingly been reported in China in recent years, the molecular aspects of those BVDV strains were barely characterized. In this study, we reported the identification and characterization of a novel BVDV isolate designated as SD-15 from cattle, which is associated with an outbreak characterized by severe hemorrhagic and mucous diarrhea with high morbidity and mortality in Shandong, China. SD-15 was revealed to be a noncytopathic BVDV, and has a complete genomic sequence of 12,285 nucleotides that contains a large open reading frame encoding 3900 amino acids. Alignment analysis showed that SD-15 has 93.8% nucleotide sequence identity with BVDV ZM-95 isolate, a previous BVDV strain isolated from pigs manifesting clinical signs and lesions resembling to classical swine fever. Phylogenetic analysis clustered SD-15 to a BVDV-1m subgenotype. Analysis of the deduced amino acid sequence of glycoproteins revealed that E2 has several highly conserved and variable regions within BVDV-1 genotypes. An additional N-glycosylation site (240NTT) was revealed exclusively in SD-15-encoded E2 in addition to four potential glycosylation sites (Asn-X-Ser/Thr) shared by all BVDV-1 genotypes. Furthermore, unique amino acid and linear epitope mutations were revealed in SD-15-encoded Erns glycoprotein compared with known BVDV-1 genotype. In conclusion, we have isolated a noncytopathic BVDV-1m strain that is associated with a disease characterized by high morbidity and mortality, revealed the complete genome sequence of the first BVDV-1m virus originated from cattle, and found a unique glycosylation site in E2 and a linear epitope mutation in Erns encoded by SD-15 strain. Those results will broaden the current understanding of BVDV infection and lay a basis for future investigation on SD-15-related pathogenesis. PMID:27764206

  17. The influence of variation in the P2Y12 receptor gene on in vitro platelet inhibition with the direct P2Y12 antagonist cangrelor.

    PubMed

    Bouman, H J; van Werkum, J W; Rudez, G; Leebeek, F W G; Kruit, A; Hackeng, C M; Ten Berg, J M; de Maat, M P M; Ruven, H J T

    2010-02-01

    Novel P2Y12 inhibitors are in development to overcome the occurrence of atherothrombotic events associated with poor responsiveness to the widely used P2Y12 inhibitor clopidogrel. Cangrelor is an intravenously administered P2Y12 inhibitor that does not need metabolic conversion to an active metabolite for its antiplatelet action, and as a consequence exhibits a more potent and consistent antiplatelet profile as compared to clopidogrel. It was the objective of this study to determine the contribution of variation in the P2Y12 receptor gene to platelet aggregation after in vitro partial P2Y12 receptor blockade with the direct antagonist cangrelor. Optical aggregometry was performed at baseline and after in vitro addition of 0.05 and 0.25 microM cangrelor to the platelet-rich plasma of 254 healthy subjects. Five haplotype-tagging (ht)-SNPs covering the entire P2Y12 receptor gene were genotyped (rs6798347C>t, rs6787801T>c, rs9859552C>a, rs6801273A>g and rs2046934T>c [T744C]) and haplotypes were inferred. The minor c allele of SNP rs6787801 was associated with a 5% lower 20 microM ADP-induced peak platelet aggregation (0.05 microM cangrelor, p<0.05). Aa homozygotes for SNP rs9859552 showed 20% and 17% less inhibition of platelet aggregation with cangrelor when compared to CC homozygotes (0.05 and 0.25 microM cangrelor respectively; p<0.05). Results of the haplotype analyses were consistent with those of the single SNPs. Polymorphisms of the P2Y12 receptor gene contribute significantly to the interindividual variability in platelet inhibition after partial in vitro blockade with the P2Y12 antagonist cangrelor.

  18. SD0006: A Potent, Selective and Orally Available Inhibitor of p38 Kinase

    PubMed Central

    Burnette, Barry L.; Selness, Shaun; Devraj, Raj; Jungbluth, Gail; Kurumbail, Ravi; Stillwell, Loreen; Anderson, Gary; Mnich, Stephen; Hirsch, Jeffrey; Compton, Robert; De Ciechi, Pamela; Hope, Heidi; Hepperle, Michael; Keith, Robert H.; Naing, Win; Shieh, Huey; Portanova, Joseph; Zhang, Yan; Zhang, Jian; Leimgruber, Richard M.; Monahan, Joseph

    2009-01-01

    SD0006 is a diarylpyrazole that was prepared as an inhibitor of p38 kinase-α (p38α). In vitro, SD0006 was selective for p38α kinase over 50 other kinases screened (including p38γ and p38δ with modest selectivity over p38β). Crystal structures with p38α show binding at the ATP site with additional residue interactions outside the ATP pocket unique to p38α that can confer advantages over other ATP competitive inhibitors. Direct correlation between inhibition of p38α activity and that of lipopolysaccharide-stimulated TNFα release was established in cellular models and in vivo, including a phase 1 clinical trial. Potency (IC50) for inhibiting tumor necrosis factor-α (TNFα) release, in vitro and in vivo, was <200 nmol/l. In vivo, SD0006 was effective in the rat streptococcal-cell-wall-induced arthritis model, with dramatic protective effects on paw joint integrity and bone density as shown by radiographic analysis. In the murine collagen-induced arthritis model, equivalence was demonstrated to anti-TNFα treatment. SD0006 also demonstrated good oral anti-inflammatory efficacy with excellent cross-species correlation between the rat, cynomolgus monkey, and human. SD0006 suppressed expression of multiple proinflammatory proteins at both the transcriptional and translational levels. These properties suggest SD0006 could provide broader therapeutic efficacy than cytokine-targeted monotherapeutics. PMID:19590255

  19. [Usefulness of a new sheet-like apparatus (SD-101) for screening of sleep apnea syndrome].

    PubMed

    Iwasaki, Yoko; Fujimoto, Keisaku; Honda, Takayuki; Urushihata, Kazutoshi; Komatsu, Yoshimichi; Asawa, Teruko; Uhara, Miho; Ii, Asami; Yamauchi, Kazuyoshi; Katsuyama, Tsutomu

    2006-07-01

    Polysomnography (PSG) is the gold standard for the diagnosis of sleep apnea syndrome (SAS). However, PSG is not suitable as a first-line examination for all people suspected as having SAS because PSG requires hospitalization. Therefore, it is hoped that a simple examination can be developed which is available for use in the home. The present study evaluated the usefulness of a new sheet-like apparatus (SD-101) which is equipped with 162 pressure sensors for SAS diagnosis. One hundred patients hospitalized for PSG were simultaneously examined using the SD-101, and 25 patients, who underwent both PSG and SAS screening with MORPHEUS R, were also studied. The SD-101 is inserted between a sheet and the bed, and detects pressure from many points on the patient's body as it presses against the bed. Continuous changes of these pressure points are converted to respiratory movement. A very close correlation was seen between the apnea hypopnea index of PSG and a respiratory disturbance index of SD-101 (r=0.90), although there was a significant but lower correlation between data obtained PSG and MORPHEUS R(r=0.84). The sensitivity and specificity of the examination using SD-101 were 98.2% and 55.8%, respectively. These findings suggested that a new apparatus, SD-101, may be useful for the screening of SAS.

  20. Microglial P2Y12 Receptors Regulate Microglial Activation and Surveillance during Neuropathic Pain

    PubMed Central

    Gu, Nan; Eyo, Ukpong B.; Murugan, Madhuvika; Peng, Jiyun; Matta, Sanjana; Dong, Hailong; Wu, Long-Jun

    2016-01-01

    Microglial cells are critical in the pathogenesis of neuropathic pain and several microglial receptors have been proposed to mediate this process. Of these receptors, the P2Y12 receptor is a unique purinergic receptor that is exclusively expressed by microglia in the central nervous system (CNS). In this study, we set forth to investigate the role of P2Y12 receptors in microglial electrophysiological and morphological (static and dynamic) activation during spinal nerve transection (SNT)-induced neuropathic pain in mice. First, we found that a genetic deficiency of the P2Y12 receptor (P2Y12−/− mice) ameliorated pain hypersensitivities during the initiation phase of neuropathic pain. Next, we characterized both the electrophysiological and morphological properties of microglia in the superficial spinal cord dorsal horn following SNT injury. We show dramatic alterations including a peak at 3 days post injury in microglial electrophysiology while high resolution two-photon imaging revealed significant changes of both static and dynamic microglial morphological properties by 7 days post injury. Finally, in P2Y12−/− mice, these electrophysiological and morphological changes were ameliorated suggesting roles for P2Y12 receptors in SNT-induced microglial activation. Our results therefore indicate that P2Y12 receptors regulate microglial electrophysiological as well as static and dynamic microglial properties after peripheral nerve injury, suggesting that the microglial P2Y12 receptor could be a potential therapeutic target for the treatment of neuropathic pain. PMID:26576724

  1. Purinergic P2Y12 Receptor Activation in Eosinophils and the Schistosomal Host Response.

    PubMed

    Muniz, Valdirene S; Baptista-Dos-Reis, Renata; Benjamim, Claudia F; Mata-Santos, Hilton A; Pyrrho, Alexandre S; Strauch, Marcelo A; Melo, Paulo A; Vicentino, Amanda R R; Silva-Paiva, Juliana; Bandeira-Melo, Christianne; Weller, Peter F; Figueiredo, Rodrigo T; Neves, Josiane S

    2015-01-01

    Identifying new target molecules through which eosinophils secrete their stored proteins may reveal new therapeutic approaches for the control of eosinophilic disorders such as host immune responses to parasites. We have recently reported the expression of the purinergic P2Y12 receptor (P2Y12R) in human eosinophils; however, its functional role in this cell type and its involvement in eosinophilic inflammation remain unknown. Here, we investigated functional roles of P2Y12R in isolated human eosinophils and in a murine model of eosinophilic inflammation induced by Schistosoma mansoni (S. mansoni) infection. We found that adenosine 5'-diphosphate (ADP) induced human eosinophils to secrete eosinophil peroxidase (EPO) in a P2Y12R dependent manner. However, ADP did not interfere with human eosinophil apoptosis or chemotaxis in vitro. In vivo, C57Bl/6 mice were infected with cercariae of the Belo Horizonte strain of S. mansoni. Analyses performed 55 days post infection revealed that P2Y12R blockade reduced the granulomatous hepatic area and the eosinophilic infiltrate, collagen deposition and IL-13/IL-4 production in the liver without affecting the parasite oviposition. As found for humans, murine eosinophils also express the P2Y12R. P2Y12R inhibition increased blood eosinophilia, whereas it decreased the bone marrow eosinophil count. Our results suggest that P2Y12R has an important role in eosinophil EPO secretion and in establishing the inflammatory response in the course of a S. mansoni infection.

  2. Synergistic inhibition of both P2Y1 and P2Y12 adenosine diphosphate receptors as novel approach to rapidly attenuate platelet-mediated thrombosis

    PubMed Central

    Gremmel, Thomas; Yanachkov, Ivan B.; Yanachkova, Milka I.; Wright, George E.; Wider, Joseph; Undyala, Vishnu V.R.; Michelson, Alan D.; Frelinger, Andrew L.; Przyklenk, Karin

    2015-01-01

    Objective Unlike currently approved adenosine diphosphate (ADP) receptor antagonists, the new diadenosine tetraphosphate derivative GLS-409 targets not only P2Y12 but also the second human platelet ADP receptor P2Y1, and may therefore be a promising antiplatelet drug candidate. The current study is the first to investigate the in vivo antithrombotic effects of GLS-409. Approach and Results We studied (1) the in vivo effects of GLS-409 on agonist-stimulated platelet aggregation in anesthetized rats, (2) the antithrombotic activity of GLS-409 and the associated effect on the bleeding time in a canine model of platelet-mediated coronary artery thrombosis, and (3) the inhibition of agonist-stimulated platelet aggregation by GLS-409 versus selective P2Y1 and P2Y12 inhibition in vitro in samples from healthy human subjects before and 2 hours after aspirin intake. In vivo treatment with GLS-409 significantly inhibited ADP- and collagen-stimulated platelet aggregation in rats. Further, GLS-409 attenuated cyclic flow variation, i.e., platelet-mediated thrombosis, in vivo in our canine model of unstable angina. The improvement in coronary patency was accompanied by a non-significant 30% increase in bleeding time. Of note, GLS-409 exerted its effects without affecting rat and canine hemodynamics. Finally, in vitro treatment with GLS-409 showed effects similar to that of cangrelor and the combination of cangrelor with the selective P2Y1 inhibitor MRS 2179 on agonist-stimulated platelet aggregation in human platelet-rich plasma and whole blood before and 2 hours after aspirin intake. Conclusions Synergistic inhibition of both P2Y1 and P2Y12 ADP receptors by GLS-409 immediately attenuates platelet-mediated thrombosis and effectively blocks agonist-stimulated platelet aggregation irrespective of concomitant aspirin therapy. PMID:26743169

  3. P2Y Receptors in Synaptic Transmission and Plasticity: Therapeutic Potential in Cognitive Dysfunction

    PubMed Central

    Guzman, Segundo J.; Gerevich, Zoltan

    2016-01-01

    ATP released from neurons and astrocytes during neuronal activity or under pathophysiological circumstances is able to influence information flow in neuronal circuits by activation of ionotropic P2X and metabotropic P2Y receptors and subsequent modulation of cellular excitability, synaptic strength, and plasticity. In the present paper we review cellular and network effects of P2Y receptors in the brain. We show that P2Y receptors inhibit the release of neurotransmitters, modulate voltage- and ligand-gated ion channels, and differentially influence the induction of synaptic plasticity in the prefrontal cortex, hippocampus, and cerebellum. The findings discussed here may explain how P2Y1 receptor activation during brain injury, hypoxia, inflammation, schizophrenia, or Alzheimer's disease leads to an impairment of cognitive processes. Hence, it is suggested that the blockade of P2Y1 receptors may have therapeutic potential against cognitive disturbances in these states. PMID:27069691

  4. P2Y Receptors in Synaptic Transmission and Plasticity: Therapeutic Potential in Cognitive Dysfunction.

    PubMed

    Guzman, Segundo J; Gerevich, Zoltan

    2016-01-01

    ATP released from neurons and astrocytes during neuronal activity or under pathophysiological circumstances is able to influence information flow in neuronal circuits by activation of ionotropic P2X and metabotropic P2Y receptors and subsequent modulation of cellular excitability, synaptic strength, and plasticity. In the present paper we review cellular and network effects of P2Y receptors in the brain. We show that P2Y receptors inhibit the release of neurotransmitters, modulate voltage- and ligand-gated ion channels, and differentially influence the induction of synaptic plasticity in the prefrontal cortex, hippocampus, and cerebellum. The findings discussed here may explain how P2Y1 receptor activation during brain injury, hypoxia, inflammation, schizophrenia, or Alzheimer's disease leads to an impairment of cognitive processes. Hence, it is suggested that the blockade of P2Y1 receptors may have therapeutic potential against cognitive disturbances in these states.

  5. [The effect of the mutant genes Ta, Ra and Sd on early embryogenesis in mice].

    PubMed

    Sakharova, N Iu; Malashenko, A M; Mezhevikina, L M; Lepikhov, K A; Fialkovskaia, L A

    1996-01-01

    We studied early embryonic mortality of mice from mutant stocks Tabby (Ta, X-chromosome) and RaSd (RaSd/++, chromosome 2) maintained in the heterozygous state in F1 CBA x C57B1/6 hybrid. Tabby and RaSd mice were reciprocally crossed with F1 mice and examined for the morphological status of embryos washed from the oviduct on the third day of pregnancy, when the stage of eight blastomeres is normally attained. Mortality was evaluated from the number of embryos which did not reach the expected stage by this time. The results have shown that 2-4 cell embryos, which have received gene Ta with the X-chromosome of the female parent, differed from embryos with F1 genotype at the same stage of development by their increased mortality rate, whereas among embryos obtained from RaSd, the mortality was mainly observed before cleavage. Death of embryos receiving the mutant gene from hemizygous Ta males or heterozygous RaSd/++ males was not significantly different from the mortality of embryos without these mutations.

  6. Hypertension during chronic exposure to cold: Comparison between Sprague Dawley (SD) and Long Evans (LE) strains

    SciTech Connect

    Riesselmann, A.; Baron, A.; Fregly, M.J. )

    1991-03-11

    Hypertension accompanies chronic exposure of SD rats to cold (5-6C), including elevation of systolic, diastolic, and mean blood pressures and cardiac hypertrophy. The renin-angiotensin system may play an important role. Earlier studies suggested that the LE strain may have a decrease in angiotensin I converting enzyme (ACE) activity. Measurement of ACE activity in plasmas of SE and LE strains revealed that basal activity of ACE in the plasma of the LE strain was significantly less than that of the SD strain. A second study was carried out in which both strains were exposed to cold for 7 weeks. There were clear differences between strains. Rats of the SD strain had a significant elevation in their blood pressure; a significantly increased urinary output of norepinephrine (NE) and epinephrine (E); and significant increases in weights of heart, kidneys, adrenals, and brown adipose tissue (IBAT) compared to their controls maintained at 26C. In contrast, rats of the LE strain were less responsive to cold in that blood pressure failed to rise as sharply and to attain as high a level; NE and E outputs, as well as weights of heart and IBAT were significantly less than those of rats of the cold-treated SD strain. Thus, the lower ACE activity in plasma of LE strain, as well as a reduced secretion of catecholamines, may protect these rats against the rise of blood pressure characteristically observed when rats of the SD strain are exposed to cold.

  7. Intracellular NAADP increase induced by extracellular NAADP via the P2Y11-like receptor.

    PubMed

    Djerada, Zoubir; Millart, Hervé

    2013-06-28

    The aim of the study was to identify a signalling pathway allowing NAADP-induced intracellular NAADP increase and involving the P2Y11-like receptor. P2Y11-like and β-adrenergic receptors may play important regulatory roles within the cardiovascular system. Both receptors have been shown to be involved in triggering myocardial preconditioning. Using a Langendorff model we report a positive inotropic response induced by extracellular NAADP via P2Y11-like receptor stimulation. In cardiomyocyte cultures, P2Y11-like receptor stimulation by extracellular NAADP ([NAADP]e) increased intracellular cADP-ribose and NAADP concentration as evidenced by direct measurements. NF546, a new selective P2Y11 receptor agonist, increased intracellular cAMP, cADP-ribose and NAADP concentration confirming the involvement of the P2Y11-like receptor in this signalling pathway. NF157, a P2Y11 receptor antagonist, suppressed the increase in intracellular cADPr, NAADP and NAAD induced by either [NAADP]e or NF546. The response profile for intracellular cADP-ribose and NAADP concentration following P2Y11-like stimulation with NF546 was similar to reported data relating β-adrenergic stimulation with isoprenaline. This response represents the signature of the Gs/ADP-ribosyl cyclase activity. Moreover, this study provides a signalling pathway: intracellular NAADP increase induced by extracellular NAADP via metabotropic activity of P2Y11-like receptor. This pathway implying P2Y11-like could take part in the intracellular calcium rise reported for extracellular NAADP.

  8. Geobacter sp. SD-1 with enhanced electrochemical activity in high-salt concentration solutions.

    PubMed

    Sun, Dan; Call, Douglas; Wang, Aijie; Cheng, Shaoan; Logan, Bruce E

    2014-12-01

    An isolate, designated strain SD-1, was obtained from a biofilm dominated by Geobacter sulfurreducens in a microbial fuel cell. The electrochemical activity of strain SD-1 was compared with type strains, G. sulfurreducens PCA and Geobacter metallireducens GS-15, and a mixed culture in microbial electrolysis cells. SD-1 produced a maximum current density of 290 ± 29 A m−3 in a high-concentration phosphate buffer solution (PBS-H, 200 mM). This current density was significantly higher than that produced by the mixed culture (189 ± 44 A m−3) or the type strains (< 70 A m−3). In a highly saline water (SW; 50 mM PBS and 650 mM NaCl), current by SD-1 (158 ± 4 A m−3) was reduced by 28% compared with 50 mM PBS (220 ± 4 A m−3), but it was still higher than that of the mixed culture (147 ± 19 A m−3), and strains PCA and GS-15 did not produce any current. Electrochemical tests showed that the improved performance of SD-1 was due to its lower charge transfer resistance and more negative potentials produced at higher current densities. These results show that the electrochemical activity of SD-1 was significantly different than other Geobacter strains and mixed cultures in terms of its salt tolerance.

  9. A New sdO+dM Binary with Extreme Eclipses and Reflection Effect

    NASA Astrophysics Data System (ADS)

    Derekas, A.; Németh, P.; Southworth, J.; Borkovits, T.; Sárneczky, K.; Pál, A.; Csák, B.; Garcia-Alvarez, D.; Maxted, P. F. L.; Kiss, L. L.; Vida, K.; Szabó, Gy. M.; Kriskovics, L.

    2015-08-01

    We report the discovery of a new totally eclipsing binary (R.A. = {06}{{h}}{40}{{m}}{29}{{s}}11; decl. = +38°56‧52″2 J = 2000.0; Rmax = 17.2 mag) with an sdO primary and a strongly irradiated red dwarf companion. It has an orbital period of Porb = 0.187284394(11) day and an optical eclipse depth in excess of 5 mag. We obtained 2 low-resolution classification spectra with GTC/OSIRIS and 10 medium-resolution spectra with WHT/ISIS to constrain the properties of the binary members. The spectra are dominated by H Balmer and He ii absorption lines from the sdO star, and phase-dependent emission lines from the irradiated companion. A combined spectroscopic and light curve analysis implies a hot subdwarf temperature of Teff(spec) = 55,000 ± 3000 K, surface gravity of log g (phot) = 6.2 ± 0.04 (cgs), and a He abundance of {log}(n{He}/n{{H}})=-2.24+/- 0.40. The hot sdO star irradiates the red dwarf companion, heating its substellar point to about 22,500 K. Surface parameters for the companion are difficult to constrain from the currently available data: the most remarkable features are the strong H Balmer and C ii-iii lines in emission. Radial velocity estimates are consistent with the sdO+dM classification. The photometric data do not show any indication of sdO pulsations with amplitudes greater than 7 mmag, and Hα-filter images do not provide evidence for the presence of a planetary nebula associated with the sdO star.

  10. Characterization of Two Segregation Distorter Revertants: Evidence That the Tandem Duplication Is Necessary for Sd Activity in Drosophila Melanogaster

    PubMed Central

    Palopoli, M. F.; Doshi, P.; Wu, C. I.

    1994-01-01

    Segregation Distorter (SD) is a naturally occurring system of meiotic drive in Drosophila melanogaster. Males heterozygous for an SD second chromosome and a normal homolog (SD(+)) transmit predominantly SD-bearing sperm. To accomplish this, the Segregation distorter (Sd) locus induces the dysfunction of those spermatids that receive the SD(+) chromosome. Recently, P. A. Powers and B. Ganetzky isolated overlapping DNA clones spanning the region of DNA known to contain the Sd gene and identified a 5-kb tandem duplication that is present on all SD chromosomes examined, but is apparently absent from wild-type chromosomes. Here we report a molecular analysis of two spontaneous revertants from an Australian SD chromosome (SD-Arm28). Both of these revertants have lost the 5-kb tandem duplication along with the ability to distort transmission; the critical observation, however, is that they retain the DNA haplotype in the flanking regions (both proximally and distally) that is characteristic of the original SD-Arm28. We propose unequal sister chromatid exchange between the tandem repeats as the only plausible explanation for loss of a repeat while retaining flanking markers. This provides direct evidence that the tandem duplication is indeed necessary for the Sd phenotype. Further, we examined testes-specific levels of both RNA and protein for the nearby Topoisomerase 2 gene. Neither revealed a consistent difference between SD and SD(+) strains. We also measured testes-specific levels of RNA using the tandem duplication itself as probe. Our results suggest that there is strong up-regulation of one or several 2.0-2.3-kb transcripts from the duplicated region in the testes of an SD strain. Whether it is this overexpression of transcripts that causes segregation distortion remains to be investigated. PMID:8138158

  11. Initial results from the Solar Dynamic (SD) Ground Test Demonstration (GTD) project at NASA Lewis

    NASA Technical Reports Server (NTRS)

    Shaltens, Richard K.; Boyle, Robert V.

    1995-01-01

    A government/industry team designed, built, and tested a 2 kWe solar dynamic space power system in a large thermal/vacuum facility with a simulated sun at the NASA Lewis Research Center. The Lewis facility provides an accurate simulation of temperatures, high vacuum, and solar flux as encountered in low earth orbit. This paper reviews the goals and status of the Solar Dynamic (SD) Ground Test Demonstration (GTD) program and describes the initial testing, including both operational and performance data. This SD technology has the potential as a future power source for the International Space Station Alpha.

  12. Activation of P2Y1 and P2Y2 receptors induces chloride secretion via calcium-activated chloride channels in kidney inner medullary collecting duct cells

    PubMed Central

    Rajagopal, Madhumitha; Kathpalia, Paru P.; Thomas, Sheela V.

    2011-01-01

    Dysregulation of urinary sodium chloride (NaCl) excretion can result in extracellular fluid (ECF) volume expansion and hypertension. Recent studies demonstrated that urinary nucleotide excretion increases in mice ingesting a high-salt diet and that these increases in extracellular nucleotides can signal through P2Y2 receptors in the kidney collecting duct to inhibit epithelial Na+ channels (ENaC). However, under conditions of ECF volume expansion brought about by high-dietary salt intake, ENaC activity should already be suppressed. We hypothesized that alternative pathways exist by which extracellular nucleotides control renal NaCl excretion. We used an inner medullary collecting duct (mIMCD-K2) cell line in an Ussing chamber system as a model to study additional ion transport pathways that are regulated by extracellular nucleotides. When ENaC was inhibited, the addition of adenosine triphosphate (ATP) to the basal side of cell sheets activated both P2Y1 and P2Y2 receptors, inducing a transient increase in short-circuit current (Isc); addition of ATP to the apical side activated only P2Y2 receptors, inducing first a transient and then a sustained increase in Isc. The ATP-induced increases in Isc were blocked by pretreatment with a phospholipase C (PLC) inhibitor, a calcium (Ca2+) chelator, or Ca2+-activated Cl− channel (CACC) inhibitors, suggesting that ATP signals through both PLC and intracellular Ca2+ to activate CACC. We propose that P2Y1 and P2Y2 receptors operate in tandem in IMCD cells to provide an adaptive mechanism for enhancing urinary NaCl excretion in the setting of high-dietary NaCl intake. PMID:21653634

  13. Transition strategies from cangrelor to oral platelet P2Y12 receptor antagonists.

    PubMed

    Schneider, David J

    2016-01-01

    Cangrelor is the first parenteral antagonist of the platelet P2Y12 receptor. This direct-acting antagonist of the platelet P2Y12 receptor should be considered an adjunct to a percutaneous coronary intervention in patients who have not been adequately pretreated with platelet P2Y12 receptor antagonists at the time of the procedure. The use of cangrelor requires transition to an oral platelet P2Y12 receptor antagonist. Transition strategies have been developed on the basis of pharmacologic characteristics of platelet P2Y12 receptor antagonists, results of pharmacodynamic studies, and results from clinical trials. Cangrelor blocks the binding to the platelet P2Y12 receptor of the active metabolite of the thienopyridines, clopidogrel and prasugrel. The active metabolite of thienopyridines is present in blood for a short interval after administration. For this reason, clopidogrel should be administered after cangrelor is stopped. Prasugrel can be administered at the end of the cangrelor infusion or up to 30 min before cangrelor is stopped. Ticagrelor is also a reversible direct-acting antagonist of the platelet P2Y12 receptor. Because there is no interaction between ticagrelor and cangrelor, ticagrelor can be administered before or during the infusion of cangrelor.

  14. Structural and functional evolution of the P2Y12-like receptor group

    PubMed Central

    Hermsdorf, Thomas; Engemaier, Eva; Engel, Kathrin; Liebscher, Ines; Thor, Doreen; Zierau, Klaas; Römpler, Holger; Schulz, Angela

    2007-01-01

    Metabotropic pyrimidine and purine nucleotide receptors (P2Y receptors) belong to the superfamily of G protein-coupled receptors (GPCR). They are distinguishable from adenosine receptors (P1) as they bind adenine and/or uracil nucleotide triphosphates or diphosphates depending on the subtype. Over the past decade, P2Y receptors have been cloned from a variety of tissues and species, and as many as eight functional subtypes have been characterized. Most recently, several members of the P2Y12-like receptor group, which includes the clopidogrel-sensitive ADP receptor P2Y12, have been deorphanized. The P2Y12-like receptor group comprises several structurally related GPCR which, however, display heterogeneous agonist specificity including nucleotides, their derivatives, and lipids. Besides the established function of P2Y12 in platelet activation, expression in macrophages, neuronal and glial cells as well as recent results from functional studies implicate that several members of this group may have specific functions in neurotransmission, inflammation, chemotaxis, and response to tissue injury. This review focuses specifically on the structure-function relation and shortly summarizes some aspects of the physiological relevance of P2Y12-like receptor members. PMID:18404440

  15. Important roles of P2Y receptors in the inflammation and cancer of digestive system

    PubMed Central

    Wan, Han-Xing; Hu, Jian-Hong; Xie, Rei; Yang, Shi-Ming; Dong, Hui

    2016-01-01

    Purinergic signaling is important for many biological processes in humans. Purinoceptors P2Y are widely distributed in human digestive system and different subtypes of P2Y receptors mediate different physiological functions from metabolism, proliferation, differentiation to apoptosis etc. The P2Y receptors are essential in many gastrointestinal functions and also involve in the occurrence of some digestive diseases. Since different subtypes of P2Y receptors are present on the same cell of digestive organs, varying subtypes of P2Y receptors may have opposite or synergetic functions on the same cell. Recently, growing lines of evidence strongly suggest the involvement of P2Y receptors in the pathogenesis of several digestive diseases. In this review, we will focus on their important roles in the development of digestive inflammation and cancer. We anticipate that as the special subtypes of P2Y receptors are studied in depth, specific modulators for them will have good potentials to become promising new drugs to treat human digestive diseases in the near future. PMID:26908460

  16. Molecular Structure of P2Y Receptors: Mutagenesis, Modeling, and Chemical Probes

    PubMed Central

    Jayasekara, M.P. Suresh; Costanzi, Stefano

    2012-01-01

    There are eight subtypes of P2Y receptors (P2YRs) that are activated, and in some cases inhibited, by a range of extracellular nucleotides. These nucleotides are ubiquitous, but their extracellular concentration can rise dramatically in response to hypoxia, ischemia, or mechanical stress, injury, and release through channels and from vesicles. Two subclasses of P2YRs were defined based on clustering of sequences, second messengers, and receptor sequence analysis. The numbering system for P2YR subtypes is discontinuous; i.e., P2Y1–14Rs have been defined, but six of the intermediate-numbered cloned receptor sequences (e.g., P2y3, P2y5, P2y7–10) are not functional mammalian nucleotide receptors. Of these two clusters, the P2Y12–14 subtypes couple via Gαi to inhibit adenylate cyclase, while the remaining subtypes couple through Gαq to activate phospholipase C. Collectively, the P2YRs respond to both purine and pyrimidine nucleotides, in the form of 5′-mono- and dinucleotides and nucleoside-5′-diphosphosugars. In recent years, the medicinal chemistry of P2Y receptors has advanced significantly, to provide selective agonists and antagonists for many but not all of the subtypes. Ligand design has been aided by insights from structural probing using molecular modelling and mutagenesis. Currently, the molecular modelling of the receptors is effectively based on the X-ray structure of the CXCR4 receptor, which is the closest to the P2Y receptors among all the currently crystallized receptors in terms of sequence similarity. It is now a challenge to develop novel and selective P2YR ligands for disease treatment (although antagonists of the P2Y12R are already widely used as antithrombotics). PMID:23336097

  17. Neuroprotection Mediated by P2Y13 Nucleotide Receptors in Neurons

    PubMed Central

    Pérez-Sen, Raquel; Queipo, Mª José; Morente, Verónica; Ortega, Felipe; Delicado, Esmerilda G.; Miras-Portugal, Mª Teresa

    2015-01-01

    ADP-specific P2Y13 receptor constitutes one of the most recently identified nucleotide receptor and the understanding of their physiological role is currently under investigation. Cerebellar astrocytes and granule neurons provide excellent models to study P2Y13 expression and function since the first identification of ADP-evoked calcium responses not attributable to the related P2Y1 receptor was performed in these cell populations. In this regard, all responses induced by ADP analogues in astrocytes resulted to be Gi-coupled activities mediated by P2Y13 instead of P2Y1 receptors. Similarly, both glycogen synthase kinase-3 (GSK3) and ERK1/2 signaling triggered by 2MeSADP in cerebellar granule neurons were also dependent on Gi-coupled receptors, and mediated by PI3K activity. In granule neurons, P2Y13 receptor was specifically coupled to the main neuronal survival PI3K/Akt-cascade targeting GSK3 phosphorylation. GSK3 inhibition led to nuclear translocation of transcriptional targets, including β-catenin and Nrf2. The activation of the Nrf2/heme oxygenase-1 (HO-1) axis was responsible for the prosurvival effect against oxidative stress. In addition, P2Y13-mediated ERK1/2 signaling in granule neurons also triggered activation of transcription factors, such as CREB, which underlined the antiapoptotic action against glutamate-induced excitotoxicity. Finally, a novel signaling mechanism has been recently described for a P2Y13 receptor in granule neurons that involved the expression of a dual protein phosphatase, DUSP2. This activity contributed to regulate MAPK activation after genotoxic stress. In conclusion, P2Y13 receptors harbored in cerebellar astrocytes and granule neurons exhibit specific signaling properties that link them to specialized functions at the level of neuroprotection and trophic activity in both cerebellar cell populations. PMID:25750704

  18. Discovery of diarylurea P2Y(1) antagonists with improved aqueous solubility.

    PubMed

    Wang, Tammy C; Qiao, Jennifer X; Clark, Charles G; Jua, Ji; Price, Laura A; Wu, Qimin; Chang, Ming; Zheng, Joanna; Huang, Christine S; Everlof, Gerry; Schumacher, William A; Wong, Pancras C; Seiffert, Dietmar A; Stewart, Anne B; Bostwick, Jeffrey S; Crain, Earl J; Watson, Carol A; Rehfuss, Robert; Wexler, Ruth R; Lam, Patrick Y S

    2013-06-01

    Preclinical data suggests that P2Y1 antagonists, such as diarylurea compound 1, may provide antithrombotic efficacy similar to P2Y12 antagonists and may have the potential of providing reduced bleeding liabilities. This manuscript describes a series of diarylureas bearing solublizing amine side chains as potent P2Y1 antagonists. Among them, compounds 2l and 3h had improved aqueous solubility and maintained antiplatelet activity compared with compound 1. Compound 2l was moderately efficacious in both rat and rabbit thrombosis models and had a moderate prolongation of bleeding time in rats similar to that of compound 1.

  19. Spin-Glass Behavior of Semiconducting KxFe2-yS2

    SciTech Connect

    H Lei; M Abeykoon; E Bozin; C Petrovic

    2011-12-31

    We report the discovery of K{sub x}Fe{sub 2-y}S{sub 2} single crystals, isostructural to K{sub x}Fe{sub 2-y}S{sub 2} superconductors. The sulfide compound is a small gap semiconductor and shows spin-glass behavior below 32 K. Our results indicate that stoichiometry, defects, and the local environment of FeCh (Ch = S,Se) tetrahedra have important effects on the physical properties of isostructural and isoelectronic K{sub x}Fe{sub 2-y}S{sub 2} compounds.

  20. 76 FR 48120 - Black Hills National Forest, Custer, SD-Mountain Pine Beetle Response Project

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-08

    ... Forest Service Black Hills National Forest, Custer, SD--Mountain Pine Beetle Response Project AGENCY...: This project proposes to treat areas newly infested by mountain pine beetles on approximately 325,000...-rocky-mountain-black-hills@fs.fed.us , with ``MPB Response Project'' in the subject line....

  1. 75 FR 31464 - Certification of the Attorney General; Shannon County, SD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-03

    ... Certification of the Attorney General; Shannon County, SD In accordance with Section 8 of the Voting Rights Act... determinations of the Attorney General and the Director of the Census made under Section 4(b) of the Voting...) and January 8, 1976 (41 FR 1503). Dated: May 27, 2010. Eric H. Holder, Jr., Attorney General of...

  2. Cluster aspects of p-shell and sd-shell nuclei

    SciTech Connect

    Kanada-En'yo, Y.; Kobayashi, F.; Suhara, T.; Kimura, M.; Taniguchi, Y.

    2011-05-06

    We report some topics on cluster structures studied by using a theoretical method of antisymmetrized molecular dynamics(AMD). Cluster features of p-shell and sd-shell nuclei are discussed. In particular, three alpha cluster structures in the excited states of {sup 12}C and {sup 14}C are focused. Dineutron correlations in neutron-rich nuclei are also discussed.

  3. Integrating SD into Engineering Courses at the Delft University of Technology: The Individual Interaction Method

    ERIC Educational Resources Information Center

    Peet, D. -J.; Mulder, K. F.; Bijma, A.

    2004-01-01

    When sustainable development (SD) is only taught in specific courses, it is questionable if engineering students are able to integrate it into their engineering practices and technical designs. For this reason, sustainability should also be integrated into regular engineering courses, e.g. design courses, materials courses or processing…

  4. Canister storage building compliance assessment SNF project NRC equivalency criteria - HNF-SD-SNF-DB-003

    SciTech Connect

    BLACK, D.M.

    1999-08-11

    This document presents the Project's position on compliance with the SNF Project NRC Equivalency Criteria--HNF-SD-SNF-DE-003, Spent Nuclear Fuel Project Path Forward Additional NRC Requirements. No non-compliances are shown The compliance statements have been reviewed and approved by DOE. Open items are scheduled to be closed prior to project completion.

  5. AmeriFlux US-SdH Nebraska SandHills Dry Valley

    SciTech Connect

    Arkebauer, Tim J.; Billesbach, Dave

    2016-01-01

    This is the AmeriFlux version of the carbon flux data for the site US-SdH Nebraska SandHills Dry Valley. Site Description - The Nebraska SandHills Dry Valley tower is located on public land owned by the University of Nebraska-Lincoln. The site is on a research cattle ranch where grazing primarily takes place.

  6. Semi-automatic geographic atrophy segmentation for SD-OCT images.

    PubMed

    Chen, Qiang; de Sisternes, Luis; Leng, Theodore; Zheng, Luoluo; Kutzscher, Lauren; Rubin, Daniel L

    2013-01-01

    Geographic atrophy (GA) is a condition that is associated with retinal thinning and loss of the retinal pigment epithelium (RPE) layer. It appears in advanced stages of non-exudative age-related macular degeneration (AMD) and can lead to vision loss. We present a semi-automated GA segmentation algorithm for spectral-domain optical coherence tomography (SD-OCT) images. The method first identifies and segments a surface between the RPE and the choroid to generate retinal projection images in which the projection region is restricted to a sub-volume of the retina where the presence of GA can be identified. Subsequently, a geometric active contour model is employed to automatically detect and segment the extent of GA in the projection images. Two image data sets, consisting on 55 SD-OCT scans from twelve eyes in eight patients with GA and 56 SD-OCT scans from 56 eyes in 56 patients with GA, respectively, were utilized to qualitatively and quantitatively evaluate the proposed GA segmentation method. Experimental results suggest that the proposed algorithm can achieve high segmentation accuracy. The mean GA overlap ratios between our proposed method and outlines drawn in the SD-OCT scans, our method and outlines drawn in the fundus auto-fluorescence (FAF) images, and the commercial software (Carl Zeiss Meditec proprietary software, Cirrus version 6.0) and outlines drawn in FAF images were 72.60%, 65.88% and 59.83%, respectively.

  7. An Atlantic streamer in stratospheric ozone observations and SD-WACCM simulation data

    NASA Astrophysics Data System (ADS)

    Hocke, Klemens; Schranz, Franziska; Maillard Barras, Eliane; Moreira, Lorena; Kämpfer, Niklaus

    2017-03-01

    Observation and simulation of individual ozone streamers are important for the description and understanding of non-linear transport processes in the middle atmosphere. A sudden increase in mid-stratospheric ozone occurred above central Europe on 4 December 2015. The GROund-based Millimeter-wave Ozone Spectrometer (GROMOS) and the Stratospheric Ozone MOnitoring RAdiometer (SOMORA) in Switzerland measured an ozone enhancement of about 30 % at 34 km altitude (8.3 hPa) from 1 to 4 December. A similar ozone increase is simulated by the Specified Dynamics Whole Atmosphere Community Climate (SD-WACCM) model. Further, the global ozone fields at 34 km altitude (8.3 hPa) from SD-WACCM and the satellite experiment Aura/MLS show a remarkable agreement for the location and timing of an ozone streamer (large-scale tongue-like structure) extending from the subtropics in northern America over the Atlantic to central Europe. This agreement indicates that SD-WACCM can inform us about the wind inside the Atlantic ozone streamer. SD-WACCM shows an eastward wind of about 100 m s-1 inside the Atlantic streamer in the mid-stratosphere. SD-WACCM shows that the Atlantic streamer flows along the edge of the polar vortex. The Atlantic streamer turns southward at an erosion region of the polar vortex located above the Caspian Sea. The spatial distribution of stratospheric water vapour indicates a filament outgoing from this erosion region. The Atlantic streamer, the polar vortex erosion region and the water vapour filament belong to the process of planetary wave breaking in the so-called surf zone of the northern midlatitude winter stratosphere.

  8. Preparation of transparent Cu2Y2O5 thin films by RF magnetron sputtering

    NASA Astrophysics Data System (ADS)

    Chiu, Te-Wei; Chang, Chih-Hao; Yang, Li-Wei; Wang, Yung-Po

    2015-11-01

    Cu2Y2O5 thin films were deposited on non-alkali glass substrates by RF magnetron sputtering. Its crystal structure, microstructure, optical property, mechanical property, and antibacterial activity were investigated by grazing-incidence X-ray diffraction, transmittance spectra, nanoindenter, and antibiotics test, respectively. A single-phase of Cu2Y2O5 was obtained while annealing at 700 °C in air and its optical transparency was >80% in the visible region. The hardness and elastic modulus of the film were 6.7 GPa and 82 GPa, respectively. Antibiotics testing result revealed that Cu2Y2O5 surface had a superior antibacterial performance even at a dark environment. Therefore, Cu2Y2O5 is a promising novel transparent antibacterial hard coating material.

  9. Silencing of P2Y2 receptors reduces intraocular pressure in New Zealand rabbits

    PubMed Central

    Martin-Gil, Alba; de Lara, María Jesús Perez; Crooke, Almudena; Santano, Concepción; Peral, Assumpta; Pintor, Jesus

    2012-01-01

    BACKGROUND AND PURPOSE P2 receptors are involved in the regulation of ocular physiological processes like intraocular pressure (IOP). In the present study, the involvement of P2Y2 receptors in the hypertensive effect of nucleotides was investigated by use of antagonists and of a siRNA designed for the P2Y2 receptor. EXPERIMENTAL APPROACH Agonists of the P2Y2 receptor a as well as P2 antagonists were applied to eyes of New Zealand rabbits, and the changes in IOP were followed for up to 6 h. Cloning of the P2Y2 receptor cDNA was done using a combination of degenerate reverse transcription PCR (RT-PCR) and rapid amplification of cDNA ends (RACE). siRNA was synthesized and tested by immunohistochemistry. KEY RESULTS Single doses of 2-thioUTP, UTP-γ-S and UTP increased IOP. This behaviour was concentration-dependent and partially antagonized by reactive blue 2. Silencing the P2Y2 receptor was observed in the ciliary body by immunohistochemistry labelling, where a reduction in the immunofluorescence was observed. This reduction in the expression of the P2Y2 receptor was concomitant with a reduction in IOP, which was measurable 24 h after treatment with the siRNA, maximal after 2 days, followed by a slow increase towards control values for the following 5 days. Application of the P2Y2 agonists after pretreatment of the animals with this siRNA did not produce any change in IOP. CONCLUSIONS AND IMPLICATIONS P2Y2 receptors increase IOP in New Zealand rabbits. The application of a siRNA for this receptor significantly reduced IOP, suggesting that this technology might be used for the treatment of glaucoma. PMID:21740413

  10. Current knowledge on the role of P2Y receptors in cardioprotection against ischemia-reperfusion.

    PubMed

    Djerada, Zoubir; Feliu, Catherine; Richard, Vincent; Millart, Hervé

    2017-04-01

    During ischemia, numerous effective endogenous extracellular mediators have been identified, particularly, nucleosides such as adenosine as well as purinergic and pyrimidinergic nucleotides. They may play important regulatory roles within the cardiovascular system and notably as cardio-protectants. Indeed, the distribution of the P2Y receptors in mammalian heart includes several cellular constituents relevant for the pathophysiology of myocardial ischemia. Beside the well-known cardioprotective effect of adenosine, the additional protective role of P2Y receptors has emerged. However, interpretation of experimental results may be sometimes perplexing. This is due to the variability of: the experimental models, the endpoints criteria, the chemical structure of agonist and antagonist ligands and their concentrations, the sequences of drug administration with respect to the model used (before and/or during and/or after ischemia). The net effect may be in the opposite direction after a transient or a prolonged stimulation. Nevertheless, the overall reading of published data highlights the beneficial role of the P2Y2/4 receptor stimulation, the useful and synergistic role of P2Y6/11 receptor activation and even of the P2Y11 receptor alone in cardioprotection. More, the P2Y11 receptor could be involved in counter-regulation of profibrotic processes. Paradoxically, transient P2X7 receptor stimulation could contribute to the net cardioprotective effect of ATP. Recently, experimental data have shown that blocking the P2Y12 receptor after ischemia confers cardioprotection independently of platelet antiaggregatory effect. This suggests for P2Y receptors an important role in primary prevention and as a therapeutic target in myocardial protection during ischemia and reperfusion.

  11. Validation of a P2Y12-receptor specific whole blood platelet aggregation assay.

    PubMed

    Amann, Michael; Ferenc, Miroslaw; Valina, Christian M; Bömicke, Timo; Stratz, Christian; Leggewie, Stefan; Trenk, Dietmar; Neumann, Franz-Josef; Hochholzer, Willibald

    2016-11-01

    Testing of P2Y12-receptor antagonist effects can support clinical decision-making. However, most platelet function assays use only ADP as agonist which is not P2Y12-receptor specific. For this reason P2Y12-receptor specific assays have been developed by adding prostaglandin E1 (PGE1) to reduce ADP-induced platelet activation via the P2Y1-receptor. The present study sought to evaluate a P2Y12-receptor specific assay for determination of pharmacodynamic and clinical outcomes. This study enrolled 400 patients undergoing coronary stenting after loading with clopidogrel or prasugrel. ADP-induced platelet reactivity was assessed by whole blood aggregometry at multiple time points with a standard ADP assay (ADPtest) and a P2Y12-receptor specific assay (ADPtest HS, both run on Multiplate Analyzer, Roche Diagnostics). Patients were clinically followed for 1 month and all events adjudicated by an independent committee. In total, 2084 pairs of test results of ADPtest and ADPtest HS were available showing a strong correlation between results of both assays (r = 0.96, p < 0.001). These findings prevailed in multiple prespecified subgroups (e.g., age; body mass index; diabetes). Calculated cutoffs for ADPtest HS and the established cutoffs of ADPtest showed a substantial agreement for prediction of ischemic and hemorrhagic events with a Cohen's κ of 0.66 and 0.66, respectively. The P2Y12-receptor specific ADPtest HS assay appears similarly predictive for pharmacodynamic and clinical outcomes as compared to the established ADPtest assay indicating its applicability for clinical use. Further evaluation in large cohorts is needed to determine if P2Y12-receptor specific testing offers any advantage for prediction of clinical outcome.

  12. Rapid Evolution of a Coadapted Gene Complex: Evidence from the Segregation Distorter (Sd) System of Meiotic Drive in Drosophila Melanogaster

    PubMed Central

    Palopoli, M. F.; Wu, C. I.

    1996-01-01

    Segregation Distorter (SD) is a system of meiotic drive found in natural populations of Drosophila melanogaster. Males heterozygous for an SD second chromosome and a normal homologue (SD(+)) produce predominantly SD-bearing sperm. The coadapted gene complex responsible for this transmission advantage spans the second chromosome centromere, consisting of three major and several minor interacting loci. To investigate the evolutionary history of this system, we surveyed levels of polymorphism and divergence at six genes that together encompass this pericentromeric region and span seven map units. Interestingly, there was no discernible divergence between SD and SD(+) chromosomes for any of these molecular markers. Furthermore, SD chromosomes harbored much less polymorphism than did SD(+) chromosomes. The results suggest that the SD system evolved recently, swept to appreciable frequencies worldwide, and carried with it the entire second chromosome centromeric region (roughly 10% of the genome). Despite its well-documented genetic complexity, this coadapted system appears to have evolved on a time scale that is much shorter than can be gauged using nucleotide substitution data. Finally, the large genomic region hitchhiking with SD indicates that a multilocus, epistatically selected system could affect the levels of DNA polymorphism observed in regions of reduced recombination. PMID:8844155

  13. Potential involvement of P2Y2 receptor in diuresis of postobstructive uropathy in rats.

    PubMed

    Zhang, Yue; Kohan, Donald E; Nelson, Raoul D; Carlson, Noel G; Kishore, Bellamkonda K

    2010-03-01

    AVP resistance of the medullary collecting duct (mCD) in postobstructive uropathy (POU) has been attributed to increased production of PGE2. P2Y2 receptor activation causes production of PGE2 by the mCD. We hypothesize that increased P2Y2 receptor expression and/or activity may contribute to the diuresis of POU. Sprague-Dawley rats were subjected to bilateral ureteral obstruction for 24 h followed by release (BUO/R, n = 17) or sham operation (SHM/O, n = 15) and euthanized after 1 wk or 12 days. BUO/R rats developed significant polydipsia, polyuria, urinary concentration defect, and increased urinary PGE2 and decreased aquaporin-2 protein abundance in the inner medulla compared with SHM/O rats. After BUO/R, the relative mRNA expression of P2Y2 and P2Y6 receptors was increased by 2.7- and 4.9-fold, respectively, without significant changes in mRNA expression of P2Y1 or P2Y4 receptor. This was associated with a significant 3.5-fold higher protein abundance of the P2Y2 receptor in BUO/R than SHM/O rats. When freshly isolated mCD fractions were challenged with different types of nucleotides (ATPgammaS, ADP, UTP, or UDP), BUO/R and SHM/O rats responded to only ATPgammaS and UTP and released PGE2, consistent with involvement of the P2Y2, but not P2Y6, receptor. ATPgammaS- or UTP-stimulated increases in PGE2 were much higher in BUO/R (3.20- and 2.28-fold, respectively, vs. vehicle controls) than SHM/O (1.68- and 1.30-fold, respectively, vs. vehicle controls) rats. In addition, there were significant 2.4- and 2.1-fold increases in relative mRNA expression of prostanoid EP1 and EP3 receptors, respectively, in the inner medulla of BUO/R vs. SHM/O rats. Taken together, these data suggest that increased production of PGE2 by the mCD in POU may be due to increased expression and activity of the P2Y2 receptor. Increased mRNA expression of EP1 and EP3 receptors in POU may also help accentuate PGE2-induced signaling in the mCD.

  14. Relaxation Mechanism of the SD Vibrational Stretch Mode in Amorphous As_2S_3

    NASA Astrophysics Data System (ADS)

    Engholm, J. R.; Rella, C. W.; Schwettman, H. A.; Happek, U.

    1996-03-01

    Impurity molecules in a glassy host such as SD in As_2S3 exhibit inhomogeneous broadening in their vibrational stretch mode absorption lines caused by a site-dependent redshift due to hydrogen bonding. We have performed pump-probe measurements using the Stanford Picosecond Free Electron Laser to study the relaxation lifetime of the SD vibrational stretch mode in As_2S3 at 1800 cm-1. We find a strongly frequency dependent lifetime across the absorption line on the order of 10-10 seconds, similar to that previously measured for SH impurity molecules in the same host. We use the temperature dependence of the stretch mode lifetimes and linear infrared spectroscopy to identify the relaxation mechanism. This work was supported in part by the Office of Naval Research, Grant No. N00014-94-1-1024.

  15. Optimising SD and LSD in Presence of Non-uniform Probabilities of Revocation

    NASA Astrophysics Data System (ADS)

    D'Arco, Paolo; de Santis, Alfredo

    Some years ago two efficient broadcast encryption schemes for stateless receivers, referred to as SD (Subset Difference Method) [NNL01] and LSD (Layered Subset Difference Method) [HS02] , were proposed. They represent one of the most suitable solution to broadcast encryption. In this paper we focus on the following issue: both schemes assume uniform probabilities of revocation of the receivers. However, in some applications, such an assumption might not hold: receivers in a certain area, due to historical and legal reasons, can be considered trustworthy, while receivers from others might exhibit more adversarial behaviours. Can we modify SD and LSD to better fit settings in which the probabilities of revocation are non-uniform?

  16. DETECTION OF PHOTOMETRIC VARIATIONS IN THE sdBV Star JL 166

    SciTech Connect

    Barlow, B. N.; Dunlap, B. H.; Clemens, J. C.; Lynas-Gray, A. E. E-mail: bhdunlap@physics.unc.edu E-mail: aelg@astro.ox.ac.uk

    2009-08-15

    We report the discovery of oscillations in the hot subdwarf B (sdB) star JL 166 from time-series photometry using the Goodman Spectrograph on the 4.1 m Southern Astrophysical Research Telescope. Previous spectroscopic and photometric observations place the star near the hot end of the empirical sdB instability strip and imply the presence of a cool companion. Amplitude spectra of the stellar light curve reveal at least 10 independent pulsation modes with periods ranging from 97 to 178 s and amplitudes from 0.9 to 4 mma. We adopt atmospheric parameters of T {sub eff} = 34,350 K and log g = 5.75 from a model atmosphere analysis of our time-averaged, medium-resolution spectrum.

  17. A relation between massive scalar field in AdSd+1 and diffusion in channels

    NASA Astrophysics Data System (ADS)

    Romero, Juan M.; Gaona, Alejandro

    2014-05-01

    It is shown that, when the diffusion coefficient is a constant and is taken a particular family of channels, the Fick-Jacobs equation is invariant under conformal symmetry. In addition, using the diffusion coefficient and the geometric parameters of the channels, a representation for the conformal algebra is obtained. Furthermore, it is found that for these systems the Fick-Jacobs equation is equivalent to the Schrödinger equation for the 1-dimensional conformal quantum mechanics. Moreover, using this equivalence, it is found a relation between a massive scalar field equation in AdSd+i background and Fick-Jacobs equation, where the geometric parameter of the channels and the geometric parameters of AdSd+1 are identified.

  18. Agonist versus antagonist action of ATP at the P2Y4 receptor is determined by the second extracellular loop.

    PubMed

    Herold, Christopher L; Qi, Ai-Dong; Harden, T Kendall; Nicholas, Robert A

    2004-03-19

    UTP is a potent full agonist at both the human P2Y(4) (hP2Y(4)) and rat P2Y(4) (rP2Y(4)) receptor. In contrast, ATP is a potent full agonist at the rP2Y(4) receptor but is a similarly potent competitive antagonist at the hP2Y(4) receptor. To delineate the structural determinants of agonism versus antagonism in these species homologues, we expressed a series of human/rat P2Y(4) receptor chimeras in 1321N1 human astrocytoma cells and assessed the capacity of ATP and UTP to mobilize intracellular Ca(2+). Replacement of the NH(2) terminus of the hP2Y(4) receptor with the corresponding region of the rP2Y(4) receptor resulted in a receptor that was activated weakly by ATP, whereas replacement of the second extracellular loop (EL2) of the hP2Y(4) receptor with that of the rP2Y(4) receptor yielded a chimeric receptor that was activated fully by UTP and near fully by ATP, albeit with lower potencies than those observed at the rP2Y(4) receptor. These potencies were increased, and ATP was converted to a full agonist by replacing both the NH(2) terminus and EL2 in the hP2Y(4) receptor with the corresponding regions from the rP2Y(4) receptor. Mutational analysis of the five divergent amino acids in EL2 between the two receptors revealed that three amino acids, Asn-177, Ile-183, and Leu-190, contribute to the capacity of EL2 to impart ATP agonism. Taken together, these results suggest that the second extracellular loop and the NH(2) terminus form a functional motif that plays a key role in determining whether ATP functions as an agonist or antagonist at mammalian P2Y(4) receptors.

  19. Inversion for Eigenvalues and Modes Using Sierra-SD and ROL.

    SciTech Connect

    Walsh, Timothy; Aquino, Wilkins; Ridzal, Denis; Kouri, Drew Philip

    2015-12-01

    In this report we formulate eigenvalue-based methods for model calibration using a PDE-constrained optimization framework. We derive the abstract optimization operators from first principles and implement these methods using Sierra-SD and the Rapid Optimization Library (ROL). To demon- strate this approach, we use experimental measurements and an inverse solution to compute the joint and elastic foam properties of a low-fidelity unit (LFU) model.

  20. The genome of Shigella dysenteriae strain Sd1617 comparison to representative strains in evaluating pathogenesis

    PubMed Central

    Vongsawan, Ajchara A.; Kapatral, Vinayak; Vaisvil, Benjamin; Burd, Henry; Serichantalergs, Oralak; Venkatesan, Malabi M.; Mason, Carl J.

    2015-01-01

    We sequenced and analyzed Shigella dysenteriae strain Sd1617 serotype 1 that is widely used as model strain for vaccine design, trials and research. A combination of next-generation sequencing platforms and assembly yielded two contigs representing a chromosome size of 4.34 Mb and the large virulence plasmid of 177 kb. This genome sequence is compared with other Shigella genomes in order to understand gene complexity and pathogenic factors. PMID:25743074

  1. Multimodal registration of SD-OCT volumes and fundus photographs using histograms of oriented gradients

    PubMed Central

    Miri, Mohammad Saleh; Abràmoff, Michael D.; Kwon, Young H.; Garvin, Mona K.

    2016-01-01

    With availability of different retinal imaging modalities such as fundus photography and spectral domain optical coherence tomography (SD-OCT), having a robust and accurate registration scheme to enable utilization of this complementary information is beneficial. The few existing fundus-OCT registration approaches contain a vessel segmentation step, as the retinal blood vessels are the most dominant structures that are in common between the pair of images. However, errors in the vessel segmentation from either modality may cause corresponding errors in the registration. In this paper, we propose a feature-based registration method for registering fundus photographs and SD-OCT projection images that benefits from vasculature structural information without requiring blood vessel segmentation. In particular, after a preprocessing step, a set of control points (CPs) are identified by looking for the corners in the images. Next, each CP is represented by a feature vector which encodes the local structural information via computing the histograms of oriented gradients (HOG) from the neighborhood of each CP. The best matching CPs are identified by calculating the distance of their corresponding feature vectors. After removing the incorrect matches the best affine transform that registers fundus photographs to SD-OCT projection images is computed using the random sample consensus (RANSAC) method. The proposed method was tested on 44 pairs of fundus and SD-OCT projection images of glaucoma patients and the result showed that the proposed method successfully registers the multimodal images and produced a registration error of 25.34 ± 12.34 μm (0.84 ± 0.41 pixels). PMID:28018740

  2. A Search for Companions to the Pulsating sdB Star EC 20117–4014

    NASA Astrophysics Data System (ADS)

    Otani, T.; Oswalt, T.; Amaral, M.; Jordan, R.

    2017-03-01

    EC 20117–4014 is known to be a spectroscopic binary system consisting of an sdB star and F5V star. It was monitored using the SARA-CT telescope in Cerro Tololo, Chile over several observing seasons. Periodic O-C variations were detected in the two highest amplitude pulsations in EC 20117–4014, permitting detection of the F5V companion, whose period and semimajor axis were previously unknown.

  3. Quantification of soil/dust (SD) on the hands of children from Hubei Province, China using hand wipes.

    PubMed

    Wang, Siyu; Ma, Jin; Pan, Libo; Lin, Chunye; Wang, Beibei; Duan, Xiaoli

    2015-10-01

    A total of 120 children (58 males and 62 females) between the ages of 2 and 17 years were randomly selected from Wuhan City and Wufeng County in Hubei Province, China. We gathered hand SD samples from these children using hand wipes. We determined approximate amounts of hand SD and concentrations of three tracer soil elements (Ce, Y, V) in these samples. The approximate amounts of hand SD ranged from 6.35 to 85.42mg with a median value of 20.62mg. In addition, mean amounts of hand SD estimated using concentrations of Ce, Y, and V in samples were 1.07, 1.00, and 0.92mg, respectively. The amounts of hand SD varied greatly among age groups: primary school children had more hand SD than kindergarten and middle school children, males had more hand SD than females, and children from rural areas had more hand SD than those from urban areas. The rates of daily ingestion of hand SD for kindergarten, primary school, and middle school children were estimated as 1.79, 2.12, and 0.49mg/d, respectively.

  4. EVALUATION OF ARMCO PH13-8Mo,

    DTIC Science & Technology

    STAINLESS STEEL, PHYSICAL PROPERTIES ), (*MARAGING STEELS, PHYSICAL PROPERTIES ), DISPERSION HARDENING, HEAT TREATMENT, TENSILE PROPERTIES , FRACTURE(MECHANICS), STRESS CORROSION, FATIGUE(MECHANICS), TOUGHNESS

  5. Diffractional Imaging of Mantle Transition Zone Discontinuities Using SdS-SS Traveltimes

    NASA Astrophysics Data System (ADS)

    Guo, Z.; Zhou, Y.

    2015-12-01

    The mantle transition zone is characterized by two discontinuities at depths of about 410 and 660 km. Mineral physics studies suggest that wavespeed and density jumps across the discontinuities are associated with olivine phase transformations and the depths at which the phase transformations occur are strongly dependent on temperature. Imaging lateral variations of the discontinuity depths is important for constraining thermal structure in the mid mantle. SS precursors (SdS) are waves reflected at the underside of the discontinuities and arrive beforethe SS phase. Their traveltime measurements at teleseismic distances can be used to map the discontinuities at a global scale. In this study, we measure frequency-dependent SS precursors traveltimes using seismograms recorded at GSN stations for earthquakes occurred between 2000 and 2015. The measurements were made using cosine tapers and multitapers and the traveltimes show significant dispersion. We calculate finite-frequency sensitivity kernels for SdS-SS differential measurements based on traveling-wave mode summation, which account for complete wave interactions within the measurement window. We will discuss preliminary results from finite-frequency imaging using SdS-SS dispersion measurements and the effects of 3-D crustal structure and mantle wavespeed structure.

  6. Metabolomics approach to serum biomarker for loperamide-induced constipation in SD rats

    PubMed Central

    Kim, Ji-Eun; Lee, Young-Ju; Kwak, Moon-Hwa; Jun, Go; Koh, Eun-Kyoung; Song, Sung-Hwa; Seong, Ji-Eun; Kim, Ji Won; Kim, Kyu-Bong; Kim, Suhkmann

    2014-01-01

    Loperamide has long been known as an opioid-receptor agonist useful as a drug for treatment of diarrhea resulting from gastroenteritis or inflammatory bowel disease as well as to induce constipation. To determine and characterize putative biomarkers that can predict constipation induced by loperamide treatment, alteration of endogenous metabolites was measured in the serum of Sprague Dawley (SD) rats treated with loperamide for 3 days using 1H nuclear magnetic resonance (1H NMR) spectral data. The amounts and weights of stool and urine excretion were significantly lower in the loperamide-treated group than the No-treated group, while the thickness of the villus, crypt layer, and muscle layer was decreased in the transverse colon of the same group. The concentrations of aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and creatinine (Cr) were also slightly changed in the loperamide-treated group, although most of the serum components were maintained at a constant level. Furthermore, pattern recognition of endogenous metabolites showed completely separate clustering of the serum analysis parameters between the No-treated group and loperamide-treated group. Among 35 endogenous metabolites, four amino acids (alanine, glutamate, glutamine and glycine) and six endogenous metabolites (acetate, glucose, glycerol, lactate, succinate and taurine) were dramatically decreased in loperamide-treated SD rats. These results provide the first data pertaining to metabolic changes in SD rats with loperamide-induced constipation. Additionally, these findings correlate the changes in 10 metabolites with constipation. PMID:24707303

  7. Geology of the USW SD-12 drill hole Yucca Mountain, Nevada

    SciTech Connect

    Rautman, C.A.; Engstrom, D.A.

    1996-11-01

    Drill hole USW SD-12 is one of several holes drilled under Site Characterization Plan Study 8.3.1.4.3.1, also known as the {open_quotes}Systematic Drilling Program,{close_quotes} as part of the U.S. Department of Energy characterization program at Yucca Mountain, Nevada, which has been proposed as the potential location of a repository for high-level nuclear waste. The SD-12 drill hole is located in the central part of the potential repository area, immediately to the west of the Main Test Level drift of the Exploratory Studies Facility and slightly south of midway between the North Ramp and planned South Ramp declines. Drill hole USW SD-12 is 2166.3 ft (660.26 m) deep, and the core recovered essentially complete sections of ash-flow tuffs belonging to the lower half of the Tiva Canyon Tuff, the Pah Canyon Tuff, and the Topopah Spring Tuff, all of which are part of the Miocene Paintbrush Group. A virtually complete section of the Calico Hills Formation was also recovered, as was core from the entire Prow Pass Tuff formation of the Crater Flat Group.

  8. Automated segmentation of serous pigment epithelium detachment in SD-OCT images

    NASA Astrophysics Data System (ADS)

    Sun, Zhuli; Shi, Fei; Xiang, Dehui; Chen, Haoyu; Chen, Xinjian

    2015-03-01

    Pigment epithelium detachment (PED) is an important clinical manifestation of multiple chorio-retinal disease processes, which can cause the loss of central vision. A 3-D method is proposed to automatically segment serous PED in SD-OCT images. The proposed method consists of five steps: first, a curvature anisotropic diffusion filter is applied to remove speckle noise. Second, the graph search method is applied for abnormal retinal layer segmentation associated with retinal pigment epithelium (RPE) deformation. During this process, Bruch's membrane, which doesn't show in the SD-OCT images, is estimated with the convex hull algorithm. Third, the foreground and background seeds are automatically obtained from retinal layer segmentation result. Fourth, the serous PED is segmented based on the graph cut method. Finally, a post-processing step is applied to remove false positive regions based on mathematical morphology. The proposed method was tested on 20 SD-OCT volumes from 20 patients diagnosed with serous PED. The average true positive volume fraction (TPVF), false positive volume fraction (FPVF), dice similarity coefficient (DSC) and positive predictive value (PPV) are 97.19%, 0.03%, 96.34% and 95.59%, respectively. Linear regression analysis shows a strong correlation (r = 0.975) comparing the segmented PED volumes with the ground truth labeled by an ophthalmology expert. The proposed method can provide clinicians with accurate quantitative information, including shape, size and position of the PED regions, which can assist diagnose and treatment.

  9. Scientific Use of the Sampler, Drill and Distribution Subsystem (SD2)

    NASA Astrophysics Data System (ADS)

    Armellin, R.; Di Lizia, P.; Crepaldi, M.; Bernelli-Zazzera, F.; Ercoli Finzi, A.

    Rosetta is the third cornerstone mission of the European Space Agency scientific program "Horizon 2000". Rosetta will be the first spacecraft to orbit around a comet nucleus. It was launched in March 2004 and will reach the comet 67P/ChurymovGerasimenko in 2014. A lander (Philae) will be released and land on the comet surface for in-situ investigation. One of the key subsystems of the lander Philae is the Sampler, Drill and Distribution (SD2) subsystem. SD2 provides in-situ operations devoted to soil drilling, samples collection, and their distribution to two evolved gas analyzers (COSAC and PTOLEMY) and one imaging instrument (ÇIVA). Recent studies have proven the existence of a correlation between the drill behavior during perforation and the mechanical characteristics of the cometary soil. This outlines the possibility of using SD2 not only as a tool to support other instruments, but also as a scientific instrument itself. In this paper the possibility of using the drill as a quasi-static penetrator is presented. Within this approach, laboratory tests on glass-foam specimens of different porosity show that the drill behaviour during penetration can be exploited for cometary soil characterization.

  10. Spin motive force induced by Rashba interaction in the strong sd coupling regime

    NASA Astrophysics Data System (ADS)

    Tatara, Gen; Nakabayashi, Noriyuki; Lee, Kyun-Jin

    2013-02-01

    Spin motive force induced by the Rashba interaction in the presence of strong sd interaction between conduction electron and localized spin is theoretically studied. The motive force is calculated by evaluating the time derivative of the current density on the basis of microscopic formalism. It is shown that there are two motive forces, one proportional to ER×ṅ, the other, perpendicular component proportional to ER×(n×ṅ), where ER and n are the Rashba electric field and localized spin direction, respectively. The second type arises in the strong sd coupling regime from the spin relaxation. The appearance of perpendicular component from the spin relaxation is understood from the analogy with the current-induced torques. In the case of domain wall motion, the two contributions to the spin motive force are the same order of magnitude, while the first term dominates in the case of precession of uniform magnetization. Our result explains the appearance of the perpendicular component in the weak sd coupling limit, recently discussed in the context of spin damping monopole. Detection of ac voltage induced by the precession of uniform magnetization serves as a experimental evidence of the Rashba interaction in films and wires.

  11. Stripped Red Giants - Helium Core White Dwarf Progenitors and their sdB Siblings

    NASA Astrophysics Data System (ADS)

    Heber, U.

    2017-03-01

    Some gaps in the mosaic of binary star evolution have recently been filled by the discoveries of helium-core white dwarf progenitors (often called extremely low mass (ELM) white dwarfs) as stripped cores of first-giant branch objects. Two varieties can be distinguished. One class is made up by SB1 binaries, companions being white dwarfs as well. Another class, the so-called EL CVn stars, are composite spectrum binaries, with A-Type companions. Pulsating stars are found among both classes. A riddle is posed by the apparently single objects. There is a one-to-one correspondence of the phenomena found for these new classes of star to those observed for sdB stars. In fact, standard evolutionary scenarios explain the origin of sdB stars as red giants that have been stripped close to the tip of first red giant branch. A subgroup of subluminous B stars can also be identified as stripped helium-cores of red giants. They form an extension of the ELM sequence to higher temperatures. Hence low mass white dwarfs of helium cores and sdB stars in binaries are close relatives in terms of stellar evolution.

  12. Multimodal segmentation of optic disc and cup from stereo fundus and SD-OCT images

    NASA Astrophysics Data System (ADS)

    Miri, Mohammad Saleh; Lee, Kyungmoo; Niemeijer, Meindert; Abràmoff, Michael D.; Kwon, Young H.; Garvin, Mona K.

    2013-03-01

    Glaucoma is one of the major causes of blindness worldwide. One important structural parameter for the diagnosis and management of glaucoma is the cup-to-disc ratio (CDR), which tends to become larger as glaucoma progresses. While approaches exist for segmenting the optic disc and cup within fundus photographs, and more recently, within spectral-domain optical coherence tomography (SD-OCT) volumes, no approaches have been reported for the simultaneous segmentation of these structures within both modalities combined. In this work, a multimodal pixel-classification approach for the segmentation of the optic disc and cup within fundus photographs and SD-OCT volumes is presented. In particular, after segmentation of other important structures (such as the retinal layers and retinal blood vessels) and fundus-to-SD-OCT image registration, features are extracted from both modalities and a k-nearest-neighbor classification approach is used to classify each pixel as cup, rim, or background. The approach is evaluated on 70 multimodal image pairs from 35 subjects in a leave-10%-out fashion (by subject). A significant improvement in classification accuracy is obtained using the multimodal approach over that obtained from the corresponding unimodal approach (97.8% versus 95.2%; p < 0:05; paired t-test).

  13. Uridine adenosine tetraphosphate is a novel neurogenic P2Y1 receptor activator in the gut

    PubMed Central

    Durnin, Leonie; Hwang, Sung Jin; Kurahashi, Masaaki; Drumm, Bernard T.; Ward, Sean M.; Sasse, Kent C.; Sanders, Kenton M.; Mutafova-Yambolieva, Violeta N.

    2014-01-01

    Enteric purinergic motor neurotransmission, acting through P2Y1 receptors (P2Y1R), mediates inhibitory neural control of the intestines. Recent studies have shown that NAD+ and ADP ribose better meet criteria for enteric inhibitory neurotransmitters in colon than ATP or ADP. Here we report that human and murine colon muscles also release uridine adenosine tetraphosphate (Up4A) spontaneously and upon stimulation of enteric neurons. Release of Up4A was reduced by tetrodotoxin, suggesting that at least a portion of Up4A is of neural origin. Up4A caused relaxation (human and murine colons) and hyperpolarization (murine colon) that was blocked by the P2Y1R antagonist, MRS 2500, and by apamin, an inhibitor of Ca2+-activated small-conductance K+ (SK) channels. Up4A responses were greatly reduced or absent in colons of P2ry1−/− mice. Up4A induced P2Y1R–SK-channel–mediated hyperpolarization in isolated PDGFRα+ cells, which are postjunctional targets for purinergic neurotransmission. Up4A caused MRS 2500-sensitive Ca2+ transients in human 1321N1 astrocytoma cells expressing human P2Y1R. Up4A was more potent than ATP, ADP, NAD+, or ADP ribose in colonic muscles. In murine distal colon Up4A elicited transient P2Y1R-mediated relaxation followed by a suramin-sensitive contraction. HPLC analysis of Up4A degradation suggests that exogenous Up4A first forms UMP and ATP in the human colon and UDP and ADP in the murine colon. Adenosine then is generated by extracellular catabolism of ATP and ADP. However, the relaxation and hyperpolarization responses to Up4A are not mediated by its metabolites. This study shows that Up4A is a potent native agonist for P2Y1R and SK-channel activation in human and mouse colon. PMID:25341729

  14. Central Role of P2Y6 UDP Receptor in Arteriolar Myogenic Tone

    PubMed Central

    Kauffenstein, Gilles; Tamareille, Sophie; Prunier, Fabrice; Roy, Charlotte; Ayer, Audrey; Toutain, Bertrand; Billaud, Marie; Isakson, Brant E.; Grimaud, Linda; Loufrani, Laurent; Rousseau, Pascal; Abraham, Pierre; Procaccio, Vincent; Monyer, Hannah; de Wit, Cor; Boeynaems, Jean-Marie; Robaye, Bernard; Kwak, Brenda R.; Henrion, Daniel

    2017-01-01

    Objective Myogenic tone (MT) of resistance arteries ensures autoregulation of blood flow in organs and relies on the intrinsic property of smooth muscle to contract in response to stretch. Nucleotides released by mechanical strain on cells are responsible for pleiotropic vascular effects, including vasoconstriction. Here, we evaluated the contribution of extracellular nucleotides to MT. Approach and Results We measured MT and the associated pathway in mouse mesenteric resistance arteries using arteriography for small arteries and molecular biology. Of the P2 receptors in mouse mesenteric resistance arteries, mRNA expression of P2X1 and P2Y6 was dominant. P2Y6 fully sustained UDP/UTP-induced contraction (abrogated in P2ry6−/− arteries). Preventing nucleotide hydrolysis with the ectonucleotidase inhibitor ARL67156 enhanced pressure-induced MT by 20%, whereas P2Y6 receptor blockade blunted MT in mouse mesenteric resistance arteries and human subcutaneous arteries. Despite normal hemodynamic parameters, P2ry6−/− mice were protected against MT elevation in myocardial infarction–induced heart failure. Although both P2Y6 and P2Y2 receptors contributed to calcium mobilization, P2Y6 activation was mandatory for RhoA–GTP binding, myosin light chain, P42–P44, and c-Jun N-terminal kinase phosphorylation in arterial smooth muscle cells. In accordance with the opening of a nucleotide conduit in pressurized arteries, MT was altered by hemichannel pharmacological inhibitors and impaired in Cx43+/− and P2rx7−/− mesenteric resistance arteries. Conclusions Signaling through P2 nucleotide receptors contributes to MT. This mechanism encompasses the release of nucleotides coupled to specific autocrine/paracrine activation of the uracil nucleotide P2Y6 receptor and may contribute to impaired tissue perfusion in cardiovascular diseases. PMID:27255725

  15. Intrinsic Josephson properties in Pb1-ySr2Y1-xCaxCu2+yO7+δ epitaxial films

    NASA Astrophysics Data System (ADS)

    Komori, Sachio; Kakeya, Itsuhiro

    2014-12-01

    We report the first observation of intrinsic Josephson junction (IJJ) characteristics in the Pb1-ySr2Y1-xCaxCu2+yO7+δ (Pb1212) epitaxial film. Pb1212 epitaxial film has been grown on SrTiO3 (100) substrates by a two-step growth technique. A small mesa structure (S = 4μm2) has been fabricated on a film surface using a standard photolithography and an Ar ion milling technique. The superconducting transition temperature of the IJJ is 43 K. At 4.2 K, the value of Jc (the critical current density) is 2.2 kA/cm2. The depth of the hysteresis defined as α = (Jc+Jr)/ Jc is 0.89, where Jr is the return current density. The temperature dependence of Jc shows good agreement with Ambegaokar-Baratoff theory.

  16. Terahertz conductivity in the under-doped Pb1-ySr2Y1-xCaxCu2+yO7+δ epitaxial film

    NASA Astrophysics Data System (ADS)

    Uzawa, Akira; Komori, Sachio; Kamei, Yuta; Kakeya, Itsuhiro

    2016-11-01

    We measured the complex conductivity at the frequencies from 0.2 THz to 1.0 THz in the under-doped Pb1-ySr2Y1-xCaxCu2+yO7+δ (Pb1212) epitaxial film with terahertz time-domain specteroscopy. By analyzing temperature and frequency dependence of the complex conductivity, we found that the superconducting fluctuation persists up to 12 K above Tc, onset. Compared with previous reports, the superconducting fluctuation in Pb1212 is observed shorter temperature range than Bi2Sr2CaCu2O8+δ and La2-xSrxCuO4. This is ascribed to the lower anisotropy of Pb1212.

  17. Geology of the USW SD-7 drill hole Yucca Mountain, Nevada

    SciTech Connect

    Rautman, C.A.; Engstrom, D.A.

    1996-09-01

    The USW SD-7 drill hole is one of several holes drilled under Site Characterization Plan Study 8.3.1.4.3.1, also known as the Systematic Drilling Program, as part of the U.S. Department of Energy characterization program at Yucca Mountain, Nevada. The Yucca Mountain site has been proposed as the potential location of a repository for high-level nuclear waste. The SD-7 drill hole is located near the southern end of the potential repository area and immediately to the west of the Main Test Level drift of the Exploratory Studies Facility. The hole is not far from the junction of the Main Test Level drift and the proposed South Ramp decline. Drill hole USW SD-7 is 2675.1 ft (815.3 m) deep, and the core recovered nearly complete sections of ash-flow tuffs belonging to the lower half of the Tiva Canyon Tuff, the Pah Canyon Tuff, and the Topopah Spring Tuff, all of which are part of the Miocene Paintbrush Group. Core was recovered from much of the underlying Calico Hills Formation, and core was virtually continuous in the Prow Pass Tuff and the Bullfrog Tuff. The SD-7 drill hole penetrated the top several tens of feet into the Tram Tuff, which underlies the Prow Pass and Bullfrog Tuffs. These latter three units are all formations of the Crater Flat Group, The drill hole was collared in welded materials assigned to the crystal-poor middle nonlithophysal zone of the Tiva Canyon Tuff; approximately 280 ft (85 m) of this ash-flow sheet was penetrated by the hole. The Yucca Mountain Tuff appears to be missing from the section at the USW SD-7 location, and the Pah Canyon Tuff is only 14.5 ft thick. The Pah Canyon Tuff was not recovered in core because of drilling difficulties, suggesting that the unit is entirely nonwelded. The presence of this unit is inferred through interpretation of down-hole geophysical logs.

  18. Moessbauer studies in Zn(2+)0.3 Mn(2+)0.7 Mn(3+) (2-y) Fe(3+) (2-y) O4

    NASA Technical Reports Server (NTRS)

    Gupta, R. G.; Mendiratta, R. G.; Escue, W. T.

    1975-01-01

    The Mossbauer effect has proven to be effective in the study of nuclear hyperfine interactions. Ferrite systems having the formula (Zn(2+)0.3)(Mn(2+)0.7)(Mn(3+)y)(Fe(3+)2-y)(O4) were prepared and studied. These systems can be interpreted as mangacese-doped zinc and a part of iron ions. A systematic study of these systems is presented to promote an understanding of their microstructure for which various theories were proposed.

  19. 40 CFR Table 28 to Subpart G of... - Deck Seam Length Factors a (SD) for Internal Floating Roof Tanks

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 9 2011-07-01 2011-07-01 false Deck Seam Length Factors a (SD) for Internal Floating Roof Tanks 28 Table 28 to Subpart G of Part 63 Protection of Environment ENVIRONMENTAL... (SD) for Internal Floating Roof Tanks Deck construction Typical deck seam length factor...

  20. 40 CFR Table 28 to Subpart G of... - Deck Seam Length Factors a (SD) for Internal Floating Roof Tanks

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 9 2010-07-01 2010-07-01 false Deck Seam Length Factors a (SD) for..., and Wastewater Pt. 63, Subpt. G, Table 28 Table 28 to Subpart G of Part 63—Deck Seam Length Factors a (SD) for Internal Floating Roof Tanks Deck construction Typical deck seam length factor...

  1. Comparison of three GPCR structural templates for modeling of the P2Y12 nucleotide receptor

    NASA Astrophysics Data System (ADS)

    Deflorian, Francesca; Jacobson, Kenneth A.

    2011-04-01

    The P2Y12 receptor (P2Y12R) is an ADP-activated G protein-coupled receptor (GPCR) that is an important target for antithrombotic drugs. Three homology models of P2Y12R were compared, based on different GPCR structural templates: bovine rhodopsin (bRHO), human A2A adenosine receptor (A2AAR), and human C-X-C chemokine receptor type 4 (CXCR4). By criteria of sequence analysis (25.6% identity in transmembrane region), deviation from helicity in the second transmembrane helix (TM2), docked poses of ligands highlighting the role of key residues, accessibility of a conserved disulfide bridge that is reactive toward irreversibly-binding antagonists, and the presence of a shared disulfide bridge between the third extracellular loop (EL3) and the N-terminus, the CXCR4-based model appeared to be the most consistent with known characteristics of P2Y12R. The docked poses of agonist 2MeSADP and charged anthraquinone antagonist PSB-0739 in the binding pocket of P2Y12R-CXC agree with previously published site-directed mutagenesis studies of Arg256 and Lys280. A sulfonate at position 2 of the anthraquinone core created a strong interaction with the Lys174(EL2) side chain. The docking poses of the irreversibly-binding, active metabolite (existing as two diastereoisomers in vivo) of the clinically utilized antagonist Clopidogrel were compared. The free thiol group of the 4S diastereoisomer, but not the 4R isomer, was found in close proximity ( 4.7 Å) to the sulfur atom of a disulfide bridge involving Cys175, suggesting greater activity in covalent binding. Therefore, ligand docking to the CXCR4-based model of the P2Y12R predicted poses of both reversibly and irreversibly-binding small molecules, consistent with observed pharmacology and mutagenesis studies.

  2. Identification of a new dysfunctional platelet P2Y12 receptor variant associated with bleeding diathesis

    PubMed Central

    Lecchi, Anna; Razzari, Cristina; Paoletta, Silvia; Dupuis, Arnaud; Nakamura, Lea; Ohlmann, Philippe; Gachet, Christian; Jacobson, Kenneth A.; Zieger, Barbara

    2015-01-01

    Defects of the platelet P2Y12 receptor (P2Y12R) for adenosine diphosphate (ADP) are associated with increased bleeding risk. The study of molecular abnormalities associated with inherited qualitative defects of the P2Y12R protein is useful to unravel structure-function relationships of the receptor. We describe the case of 2 brothers, sons of first cousins, with lifelong history of abnormal bleeding, associated with dysfunctional P2Y12R and a previously undescribed missense mutation in the encoding gene. ADP (4-20 µM)–induced aggregation of patients’ platelets was markedly reduced and rapidly reversible. Other agonists induced borderline-normal aggregation. Inhibition of vasodilator-stimulated phosphoprotein phosphorylation and prostaglandin E1–induced increase in cyclic adenosine monophosphate (cAMP) by ADP was impaired, whereas inhibition of cAMP increase by epinephrine was normal. [3H]PSB-0413, a selective P2Y12R antagonist, bound to a normal number of binding sites; however, its affinity, and that of the agonists ADP and 2-methylthio-adenosine-5′-diphosphate, was reduced. Patients’ DNA showed a homozygous c.847T>A substitution that changed the codon for His-187 to Gln (p.His187Gln). Crystallographic data and molecular modeling studies indicated that His187 in transmembrane 5 is important for agonist and nucleotide antagonist binding and located in a region undergoing conformational changes. These studies delineate a region of P2Y12R required for normal function after ADP binding. PMID:25428217

  3. Uridine Triphosphate Thio Analogues Inhibit Platelet P2Y12 Receptor and Aggregation

    PubMed Central

    Gündüz, Dursun; Tanislav, Christian; Sedding, Daniel; Parahuleva, Mariana; Santoso, Sentot; Troidl, Christian; Hamm, Christian W.; Aslam, Muhammad

    2017-01-01

    Platelet P2Y12 is an important adenosine diphosphate (ADP) receptor that is involved in agonist-induced platelet aggregation and is a valuable target for the development of anti-platelet drugs. Here we characterise the effects of thio analogues of uridine triphosphate (UTP) on ADP-induced platelet aggregation. Using human platelet-rich plasma, we demonstrate that UTP inhibits P2Y12 but not P2Y1 receptors and antagonises 10 µM ADP-induced platelet aggregation in a concentration-dependent manner with an IC50 value of ~250 µM. An eight-fold higher platelet inhibitory activity was observed with a 2-thio analogue of UTP (2S-UTP), with an IC50 of 30 µM. The 4-thio analogue (4S-UTP) with an IC50 of 7.5 µM was 33-fold more effective. A three-fold decrease in inhibitory activity, however, was observed by introducing an isobutyl group at the 4S- position. A complete loss of inhibition was observed with thio-modification of the γ phosphate of the sugar moiety, which yields an enzymatically stable analogue. The interaction of UTP analogues with P2Y12 receptor was verified by P2Y12 receptor binding and cyclic AMP (cAMP) assays. These novel data demonstrate for the first time that 2- and 4-thio analogues of UTP are potent P2Y12 receptor antagonists that may be useful for therapeutic intervention. PMID:28146050

  4. The Mysterious sdO X-ray Binary BD+37°442

    NASA Astrophysics Data System (ADS)

    Heber, U.; Geier, S.; Irrgang, A.; Schneider, D.; Barbu-Barna, I.; Mereghetti, S.; La Palombara, N.

    2014-04-01

    Pulsed X-ray emission in the luminous, helium-rich sdO BD +37°442 has recently been discovered (La Palombara et al. 2012). It was suggested that the sdO star has a neutron star or white dwarf companion with a spin period of 19.2 s. After HD 49798, which has a massive white dwarf companion spinning at 13.2 s in an 1.55 day orbit, this is only the second O-type subdwarf from which X-ray emission has been detected. We report preliminary results of our ongoing campaign to obtain time-resolved high-resolution spectroscopy using the CAFE instrument at Calar Alto observatory and SARG at the Telescopio Nationale Galileo. Atmospheric parameters were derived via a quantitative NLTE spectral analysis. The line fits hint at an unusually large projected rotation velocity. Therefore it seemed likely that BD +37°442 is a binary similar to HD 49798 and that the orbital period is also similar. The level of X-ray emission from BD +37°442 could be explained by accretion from the sdO wind by a neutron star orbiting at a period of less than ten days. Hence, we embarked on radial velocity monitoring in order to derive the binary parameters of the BD+37°442 system and obtained 41 spectra spread out over several month in 2012. Unlike for HD 49798, no radial velocity variations were found and, hence, there is no dynamical evidence for the existence of a compact companion yet. The origin of the pulsed X-ray emission remains as a mystery.

  5. A complex noise reduction method for improving visualization of SD-OCT skin biomedical images

    NASA Astrophysics Data System (ADS)

    Myakinin, Oleg O.; Zakharov, Valery P.; Bratchenko, Ivan A.; Kornilin, Dmitry V.; Khramov, Alexander G.

    2014-05-01

    In this paper we consider the original method of solving noise reduction problem for visualization's quality improvement of SD-OCT skin and tumors biomedical images. The principal advantages of OCT are high resolution and possibility of in vivo analysis. We propose a two-stage algorithm: 1) process of raw one-dimensional A-scans of SD-OCT and 2) remove a noise from the resulting B(C)-scans. The general mathematical methods of SD-OCT are unstable: if the noise of the CCD is 1.6% of the dynamic range then result distortions are already 25-40% of the dynamic range. We use at the first stage a resampling of A-scans and simple linear filters to reduce the amount of data and remove the noise of the CCD camera. The efficiency, improving productivity and conservation of the axial resolution when using this approach are showed. At the second stage we use an effective algorithms based on Hilbert-Huang Transform for more accurately noise peaks removal. The effectiveness of the proposed approach for visualization of malignant and benign skin tumors (melanoma, BCC etc.) and a significant improvement of SNR level for different methods of noise reduction are showed. Also in this study we consider a modification of this method depending of a specific hardware and software features of used OCT setup. The basic version does not require any hardware modifications of existing equipment. The effectiveness of proposed method for 3D visualization of tissues can simplify medical diagnosis in oncology.

  6. Correlation between SD-OCT, immunocytochemistry and functional findings in an animal model of retinal degeneration

    PubMed Central

    Cuenca, Nicolás; Fernández-Sánchez, Laura; Sauvé, Yves; Segura, Francisco J.; Martínez-Navarrete, Gema; Tamarit, José Manuel; Fuentes-Broto, Lorena; Sanchez-Cano, Ana; Pinilla, Isabel

    2014-01-01

    Purpose: The P23H rhodopsin mutation is an autosomal dominant cause of retinitis pigmentosa (RP). The degeneration can be tracked using different anatomical and functional methods. In our case, we evaluated the anatomical changes using Spectral-Domain Optical Coherence Tomography (SD-OCT) and correlated the findings with retinal thickness values determined by immunocytochemistry.Methods: Pigmented rats heterozygous for the P23H mutation, with ages between P18 and P180 were studied. Function was assessed by means of optomotor testing and ERGs. Retinal thicknesses measurements, autofluorescence and fluorescein angiography were performed using Spectralis OCT. Retinas were studied by means of immunohistochemistry. Results: Between P30 and P180, visual acuity decreased from 0.500 to 0.182 cycles per degree (cyc/deg) and contrast sensitivity decreased from 54.56 to 2.98 for a spatial frequency of 0.089 cyc/deg. Only cone-driven b-wave responses reached developmental maturity. Flicker fusions were also comparable at P29 (42 Hz). Double flash-isolated rod-driven responses were already affected at P29. Photopic responses revealed deterioration after P29.A reduction in retinal thicknesses and morphological modifications were seen in OCT sections. Statistically significant differences were found in all evaluated thicknesses. Autofluorescence was seen in P23H rats as sparse dots. Immunocytochemistry showed a progressive decrease in the outer nuclear layer (ONL), and morphological changes. Although anatomical thickness measures were significantly lower than OCT values, there was a very strong correlation between the values measured by both techniques.Conclusions: In pigmented P23H rats, a progressive deterioration occurs in both retinal function and anatomy. Anatomical changes can be effectively evaluated using SD-OCT and immunocytochemistry, with a good correlation between their values, thus making SD-OCT an important tool for research in retinal degeneration. PMID:25565976

  7. SD-OCT and Adaptive Optics Imaging of Outer Retinal Tubulation

    PubMed Central

    King, Brett J.; Sapoznik, Kaitlyn A.; Elsner, Ann E.; Gast, Thomas J.; Papay, Joel A.; Clark, Christopher A.; Burns, Stephen A.

    2017-01-01

    ABSTRACT Purpose To investigate outer retinal tubulation (ORT) using spectral domain optical coherence tomography (SD-OCT) and an adaptive optics scanning laser ophthalmoscope (AOSLO). To document the frequency of ORT in atrophic retinal conditions and quantify ORT dimensions versus adjacent retinal layers. Methods SD-OCT images were reviewed for the presence of retinal atrophy, scarring, and/or exudation. The greatest width of each ORT was quantified. Inner and outer retinal thicknesses adjacent to and within the area of ORT were measured for 18 patients. AOSLO imaged ORTs in five subjects with direct and scattered light imaging. Results ORT was identified in 47 of 76 subjects (61.8%) and in 65 eyes via SD-OCT in a wide range of conditions and ages, and in peripapillary atrophy. ORTs appeared as finger-like projections in atrophy, seen in the en face images. AOSLO showed some ORTs with bright cones that guide light within atrophic areas. Multiply scattered light mode AOSLO visualized variegated lines (18–35 μm) radiating from ORTs. The ORTs’ width on OCT b-scan images varied from 70 to 509 μm. The inner retina at the ORT was significantly thinner than the adjacent retina, 135 vs.170 μm (P = .004), whereas the outer retina was significantly thicker, 115 vs. 80 μm (P = .03). Conclusions ORTs are quite common in eyes with retinal atrophy in various disorders. ORTs demonstrate surviving photoreceptors in tubular structures found within otherwise nonsupportive atrophic areas that lack retinal pigment epithelium and choriocapillaris. PMID:27984506

  8. Discovery of Potential Orthosteric and Allosteric Antagonists of P2Y1R from Chinese Herbs by Molecular Simulation Methods

    PubMed Central

    Lu, Fang; Jiang, Lu-di; Qiao, Lian-sheng; Xiang, Yu-hong

    2016-01-01

    P2Y1 receptor (P2Y1R), which belongs to G protein-coupled receptors (GPCRs), is an important target in ADP-induced platelet aggregation. The crystal structure of P2Y1R has been solved recently, which revealed orthosteric and allosteric ligand-binding sites with the details of ligand-protein binding modes. And it suggests that P2Y1R antagonists, which recognize two distinct sites, could potentially provide an efficacious and safe antithrombotic profile. In present paper, 2D similarity search, pharmacophore based screening, and molecular docking were used to explore the potential natural P2Y1R antagonists. 2D similarity search was used to classify orthosteric and allosteric antagonists of P2Y1R. Based on the result, pharmacophore models were constructed and validated by the test set. Optimal models were selected to discover potential P2Y1R antagonists of orthosteric and allosteric sites from Traditional Chinese Medicine (TCM). And the hits were filtered by Lipinski's rule. Then molecular docking was used to refine the results of pharmacophore based screening and analyze the binding mode of the hits and P2Y1R. Finally, two orthosteric and one allosteric potential compounds were obtained, which might be used in future P2Y1R antagonists design. This work provides a reliable guide for discovering natural P2Y1R antagonists acting on two distinct sites from TCM. PMID:27635149

  9. EXOTIME: Searching for planets and measuring \\dot{P} in sdB pulsators

    NASA Astrophysics Data System (ADS)

    Lutz, R.; Schuh, S.; Silvotti, R.

    2012-12-01

    We review the status of the EXOTIME project (EXOplanet search with the TIming MEthod). The two main goals of EXOTIME are to search for sub-stellar companions to sdB stars in wide orbits, and to measure the secular variation of the pulsation periods, which are related to the evolutionary change of the stellar structure. Now, after four years of dense monitoring, we start to see some results and present the brown dwarf and exoplanet candidates V1636 Ori b and DW Lyn b.

  10. Geology of the USW SD-9 drill hole, Yucca Mountain, Nevada

    SciTech Connect

    Engstrom, D.A.; Rautman, C.A.

    1996-10-01

    Drill hole USW SD-9 is one of several holes drilled under Site Characterization Plan Study as part of the characterization program at Yucca Mountain, Nevada, which has been proposed as the potential location of a repository for high-level nuclear waste. The SD-9 drill hole is located in the northern part of the potential repository area. Quantitative and semiquantitative data are included in this report for cover recovery, rock-quality designation (RQD), lithophysal cavity abundance, and fracturing. These data are spatially variable, both within and among the major formational-level stratigraphic units. Nonwelded intervals in general exhibit higher recoveries and more intact (higher) RQD values than welded intervals. The most intact, highest-RQD materials encountered within the Topopah Spring belong to the lower 33.3 ft of the middle nonlithophysal zone. This report includes quantitative data for the framework material properties of porosity, bulk and particle density, and saturated hydraulic conductivity. Graphical analysis of variations in these laboratory hydrologic properties indicates first-order control of material properties by the degree of welding and the presence of zeolite minerals. Many major lithostratigraphic contacts are not well expressed in the material-property profiles; contacts of material-property units are related more to changes in the intensity of welding. Approximate in-situ saturation data of samples preserved immediately upon recovery from the hole are included in the data tabulation.

  11. EC 03089-6421: a new, very rapidly pulsating sdO star

    NASA Astrophysics Data System (ADS)

    Kilkenny, D.; Worters, H. L.; Østensen, R. H.

    2017-01-01

    EC 03089-6421, classified sdO in the Edinburgh-Cape (EC) blue object survey, is shown to have unusually rapid pulsations with a dominant frequency near 32 mHz (amplitude ˜0.02 mag; period 31.1s) - which appears to be strongly variable in amplitude on timescales of hours and days - and a generally weaker frequency near 29 mHz (amplitude ˜0.004 mag; period 34.2s) which is also variable in amplitude. This star varies at twice the frequency of any known hot subdwarf pulsator. Although the low resolution EC spectrogram appears very similar to those of DAO stars, our analysis derives Teff = 40200 ± 1600 K; log g = 6.25 ± 0.23 and log N(He)/N(H) = -1.63 ± 0.55; more recent spectrograms give Teff = 37400 ± 1000 K; log g = 5.70 ± 0.13 and log N(He)/N(H) = -2.02 ± 0.17, both of which indicate that the gravity is too low for a white dwarf star, although the low temperature derived from the Balmer lines is at odds with the absence of neutral Helium and the strength of He II 4686. It is possible that EC 03089-6421 is a field analogue of the ω Cen sdO variables.

  12. A framework for classification and segmentation of branch retinal artery occlusion in SD-OCT

    NASA Astrophysics Data System (ADS)

    Guo, Jingyun; Shi, Fei; Zhu, Weifang; Chen, Haoyu; Chen, Xinjian

    2016-03-01

    Branch retinal artery occlusion (BRAO) is an ocular emergency which could lead to blindness. Quantitative analysis of BRAO region in the retina is very needed to assessment of the severity of retinal ischemia. In this paper, a fully automatic framework was proposed to classify and segment BRAO based on 3D spectral-domain optical coherence tomography (SD-OCT) images. To the best of our knowledge, this is the first automatic 3D BRAO segmentation framework. First, a support vector machine (SVM) based classifier is designed to differentiate BRAO into acute phase and chronic phase, and the two types are segmented separately. To segment BRAO in chronic phase, a threshold-based method is proposed based on the thickness of inner retina. While for segmenting BRAO in acute phase, a two-step segmentation is performed, which includes the bayesian posterior probability based initialization and the graph-search-graph-cut based segmentation. The proposed method was tested on SD-OCT images of 23 patients (12 of acute and 11 of chronic phase) using leave-one-out strategy. The overall classification accuracy of SVM classifier was 87.0%, and the TPVF and FPVF for acute phase were 91.1%, 5.5%; for chronic phase were 90.5%, 8.7%, respectively.

  13. FUV, UV, and Optical Observations of the He-sdO Star BD+39 3226

    NASA Astrophysics Data System (ADS)

    Chayer, Pierre; Green, E. M.; Fontaine, G.

    2014-01-01

    Based on observations carried out with the Far Ultraviolet Spectroscopic Explorer, the Space Telescope Imaging Spectrograph, the MMT Observatory, and the Keck telescope HIRES spectrograph, we present a spectral analysis of the He-sdO star BD+39 3226. By fitting the MMT spectrum we obtain a gravity that is 0.7 dex higher than the one reported in the literature. The new atmospheric parameters will have an impact on the measurement of the HI column density toward BD+39 3226, and by this very fact on the deuterium abundance. The high-resolution spectra show stellar absorption lines coming from C, N, O, Si, P, S, Fe, and Ni. The spectra also show lines from heavy elements such as Ge, As, and Sn. On the other hand, neither Zr nor Pb absorption lines are detected. The non-detection of lead in BD+39 3226 indicates that the star does not belong to the newly discovered group of lead-rich He-sdO stars. P.C. is supported by the Canadian Space Agency under a Public Works and Government Services of Canada contract.

  14. HS 0705+6700: a New Eclipsing sdB Binary

    NASA Astrophysics Data System (ADS)

    Drechsel, H.; Heber, U.; Napiwotzki, R.; Ostensen, R.; Solheim, J.-E.; Deetjen, J.; Schuh, S.

    HS 0705+6700 is a newly discovered eclipsing sdB binary system consisting of an sdB primary and a cool secondary main sequence star. CCD photometry obtained in October and November 2000 with the 2.5m Nordic (NOT) telescope (La Palma, Tenerife) in the B passband and with the 2.2m Calar Alto telescope (CAFOS, R filter) yielded eclipse light curves with complete orbital phase coverage at high time resolution. A periodogram analysis of 12 primary minimum times distributed over the time span from October 2000 to March 2001 allowed to derive the following exact period and linear ephemeris: prim. min. = HJD 2451822.759782(22) + 0.09564665(39) ṡ E A total of 15 spectra taken with the 3.5m Calar Alto telescope (TWIN spectrograph) on March 11-12, 2001, were used to establish the radial velocity curve of the primary star (K1 = 85.8 km/s) , and to determine its basic atmospheric parameters (Teff = 29300 K, log g = 5.47). The B and R light curves were solved using our Wilson-Devinney based light curve analysis code MORO (Drechsel et al. 1995, A&A 294, 723). The best fit solution yielded exact system parameters consistent with the spectroscopic results. Detailed results will be published elsewhere (Drechsel et al. 2001, A&A, in preparation).

  15. Analysis of the variability in the sdB star KIC 10670103: DFA approach

    NASA Astrophysics Data System (ADS)

    Zebende, Gilney F.; Fernandez, Basilio F.; Pereira, Marildo G.

    2017-01-01

    The brightness variation of the stars is an object of study in astronomy and astrophysics for representing the rich inherent source of physical information. Launched in 2009, the Kepler spacecraft with the primary mission of identifying equivalent to the Earth by the Sun transits also gave birth to thousands of light curves of targets of scientific interest. KIC 10670103, the richest pulsating sub-dwarf B (sdB) star, is one of the many stars identified by the mission. With 3.72 yr of Kepler spacecraft observations, we analysed in this paper the light curve of this sdB star, by the detrended fluctuation analysis (DFA) method. The behaviour of this pulsating star reveals self-affinity at specific time-scales, with changes in DFA exponent, αDFA. This fact suggests some light variability in KIC 10670103, as for example, from a non-periodic to a periodic case, among others. Therefore, we propose to connect the pulsation pattern of the KIC 10670103 star, which presents trends and non-stationarity, with the αDFA exponent. In this sense, we obtain five values of αDFA related to the light variability properties of KIC 10670103. A pictorial figure will describe the relationship between these variables.

  16. Crucial factor for increasing the conjugation frequency in Streptomyces netropsis SD-07 and other strains.

    PubMed

    Wang, Xian-Kun; Jin, Jian-Ling

    2014-08-01

    Streptomyces netropsis SD-07, the producer of novel polyene macrolide antifungal antibiotics, was isolated from soil. For the investigation of the functions of its biosynthesis genes and regulation mechanisms, a genetic operating system is necessary. In this study, we successfully transferred the plasmid DNA of pSET152 from the methylation deficient donor, Escherichia coli ET12567/pSET152/pUZ8002, to S. netropsis SD-07 by conjugation and evaluated the crucial factors influencing the conjugation frequency. Ca(2+) ions in presence the conjugation media may increase the conjugation frequency by 1000-10 000 times than Ca(2+) ions absence in the same conjugation media, and 10-100 time higher than Mg(2+) ions. Similar results (increasing the conjugation frequency by 10-100 times when media containing 60 mM CaCl2 ) were also obtained from the conjugation between E. coli ET12567 and Streptomyces coelicolor, S. lavendulae, S. venezuelae, despite their conjugation media were different (MS, CM, GS). So, CaCl2 concentration is a crucial factor for increasing the conjugation frequency, and the suitable concentration may probably be 60 mM. In addition, synthetic medium containing a small amount of organic nitrogen source may benefit increasing the conjugation frequency. These findings could be valuable for the development of a practical method for achieving conjugation in other Streptomyces spp.

  17. Complex dynamics of an archetypal self-excited SD oscillator driven by moving belt friction

    NASA Astrophysics Data System (ADS)

    Zhi-Xin, Li; Qing-Jie, Cao; Léger, Alain

    2016-01-01

    We propose an archetypal self-excited system driven by moving belt friction, which is constructed with the smooth and discontinuous (SD) oscillator proposed by the Cao et al. and the classical moving belt. The moving belt friction is modeled as the Coulomb friction to formulate the mathematical model of the proposed self-excited SD oscillator. The equilibrium states of the unperturbed system are obtained to show the complex equilibrium bifurcations. Phase portraits are depicted to present the hyperbolic structure transition, the multiple stick regions, and the friction-induced asymmetry phenomena. The numerical simulations are carried out to demonstrate the friction-induced vibration of multiple stick-slip phenomena and the stick-slip chaos in the perturbed self-excited system. The results presented here provide an opportunity for us to get insight into the mechanism of the complex friction-induced nonlinear dynamics in mechanical engineering and geography. Project supported by the National Natural Science Foundation of China (Grant Nos. 11372082 and 11572096) and the National Basic Research Program of China (Grant No. 2015CB057405).

  18. Evaluation of SD-208, a TGF-β-RI Kinase Inhibitor, as an Anticancer Agent in Retinoblastoma.

    PubMed

    Fadakar, Puran; Akbari, Abolfazl; Ghassemi, Fariba; Mobini, Gholam Reza; Mohebi, Masoumeh; Bolhassani, Manzar; Abed Khojasteh, Hoda; Heidari, Mansour

    2016-06-01

    Retinoblastoma is the most common intraocular tumor in children resulting from genetic alterations and transformation of mature retinal cells. The objective of this study was to investigate the effects of SD-208, TGF-β-RI kinase inhibitor, on the expression of some miRNAs including a miR-17/92 cluster in retinoblastoma cells. Prior to initiate this work, the cell proliferation was studied by Methyl Thiazolyl Tetrazolium (MTT) and bromo-2'-deoxyuridine (BrdU) assays. Then, the expression patterns of four miRNAs (18a, 20a, 22, and 34a) were investigated in the treated SD-208 (0.0, 1, 2 and 3 µM) and untreated Y-79 cells. A remarkable inhibition of the cell proliferation was found in Y-79 cells treated with SD-208 versus untreated cells. Also, the expression changes were observed in miRNAs 18a, 20a, 22 and 34a in response to SD-208 treatment (P<0.05). The findings of the present study suggest that the anti-cancer effect of SD-208 may be exerted due to the regulation of specific miRNAs, at least in this particular retinoblastoma cell line. To the best of the researchers' knowledge, this is the first report demonstrating that the SD-208 could alter the expression of tumor suppressive miRNAs as well as oncomiRs in vitro. In conclusion, the present data suggest that SD-208 could be an alternative agent in retinoblastoma treatment.

  19. Personalized antiplatelet therapy with P2Y12 receptor inhibitors: benefits and pitfalls

    PubMed Central

    Winter, Max-Paul; Koziński, Marek; Kubica, Jacek; Aradi, Daniel

    2015-01-01

    Antiplatelet therapy with P2Y12 receptor inhibitors has become the cornerstone of medical treatment in patients with acute coronary syndrome, after percutaneous coronary intervention and in secondary prevention of atherothrombotic events. Clopidogrel used to be the most broadly prescribed P2Y12 receptor inhibitor with undisputable benefits especially in combination with aspirin, but a considerable number of clopidogrel-treated patients experience adverse thrombotic events in whom insufficient P2Y12-inhibition and a consequential high on-treatment platelet reactivity is a common finding. This clinically relevant limitation of clopidogrel has driven the increased use of new antiplatelet agents. Prasugrel (a third generation thienopyridine) and ticagrelor (a cyclopentyl-triazolo-pyrimidine) feature more potent and predictable P2Y12-inhibition compared to clopidogrel, which translates into improved ischemic outcomes. However, excessive platelet inhibition and consequential low on-treatment platelet reactivity comes at the price of increased risk of major bleeding. The majority of randomized clinical trials failed to demonstrate improved clinical outcomes with platelet function testing and tailored antiplatelet therapy, but results of all recent trials of potent antiplatelets and prolonged antiplatelet durations point towards a need for individualized antiplatelet approach in order to decrease thrombotic events without increasing bleeding. This review focuses on potential strategies for personalizing antiplatelet treatment. PMID:26677375

  20. Molecular determinants of P2Y2 nucleotide receptor function: implications for proliferative and inflammatory pathways in astrocytes.

    PubMed

    Weisman, Gary A; Wang, M; Kong, Q; Chorna, N E; Neary, J T; Sun, Grace Y; González, Fernando A; Seye, C I; Erb, L

    2005-01-01

    In the mammalian nervous system, P2 nucleotide receptors mediate neurotransmission, release of proinflammatory cytokines, and reactive astrogliosis. Extracellular nucleotides activate multiple P2 receptors in neurons and glial cells, including G protein-coupled P2Y receptors and P2X receptors, which are ligand-gated ion channels. In glial cells, the P2Y2 receptor subtype, distinguished by its ability to be equipotently activated by ATP and UTP, is coupled to pro-inflammatory signaling pathways. In situ hybridization studies with rodent brain slices indicate that P2Y2 receptors are expressed primarily in the hippocampus and cerebellum. Astrocytes express several P2 receptor subtypes, including P2Y2 receptors whose activation stimulates cell proliferation and migration. P2Y2 receptors, via an RGD (Arg-Gly-Asp) motif in their first extracellular loop, bind to alphavbeta3/beta5 integrins, whereupon P2Y2 receptor activation stimulates integrin signaling pathways that regulate cytoskeletal reorganization and cell motility. The C-terminus of the P2Y2 receptor contains two Src-homology-3 (SH3)-binding domains that upon receptor activation, promote association with Src and transactivation of growth factor receptors. Together, our results indicate that P2Y2 receptors complex with both integrins and growth factor receptors to activate multiple signaling pathways. Thus, P2Y2 receptors present novel targets to control reactive astrogliosis in neurodegenerative diseases.

  1. The purinergic P2Y14 receptor axis is a molecular determinant for organism survival under in utero radiation toxicity.

    PubMed

    Kook, S H; Cho, J S; Morrison, A; Wiener, E; Lee, S B; Scadden, D; Lee, B-C

    2013-07-04

    In utero exposure of the embryo and fetus to radiation has been implicated in malformations or fetal death, and often produces lifelong health consequences such as cancers and mental retardation. Here we demonstrate that deletion of a G-protein-coupled purinergic receptor, P2Y14, confers potent resistance to in utero radiation. Intriguingly, a putative P2Y14 receptor ligand, UDP-glucose, phenocopies the effect of P2Y14 deficiency. These data indicate that P2Y14 is a receptor governing in utero tolerance to genotoxic stress that may be pharmacologically targeted to mitigate radiation toxicity in pregnancy.

  2. Longitudinal fundus and retinal studies with SD-OCT: a comparison of five mouse inbred strains.

    PubMed

    Puk, Oliver; de Angelis, Martin Hrabĕ; Graw, Jochen

    2013-06-01

    Spectral domain optical coherence tomography (SD-OCT) has recently been established as a method for in vivo imaging of fundus and retina in the mouse. It enables more effective studies of retinal diseases including investigations of etiopathologic mechanisms. In order to learn more about longitudinal fundus development and to enable recognition of disease-associated irregularities, we performed confocal scanning laser ophthalmoscopy (cSLO) and SD-OCT measurements in the inbred strains C57BL/6J, C3HeB/FeJ, FVB/NCrl, BALB/cByJ, and 129S2/SvJ when they were between 2 and 6 months of age. In general, cSLO and SD-OCT data did not reveal sex-specific or unilateral differences. C3HeB/FeJ and FVB/NCrl mice showed diffuse choroidal dysplasia. Choroidal vein-like structures appeared as dark fundus stripes in C3HeB/FeJ. In FVB/NCrl, fundus fleck accumulation was found. In contrast, only minor time-dependent changes of fundus appearance were observed in C57BL/6J, BALB/cByJ, and 129S2/SvJ. This was also found for individual fundic main blood vessel patterns in all inbred strains. Vessel numbers varied between 6 and 13 in C57BL/6J. This was comparable in most cases. We further found that retinae were significantly thicker in C57BL/6J compared to the other strains. Total retinal thickness generally did not change between 2 and 6 months of age. As a conclusion, our results indicate lifelong pathologic processes in C3HeB/FeJ and FVB/NCrl that affect choroid and orbital tissues. Inbred strains with regular retinal development did not reveal major time-dependent variations of fundus appearance, blood vessel pattern, or retinal thickness. Consequently, progressive changes of these parameters are suitable indicators for pathologic outliers.

  3. Electronic disorder, spin glass and large magnetoresistance in FeSr2Y2-yCeyCu2O8+x

    NASA Astrophysics Data System (ADS)

    Sambale, Sebastian; Williams, Grant; Stephan, Jibu; Chong, Shen

    2014-03-01

    We have successfully synthesized FeSr2Y2-yCeyCu2O8+x (Fe1222) with a wide range of Ce and oxygen concentrations. Fe1222 belongs to an interesting group of compounds that contains a 2D-like CuO2 layer and an oxygen deficient FeOx layer. They are structural very similar to the well-studied superconducting and magnetically ordered RuSr2R2-xCexCu2O10-x (Ru1222). However, we do not observe superconductivity in Fe1222 and there is a spin-glass transition with antiferromagnetic exchange interactions arising from the disordered FeOx layer at ~25 K, which does not depend on the Ce or oxygen concentration. The electronic transport in the oxygen reduced samples is highly disordered and involves variable range hopping between localized states where there is a large negative magnetoresistance of ~-22% at 8 T. The oxygen saturated samples are highly conducting at room temperature and display weak localization at low temperatures. The absence of superconductivity may be due to pair-breaking by a small Fe fraction in the CuO2 planes. NZ Marsden Fund

  4. Spectral Analysis of the sdO Standard Star Feige 34

    NASA Astrophysics Data System (ADS)

    Latour, M.; Chayer, P.; Green, E. M.; Fontaine, G.

    2017-03-01

    We present our current work on the spectral analysis of the hot sdO star Feige 34. We combine high S/N optical spectra and fully-blanketed non-LTE model atmospheres to derive its fundamental parameters (Teff, log g) and helium abundance. Our best fits indicate Teff = 63 000 K, log g = 6.0 and log N(He)/N(H) = –1.8. We also use available ultraviolet spectra (IUE and FUSE) to measure metal abundances. We find the star to be enriched in iron and nickel by a factor of ten with respect to the solar values, while lighter elements have subsolar abundances. The FUSE spectrum suggests that the spectral lines could be broadened by rotation.

  5. Pressure-induced s-->d transfer and the equation of state of molybdenum

    NASA Astrophysics Data System (ADS)

    Godwal, B. K.; Jeanloz, Raymond

    1990-04-01

    The equations of state of crystalline (bcc) and liquid molybdenum are calculated to pressure-temperature conditions of 600 GPa and 14 000 K with use of the linear muffin-tin orbitals (LMTO) model and corrected rigid-ion sphere (CRIS) model. Our results agree with those of previous work in documenting a pressure-induced shift of electrons from 5s to 4d states, especially above 100 GPa. An analysis of ultrasonic and shock-wave measurements, along with our theoretical findings, documents that the compressibility of bcc Mo becomes enhanced at pressures of 100-200 GPa. The enhanced compression, and possibly an anomalous increase in rigidity, are caused by the pressure-induced s-->d transfer. Our study reinforces the use of the Mo equation of state as a calibration standard for ultrahigh-pressure static experiments and, in particular, for the ruby-fluorescence technique.

  6. Electrical Characterization of the RCA CDP1822SD Random Access Memory, Volume 1, Appendix a

    NASA Technical Reports Server (NTRS)

    Klute, A.

    1979-01-01

    Electrical characteristization tests were performed on 35 RCA CDP1822SD, 256-by-4-bit, CMOS, random access memories. The tests included three functional tests, AC and DC parametric tests, a series of schmoo plots, rise/fall time screening, and a data retention test. All tests were performed on an automated IC test system with temperatures controlled by a thermal airstream unit. All the functional tests, the data retention test, and the AC and DC parametric tests were performed at ambient temperatures of 25 C, -20 C, -55 C, 85 C, and 125 C. The schmoo plots were performed at ambient temperatures of 25 C, -55 C, and 125 C. The data retention test was performed at 25 C. Five devices failed one or more functional tests and four of these devices failed to meet the expected limits of a number of AC parametric tests. Some of the schmoo plots indicated a small degree of interaction between parameters.

  7. Source identification in acoustics and structural mechanics using Sierra/SD.

    SciTech Connect

    Walsh, Timothy Francis; Aquino, Wilkins; Ross, Michael

    2013-03-01

    In this report we derive both time and frequency-domain methods for inverse identification of sources in elastodynamics and acoustics. The inverse/design problem is cast in a PDE-constrained optimization framework with efficient computation of gradients using the adjoint method. The implementation of source inversion in Sierra/SD is described, and results from both time and frequency domain source inversion are compared to actual experimental data for a weapon store used in captive carry on a military aircraft. The inverse methodology is advantageous in that it provides a method for creating ground based acoustic and vibration tests that can reduce the actual number of flight tests, and thus, saving costs and time for the program.

  8. Molecular hydrogen 3s,d 3Λg+ complex revisited

    NASA Astrophysics Data System (ADS)

    Pazyuk, E. A.; Pupyshev, V. I.; Stolyarov, A. V.; Kiyoshima, T.

    2002-04-01

    The rovibronic term values, Landé factors, and radiative properties of all bound levels in the 3s,d 3Λg+ complex of H2, D2, and HD are evaluated in the framework of fully ab initio channel-coupling approach. The modified multichannel quantum-defect theory is employed to transform highly accurate ab initio Born-Oppenheimer electronic matrix elements borrowed from a literature to their diabatic counterparts avoiding explicit consideration of radial coupling effects. The radiative lifetimes of the most critical levels in the H2 complex are remeasured by a delayed coincidence method. The accuracy of the predicted term values, Landé factors, transition probabilities and experimental lifetimes is sufficient to indicate the sources of disagreement in existing theory and experimental data.

  9. Virus removal capacity at varying ionic strength during nanofiltration of AlphaNine® SD.

    PubMed

    Jorba, Nuria; Shitanishi, Kenneth T; Winkler, Clint J; Herring, Steven W

    2014-09-01

    Nanofiltration is incorporated into the manufacturing processes of many protein biopharmaceuticals to enhance safety by providing the capacity to retain pathogens while allowing protein drugs to pass through the filter. Retention is mainly a function of size; however, the shape of the pathogen may also influence retention. The ability of the Viresolve(®) Pro nanofilter to remove different sized viruses during the manufacture of a Coagulation Factor IX (Alphanine(®) SD) was studied at varying ionic strength, a process condition with the potential to affect virus shape and, hence, virus retention. Eight viruses were tested in a scale-down of the nanofiltration process. Five of the viruses (EMCV, Reo, BVDV, HIV, PRV) were nanofiltered at normal sodium processing conditions and three (PPV, HAV and WNV) were nanofiltered at higher and lower sodium. Representative Reduction Factors for all viruses were ≥4.50 logs and removal was consistent over a wide range of ionic strength.

  10. Hepatoprotective potential of ethanolic extract of Aquilaria agallocha leaves against paracetamol induced hepatotoxicity in SD rats.

    PubMed

    Alam, Janey; Mujahid, Md; Badruddeen; Jahan, Yasmeen; Bagga, Paramdeep; Rahman, Md Azizur

    2017-01-01

    Many traditional systems of medicines employ herbal drugs for the hepatoprotection. Aim of the study was designed to evaluate the hepatoprotective potential of 'ethanolic extract of Aquilaria agallocha ( Chen Xiang) leaves' (AAE) against paracetamol (PCM) induced hepatotoxicity in SD rats. Group I animals were treated with 1% CMC for 8 days. Group II, III, IV and V animals were first treated with '1% CMC' 1 ml/kg/day, AAE 200 mg/kg/day, AAE 400 mg/kg/day and silymarin 100 mg/kg/day respectively for 7 days and then, orally administered with PCM 3 g/kg b. wt. on 8th day in a single dose. 24 h after the last dosing by PCM, the blood was obtained through the retro-orbital plexus under light anesthesia and the animals were sacrificed. Hepatoprotective potential was assessed by various biochemical parameters such as ALT, AST, ALP, LDH, bilirubin, cholesterol, TP and ALB. Group IV rats showed significant (p < 0.01) decrease in ALT, AST, ALP, LDH, cholesterol, bilirubin, liver wt. and relative liver wt. levels while significant (p < 0.01) increase in final b. wt., TP and ALB levels as compared to group II rats. Hepatoprotective potential of AAE 400 mg/kg/day was comparable to that of standard drug silymarin 100 mg/kg/day. Results of the study were well supported by the histopathological observations. This study confirms that AAE possesses hepatoprotective potential comparable to that of standard drug silymarin as it exhibited comparable protective potential against PCM induced hepatotoxicity in SD rats.

  11. Does repetitive Ritalin injection produce long-term effects on SD female adolescent rats?

    PubMed

    Lee, Min J; Yang, Pamela B; Wilcox, Victor T; Burau, Keith D; Swann, Alan C; Dafny, Nachum

    2009-09-01

    Methylphenidate (MPD), or Ritalin, is a psychostimulant that is prescribed for an extended period of time to children and adolescents with attention deficit hyperactivity disorder. Adolescence is a time of critical brain maturation and development, and the drug exposure during this time could lead to lasting changes in the brain that endure into the adulthood. Circadian rhythms are 24 h rhythms of physiological processes that are synchronized by the master-clock, the suprachiasmatic nucleus, to keep the body stable in a changing environment. The aim of present study is to observe the effect of repeated MPD exposure on the locomotor diurnal rhythm activity patterns of female adolescent Sprague-Dawley (SD) rats using the open field assay. 31 female adolescent SD rats were divided into four groups: control, 0.6 mg/kg, 2.5 mg/kg, and 10 mg/kg MPD group. On experimental day 1, all groups were given an injection of saline. On experimental days 2-7, animals were injected once a day with either saline, 0.6 mg/kg, 2.5 mg/kg, or 10 mg/kg MPD, and experimental days 8-10 were the washout period. A re-challenge injection was given to each animal on experimental day 11 with the similar dose as the experimental days 2-7. The locomotor movements were counted by the computerized animal activity monitoring system. The data were analyzed statistically to find out whether the diurnal rhythm activity patterns were altered. The obtained data showed that repeated administrations of 2.5 mg/kg and 10 mg/kg MPD were able to change the locomotor diurnal rhythm patterns, which suggests that these MPD doses exerts long-term effects.

  12. Effect of Portal Glucose Sensing on Systemic Glucose Levels in SD and ZDF Rats

    PubMed Central

    Pal, Atanu; Rhoads, David B.; Tavakkoli, Ali

    2016-01-01

    Background The global epidemic of Type-2-Diabetes (T2D) highlights the need for novel therapeutic targets and agents. Roux-en-Y-Gastric-Bypass (RYGB) is the most effective treatment. Studies investigating the mechanisms of RYGB suggest a role for post-operative changes in portal glucose levels. We investigate the impact of stimulating portal glucose sensors on systemic glucose levels in health and T2D, and evaluated the role of sodium-glucose-cotransporter-3 (SGLT3) as the possible sensor. Methods Systemic glucose and hormone responses to portal stimulation were measured. In Sprague-Dawley (SD) rats, post-prandial state was simulated by infusing glucose into the portal vein. The SGLT3 agonist, alpha-methyl-glucopyranoside (αMG), was then added to further stimulate the portal sensor. To elucidate the neural pathway, vagotomy or portal denervation was followed by αMG+glucose co-infusion. The therapeutic potential of portal glucose sensor stimulation was investigated by αMG-only infusion (vs. saline) in SD and Zucker-Diabetic-Fatty (ZDF) rats. Hepatic mRNA expression was also measured. Results αMG+glucose co-infusion reduced peak systemic glucose (vs. glucose alone), and lowered hepatic G6Pase expression. Portal denervation, but not vagotomy, abolished this effect. αMG-only infusion lowered systemic glucose levels. This glucose-lowering effect was more pronounced in ZDF rats, where portal αMG infusion increased insulin, C-peptide and GIP levels compared to saline infusions. Conclusions The portal vein is capable of sensing its glucose levels, and responds by altering hepatic glucose handling. The enhanced effect in T2D, mediated through increased GIP and insulin, highlights a therapeutic target that could be amenable to pharmacological modulation or minimally-invasive surgery. PMID:27806092

  13. Lactogenic Activity of an Enzymatic Hydrolysate from Octopus vulgaris and Carica papaya in SD Rats.

    PubMed

    Cai, Bingna; Chen, Hua; Sun, Han; Sun, Huili; Wan, Peng; Chen, Deke; Pan, Jianyu

    2015-11-01

    The traditional Chinese medicine theory believes that octopus papaya soup can stimulate milk production in lactating women. The objective of this study was to determine whether dietary supplementation with an enzymatic hydrolysate of Octopus vulgaris and Carica papaya (EHOC) could increase milk production and nutritional indexes in Sprague Dawley (SD) rats. Female SD rats (n = 24) were fed a control diet (n = 8), EHOC-supplemented diet, or a positive control diet (Shengruzhi) from day 10 of pregnancy to day 10 of lactation. Maternal serum, mammary gland (day 10 of lactation), milk, and pup weight (daily) were collected for analysis. Results showed that the EHOC diet obviously elevated daily milk yield and pup weight compared to the control group (P < .05). The EHOC diet was found to increase the concentration of prolactin (PRL), progesterone (P), estradiol (E2), and growth hormone (GH) significantly in the circulation and mammary gland. Mammary glands of EHOC-treated dams showed clear lobuloalveolar development and proliferation of myoepithelial cells, but no striking variations were observed among the groups. Furthermore, the nutrition content and immune globulin concentration in the milk of EHOC-supplemented dams were higher than those of the control group, especially the cholesterol, glucose, and IgG were higher by 44.98% (P < .001), 42.76% (P < .01), and 42.23% (P < .01), respectively. In conclusion, this article demonstrates that EHOC administration has beneficial effects on milk production in the dams and on performance of the dam and pup. These results indicate that EHOC could be explored as a potentially lactogenic nutriment for lactating women.

  14. Local Variability of Macular Thickness Measurements With SD-OCT and Influencing Factors

    PubMed Central

    Miraftabi, Arezoo; Amini, Navid; Gornbein, Jeff; Henry, Sharon; Romero, Pablo; Coleman, Anne L.; Caprioli, Joseph; Nouri-Mahdavi, Kouros

    2016-01-01

    Purpose To compare the intrasession variability of spectral-domain optical coherence tomography (SD-OCT)-derived local macular thickness measures and explore influencing factors. Methods One hundred two glaucomatous eyes (102 patients) and 21 healthy eyes (21 subjects) with three good quality macular images during the same session were enrolled. Thickness measurements were calculated for 3° superpixels for the inner plexiform (IPL), ganglion cell (GCL), or retinal nerve fiber layers (mRNFL), GC/IPL, ganglion cell complex, and full macular thickness. Spatial distribution and magnitude of measurement errors (ME; differences between the 3 individual superpixel values and their mean) and association between MEs and thickness, age, axial length, and image quality were explored. Results MEs had a normal distribution with mostly random noise along with a small fraction of outliers (1.2%–6.6%; highest variability in mRNFL and on the nasal border) based on M-estimation. Boundaries of 95% prediction intervals for variability reached a maximum of 3 μm for all layers and diagnostic groups after exclusion of outliers. Correlation between proportion of outliers and thickness measures varied among various parameters. Age, axial length, or image quality did not influence MEs (P > 0.05 for both groups). Conclusions Local variability of macular SD-OCT measurements is low and uniform across the macula. The relationship between superpixel thickness and outlier proportion varied as a function of the parameter of interest. Translational Relevance Given the low and uniform variability within and across eyes, definition of an individualized ‘variability space' seems unnecessary. The variability measurements from this study could be used for designing algorithms for detection of glaucoma progression. PMID:27486555

  15. Modeling ligand recognition at the P2Y12 receptor in light of X-ray structural information

    NASA Astrophysics Data System (ADS)

    Paoletta, Silvia; Sabbadin, Davide; von Kügelgen, Ivar; Hinz, Sonja; Katritch, Vsevolod; Hoffmann, Kristina; Abdelrahman, Aliaa; Straßburger, Jens; Baqi, Younis; Zhao, Qiang; Stevens, Raymond C.; Moro, Stefano; Müller, Christa E.; Jacobson, Kenneth A.

    2015-08-01

    The G protein-coupled P2Y12 receptor (P2Y12R) is an important antithrombotic target and of great interest for pharmaceutical discovery. Its recently solved, highly divergent crystallographic structures in complex either with nucleotides (full or partial agonist) or with a nonnucleotide antagonist raise the question of which structure is more useful to understand ligand recognition. Therefore, we performed extensive molecular modeling studies based on these structures and mutagenesis, to predict the binding modes of major classes of P2Y12R ligands previously reported. Various nucleotide derivatives docked readily to the agonist-bound P2Y12R, but uncharged nucleotide-like antagonist ticagrelor required a hybrid receptor resembling the agonist-bound P2Y12R except for the top portion of TM6. Supervised molecular dynamics (SuMD) of ticagrelor binding indicated interactions with the extracellular regions of P2Y12R, defining possible meta-binding sites. Ureas, sulfonylureas, sulfonamides, anthraquinones and glutamic acid piperazines docked readily to the antagonist-bound P2Y12R. Docking dinucleotides at both agonist- and antagonist-bound structures suggested interactions with two P2Y12R pockets. Thus, our structure-based approach consistently rationalized the main structure-activity relationships within each ligand class, giving useful information for designing improved ligands.

  16. Tank Tests of an Alternate Hull Form for the Consolidated Vultee PB2Y-3 Airplane

    NASA Technical Reports Server (NTRS)

    Land, Norman S.; Posner, Jack

    1946-01-01

    Tests have been made in Langley tank no. I of a dynamic model of the Consolidated Vultee PB2Y-3 airplane. These tests were made using an alternate hull form, the purpose of which was to reduce the bow spray and eliminate the landing instability which are objectionable features of the production design. The major differences from the PB2Y-3 hull included a deeper step to improve the landing stability , and a lengthened forebody and increased beam to reduce the sway in the propellers and on the flaps. The tests showed that the spray characteristics of the revised hull form were much better than that ot the production design. In addition the take-off and landing stability of the model with the alternate hull were satisfactory.

  17. P2X and P2Y nucleotide receptors as targets in cardiovascular disease.

    PubMed

    Kennedy, Charles; Chootip, Krongkarn; Mitchell, Callum; Syed, Nawazish-i-Husain; Tengah, Asrin

    2013-03-01

    Endogenous nucleotides have widespread actions in the cardiovascular system, but it is only recently that the P2X and P2Y receptor subtypes, at which they act, have been identified and subtype-selective agonists and antagonists developed. These advances have greatly increased our understanding of the physiological and pathophysiological functions of P2X and P2Y receptors, but investigation of the clinical usefulness of selective ligands is at an early stage. Nonetheless, the evidence considered in this review demonstrates clearly that various cardiovascular disorders, including vasospasm, hypertension, congestive heart failure and cardiac damage during ischemic episodes, may be viable targets. With further development of novel, selective agonists and antagonists, our understanding will continue to improve and further therapeutic applications are likely to be discovered.

  18. Extracellular ATP acts on P2Y2 purinergic receptors to facilitate HIV-1 infection.

    PubMed

    Séror, Claire; Melki, Marie-Thérèse; Subra, Frédéric; Raza, Syed Qasim; Bras, Marlène; Saïdi, Héla; Nardacci, Roberta; Voisin, Laurent; Paoletti, Audrey; Law, Frédéric; Martins, Isabelle; Amendola, Alessandra; Abdul-Sater, Ali A; Ciccosanti, Fabiola; Delelis, Olivier; Niedergang, Florence; Thierry, Sylvain; Said-Sadier, Najwane; Lamaze, Christophe; Métivier, Didier; Estaquier, Jérome; Fimia, Gian Maria; Falasca, Laura; Casetti, Rita; Modjtahedi, Nazanine; Kanellopoulos, Jean; Mouscadet, Jean-François; Ojcius, David M; Piacentini, Mauro; Gougeon, Marie-Lise; Kroemer, Guido; Perfettini, Jean-Luc

    2011-08-29

    Extracellular adenosine triphosphate (ATP) can activate purinergic receptors of the plasma membrane and modulate multiple cellular functions. We report that ATP is released from HIV-1 target cells through pannexin-1 channels upon interaction between the HIV-1 envelope protein and specific target cell receptors. Extracellular ATP then acts on purinergic receptors, including P2Y2, to activate proline-rich tyrosine kinase 2 (Pyk2) kinase and transient plasma membrane depolarization, which in turn stimulate fusion between Env-expressing membranes and membranes containing CD4 plus appropriate chemokine co-receptors. Inhibition of any of the constituents of this cascade (pannexin-1, ATP, P2Y2, and Pyk2) impairs the replication of HIV-1 mutant viruses that are resistant to conventional antiretroviral agents. Altogether, our results reveal a novel signaling pathway involved in the early steps of HIV-1 infection that may be targeted with new therapeutic approaches.

  19. Extracellular ATP acts on P2Y2 purinergic receptors to facilitate HIV-1 infection

    PubMed Central

    Séror, Claire; Melki, Marie-Thérèse; Subra, Frédéric; Raza, Syed Qasim; Bras, Marlène; Saïdi, Héla; Nardacci, Roberta; Voisin, Laurent; Paoletti, Audrey; Law, Frédéric; Martins, Isabelle; Amendola, Alessandra; Abdul-Sater, Ali A.; Ciccosanti, Fabiola; Delelis, Olivier; Niedergang, Florence; Thierry, Sylvain; Said-Sadier, Najwane; Lamaze, Christophe; Métivier, Didier; Estaquier, Jérome; Fimia, Gian Maria; Falasca, Laura; Casetti, Rita; Modjtahedi, Nazanine; Kanellopoulos, Jean; Mouscadet, Jean-François; Ojcius, David M.; Piacentini, Mauro; Gougeon, Marie-Lise

    2011-01-01

    Extracellular adenosine triphosphate (ATP) can activate purinergic receptors of the plasma membrane and modulate multiple cellular functions. We report that ATP is released from HIV-1 target cells through pannexin-1 channels upon interaction between the HIV-1 envelope protein and specific target cell receptors. Extracellular ATP then acts on purinergic receptors, including P2Y2, to activate proline-rich tyrosine kinase 2 (Pyk2) kinase and transient plasma membrane depolarization, which in turn stimulate fusion between Env-expressing membranes and membranes containing CD4 plus appropriate chemokine co-receptors. Inhibition of any of the constituents of this cascade (pannexin-1, ATP, P2Y2, and Pyk2) impairs the replication of HIV-1 mutant viruses that are resistant to conventional antiretroviral agents. Altogether, our results reveal a novel signaling pathway involved in the early steps of HIV-1 infection that may be targeted with new therapeutic approaches. PMID:21859844

  20. Contribution of the P2Y12 receptor-mediated pathway to platelet hyperreactivity in hypercholesterolemia

    PubMed Central

    Nagy, Béla; Jin, Jianguo; Ashby, Barrie; Reilly, Michael P.; Kunapuli, Satya P.

    2011-01-01

    Summary Background In hypercholesterolemia, platelets demonstrate increased reactivity and promote the development of cardiovascular disease. Objective This study was carried out to investigate the contribution of the ADP receptor P2Y12-mediated pathway in platelet hyperreactivity due to hypercholesterolemia. Methods Low-density lipoprotein receptor deficient mice and C57Bl/6 wild type mice were fed on normal chow and high-fat (Western or Paigen) diets for 8 weeks to generate differently elevated cholesterol levels. P2Y12 receptor induced functional responses via Gi signaling were studied ex vivo when washed murine platelets were activated by 2MeSADP and PAR4 agonist AYPGKF in the presence and absence of indomethacin. Platelet aggregation, secretion, αIIbβ3 receptor activation and the phosphorylation of extracellular signal-regulated protein kinase (ERK) and Akt were analyzed. Results Plasma cholesterol levels ranged from 69±10 to 1011±185 mg/dl depending on diet in mice with different genotypes. Agonist-dependent aggregation, dense and α-granule secretion and JON/A binding were gradually and significantly (P < 0.05) augmented at low agonist concentration in correlation with the increasing plasma cholesterol levels even if elevated thromboxane generation was blocked. These functional responses were induced via increased level of Gi mediated ERK and Akt phosphorylation in hypercholesterolemic mice versus normocholesterolemic animals. In addition, blocking of the P2Y12 receptor by AR-C69931MX (Cangrelor) resulted in strongly reduced platelet aggregation in mice with elevated cholesterol levels compared to normocholesterolemic controls. Conclusions These data revealed that the P2Y12 receptor pathway was substantially involved in platelet hyperreactivity associated with mild and severe hypercholesterolemia. PMID:21261805

  1. Adenine Nucleotides Control Proliferation In Vivo of Rat Retinal Progenitors by P2Y1 Receptor.

    PubMed

    de Almeida-Pereira, Luana; Magalhães, Camila Feitosa; Repossi, Marinna Garcia; Thorstenberg, Maria Luiza Prates; Sholl-Franco, Alfred; Coutinho-Silva, Robson; Ventura, Ana Lucia Marques; Fragel-Madeira, Lucianne

    2016-08-24

    Previous studies demonstrated that exogenous ATP is able to regulate proliferation of retinal progenitor cells (RPCs) in vitro possibly via P2Y1 receptor, a G protein-coupled receptor. Here, we evaluated the function of adenine nucleotides in vivo during retinal development of newborn rats. Intravitreal injection of apyrase, an enzyme that hydrolyzes nucleotides, reduced cell proliferation in retinas at postnatal day 2 (P2). This decrease was reversed when retinas were treated together with ATPγ-S or ADPβ-S, two hydrolysis-resistant analogs of ATP and ADP, respectively. During early postnatal days (P0 to P5), an increase in ectonucleotidase (E-NTPDase) activity was observed in the retina, suggesting a decrease in the availability of adenine nucleotides, coinciding with the end of proliferation. Interestingly, intravitreal injection of the E-NTPDase inhibitor ARL67156 increased proliferation by around 60 % at P5 rats. Furthermore, immunolabeling against P2Y1 receptor was observed overall in retina layers from P2 rats, including proliferating Ki-67-positive cells in the neuroblastic layer (NBL), suggesting that this receptor could be responsible for the action of adenine nucleotides upon proliferation of RPCs. Accordingly, intravitreal injection of MRS2179, a selective antagonist of P2Y1 receptors, reduced cell proliferation by approximately 20 % in P2 rats. Moreover, treatment with MRS 2179 caused an increase in p57(KIP2) and cyclin D1 expression, a reduction in cyclin E and Rb phosphorylated expression and in BrdU-positive cell number. These data suggest that the adenine nucleotides modulate the proliferation of rat RPCs via activation of P2Y1 receptors regulating transition from G1 to S phase of the cell cycle.

  2. P2Y6 Receptor-Mediated Proinflammatory Signaling in Human Bronchial Epithelia

    PubMed Central

    Hao, Yuan; Liang, Jocelyn F.; Chow, Alison W.; Cheung, Wing-tai; Ko, Wing-hung

    2014-01-01

    P2Y receptors are expressed in virtually all epithelia and are responsible for the control of fluid and electrolyte transport. In asthmatic inflammation, the bronchial epithelia are damaged by eosinophil-derived, highly toxic cationic proteins, such as major basic protein (MBP). Consequently, extracellular nucleotides are released into the extracellular space from airway epithelial cells, and act in an autocrine or paracrine fashion to regulate immune functions. Our data show damage to the human bronchial epithelial cell line, 16HBE14o-, by poly-L-arginine-induced UDP release into the extracellular medium. Activation of P2Y6 receptor by its natural ligand, UDP, or its specific agonist, MRS 2693, led to the production of two proinflammatory cytokines, interleukin (IL)-6 and IL-8. This may have resulted from increased IL-6 and IL-8 mRNA expression, and activation of p38 and ERK1/2 MAPK, and NF-κB pathways. Our previous study demonstrated that UDP stimulated transepithelial Cl− secretion via both Ca2+- and cAMP-dependent pathways in 16HBE14o- epithelia. This was further confirmed in this study by simultaneous imaging of Ca2+ and cAMP levels in single cells using the Fura-2 fluorescence technique and a FRET-based approach, respectively. Moreover, the P2Y6 receptor-mediated production of IL-6 and IL-8 was found to be dependent on Ca2+, but not the cAMP/PKA pathway. Together, these studies show that nucleotides released during the airway inflammatory processes will activate P2Y6 receptors, which will lead to further release of inflammatory cytokines. The secretion of cytokines and the formation of such “cytokine networks” play an important role in sustaining the airway inflammatory disease. PMID:25243587

  3. Cangrelor inhibits the binding of the active metabolites of clopidogrel and prasugrel to P2Y12 receptors in vitro.

    PubMed

    Judge, Heather M; Buckland, Robert J; Jakubowski, Joseph A; Storey, Robert F

    2016-01-01

    Cangrelor is a rapid-acting, direct-binding, and reversible P2Y12 antagonist which has been studied for use during percutaneous coronary intervention (PCI) in patients with or without pretreatment with an oral P2Y12 antagonist. As cangrelor is administered intravenously, it is necessary to switch to an oral P2Y12 antagonist following PCI, such as the thienopyridines clopidogrel, and prasugrel or the non-pyridine ticagrelor. Previous studies have suggested a negative pharmacodynamic interaction between cangrelor and thienopyridines. This in vitro study evaluated the receptor-level interaction between cangrelor and the active metabolite (AM) of clopidogrel or prasugrel by assessing functional P2Y12 receptor number using a (33)P-2MeSADP binding assay. All P2Y12 antagonists studied resulted in strong P2Y12 receptor blockade (cangrelor: 93.6%; clopidogrel AM: 93.0%; prasugrel AM: 97.9%). Adding a thienopyridine AM in the presence of cangrelor strongly reduces P2Y12 receptor blockade by the AM (clopidogrel AM: 7%, prasugrel AM: 3.2%). The thienopyridine AMs had limited ability to compete with cangrelor for binding to P2Y12 (% P2Y12 receptor blockade after co-incubation with cangrelor 1000 nmol/L: 11.7% for clopidogrel AM 3 µmol/L; 34.1% for prasugrel AM 3 µmol/L). In conclusion, in vitro cangrelor strongly inhibits the binding of clopidogrel and prasugrel AMs to the P2Y12 receptor, consistent with the previous observation of a negative pharmacodynamic interaction. Care may need to be taken to not overlap exposure to thienopyridine AMs and cangrelor in order to reduce the risk of thrombotic complications following PCI.

  4. Identification of Determinants Required for Agonistic and Inverse Agonistic Ligand Properties at the ADP Receptor P2Y12

    PubMed Central

    Schmidt, Philipp; Ritscher, Lars; Dong, Elizabeth N.; Hermsdorf, Thomas; Cöster, Maxi; Wittkopf, Doreen; Meiler, Jens

    2013-01-01

    The ADP receptor P2Y12 belongs to the superfamily of G protein–coupled receptors (GPCRs), and its activation triggers platelet aggregation. Therefore, potent antagonists, such as clopidogrel, are of high clinical relevance in prophylaxis and treatment of thromboembolic events. P2Y12 displays an elevated basal activity in vitro, and as such, inverse agonists may be therapeutically beneficial compared with antagonists. Only a few inverse agonists of P2Y12 have been described. To expand this limited chemical space and improve understanding of structural determinants of inverse agonist-receptor interaction, this study screened a purine compound library for lead structures using wild-type (WT) human P2Y12 and 28 constitutively active mutants. Results showed that ATP and ATP derivatives are agonists at P2Y12. The potency at P2Y12 was 2-(methylthio)-ADP > 2-(methylthio)-ATP > ADP > ATP. Determinants required for agonistic ligand activity were identified. Molecular docking studies revealed a binding pocket for the ATP derivatives that is bordered by transmembrane helices 3, 5, 6, and 7 in human P2Y12, with Y105, E188, R256, Y259, and K280 playing a particularly important role in ligand interaction. N-Methyl-anthraniloyl modification at the 3′-OH of the 2′-deoxyribose leads to ligands (mant-deoxy-ATP [dATP], mant-deoxy-ADP) with inverse agonist activity. Inverse agonist activity of mant-dATP was found at the WT human P2Y12 and half of the constitutive active P2Y12 mutants. This study showed that, in addition to ADP and ATP, other ATP derivatives are not only ligands of P2Y12 but also agonists. Modification of the ribose within ATP can result in inverse activity of ATP-derived ligands. PMID:23093496

  5. Macular SD-OCT Outcome Measures: Comparison of Local Structure-Function Relationships and Dynamic Range

    PubMed Central

    Miraftabi, Arezoo; Amini, Navid; Morales, Esteban; Henry, Sharon; Yu, Fei; Afifi, Abdolmonem; Coleman, Anne L.; Caprioli, Joseph; Nouri-Mahdavi, Kouros

    2016-01-01

    Purpose We tested the hypothesis that the macular ganglion cell layer (GCL) thickness demonstrates a stronger structure-function (SF) relationship and extends the useful range of macular measurements compared with combined macular inner layer or full thickness. Methods Ninety-eight glaucomatous eyes and eight normal eyes with macular spectral domain optical coherence tomography (SD-OCT) volume scans and 10-2 visual fields were enrolled. Inner plexiform layer (IPL), GCL, macular retinal nerve fiber layer (mRNFL), ganglion cell-inner plexiform layer (GCIPL), ganglion cell complex (GCC), and full thickness (FT) measurements were calculated for 8 × 8 arrays of 3° superpixels. Main outcome measures were local structure-function relationships between macular superpixels and corresponding sensitivities on 10-2 fields after adjusting for ganglion cell displacement, dynamic range of measurements, and the change point (total deviation value where macular parameters reached measurement floor). Results Median (interquartile range [IQR]) mean deviation was −7.2 (−11.6 to −3.2) dB in glaucoma eyes. Strength of SF relationships was highest for GCIPL, GCL, GCC, and IPL (ρ = 0.635, 0.627, 0.621, and 0.577, respectively; P ≤ 0.046 for comparisons against GCIPL). Highest SF correlations coincided with the peak of GCL thickness, where the dynamic range was widest for FT (81.1 μm), followed by GCC (65.7 μm), GCIPL (54.9 μm), GCL (35.2 μm), mRNFL (27.5 μm), and IPL (20.9 μm). Change points were similar for all macular parameters (−7.8 to −8.9 dB). Conclusions GCIPL, GCL, and GCC demonstrated comparable SF relationships while FT, GCC, and GCIPL had the widest dynamic range. Measurement of GCL did not extend the range of useful structural measurements. Measuring GCL does not provide any advantage for detection of progression with current SD-OCT technology. PMID:27623336

  6. Concomitant activation of P2Y(2) and P2Y(6) receptors on monocytes is required for TLR1/2-induced neutrophil migration by regulating IL-8 secretion.

    PubMed

    Ben Yebdri, Fethia; Kukulski, Filip; Tremblay, Alain; Sévigny, Jean

    2009-10-01

    Extracellular nucleotides regulate a variety of cellular responses involved in inflammation via the activation of P2 receptors. Here, we show that nucleotides regulate TLR2-induced neutrophil migration both in vivo and in vitro. The nucleotide scavenger apyrase inhibited neutrophil recruitment in murine air pouches injected with the TLR2 agonist Pam(3)CSK(4). In agreement, the supernatants of either human primary monocytes or monocytic cells (THP-1 and U937) treated with Pam(3)CSK(4) recruited significantly fewer neutrophils when the former cells were treated in the presence of apyrase. As demonstrated with inhibitory Ab, these supernatants induced neutrophil migration due to IL-8 secretion. In addition, IL-8 secretion was markedly diminished by the non-selective P2 receptor antagonists reactive blue 2 and suramin, and by a selective P2Y(6) antagonist, MRS2578. Selective antagonists of P2Y(1) (MRS2500) and P2Y(11) (NF157) did not affect IL-8 release. The knockdown of either P2Y(2) or P2Y(6) with specific shRNA diminished IL-8 secretion from Pam(3)CSK(4)-treated THP-1 cells. Altogether, these results show that extracellular nucleotides, via P2Y(2) and P2Y(6) receptors, regulate neutrophil migration by controlling TLR2-induced IL-8 release from human monocytes. In line with our previous work on TLR4, this study further supports the importance of nucleotides in bacterial-induced neutrophil migration.

  7. Succinate reverses in-vitro platelet inhibition by acetylsalicylic acid and P2Y receptor antagonists.

    PubMed

    Spath, Brigitte; Hansen, Arne; Bokemeyer, Carsten; Langer, Florian

    2012-01-01

    High on-treatment platelet reactivity has been associated with adverse cardiovascular events in patients receiving anti-platelet agents, but the molecular mechanisms underlying this phenomenon remain incompletely understood. Succinate, a citric acid cycle intermediate, is released into the circulation under conditions of mitochondrial dysfunction due to hypoxic organ damage, including sepsis, stroke, and myocardial infarction. Because the G protein-coupled receptor (GPCR) for succinate, SUCNR1 (GPR91), is present on human platelets, we hypothesized that succinate-mediated platelet stimulation may counteract the pharmacological effects of cyclooxygenase-1 and ADP receptor antagonists. To test this hypothesis in a controlled in-vitro study, washed platelets from healthy donors were treated with acetylsalicylic acid (ASA) or small-molecule P2Y(1) or P2Y(12) inhibitors and subsequently analyzed by light transmittance aggregometry using arachidonic acid (AA), ADP and succinate as platelet agonists. Aggregation in response to succinate alone was highly variable with only 29% of donors showing a (mostly delayed) platelet response. In contrast, succinate reproducibly and concentration-dependently (10-1000 µM) enhanced platelet aggregation in response to low concentrations of exogenous ADP. Furthermore, while succinate alone had no effect in the presence of platelet inhibitors, responsiveness of platelets to ADP after pretreatment with P2Y(1) or P2Y(12) antagonists was fully restored, when platelets were co-stimulated with 100 µM succinate. Similarly, succinate completely (at 1000 µM) or partially (at 100 µM) reversed the inhibitory effect of ASA on AA-induced platelet aggregation. In contrast, succinate failed to restore platelet responsiveness in the presence of both ASA and the P2Y(12) antagonist, suggesting that concomitant signaling via different GPCRs was required. Essentially identical results were obtained, when flow cytometric analysis of surface CD62P

  8. Purinergic P2Y2 Receptor Control of Tissue Factor Transcription in Human Coronary Artery Endothelial Cells

    PubMed Central

    Liu, Yiwei; Zhang, Lingxin; Wang, Chuan; Roy, Shama; Shen, Jianzhong

    2016-01-01

    We recently reported that the P2Y2 receptor (P2Y2R) is the predominant nucleotide receptor expressed in human coronary artery endothelial cells (HCAEC) and that P2Y2R activation by ATP or UTP induces dramatic up-regulation of tissue factor (TF), a key initiator of the coagulation cascade. However, the molecular mechanism of this P2Y2R-TF axis remains unclear. Here, we report the role of a newly identified AP-1 consensus sequence in the TF gene promoter and its original binding components in P2Y2R regulation of TF transcription. Using bioinformatics tools, we found that a novel AP-1 site at −1363 bp of the human TF promoter region is highly conserved across multiple species. Activation of P2Y2R increased TF promoter activity and mRNA expression in HCAEC. Truncation, deletion, and mutation of this distal AP-1 site all significantly suppressed TF promoter activity in response to P2Y2R activation. EMSA and ChIP assays further confirmed that upon P2Y2R activation, c-Jun, ATF-2, and Fra-1, but not the typical c-Fos, bound to the new AP-1 site. In addition, loss-of-function studies using siRNAs confirmed a positive transactivation role of c-Jun and ATF-2 but unexpectedly revealed a strong negative role of Fra-1 in P2Y2R-induced TF up-regulation. Furthermore, we found that P2Y2R activation promoted ERK1/2 phosphorylation through Src, leading to Fra-1 activation, whereas Rho/JNK mediated P2Y2R-induced activation of c-Jun and ATF-2. These findings reveal the molecular basis for P2Y G protein-coupled receptor control of endothelial TF expression and indicate that targeting the P2Y2R-Fra-1-TF pathway may be an attractive new strategy for controlling vascular inflammation and thrombogenicity associated with endothelial dysfunction. PMID:26631725

  9. Classification of SD-OCT Volumes Using Local Binary Patterns: Experimental Validation for DME Detection

    PubMed Central

    Cheung, Carol Y.; Wong, Tien Y.; Lamoureux, Ecosse; Milea, Dan; Mériaudeau, Fabrice; Sidibé, Désiré

    2016-01-01

    This paper addresses the problem of automatic classification of Spectral Domain OCT (SD-OCT) data for automatic identification of patients with DME versus normal subjects. Optical Coherence Tomography (OCT) has been a valuable diagnostic tool for DME, which is among the most common causes of irreversible vision loss in individuals with diabetes. Here, a classification framework with five distinctive steps is proposed and we present an extensive study of each step. Our method considers combination of various preprocessing steps in conjunction with Local Binary Patterns (LBP) features and different mapping strategies. Using linear and nonlinear classifiers, we tested the developed framework on a balanced cohort of 32 patients. Experimental results show that the proposed method outperforms the previous studies by achieving a Sensitivity (SE) and a Specificity (SP) of 81.2% and 93.7%, respectively. Our study concludes that the 3D features and high-level representation of 2D features using patches achieve the best results. However, the effects of preprocessing are inconsistent with different classifiers and feature configurations. PMID:27555965

  10. Age-related Histological Findings in the Pineal Gland of Crl:CD(SD) Rats.

    PubMed

    Tomonari, Yuki; Sato, Junko; Wako, Yumi; Tsuchitani, Minoru

    2012-12-01

    To provide background data as the pathologic basis, the pineal glands of 190 male and 193 female Crl:CD(SD) rats at ages of 0-7, 51-58, 70-85 and 111 weeks were examined histologically in this study. Mineralization and fibrosis were common findings in the aged rats, whereas they were rarely found in the young ones; mineralization was present in 7, 44, 67 and 79% of males and in 0, 32, 67 and 79% in females, and fibrosis was present in 0, 29, 48 and 44% of males and 0, 18, 40 and 35% of females at ages of 0-7, 51-58, 70-85 and 111 weeks, respectively. Striated muscle fiber appeared regularly in the fibrosis region from 51-58 weeks of age when fibrosis increased, while the origin of this fiber remained unclear. Vacuolation of pineal cells also increased with age in both sexes, though the total incidence was low. There was a low incidence of lymphocytic infiltration in both sexes, but this was not related to age.

  11. The estrogenic effects of benzylparaben at low doses based on uterotrophic assay in immature SD rats.

    PubMed

    Hu, Ying; Zhang, Zhaobin; Sun, Libei; Zhu, Desheng; Liu, Qingchun; Jiao, Jian; Li, Jun; Qi, Mingwen

    2013-03-01

    Benzylparaben (BzP), a type of parabens being used as a preservative agent in cosmetics, food, and pharmaceutical products, may be ingested by humans. In this study, we performed an immature uterotrophic assay using Sprague Dawley (SD) rats by intragastric administration to determine the estrogenic effects of BzP and found significant increases in uterine weight with doses of 0.16 mg/kg body weight and higher (P<0.05). The in vivo estrogenicity of BzP was supported by in vitro results from the human estrogen receptor α (hERα)-coactivator recruiting assay and in silico molecular docking analysis performed in this study. The in vitro estrogenic activity of BzP can be observed at concentrations of 1.0×10(-8) M and higher. Molecular docking analysis showed that BzP fits well into the agonist pocket of hERα. The lowest observed effect dose (LOED) (0.16 mg/kg/day) of BzP is much lower than the documented LOEDs of other parabens. Actual risk may exist for people who consume a diet high in BzP or use BzP-laden cosmetics. In addition, we tested the sensitivity of Wistar rats to 17β-estradiol by immature uterotrophic assay, and no obvious uterotrophic response was observed in the rats given doses up to 100 μg/kg body weight.

  12. Spectrum of {gamma} rays from the decay of SD to normal states in {sup 191}Hg

    SciTech Connect

    Gassmann, D.; Khoo, T.L.; Lauritsen, T.

    1995-08-01

    In B.a.7. we propose that the statistical spectrum emitted from a sharp single excited state serves as a probe of pairing in excited states. A specific test of this proposal is the comparison of the spectra from even-even and odd-even nuclei. Whereas a pair gap exists in an even-even nucleus, it gets filled in an odd-even nucleus. Consequently, low-energy transitions can arise in the latter case, whereas they are calculated to be absent in the former case because very few levels exist in the cold gap region. In addition, transitions between 1.4 - 2.2 MeV, which {open_quotes}jump{close_quotes} across the gap, are predicted to have lower yield in the odd-even nuclei. Serendipitously, decay from a superdeformed state serves as a good initial excited sharp state. We extracted the spectrum pairwise-coincident with SD lines in {sup 191}Hg from Gammasphere data and compared it with the equivalent spectra from the even-even nuclei {sup 192,194}Hg. The differences that are predicted to occur are indeed observed. Thus, the data support our proposal that the reduction of pairing with thermal excitation energy can be probed with statistical decay spectra.

  13. Classification of SD-OCT Volumes Using Local Binary Patterns: Experimental Validation for DME Detection.

    PubMed

    Lemaître, Guillaume; Rastgoo, Mojdeh; Massich, Joan; Cheung, Carol Y; Wong, Tien Y; Lamoureux, Ecosse; Milea, Dan; Mériaudeau, Fabrice; Sidibé, Désiré

    2016-01-01

    This paper addresses the problem of automatic classification of Spectral Domain OCT (SD-OCT) data for automatic identification of patients with DME versus normal subjects. Optical Coherence Tomography (OCT) has been a valuable diagnostic tool for DME, which is among the most common causes of irreversible vision loss in individuals with diabetes. Here, a classification framework with five distinctive steps is proposed and we present an extensive study of each step. Our method considers combination of various preprocessing steps in conjunction with Local Binary Patterns (LBP) features and different mapping strategies. Using linear and nonlinear classifiers, we tested the developed framework on a balanced cohort of 32 patients. Experimental results show that the proposed method outperforms the previous studies by achieving a Sensitivity (SE) and a Specificity (SP) of 81.2% and 93.7%, respectively. Our study concludes that the 3D features and high-level representation of 2D features using patches achieve the best results. However, the effects of preprocessing are inconsistent with different classifiers and feature configurations.

  14. Optimization of a bioactive exopolysaccharide production from endophytic Fusarium solani SD5.

    PubMed

    Mahapatra, Subhadip; Banerjee, Debdulal

    2013-09-12

    Endophytic fungi were less investigated for exopolysaccharide production. In this study endophytic Fusarium solani SD5 was used for optimization of exopolysaccharide production. One variable at a time method and response surface methodology were employed to explore the optimum medium compositions and fermentation conditions. The organism produced maximum exopolysaccharide after 13.68 days of incubation at 28 °C in potato dextrose broth supplemented with (g%/l) glucose, 9.8; yeast extract, 0.69; KCl, 0.05; KH₂PO₄, 0.05 with medium pH 6.46. Use of 50 ml medium in 250 ml Erlenmeyer flask gives highest exopolysaccharide production. The organism produced more than two times higher exopolysaccharide (2.276 ± 0.032 g/l EPS) at optimized condition compared to pre-optimized condition (0.96 ± 0.021). In vivo toxicity test established nontoxic nature of the EPS (≤400 mg EPS/Kg of body weight). The EPS slightly altered intestinal indigenous bacteria and influenced the growth of beneficial Lactobacillus spp.

  15. Dynamic 3-D vortex structure of the laminar separation bubble on SD7003 airfoil

    NASA Astrophysics Data System (ADS)

    Zhang, Wei; Hain, Rainer; Kähler, Christian J.

    2008-11-01

    Recent increasing interest in laminar separation bubble (LSB) is aroused by the development of the micro air vehicles (MAVs), which normally cruise in the Reynolds number range of 50,000-200,000. This paper studies the LSB over the SD 7003 airfoil at the angle of attack α=4^o and at Re=60,000 using the time-resolved PIV technique. A Nd:Yag laser operated at 1000 Hz and a high speed CMOS camera was synchronized to capture the particle images with the full resolution of 1504 x 1128 pixels at 1000 fps. Measurements were carried out from two orthogonal views: in the stream-wise wall-normal plane and the quasi-surface-parallel plane. 3-D disturbance was observed to start even prior to the point of transition. Vortex shedding in transition near the reattachment region of the LSB was clearly identified in the span-wise wall-normal plane, with the dominant K-H frequency of around 10.7 Hz. And subsequent vortex evolution in the reattached turbulent boundary layer was found to be characterized by paired positive and negative vorticity packets transported downstream.

  16. Preparation and evaluation of kaempferol-phospholipid complex for pharmacokinetics and bioavailability in SD rats.

    PubMed

    Zhang, Kexia; Gu, Liqiang; Chen, Jinpeng; Zhang, Yuanyuan; Jiang, Yu; Zhao, Longshan; Bi, Kaishun; Chen, Xiaohui

    2015-10-10

    As one of the dietary flavonoids, kaempferol (KP) has been well known to show strong anti-oxidative effect along with other biological properties. However, the oral bioavailability of KP is relatively low due to its poor solubility. In this study, we intended to increase the solubility and bioavailability of KP by preparing kaempferol-phospholipid complex (KP-PC). The KP-PC's physicochemical properties were characterized in terms of infrared spectroscopy (IR), differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD), water/n-Octanol solubility and in vitro dissolution. KP-PC exhibited higher solubility and dissolution rate than KP, indicating a significant improvement in hydrophilicity. A UPLC-ESI-MS/MS method was developed and validated for the determination of KP in Sprague-Dawley (SD) rat plasma, so as to investigate the oral bioavailability of KP-PC versus KP. Results showed that Cmax and AUC(0-48 h) of KP from the complex (Cmax: 3.94 ± 0.83 μg/mL, AUC(0-48 h): 57.81 ± 9.43 mg/Lh) were higher than that of KP (Cmax: 1.43 ± 0.21 μg/mL, AUC(0-48 h): 13.65 ± 3.12 mg/Lh). This research indicated that phospholipid complex (PC) might be one of the suitable approachs to improve the oral bioavailability of KP and other poor-solubility flavonoids.

  17. Threshold of Multiple Stick-Slip Chaos for an Archetypal Self-Excited SD Oscillator Driven by Moving Belt Friction

    NASA Astrophysics Data System (ADS)

    Li, Z. X.; Cao, Q. J.; Léger, A.

    In this paper, we investigate the multiple stick-slip chaotic motion of an archetypal self-excited smooth and discontinuous (SD) oscillator driven by moving belt friction, which is constructed with the SD oscillator and the classical moving belt. The friction force between the mass and the belt is modeled as a Coulomb friction for this system. The energy introduction or dissipation during the slip and stick modes in the system is analyzed. The analytical expressions of homoclinic orbits of the unperturbed SD oscillator are derived by using a special coordinate transformation without any pronominal truncation to retain the natural characteristics, which allows us to utilize the Melnikov’s method to obtain the chaotic thresholds of the self-excited SD oscillator in the presence of the damping and external excitation. Numerical simulations are carried out to demonstrate the multiple stick-slip dynamics of the system, which show the efficiency of the prediction for stick-slip chaos of the perturbed self-excited system. The results presented herein this paper demonstrate the complicated dynamics of stick-slip periodic solutions, multiple stick-slip chaotic solutions and also coexistence of multiple solutions for the perturbed self-excited SD oscillator.

  18. Leveraging master-slave OpenFlow controller arrangement to improve control plane resiliency in SD-EONs.

    PubMed

    Chen, Xiaoliang; Zhao, Bin; Ma, Shoujiang; Chen, Cen; Hu, Daoyun; Zhou, Wenshuang; Zhu, Zuqing

    2015-03-23

    In this paper, we study how to improve the control plane resiliency of software-defined elastic optical networks (SD-EONs) and design a master-slave OpenFlow (OF) controller arrangement. Specifically, we introduce two OF controllers (OF-Cs), i.e., the master and slave OF-Cs, and make them work in a collaborative way to protect the SD-EON against controller failures. We develop a controller communication protocol (CCP) to facilitate the cooperation of the two OF-Cs. With the CCP, the master OF-C (M-OF-C) can synchronize network status to the slave OF-C (S-OF-C) in real time, while S-OF-C can quickly detect the failure of M-OF-C and take over the network control and management (NC&M) tasks timely to avoid service disruption. We implement the proposed framework in an SD-EON control plane testbed built with high-performance servers, and perform NC&M experiments with different network failure scenarios to demonstrate its effectiveness. Experimental results indicate that the proposed system can restore services in both the data and control planes of SD-EON jointly while maintaining relatively good scalability. To the best of our knowledge, this is the first demonstration that realizes control plane resiliency in SD-EONs.

  19. Evaluation of Corneal Epithelial Healing Under Contact Lens with Spectral-Domain Anterior Segment Optical Coherence Tomography (SD-OCT)

    PubMed Central

    Pang, Claudine E; M, Vanathi; Tan, Donald T.H; Mehta, Jodhbir S

    2011-01-01

    Purpose: To describe a novel technique of using Spectral-domain (SD) anterior segment optical coherence tomography (SD-OCT) in the evaluation of corneal epithelial healing under a therapeutic contact lens (TCL) after lamellar keratoplasty and Epi-LASIK procedures. Design: Prospective, non-comparative, observational case series. Methods: Ten eyes of eight patients undergoing lamellar corneal transplantation and Epi-LASIK procedures at the Singapore National Eye Centre were included in the study. Ultra-high resolution SD-OCT scans of the cornea with a TCL in-situ were performed sequentially on the first, third and fifth day after procedure, with the RTVue (Optovue, Inc, Fremont, CA, USA), and the image findings were correlated with the clinical picture. Complete epithelial healing was verified with removal of TCL and fluorescein staining. Results: 5 eyes underwent Descemet’s stripping automated endothelial keratoplasty (DSAEK), 1 eye underwent deep anterior lamellar keratoplasty (DALK) and 4 eyes underwent Epi-LASIK. All eyes had complete epithelial healing with TCL in-situ by the third post-operative day. SD-OCT images were able to demonstrate the epithelial layer distinctly under the TCL in all cases. Conclusions: SD-OCT is a valuable imaging tool for monitoring the progression of epithelial healing with TCL in situ in patients following corneal surgical procedures. PMID:21686324

  20. P2Y6 contributes to ovalbumin-induced allergic asthma by enhancing mast cell function in mice

    PubMed Central

    Shi, Jue-ping; Wang, Shao-ying; Chen, Li-li; Zhang, Xiao-yu; Zhao, Yi-han; Du, Bing; Jiang, Wen-zheng; Qian, Min; Ren, Hua

    2016-01-01

    Extracelluar nucleotides have been identified as regulatory factors in asthmatic pathogenesis by activating purinergic receptors. This research aimed to investigate the function of the purinergic receptor P2Y6 in mediating airway inflammation in allergic asthma. Wild-type (WT) and P2Y6-deficient mice were stimulated with ovalbumin (OVA) to construct asthmatic mouse models. Overexpression of P2Y6 and uridine 5′-diphosphate (UDP)-releasing were demonstrated in lung tissues in ovalbumin-induced asthmatic mice. The release of the cytokine IL-4, mast cell invasion, and the airway remodeling phenotypes were more severe following the application of UDP in asthmatic mice. However, P2Y6 deficiency reduced these asthmatic pathogeneticsymptoms markedly in a mouse model. In vitro, we found that P2Y6 in purified mast cells enhanced the functions of mast cells in the inflammatory response in the asthmatic process by triggering their capability for migration, cytokine secretion and granule release. Moreover, P2Y6 stimulated the function of mast cells through activation of the AKT signaling pathway. Our data provides evidence that P2Y6 contributes to allergic airway inflammation and remodeling by enhancing the functions of mast cells in ovalbumin-induced asthmatic mice. PMID:27590515

  1. Characterization of a Novel Function-Blocking Antibody Targeted Against The Platelet P2Y1 Receptor

    PubMed Central

    Karim, Zubair A.; Vemana, Hari Priya; Alshbool, Fatima Z.; Lin, Olivia A.; Alshehri, Abdullah M.; Javaherizadeh, Payam; Paez Espinosa, Enma V.; Khasawneh, Fadi T.

    2015-01-01

    Objective Platelet hyperactivity is associated with vascular disease and contributes to the genesis of thrombotic disorders. ADP plays an important role in platelet activation, and activates platelets through two G-Protein Coupled Receptors, the Gq-coupled P2Y1 receptor (P2Y1R), and the Gi-coupled P2Y12 receptor (P2Y12R). While the involvement of the P2Y1R in thrombogenesis is well established, there are no antagonists that are currently available for clinical use. Approach and Results Our goal is to determine whether a novel antibody targeting the ligand binding domain, i.e., second extracellular loop (EL2) of the P2Y1R [abbreviated as EL2Ab] could inhibit platelet function and protect against thrombogenesis. Our results revealed that the EL2Ab does indeed inhibit ADP-induced platelet aggregation, in a dose-dependent manner. Furthermore, EL2Ab was found to inhibit integrin GPIIb-IIIa activation, dense and alpha granule secretion and phosphatidylserine exposure. These inhibitory effects translated into protection against thrombus formation, as evident by a prolonged time for occlusion in a FeCl3 induced thrombosis model, but this was accompanied by a prolonged tail bleeding time. We also observed a dose dependent displacement of the radiolabelled P2Y1R antagonist [3H]MRS25000 from its ligand binding site by EL2Ab. Conclusions Collectively, our findings demonstrate that EL2Ab binds to and exhibits P2Y1R-dependent function-blocking activity in the context of platelets. These results add further evidence for a role of the P2Y1R in thrombosis and validate the concept that targeting it is a relevant alternative or complement to current antiplatelet strategies. PMID:25593131

  2. P2Y2 purinergic receptor activation is essential for efficient hepatocyte proliferation in response to partial hepatectomy

    PubMed Central

    Tackett, Bryan C.; Sun, Hongdan; Mei, Yu; Maynard, Janielle P.; Cheruvu, Sayuri; Mani, Arunmani; Hernandez-Garcia, Andres; Vigneswaran, Nadarajah; Karpen, Saul J.

    2014-01-01

    Extracellular nucleotides via activation of P2 purinergic receptors influence hepatocyte proliferation and liver regeneration in response to 70% partial hepatectomy (PH). Adult hepatocytes express multiple P2Y (G protein-coupled) and P2X (ligand-gated ion channels) purinergic receptor subtypes. However, the identity of key receptor subtype(s) important for efficient hepatocyte proliferation in regenerating livers remains unknown. To evaluate the impact of P2Y2 purinergic receptor-mediated signaling on hepatocyte proliferation in regenerating livers, wild-type (WT) and P2Y2 purinergic receptor knockout (P2Y2−/−) mice were subjected to 70% PH. Liver tissues were analyzed for activation of early events critical for hepatocyte priming and subsequent cell cycle progression. Our findings suggest that early activation of p42/44 ERK MAPK (5 min), early growth response-1 (Egr-1) and activator protein-1 (AP-1) DNA-binding activity (30 min), and subsequent hepatocyte proliferation (24–72 h) in response to 70% PH were impaired in P2Y2−/− mice. Interestingly, early induction of cytokines (TNF-α, IL-6) and cytokine-mediated signaling (NF-κB, STAT-3) were intact in P2Y2−/− remnant livers, uncovering the importance of cytokine-independent and nucleotide-dependent early priming events critical for subsequent hepatocyte proliferation in regenerating livers. Hepatocytes isolated from the WT and P2Y2−/− mice were treated with ATP or ATPγS for 5–120 min and 12–24 h. Extracellular ATP alone, via activation of P2Y2 purinergic receptors, was sufficient to induce ERK phosphorylation, Egr-1 protein expression, and key cyclins and cell cycle progression of hepatocytes in vitro. Collectively, these findings highlight the functional significance of P2Y2 purinergic receptor activation for efficient hepatocyte priming and proliferation in response to PH. PMID:25301185

  3. Role of the P2Y12 receptor in the modulation of murine dendritic cell function by ADP.

    PubMed

    Ben Addi, Abduelhakem; Cammarata, Dorothée; Conley, Pamela B; Boeynaems, Jean-Marie; Robaye, Bernard

    2010-11-15

    The effects of ADP on the biology of dendritic cells have been studied much less than those of ATP or adenosine. In this study, we showed that adenosine-5'-O-(2-thiodiphosphate) (ADPβS) induced intracellular Ca(2+) transients in murine dendritic cells (DCs). This effect was abolished by AR-C69931MX, a dual P2Y(12) and P2Y(13) receptor antagonist. RT-PCR experiments revealed the expression of both P2Y(12) and P2Y(13) mRNA in DCs. The Ca(2+) response to ADPβS was maintained in P2Y(13)-deficient DCs, whereas it was abolished completely in P2Y(12)(-/-) DCs. ADPβS stimulated FITC-dextran and OVA capture in murine DCs through macropinocytosis, and this effect was abolished in P2Y(12)(-/-) DCs. ADPβS had a similar effect on FITC-dextran uptake by human monocyte-derived DCs. OVA loading in the presence of ADPβS increased the capacity of DCs to stimulate OVA-specific T cells, whereas ADPβS had no effect on the ability of DCs to stimulate allogeneic T cells. Moreover, after immunization against OVA, the serum level of anti-OVA IgG1 was significantly lower in P2Y(12)(-/-) mice than that in wild-type controls. In conclusion, we have shown that the P2Y(12) receptor is expressed in murine DCs and that its activation increased Ag endocytosis by DCs with subsequent enhancement of specific T cell activation.

  4. P2Y12 antagonists in non-ST-segment elevation acute coronary syndromes: latest evidence and optimal use

    PubMed Central

    DiNicolantonio, James J.

    2015-01-01

    Dual antiplatelet therapy (DAPT), which includes the combination of aspirin and a P2Y12 platelet receptor inhibitor, is a well-established antiplatelet regimen in the treatment of patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Three P2Y12 inhibitor options (clopidogrel, prasugrel and ticagrelor) are currently available, all having different efficacy and safety profiles along with contrasting contraindications, special warnings and precautions for use. This review compares and contrasts the unique P2Y12 antagonists in the NSTE-ACS setting, covering the latest evidence and their optimal use. PMID:26137210

  5. Chemical analyses of pore water from boreholes USW SD-6 and USW WT-24, Yucca Mountain, Nevada.

    PubMed

    Yang, In C; Peterman, Zell E; Scofield, Kevin M

    2003-01-01

    Analyses of pore water extracted from cores of boreholes USW SD-6 in the central part and USW WT-24 in the northern part of Yucca Mountain, Nevada, show significant vertical and lateral variations in dissolved-ion concentrations. Analyses of samples of only a few milliliters of pore water extracted by uniaxial or triaxial compression and by ultracentrifugation methods from adjacent core samples are generally in agreement, within the analytical error of 10% to 15%. However, the values of silica for water obtained by ultracentrifugation are consistently lower than values for water obtained by compression. The larger concentrations probably are due to localized pressure solution of silicate minerals during compression. The shallower water from core in borehole USW SD-6 was extracted from nonwelded units collectively referred to as the Paintbrush Tuff nonwelded (PTn). The deeper water was from core in both boreholes USW SD-6 and USW WT-24 in the nonwelded units referred to as the Calico Hills nonwelded (CHn). Significant differences in mean dissolved-ion concentrations in pore water between the PTn and CHn are (1) decreases in Ca, Mg, SO(4), and NO(3) and (2) increases in HCO(3) and (Na+K)/(Ca+Mg) ratios. The decrease in NO(3) and the increase in HCO(3) could be the result of denitrification through the oxidation of organic matter. The decrease in Ca and associated increase in (Na+K)/(Ca+Mg) is the result of ion exchange with zeolites in the CHn in borehole USW WT-24. This effect is not nearly as pronounced in borehole USW SD-6, probably reflecting a smaller amount of zeolitization of the CHn in USW SD-6. Geochemical calculations using the PHREEQC code indicate that the pore water from both boreholes USW SD-6 and USW WT-24 is uniformly undersaturated in anhydrite, gypsum, and amorphous silica, but supersaturated in quartz and chalcedony. The saturation of calcite, aragonite, sepiolite, and dolomite is more variable from sample to sample.

  6. Discovery, characterization and in vivo activity of pyocin SD2, a protein antibiotic from Pseudomonas aeruginosa

    PubMed Central

    McCaughey, Laura C.; Josts, Inokentijs; Grinter, Rhys; White, Paul; Byron, Olwyn; Tucker, Nicholas P.; Matthews, Jacqueline M.; Kleanthous, Colin; Whitchurch, Cynthia B.; Walker, Daniel

    2016-01-01

    Increasing rates of antibiotic resistance among Gram-negative pathogens such as Pseudomonas aeruginosa means alternative approaches to antibiotic development are urgently required. Pyocins, produced by P. aeruginosa for intraspecies competition, are highly potent protein antibiotics known to actively translocate across the outer membrane of P. aeruginosa. Understanding and exploiting the mechanisms by which pyocins target, penetrate and kill P. aeruginosa is a promising approach to antibiotic development. In this work we show the therapeutic potential of a newly identified tRNase pyocin, pyocin SD2, by demonstrating its activity in vivo in a murine model of P. aeruginosa lung infection. In addition, we propose a mechanism of cell targeting and translocation for pyocin SD2 across the P. aeruginosa outer membrane. Pyocin SD2 is concentrated at the cell surface, via binding to the common polysaccharide antigen (CPA) of P. aeruginosa lipopolysaccharide (LPS), from where it can efficiently locate its outer membrane receptor FpvAI. This strategy of utilizing both the CPA and a protein receptor for cell targeting is common among pyocins as we show that pyocins S2, S5 and SD3 also bind to the CPA. Additional data indicate a key role for an unstructured N-terminal region of pyocin SD2 in the subsequent translocation of the pyocin into the cell. These results greatly improve our understanding of how pyocins target and translocate across the outer membrane of P. aeruginosa. This knowledge could be useful for the development of novel anti-pseudomonal therapeutics and will also support the development of pyocin SD2 as a therapeutic in its own right. PMID:27252387

  7. Alleviating anastrozole induced bone toxicity by selenium nanoparticles in SD rats

    SciTech Connect

    Vekariya, Kiritkumar K.; Kaur, Jasmine; Tikoo, Kulbhushan

    2013-04-15

    Aromatase inhibitors like anastrozole play an undisputed key role in the treatment of breast cancer, but on the other hand, various side effects like osteoporosis and increased risk of bone fracture accompany the chronic administration of these drugs. Here we show for the first time that selenium nanoparticles, when given in conjugation to anastrozole, lower the bone toxicity caused by anastrozole and thus reduce the probable damage to the bone. Selenium nanoparticles at a dose of 5 μg/ml significantly reduced the cell death caused by anastrozole (1 μM) in HOS (human osteoblast) cells. In addition, our results also highlighted that in female SD rat model, SeNPs (0.25, 0.5, 1 mg/kg/day) significantly prevented the decrease in bone density and increase in biochemical markers of bone resorption induced by anastrozole (0.2 mg/kg/day) treatment. Histopathological examination of the femurs of SeNP treated group revealed ossification, mineralization, calcified cartilaginous deposits and a marginal osteoclastic activity, all of which indicate a marked restorative action, suggesting the protective action of the SeNPs. Interestingly, SeNPs (1 mg/kg/day) also exhibited protective effect in ovariectomized rat model, by preventing osteoporosis, which signifies that bone loss due to estrogen deficiency can be effectively overcome by using SeNPs. - Highlights: ► SeNPs significantly reduce bone toxicity in anastrozole treated rats. ► SeNPs successfully prevented osteoporosis in ovariectomized rats. ► SeNP treatment lowered the levels of TRAP and increased the levels of ALKP.

  8. The effect of childbirth on carcinogenesis of DMBA-induced breast cancer in female SD rats.

    PubMed

    Zhao, Ji-An; Chen, Jin-Jun; Ju, Ying-Chao; Wu, Jian-Hua; Geng, Cui-Zhi; Yang, Hui-Chai

    2011-11-01

    Many epidemiologic and clinical studies have indicated that the frequency of breast cancer was lower in parous women than in nulliparous women. Moreover, the incidence of breast cancer has been reported to be lower in women with early childbirth than in women with late childbirth. To verify the effect of childbirth and the age at first childbirth on carcinogenesis and progression of breast cancer, we induced breast cancer by 7,12-dimethylbenanthracene (DMBA) in 120 female Sprague-Dawley (SD) rats, and divided them into control or experimental (DMBA-treated) nulliparous, early childbirth, and late childbirth groups to observe the incidence, latency, and size of breast cancer. Argyrophilic nucleolar organizer regions (AgNOR) count and the expression of C-erbB-2, proliferating cell nuclear antigen (PCNA), Ki-67, and minichromosome maintenance protein 2 (MCM2) in breast cancer tissues were detected by immunohistochemistry. The breast cancer incidences were 95.0%, 16.7%, and 58.8% in the experimental nulliparous, early childbirth, and late childbirth groups, respectively (all P < 0.05). Between any two of these groups, the latency was significantly different, but tumor size was similar. AgNOR count and the expression of C-erbB-2, PCNA, Ki-67, and MCM2 were significantly higher in the experimental nulliparous group than in the experimental early or late childbirth groups (P < 0.05), but no significant differences were observed between the latter two groups. Taken together, the results suggest that childbirth, especially early childbirth, can reduce the incidence and postpone the onset of DMBA-induced breast cancer.

  9. Reproductive toxicity study with a novel deoxyguanosine analogue (Metacavir) in pregnant SD rats.

    PubMed

    Luo, Qihui; Chen, Zhengli; Cheng, Anchun; Wang, Mingshu; Fang, Jing; Peng, Xi; Tang, Li

    2015-03-01

    Our preliminary studies demonstrated that Metacavir has potential to become a new anti-HBV agent. The main targets of the toxic effects of Metacavir, in rhesus monkeys, were gastrointestinal tracts, liver, blood, and kidneys, which were not related to mitochondrial effects. In this study, the maternal toxicity, embryo-fetal developmental toxicity and teratogenicity were studied in pregnant Sprague-Dawley rats after intragastric administration of Metacavir (200, 100, 50, 0 mg/kg body weight) during the first 6-15 days of pregnancy. Slower weight gain was observed in 5 out of 21 rats subjected to a 200 mg/kg dose, as well as 2 out of 20 subjected to a 100 mg/kg dose. Compared with the solvent control group, the calibration weight gain in the 200 mg/kg and 100 mg/kg dosage groups respectively, during first 6-20 pregnant days were significantly different (P < 0.01, P < 0.05). Significant dose related adverse effects to other reproductive parameters were not seen in F0 and F1, but the number of stillbirths in high dose group showed notably difference compared with the control group (P < 0.05), while the litter incidence showed no difference. No Metacavir-associated pathological changes were observed. The present research indicated that at a dose of 200 mg/(kg·d) (i.e., 40 times the effective dose in rats), Metacavir shows some maternal toxicity to SD rats. The embryotoxicity in the 200 mg/kg group encompass decreased fetal body weight, and higher fetal mortality rates, compared with the control group. However, the litter incidence showed no statistical difference. All the treated rats displayed normal bone development, no teratogenicity and without adverse effects on fetal development, thus indicating that below a dose of 200 mg/(kg·d) there is no teratogenic side effects.

  10. Coenzyme Q10 attenuated DMH-induced precancerous lesions in SD rats.

    PubMed

    Kim, Jung-Mi; Park, Eunju

    2010-01-01

    Coenzyme Q10 (CoQ10) is known to be a compound with mitochondrial bioenergetic functions and antioxidant activity. In this study, we evaluated the effect of CoQ10 on the formation of aberrant crypt foci (ACF) induced by 1,2-dimethylhydrazine (DMH), DMH-induced leukocytic DNA damage and gene expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) by real-time PCR in colonic mucosa of male SD rats. The animals were divided into three groups and fed a casein-based high-fat and low fiber diet (100 g lard+20 g cellulose/kg diet) with or without CoQ10 (0.4 mg in soybean oil/kg BW/d, i.p.). One week after beginning the diets, the rats were subjected to 6 wk of treatment with DMH (30 mg/kg/wk, s.c.) and CoQ10 treatments continued over the entirety of the experimental period (59 d). Administration of CoQ10 resulted in reduction of ACF numbers, to 20% of the carcinogen control value. CoQ10 supplementation induced an antigenotoxic effect on DMH-induced DNA damage in the blood cells. Colonic mucosa of DMH-injected rats had significantly greater COX-2 and iNOS gene expression than those of control rats, while treatment with CoQ10 induced an inhibitory effect on over-expression of COX-2 and iNOS in colon tumors. Our results provide evidence that CoQ10 has a protective effect on the process of colon carcinogenesis, suppressing the development of preneoplastic lesions, possibly by modulating COX-2 and iNOS gene expression in colonic mucosa and DNA damage in leukocytes, suggesting that CoQ10 has chemotherapeutic activity.

  11. Improved determination of the atmospheric parameters of the pulsating sdB star Feige 48

    SciTech Connect

    Latour, M.; Fontaine, G.; Brassard, P.; Green, E. M.; Chayer, P.

    2014-06-10

    As part of a multifaceted effort to better exploit the asteroseismological potential of the pulsating sdB star Feige 48, we present an improved spectroscopic analysis of that star based on new grids of NLTE, fully line-blanketed model atmospheres. To that end, we gathered four high signal-to-noise ratio time-averaged optical spectra of varying spectral resolutions from 1.0 Å to 8.7 Å, and we made use of the results of four independent studies to fix the abundances of the most important metals in the atmosphere of Feige 48. The mean atmospheric parameters we obtained from our four spectra of Feige 48 are: T {sub eff} = 29,850 ± 60 K, log g = 5.46 ± 0.01, and log N(He)/N(H) = –2.88 ± 0.02. We also modeled, for the first time, the He II line at 1640 Å from the STIS archive spectrum of the star, and with this line we found an effective temperature and a surface gravity that match well with the values obtained with the optical data. With some fine tuning of the abundances of the metals visible in the optical domain, we were able to achieve a very good agreement between our best available spectrum and our best-fitting synthetic one. Our derived atmospheric parameters for Feige 48 are in rather good agreement with previous estimates based on less sophisticated models. This underlines the relatively small effects of the NLTE approach combined with line blanketing in the atmosphere of this particular star, implying that the current estimates of the atmospheric parameters of Feige 48 are reliable and secure.

  12. Purification and Characterization of the Manganese(II) Oxidizing Protein from Erythrobacter sp. SD-21

    NASA Astrophysics Data System (ADS)

    Nakama, K. R.; Lien, A.; Johnson, H. A.

    2013-12-01

    The manganese(II) oxidizing protein (Mop) found in the alpha-proteobacterium Erythrobacter sp. SD-21 catalyzes the formation of insoluble Mn(III/IV) oxides from soluble Mn(II). These Mn(III/IV) oxides formed are one of the strongest naturally occurring oxides, next to oxygen, and can be used to adsorb and oxidize toxic chemicals from the surrounding environment. Because of the beneficial use in the treatment of contaminated sources, the mechanism and biochemical properties of this novel enzyme are being studied. Due to low expression levels in the native host strain, purification of Mop has been problematic. To overcome this problem the gene encoding Mop, mopA, was cloned from the native host into a C-terminal histidine tag vector and expressed in Escherichia coli cells. Affinity chromatography under denaturing conditions have been applied in attempts to purify an active Mop. Western blots have confirmed that the protein is being expressed and is at the expected size of 250 kDa. Preliminary characterization on crude extract containing Mop has shown a Km and vmax value of 2453 uM and 0.025 uM min-1, respectively. Heme and pyrroloquinoline quinone can stimulate Mn(II) oxidizing activity, but hydrogen peroxide does not affect activity, despite the sequence similarity to animal heme peroxidase proteins. Research has been shown that calcium is essential for Mop activity. Purifying an active Mn(II) oxidizing protein will allow for a better understanding behind the enigmatic process of Mn(II) oxidation.

  13. Primordial SdS universe from a 5D vacuum: scalar field fluctuations on Schwarzschild and Hubble horizons

    SciTech Connect

    Aguilar, José Edgar Madriz; Bellini, Mauricio E-mail: mbellini@mdp.edu.ar

    2010-11-01

    We study scalar field fluctuations of the inflaton field in an early inflationary universe on an effective 4D Schwarzschild-de Sitter (SdS) metric, which is obtained after make a planar coordinate transformation on a 5D Ricci-flat Schwarzschild-de Sitter (SdS) static metric. We obtain the important result that the spectrum of fluctuations at zeroth order is independent of the scalar field mass M on Schwarzschild scales, while on cosmological scales it exhibits a mass dependence. However, in the first-order expansion, the spectrum depends of the inflaton mass and the amplitude is linear with the Black-Hole (BH) mass m.

  14. The SD1 Subdomain of Venezuelan Equine Encephalitis Virus Capsid Protein Plays a Critical Role in Nucleocapsid and Particle Assembly

    PubMed Central

    Reynaud, Josephine M.; Lulla, Valeria; Kim, Dal Young; Frolova, Elena I.

    2015-01-01

    ABSTRACT Venezuelan equine encephalitis virus (VEEV) is an important human and animal pathogen, for which no safe and efficient vaccines or therapeutic means have been developed. Viral particle assembly and budding processes represent potential targets for therapeutic intervention. However, our understanding of the mechanistic process of VEEV assembly, RNA encapsidation, and the roles of different capsid-specific domains in these events remain to be described. The results of this new study demonstrate that the very amino-terminal VEEV capsid-specific subdomain SD1 is a critical player in the particle assembly process. It functions in a virus-specific mode, and its deletion, mutation, or replacement by the same subdomain derived from other alphaviruses has strong negative effects on infectious virus release. VEEV variants with mutated SD1 accumulate adaptive mutations in both SD1 and SD2, which result in a more efficiently replicating phenotype. Moreover, efficient nucleocapsid and particle assembly proceeds only when the two subdomains, SD1 and SD2, are derived from the same alphavirus. These two subdomains together appear to form the central core of VEEV nucleocapsids, and their interaction is one of the driving forces of virion assembly and budding. The similar domain structures of alphavirus capsid proteins suggest that this new knowledge can be applied to other alphaviruses. IMPORTANCE Alphaviruses are a group of human and animal pathogens which cause periodic outbreaks of highly debilitating diseases. Despite significant progress made in understanding the overall structure of alphavirus and VEEV virions, and glycoprotein spikes in particular, the mechanistic process of nucleocapsid assembly, RNA encapsidation, and the roles of different capsid-specific domains in these processes remain to be described. Our new data demonstrate that the very amino-terminal subdomain of Venezuelan equine encephalitis virus capsid protein, SD1, plays a critical role in the

  15. P2Y2 receptor deficiency aggravates chronic kidney disease progression

    PubMed Central

    Potthoff, Sebastian A.; Stegbauer, Johannes; Becker, Jan; Wagenhaeuser, P. Johannes; Duvnjak, Blanka; Rump, Lars C.; Vonend, Oliver

    2013-01-01

    Purinergic signaling is involved in a variety of physiological states. P2 receptors are mainly activated by adenosine triphosphate (ATP). Activation of specific P2Y receptor subtypes might influence progression of kidney disease. To investigate the in vivo effect of a particular P2 receptor subtype on chronic kidney disease progression, subtotal nephrectomy was performed on wild type (WT) and P2Y2 receptor knockout (KO) mice. During the observational period of 56 ± 2 days, survival of KO mice was inferior compared to WT mice after SNX. Subtotal nephrectomy reduced creatinine clearance in both groups of mice, but the decrease was significantly more pronounced in KO compared to WT mice (53.9 ± 7.7 vs. 84.3 ± 8.7μl/min at day 56). The KO mice also sustained a greater increase in systolic blood pressure after SNX compared to WT mice (177 ± 2 vs. 156 ± 7 mmHg) and a 2.5-fold increase in albuminuria compared to WT. In addition, WT kidneys showed a significant increase in remnant kidney mass 56 days after SNX, but significant attenuation of hypertrophy in KO mice was observed. In line with the observed hypertrophy in WT SNX mice, a significant dose-dependent increase in DNA synthesis, a marker of proliferation, was present in cultured WT glomerular epithelial cells upon ATP stimulation. Markers for tissue damage (TGF-β 1, PAI-1) and proinflammatory target genes (MCP1) were significantly upregulated in KO mice after SNX compared to WT SNX mice. In summary, deletion of the P2Y2 receptor leads to greater renal injury after SNX compared to WT mice. Higher systolic blood pressure and inability of compensatory hypertrophy in KO mice are likely causes for the accelerated progression of chronic kidney disease. PMID:24065922

  16. Extracellular nucleotides inhibit growth of human oesophageal cancer cells via P2Y2-receptors

    PubMed Central

    Maaser, K; Höpfner, M; Kap, H; Sutter, A P; Barthel, B; von Lampe, B; Zeitz, M; Scherübl, H

    2002-01-01

    Extracellular ATP is known to inhibit growth of various tumours by activating specific purinergic receptors (P2-receptors). Since the therapy of advanced oesophageal cancer is unsatisfying, new therapeutic approaches are mandatory. Here, we investigated the functional expression and potential antiproliferative effects of P2-purinergic receptors in human oesophageal cancer cells. Prolonged incubation of primary cell cultures of human oesophageal cancers as well as of the squamous oesophageal cancer cell line Kyse-140 with ATP or its stable analogue ATPγS dose-dependently inhibited cell proliferation. This was due to both an induction of apoptosis and cell cycle arrest. The expression of P2-receptors was examined by RT-PCR, immunocytochemistry, and [Ca2+]i-imaging. Application of various extracellular nucleotides dose-dependently increased [Ca2+]i. The rank order of potency was ATP=UTP>ATPγS>ADP=UDP. 2-methylthio-ATP and α,β-methylene-ATP had no effects on [Ca2+]i. Complete cross-desensitization between ATP and UTP was observed. Moreover, the phospholipase C inhibitor U73122 dose-dependently reduced the ATP triggered [Ca2+]i signal. The pharmacological features strongly suggest the functional expression of G-protein coupled P2Y2-receptors in oesophageal squamous cancer cells. P2Y2-receptors are involved in the antiproliferative actions of extracellular nucleotides. Thus, P2Y2-receptors are promising target proteins for innovative approaches in oesophageal cancer therapy. British Journal of Cancer (2002) 86, 636–644. DOI: 10.1038/sj/bjc/6600100 www.bjcancer.com © 2002 Cancer Research UK PMID:11870549

  17. Structural and spectroscopic studies of Ba2Y1-δUO6+x

    NASA Astrophysics Data System (ADS)

    Reynolds, Emily; Kennedy, Brendan J.; Avdeev, Maxim; Thorogood, Gordon J.; Zhang, Zhaoming; Brand, Helen E. A.

    2016-11-01

    A combination of S-XRD and NPD demonstrate the structure of Ba2Y0.879UO6+x to be monoclinic in space group I2/m. That the U is hexavalent is evident from the U L2-edge XANES measurements. This appears to be a rare example of a double perovskite containing vacancies at the octahedral B-sites and interstitial oxygen defects, which combine to stabilise hexavalent U and appears to be a consequence of the preparation of the sample in air. The Y vacancies, coupled with anion disorder, results in a distortion of the BO6 octahedra.

  18. Enhanced 77 K vortex-pinning in Y Ba2Cu3O7-x films with Ba2Y TaO6 and mixed Ba2Y TaO6 + Ba2Y NbO6 nano-columnar inclusions with irreversibility field to 11 T

    NASA Astrophysics Data System (ADS)

    Rizzo, F.; Augieri, A.; Angrisani Armenio, A.; Galluzzi, V.; Mancini, A.; Pinto, V.; Rufoloni, A.; Vannozzi, A.; Bianchetti, M.; Kursumovic, A.; MacManus-Driscoll, J. L.; Meledin, A.; Van Tendeloo, G.; Celentano, G.

    2016-06-01

    Pulsed laser deposited thin Y Ba2Cu3O7-x (YBCO) films with pinning additions of 5 at. % Ba2Y TaO6 (BYTO) were compared to films with 2.5 at. % Ba2Y TaO6 + 2.5 at. % Ba2Y NbO6 (BYNTO) additions. Excellent magnetic flux-pinning at 77 K was obtained with remarkably high irreversibility fields greater than 10 T (YBCO-BYTO) and 11 T (YBCO-BYNTO), representing the highest ever achieved values in YBCO films.

  19. Inhaled P2Y2 receptor agonists as a treatment for patients with Cystic Fibrosis lung disease.

    PubMed

    Kellerman, Don; Evans, Richard; Mathews, Dave; Shaffer, Christy

    2002-12-05

    P2Y(2) receptor agonists are a new class of compounds that are being evaluated as a treatment for the pulmonary manifestations of Cystic Fibrosis (CF). Results of preclinical research suggest that these compounds inhibit sodium absorption, restore chloride conductance and rehydrate the CF airway surface. In addition, P2Y(2) receptor agonists have been shown to enhance ciliary beat frequency and increase mucociliary clearance in animals and subjects with impaired mucociliary clearance. The normalization of airway surface liquid and enhancement of lung clearance is expected to provide a clinical benefit to CF patients. A number of P2Y(2) agonist compounds have been evaluated in healthy subjects and patients with CF. Most recently, INS37217, a metabolically stable and potent P2Y(2) agonist has been developed and studies have shown it to be well-tolerated when given via inhalation. This compound is currently being evaluated in children and adults with CF lung disease.

  20. Involvement of glial P2Y1 receptors in cognitive deficit after focal cerebral stroke in a rodent model

    PubMed Central

    2013-01-01

    Background Neuroinflammation is associated with many conditions that lead to dementia, such as cerebrovascular disorders or Alzheimer’s disease. However, the specific role of neuroinflammation in the progression of cognitive deficits remains unclear. To understand the molecular mechanisms underlying these events we used a rodent model of focal cerebral stroke, which causes deficits in hippocampus-dependent cognitive function. Methods Cerebral stroke was induced by middle cerebral artery occlusion (MCAO). Hippocampus-dependent cognitive function was evaluated by a contextual fear conditioning test. The glial neuroinflammatory responses were investigated by immunohistochemical evaluation and diffusion tensor MRI (DTI). We used knockout mice for P2Y1 (P2Y1KO), a glial ADP/ATP receptor that induces the release of proinflammatory cytokines, to examine the links among P2Y1-mediated signaling, the neuroinflammatory response, and cognitive function. Results Declines in cognitive function and glial neuroinflammatory response were observed after MCAO in both rats and mice. Changes in the hippocampal tissue were detected by DTI as the mean diffusivity (MD) value, which corresponded with the cognitive decline at 4 days, 1 week, 3 weeks, and 2 months after MCAO. Interestingly, the P2Y1KO mice with MCAO showed a decline in sensory-motor function, but not in cognition. Furthermore, the P2Y1KO mice showed neither a hippocampal glial neuroinflammatory response (as assessed by immunohistochemistry) nor a change in hippocampal MD value after MCAO. In addition, wild-type mice treated with a P2Y1-specific antagonist immediately after reperfusion did not show cognitive decline. Conclusion Our findings indicate that glial P2Y1 receptors are involved in the hippocampal inflammatory response. The findings from this study may contribute to the development of a therapeutic strategy for brain infarction, targeting the P2Y1 receptor. PMID:23890321

  1. Comparison of VerifyNow P2Y12 and thrombelastography for assessing clopidogrel response in stroke patients in China.

    PubMed

    Lv, Hui-Hui; Wu, Shuai; Liu, Xu; Yang, Xiao-Li; Xu, Jian-Feng; Guan, Yang-Tai; Dong, Qiang; Zheng, S Lilly; Jiang, Jian-Ming; Li, Shi-Xu; Luo, Zheng; Li, Li; An, Li-Xian; Han, Yan

    2016-02-01

    Poor response to clopidogrel is often associated with recurrent ischemic events, and reliable platelet function tests are needed to identify clopidogrel low response (CLR). The aim of the study was to compare the consistency of VerifyNow P2Y12 and thrombelastography (TEG) in acute ischemic stroke patients treated with clopidogrel. Patients hospitalized in Changhai Hospital from August 2012 to September 2013 and assigned to treatment with a daily 75-mg dose of clopidogrel. The blood samples were taken on the 5-7th day to assess the capability of VerifyNow P2Y12 and TEG for evaluation of clopidogrel response, and all instrument parameters were used to perform correlation analysis. Patients with CLR were detected by using the methods and criteria published earlier (PRU ≥ 230 assayed by VerifyNow P2Y12 or TEG-Inhib% ≤30 % measured by TEG). Totally 58 patients were enrolled for the study and there were wide varieties in parameters of VerifyNow P2Y12 and TEG. Results showed a total of 17 and 9 patients, respectively, identified as CLR assessed by VerifyNow P2Y12 and TEG, but only three patients were detected to be clopidogrel low responders with both tests. The kappa consistency analysis showed poor consistency between VerifyNow P2Y12 and TEG results in terms of CLR (Kappa = -0.0349, p = 0.7730). Linear regression also demonstrated poor correlation between VerifyNow-PRU/VerifyNow-Inhib% and TEG-Inhib% (p = 0.07901 and p = 0.3788, respectively). Our study demonstrated that there was poor correlation between VerifyNow P2Y12 and TEG results, and VerifyNow P2Y12 showed a larger proportion of CLR than TEG.

  2. Inverse agonism at the P2Y12 receptor and ENT1 transporter blockade contribute to platelet inhibition by ticagrelor

    PubMed Central

    Aungraheeta, Riyaad; Conibear, Alexandra; Butler, Mark; Kelly, Eamonn; Nylander, Sven; Mumford, Andrew

    2016-01-01

    Ticagrelor is a potent antagonist of the P2Y12 receptor (P2Y12R) and consequently an inhibitor of platelet activity effective in the treatment of atherothrombosis. Here, we sought to further characterize its molecular mechanism of action. Initial studies showed that ticagrelor promoted a greater inhibition of adenosine 5′-diphosphate (ADP)–induced Ca2+ release in washed platelets vs other P2Y12R antagonists. This additional effect of ticagrelor beyond P2Y12R antagonism was in part as a consequence of ticagrelor inhibiting the equilibrative nucleoside transporter 1 (ENT1) on platelets, leading to accumulation of extracellular adenosine and activation of Gs-coupled adenosine A2A receptors. This contributed to an increase in basal cyclic adenosine monophosphate (cAMP) and vasodilator-stimulated phosphoprotein phosphorylation (VASP-P). In addition, ticagrelor increased platelet cAMP and VASP-P in the absence of ADP in an adenosine receptor–independent manner. We hypothesized that this increase originated from a direct effect on basal agonist-independent P2Y12R signaling, and this was validated in 1321N1 cells stably transfected with human P2Y12R. In these cells, ticagrelor blocked the constitutive agonist-independent activity of the P2Y12R, limiting basal Gi-coupled signaling and thereby increasing cAMP levels. These data suggest that ticagrelor has the pharmacological profile of an inverse agonist. Based on our results showing insurmountable inhibition of ADP-induced Ca2+ release and forskolin-induced cAMP, the mode of antagonism of ticagrelor also appears noncompetitive, at least functionally. In summary, our studies describe 2 novel modes of action of ticagrelor, inhibition of platelet ENT1 and inverse agonism at the P2Y12R that contribute to its effective inhibition of platelet activation. PMID:27694321

  3. Boranophosphate Isoster Controls P2Y-Receptor Subtype Selectivity and Metabolic Stability of Dinucleoside Polyphosphate Analogues

    PubMed Central

    Yelovitch, Shir; Camden, Jean; Weisman, Gary A.; Fischer, Bilha

    2015-01-01

    Dinucleoside polyphosphates, NpnN′, exert their physiological effects via P2 receptors (P2Rs). NpnN′ are attractive drug candidates as they offer better stability and specificity compared to nucleotides, the most common P2R ligands. To further improve the agonist properties of NpnN′, we synthesized novel isosters of dinucleoside polyphosphates where N and N′ are A or U and where the Pα or Pβ phosphate groups are replaced by boranophosphate, denoted as Npn(α-B)N′ or Npn(β-B)N′ (n = 3, 4), respectively. The potency of Npn(α/β-B)N′ analogues was evaluated at tP2Y1, hP2Y2, hP2Y4, and rP2Y6 receptors. The most potent P2Y1R and P2Y6R agonists were the Up4(β-B)A (A isomer, EC50 of 0.5 μM vs 0.004 μM for 2-SMe-ADP) and Up3(α-B)U (B isomer, EC50 of 0.3 μM vs 0.2 μM for UDP), respectively. The receptor subtype selectivity is controlled by the position of the borano moiety on the NpnN′ polyphosphate chain and the type of the nucleobase. In addition, Npn(α/β-B)N′ proved ~22-fold more resistant to hydrolysis by e-NPP1, as compared to the corresponding NpnN′ analogues. In summary, Up4(β-B)A and Up3(α-B)U are potent, stable, and highly selective P2Y1 and P2Y6 receptor agonists, respectively. PMID:22107038

  4. A CHANDRA OBSERVATION OF THE NEARBY SCULPTOR GROUP Sd GALAXY NGC 7793

    SciTech Connect

    Pannuti, Thomas G.; Staggs, Wayne D.; Schlegel, Eric M.; Filipovic, Miroslav D.; Payne, Jeffrey L.; Petre, Robert

    2011-07-15

    We conducted a Chandra ACIS observation of the nearby Sculptor Group Sd galaxy NGC 7793 as part of a multiwavelength study of supernova remnants (SNRs) in nearby galaxies. At the assumed distance to NGC 7793 of 3.91 Mpc, the limiting unabsorbed luminosity of the detected discrete X-ray sources is L{sub X} (0.2-10.0 keV) {approx}3x10{sup 36} erg s{sup -1}. A total of 22 discrete sources were detected at the {approx}3{sigma} level or greater including one ultraluminous X-ray source (ULX). Based on multiwavelength comparisons, we identify X-ray sources coincident with one SNR, the candidate microquasar N7793-S26, one H II region, and two foreground Galactic stars. We also find that the X-ray counterpart to the candidate radio SNR R3 is time variable in its X-ray emission: we therefore rule out the possibility that this source is a single SNR. A marked asymmetry is seen in the distribution of the discrete sources with the majority lying in the eastern half of this galaxy. All of the sources were analyzed using quantiles to estimate spectral properties and spectra of the four brightest sources (including the ULX) were extracted and analyzed. We searched for time variability in the X-ray emission of the detected discrete sources using our measured fluxes along with fluxes measured from prior Einstein and Roentgensatellit observations. From this study, three discrete X-ray sources are established to be significantly variable. A spectral analysis of the galaxy's diffuse emission is characterized by a temperature of kT = 0.19-0.25 keV. The luminosity function of the discrete sources shows a slope with an absolute value of {Gamma} = -0.65 {+-} 0.11 if we exclude the ULX. If the ULX is included, the luminosity function has a long tail to high L{sub X} with a poor-fitting slope of {Gamma} = -0.62 {+-} 0.2. The ULX-less slope is comparable to the slopes measured for the distributions of NGC 6946 and NGC 2403 but much shallower than the slopes measured for the distributions of

  5. Uranium, Thorium, Potassium Contents of Materials in the Homestake Underground, Lead, SD

    NASA Astrophysics Data System (ADS)

    Roggenthen, W.; Smith, A.

    2008-12-01

    The uranium, thorium, and potassium contents (UTK) of materials in the underground laboratory at the Homestake DUSEL in Lead, SD, can significantly affect the radioactive backgrounds experienced by detectors in physics experiments planned for the facility. Many highly sensitive experiments require low activities both in terms of direct gamma and neutron radiation as well as radon that might emanate from the materials. Specific issues requiring characterization include evaluation of the rock in which laboratory rooms will be emplaced, the design of the cement and aggregate used in shotcreting the laboratory areas used for the physics experiments, estimates of requirements for shielding from radiation from the country rock, and estimates of radon emanation. The rocks of most importance from this standpoint in the laboratory underground include the Poorman Formation, the Yates Member of the Poorman Formation, and Tertiary igneous rocks. The laboratory at the 7400 level currently is planned for construction in the Yates, whereas the laboratories at the 4850 level are scheduled for construction in both the general Poorman Fm. and the Yates. The UTK contents of Poorman and Yates from the underground are generally very low (0.1 - 0.2 ppm U and 0.2 - 0.4 ppm Th). Rhyolitic intrusive rocks, which occur as thin dikes in the vicinity of the 4850 level laboratory, have substantially higher values that are reflective of their more silicic nature with typical U values in the range of 8 - 9 ppm. Many of the laboratory rooms for the detector experiments will have walls that have been shotcreted and floors finished with concrete. The concrete consists of at least two components, the cement and the aggregate. The choices for cement material are limited by local availability but the UTK content is in the 3 ppm range for U. Analyses of potential aggregates show that sources of aggregate from standard regional aggregate resources appear to have higher values of UTK content than is

  6. Positional cloning of rice semidwarfing gene, sd-1: rice "green revolution gene" encodes a mutant enzyme involved in gibberellin synthesis.

    PubMed

    Monna, Lisa; Kitazawa, Noriyuki; Yoshino, Rika; Suzuki, Junko; Masuda, Haruka; Maehara, Yumiko; Tanji, Masao; Sato, Mizuho; Nasu, Shinobu; Minobe, Yuzo

    2002-02-28

    A rice semidwarfing gene, sd-1, known as the "green revolution gene," was isolated by positional cloning and revealed to encode gibberellin 20-oxidase, the key enzyme in the gibberellin biosynthesis pathway. Analysis of 3477 segregants using several PCR-based marker technologies, including cleaved amplified polymorphic sequence, derived-CAPS, and single nucleotide polymorphisms revealed 1 ORF in a 6-kb candidate interval. Normal-type rice cultivars have an identical sequence in this region, consisting of 3 exons (558, 318, and 291 bp) and 2 introns (105 and 1471 bp). Dee-Geo-Woo-Gen-type sd-1 mutants have a 383-bp deletion from the genome (278-bp deletion from the expressed sequence), from the middle of exon 1 to upstream of exon 2, including a 105-bp intron, resulting in a frame-shift that produces a termination codon after the deletion site. The radiation-induced sd-1 mutant Calrose 76 has a 1-bp substitution in exon 2, causing an amino acid substitution (Leu [CTC] to Phe [TTC]). Expression analysis suggests the existence of at least one more locus of gibberellin 20-oxidase which may prevent severe dwarfism from developing in sd-1 mutants.

  7. Application of chirally-deuterated (S)-D-(6-2H1)glucose to conformational studies

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Deuterated sugars are widely used to elucidate mechanisms of biosynthesis and of chemical reactions, and to confirm assignments of complex NMR or mass spectra. To date, however, there are few reported syntheses for regio and stereospecifically deuterated pyranoses. Chirally-deuterated (S)-D-(6-**2...

  8. Isolation and characterization of Aurantiochytrium species: high docosahexaenoic acid (DHA) production by the newly isolated microalga, Aurantiochytrium sp. SD116.

    PubMed

    Gao, Mang; Song, Xiaojin; Feng, Yingang; Li, Wenli; Cui, Qiu

    2013-01-01

    A heterotrophic microalga, strain SD116, with the ability to produce high concentrations of docosahexaenoic acid (DHA, C22:6n-3) was isolated from Shuidong Bay, Guangdong Province, China. Nucleotide sequence analysis of the 18S rDNA of SD116 showed that the strain has a close phylogenetic relationship to Aurantiochytrium species. The highest rates for growth and DHA accumulation for SD116 were obtained in 6.0% glucose, 2.0% yeast extract, and 50% artificial seawater (ASW) at a pH of 7 at 28°C. The maximum total lipid content reached 56.3% of the dry cell weight (DCW), and the maximum DHA content accounted for 50.9% of the total fatty acid (TFA) content. It was further found that urea may be a potential nitrogen source for industrial fermentation because of its cheap price and ability to induce a relatively high biomass and lipid production capacity. Using 5 L fermenters, the DCW, total lipid content, and DHA yield were found to be 70.43 g L(-1), 71.09% of the DCW, and 17.42 g L(-1) (34.79% of the TFA), respectively. The results show that Aurantiochytrium sp. SD116 is a promising candidate for commercial DHA production and could be useful for the synthesis of biomass-related products.

  9. 76 FR 53400 - Black Hills National Forest, SD; Thunder Basin National Grassland, WY; Teckla-Osage-Rapid City...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-26

    ... Forest Service Black Hills National Forest, SD; Thunder Basin National Grassland, WY; Teckla-Osage-Rapid... Basin National Grasslands, private lands, BLM lands, and state lands in Wyoming. The line would be... Geri Proctor, Thunder Basin National Grasslands, 2250 East Richards Street, Douglas, WY...

  10. Identification of a New Marine Bacterial Strain SD8 and Optimization of Its Culture Conditions for Producing Alkaline Protease.

    PubMed

    Cui, Hongxia; Yang, Muyang; Wang, Liping; Xian, Cory J

    2015-01-01

    While much attention has been given to marine microorganisms for production of enzymes, which in general are relatively more stable and active compared to those from plants and animals, studies on alkaline protease production from marine microorganisms have been very limited. In the present study, the alkaline protease producing marine bacterial strain SD8 isolated from sea muds in the Geziwo Qinhuangdao sea area of China was characterized and its optimal culture conditions were investigated. Strain SD8 was initially classified to belong to genus Pseudomonas by morphological, physiological and biochemical characterizations, and then through 16S rDNA sequence it was identified to be likely Pseudomonas hibiscicola. In addition, the culture mediums, carbon sources and culture conditions of strain SD8 were optimized for maximum production of alkaline protease. Optimum enzyme production (236U/mL when cultured bacteria being at 0.75 mg dry weight/mL fermentation broth) was obtained when the isolate at a 3% inoculum size was grown in LB medium at 20 mL medium/100mL Erlenmeyer flask for 48h culture at 30°C with an initial of pH 7.5. This was the first report of strain Pseudomonas hibiscicola secreting alkaline protease, and the data for its optimal cultural conditions for alkaline protease production has laid a foundation for future exploration for the potential use of SD8 strain for alkaline protease production.

  11. Nocardiopsis sp. SD5: a potent feather degrading rare actinobacterium isolated from feather waste in Tamil Nadu, India.

    PubMed

    Saha, Subhasish; Dhanasekaran, D; Shanmugapriya, S; Latha, S

    2013-07-01

    Feather waste, generated in large quantities as a byproduct of commercial poultry processing, is nearly pure keratin protein, and keratin in its native state is not degradable by common proteolytic enzymes. The aim of the study was to find a potent feather degrading actinobacteria from feather waste soil. Out of 91 actinobacterial isolates recorded from feather waste soil in Tiruchirappalli and Nammakkal District, Tamil Nadu, India, isolate SD5 was selected for characterization because it exhibited significant keratinolytic activity. On the basis of the phenotypic, biochemical characterization and 16S rRNA gene-sequencing studies, the isolate was identified as Nocardiopsis sp. SD5. Protease and keratinase activity of Nocardiopsis sp. SD5 were analyzed. The enzyme was more stable over the neutral pH and the temperature of 40 °C. The optimum temperature and pH for both proteolytic and keratinolytic activity was determined at 50 °C and pH 9, respectively. Enzyme inhibitors, detergents and chelator declined the enzyme activity with increasing concentration. Nondenaturing polyacrylamide gel electrophoresis and zymogram elucidated the presence of 30 and 60 kDa protease enzymes. These findings indicated that thermo alkaliphilic feather degrading strain Nocardiopsis sp. SD5 could be used to control the feather waste pollution and to convert keratin rich feather waste into useful feedstock for poultry industry.

  12. 77 FR 27714 - Foreign-Trade Zone 220-Sioux Falls, SD; Application for Reorganization and Expansion Under...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-11

    ... Foreign-Trade Zones Board Foreign-Trade Zone 220--Sioux Falls, SD; Application for Reorganization and...) Board (the Board) by the Sioux Falls Development Foundation, grantee of FTZ 220, requesting authority to... following sites: Site 1 (130 acres)--Joe Foss Field, 2801 Jaycee Lane, Sioux Falls; Site 2 (123...

  13. Identification of a New Marine Bacterial Strain SD8 and Optimization of Its Culture Conditions for Producing Alkaline Protease

    PubMed Central

    Cui, Hongxia; Yang, Muyang; Wang, Liping; Xian, Cory J.

    2015-01-01

    While much attention has been given to marine microorganisms for production of enzymes, which in general are relatively more stable and active compared to those from plants and animals, studies on alkaline protease production from marine microorganisms have been very limited. In the present study, the alkaline protease producing marine bacterial strain SD8 isolated from sea muds in the Geziwo Qinhuangdao sea area of China was characterized and its optimal culture conditions were investigated. Strain SD8 was initially classified to belong to genus Pseudomonas by morphological, physiological and biochemical characterizations, and then through 16S rDNA sequence it was identified to be likely Pseudomonas hibiscicola. In addition, the culture mediums, carbon sources and culture conditions of strain SD8 were optimized for maximum production of alkaline protease. Optimum enzyme production (236U/mL when cultured bacteria being at 0.75 mg dry weight/mL fermentation broth) was obtained when the isolate at a 3% inoculum size was grown in LB medium at 20 mL medium/100mL Erlenmeyer flask for 48h culture at 30°C with an initial of pH 7.5. This was the first report of strain Pseudomonas hibiscicola secreting alkaline protease, and the data for its optimal cultural conditions for alkaline protease production has laid a foundation for future exploration for the potential use of SD8 strain for alkaline protease production. PMID:26716833

  14. P2Y12-ADP receptor antagonists: Days of future and past

    PubMed Central

    Laine, Marc; Paganelli, Franck; Bonello, Laurent

    2016-01-01

    Antiplatelet therapy is the cornerstone of the therapeutic arsenal in coronary artery disease. Thanks to a better understanding in physiology, pharmacology and pharmacogenomics huge progress were made in the field of platelet reactivity inhibition thus allowing the expansion of percutaneous coronary intervention. Stent implantation requires the combination of two antiplatelet agents acting in a synergistic way. Asprin inhibit the cyclo-oxygenase pathway of platelet activation while clopidogrel is a P2Y12 adenosine diphosphate (ADP)-receptor antagonist. This dual antiplatelet therapy has dramatically improved the prognosis of stented patients. However, due to pharmacological limitations of clopidogrel (interindividual variability in its biological efficacy, slow onset of action, mild platelet reactivity inhibition) ischemic recurrences remained high following stent implantation especially in acute coronary syndrome patients. Thus, more potent P2Y12-ADP receptor inhibitors were developped including prasugrel, ticagrelor and more recently cangrelor to overcome these pitfalls. These new agents reduced the rate of thrombotic events in acute coronary syndrome patients at the cost of an increased bleeding risk. The abundance in antiplatelet agents allow us to tailor our strategy based on the thrombotic/bleeding profile of each patient. Recently, the ACCOAST trial cast a doubt on the benefit of pre treatment in non-ST segment elevation acute coronary syndrome. The aim of the present review is to summarize the results of the main studies dealing with antiplatelet therapy in stented/acute coronary syndromes patients. PMID:27231519

  15. A theoretical study of models for X sub 2 Y sub 2 zintl ions

    SciTech Connect

    Cave, R.J.; Davidson, E.R. ); Sautet, P.; Canadell, E.; Eisenstein, O. )

    1989-10-11

    Ab initio and extended Hueckel calculations have been used to discuss the bonding scheme in X{sub 2}Y{sub 2} neutral and ionic main group clusters. A qualitative analysis suggests that two different electron counts, 20 and 22, are possible for the butterfly structures of these systems. This results from two orbital crossings in the correlation diagram for the tetrahedral (T{sub d}) {yields} butterfly (C{sub 2{nu}}) {yields} square-planar (D{sub 2h}) transformation. Detailed ab initio computations substantiate this analysis and show that the 20-electron butterfly structure becomes increasingly favored over the tetrahedral one in X{sub 2}Y{sub 2} clusters when the 2 atoms have increasing electronegativity difference. These results are in agreement with the known structures for the Pb{sub 2}Sb{sub 2}{sup 2{minus}} and Sb{sub 2}Bi{sub 2}{sup 2{minus}} clusters (tetrahedral-like) and the Tl{sub 2}Te{sub 2}{sup 2{minus}} one (butterfly-like).

  16. Two different P2Y receptors linked to steroidogenesis in bovine adrenocortical cells.

    PubMed

    Nishi, H

    1999-10-01

    Both extracellular adenosine 5'-triphosphate (ATP) and uridine 5'-triphosphate (UTP) induced corticoid production (steroidogenesis) concentration-dependently in bovine adrenocortical cells (BA cells). Pertussis toxin (PTX, approx. 2 microg/ml) partially inhibited (approx. 55% inhibition) extracellular ATP (100 microM)-induced steroidogenesis in BA cells. However, PTX did not inhibit extracellular UTP (100 microM)-induced steroidogenesis. Both ATP- and UTP-induced steroidogeneses were significantly inhibited by suramin (50-200 microM). These effects were inhibited significantly by reactive blue-2 (more than 100 microM) and pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (more than 100 microM). Both nucleotides (1-100 microM) induced inositol phosphates accumulation and intracellular Ca2+ mobilization, but PTX did not inhibit them. The RT-PCR procedure identified only P2Y2-receptor mRNA in BA cells. These results suggest that extracellular ATP induces steroidogenesis via a unique P2 receptor linked to PTX-sensitive guanine nucleotide-binding protein (G-protein), while extracellular UTP induces steroidogenesis via P2 receptor linked to PTX-insensitive G-protein. Thus, it was concluded that at least two different P2Y-like receptors linking to steroidogenesis exist in BA cells.

  17. Suppression of exchange bias effect in maghemite nanoparticles functionalized with H2Y

    NASA Astrophysics Data System (ADS)

    Guivar, Juan A. Ramos; Morales, M. A.; Litterst, F. Jochen

    2016-12-01

    The structural, vibrational, morphological and magnetic properties of maghemite (γ-Fe2O3) nanoparticles functionalized with polar molecules EDTA(or H4Y) and H2Y are reported. The samples were functionalized before and after total synthesis of γ-Fe2O3 nanoparticles. The molecules are anchored on the monodentate mode on the nanoparticles surface. Transmission electron microscopy (TEM) revealed the formation of maghemite nanoparticles with small diameter of 4 nm for the sample functionalized upon synthesis and 7.6 and 6.9 nm for the samples functionalized with EDTA and H2Y after the formation of nanoparticles. Exchange bias phenomena were observed in some of the samples functionalized with EDTA at temperatures below 70 K. The presence of the bias effect was discussed in terms of the formation of a thin layer of a secondary phase like lepidocrocite, and the absence of this effect was explained in terms of the chemisorption of carboxylic groups from EDTA which suppressed the canting. Studies of Mössbauer spectroscopy as a function of temperature showed slow relaxation effects and allowed discussion of the secondary phase. In the M-T curves a maximum around 116 K was associated with this secondary phase also in agreement with the Mössbauer studies. The dynamic properties were studied by AC susceptibility, the out of phase signal revealed a spin glass like regime below 36.5 K.

  18. The G Protein-coupled Receptor P2Y14 Influences Insulin Release and Smooth Muscle Function in Mice*

    PubMed Central

    Meister, Jaroslawna; Le Duc, Diana; Ricken, Albert; Burkhardt, Ralph; Thiery, Joachim; Pfannkuche, Helga; Polte, Tobias; Grosse, Johannes; Schöneberg, Torsten; Schulz, Angela

    2014-01-01

    UDP sugars were identified as extracellular signaling molecules, assigning a new function to these compounds in addition to their well defined role in intracellular substrate metabolism and storage. Previously regarded as an orphan receptor, the G protein-coupled receptor P2Y14 (GPR105) was found to bind extracellular UDP and UDP sugars. Little is known about the physiological functions of this G protein-coupled receptor. To study its physiological role, we used a gene-deficient mouse strain expressing the bacterial LacZ reporter gene to monitor the physiological expression pattern of P2Y14. We found that P2Y14 is mainly expressed in pancreas and salivary glands and in subpopulations of smooth muscle cells of the gastrointestinal tract, blood vessels, lung, and uterus. Among other phenotypical differences, knock-out mice showed a significantly impaired glucose tolerance following oral and intraperitoneal glucose application. An unchanged insulin tolerance suggested altered pancreatic islet function. Transcriptome analysis of pancreatic islets showed that P2Y14 deficiency significantly changed expression of components involved in insulin secretion. Insulin secretion tests revealed a reduced insulin release from P2Y14-deficient islets, highlighting P2Y14 as a new modulator of proper insulin secretion. PMID:24993824

  19. Reproducibility of SD-OCT–Based Ganglion Cell–Layer Thickness in Glaucoma Using Two Different Segmentation Algorithms

    PubMed Central

    Garvin, Mona K.; Lee, Kyungmoo; Burns, Trudy L.; Abràmoff, Michael D.; Sonka, Milan; Kwon, Young H.

    2013-01-01

    Purpose. To compare the reproducibility of spectral-domain optical coherence tomography (SD-OCT)–based ganglion cell–layer-plus-inner plexiform–layer (GCL+IPL) thickness measurements for glaucoma patients obtained using both a publicly available and a commercially available algorithm. Methods. Macula SD-OCT volumes (200 × 200 × 1024 voxels, 6 × 6 × 2 mm3) were obtained prospectively from both eyes of patients with open-angle glaucoma or with suspected glaucoma on two separate visits within 4 months. The combined GCL+IPL thickness was computed for each SD-OCT volume within an elliptical annulus centered at the fovea, based on two algorithms: (1) a previously published graph-theoretical layer segmentation approach developed at the University of Iowa, and (2) a ganglion cell analysis module of version 6 of Cirrus software. The mean overall thickness of the elliptical annulus was computed as was the thickness within six sectors. For statistical analyses, eyes with an SD-OCT volume with low signal strength (<6), image acquisition errors, or errors in performing the commercial GCL+IPL analysis in at least one of the repeated acquisitions were excluded. Results. Using 104 eyes (from 56 patients) with repeated measurements, we found the intraclass correlation coefficient for the overall elliptical annular GCL+IPL thickness to be 0.98 (95% confidence interval [CI]: 0.97–0.99) with the Iowa algorithm and 0.95 (95% CI: 0.93–0.97) with the Cirrus algorithm; the intervisit SDs were 1.55 μm (Iowa) and 2.45 μm (Cirrus); and the coefficients of variation were 2.2% (Iowa) and 3.5% (Cirrus), P < 0.0001. Conclusions. SD-OCT–based GCL+IPL thickness measurements in patients with early glaucoma are highly reproducible. PMID:24045993

  20. Platelet collagen receptor integrin alpha2beta1 activation involves differential participation of ADP-receptor subtypes P2Y1 and P2Y12 but not intracellular calcium change.

    PubMed

    Jung, S M; Moroi, M

    2001-06-01

    In agonist-induced platelet activation, the collagen platelet receptor integrin alpha2beta1 is activated to high-affinity states through ADP involvement [Jung, S.M. & Moroi, M. (2000) J. Biol. Chem. 275, 8016-8026]. Here we determined the ADP-receptor subtypes involved and their relative contributions to alpha2beta1 activation (assessed by soluble-collagen binding) using the P2Y12 antagonist AR-C69931MX and P2Y1 antagonists adenosine 3',5'-diphosphate (Ado(3,5)PP) and adenosine 3'-phosphate 5'-phosphosulfate (AdoPPS). All three inhibited alpha2beta1 activation induced by low or high ADP, low thrombin, or low collagen-related peptide (CRP) concentrations; however, AR-C69931MX was markedly more inhibitory than the P2Y1 antagonists, suggesting the greater contribution of P2Y12. Inhibition patterns by various combinations of AR-C69931MX, AdoPPS, and wortmannin suggested that P2Y1 and P2Y12 mediate alpha2beta1 activation through different pathways, with possible involvement of phosphoinositide 3-kinase in both. Low concentrations of the acetoxy-methyl derivative of 1,2-bis(o-aminophenoxy) ethane-N,N,N',N'-tetra-acetic acid (calcium chelator) markedly decreased alpha2beta1 activation by low thrombin or CRP, but did not affect that by low or high ADP. Measurements of intracellular Ca2+ level (fluorimetric method) and alpha2beta1 activation (soluble-collagen binding) in the same platelet preparation indicated that alpha2beta1 activation via ADP receptors was independent of intracellular Ca2+ release. Our data indicate that integrin alpha2beta1 activation by ADP occurs through an inside-out signaling mechanism involving differential contributions by P2Y1 and P2Y12 wherein each contributes to some portion of the activation, with the stronger contribution of P2Y12. Furthermore, intracellular Ca2+ increase is not directly related to integrin alpha2beta1 activation, meaning that it is separate from the calcium mobilization pathways that these two ADP receptors are involved in.

  1. Chemical analyses of pore water from boreholes USW SD-6 and USW WT-24, Yucca Mountain, Nevada

    USGS Publications Warehouse

    Yang, I.C.; Peterman, Z.E.; Scofield, K.M.

    2003-01-01

    Analyses of pore water extracted from cores of boreholes USW SD-6 in the central part and USW WT-24 in the northern part of Yucca Mountain, Nevada, show significant vertical and lateral variations in dissolved-ion concentrations. Analyses of samples of only a few milliliters of pore water extracted by uniaxial or triaxial compression and by ultracentrifugation methods from adjacent core samples are generally in agreement, within the analytical error of 10% to 15%. However, the values of silica for water obtained by ultracentrifugation are consistently lower than values for water obtained by compression. The larger concentrations probably are due to localized pressure solution of silicate minerals during compression. The shallower water from core in borehole USW SD-6 was extracted from nonwelded units collectively referred to as the Paintbrush Tuff nonwelded (PTn). The deeper water was from core in both boreholes USW SD-6 and USW WT-24 in the nonwelded units referred to as the Calico Hills nonwelded (CHn). Significant differences in mean dissolved-ion concentrations in pore water between the PTn and CHn are (1) decreases in Ca, Mg, SO4, and NO3 and (2) increases in HCO3 and (Na+K)/(Ca+Mg) ratios. The decrease in NO3 and the increase in HCO3 could be the result of denitrification through the oxidation of organic matter. The decrease in Ca and associated increase in (Na+K)/(Ca+Mg) is the result of ion exchange with zeolites in the CHn in borehole USW WT-24. This effect is not nearly as pronounced in borehole USW SD-6, probably reflecting a smaller amount of zeolitization of the CHn in USW SD-6. Geochemical calculations using the PHREEQC code indicate that the pore water from both boreholes USW SD-6 and USW WT-24 is uniformly undersaturated in anhydrite, gypsum, and amorphous silica, but supersaturated in quartz and chalcedony. The saturation of calcite, aragonite, sepiolite, and dolomite is more variable from sample to sample. ?? 2002 Elsevier Science B.V. All rights

  2. Incidence and Clinical Features of Early Stent Thrombosis in the Era of New P2y12 Inhibitors (PLATIS-2)

    PubMed Central

    Asher, Elad; Abu-Much, Arsalan; Goldenberg, Ilan; Segev, Amit; Sabbag, Avi; Mazin, Israel; Shlezinger, Meital; Atar, Shaul; Zahger, Doron; Polak, Arthur; Beigel, Roy; Matetzky, Shlomi

    2016-01-01

    Early stent thrombosis (EST) (≤ 30 days after stent implantation) is a relatively rare but deleterious complication of percutaneous coronary intervention (PCI). Administration of newer P2Y12 inhibitors (prasugrel and ticagrelor) combined with aspirin has been shown to reduce the incidence of sub-acute and late stent thrombosis, compared with clopidogrel. We investigated the “real life” incidence of EST in patients from a large acute coronary syndrome (ACS) national registry, where newer P2Y12 inhibitors are widely used. Patients were derived from the ACS Israeli Survey (ACSIS), conducted during 2006, 2008, 2010 and 2013. Major adverse cardiac events (MACE) at 30days were defined as all-cause death, recurrent ACS, EST and stroke.Of the 4717 ACS patients who underwent PCI and stenting, 83% received clopidogrel and 17% newer P2Y12 inhibitors. The rate of EST was similar in both groups (1.7% in the newer P2Y12 inhibitor group vs. 1.4% in the clopidogrel-treated patients, p = 0.42). Results were consistent after multivariate analysis (adjusted HR = 1.06 [p = 0.89]). MACE occurred in 6.4% in the newer P2Y12 inhibitor group compared with 9.2% in the clopidogrel group (P<0.01). However, multivariate logistic regression modeling showed that treatment with newer P2Y12 inhibitors was not significantly associated with the secondary endpoint of MACE when compared with clopidogrel therapy [OR = 1.26 95%CI (0.93–1.73), P = 0.136]. The incidence of "real life" EST at 1month is relatively low, and appears to be similar in patients who receive newer P2Y12 inhibitors as well as in those who receive clopidogrel. PMID:27310147

  3. In silico Approach for Anti-Thrombosis Drug Discovery: P2Y1R Structure-Based TCMs Screening

    PubMed Central

    Yi, Fan; Sun, Le; Xu, Li-jia; Peng, Yong; Liu, Hai-bo; He, Chun-nian; Xiao, Pei-gen

    2017-01-01

    Cardiovascular diseases (CVDs), including thrombosis, which is induced by platelet aggregation, are the leading cause of mortality worldwide. The P2Y1 receptor (P2Y1R) facilitates platelet aggregation and is thus an important potential anti-thrombotic drug target. The P2Y1R protein structure contains a binding site for receptor antagonist MRS2500 within its seven-transmembrane bundle, which also provides suitable pockets for numerous other ligands to act as nucleotide antagonists of P2Y1R. The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) comprises 499 Chinese Pharmacopoeia-registered herbs and the structure information for 29,384 ingredients. In silico docking of these compounds into the P2Y1R protein structure within the MRS2500 pocket can identify potential antithrombotic drugs from natural medicinal plants. Docking studies were performed and scored to evaluate ligand-binding affinities. In this study, a total of 8987 compounds from Traditional Chinese Medicine (TCM) were filtered by Lipinski's rule of five, and their ideal oral-intake properties were evaluated. Of these, 1656 compounds distributed in 443 herbs docked into the P2Y1R-MRS2500 structure in 16,317 poses. A total of 38 compounds were ranked with a DockScore above 70, and these may have significant potential for development into anti-thrombosis drugs. These computational results suggested that licorice (Glycyrrhiza uralensis Fisch), cimicifugae (Cimicifuga foetida L.), and ganoderma (Ganoderma lucidum Karst) and their chemical constituents, which have not previously been widely used for anti-thrombosis, may have unexpected effects on platelet aggregation. Moreover, two types of triterpene scaffolds summarized from 10 compounds were distributed in these three herbs and also docked into P2Y1R. These scaffold structures may be utilized for the development of drugs to inhibit platelet aggregation. PMID:28119608

  4. Cytoprotection against oxidative stress-induced damage of astrocytes by extracellular ATP via P2Y1 receptors.

    PubMed

    Shinozaki, Youichi; Koizumi, Schuichi; Ishida, Seiichi; Sawada, Jun-Ichi; Ohno, Yasuo; Inoue, Kazuhide

    2005-01-15

    Oxidative stress is the main cause of neuronal damage in traumatic brain injury, hypoxia/reperfusion injury, and neurodegenerative disorders. Although extracellular nucleosides, especially adenosine, are well known to protect against neuronal damage in such pathological conditions, the effects of these nucleosides or nucleotides on glial cell damage remain largely unknown. We report that ATP but not adenosine protects against the cell death of cultured astrocytes induced by hydrogen peroxide (H2O2). ATP ameliorated the H2O2-induced decrease in cell viability of astrocytes in an incubation time- and concentration-dependent fashion. Protection by ATP was inhibited by P2 receptor antagonists and was mimicked by P2Y1 receptor agonists but not by adenosine. The expressions of P2Y1 mRNAs and functional P2Y1 receptors in astrocytes were confirmed. Thus, ATP, acting on P2Y1 receptors in astrocytes, showed a protective action against H2O2. The astrocytic protection by the P2Y1 receptor agonist 2-methylthio-ADP was inhibited by an intracellular Ca2+ chelator and a blocker of phospholipase C, indicating the involvement of intracellular signals mediated by Gq/11-coupled P2Y1 receptors. The ATP-induced protection was inhibited by cycloheximide, a protein synthesis inhibitor, and it took more than 12 h for the onset of the protective action. In the DNA microarray analysis, ATP induced a dramatic upregulation of various oxidoreductase genes. Taken together, ATP acts on P2Y1 receptors coupled to Gq/11, resulting in the upregulation of oxidoreductase genes, leading to the protection of astrocytes against H2O2.

  5. Clopidogrel Resistance by P2Y12 Platelet Function Testing in Patients Undergoing Neuroendovascular Procedures

    PubMed Central

    Nordeen, Jerah D.; Patel, Alden V.; Darracott, Robert M.; Johns, Gretchen S.; Taussky, Philipp; Tawk, Rabih G.; Miller, David A.; Freeman, William D.; Hanel, Ricardo A.

    2013-01-01

    Purpose: The purpose of the study was to assess clopidogrel resistance and whether “intensified” antiplatelet therapy guided by platelet inhibition tests during neuroendovascular procedures would reduce ischemic complications. Methods: We conducted a retrospective review of patients at Mayo Clinic in Jacksonville, Florida, who underwent neuroendovascular (NV) procedures and had P2Y12 platelet function testing from October 1, 2009, to September 30, 2010. The primary end-point was to determine P2Y12 resistance to antiplatelet therapy in patients who underwent NV procedures. Secondary objectives included incidence of hemorrhagic and ischemic events and a correlation between resistance and genetic CYP2C19 testing. Results: 160 patients underwent P2Y12 platelet function tests. Eighty-one patients (81/160, 50.6%) met inclusion criteria. Platelet function tests identified 64 patients (79%) as non-resistant (≥20% P2Y12 inhibition) and 17 (21%) as resistant (<20% inhibition) after initial clopidogrel loading. There was an increased rate of death when a complication occurred in the resistant group by 30 day (17% versus 3%; p=0.059) and 90 day follow-up (23% versus 4%; p=0.032). There was no significant association found between complication and loading dose (p=0.0721). Conclusions: 21% of patients undergoing NV procedures were resistant to clopidogrel. Intensifying antiplatelet therapy to achieve ≥20% inhibition on platelet function testing did not result in higher numbers of ischemic or hemorrhagic events, but there was a trend toward more death in the resistant group by 30 and 90 days of those experiencing complication(s). Author Justifications: Jerah D. Nordeen, Pharm.D.: Primary author Alden V. Patel, Pharm.D.: Contributor of professional content, study design Robert M. Darracott, Pharm.D.: Contributor of professional content, study design Gretchen S. Johns, M.D.: Contributor of professional content, study design Philipp Taussky, M.D.: Contributor of professional

  6. Stabilization of the fluorite phase in the ZrO2-Y2O3 system

    NASA Astrophysics Data System (ADS)

    Popov, V. V.; Yastrebtsev, A. A.; Smirnov, I. S.; Monakhov, I. S.; Novoselova, E. G.; Tsarenko, N. A.; Udovskii, A. L.

    2016-09-01

    The calculated and experimental vertical ZrO2-Y2O3 sections of the Zr-Y-O system are compared to find the region of a stable fluorite structure of yttrium-stabilized zirconia (YSZ). X-ray diffraction (XRD) and Raman scattering are used to study the crystal and local structures of mixed oxide 0.82ZrO2 · 0.18Y2O3 (18YSZ) powders prepared by isothermal annealing of a precursor precipitated from a salt solution. The formation of a fluorite-type fcc structure (space group Fmoverline 3 m) in the powders is detected by XRD. Raman scattering study of the local structure of the cubic 18YSZ powders revealed traces of the tetragonal phase in them.

  7. Credit WCT. Original 2¾" x 2Y4" color negative is housed ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Credit WCT. Original 2-¾" x 2-Y4" color negative is housed in the JPL Photography Laboratory, Pasadena, California. View shows JPL staff member John Morrow loading the grinder hopper. The hopper has a 10 mesh screen to filter out particles too large for the mill. Oxidizer is passed steadily to the hammers by a stainless steel feed screw. Oxidizer may be passed through the mill several times depending on the fineness required by a given propellant formula; the maximum charge is 130 pounds (59.0 Kg). The drum below the mill has an electrically conductive plastic liner which receives the ground oxidizer (JPL negative no. JPL10279AC, 27 January 1989) - Jet Propulsion Laboratory Edwards Facility, Oxidizer Grinder Building, Edwards Air Force Base, Boron, Kern County, CA

  8. Microglial P2Y12 is necessary for synaptic plasticity in mouse visual cortex

    PubMed Central

    Sipe, G. O.; Lowery,, R. L.; Tremblay, M-È; Kelly, E. A.; Lamantia, C. E.; Majewska, A. K.

    2016-01-01

    Microglia are the resident immune cells of the brain. Increasingly, they are recognized as important mediators of normal neurophysiology, particularly during early development. Here we demonstrate that microglia are critical for ocular dominance plasticity. During the visual critical period, closure of one eye elicits changes in the structure and function of connections underlying binocular responses of neurons in the visual cortex. We find that microglia respond to monocular deprivation during the critical period, altering their morphology, motility and phagocytic behaviour as well as interactions with synapses. To explore the underlying mechanism, we focused on the P2Y12 purinergic receptor, which is selectively expressed in non-activated microglia and mediates process motility during early injury responses. We find that disrupting this receptor alters the microglial response to monocular deprivation and abrogates ocular dominance plasticity. These results suggest that microglia actively contribute to experience-dependent plasticity in the adolescent brain. PMID:26948129

  9. P2X and P2Y receptor signaling in red blood cells.

    PubMed

    Sluyter, Ronald

    2015-01-01

    Purinergic signaling involves the activation of cell surface P1 and P2 receptors by extracellular nucleosides and nucleotides such as adenosine and adenosine triphosphate (ATP), respectively. P2 receptors comprise P2X and P2Y receptors, and have well-established roles in leukocyte and platelet biology. Emerging evidence indicates important roles for these receptors in red blood cells. P2 receptor activation stimulates a number of signaling pathways in progenitor red blood cells resulting in microparticle release, reactive oxygen species formation, and apoptosis. Likewise, activation of P2 receptors in mature red blood cells stimulates signaling pathways mediating volume regulation, eicosanoid release, phosphatidylserine exposure, hemolysis, impaired ATP release, and susceptibility or resistance to infection. This review summarizes the distribution of P2 receptors in red blood cells, and outlines the functions of P2 receptor signaling in these cells and its implications in red blood cell biology.

  10. P2Y purinergic receptor regulation of CFTR chloride channels in mouse cardiac myocytes.

    PubMed

    Yamamoto-Mizuma, Shintaro; Wang, Ge-Xin; Hume, Joseph R

    2004-05-01

    The intracellular signalling pathways and molecular mechanisms responsible for P2-purinoceptor-mediated chloride (Cl(-)) currents (I(Cl,ATP)) were studied in mouse ventricular myocytes. In standard NaCl-containing extracellular solutions, extracellular ATP (100 microm) activated two different currents, I(Cl,ATP) with a linear I-V relationship in symmetrical Cl(-) solutions, and an inwardly rectifying cation conductance (cationic I(ATP)). Cationic I(ATP) was selectively inhibited by Gd(3+) and Zn(2+), or by replacement of extracellular NaCl by NMDG; I(Cl,ATP) was Cl(-) selective, and inhibited by replacement of extracellular Cl(-) by Asp(-); both currents were prevented by suramin or DIDS pretreatment. In GTPgammaS-loaded cells, I(Cl,ATP) was irreversibly activated by ATP, but cationic I(ATP) was still regulated reversibly. GDPbetaS prevented activation of the I(Cl,ATP,) even though pertussis toxin pretreatment did not modulate I(Cl,ATP). These results suggest that activation of I(Cl,ATP) occurs via a G-protein coupled P2Y purinergic receptor. The I(Cl,ATP) persistently activated by GTPgammaS, was inhibited by glibenclamide but not by DIDS, thus exhibiting known pharmacological properties of cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channels. In ventricular cells of cftr(-/-) mice, extracellular ATP activated cationic I(ATP), but failed to activate any detectable I(Cl,ATP). These results provide compelling evidence that activation of CFTR Cl(-) channels in mouse heart are coupled to G-protein coupled P2Y purinergic receptors.

  11. Purinergic P2Y receptors in airway epithelia: from ion transport to immune functions.

    PubMed

    Hao, Yuan; Ko, Wing-hung

    2014-02-25

    The regulated transport of salt and water is essential to the integrated function of many organ systems, including the respiratory, reproductive, and digestive tracts. Airway epithelial fluid secretion is a passive process that is driven by osmotic forces, which are generated by ion transport. The main determinant of a luminally-directed osmotic gradient is the mucosal transport of chloride ions (Cl(-)) into the lumen. As with many epithelial cells, a number of classic signal transduction cascades are involved in the regulation of ion transport. There are two well-known intracellular signaling systems: an increase in intracellular Ca(2+) concentration ([Ca(2+)]i) and an increase in the rate of synthesis of cyclic nucleotides, such as cyclic adenosine monophosphate (cAMP). Therefore, Cl(-) secretion is primarily activated via the opening of apical Ca(2+)- or cAMP-dependent Cl(-) channels at the apical membrane. The opening of basolateral Ca(2+)- or cAMP-activated K(+) channels, which hyperpolarizes the cell to maintain the driving force for Cl(-) exit through apical Cl(-) channels that are constitutively open, is also important in regulating transepithelial ion transport. P2Y receptors are expressed in the apical and/or basolateral membranes of virtually all polarized epithelia to control the transport of fluid and electrolytes. Human airway epithelial cells express multiple nucleotide receptors. Extracellular nucleotides, such as UTP and ATP, are calcium-mobilizing secretagogues. They are released into the extracellular space from airway epithelial cells and act on the same cell in an autocrine fashion to stimulate transepithelial ion transport. In addition, recent data support the role of P2Y receptors in releasing inflammatory cytokines in the bronchial epithelium and other immune cells.

  12. Platelet P2Y12 Blockers Confer Direct Postconditioning-like Protection in Reperfused Rabbit Hearts

    PubMed Central

    Yang, Xi-Ming; Liu, Yanping; Cui, Lin; Yang, Xiulan; Liu, Yongge; Tandon, Narendra; Kambayashi, Junichi; Downey, James M.; Cohen, Michael V.

    2012-01-01

    Background Blockade of platelet activation during primary percutaneous intervention for acute myocardial infarction is standard care to minimize stent thrombosis. To determine whether antiplatelet agents offer any direct cardioprotective effect, we tested whether they could modify infarction in a rabbit model of ischemia/reperfusion caused by reversible ligation of a coronary artery. Methods and Results The P2Y12 (adenosine diphosphate) receptor blocker cangrelor administered shortly before reperfusion in rabbits undergoing 30-minute regional ischemia/3-hour reperfusion reduced infarction from 38% of ischemic zone in control hearts to only 19%. Protection was dose dependent and correlated with the degree of inhibition of platelet aggregation. Protection was comparable to that seen with ischemic postconditioning (IPOC). Cangrelor protection, but not its inhibition of platelet aggregation, was abolished by the same signaling inhibitors that block protection from IPOC suggesting protection resulted from protective signaling rather than anticoagulation. As with IPOC, protection was lost when cangrelor administration was delayed until 10 minutes after reperfusion and no added protection was seen when cangrelor and IPOC were combined. These findings suggest both IPOC and cangrelor may protect by the same mechanism. No protection was seen when cangrelor was used in crystalloid-perfused isolated hearts indicating some component in whole blood is required for protection. Clopidogrel had a very slow onset of action requiring 2 days of treatment before platelets were inhibited, and only then the hearts were protected. Signaling inhibitors given just prior to reperfusion blocked clopidogrel’s protection. Neither aspirin nor heparin was protective. Conclusions Clopidogrel and cangrelor protected rabbit hearts against infarction. The mechanism appears to involve signal transduction during reperfusion rather than inhibition of intravascular coagulation. We hypothesize that both

  13. High-spin structure of {sup 37}Cl, intruder excitations, and the sd-fp shell gap

    SciTech Connect

    Ionescu-Bujor, M.; Iordachescu, A.; Marginean, N.; Bucurescu, D.; Lenzi, S. M.; Bazzacco, D.; Della Vedova, F.; Farnea, E.; Menegazzo, R.; Lunardi, S.; Zilio, S.; Napoli, D. R.; De Angelis, G.; Gadea, A.; Medina, N. H.; Ur, C. A.; Otsuka, T.; Utsuno, Y.

    2009-09-15

    The structure of the N=20 nucleus {sup 37}Cl has been investigated in the {sup 24}Mg({sup 16}O,3p) reaction with a 70 MeV {sup 16}O beam. A complex level scheme extended up to an excitation energy of 17 MeV and spins (29/2{sup +}) and (27/2{sup -}) on positive and negative parity, respectively, has been established. Lifetimes for the new states have been investigated by the Doppler shift attenuation method. Large-scale shell-model calculations have been performed in a valence space involving orbitals in the sd and fp shells using the sdfp and SDPF-M effective interactions. The comparison with the experimental data indicates the need for slight changes of the sd-fp energy gaps produced by these interactions.

  14. Conjunctival expression of the P2Y2 receptor and the effects of 3% diquafosol ophthalmic solution in dogs.

    PubMed

    Terakado, Kunihiko; Yogo, Takuya; Kohara, Yukihiro; Soeta, Satoshi; Nezu, Yoshinori; Harada, Yasuji; Hara, Yasushi; Amasaki, Hajime; Tagawa, Masahiro

    2014-10-01

    Conjunctival epithelial and goblet cell P2Y2 nucleotide receptors regulate ion transport and secretory function. Diquafosol is a P2Y2 purinergic receptor agonist that stimulates secretion of aqueous tear components from conjunctival epithelial cells and secretion of mucin from conjunctival goblet cells. In humans suffering from keratoconjunctivitis sicca (dry eye), topical administration of diquafosol improves corneal epithelial integrity and stabilises the tear film. The aim of the present study was to investigate P2Y2 receptor expression and to determine the effect of topical administration of diquafosol on mucin and aqueous tear production in dogs. Canine conjunctival P2Y2 receptor expression was evaluated by Western blotting and immunohistochemical analysis. The effect of diquafosol on mucin secretion was evaluated by examining mucin-5 subtype AC (MUC5AC) concentration in tears. The effect of diquafosol on aqueous secretions was evaluated by performing the Schirmer tear test (STT) and phenol red thread test. Expression of the P2Y2 receptor was confirmed in canine bulbar and palpebral conjunctivae and receptors were identified at the conjunctival epithelial and goblet cell surface. Tear MUC5AC concentration significantly increased after administration of 3% diquafosol ophthalmic solution, although neither STT nor phenol red thread test values showed any significant change after diquafosol instillation. Topical ocular administration of 3% diquafosol might improve corneal epithelial disorders in dogs through stabilisation of the tear film, by virtue of an increase in MUC5AC secretion.

  15. Estimation of the daily soil/dust (SD) ingestion rate of children from Gansu Province, China via hand-to-mouth contact using tracer elements.

    PubMed

    Ma, Jin; Pan, Li-Bo; Wang, Qin; Lin, Chun-Ye; Duan, Xiao-Li; Hou, Hong

    2016-12-19

    A total of 60 children (31 males and 29 females) between the ages of 3 and 12 years were randomly selected from Lanzhou City in Gansu Province, northwest China. Hand (soil/dust) SD samples from these children were collected using hand wipes. We determined the approximate amounts of hand SD and the concentrations of three tracer soil elements (Ce, Y, and V) in these samples. The approximate amounts of hand SD ranged from 42.28 to 173.76 mg, with a median value of 85.42 mg. In addition, the mean amounts of hand SD estimated using the concentrations of Ce, Y, and V in the samples were 4.63, 3.43, and 3.42 mg, respectively. The amount of hand SD varied greatly among the age groups: primary school children had more hand SD than kindergarten children, males had more hand SD than females, and children from rural areas had more hand SD than those from urban areas. The rates of daily ingestion of hand SD for kindergarten and primary school children were estimated to be 7.73 and 6.61 mg/day, respectively.

  16. Using asymmetry analysis to reduce normal variability of Spectral Domain Optical Coherence Tomography (SD-OCT) macular thickness

    NASA Astrophysics Data System (ADS)

    Alluwimi, Muhammed Saad

    Purpose: To investigate the use of asymmetry analysis to reduce normal between-subject variability of macular thickness measurements using SD-OCT. Methods: 63 volunteers free of eye disease were recruited: 33 young subjects (ages 21 to 35 years with mean and SD of 25 +/- 1.7), and 30 older subjects (ages 45 to 85 years with mean and SD of 66.7 +/- 9.0). All participants passed a comprehensive ophthalmic examination within the past two years. Macular images were gathered with the Spectralis OCT (V 5.4, Heidelberg Engineering, GmbH). The overlay 8x8 grid was manually centered on the fovea and aligned with the foveal-disc axis, then divided into five zones per hemifield following the method of Um et al (2012 IOVS 53:1139); asymmetry was computed as the difference between superior and inferior zone thicknesses. We assumed that the lowest variation and the highest density of ganglion cells will be found ~3° to 6° from the foveal center, corresponding to zones 1 and 2. For each zone and age group, between-subject standard deviations (SDs) were compared for retinal thickness (RT) versus asymmetry using an F-test. To account for repeated measures, a probability of p < 0.0125 was required for statistical significance. Axial length (AL) and corneal curvature (CC) were measured with an IOLMaster by the same operator and during the same imaging session. Results: For OD, asymmetry analysis reduced between-subject variability in zones 1 and 2 in both groups (F > 3.2, p < 0.001). SD for zone 1 dropped from 12.0 to 3.0 mum in the young group and from 11.7 to 2.6 mum in the older group. SD for zone 2 dropped from 13.6 to 5.3 mum (young) and from 11.1 to 5.8 mum (older). Combining all subjects, neither RT nor asymmetry showed a strong correlation with AL or CC (R2 < 0.01). Analysis for OS yielded the same pattern of results, as did asymmetry analyses between eyes (F > 3.8, p < 0.0001). Conclusions: Asymmetry analysis reduced between-subject variability. These findings demonstrate

  17. Fundamental Bulk/Surface Structure Photoactivity Relationships of Supported (Rh2-yCryO3)/GaN Photocatalysts

    SciTech Connect

    Phivilay, Somphonh; Roberts, Charles; Puretzky, Alexander A; Domen, Kazunari Domen; Wachs, Israel

    2013-01-01

    ABSTRACT. The supported (Rh2-yCryO3)/GaN photocatalyst was examined as a model nitride photocatalyst system to assist in the development of fundamental structure photoactivity relationships for UV activated water splitting. Surface characterization of the outermost surface layers by High Sensitivity-LEIS and High Resolution-XPS revealed for the first time that the GaN support consists of a GaOx outermost surface layer and a thin film of GaOxNy in the surface region. HR-XPS also demonstrates that the supported (Rh2-yCryO3) mixed oxide nanoparticles (NPs) exclusively consist of Cr+3 and Rh+3 cations and are surface enriched for the supported (Rh2-yCryO3)/GaN photocatalyst. Bulk analysis by Raman and UV-vis spectroscopy show that the bulk molecular and electronic structures, respectively, of the GaN support are not perturbed by the deposition of the (Rh2-yCryO3) mixed oxide NPs. The function of the GaN bulk lattice is to generate photoexcited electrons/holes, with the electrons harnessed by the surface Rh+3 sites for evolution of H2 and the holes trapped at the Ga oxide/oxynitride surface sites for splitting of water and evolving O2. These new structure-photoactivity relationships for supported (Rh2-yCryO3)/GaN also extend to the best performing visible light activated supported (Rh2-yCryO3)/(Ga1-xZnx)(N1-xOx) photocatalyst.

  18. The qSD12 Underlying Gene Promotes Abscisic Acid Accumulation in Early Developing Seeds to Induce Primary Dormancy in Rice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Seeds acquire primary dormancy during their development and the phytohormone abscisic acid (ABA) is considered to play a role in inducing the dormancy. qSD12 is a major seed dormancy QTL identified from weedy rice. This research was conducted to identify qSD12 candidate genes, isolate the candidat...

  19. Low-Temperature Synthesis, Structure, and Stability of Ba 2+ yCu 3O 6

    NASA Astrophysics Data System (ADS)

    Brosha, Eric L.; Garzon, Fernando H.; Raistrick, Ian D.; Davies, Peter K.

    1996-02-01

    Single-phase powders of Ba2Cu3O6have been prepared at 620°C under 1 atm of oxygen using freeze-dried nitrate precursors. Calcinations utilizing a precursor with a 1:1 Ba:Cu stoichiometry produced a two-phase mixture of BaO2+ Ba2Cu3O6and confirmed the stable, oxidized barium cuprate exists with a metal ion ratio close to 2:3. Diffraction studies suggest that Ba2Cu3O6(Ba0.67CuO2) crystallizes in a structure closely related to the linear chain KCuO2and NaCuO2cuprates. It is proposed that the reduction of copper and accompanying loss of oxygen observed above 620°C are accommodated by an increase in the Ba content of the structure and the formation of Ba2+yCu3O6with 0 ≤y≤ 0.25. Above 710°C, the high-yend member is metastable with respect to BaCuO2, although it decomposes slowly even at elevated temperatures.

  20. Cellulose film regenerated from Styela clava tunics have biodegradability, toxicity and biocompatibility in the skin of SD rats.

    PubMed

    Song, Sung Hwa; Kim, Ji Eun; Lee, Young Ju; Kwak, Moon Hwa; Sung, Geum Yong; Kwon, Soon Hong; Son, Hong Joo; Lee, Hee Seob; Jung, Young Jin; Hwang, Dae Youn

    2014-06-01

    Cellulose is one of the most widespread biomolecules in nature and has been exploited in various applications including scaffolding, tissue engineering, and tissue formation. To evaluate the biocompatibility of cellulose film manufactured from Styela clava tunics (SCT-CF), these films were implanted in Sprague-Dawley (SD) rats for various lengths of time, after which they were subjected to mechanical and biological analyses. The cellulose powders (12-268 m) obtained from SCT was converted into films via casting methods without adding any additives. SCT-CF contained about 98 % α-cellulose and very low concentrations of ββ-cellulose. Additionally, the crystallinity index (CrI) of SCT-CF was lower (10.71 %) than that of wood pulp-cellulose films (WP-CF) (33.78 %). After implantation for 90 days, the weight loss and formation of surface corrugations were greater in SCT-CF than that of WP-CF, while the surface roughness was significantly higher in WP-CF than SCT-CF. However, there were no differences in the number of white blood cells between SCT-CF implanted rats and vehicle implanted rats. The level of metabolic enzymes representing liver and kidney toxicity in the serum of SCT-CF implanted rats was maintained at levels consistent with vehicle implanted rats. Moreover, no significant alteration of the epidermal hyperplasia, inflammatory cell infiltration, redness, and edema were observed in SD rats implanted with SCT-CF. Taken together, these results indicate that SCT-CF showed good degradability and non-toxicity without inducing an immune response in SD rats. Further, the data presented here constitute strong evidence that SCT-CF has the potential for use as a powerful biomaterial for medical applications including stitching fiber, wound dressing, scaffolding, absorbable hemostats and hemodialysis membrane.

  1. New extrapolation method for low-lying states of nuclei in the sd and the pf shells

    SciTech Connect

    Shen, J. J.; Zhao, Y. M.; Arima, A.; Yoshinaga, N.

    2011-04-15

    We study extrapolation approaches to evaluate energies of low-lying states for nuclei in the sd and pf shells, by sorting the diagonal matrix elements of the nuclear shell-model Hamiltonian. We introduce an extrapolation method with perturbation and apply our new method to predict both low-lying state energies and E2 transition rates between low-lying states. Our predicted results arrive at an accuracy of the root-mean-squared deviations {approx}40-60 keV for low-lying states of these nuclei.

  2. The NPOESS Preparatory Project Science Data Segment (SDS) Data Depository and Distribution Element (SD3E) System Architecture

    NASA Technical Reports Server (NTRS)

    Ho, Evelyn L.; Schweiss, Robert J.

    2008-01-01

    The National Polar-orbiting Operational Environmental Satellite System (NPOESS) Preparatory Project (NPP) Science Data Segment (SDS) will make daily data requests for approximately six terabytes of NPP science products for each of its six environmental assessment elements from the operational data providers. As a result, issues associated with duplicate data requests, data transfers of large volumes of diverse products, and data transfer failures raised concerns with respect to the network traffic and bandwidth consumption. The NPP SDS Data Depository and Distribution Element (SD3E) was developed to provide a mechanism for efficient data exchange, alleviate duplicate network traffic, and reduce operational costs.

  3. K2 observations of the pulsating subdwarf B star EQ Piscium: an sdB+dM binary

    NASA Astrophysics Data System (ADS)

    Jeffery, C. S.; Ramsay, G.

    2014-07-01

    K2, the two-wheel mission of the Kepler space telescope, observed the pulsating subdwarf B star EQ PSc during engineering tests in 2014 February. In addition to a rich spectrum of g-mode pulsation frequencies, the observations demonstrate a light variation with a period of 19.2 h and full amplitude of 2 per cent. We suggest that this is due to reflection from a cool companion, making EQ Psc the longest-period member of some 30 binaries comprising a hot subdwarf and a cool dwarf companion (sdB+dM), and hence useful for exploring the common-envelope ejection mechanism in low-mass binaries.

  4. The P2Y13 receptor regulates phosphate metabolism and FGF-23 secretion with effects on skeletal development.

    PubMed

    Wang, Ning; Robaye, Bernard; Gossiel, Fatima; Boeynaems, Jean-Marie; Gartland, Alison

    2014-05-01

    Purinergic signaling mediates many cellular processes, including embryonic development and regulation of endocrine signaling. The ADP P2Y13 receptor is known to regulate bone and stem cells activities, although relatively little is known about its role in bone development. In this study we demonstrate, using contemporary techniques, that deletion of the P2Y13 receptor results in an age-dependent skeletal phenotype that is governed by changes in phosphate metabolism and hormone levels. Neonatal and postnatal (2 wk) P2Y13 receptor-knockout (KO) mice were indistinguishable from their wild-type (WT) littermate controls. A clear bone phenotype was observed in young (4-wk-old) KO mice compared WT controls, with 14% more trabecular bone, 35% more osteoblasts, 73% fewer osteoclasts, and a 17% thicker growth plate. Mature (>10 wk of age) KO mice showed the opposite bone phenotype, with 14% less trabecular bone, 22% fewer osteoblasts, and 10% thinner growth plate. This age-dependent phenotype correlated with serum fibroblast growth factor-23 (FGF-23) and phosphorus levels that were 65 and 16% higher, respectively, in young KO mice but remained unchanged in mature mice. These findings provide novel insights for the role of the P2Y13 receptor in skeletal development via coordination with hormonal regulators of phosphate homeostasis.

  5. Regulation of Phospholipase D Activity and Phosphatidic Acid Production after Purinergic (P2Y6) Receptor Stimulation*

    PubMed Central

    Scott, Sarah A.; Xiang, Yun; Mathews, Thomas P.; Cho, Hyekyung P.; Myers, David S.; Armstrong, Michelle D.; Tallman, Keri A.; O'Reilly, Matthew C.; Lindsley, Craig W.; Brown, H. Alex

    2013-01-01

    Phosphatidic acid (PA) is a lipid second messenger located at the intersection of several lipid metabolism and cell signaling events including membrane trafficking, survival, and proliferation. Generation of signaling PA has long been primarily attributed to the activation of phospholipase D (PLD). PLD catalyzes the hydrolysis of phosphatidylcholine into PA. A variety of both receptor-tyrosine kinase and G-protein-coupled receptor stimulations have been shown to lead to PLD activation and PA generation. This study focuses on profiling the PA pool upon P2Y6 receptor signaling manipulation to determine the major PA producing enzymes. Here we show that PLD, although highly active, is not responsible for the majority of stable PA being produced upon UDP stimulation of the P2Y6 receptor and that PA levels are tightly regulated. By following PA flux in the cell we show that PLD is involved in an initial increase in PA upon receptor stimulation; however, when PLD is blocked, the cell compensates by increasing PA production from other sources. We further delineate the P2Y6 signaling pathway showing that phospholipase Cβ3 (PLCβ3), PLCδ1, DGKζ and PLD are all downstream of receptor activation. We also show that DGKζ is a novel negative regulator of PLD activity in this system that occurs through an inhibitory mechanism with PKCα. These results further define the downstream events resulting in PA production in the P2Y6 receptor signaling pathway. PMID:23723068

  6. Pyrimidine Nucleotides with 4-Alkyloxyimino and Terminal Tetraphosphate δ-Ester Modifications as Selective Agonists of the P2Y4 Receptor

    PubMed Central

    Maruoka, Hiroshi; Jayasekara, M.P. Suresh; Barrett, Matthew O.; Franklin, Derek A.; de Castro, Sonia; Kim, Nathaniel; Costanzi, Stefano; Harden, T. Kendall; Jacobson, Kenneth A.

    2011-01-01

    P2Y2 and P2Y4 receptors are G protein-coupled receptors, activated by UTP and dinucleoside tetraphosphates, which are difficult to distinguish pharmacologically for lack of potent and selective ligands. We varied structurally phosphate and uracil moieties in analogues of pyrimidine nucleoside 5′-triphosphates and 5′-tetraphosphate esters. P2Y4 receptor potency in phospholipase C stimulation in transfected 1321N1 human astrocytoma cells was enhanced in N4-alkyloxycytidine derivatives. OH groups on a terminal δ-glucose phosphoester of uridine 5′-tetraphosphate were inverted or substituted with H or F to probe H-bonding effects. N4-(Phenylpropoxy)-CTP 16 (MRS4062), Up4-[1]3′-deoxy-3′-fluoroglucose 34 (MRS2927) and N4-(phenylethoxy)-CTP 15 exhibit ≥10-fold selectivity for human P2Y4 over P2Y2 and P2Y6 receptors (EC50 values 23, 62 and 73 nM, respectively). δ-3-Chlorophenyl phosphoester 21 of Up4 activated P2Y2 but not P2Y4 receptor. Selected nucleotides tested for chemical and enzymatic stability were much more stable than UTP. Agonist docking at CXCR4-based P2Y2 and P2Y4 receptor models indicated greater steric tolerance of N4-phenylpropoxy group at P2Y4. Thus, distal structural changes modulate potency, selectivity, and stability of extended uridine tetraphosphate derivatives, and we report the first P2Y4 receptor-selective agonists. PMID:21528910

  7. Molecular modeling of the human P2Y14 receptor: A template for structure-based design of selective agonist ligands.

    PubMed

    Trujillo, Kevin; Paoletta, Silvia; Kiselev, Evgeny; Jacobson, Kenneth A

    2015-07-15

    The P2Y14 receptor (P2Y14R) is a Gi protein-coupled receptor that is activated by uracil nucleotides UDP and UDP-glucose. The P2Y14R structure has yet to be solved through X-ray crystallography, but the recent agonist-bound crystal structure of the P2Y12R provides a potentially suitable template for its homology modeling for rational structure-based design of selective and high-affinity ligands. In this study, we applied ligand docking and molecular dynamics refinement to a P2Y14R homology model to qualitatively explain structure-activity relationships of previously published synthetic nucleotide analogues and to probe the quality of P2Y14R homology modeling as a template for structure-based design. The P2Y14R model supports the hypothesis of a conserved binding mode of nucleotides in the three P2Y12-like receptors involving functionally conserved residues. We predict phosphate group interactions with R253(6.55), K277(7.35), Y256(6.58) and Q260(6.62), nucleobase (anti-conformation) π-π stacking with Y102(3.33) and the role of F191(5.42) as a means for selectivity among P2Y12-like receptors. The glucose moiety of UDP-glucose docked in a secondary subpocket at the P2Y14R homology model. Thus, P2Y14R homology modeling may allow detailed prediction of interactions to facilitate the design of high affinity, selective agonists as pharmacological tools to study the P2Y14R.

  8. Nucleotides protect rat brain astrocytes against hydrogen peroxide toxicity and induce antioxidant defense via P2Y receptors.

    PubMed

    Förster, Daniel; Reiser, Georg

    2016-03-01

    Consequences of neurodegenerative diseases or stroke also depend on astroglial survival during oxidative stress. P2Y receptors that are widely distributed in the central nervous system are suggested to be involved in cytoprotection. However, knowledge about the efficacy of protection by P2Y receptors and their involvement in antioxidant protective pathways is scarce. Here, we investigate the viability and reactive oxygen species (ROS) production after exposure of rat astrocytes to hydrogen peroxide. We determined the influence of treatment with the P2Y1 receptor-specific agonist 2-methyl-thio-ADP (2MeSADP) and the broad range P2Y receptor agonist adenosine 5'-(3-thiotriphosphate) (ATPγS). Preincubation (24-h before hydrogen peroxide application) and incubation with ATPγS and 2MeSADP protected astrocytes. The ROS production in hydrogen peroxide-treated astrocytes was reduced by pre- and co-incubation with ATPγS or 2MeSADP. Changes of levels of expression of antioxidant defense systems in astrocytes by treatment with P2Y receptor agonists were analyzed. Incubation with ATPγS and 2MeSADP increased mRNA levels of CAT encoding catalase and SOD2, encoding mitochondrial manganese dependent superoxide dismutase. ATPγS additionally increased mRNA levels of SOD3, encoding extracellular superoxide dismutase (ECSOD). Levels of total glutathione (GSH) increased in ATPγS/2MeSADP-treated astrocytes. mRNA levels of genes involved in GSH synthesis and in import of GSH precursors were analyzed after treatment with ATPγS and 2MeSADP. Both agonists significantly increased mRNA levels of a subunit of glutamate cysteine ligase, and a subunit of antiporter system xc(-). Changes in mRNA levels of antioxidant enzymes and genes of GSH metabolism depend on rise of intracellular Ca(2+) by P2Y receptor and basal activity of protein kinase A (PKA). SOD3 induction is suggested to depend on increased intracellular Ca(2+), increased cyclic AMP levels and PKA activity. Thus, we confirm a

  9. P2Y1 Receptor Activation of the TRPV4 Ion Channel Enhances Purinergic Signaling in Satellite Glial Cells*

    PubMed Central

    Rajasekhar, Pradeep; Poole, Daniel P.; Liedtke, Wolfgang; Bunnett, Nigel W.; Veldhuis, Nicholas A.

    2015-01-01

    Transient receptor potential (TRP) ion channels of peripheral sensory pathways are important mediators of pain, itch, and neurogenic inflammation. They are expressed by primary sensory neurons and by glial cells in the central nervous system, but their expression and function in satellite glial cells (SGCs) of sensory ganglia have not been explored. SGCs tightly ensheath neurons of sensory ganglia and can regulate neuronal excitability in pain and inflammatory states. Using a modified dissociation protocol, we isolated neurons with attached SGCs from dorsal root ganglia of mice. SGCs, which were identified by expression of immunoreactive Kir4.1 and glutamine synthetase, were closely associated with neurons, identified using the pan-neuronal marker NeuN. A subpopulation of SGCs expressed immunoreactive TRP vanilloid 4 (TRPV4) and responded to the TRPV4-selective agonist GSK1016790A by an influx of Ca2+ ions. SGCs did not express functional TRPV1, TRPV3, or TRP ankyrin 1 channels. Responses to GSK1016790A were abolished by the TRPV4 antagonist HC067047 and were absent in SGCs from Trpv4−/− mice. The P2Y1-selective agonist 2-methylthio-ADP increased [Ca2+]i in SGCs, and responses were prevented by the P2Y1-selective antagonist MRS2500. P2Y1 receptor-mediated responses were enhanced in TRPV4-expressing SGCs and HEK293 cells, suggesting that P2Y1 couples to and activates TRPV4. PKC inhibitors prevented P2Y1 receptor activation of TRPV4. Our results provide the first evidence for expression of TRPV4 in SGCs and demonstrate that TRPV4 is a purinergic receptor-operated channel in SGCs of sensory ganglia. PMID:26475857

  10. Enhancement of acid-sensing ion channel activity by metabotropic P2Y UTP receptors in primary sensory neurons.

    PubMed

    Ren, Cuixia; Gan, Xiong; Wu, Jing; Qiu, Chun-Yu; Hu, Wang-Ping

    2016-03-01

    Peripheral purinergic signaling plays an important role in nociception. Increasing evidence suggests that metabotropic P2Y receptors are also involved, but little is known about the underlying mechanism. Herein, we report that selective P2Y receptor agonist uridine 5'-triphosphate (UTP) can exert an enhancing effect on the functional activity of acid-sensing ion channels (ASICs), key sensors for extracellular protons, in rat dorsal root ganglia (DRG) neurons. First, UTP dose-dependently increased the amplitude of ASIC currents. UTP also shifted the concentration-response curve for proton upwards, with a 56.6 ± 6.4% increase of the maximal current response to proton. Second, UTP potentiation of proton-gated currents can be mimicked by adenosine 5'-triphosphate (ATP), but not by P2Y1 receptor agonist ADP. Potentiation of UTP was blocked by P2Y receptor antagonist suramin and by inhibition of intracellular G protein, phospholipase C (PLC), protein kinase C (PKC), or protein interacting with C-kinase 1 (PICK1) signaling. Third, UTP altered acidosis-evoked membrane excitability of DRG neurons and caused a significant increase in the amplitude of the depolarization and the number of spikes induced by acid stimuli. Finally, UTP dose-dependently exacerbated nociceptive responses to injection of acetic acid in rats. These results suggest that UTP enhanced ASIC-mediated currents and nociceptive responses, which reveal a novel peripheral mechanism underlying UTP-sensitive P2Y2 receptor involvement in hyperalgesia by sensitizing ASICs in primary sensory neurons.

  11. Extracellular ATP and P2Y Receptor Activation Induce a Proinflammatory Host Response in the Human Urinary Tract▿

    PubMed Central

    Säve, Susanne; Persson, Katarina

    2010-01-01

    Extracellular ATP can be released by many cell types under conditions of cellular stress and signals through activation of purinergic receptors. Bladder uroepithelial cells grown in vitro have previously been shown to release ATP in response to stretch. In the present study, we investigated ATP release from uroepithelial cells infected with bacteria and the effect of ATP on the host cell proinflammatory interleukin 8 (IL-8) response. The human kidney epithelial cell line A498 and the human uroepithelial cell line UROtsa were grown in culture and stimulated by the uropathogenic Escherichia coli (UPEC) IA2 strain or the stable ATP analogue ATP-γ-S. ATP and IL-8 levels were measured in cell culture medium with a luciferin-luciferase assay and enzyme-linked immunosorbent assay (ELISA), respectively. The results showed that UPEC infection of uroepithelial cells for 1 h significantly increased (P < 0.01) the extracellular ATP levels. ATP-γ-S (10 and 100 μM) stimulated release of IL-8 from UROtsa and A498 cells after 6 and 24 h. Experiments with different purinoceptor agonists suggested that P2Y receptors, and not P2X receptors, were responsible for the ATP-γ-S-induced IL-8 release. The potency profile further suggested involvement of P2Y1, P2Y2, and/or P2Y11 receptors, and reverse transcription-PCR (RT-PCR) studies confirmed that the cells expressed these receptors. The amount of IL-8 released increased 12-fold in UPEC-infected cells, and apyrase, an enzyme that degrades ATP, reduced this increase by approximately 50%. The present study suggests that enhanced ATP release and P2Y receptor activation during urinary tract infection may represent a novel, non-TLR4-mediated mechanism for production of proinflammatory IL-8 in human urinary tract epithelial cells. PMID:20515921

  12. Pattern of inner retinal layers involvement in pigmented paravenous retinochoroidal atrophy as determined by SD-OCT: case report.

    PubMed

    Junqueira, Daniela Laura Melo; Lopes, Flavio Siqueira Santos; Biteli, Luís Gustavo; Prata, Tiago Santos

    2013-01-01

    Pigmented paravenous retinochoroidal atrophy is an ocular disease characterized by outer retina and choroidal atrophy often with overlying intraretinal bone spicule pigment deposition along the retinal veins. As a rare condition, there is scant information in the literature regarding the pattern of inner retinal layers involvement. We present a case of a 41-year-old white man initially referred for a glaucoma evaluation. Fundoscopy revealed patches of retinochoroidal atrophy and light pigmentation extending from the optic nerve head along the inferior-temporal retinal veins in both eyes. Using different spectral-domain optical coherence tomography (SD-OCT) protocols we identified a significant thinning of the inner retinal layers along the inferior-temporal veins, but with a lucid interval surrounding the optic nerve head. Standard automated perimetry revealed a superior absolute arcuate scotoma sparing the central fixation (good structure-functional correlation). This pattern of inner retinal layers involvement was not previously described. We believe SD-OCT added significantly to the anatomical description of this case. Physicians should consider these new anatomical findings and correlate them with functional status while assessing these patients.

  13. Identification of neutral genes at pollen sterility loci Sd and Se of cultivated rice (Oryza sativa) with wild rice (O. rufipogon) origin.

    PubMed

    Liu, B; Li, J Q; Liu, X D; Shahid, M Q; Shi, L G; Lu, Y G

    2011-10-31

    Pollen sterility is one of the main hindrances against the utilization of strong intersubspecific (indica-japonica) heterosis in rice. We looked for neutral alleles at known pollen sterility loci Sd and Se that could overcome this pollen sterility characteristic. Taichung 65, a typical japonica cultivar, and its near isogenic lines E7 and E8 for pollen sterility loci Sd and Se were employed as tester lines for crossing with 13 accessions of wild rice (O. rufipogon). Pollen fertility and genotypic segregations of the molecular markers tightly linked with Sd and Se loci were analyzed in the paired F(1)s and F(2) populations. One accession of wild rice (GZW054) had high pollen fertility in the paired F(1)s between Taichung 65 and E7 or E8. Genotypic segregations of the molecular markers tightly linked with Sd and Se loci fit the expected Mendelian ratio (1:2:1), and non-significances were shown among the mean pollen fertilities with the maternal, parental, and heterozygous genotypes of each molecular markers tightly linked with Sd and Se loci. Evidentially, it indicated that the alleles of Sd and Se loci for GZW054 did not interact with those of Taichung 65 and its near isogenic lines, and, thus were identified as neutral alleles Sd(n) and Se(n). These neutral genes could become important germplasm resources for overcoming pollen sterility in indica-japonica hybrids, making utilization of strong heterosis in such hybrids viable.

  14. Evaluation of the Microvision Spectrum SD2500 Helmet-Mounted Display for the Air Warrior Block 3 Day/Night HMD Program

    DTIC Science & Technology

    2006-03-01

    USAARL Report No. 2006-08 Evaluation of the Microvision Spectrum SD2500 Helmet-Mounted Display for the Air Warrior Block 3 Day/Night HMD Program by... Microvision Spectrum SD2500 Helmet-Mounted Display for the Air PE 622787 Warrior Block 3 Day/Night HMD Program PR 879 TA P WU DA361539 6. AUTHOR(S) Clarence E...ABSTRACT (Maximum 200 words) The Microvision Spectrum SD2500 HMD, a monocular, full-color scanning laser display, display, was evaluated for optical image

  15. miR-185/P2Y6 Axis Inhibits Angiotensin II-Induced Human Aortic Vascular Smooth Muscle Cell Proliferation.

    PubMed

    Wang, Shunmin; Tang, Lujun; Zhou, Qian; Lu, Duomei; Duan, Wulei; Chen, Cheng; Huang, Lu; Tan, Yuansheng

    2017-03-09

    The abnormal proliferation and apoptosis of human aortic vascular smooth muscle cells (HAVSMCs) play an important role in the pathogenesis of hypertension. Recent study revealed that angiotensin II (Ang II) could elicit HAVSMC dysfunction, to induce or aggravate hypertension. Purinergic receptor P2Y6, an inflammation-inducible G protein-coupled receptor, promoted Ang II-induced hypertension. In the present study, we revealed that Ang II induced HAVSMC proliferation and upregulated P2Y6 protein levels. After knockdown of P2Y6, the promotive effect of Ang II on HAVSMC proliferation was restored. microRNAs (miRNAs) involve in most biological processes. In this study, we scanned out seven candidate miRNAs, which were predicted to contain binding site of P2Y6's 3'-UTR by online tools. Among them, miR-185 was significantly downregulated by Ang II treatment. miR-185 reduced P2Y6 protein levels by direct binding to the 3'UTR of P2Y6. miR-185 overexpression suppressed HAVSMC proliferation; P2Y6 overexpression or Ang II treatment promoted HAVSMC proliferation, and restored the suppressive effect of miR-185 on HAVSMC proliferation. Besides, miR-185/P2Y6 axis also affected pERK1/2 protein levels. Taken together, the present study indicated that miR-185/P2Y6 axis might inhibit Ang II-induced HAVSMC proliferation through miR-185 negatively regulating P2Y6 expression and the downstream ERK pathway; rescuing miR-185 expression to inhibit P2Y6 may represent a therapeutic strategy against HAVSMC dysfunction and hypertension.

  16. sdA in SDSS DR12 are Overwhelmingly Not Extremely Low-Mass (ELM) White Dwarfs

    NASA Astrophysics Data System (ADS)

    Hermes, J. J.; Gänsicke, B. T.; Breedt, E.

    2017-03-01

    In a search for new white dwarfs in DR12 of the Sloan Digital Sky Survey, Kepler et al. 2016 found atmospheric parameters for thousands of objects with effective temperatures below 20,000 K and surface gravities between 5.5 < log g < 6.5. They classified these objects as cool subdwarfs – sdA – and speculated that many may be extremely low-mass (ELM) white dwarfs (helium-core white dwarfs with masses below 0.3 M⊙). We present evidence – using radial velocities, photometric colors, and reduced proper motions – that the vast majority (>99%) of these objects are unlikely to be ELM white dwarfs. Their true identity remains an interesting question.

  17. Chemical profile of the secondary metabolites produced by a deep-sea sediment-derived fungus Penicillium commune SD-118

    NASA Astrophysics Data System (ADS)

    Shang, Zhuo; Li, Xiaoming; Meng, Li; Li, Chunshun; Gao, Shushan; Huang, Caiguo; Wang, Bingui

    2012-03-01

    Bioassay-guided fractionation of the crude extract from Penicillium commune SD-118, a fungus obtained from a deep-sea sediment sample, resulted in the isolation of a known antibacterial compound, xanthocillin X ( 1), and 14 other known compounds comprising three steroids ( 2-4), two ceramides ( 5 and 6), six aromatic compounds ( 7-12), and three alkaloids ( 13-15). Xanthocillin X ( 1) was isolated for the first time from a marine fungus. In the bioassay, xanthocillin X ( 1) displayed remarkable antimicrobial activity against Staphylococcus aureus and Escherichia coli, and significant cytotoxicity against MCF-7, HepG2, H460, Hela, Du145, and MDA-MB-231 cell lines. Meleagrin ( 15) exhibited cytotoxicity against HepG2, Hela, Du145, and MDA-MB-231 cell lines. This is the first report of the cytotoxicity of xanthocillin X ( 1).

  18. Continuous imaging of the blood vessels in tumor mouse dorsal skin window chamber model by using SD-OCT

    NASA Astrophysics Data System (ADS)

    Peng, Xiao; Yang, Shaozhuang; Yu, Bin; Wang, Qi; Lin, Danying; Gao, Jian; Zhang, Peiqi; Ma, Yiqun; Qu, Junle; Niu, Hanben

    2016-03-01

    Optical Coherence Tomography (OCT) has been widely applied into microstructure imaging of tissues or blood vessels with a series of advantages, including non-destructiveness, real-time imaging, high resolution and high sensitivity. In this study, a Spectral Domain OCT (SD-OCT) system with higher sensitivity and signal-to-noise ratio (SNR) was built up, which was used to observe the blood vessel distribution and blood flow in the dorsal skin window chamber of the nude mouse tumor model. In order to obtain comparable data, the distribution images of blood vessels were collected from the same mouse before and after tumor injection. In conclusion, in vivo blood vessel distribution images of the tumor mouse model have been continuously obtained during around two weeks.

  19. International Union of Pharmacology LVIII: update on the P2Y G protein-coupled nucleotide receptors: from molecular mechanisms and pathophysiology to therapy.

    PubMed

    Abbracchio, Maria P; Burnstock, Geoffrey; Boeynaems, Jean-Marie; Barnard, Eric A; Boyer, José L; Kennedy, Charles; Knight, Gillian E; Fumagalli, Marta; Gachet, Christian; Jacobson, Kenneth A; Weisman, Gary A

    2006-09-01

    There have been many advances in our knowledge about different aspects of P2Y receptor signaling since the last review published by our International Union of Pharmacology subcommittee. More receptor subtypes have been cloned and characterized and most orphan receptors de-orphanized, so that it is now possible to provide a basis for a future subdivision of P2Y receptor subtypes. More is known about the functional elements of the P2Y receptor molecules and the signaling pathways involved, including interactions with ion channels. There have been substantial developments in the design of selective agonists and antagonists to some of the P2Y receptor subtypes. There are new findings about the mechanisms underlying nucleotide release and ectoenzymatic nucleotide breakdown. Interactions between P2Y receptors and receptors to other signaling molecules have been explored as well as P2Y-mediated control of gene transcription. The distribution and roles of P2Y receptor subtypes in many different cell types are better understood and P2Y receptor-related compounds are being explored for therapeutic purposes. These and other advances are discussed in the present review.

  20. Structure-Based Design of 3-(4-Aryl-1H-1,2,3-triazol-1-yl)-Biphenyl Derivatives as P2Y14 Receptor Antagonists

    PubMed Central

    2016-01-01

    UDP and UDP-glucose activate the P2Y14 receptor (P2Y14R) to modulate processes related to inflammation, diabetes, and asthma. A computational pipeline suggested alternatives to naphthalene of a previously reported P2Y14R antagonist (3, PPTN) using docking and molecular dynamics simulations on a hP2Y14R homology model based on P2Y12R structures. By reevaluating the binding of 3 to P2Y14R computationally, two alternatives, i.e., alkynyl and triazolyl derivatives, were identified. Improved synthesis of fluorescent antagonist 4 enabled affinity quantification (IC50s, nM) using flow cytometry of P2Y14R-expressing CHO cells. p-F3C-phenyl-triazole 65 (32) was more potent than a corresponding alkyne 11. Thus, additional triazolyl derivatives were prepared, as guided by docking simulations, with nonpolar aryl substituents favored. Although triazoles were less potent than 3 (6), simpler synthesis facilitated further structural optimization. Additionally, relative P2Y14R affinities agreed with predicted binding of alkynyl and triazole analogues. These triazoles, designed through a structure-based approach, can be assessed in disease models. PMID:27331270

  1. Activation of c-myb by 5' retrovirus promoter insertion in myeloid neoplasms is dependent upon an intact alternative splice donor site (SD') in gag

    SciTech Connect

    Ramirez, Jean Marie; Houzet, Laurent; Koller, Richard; Bies, Juraj; Wolff, Linda; Mougel, Marylene . E-mail: mmougel@univ-montp1.fr

    2004-12-20

    Alternative splicing in Mo-MuLV recruits a splice donor site, SD', within the gag that is required for optimal replication in vitro. Remarkably, this SD' site was also found to be utilized for production of oncogenic gag-myb fusion RNA in 100% of murine-induced myeloid leukemia (MML) in pristane-treated BALB/c mice. Therefore, we investigated the influence of silent mutations of SD' in this model. Although there was no decrease in the overall incidence of disease, there was a decrease in the incidence of myeloid leukemia with a concomitant increase in lymphoid leukemia. Importantly, there was a complete lack of myeloid tumors associated with 5' insertional mutagenic activation of c-myb, suggesting the specific requirement of the SD' site in this mechanism.

  2. Quantitatively evaluating detoxification of the hepatotoxic microcystin-LR through the glutathione (GSH) pathway in SD rats.

    PubMed

    Guo, Xiaochun; Chen, Liang; Chen, Jun; Xie, Ping; Li, Shangchun; He, Jun; Li, Wei; Fan, Huihui; Yu, Dezhao; Zeng, Cheng

    2015-12-01

    Glutathione (GSH) plays crucial roles in antioxidant defense and detoxification metabolism of microcystin-LR (MC-LR). However, the detoxification process of MC-LR in mammals remains largely unknown. This paper, for the first time, quantitatively analyzes MC-LR and its GSH pathway metabolites (MC-LR-GSH and MC-LR-Cys) in the liver of Sprague-Dawley (SD) rat after MC-LR exposure. Rats received intraperitoneal (i.p.) injection of 0.25 and 0.5 lethal dose 50 (LD50) of MC-LR with or without pretreatment of buthionine-(S,R)-sulfoximine (BSO), an inhibitor of GSH synthesis. The contents of MC-LR-GSH were relatively low during the experiment; however, the ratio of MC-LR-Cys to MC-LR reached as high as 6.65 in 0.5 LD50 group. These results demonstrated that MC-LR-GSH could be converted to MC-LR-Cys efficiently, and this metabolic rule was in agreement with the data of aquatic animals previously reported. MC-LR contents were much higher in BSO + MC-LR-treated groups than in the single MC-LR-treated groups. Moreover, the ratio of MC-LR-Cys to MC-LR decreased significantly after BSO pretreatment, suggesting that the depletion of GSH induced by BSO reduced the detoxification of MCs. Moreover, MC-LR remarkably induced liver damage, and the effects were more pronounced in BSO pretreatment groups. In conclusion, this study verifies the role of GSH in the detoxification of MC-LR and furthers our understanding of the biochemical mechanism for SD rats to counteract toxic cyanobacteria.

  3. Adjustment of the Retinal Angle in SD-OCT of Glaucomatous Eyes Provides Better Intervisit Reproducibility of Peripapillary RNFL Thickness

    PubMed Central

    Lee, Kyungmoo; Sonka, Milan; Kwon, Young H.; Garvin, Mona K.; Abràmoff, Michael D.

    2013-01-01

    Purpose. To report an automated method for adjustment of the retinal angle in spectral-domain optical coherence tomography (SD-OCT) and compare its intervisit reproducibility of the peripapillary retinal nerve fiber layer (RNFL) thicknesses of glaucomatous eyes to that obtained by the Cirrus algorithm. Methods. Fifty-six glaucoma and glaucoma suspect subjects were repeatedly imaged, and optic nerve head (ONH)–centered OCT image volumes (200 × 200 × 1024 voxels, 6 × 6 × 2 mm3, Cirrus HD-OCT machine) were acquired within a 4-month period from one eye of the 56 patients. Retinal angle correction in B-scans was accomplished by adjusting the angle using the voxel aspect ratio of the SD-OCT followed by straightening of rotated A-scans. The RNFL layer was automatically segmented using the Iowa Reference Algorithm. Reproducibility of the peripapillary RNFL thicknesses was determined by intraclass correlation coefficient (ICC), coefficient of variation (CV), repeatability coefficient (RC), and 95% tolerance limit (TL) for the Iowa Reference Algorithm without and with the retinal angle correction and for the Cirrus algorithm (Cirrus version 5.1.0.96). Results. The angle corrected Iowa Reference Algorithm (ICC: 0.990, 95% confidence interval [CI]: 0.983–0.994) for peripapillary RNFL thicknesses showed significantly better reproducibility than the nonangle corrected algorithm (ICC: 0.964, 95% CI: 0.940–0.979) and the Cirrus algorithm (ICC: 0.960, 95% CI: 0.933–0.976) based on the 95% CIs for the ICCs. Conclusions. Angle correction leads to more consistent peripapillary RNFL thicknesses. This may lead to improved management of patients with glaucoma. PMID:23788372

  4. Effects of Methane-Rich Saline on the Capability of One-Time Exhaustive Exercise in Male SD Rats

    PubMed Central

    Xin, Lei; Sun, Xuejun; Lou, Shujie

    2016-01-01

    Purpose To explore the effects of methane-rich saline (CH4 saline) on the capability of one-time exhaustive exercise in male SD rats. Methods Thirty rats were equally divided into to three groups at random: control group (C), placebo group (P) and methane saline group (M). Rats in M group underwent intraperitoneal injection of CH4 saline, and the other two groups simultaneously underwent intraperitoneal injection of normal saline. Then, the exercise capability of rats was tested through one-time exhaustive treadmill exercise except C group. Exercise time and body weight were recorded before and after one-time exhaustive exercise. After exhaustive exercise, the blood and gastrocnemius samples were collected from all rats to detect biochemical parameters in different methods. Results It was found that the treadmill running time was significantly longer in rats treated with CH4 saline. At the same time, CH4 saline reduced the elevation of LD and UN in blood caused by one-time exhaustive exercise. The low level of blood glucose induced by exhaustive exercise was also normalized by CH4 saline. Also CH4 saline lowered the level of CK in plasma. Furthermore, this research indicated that CH4 saline markedly increased the volume of T-AOC in plasma and alleviated the peak of TNF-α in both plasma and gastrocnemius. From H&E staining, CH4 saline effectively improved exercise-induced structural damage in gastrocnemius. Conclusions CH4 saline could enhance exercise capacity in male SD rats through increase of glucose aerobic oxidation, improvement of metabolic clearance and decrease of exhaustive exercise-induced gastrocnemius injury. PMID:26942576

  5. Integrating the SD-CLUE-S and InVEST models into assessment of oasis carbon storage in northwestern China

    PubMed Central

    Huang, Jiejun

    2017-01-01

    Spatio-temporal integrated assessment of land-use change impacts on carbon storage services is a new and important research field in land science and landscape ecology. The objective of this paper is to use an integrated SD-CLUE-S and InVEST model to simulate and predict land-use changes impacts during 2000–2018 on carbon storage at pixel and regional scales in the Zhangye oasis, Northwest China. The SD-CLUE-S model was used to simulate land-use change, and three land-use scenarios (current trend, moderate protection, and strict protection) were defined in collaboration with oasis socioeconomic development and ecological environment conservation by local government. The InVEST model was then used to simulate land-use change impacts on carbon storage at different scales in the oasis. The results showed that: (1) the effects of built-up land expansion were especially notable, with a rapid decrease in cropland during 2009–2018; (2) the strict protection scenario saved the largest amount of carbon storage for the oasis compared with the current trend and moderate protection scenarios. The scientific value of this study has been to show that the proposed modeling method can be used to reflect different land-use patterns and their effects on ecosystem services at multiple scales in the oasis. Furthermore, this research can be used to help government managers encourage stakeholders to contribute funds and strategies to maintain oasis landscape patterns and ecological processes by implementing local plans for potential conservation projects. PMID:28231328

  6. Strong correlations between vacancy and magnetic ordering in superconducting K0.8Fe2 -ySe2

    NASA Astrophysics Data System (ADS)

    Yang, J.; Duan, C.; Huang, Q.; Brown, C.; Neuefeind, J.; Louca, Despina

    2016-07-01

    The coexistence of magnetic and nonmagnetic phases in the superconducting potassium iron selenide, KxFe2 -ySe2 , has been intensely debated. With superconductivity proposed to appear in a stoichiometric, nonmagnetic phase with I4/mmm crystal symmetry, the proposed nonsuperconducting phase is magnetic and has a lower symmetry, I4/m. The latter consists of Fe vacancies that go through a disordered-to-ordered transition in which the partially filled Fe sites create a supercell upon ordering. We show, using neutron scattering on the optimally doped composition, K0.8Fe2 -ySe2 , that the absence of magnetism does not signal the presence of superconductivity. Moreover, the degree of vacancy order is coupled to the strength of the magnetic order. Superconductivity coincides with the presence of the magnetic order parameter, albeit the latter is significantly weaker than previously reported, contradicting the current understanding of this ˜30 K superconductor.

  7. Structures and aromaticity of X(2)Y(2)(-) (X = C, Si, Ge and Y = N, P, As) anions.

    PubMed

    Xu, Wen Guo; Zhang, Yuan Chun; Lu, Shi Xiang; Zhang, Rui Chun

    2009-11-01

    The equilibrium geometries, total energies, and vibrational frequencies of anions X(2)Y(2)(-) (X = C, Si, Ge and Y = N, P, As) are theoretically investigated with density functional theory (DFT) method. Our calculation shows that for C(2)N(2)(-) species, the D(2h) isomer is the most stable four-membered structure, and for other species the C(2v) isomer in which two X atoms are contrapuntal is the most stable structure at the B3LYP/6-311 +G(*) level. Wiberg bond index (WBI) and negative nucleus-independent chemical shift (NICS) value indicate the existence of delocalization in stable X(2)Y(2)(-) structures. A detailed molecular orbital (MO) analysis further reveals that stable isomers of these species have strongly aromatic character, which strengthens the structural stability and makes them closely connected with the concept of aromaticity.

  8. Supercontinuum generation in nonlinear fibers using high-energy figure-of-eight mode-locked fiber laser for SD-OCT application

    NASA Astrophysics Data System (ADS)

    Xu, Bo; Nagata, Tsubasa; Yamashita, Shinji

    2014-05-01

    Generation of flat and broadband supercontinum is demonstrated in an all fiber system using the high-energy noise-like pulses from a stable figure-of-eight fiber laser and nonlinear fibers. This SC source is successfully applied to the spectral domain optical coherence tomography (SD-OCT). The axial resolution is significantly improved compared with the case of the superluminescent diode source. SD-OCT imaging is also demonstrated.

  9. Complete Genome Sequence of Herbinix luporum SD1D, a New Cellulose-Degrading Bacterium Isolated from a Thermophilic Biogas Reactor

    PubMed Central

    Koeck, Daniela E.; Maus, Irena; Wibberg, Daniel; Winkler, Anika; Zverlov, Vladimir V.; Liebl, Wolfgang; Pühler, Alfred; Schwarz, Wolfgang H.

    2016-01-01

    A novel cellulolytic bacterial strain was isolated from an industrial-scale biogas plant. The 16S rRNA gene sequence of the strain SD1D showed 96.4% similarity to Herbinix hemicellulosilytica T3/55T, indicating a novel species within the genus Herbinix (family Lachnospiraceae). Here, the complete genome sequence of Herbinix luporum SD1D is reported. PMID:27445379

  10. Comparison of the Abilities of SD-OCT and SS-OCT in Evaluating the Thickness of the Macular Inner Retinal Layer for Glaucoma Diagnosis

    PubMed Central

    Lee, Kyoung Min; Lee, Eun Ji; Kim, Tae-Woo; Kim, Hyunjoong

    2016-01-01

    Purpose To compare the abilities of spectral-domain optical coherence tomography (OCT) (SD-OCT; Spectralis, Heidelberg Engineering) and swept-source OCT (SS-OCT; DRI-OCT1 Atlantis system, Topcon) for analyzing the macular inner retinal layers in diagnosing glaucoma. Methods The study included 60 patients with primary open-angle glaucoma (POAG) and 60 healthy control subjects. Macular cube area was scanned using SD-OCT and SS-OCT on the same day to assess the thicknesses of the macular retinal nerve fiber layer (mRNFL), ganglion cell layer plus inner plexiform layer (GCIPL), and total retinal layer in nine subfields defined by the Early Treatment Diabetic Retinopathy Study (ETDRS). The abilities of the parameters to discriminate between the POAG and control groups were assessed using areas under the receiver operating characteristic curves (AUCs). Results Glaucoma-associated mRNFL and GCIPL thinning was more common in the outer zones than inner zones for both SD-OCT and SS-OCT. The mRNFL and GCIPL measurements showed distinct pattern differences between SD-OCT and SS-OCT in each ETDRS subfield. Although the glaucoma-diagnosis ability was comparable between SD-OCT and SS-OCT for most of the parameters, AUC was significantly larger for SD-OCT measurements of the GCIPL thickness in the outer temporal zones (p = 0.003) and of the mRNFL thickness in the outer nasal zones (p = 0.001), with the former having the largest AUC for discriminating POAG from healthy eyes (AUC = 0.894). Conclusion Spectralis SD-OCT and DRI SS-OCT have similar glaucoma-diagnosis abilities based on macular inner layer thickness analysis. However, Spectralis SD-OCT was potentially superior to DRI SS-OCT in detecting GCIPL thinning in the outer temporal zone, where the glaucomatous damage predominantly occurs. PMID:26812064

  11. High platelet reactivity after P2Y12-inhibition in patients with atrial fibrillation and coronary stenting.

    PubMed

    Rilinger, Jonathan; Meyer, Melanie; Schnabel, Katharina; Weik, Patrick; Charlet, Anne; Esser, Jennifer S; Zhou, Qian; Bode, Christoph; Moser, Martin; Diehl, Philipp; Olivier, Christoph B

    2016-11-01

    High platelet reactivity (HPR) after P2Y12-inhibition in patients undergoing coronary stenting is associated with an increased risk for thromboembolic events and coronary death. So far it is not known how HPR affects the clinical outcome of different treatment strategies in patients with atrial fibrillation (AF) undergoing coronary stenting. In this single centre, observational study the antiplatelet effect of P2Y12-inhibitors in AF patients undergoing coronary stenting was investigated using impedance aggregometry. Patients received either dual antiplatelet therapy (DAPT) or triple therapy (TT). HPR was defined as the ratio of ADP-to TRAP-induced aggregation (r-ADP-agg) ≥50 %. Thromboembolic and bleeding events were assessed within the first 30 days after stenting. Out of 910 screened patients 167 patients were available for the present analysis. HPR was found in 5 of 43 (12 %) patients treated with DAPT and in 18 of 124 (15 %) patients treated with TT. In patients receiving TT, HPR was not a risk factor for thromboembolic events compared to patients with adequate response to P2Y12-inhibitors (6 vs. 8 %, p = 0.712). There was a trend for less bleeding events in patients with HPR compared to r-ADP-agg <50 % in the TT group (0 vs. 16 %, p = 0.077). Our data suggest that HPR after P2Y12-antagonism in patients receiving TT due to AF and coronary stenting might protect from bleeding without increasing thromboembolic risk. Future studies will need to investigate if patients with AF receiving coronary stenting benefit from a reduction of antithrombotic therapy.

  12. Purinergic 2Y1 receptor stimulation decreases cerebral edema and reactive gliosis in a traumatic brain injury model.

    PubMed

    Talley Watts, Lora; Sprague, Shane; Zheng, Wei; Garling, R Justin; Jimenez, David; Digicaylioglu, Murat; Lechleiter, James

    2013-01-01

    Traumatic brain injury (TBI) is the leading cause of death and disability in children and young adults. Neuroprotective agents that may promote repair or counteract damage after injury do not currently exist. We recently reported that stimulation of the purinergic receptor subtype P2Y(1)R using 2-methylthioladenosine 5' diphosphate (2MeSADP) significantly reduced cytotoxic edema induced by photothrombosis. Here, we tested whether P2Y(1)R stimulation was neuroprotective after TBI. A controlled closed head injury model was established for mice using a pneumatic impact device. Brains were harvested at 1, 3, or 7 days post-injury and assayed for morphological changes by immunocytochemistry, Western blot analysis, and wet/dry weight. Cerebral edema and expression of both aquaporin type 4 and glial fibrillary acidic protein were increased at all time points examined. Immunocytochemical measurements in both cortical and hippocampal slices also revealed significant neuronal swelling and reactive gliosis. Treatment of mice with 2MeSADP (100 μM) or MRS2365 (100 μM) 30 min after trauma significantly reduced all post-injury symptoms of TBI including edema, neuronal swelling, reactive gliosis, and AQ4 expression. The neuroprotective effect was lost in IP(3)R2-/- mice treated with 2MeSADP. Immunocytochemical labeling of brain slices confirmed that P2Y(1)R expression was defined to cortical and hippocampal astrocytes, but not neurons. Taken together, the data show that stimulation of astrocytic P2Y(1)Rs significantly reduces brain injury after acute trauma and is mediated by the IP(3)-signaling pathway. We suggest that enhancing astrocyte mitochondrial metabolism offers a promising neuroprotective strategy for a broad range of brain injuries.

  13. Synthesis, characterization, and in vitro evaluation of the selective P2Y2 receptor antagonist AR-C118925.

    PubMed

    Rafehi, Muhammad; Burbiel, Joachim C; Attah, Isaac Y; Abdelrahman, Aliaa; Müller, Christa E

    2017-03-01

    The Gq protein-coupled, ATP- and UTP-activated P2Y2 receptor is a potential drug target for a range of different disorders, including tumor metastasis, inflammation, atherosclerosis, kidney disorders, and osteoporosis, but pharmacological studies are impeded by the limited availability of suitable antagonists. One of the most potent and selective antagonists is the thiouracil derivative AR-C118925. However, this compound was until recently not commercially available and little is known about its properties. We therefore developed an improved procedure for the synthesis of AR-C118925 and two derivatives to allow up-scaling and assessed their potency in calcium mobilization assays on the human and rat P2Y2 receptors recombinantly expressed in 1321N1 astrocytoma cells. The compound was further evaluated for inhibition of P2Y2 receptor-induced β-arrestin translocation. AR-C118925 behaved as a competitive antagonist with pA 2 values of 37.2 nM (calcium assay) and 51.3 nM (β-arrestin assay). Selectivity was assessed vs. related receptors including P2X, P2Y, and adenosine receptor subtypes, as well as ectonucleotidases. AR-C118925 showed at least 50-fold selectivity against the other investigated targets, except for the P2X1 and P2X3 receptors which were blocked by AR-C118925 at concentrations of about 1 μM. AR-C118925 is soluble in buffer at pH 7.4 (124 μM) and was found to be metabolically highly stable in human and mouse liver microsomes. In Caco2 cell experiments, the compound displayed moderate permeability indicating that it may show limited peroral bioavailability. AR-C118925 appears to be a useful pharmacological tool for in vitro and in vivo studies.

  14. Denufosol: a review of studies with inhaled P2Y(2) agonists that led to Phase 3.

    PubMed

    Kellerman, Donald; Rossi Mospan, Andrea; Engels, Jean; Schaberg, Amy; Gorden, Joann; Smiley, Lynn

    2008-08-01

    Among the most promising of the new therapies being developed for the treatment of Cystic Fibrosis (CF) are those targeted at increasing mucosal hydration on the surface of the airways. One of these therapies, P2Y(2) receptor agonists, bypasses the defective CFTR chloride channel, and activates an alternative chloride channel. This activation results in an increase in airway surface epithelial hydration, and through these actions and effects on cilia beat frequency, increases mucociliary clearance. The pharmacology of P2Y(2) agonists has been confirmed in several preclinical and clinical studies. Denufosol tetrasodium is a novel second-generation, metabolically stable, selective P2Y(2) receptor agonist currently in Phase 3 clinical development. In radiolabelled deposition studies of P2Y(2) agonists in healthy non-smokers and smokers, approximately 7mg of a 40-mg nebulizer (PARI LC Star) load was deposited in the lungs. In a pharmacokinetic study in healthy volunteers, very limited systemic exposure was observed when doses of 200mg of denufosol were nebulized. Thus, it appears that high concentrations of denufosol can be achieved in the airways with very low systemic absorption. Denufosol has been generally well-tolerated in healthy volunteers and patients with CF. The most common adverse events were in the respiratory system, with cough having the highest frequency. Doses of 20-60mg have been evaluated in Phase 2 trials of up to 28 days duration, and superiority relative to placebo on FEV1 has been observed in patients with relatively normal lung function (FEV1 greater than or equal to 75% of predicted). The first Phase 3 trial is a comparison of denufosol 60mg and placebo in 350 patients with CF with FEV1 at study entry greater than or equal to 75% of predicted.

  15. Ectopic Expression of Capsicum-Specific Cell Wall Protein Capsicum annuum Senescence-Delaying 1 (CaSD1) Delays Senescence and Induces Trichome Formation in Nicotiana benthamiana

    PubMed Central

    Seo, Eunyoung; Yeom, Seon-In; Jo, SungHwan; Jeong, Heejin; Kang, Byoung-Cheorl; Choi, Doil

    2012-01-01

    Secreted proteins are known to have multiple roles in plant development, metabolism, and stress response. In a previous study to understand the roles of secreted proteins, Capsicum annuum secreted proteins (CaS) were isolated by yeast secretion trap. Among the secreted proteins, we further characterized Capsicum annuum senescence-delaying 1 (CaSD1), a gene encoding a novel secreted protein that is present only in the genus Capsicum. The deduced CaSD1 contains multiple repeats of the amino acid sequence KPPIHNHKPTDYDRS. Interestingly, the number of repeats varied among cultivars and species in the Capsicum genus. CaSD1 is constitutively expressed in roots, and Agrobacterium-mediated transient overexpression of CaSD1 in Nicotiana benthamiana leaves resulted in delayed senescence with a dramatically increased number of trichomes and enlarged epidermal cells. Furthermore, senescence- and cell division-related genes were differentially regulated by CaSD1-overexpressing plants. These observations imply that the pepper-specific cell wall protein CaSD1 plays roles in plant growth and development by regulating cell division and differentiation. PMID:22441673

  16. Ectopic expression of Capsicum-specific cell wall protein Capsicum annuum senescence-delaying 1 (CaSD1) delays senescence and induces trichome formation in Nicotiana benthamiana.

    PubMed

    Seo, Eunyoung; Yeom, Seon-In; Jo, Sunghwan; Jeong, Heejin; Kang, Byoung-Cheorl; Choi, Doil

    2012-04-01

    Secreted proteins are known to have multiple roles in plant development, metabolism, and stress response. In a previous study to understand the roles of secreted proteins, Capsicum annuum secreted proteins (CaS) were isolated by yeast secretion trap. Among the secreted proteins, we further characterized Capsicum annuum senescence-delaying 1 (CaSD1), a gene encoding a novel secreted protein that is present only in the genus Capsicum. The deduced CaSD1 contains multiple repeats of the amino acid sequence KPPIHNHKPTDYDRS. Interestingly, the number of repeats varied among cultivars and species in the Capsicum genus. CaSD1 is constitutively expressed in roots, and Agrobacterium-mediated transient overexpression of CaSD1 in Nicotiana benthamiana leaves resulted in delayed senescence with a dramatically increased number of trichomes and enlarged epidermal cells. Furthermore, senescence- and cell division-related genes were differentially regulated by CaSD1-overexpressing plants. These observations imply that the pepper-specific cell wall protein CaSD1 plays roles in plant growth and development by regulating cell division and differentiation.

  17. P2Y12 receptor blockade synergizes strongly with nitric oxide and prostacyclin to inhibit platelet activation

    PubMed Central

    Chan, Melissa V.; Knowles, Rebecca B. M.; Lundberg, Martina H.; Tucker, Arthur T.; Mohamed, Nura A.; Kirkby, Nicholas S.; Armstrong, Paul C. J.; Mitchell, Jane A.

    2016-01-01

    Aims In vivo platelet function is a product of intrinsic platelet reactivity, modifiable by dual antiplatelet therapy (DAPT), and the extrinsic inhibitory endothelial mediators, nitric oxide (NO) and prostacyclin (PGI2), that are powerfully potentiated by P2Y12 receptor blockade. This implies that for individual patients endothelial mediator production is an important determinant of DAPT effectiveness. Here, we have investigated this idea using platelets taken from healthy volunteers treated with anti‐platelet drugs. Methods Three groups of male volunteers (n = 8) received either prasugrel (10 mg), aspirin (75 mg) or DAPT (prasugrel + aspirin) once daily for 7 days. Platelet reactivity in the presence of diethylammonium (Z)‐1‐(N,N‐diethylamino)diazen‐1‐ium‐1,2‐diolate (DEA/NONOate) and PGI2 was studied before and following treatment. Results Ex vivo, PGI2 and/or DEA/NONOate had little inhibitory effect on TRAP‐6‐induced platelet reactivity in control conditions. However, in the presence of DAPT, combination of DEA/NONOate + PGI2 reduced platelet aggregation (74 ± 3% to 19 ± 6%, P < 0.05). In vitro studies showed even partial (25%) P2Y12 receptor blockade produced a significant (67 ± 2% to 39 ± 10%, P < 0.05) inhibition when DEA/NONOate + PGI2 was present. Conclusions We have demonstrated that PGI2 and NO synergize with P2Y12 receptor antagonists to produce powerful platelet inhibition. Furthermore, even with submaximal P2Y12 blockade the presence of PGI2 and NO greatly enhances platelet inhibition. Our findings highlight the importance of endothelial mediator in vivo modulation of P2Y12 inhibition and introduces the concept of refining ex vivo platelet function testing by incorporating an assessment of endothelial function to predict thrombotic outcomes better and adjust therapy to prevent adverse outcomes in individual patients. PMID:26561399

  18. Purinergic P2Y2 Receptor Control of Tissue Factor Transcription in Human Coronary Artery Endothelial Cells: NEW AP-1 TRANSCRIPTION FACTOR SITE AND NEGATIVE REGULATOR.

    PubMed

    Liu, Yiwei; Zhang, Lingxin; Wang, Chuan; Roy, Shama; Shen, Jianzhong

    2016-01-22

    We recently reported that the P2Y2 receptor (P2Y2R) is the predominant nucleotide receptor expressed in human coronary artery endothelial cells (HCAEC) and that P2Y2R activation by ATP or UTP induces dramatic up-regulation of tissue factor (TF), a key initiator of the coagulation cascade. However, the molecular mechanism of this P2Y2R-TF axis remains unclear. Here, we report the role of a newly identified AP-1 consensus sequence in the TF gene promoter and its original binding components in P2Y2R regulation of TF transcription. Using bioinformatics tools, we found that a novel AP-1 site at -1363 bp of the human TF promoter region is highly conserved across multiple species. Activation of P2Y2R increased TF promoter activity and mRNA expression in HCAEC. Truncation, deletion, and mutation of this distal AP-1 site all significantly suppressed TF promoter activity in response to P2Y2R activation. EMSA and ChIP assays further confirmed that upon P2Y2R activation, c-Jun, ATF-2, and Fra-1, but not the typical c-Fos, bound to the new AP-1 site. In addition, loss-of-function studies using siRNAs confirmed a positive transactivation role of c-Jun and ATF-2 but unexpectedly revealed a strong negative role of Fra-1 in P2Y2R-induced TF up-regulation. Furthermore, we found that P2Y2R activation promoted ERK1/2 phosphorylation through Src, leading to Fra-1 activation, whereas Rho/JNK mediated P2Y2R-induced activation of c-Jun and ATF-2. These findings reveal the molecular basis for P2Y G protein-coupled receptor control of endothelial TF expression and indicate that targeting the P2Y2R-Fra-1-TF pathway may be an attractive new strategy for controlling vascular inflammation and thrombogenicity associated with endothelial dysfunction.

  19. Automated 3D Segmentation of Intraretinal Surfaces in SD-OCT Volumes in Normal and Diabetic Mice

    PubMed Central

    Antony, Bhavna J.; Jeong, Woojin; Abràmoff, Michael D.; Vance, Joseph; Sohn, Elliott H.; Garvin, Mona K.

    2014-01-01

    Purpose To describe an adaptation of an existing graph-theoretic method (initially developed for human optical coherence tomography [OCT] images) for the three-dimensional (3D) automated segmentation of 10 intraretinal surfaces in mice scans, and assess the accuracy of the method and the reproducibility of thickness measurements. Methods Ten intraretinal surfaces were segmented in repeat spectral domain (SD)-OCT volumetric images acquired from normal (n = 8) and diabetic (n = 10) mice. The accuracy of the method was assessed by computing the border position errors of the automated segmentation with respect to manual tracings obtained from two experts. The reproducibility was statistically assessed for four retinal layers within eight predefined regions using the mean and SD of the differences in retinal thickness measured in the repeat scans, the coefficient of variation (CV) and the intraclass correlation coefficients (ICC; with 95% confidence intervals [CIs]). Results The overall mean unsigned border position error for the 10 surfaces computed over 97 B-scans (10 scans, 10 normal mice) was 3.16 ± 0.91 μm. The overall mean differences in retinal thicknesses computed from the normal and diabetic mice were 1.86 ± 0.95 and 2.15 ± 0.86 μm, respectively. The CV of the retinal thicknesses for all the measured layers ranged from 1.04% to 5%. The ICCs for the total retinal thickness in the normal and diabetic mice were 0.78 [0.10, 0.92] and 0.83 [0.31, 0.96], respectively. Conclusion The presented method (publicly available as part of the Iowa Reference Algorithms) has acceptable accuracy and reproducibility and is expected to be useful in the quantitative study of intraretinal layers in mice. Translational Relevance The presented method, initially developed for human OCT, has been adapted for mice, with the potential to be adapted for other animals as well. Quantitative in vivo assessment of the retina in mice allows changes to be measured longitudinally, decreasing

  20. P2Y12 receptor is expressed on human microglia under physiological conditions throughout development and is sensitive to neuroinflammatory diseases.

    PubMed

    Mildner, Alexander; Huang, Hao; Radke, Josefine; Stenzel, Werner; Priller, Josef

    2017-02-01

    Microglia are resident immune cells in the central nervous system (CNS), which are essential for immune defence and critically contribute to neuronal functions during homeostasis. Until now, little is known about microglia biology in humans in part due to the lack of microglia-specific markers. We therefore investigated the expression of the purinergic receptor P2Y12 in human brain tissue. Compared to classical markers used to identify microglia such as Iba1, CD68 or MHCII, we found that P2Y12 is expressed on parenchymal microglia but is absent from perivascular or meningeal macrophages. We further demonstrate that P2Y12 expression is stable throughout human brain development, including fetal phases, and quantification of P2 Y12+ microglia revealed that the density of human microglia is constant throughout lifetime. In contrast, CD68 expression increases during aging in cerebellar but not in cortical microglia, indicating regional heterogeneity. CNS pathologies such as Alzheimer's disease or multiple sclerosis-but not schizophrenia-result in decreased P2Y12 immunoreactivity in plaque- or lesion-associated myeloid cells, whereas Iba1 expression remains detectable. Our results suggest that P2Y12 is a useful marker for the identification of human microglia throughout the lifespan. Moreover, P2Y12 expression might help to discriminate activated microglia and infiltrating myeloid cells from quiescent microglia in the human CNS. GLIA 2017;65:375-387.

  1. Extracellular UDP and P2Y6 function as a danger signal to protect mice from vesicular stomatitis virus infection through an increase in IFN-β production.

    PubMed

    Li, Ruimei; Tan, Binghe; Yan, Yan; Ma, Xiaobin; Zhang, Na; Zhang, Zhi; Liu, Mingyao; Qian, Min; Du, Bing

    2014-11-01

    Extracellular nucleotides that constitute a "danger signal" play an important role in the regulation of immune responses. However, the function and mechanism of extracellular UDP and P2Y6 in antiviral immunity remain unknown. In this study, we demonstrated the in vitro and in vivo protection of UDP/P2Y6 signaling in vesicular stomatitis virus (VSV) infection. First, we demonstrated that VSV-infected cells secrete UDP from the cytoplasm as a danger signal to arouse surrounding cells. Meanwhile, expression of the UDP-specific receptor P2Y6 also was enhanced by VSV. Consequently, UDP protects RAW 264.7 cells, murine embryonic fibroblasts, bone marrow-derived macrophages, and L929 cells from VSV and GFP lentivirus infection. This protection can be blocked by the P2Y6 selective antagonist MRS2578 or IFN-α/β receptor-blocking Ab. VSV-induced cell death and virus replication were both enhanced significantly by knocking down and knocking out P2Y6 in different cells. Mechanistically, UDP facilitates IFN-β secretion through the p38/JNK- and ATF-2/c-Jun-signaling pathways, which are crucial in promoting antiviral immunity. Interestingly, UDP was released through a caspase-cleaved pannexin-1 channel in VSV-induced apoptotic cells and protected cells from infection through P2Y6 receptor in an autocrine or paracrine manner. Furthermore, UDP also protected mice from VSV infection through P2Y6 receptors in an acute neurotropic infection mouse model. Taken together, these results demonstrate the important role of extracellular UDP and P2Y6 as a danger signal in antiviral immune responses and suggest a potential therapeutic role for UDP/P2Y6 in preventing and controlling viral diseases.

  2. P2Y receptor mediated inhibitory modulation of noradrenaline release in response to electrical field stimulation and ischemic conditions in superfused rat hippocampus slices.

    PubMed

    Csölle, Cecília; Heinrich, Attila; Kittel, Agnes; Sperlágh, Beáta

    2008-07-01

    In this study, the inhibitory regulation of the release of noradrenaline (NA) by P2 receptors was investigated in hippocampus slices pre-incubated with [(3)H]NA. Electrical field stimulation (EFS; 2 Hz, 240 shocks, and 1 ms) released NA in an outside [Ca(2+)]-dependent manner, and agonists of P2Y receptors inhibited the EFS-evoked [(3)H]NA release with pharmacological profile similar to that of the P2Y(1) and P2Y(13) receptor subtypes. This inhibitory modulation was counteracted by bicuculline and 6-cyano-2,3-dihydroxy-7-nitro-quinoxaline + 2-amino-5-phosphonovalerate and 2-amino-4-phosphonobutyrate. In contrast, the excess release in response to 30 min combined oxygen and glucose deprivation was outside [Ca(2+)] independent, but still sensitive to the inhibition of both facilitatory P2X(1) and inhibitory P2Y(1) receptors. Whereas mRNA encoding P2Y(12) and P2Y(13) receptor subunits were expressed in the brainstem, P2Y(1) receptor immunoreactivity was localized to neuronal somata and dendrites innervated by the mossy fiber terminals in the CA3 region of the hippocampus, as well as somata of granule cells and interneurons in the dentate gyrus. In summary, in addition to the known facilitatory modulation via P2X receptors, EFS-evoked [(3)H]NA outflow in the hippocampus is subject to inhibitory modulation by P2Y(1)/P2Y(13) receptors. Furthermore, endogenous activation of both facilitatory and inhibitory P2 receptors may participate in the modulation of pathological NA release under ischemic-like conditions.

  3. P2Y2 receptor antagonists as anti-allodynic agents in acute and sub-chronic trigeminal sensitization: role of satellite glial cells.

    PubMed

    Magni, Giulia; Merli, Davide; Verderio, Claudia; Abbracchio, Maria P; Ceruti, Stefania

    2015-07-01

    Trigeminal (TG) pain often lacks a satisfactory pharmacological control. A better understanding of the molecular cross-talk between TG neurons and surrounding satellite glial cells (SGCs) could help identifying innovative targets for the development of more effective analgesics. We have previously demonstrated that neuronal pro-algogenic mediators upregulate G protein-coupled nucleotide P2Y receptors (P2YRs) expressed by TG SGCs in vitro. Here, we have identified the specific P2YR subtypes involved (i.e., the ADP-sensitive P2Y1 R and the UTP-responsive P2Y2 R subtypes), and demonstrated the contribution of neuron-derived prostaglandins to their upregulation. Next, we have translated these data to an in vivo model of TG pain (namely, rats injected with Complete Freund's adjuvant in the temporomandibular joint), by demonstrating activation of SGCs and upregulation of P2Y1 R and P2Y2 R in the ipsi-lateral TG. To unequivocally link P2YRs to the development of facial allodynia, we treated animals with various purinergic antagonists. The selective P2Y2 R antagonist AR-C118925 completely inhibited SGCs activation, exerted a potent anti-allodynic effect that lasted over time, and was still effective when administration was started 6-days post induction of allodynia, i.e. under subchronic pain conditions. Conversely, the selective P2Y1 R antagonist MRS2179 was completely ineffective. Moreover, similarly to the anti-inflammatory drug acetylsalicylic acid and the known anti-migraine agent sumatriptan, the P2X/P2Y nonselective antagonist PPADS was only partially effective, and completely lost its activity under sub-chronic conditions. Taken together, our results highlight glial P2Y2 Rs as potential "druggable" targets for the successful management of TG-related pain.

  4. Digital gene expression profiling analysis of duodenum transcriptomes in SD rats administered ferrous sulfate or ferrous glycine chelate by gavage.

    PubMed

    Zhuo, Zhao; Fang, Shenglin; Hu, Qiaoling; Huang, Danping; Feng, Jie

    2016-11-30

    The absorption of different iron sources is a trending research topic. Many studies have revealed that organic iron exhibits better bioavailability than inorganic iron, but the concrete underlying mechanism is still unclear. In the present study, we examined the differences in bioavailability of ferrous sulfate and ferrous glycinate in the intestines of SD rats using Illumina sequencing technology. Digital gene expression analysis resulted in the generation of almost 128 million clean reads, with expression data for 17,089 unigenes. A total of 123 differentially expressed genes with a |log2(fold change)| >1 and q-value < 0.05 were identified between the FeSO4 and Fe-Gly groups. Gene Ontology functional analysis revealed that these genes were involved in oxidoreductase activity, iron ion binding, and heme binding. Kyoto Encyclopedia of Genes and Genomes pathway analysis also showed relevant important pathways. In addition, the expression patterns of 9 randomly selected genes were further validated by qRT-PCR, which confirmed the digital gene expression results. Our study showed that the two iron sources might share the same absorption mechanism, and that differences in bioavailability between FeSO4 and Fe-Gly were not only in the absorption process but also during the transport and utilization process.

  5. An sd(2) hybridized transition-metal monolayer with a hexagonal lattice: reconstruction between the Dirac and kagome bands.

    PubMed

    Zhou, Baozeng; Dong, Shengjie; Wang, Xiaocha; Zhang, Kailiang; Mi, Wenbo

    2017-03-15

    Graphene-like two-dimensional materials have garnered tremendous interest as emerging device materials due to their remarkable properties. However, their applications in spintronics have been limited by the lack of intrinsic magnetism. Here, we perform an ab initio simulation on the structural and electronic properties of several transition-metal (TM) monolayers (TM = Cr, Mo and W) with a honeycomb lattice on a 1/3 monolayer Cl-covered Si(111) surface. Due to the template effect from the halogenated Si substrate, the TM-layers will be maintained in an expanded lattice which is nearly 60% larger than that of the freestanding case. All these isolated TM-layers exhibit ferromagnetic coupling with kagome band structures related to sd(2) hybridization and a strong interfacial interaction may destroy the topological bands. Interestingly, the W-monolayer on the Cl-covered Si substrate shows a half-metallic behavior. A Dirac point formed at the K point in the spin-down channel is located exactly at the Fermi level which is crucial for the realization of a quantum spin Hall state. Moreover, the reconstruction process between the Dirac and kagome bands is discussed in detail, providing an interesting platform to study the interplay between massless Dirac fermions and heavy fermions.

  6. Liraglutide-loaded multivesicular liposome as a sustained-delivery reduces blood glucose in SD rats with diabetes.

    PubMed

    Zhang, Lixue; Ding, Lei; Tang, Chengcheng; Li, Yang; Yang, Li

    2016-11-01

    Subcutaneous liraglutide-loaded multivesicular liposomes (Lrg-MVLs) were developed as a sustained drug-delivery system for treating diabetes and their properties were characterized. The Lrg-MVLs prepared using a two-step water-in-oil-in-water double emulsification process had a spherical appearance with a mean diameter of 6.69 μm and an encapsulation efficiency of 82.23 ± 4.78% without any initial burst release. Their pharmacodynamics (PD) and pharmacokinetics (PK) were also studied after a single subcutaneous administration to Sprague-Dawley (SD) rats with diabetes. The PD results demonstrated that Lrg-MVLs presented sustained glucose-lowering effects for nearly a week, while the pharmacokinetic parameters showed that the plasma liraglutide concentration of the designed preparation produced Cmax of 81.979 ± 12.140 pg/ml and an MRT0-t of 88.224 ± 3.893 h. Furthermore, retention of Lrg-MVLs at the injection site was studied semiquantitatively by an in vivo imaging system, which can be used to evaluate the drug release from MVLs in vivo. In conclusion, MVLs are a promising carrier for liraglutide and Lrg-MVLs deserve further study for the treatment of diabetes.

  7. Optically deviated focusing method based high-speed SD-OCT for in vivo retinal clinical applications

    NASA Astrophysics Data System (ADS)

    Wijesinghe, Ruchire Eranga; Park, Kibeom; Kim, Pilun; Oh, Jaeryung; Kim, Seong-Woo; Kim, Kwangtae; Kim, Beop-Min; Jeon, Mansik; Kim, Jeehyun

    2016-04-01

    The aim of this study is to provide accurately focused, high-resolution in vivo human retinal depth images using an optically deviated focusing method with spectral-domain optical coherence tomography (SD-OCT) system. The proposed method was applied to increase the retinal diagnosing speed of patients with various values of retinal distances (i.e., the distance between the crystalline eye lens and the retina). The increased diagnosing speed was facilitated through an optical modification in the OCT sample arm configuration. Moreover, the optical path length matching process was compensated using the proposed optically deviated focusing method. The developed system was mounted on a bench-top cradle to overcome the motion artifacts. Further, we demonstrated the capability of the system by carrying out in vivo retinal imaging experiments. The clinical trials confirmed that the system was effective in diagnosing normal and abnormal retinal layers as several retinal abnormalities were identified using non-averaged single-shot OCT images, which demonstrate the feasibility of the method for clinical applications.

  8. Digital gene expression profiling analysis of duodenum transcriptomes in SD rats administered ferrous sulfate or ferrous glycine chelate by gavage

    PubMed Central

    Zhuo, Zhao; Fang, Shenglin; Hu, Qiaoling; Huang, Danping; Feng, Jie

    2016-01-01

    The absorption of different iron sources is a trending research topic. Many studies have revealed that organic iron exhibits better bioavailability than inorganic iron, but the concrete underlying mechanism is still unclear. In the present study, we examined the differences in bioavailability of ferrous sulfate and ferrous glycinate in the intestines of SD rats using Illumina sequencing technology. Digital gene expression analysis resulted in the generation of almost 128 million clean reads, with expression data for 17,089 unigenes. A total of 123 differentially expressed genes with a |log2(fold change)| >1 and q-value < 0.05 were identified between the FeSO4 and Fe-Gly groups. Gene Ontology functional analysis revealed that these genes were involved in oxidoreductase activity, iron ion binding, and heme binding. Kyoto Encyclopedia of Genes and Genomes pathway analysis also showed relevant important pathways. In addition, the expression patterns of 9 randomly selected genes were further validated by qRT-PCR, which confirmed the digital gene expression results. Our study showed that the two iron sources might share the same absorption mechanism, and that differences in bioavailability between FeSO4 and Fe-Gly were not only in the absorption process but also during the transport and utilization process. PMID:27901057

  9. Mean-field dynamics with stochastic decoherence (MF-SD): A new algorithm for nonadiabatic mixed quantum/classical molecular-dynamics simulations with nuclear-induced decoherence

    NASA Astrophysics Data System (ADS)

    Bedard-Hearn, Michael J.; Larsen, Ross E.; Schwartz, Benjamin J.

    2005-12-01

    The key factors that distinguish algorithms for nonadiabatic mixed quantum/classical (MQC) simulations from each other are how they incorporate quantum decoherence—the fact that classical nuclei must eventually cause a quantum superposition state to collapse into a pure state—and how they model the effects of decoherence on the quantum and classical subsystems. Most algorithms use distinct mechanisms for modeling nonadiabatic transitions between pure quantum basis states ("surface hops") and for calculating the loss of quantum-mechanical phase information (e.g., the decay of the off-diagonal elements of the density matrix). In our view, however, both processes should be unified in a single description of decoherence. In this paper, we start from the density matrix of the total system and use the frozen Gaussian approximation for the nuclear wave function to derive a nuclear-induced decoherence rate for the electronic degrees of freedom. We then use this decoherence rate as the basis for a new nonadiabatic MQC molecular-dynamics (MD) algorithm, which we call mean-field dynamics with stochastic decoherence (MF-SD). MF-SD begins by evolving the quantum subsystem according to the time-dependent Schrödinger equation, leading to mean-field dynamics. MF-SD then uses the nuclear-induced decoherence rate to determine stochastically at each time step whether the system remains in a coherent mixed state or decoheres. Once it is determined that the system should decohere, the quantum subsystem undergoes an instantaneous total wave-function collapse onto one of the adiabatic basis states and the classical velocities are adjusted to conserve energy. Thus, MF-SD combines surface hops and decoherence into a single idea: decoherence in MF-SD does not require the artificial introduction of reference states, auxiliary trajectories, or trajectory swarms, which also makes MF-SD much more computationally efficient than other nonadiabatic MQC MD algorithms. The unified definition of

  10. A population of serumdeprivation-induced bone marrow stem cells (SD-BMSC) expresses marker typical for embryonic and neural stem cells

    SciTech Connect

    Sauerzweig, Steven Munsch, Thomas; Lessmann, Volkmar; Reymann, Klaus G.; Braun, Holger

    2009-01-01

    The bone marrow represents an easy accessible source of adult stem cells suitable for various cell based therapies. Several studies in recent years suggested the existence of pluripotent stem cells within bone marrow stem cells (BMSC) expressing marker proteins of both embryonic and tissue committed stem cells. These subpopulations were referred to as MAPC, MIAMI and VSEL-cells. Here we describe SD-BMSC (serumdeprivation-induced BMSC) which are induced as a distinct subpopulation after complete serumdeprivation. SD-BMSC are generated from small-sized nestin-positive BMSC (S-BMSC) organized as round-shaped cells in the top layer of BMSC-cultures. The generation of SD-BMSC is caused by a selective proliferation of S-BMSC and accompanied by changes in both morphology and gene expression. SD-BMSC up-regulate not only markers typical for neural stem cells like nestin and GFAP, but also proteins characteristic for embryonic cells like Oct4 and SOX2. We hypothesize, that SD-BMSC like MAPC, MIAMI and VSEL-cells represent derivatives from a single pluripotent stem cell fraction within BMSC exhibiting characteristics of embryonic and tissue committed stem cells. The complete removal of serum might offer a simple way to specifically enrich this fraction of pluripotent embryonic like stem cells in BMSC cultures.

  11. Evaluation of the SD BIOLINE Dengue Duo rapid test in the course of acute and convalescent dengue infections in a Mexican endemic region.

    PubMed

    Sánchez-Vargas, Luis A; Sánchez-Marce, Elvis E; Vivanco-Cid, Héctor

    2014-04-01

    In this study, we evaluated the performance of a rapid test, the SD BIOLINE Dengue Duo (SD BDD) kit, with a panel of serum samples from 310 Mexican patients with diagnosis of dengue infection previously confirmed by reference enzyme-linked immunosorbent assay tests. Eighty-seven negative samples from other febrile illnesses were included as controls. The SD BDD showed an overall sensitivity of 90.65% and specificity of 89.66%. No statistically significant differences were found in the sensitivity of the SD BDD kit compared between primary or secondary infections (87.05% versus 93.57%, respectively, P = 0.0761) and dengue fever or dengue hemorrhagic fever cases (90.77% versus 89.74%, respectively, P = 0.7716). However, a higher sensitivity in the acute phase of dengue infection was found compared with the convalescent phase (93.03% versus 81.82%, respectively, P = 0.0089). These results indicate that the SD BDD kit is a useful tool to diagnose dengue infections, both in primary or secondary infections and mainly during the acute phase.

  12. A pharmacodynamic study of the optimal P2Y12 inhibitor regimen for East Asian patients with acute coronary syndrome

    PubMed Central

    Lee, Ji Hyun; Ahn, Sung Gyun; Park, Bonil; Park, Sang Wook; Kang, Yong Seok; Lee, Jun-Won; Youn, Young Jin; Ahn, Min-Soo; Kim, Jang-Young; Yoo, Byung-Su; Lee, Seung-Hwan; Yoon, Junghan

    2015-01-01

    Background/Aims: Newer P2Y12 inhibitors, such as prasugrel and ticagrelor, have greater antiplatelet efficacy but may increase the risk of bleeding. In this study, we compared the pharmacodynamic efficacy of prasugrel and ticagrelor in East Asian patients with acute coronary syndrome (ACS). Methods: We selected 83 ACS patients undergoing percutaneous coronary intervention who were discharged with 90 mg ticagrelor twice daily (n = 24), 10 mg prasugrel daily (n = 39) or 5 mg prasugrel daily (n = 20). After 2 to 4 weeks, on-treatment platelet reactivity (OPR) was assessed in terms of P2Y12 reaction units (PRUs) using the VerifyNow P2Y12 assay (Accumetrics). We compared East Asian (85 < PRU ≤ 275) and Caucasian (85 < PRU ≤ 208) criteria for assessing the therapeutic window of OPR. Results: OPR was lowest in the ticagrelor group, followed by the 10 mg prasugrel and 5 mg prasugrel groups (49.1 ± 29.9 vs. 83.7 ± 57.1 vs. 168.5 ± 60.8, respectively; p < 0.001). The 5 mg prasugrel group had the highest proportion of patients with OPR values within the therapeutic window, followed by the 10 mg prasugrel and ticagrelor groups (90.0% vs. 46.2% vs. 12.5%, respectively; p < 0.001 for East Asian criteria; 60.0% vs. 43.6% vs. 12.5%, respectively; p < 0.001 for Caucasian criteria). Conclusions: Short-term administration of 5 mg prasugrel facilitated maintenance within the therapeutic window of OPR compared with the 10 mg prasugrel and ticagrelor groups. Thus, 5 mg prasugrel daily may be the optimal antiplatelet regimen for stabilized East Asian ACS patients. PMID:26354056

  13. Direct excitation of inhibitory interneurons by extracellular ATP mediated by P2Y1 receptors in the hippocampal slice.

    PubMed

    Kawamura, Masahito; Gachet, Christian; Inoue, Kazuhide; Kato, Fusao

    2004-12-01

    ATP is an important cell-to-cell signaling molecule mediating the interactions between astrocytes and neurons in the CNS. In the hippocampal slices, ATP suppresses excitatory transmission mostly through activation of adenosine A1 receptors, because the ectoenzyme activity for the extracellular breakdown of ATP to adenosine is high in slice preparations in contrast to culture environments. Because the hippocampus is also rich in the expression of P2 receptors activated specifically by ATP, we examined whether ATP modulates neuronal excitability in the acute slice preparations independently of adenosine receptors. Although ATP decreased the frequency of spontaneously occurring EPSCs in the CA3 pyramidal neurons through activation of adenosine A1 receptors, ATP concurrently increased the frequency of IPSCs in a manner dependent on action potential generation. This effect was mediated by P2Y1 receptors because (1) 2-methylthio-ATP (2meSATP) was the most potent agonist, (2) 2'-deoxy-N6-methyladenosine-3',5'-bisphosphate diammonium (MRS2179) abolished this effect, and (3) this increase in IPSC frequency was not observed in the transgenic mice lacking P2Y1 receptor proteins. Application of 2meSATP elicited MRS2179-sensitive time- and voltage-dependent inward currents in the interneurons, which depolarized the cell to firing threshold. Also, it increased [Ca2+]i in both astrocytes and interneurons, but, unlike the former effect, the latter was entirely dependent on Ca2+ entry. Thus, in hippocampal slices, in addition to activating A1 receptors of the excitatory terminals after being converted to adenosine, ATP activates P2Y1 receptors in the interneurons, which is linked to activation of unidentified excitatory conductance, through mechanisms distinct from those in the astrocytes.

  14. The orbits of subdwarf B + main-sequence binaries. I. The sdB+G0 system PG 1104+243

    NASA Astrophysics Data System (ADS)

    Vos, J.; Østensen, R. H.; Degroote, P.; De Smedt, K.; Green, E. M.; Heber, U.; Van Winckel, H.; Acke, B.; Bloemen, S.; De Cat, P.; Exter, K.; Lampens, P.; Lombaert, R.; Masseron, T.; Menu, J.; Neyskens, P.; Raskin, G.; Ringat, E.; Rauch, T.; Smolders, K.; Tkachenko, A.

    2012-12-01

    Context. The predicted orbital period histogram of a subdwarf B (sdB) population is bimodal with a peak at short (<10 days) and long (>250 days) periods. Observationally, however, there are many short-period sdB systems known, but only very few long-period sdB binaries are identified. As these predictions are based on poorly understood binary interaction processes, it is of prime importance to confront the predictions to well constrained observational data. We therefore initiated a monitoring program to find and characterize long-period sdB stars. Aims: In this contribution we aim to determine the absolute dimensions of the long-period binary system PG 1104+243 consisting of an sdB and a main-sequence (MS) component, and determine its evolution history. Methods: High-resolution spectroscopy time-series were obtained with HERMES at the Mercator telescope at La Palma, and analyzed to determine the radial velocities of both the sdB and MS components. Photometry from the literature was used to construct the spectral energy distribution (SED) of the binary. Atmosphere models were used to fit this SED and determine the surface gravity and temperature of both components. The gravitational redshift provided an independent confirmation of the surface gravity of the sdB component. Results: An orbital period of 753 ± 3 d and a mass ratio of q = 0.637 ± 0.015 were found for PG 1104+243 from the radial velocity curves. The sdB component has an effective temperature of Teff = 33 500 ± 1200 K and a surface gravity of log g = 5.84 ± 0.08 dex, while the cool companion is found to be a G-type star with Teff = 5930 ± 160 K and log g = 4.29 ± 0.05 dex. When a canonical mass of MsdB = 0.47 M⊙ is assumed, the MS component has a mass of MMS = 0.74 ± 0.07 M⊙, and its temperature corresponds to what is expected for a terminal age main-sequence star with sub-solar metalicity. Conclusions: PG 1104+243 is the first long-period sdB binary in which accurate and consistent physical

  15. Incorporation of learned shape priors into a graph-theoretic approach with application to the 3D segmentation of intraretinal surfaces in SD-OCT volumes of mice

    NASA Astrophysics Data System (ADS)

    Antony, Bhavna J.; Song, Qi; Abràmoff, Michael D.; Sohn, Eliott; Wu, Xiaodong; Garvin, Mona K.

    2014-03-01

    Spectral-domain optical coherence tomography (SD-OCT) finds widespread use clinically for the detection and management of ocular diseases. This non-invasive imaging modality has also begun to find frequent use in research studies involving animals such as mice. Numerous approaches have been proposed for the segmentation of retinal surfaces in SD-OCT images obtained from human subjects; however, the segmentation of retinal surfaces in mice scans is not as well-studied. In this work, we describe a graph-theoretic segmentation approach for the simultaneous segmentation of 10 retinal surfaces in SD-OCT scans of mice that incorporates learned shape priors. We compared the method to a baseline approach that did not incorporate learned shape priors and observed that the overall unsigned border position errors reduced from 3.58 +/- 1.33 μm to 3.20 +/- 0.56 μm.

  16. Control of grain protein contents through SEMIDWARF1 mutant alleles: sd1 increases the grain protein content in Dee-geo-woo-gen but not in Reimei.

    PubMed

    Terao, Tomio; Hirose, Tatsuro

    2015-06-01

    A new possibility for genetic control of the protein content of rice grains was suggested by the allele differences of the SEMIDWARF1 (SD1) mutation. Two quantitative trait loci-qPROT1 and qPROT12-were found on chromosomes 1 and 12, respectively, using backcrossed inbred lines of Sasanishiki/Habataki//Sasanishiki///Sasanishiki. One of them, qPROT1, increased almost all grain proteins instead of only certain proteins in the recessive Habataki allele. Fine mapping of qPROT1 revealed that two gene candidates-Os01g0883800 and Os01g0883900-were included in this region. Os01g0883800 encoded Gibberellin 20 oxidase 2 as well as SD1, the dwarf gene used in the so-called 'Green Revolution'. Mutant analyses as well as sequencing analysis using the semi-dwarf mutant cultivars Dee-geo-woo-gen and Calrose 76 revealed that the sd1 mutant showed significantly higher grain protein contents than their corresponding wild-type cultivars, strongly suggesting that the high protein contents were caused by sd1 mutation. However, the sd1 mutant Reimei did not have high grain protein contents. It is possible to control the grain protein content and column length separately by selecting for sd1 alleles. From this finding, the genetic control of grain protein content, as well as the column length of rice cultivars, might be possible. This ability might be useful to improve rice nutrition, particularly in areas where the introduction of semi-dwarf cultivars is not advanced.

  17. Field Application of SD Bioline Malaria Ag Pf/Pan Rapid Diagnostic Test for Malaria in Greece

    PubMed Central

    Tseroni, Maria; Pervanidou, Danai; Tserkezou, Persefoni; Rachiotis, George; Pinaka, Ourania; Baka, Agoritsa; Georgakopoulou, Theano; Vakali, Annita; Dionysopoulou, Martha; Terzaki, Irene; Marka, Andriani; Detsis, Marios; Evlampidou, Zafiroula; Mpimpa, Anastasia; Vassalou, Evdokia; Tsiodras, Sotirios; Tsakris, Athanasios; Kremastinou, Jenny; Hadjichristodoulou, Christos

    2015-01-01

    Greece, a malaria-free country since 1974, has experienced re-emergence of Plasmodium vivax autochthonous malaria cases in some agriculture areas over the last three years. In early 2012, an integrated control programme (MALWEST Project) was launched in order to prevent re-establishment of the disease. In the context of this project, the rapid diagnostic tests (RDT) of SD Bioline Malaria Ag Pf/Pan that detects hrp-2 and pan-LDH antigens were used. The aim of this study was to assess the field application of the RDT for the P. vivax diagnosis in comparison to light microscopy and polymerase chain reaction (PCR). A total of 955 samples were tested with all three diagnostic tools. Agreement of RDT against microscopy and PCR for the diagnosis of P. vivax was satisfactory (K value: 0.849 and 0.976, respectively). The sensitivity, specificity and positive predictive value of RDT against PCR was 95.6% (95% C.I.: 84.8-99.3), 100% (95% C.I.: 99.6-100.0) and 100% (95% CI: 91.7-100.0) respectively, while the sensitivity, specificity and positive predictive value of RDT against microscopic examination was 97.4% (95% C.I.: 86.1-99.6), 99.4% (95% C.I.: 98.6-99.8) and 86.1% (95% CI: 72.1-94.7), respectively. Our results indicate that RDT performed satisfactory in a non-endemic country and therefore is recommended for malaria diagnosis, especially in areas where health professionals lack experience on light microscopy. PMID:25803815

  18. Quantitative spectral analysis of the sdB star HD 188112: A helium-core white dwarf progenitor

    NASA Astrophysics Data System (ADS)

    Latour, M.; Heber, U.; Irrgang, A.; Schaffenroth, V.; Geier, S.; Hillebrandt, W.; Röpke, F. K.; Taubenberger, S.; Kromer, M.; Fink, M.

    2016-01-01

    Context. HD 188112 is a bright (V = 10.2 mag) hot subdwarf B (sdB) star with a mass too low to ignite core helium burning and is therefore considered a pre-extremely low-mass (ELM) white dwarf (WD). ELM WDs (M ≲ 0.3 M⊙) are He-core objects produced by the evolution of compact binary systems. Aims: We present in this paper a detailed abundance analysis of HD 188112 based on high-resolution Hubble Space Telescope (HST) near- and far-ultraviolet spectroscopy. We also constrain the mass of the star's companion. Methods: We use hybrid non-LTE model atmospheres to fit the observed spectral lines, and to derive the abundances of more than a dozen elements and the rotational broadening of metallic lines. Results: We confirm the previous binary system parameters by combining radial velocities measured in our UV spectra with the previously published values. The system has a period of 0.60658584 days and a WD companion with M ≥ 0.70 M⊙. By assuming a tidally locked rotation combined with the projected rotational velocity (v sin i = 7.9 ± 0.3 km s-1), we constrain the companion mass to be between 0.9 and 1.3 M⊙. We further discuss the future evolution of the system as a potential progenitor of an underluminous type Ia supernova. We measure abundances for Mg, Al, Si, P, S, Ca, Ti, Cr, Mn, Fe, Ni, and Zn, and for the trans-iron elements Ga, Sn, and Pb. In addition, we derive upper limits for the C, N, O elements and find HD 188112 to be strongly depleted in carbon. We find evidence of non-LTE effects on the line strength of some ionic species such as Si ii and Ni ii. The metallic abundances indicate that the star is metal-poor, with an abundance pattern most likely produced by diffusion effects.

  19. Nano-hydroxyapatite particles induce apoptosis on MC3T3-E1 cells and tissue cells in SD rats

    NASA Astrophysics Data System (ADS)

    Wang, Liting; Zhou, Gang; Liu, Haifeng; Niu, Xufeng; Han, Jingyun; Zheng, Lisha; Fan, Yubo

    2012-04-01

    While the advantages of nanomaterials are being increasingly recognized, their potential toxicity is drawing more and more attention and concern. In this study, we explore the toxicity mechanism of 20-30 nm rod-shaped hydroxyapatite (HA) nanoparticles in vitro and in vivo. The nanoparticles were prepared by precipitation and characterized by IR, XRD and TEM. Concentrations of 0 μg mL-1, 10 μg mL-1, 100 μg mL-1, 1 mg mL-1, and 10 mg mL-1 were applied to the MC3T3-E1 cells for viability (MTT-test). Based on the characteristic differences of the two methods of cell death, the morphological features of the MC3T3-E1 cell line co-cultured with nano-hydroxyapatite (n-HA) (10 mg mL-1) for 24 h were also observed by TEM. Furthermore, important serum biochemical markers and histopathological examinations were used to evaluate the potential toxicological effect of n-HA on the major organs of SD rats injected intraperitoneally with n-HA (33.3 mg kg-1 body weight). In the results, we found cell growth inhibition and apoptosis in MC3T3-E1 cells co-cultured with n-HA. Moreover, apoptosis but not necrosis was illustrated in liver and renal tissue by using histopathology slices and serum biochemical markers. It suggests that apoptosis may be the possible mechanism of n-HA toxicity and provides a better understanding of the biocompatibility of nanomaterials applied in human bone repair.

  20. Plasma Intermedin Level Indicates Severity and Treatment Efficacy of Septic Shock in Sprague-Dawley (SD) Rats

    PubMed Central

    Yang, Su-Xian; Chen, Yun-Xiu; Xu, Jing; Yang, Zhao-Hui

    2016-01-01

    Background The aim of this study was to investigate the value of plasma intermedin (IMD) in assessing severity and treatment efficacy of septic shock. Material/Methods Healthy male Sprague-Dawley (SD) rats were chosen and divided into a normal control group (n=15) and a shock model group (n=27) that received intravenous injection of lipopolysaccharide (LPS). Then, 3 specimens were taken from each group. The shock model group rats were divided into an LPS group and a treatment group with 12 rats each. The treatment group received intravenous injection of compound sodium lactate solution. Plasma IMD and IMD1-47 mRNA expressions were compared and analyzed. Results Mean arterial pressure (MAP) was lower while white blood cell count and TNF-α were higher in the shock model group than in the normal control group (P<0.05). After 10 h and 20 h, the treatment group had lower plasma IMD and IMD1-47 mRNA expressions compared with the LPS group (P<0.05). Plasma IMD and IMD1-47 mRNA expressions in the LPS group after 20 h were significantly higher than after 10 h (P<0.05). IMD was positively correlated with interleukins (IL-3, IL-6, and IL-8), white blood cell count, and body temperature (all P<0.05), but were negatively correlated with systolic pressure (r=−0.8474, P=0.0040). Conclusions Plasma IMD level can effectively reflect the severity of septic shock and can be used as an important indicator of septic shock treatment effectiveness. PMID:27999422

  1. Effect of Cage Space on Behavior and Reproduction in Crl:CD(SD) and BN/Crl Laboratory Rats.

    PubMed

    Gaskill, Brianna N; Pritchett-Corning, Kathleen R

    2015-09-01

    The 2011 Guide for the Care and Use of Laboratory Animals contains recommendations regarding the amount of cage space for mothers with litters. Literature on cage-space use in breeding rats is sparse. We hypothesized that, if present, differences in behavior and reproduction would be detected between the smallest and largest cages tested. BN/Crl and Crl:CD(SD) rats were assigned to a cage treatment (580 cm(2), 758 cm(2), 903 cm(2), or 1355 cm(2)) and breeding configuration (single: male removed after birth of pups; pair: 1 male, 1 female) in a factorial design for 12 wk. All cages received 20 to 25 g of nesting material, and nests were scored weekly. Pups were weaned, sexed, and weighed between postnatal days 18 and 26. Adult behavior and location in the cage were videorecorded by scan-sampling on the litter's postnatal days 0 through 8 and 14 through 21. Press posture in adults and play behavior in pups were recorded according to a 1-0 sampling method. Differences in reproductive parameters were limited to expected differences related to rat genetic background and weaning weight in pups, which was lowest in the pair-bred CD rats in the smallest cages. Press posture in adults in the smaller cages increased as the pups became mobile. Pair-housed outbred rats in the smallest commercially available cage we tested showed behavioral changes and a lower pup weaning weight. Both laboratory animal scientists and caging manufacturers should address the challenge of providing more biologically relevant cage complexity rather than merely increasing floor space.

  2. Nucleotide P2Y13-stimulated phosphorylation of CREB is required for ADP-induced proliferation of late developing retinal glial progenitors in culture.

    PubMed

    Jacques, Flavia Jesus; Silva, Thayane Martins; da Silva, Flavia Emenegilda; Ornelas, Isis Moraes; Ventura, Ana Lucia Marques

    2017-03-24

    Nucleotides stimulate phosphorylation of CREB to induce cell proliferation and survival in diverse cell types. We report here that ADP induces the phosphorylation of CREB in a time- and concentration-dependent manner in chick embryo retinal progenitors in culture. ADP-induced increase in phospho-CREB is mediated by P2 receptors as it is blocked by PPADS but not by the adenosine antagonists DPCPX or ZM241385. Incubation of the cultures with the CREB inhibitor KG-501 prevents ADP-induced incorporation of [(3)H]-thymidine, indicating that CREB is involved in retinal cell proliferation. No effect of this compound is observed on the viability of retinal progenitors. While no significant increase in CREB phosphorylation is observed with the P2Y1 receptor agonist MRS2365, ADP-induced phosphorylation of CREB is blocked by the P2Y13 receptor selective antagonist MRS2211, but not by MRS2179 or PSB0739, two antagonists of the P2Y1 and P2Y12 receptors, respectively, suggesting that ADP-induced CREB phosphorylation is mediated by P2Y13 receptors. ADP-induced increase in phospho-CREB is attenuated by the PI3K inhibitor LY241385 and completely prevented by the MEK inhibitor U0126, suggesting that at least ERK is involved in ADP-induced CREB phosphorylation. A pharmacological profile similar to the activation and inhibition of CREB phosphorylation is observed in the phosphorylation of ERK, suggesting that P2Y13 receptors mediate ADP induced ERK/CREB pathway in the cultures. While no increase in [(3)H]-thymidine incorporation is observed with the P2Y1 receptor agonist MRS2365, both MRS2179 and MRS2211 prevent ADP-mediated increase in [(3)H]-thymidine incorporation, but not progenitor's survival, suggesting that both P2Y1 and P2Y13 receptor subtypes are involved in ADP-induced cell proliferation. P2Y1 receptor-mediated increase in [Ca(2+)]i is observed in glial cells only when cultures maintained for 9days are used. In glia from cultures cultivated for only 2days, no increase in [Ca

  3. Molecular characterization and specific detection of Anaplasma species (AP-sd) in sika deer and its first detection in wild brown bears and rodents in Hokkaido, Japan.

    PubMed

    Moustafa, Mohamed Abdallah Mohamed; Lee, Kyunglee; Taylor, Kyle; Nakao, Ryo; Sashika, Mariko; Shimozuru, Michito; Tsubota, Toshio

    2015-12-01

    A previously undescribed Anaplasma species (herein referred to as AP-sd) has been detected in sika deer, cattle and ticks in Japan. Despite being highly similar to some strains of A. phagocytophilum, AP-sd has never been detected in humans. Its ambiguous epidemiology and the lack of tools for its specific detection make it difficult to understand and interpret the prevalence of this Anaplasma species. We developed a method for specific detection, and examined AP-sd prevalence in Hokkaido wildlife. Our study included 250 sika deer (Cervus nippon yesoensis), 13 brown bears (Ursus arctos yesoensis) and 252 rodents including 138 (Apodemus speciosus), 45 (Apodemus argenteus), 42 (Myodes rufocanus) and 27 (Myodes rutilus) were collected from Hokkaido island, northern Japan, collected during 2010 to 2015. A 770 bp and 382 bp segment of the 16S rRNA and gltA genes, respectively, were amplified by nested PCR. Results were confirmed by cloning and sequencing of the positive PCR products. A reverse line blot hybridization (RLB) based on the 16S rRNA gene was then developed for the specific detection of AP-sd. The prevalence of AP-sd by nested PCR in sika deer was 51% (128/250). We detected this Anaplasma sp. for the first time in wild brown bears and rodents with a prevalence of 15% (2/13) and 2.4% (6/252), respectively. The sequencing results of the 16S rRNA and gltA gene amplicons were divergent from the selected A. phagocytophilum sequences in GenBank. Using a newly designed AP-sd specific probe for RLB has enabled us to specifically detect this Anaplasma species. Besides sika deer and cattle, wild brown bears and rodents were identified as potential reservoir hosts for AP-sd. This study provided a high throughput molecular method that specifically detects AP-sd, and which can be used to investigate its ecology and its potential as a threat to humans in Japan.

  4. Raman spectroscopy of K x Co2-y Se2 single crystals near the ferromagnet-paramagnet transition

    NASA Astrophysics Data System (ADS)

    Opačić, M.; Lazarević, N.; Radonjić, M. M.; Šćepanović, M.; Ryu, Hyejin; Wang, Aifeng; Tanasković, D.; Petrovic, C.; Popović, Z. V.

    2016-12-01

    Polarized Raman scattering spectra of the K x Co2-y Se2 single crystals reveal the presence of two phonon modes, assigned as of the A 1g and B 1g symmetry. The absence of additional modes excludes the possibility of vacancy ordering, unlike in K x Fe2-y Se2. The ferromagnetic (FM) phase transition at {{T}\\text{c}}≈ 74 K leaves a clear fingerprint on the temperature dependence of the Raman mode energy and linewidth. For T>{{T}\\text{c}} the temperature dependence looks conventional, driven by the thermal expansion and anharmonicity. The Raman modes are rather broad due to the electron-phonon coupling increased by the disorder and spin fluctuation effects. In the FM phase the phonon frequency of both modes increases, while an opposite trend is seen in their linewidth: the A 1g mode narrows in the FM phase, whereas the B 1g mode broadens. We argue that the large asymmetry and anomalous frequency shift of the B 1g mode is due to the coupling of spin fluctuations and vibration. Our density functional theory (DFT) calculations for the phonon frequencies agree rather well with the Raman measurements, with some discrepancy being expected since the DFT calculations neglect the spin fluctuations.

  5. Diurnal dynamic behavior of microglia in response to infected bacteria through the UDP-P2Y6 receptor system

    PubMed Central

    Takayama, Fumiko; Hayashi, Yoshinori; Wu, Zhou; Liu, Yicong; Nakanishi, Hiroshi

    2016-01-01

    It has long been believed that microglia morphologically transform into the activated state by retracting their long processes and consuming pathogens when bacteria infect into the brain parenchyma. In the present study, however, we showed for the first time that murine cortical microglia extend their processes towards focally injected Porphyromonas gingivalis. This P. gingivalis-induced microglial process extension was significantly increased during the light (sleeping) phase than the dark (waking) phase. In contrast, focally injected ATP-induced microglial process extension was significantly increased during the dark phase than the light phase. Furthermore, in contrast to the P2Y12 receptor-mediated mechanism of ATP-induced microglial process extension, the P. gingivalis-mediated microglial process extension was mediated by P2Y6 receptors. The infection of bacteria such as P. gingivalis to the brain parenchyma may induce the secretion of UDP from microglia at the site of infection, which in turn induces the process extension of the neighboring microglia. PMID:27445174

  6. Raman spectroscopy of KxCo2-ySe2 single crystals near the ferromagnet-paramagnet transition

    DOE PAGES

    Opacic, M.; Lazarevic, N.; Radonjic, M. M.; ...

    2016-10-05

    Polarized Raman scattering spectra of the KxCo2-ySe2 (x = :::; y = :::) single crystals reveal the presence of two phonon modes, assigned as of the A1g and B1g symmetry. Absence of additional modes excludes the possibility of vacancy ordering, unlike in KxCo2-ySe2 . The ferromagnetic (FM) phase transition at Tc 74 K leaves a clear fingerprint on the temperature dependence of the Raman mode energy and linewidth. For T > Tc the temperature dependence looks conventional, driven by the thermal expansion and anharmonicity. The Raman modes are rather broad due to the electron-phonon coupling increased by the disorder andmore » spin fluctuation e ects. In the FM phase the phonon frequency of both modes increases, while an opposite trend is seen in their linewidth: the A1g mode narrows in the FM phase, whereas the B1g mode broadens. We argue that the large asymmetry and anomalous frequency shift of the B1g mode is due to the coupling of spin fluctuations and vibration. Our density functional theory (DFT) calculations for the phonon frequencies agree rather well with the Raman measurements, with some discrepancy being expected since the DFT calculations neglect the spin fluctuations.« less

  7. Raman spectroscopy of KxCo2-ySe2 single crystals near the ferromagnet-paramagnet transition

    SciTech Connect

    Opacic, M.; Lazarevic, N.; Radonjic, M. M.; Scepanovic, M.; Ryu, Hyejin; Wang, Aifeng; Tanaskovic, D.; Petrovic, C.; Popovic, Z. V.

    2016-10-05

    Polarized Raman scattering spectra of the KxCo2-ySe2 (x = :::; y = :::) single crystals reveal the presence of two phonon modes, assigned as of the A1g and B1g symmetry. Absence of additional modes excludes the possibility of vacancy ordering, unlike in KxCo2-ySe2 . The ferromagnetic (FM) phase transition at Tc 74 K leaves a clear fingerprint on the temperature dependence of the Raman mode energy and linewidth. For T > Tc the temperature dependence looks conventional, driven by the thermal expansion and anharmonicity. The Raman modes are rather broad due to the electron-phonon coupling increased by the disorder and spin fluctuation e ects. In the FM phase the phonon frequency of both modes increases, while an opposite trend is seen in their linewidth: the A1g mode narrows in the FM phase, whereas the B1g mode broadens. We argue that the large asymmetry and anomalous frequency shift of the B1g mode is due to the coupling of spin fluctuations and vibration. Our density functional theory (DFT) calculations for the phonon frequencies agree rather well with the Raman measurements, with some discrepancy being expected since the DFT calculations neglect the spin fluctuations.

  8. Structure and phase composition of nanocrystalline Ce{sub 1-x}Lu{sub x}O{sub 2-y}

    SciTech Connect

    Malecka, Malgorzata A.; Kepinski, Leszek Maczka, Miroslaw

    2008-09-15

    The microstructure and phase stability of nanocrystalline mixed oxide Lu{sub x}Ce{sub 1-x}O{sub 2-y} (x=0-1) are described. Nano-sized (3-4 nm) oxide particles were prepared by the reverse microemulsion method. Morphological and structural changes upon heat treatment in an oxidizing atmosphere were studied by transmission electron microscopy (TEM), X-ray diffraction (XRD), Raman and Yb{sup 3+} emission spectroscopy, the latter ion being present as an impurity in the Lu{sub 2}O{sub 3} starting material. Up to 950 deg. C, the samples were single phase, with structure changing smoothly with Lu content from fluorite type (F) to bixbyite type (C). For the samples heated at 1100 deg. C phase separation into coexisting F- and C-type structures was observed for 0.352-y} mixed oxide heated in air at 1100 deg. C.

  9. Nucleoside 5′-O-monophosphorothioates as modulators of the P2Y14 receptor and mast cell degranulation

    PubMed Central

    Gendaszewska-Darmach, Edyta; Węgłowska, Edyta; Walczak-Drzewiecka, Aurelia; Karaś, Kaja

    2016-01-01

    Mast cells (MCs) are long-lived resident cells known for their substantial role in antigen-induced anaphylaxis and other immunoglobulin E-mediated allergic reactions as well as tumor promotion. MCs' activation results in the release of pro-inflammatory factors such as histamine, tryptase, tumor necrosis factor or carboxypeptidase A stored in secretory granules. IgE-dependent hypersensitivity has been thought to be the major pathway mediating degranulation of mast cells, but the P2Y14 nucleotide receptor activated by UDP-glucose (UDPG) may also enhance this process. In this study we identified thymidine 5'-O-monophosphorothioate (TMPS) as a molecule inhibiting UDPG-induced degranulation in a rat mast cell line (RBL-2H3). Additionally, TMPS diminished UDPG-evoked intracellular calcium mobilization in a stable HEK293T cell line overexpressing the P2Y14 receptor. Therefore, we demonstrate that the use of thymidine 5'-O-monophosphorothioate might be a novel anti-inflammatory approach based on preventingmast cell activation. PMID:27732965

  10. Investigation of surface defect states in CeO{sub 2-y} nanocrystals by Scanning−tunneling microscopy/spectroscopy and ellipsometry

    SciTech Connect

    Radović, Marko; Stojadinović, Bojan; Tomić, Nataša; Golubović, Aleksandar; Dohčević-Mitrović, Zorana; Matović, Branko; Veljković, Ivana

    2014-12-21

    Synthesis process strongly influences the nanocrystalline CeO{sub 2-y} defective structure. The presence of surface defects, in the form of oxygen vacancies in different charge states (F centers), can change the electronic properties of ceria nanocrystals. Nanocrystalline CeO{sub 2-y} samples were synthesized using three different methods (precipitation, self-propagating room temperature, and hydrothermal synthesis). Raman spectroscopy was used to identify the presence of oxygen vacancies which presumably were formed at the nanoparticle surface. The defect concentration depended on the crystallite size of differently prepared CeO{sub 2-y} samples. Scanning tunneling microscopy/spectroscopy and ellipsometry were employed to investigate the electronic band structure of defective CeO{sub 2-y} nanocrystals. Scanning tunneling spectroscopy measurements demonstrated that inside the band gap of CeO{sub 2-y} nanocrystals, besides the filled 4 f states, appeared additional states which were related to occupied and empty F center defect states. From the ellipsometric measurements, using the critical points model, the energy positions of different F centers states and the values of the reduced band gap energies were determined. The analysis of obtained data pointed out that depending on the synthesis method, different types of F centers (F{sup +} and F{sup 0}) can be formed in the CeO{sub 2-y} nanocrystals. The formation of different F center defect states inside the ceria gap have a strong impact on the electrical, optical, and magnetic properties of ceria nanocrystals.

  11. Towards understanding the rate capability of layered transition metal oxides LiNiyMnyCo1-2yO2

    NASA Astrophysics Data System (ADS)

    Li, Zheng; Ban, Chunmei; Chernova, Natasha A.; Wu, Zhuangchun; Upreti, Shailesh; Dillon, Anne; Whittingham, M. Stanley

    2014-12-01

    This work attempts to understand the rate capability of layered transition metal oxides LiNiyMnyCo1-2yO2 (0.33 ≤ y ≤ 0.5). The rate capability of LiNiyMnyCo1-2yO2 increase with increasing Co in the compounds and with increasing amount of carbon additives in the electrodes. The lithium diffusion coefficients and electronic conductivities of LixNiyMnyCo1-2yO2 are investigated and compared. The 333 compound has higher diffusivity and electronic conductivity and thus better rate performance than 550. Chemical diffusion coefficients for both delithiation and lithiation of LixNiyMnyCo1-2yO2 investigated by GITT and PITT experiments are calculated to be around 10-10 cm2 s-1, lower than that of LixCoO2. The electronic conductivity of LixNiyMnyCo1-2yO2 is inferior compared to LixCoO2 at same temperature and delithiation stage. However, the LixNiyMnyCo1-2yO2 are able to deliver 55%-80% of theoretical capacity at 5 C with good electronic wiring in the composite electrode that make them very promising candidates for electric propulsion in terms of rate capability.

  12. Investigation of surface defect states in CeO2-y nanocrystals by Scanning-tunneling microscopy/spectroscopy and ellipsometry

    NASA Astrophysics Data System (ADS)

    Radović, Marko; Stojadinović, Bojan; Tomić, Nataša; Golubović, Aleksandar; Matović, Branko; Veljković, Ivana; Dohčević-Mitrović, Zorana

    2014-12-01

    Synthesis process strongly influences the nanocrystalline CeO2-y defective structure. The presence of surface defects, in the form of oxygen vacancies in different charge states (F centers), can change the electronic properties of ceria nanocrystals. Nanocrystalline CeO2-y samples were synthesized using three different methods (precipitation, self-propagating room temperature, and hydrothermal synthesis). Raman spectroscopy was used to identify the presence of oxygen vacancies which presumably were formed at the nanoparticle surface. The defect concentration depended on the crystallite size of differently prepared CeO2-y samples. Scanning tunneling microscopy/spectroscopy and ellipsometry were employed to investigate the electronic band structure of defective CeO2-y nanocrystals. Scanning tunneling spectroscopy measurements demonstrated that inside the band gap of CeO2-y nanocrystals, besides the filled 4 f states, appeared additional states which were related to occupied and empty F center defect states. From the ellipsometric measurements, using the critical points model, the energy positions of different F centers states and the values of the reduced band gap energies were determined. The analysis of obtained data pointed out that depending on the synthesis method, different types of F centers (F+ and F0) can be formed in the CeO2-y nanocrystals. The formation of different F center defect states inside the ceria gap have a strong impact on the electrical, optical, and magnetic properties of ceria nanocrystals.

  13. Rescue of Cyclic AMP Mediated Long Term Potentiation Impairment in the Hippocampus of Mecp2 Knockout (Mecp2(-/y) ) Mice by Rolipram.

    PubMed

    Balakrishnan, Saju; Niebert, Marcus; Richter, Diethelm W

    2016-01-01

    Rett syndrome (RTT) patients experience learning difficulties and memory loss. Analogous deficits of hippocampal plasticity are reported in mouse models of RTT. To elucidate the underlying pathophysiology, we studied long term potentiation (LTP) at the CA3 to CA1 synapses in the hippocampus in acute brain slices from WT and Mecp2(-/y) mice, by either activating cAMP dependent pathway or using high frequency stimulation, by means of patch clamp. We have observed that, the NMDA channel current characteristics remain unchanged in the Mecp2(-/y) mice. The adenylyl cyclase (AC) agonist forskolin evoked a long lasting potentiation of evoked EPSCs in WT CA1 neurons, but only minimally enhanced the EPSCs in the Mecp2(-/y) mice. This weaker potentiation in Mecp2 (-/) (y) mice was ameliorated by application of phosphodiesterase 4 inhibitor rolipram. The hyperpolarization activated cyclic nucleotide gated channel current (I h) was potentiated to similar extent by forskolin in both phenotypes. Multiple tetanus induced cAMP-dependent plasticity was also impaired in the Mecp2 (-/) (y) mice, and was also partially rescued by rolipram. Western blot analysis of CA region of Mecp2 (-/) (y) mice hippocampus revealed more than twofold up-regulation of protein kinase A (PKA) regulatory subunits, while the expression of the catalytic subunit remained unchanged. We hypothesize that the overexpressed PKA regulatory subunits buffer cAMP and restrict the PKA mediated phosphorylation of target proteins necessary for LTP. Blocking the degradation of cAMP, thereby saturating the regulatory subunits alleviated this defect.

  14. The temporal spectrum of the sdB pulsating star HS 2201+2610 at 2 ms resolution

    NASA Astrophysics Data System (ADS)

    Silvotti, R.; Janulis, R.; Schuh, S. L.; Charpinet, S.; Oswalt, T.; Silvestri, N.; Gonzalez Perez, J. M.; Kalytis, R.; Meištas, E.; Ališauskas, D.; Marinoni, S.; Jiang, X. J.; Reed, M. D.; Riddle, R. L.; Bernabei, S.; Heber, U.; Bärnbantner, O.; Cordes, O.; Dreizler, S.; Goehler, E.; Østensen, R.; Bochanski, J.; Carlson, G.

    2002-07-01

    In this article we present the results of more than 180 hours of time-series photometry on the low gravity (log g=5.4, Teff=29 300 K, log He/H=-3.0 by number) sdB pulsating star HS 2201+2610, obtained between September 2000 and August 2001. The temporal spectrum is resolved and shows 5 close frequencies: three main signals at 2860.94, 2824.10 and 2880.69 mu Hz, with amplitudes of about 1%, 0.5% and 0.1% respectively, are detected from single run observations; two further peaks with very low amplitude (<0.07%) at 2738.01 and 2921.82 mu Hz are confirmed by phase analysis on several independent runs. Due to the small number of detected frequencies, it is not possible to obtain a univocal identification of the excited modes and perform a detailed seismological analysis of the star. No clear signatures of rotational splitting are seen. Nevertheless, the observed period spectrum is well inside the excited period window obtained from pulsation calculations with nonadiabatic models having effective temperature and surface gravity close to the spectroscopic estimates. Due to its relatively simple temporal spectrum, HS 2201+2610 is a very good candidate for trying to measure the secular variation of the pulsation periods in time. With this purpose a long-term monitoring of the star was started. The results of the first 11 months show amplitude variations up to ~ 20% on time-scales of months, which are probably real, and allow us to measure the pulsation frequencies with an unprecedented 0.02 mu Hz resolution. Based on observations obtained at the following telescopes: Loiano 1.5 m (Bologna Astronomical Observatory), Moletai 1.65 m (Institute of Theoretical Physics and Astronomy, Vilnius), Calar Alto 2.2 and 1.2 m (German-Spanish Astronomical Center operated by the Max-Plank-Institute für Astronomie Heidelberg jointly with the Spanish National Commission for Astronomy), SARA 0.9 m (Southeastern Association for Research in Astronomy, at Kitt Peak, Arizona), Tenerife 0.8 m

  15. How to predict return to work after lumbar discectomy: answers from the NeuroPoint-SD registry.

    PubMed

    Than, Khoi D; Curran, Jill N; Resnick, Daniel K; Shaffrey, Christopher I; Ghogawala, Zoher; Mummaneni, Praveen V

    2016-08-01

    OBJECTIVE To date, the factors that predict whether a patient returns to work after lumbar discectomy are poorly understood. Information on postoperative work status is important in analyzing the cost-effectiveness of the procedure. METHODS An observational prospective cohort study was completed at 13 academic and community sites (NeuroPoint-Spinal Disorders [NeuroPoint-SD] registry). Patients undergoing single-level lumbar discectomy were included. Variables assessed included age, sex, body mass index (BMI), SF-36 physical function score, Oswestry Disability Index (ODI) score, presence of diabetes, smoking status, systemic illness, workers' compensation status, and preoperative work status. The primary outcome was working status within 3 months after surgery. Stepwise logistic regression analysis was performed to determine which factors were predictive of return to work at 3 months following discectomy. RESULTS There were 127 patients (of 148 total) with data collected 3 months postoperatively. The patients' average age at the time of surgery was 46 ± 1 years, and 66.9% of patients were working 3 months postoperatively. Statistical analyses demonstrated that the patients more likely to return to work were those of younger age (44.5 years vs 50.5 years, p = 0.008), males (55.3% vs 28.6%, p = 0.005), those with higher preoperative SF-36 physical function scores (44.0 vs 30.3, p = 0.002), those with lower preoperative ODI scores (43.8 vs 52.6, p = 0.01), nonsmokers (83.5% vs 66.7%, p = 0.03), and those who were working preoperatively (91.8% vs 26.2%, p < 0.0001). When controlling for patients who were working preoperatively (105 patients), only age was a statistically significant predictor of postoperative return to work (44.1 years vs 51.1 years, p = 0.049). CONCLUSIONS In this cohort of lumbar discectomy patients, preoperative working status was the strongest predictor of postoperative working status 3 months after surgery. Younger age was also a predictor

  16. DIAGNOSTIC PERFORMANCE EVALUATION OF THE SD BIOLINE MALARIA ANTIGEN AG PF/PAN TEST (05FK60) IN A MALARIA ENDEMIC AREA OF SOUTHERN ETHIOPIA

    PubMed Central

    TADESSE, Endale; WORKALEMAHU, Bereket; SHIMELIS, Techalew

    2016-01-01

    SUMMARY Rapid diagnostic tests (RDTs) capable of detecting and differentiating Plasmodium species are needed in areas in which microscopy is unsuitable. This study was conducted to assess the diagnostic performance of the rapid test kit - SD BIOLINE Malaria Ag Pf/Pan(r) (05FK60) in an endemic area. Microscopy of Giemsa-stained blood films were performed to detect and estimate the Plasmodium density in malaria suspected patients. The performance of the SD BIOLINE Malaria Ag Pf/Pan test was evaluated using 272 Plasmodium-positive and 102 negative blood samples. The overall sensitivity of the SD BIOLINE Malaria Ag Pf/Pan test was 99.5% for P. falciparum and 92.6% for non-P. falciparum malaria infections. The respective specificity, PPV, and NPV of the test were 98.0, 98.4, and 99.0% for the diagnosis of P. falciparum, and 100.0 %, 100.0%, and 94.4% for non-P. falciparum species. The SD BIOLINE Malaria Ag Pf/Pan test showed an excellent performance in diagnosing Plasmodium infections in an endemic setting. Therefore, this point-of-care test could be used as an alternative to microscopy in places where P. falciparum is endemic and microscopy is unsuitable. PMID:27680164

  17. [Isolation, culture and identification of adipose-derived stem cells from SD rat adipose tissues subjected to long-term cryopreservation].

    PubMed

    Liu, Qin; Wang, Liping; Chen, Fang; Zhang, Yi

    2017-02-01

    Objective To study the feasibility of isolation and culture of adipose-derived stem cells (ADSCs) from SD rat adipose tissues subjected to long-term cryopreservation. Methods We took inguinal fat pads from healthy SD rats. Adipose tissues were stored with 100 mL/L dimethyl sulfoxide (DMSO) combined with 900 mL/L fetal bovine serum (FBS) in liquid nitrogen. Three months later, the adipose tissues were resuscitated for the isolation and culture of ADSCs. The growth status and morphology were observed. The growth curve and cell surface markers CD29, CD45, CD90 of the 3rd passage cells were analyzed respectively by CCK-8 assay and immunocytochemistry. The 3rd passage cells were induced towards adipogenic lineages and osteogenic lineages by different inducers, and the resulting cells were examined separately by oil red O staining and alizarin red staining. Results The ADSCs obtained from SD rat adipose tissues subjected to long-term cryopreservation showed a spindle-shape appearance and had a good proliferation ability. The cell growth curve was typical "S" curve. Immunocytochemistry showed that the 3rd passage cells were positive for CD29 and CD90, while negative for CD45. The cells were positive for oil red O staining after adipogenic induction, and also positive for alizarin red staining after osteogenic induction. Conclusion The ADSCs can be isolated from SD rat adipose tissues subjected to long-term cryopreservation.

  18. Detailed Morphological Changes of Foveoschisis in Patient with X-Linked Retinoschisis Detected by SD-OCT and Adaptive Optics Fundus Camera

    PubMed Central

    Akeo, Keiichiro; Kameya, Shuhei; Gocho, Kiyoko; Kubota, Daiki; Yamaki, Kunihiko; Takahashi, Hiroshi

    2015-01-01

    Purpose. To report the morphological and functional changes associated with a regression of foveoschisis in a patient with X-linked retinoschisis (XLRS). Methods. A 42-year-old man with XLRS underwent genetic analysis and detailed ophthalmic examinations. Functional assessments included best-corrected visual acuity (BCVA), full-field electroretinograms (ERGs), and multifocal ERGs (mfERGs). Morphological assessments included fundus photography, spectral-domain optical coherence tomography (SD-OCT), and adaptive optics (AO) fundus imaging. After the baseline clinical data were obtained, topical dorzolamide was applied to the patient. The patient was followed for 24 months. Results. A reported RS1 gene mutation was found (P203L) in the patient. At the baseline, his decimal BCVA was 0.15 in the right and 0.3 in the left eye. Fundus photographs showed bilateral spoke wheel-appearing maculopathy. SD-OCT confirmed the foveoschisis in the left eye. The AO images of the left eye showed spoke wheel retinal folds, and the folds were thinner than those in fundus photographs. During the follow-up period, the foveal thickness in the SD-OCT images and the number of retinal folds in the AO images were reduced. Conclusions. We have presented the detailed morphological changes of foveoschisis in a patient with XLRS detected by SD-OCT and AO fundus camera. However, the findings do not indicate whether the changes were influenced by topical dorzolamide or the natural history. PMID:26356828

  19. EFFECTS OF 20 WEEK EXPOSURES IN FEMALE SPRAGUE-DAWLEY (S-D) RATS TO THE DRINKING WATER DISINFECTION BY-PRODUCT DIBROMOACETIC ACID

    EPA Science Inventory

    Effects of 20 week exposures in female Sprague-Dawley (S-D) rats to the drinking water disinfection by-product dibromoacetic acid. A S Murr and J M Goldman, Endocrinol. Br., RTD, NHEERL, ORD, US EPA, Res. Tri. Pk, NC. Sponsor: Audrey Cummings

    The drinking water disinfect...

  20. EFFECTS OF 20 WEEK EXPOSURES IN FEMALE SPRAGUE-DAWLEY (S-D) RATS TO DIBROMOACETIC ACID, A DRINKING WATER DISINFECTANT BY-PRODUCT

    EPA Science Inventory

    Effects of 20 week exposures in female Sprague-Dawley (S-D) rats to the drinking water disinfection by-product dibromoacetic acid. A S Murr and J M Goldman, Endocrinol. Br., RTD, NHEERL, ORD, US EPA, Res. Tri. Pk, NC. Sponsor: Audrey Cummings

    The drinking water disinfect...

  1. Planning and implementation of the on-comet operations of the instrument SD2 onboard the lander Philae of Rosetta mission

    NASA Astrophysics Data System (ADS)

    Di Lizia, P.; Bernelli-Zazzera, F.; Ercoli-Finzi, A.; Mottola, S.; Fantinati, C.; Remetean, E.; Dolives, B.

    2016-08-01

    The lander Philae of the Rosetta mission landed on the surface of the comet 67 P/Churyumov-Gerasimenko on November 12, 2014. Among the specific subsystems and instruments carried on Philae, the sampling, drilling and distribution (SD2) subsystem had the role of providing in-situ operations devoted to soil drilling, sample collection, and their distribution to three scientific instruments. After landing, a first sequence of scientific activities was carried out, relying mainly on the energy stored in the lander primary battery. Due to the limited duration and the communication delay, these activities had to be carried out automatically, with a limited possibility of developing and uploading commands from the ground. Philae's landing was not nominal and SD2 was operated in unexpected conditions: the lander was not anchored to the soil and leant on the comet surface shakily. Nevertheless, one sampling procedure was attempted. This paper provides an overview of SD2 operation planning and on-comet operations, and analyses SD2 achievements during the first science sequence of Philae's on-comet operations.

  2. Thermal and mechanical stability, electronic structure and energetic properties of Pu-containing pyrochlores: La2-yPuyZr2O7 and La2Zr2-yPuyO7 (0 ≤ y ≤ 2)

    NASA Astrophysics Data System (ADS)

    Xiao, H. Y.; Jiang, M.; Zhao, F. A.; Liu, Z. J.; Zu, X. T.

    2015-11-01

    Density functional theory calculations have been carried out to study Pu accommodation in La2Zr2O7. Our calculations show that Pu can be incorporated into both the La and Zr lattice sites in La2Zr2O7, which agrees well with the recent experimental observations. As Pu substitutes for the Zr-site, the interaction is stronger than that in La2-yPuyZr2O7 and the mechanical properties are influenced significantly. Also, it is found that order-disorder transition occurs more easily in Pu-containing La2Zr2O7 than the pure zirconate, suggesting that the radiation tolerance of La2Zr2O7 can be enhanced by Pu incorporation.

  3. Automated geographic atrophy segmentation for SD-OCT images using region-based C-V model via local similarity factor.

    PubMed

    Niu, Sijie; de Sisternes, Luis; Chen, Qiang; Leng, Theodore; Rubin, Daniel L

    2016-02-01

    Age-related macular degeneration (AMD) is the leading cause of blindness among elderly individuals. Geographic atrophy (GA) is a phenotypic manifestation of the advanced stages of non-exudative AMD. Determination of GA extent in SD-OCT scans allows the quantification of GA-related features, such as radius or area, which could be of important value to monitor AMD progression and possibly identify regions of future GA involvement. The purpose of this work is to develop an automated algorithm to segment GA regions in SD-OCT images. An en face GA fundus image is generated by averaging the axial intensity within an automatically detected sub-volume of the three dimensional SD-OCT data, where an initial coarse GA region is estimated by an iterative threshold segmentation method and an intensity profile set, and subsequently refined by a region-based Chan-Vese model with a local similarity factor. Two image data sets, consisting on 55 SD-OCT scans from twelve eyes in eight patients with GA and 56 SD-OCT scans from 56 eyes in 56 patients with GA, respectively, were utilized to quantitatively evaluate the automated segmentation algorithm. We compared results obtained by the proposed algorithm, manual segmentation by graders, a previously proposed method, and experimental commercial software. When compared to a manually determined gold standard, our algorithm presented a mean overlap ratio (OR) of 81.86% and 70% for the first and second data sets, respectively, while the previously proposed method OR was 72.60% and 65.88% for the first and second data sets, respectively, and the experimental commercial software OR was 62.40% for the second data set.

  4. P2Y(6) agonist uridine 5'-diphosphate promotes host defense against bacterial infection via monocyte chemoattractant protein-1-mediated monocytes/macrophages recruitment.

    PubMed

    Zhang, Zhi; Wang, Ziqiang; Ren, Hua; Yue, Miaomiao; Huang, Kan; Gu, Hongjie; Liu, Mingyao; Du, Bing; Qian, Min

    2011-05-01

    Extracellular nucleotides are important messengers involved in series crucial physiological functions through the activation of P2 purinergic receptors. The detailed function and mechanism of the P2Y family in regulating immune response against invaded pathogens still remains unknown. In this study, the activation of purinoreceptor P2Y(6) by UDP was found to play a crucial role in promoting host defense against invaded bacteria through monocytes/macrophages recruitment. The expression level of P2Y(6) was much higher than other purinoreceptors in RAW264.7 cells, bone marrow macrophages, and peritoneal macrophages determined by real-time PCR. The supernatant of UDP (P2Y(6)-specific agonist)-treated RAW264.7 cells exhibited direct chemotaxis to monocytes/macrophages in vitro through Boyden Chambers assay. Meanwhile, the releasing of MCP-1 (MCP-1/CCL2) was enhanced obviously by UDP both in mRNA and protein level. Furthermore, the activation of P2Y(6) receptor by UDP also promotes ERK phosphorylation and AP-1 activation in a concentration- and time-dependent manner in RAW264.7 cells. This UDP-induced activation could be inhibited by P2Y(6) selectivity antagonist (MRS2578), MEK inhibitor (U0126), and MCP-1 blocking Ab, respectively. Moreover, i.p. injection with UDP resulted in a more efficacious clearance of invaded Escherichia coli and lower mortality in peritonitis mouse model. Together, our studies demonstrate that P2Y(6) receptor could be a novel mediator in upregulating innate immune response against the invaded pathogens through recruiting monocytes/macrophages.

  5. UTP Controls Cell Surface Distribution and Vasomotor Activity of the Human P2Y2 Receptor through an Epidermal Growth Factor Receptor-transregulated Mechanism*

    PubMed Central

    Norambuena, Andrés; Palma, Francisco; Poblete, M. Inés; Donoso, M. Verónica; Pardo, Evelyn; González, Alfonso; Huidobro-Toro, J. Pablo

    2010-01-01

    Extracellular nucleotides transmit signals into the cells through the P2 family of cell surface receptors. These receptors are amply expressed in human blood vessels and participate in vascular tone control; however, their signaling mechanisms remain unknown. Here we show that in smooth muscle cells of isolated human chorionic arteries, the activation of the P2Y2 receptor (P2Y2R) induces not only its partition into membrane rafts but also its rapid internalization. Cholesterol depletion with methyl-β-cyclodextrin reduced the association of the agonist-activated receptor into membrane rafts but did not affect either the UTP-mediated vasoconstrictions or the vasomotor responses elicited by both serotonin and KCl. Ex vivo perfusion of human chorionic artery segments with 1–10 μm UTP, a selective P2Y2R agonist, displaced the P2Y2R localization into membrane rafts within 1 min, a process preceded by the activation of both RhoA and Rac1 GTPases. AG1478, a selective and potent inhibitor of the epidermal growth factor receptor tyrosine kinase activity, not only blocked the UTP-induced vasomotor activity but also abrogated both RhoA and Rac1 activation, the P2Y2R association with membrane rafts, and its internalization. Altogether, these results show for the first time that the plasma membrane distribution of the P2Y2R is transregulated by the epidermal growth factor receptor, revealing an unsuspected functional interplay that controls both the membrane distribution and the vasomotor activity of the P2Y2R in intact human blood vessels. PMID:19996104

  6. P2Y12 Receptor Localizes in the Renal Collecting Duct and Its Blockade Augments Arginine Vasopressin Action and Alleviates Nephrogenic Diabetes Insipidus.

    PubMed

    Zhang, Yue; Peti-Peterdi, Janos; Müller, Christa E; Carlson, Noel G; Baqi, Younis; Strasburg, David L; Heiney, Kristina M; Villanueva, Karie; Kohan, Donald E; Kishore, Bellamkonda K

    2015-12-01

    P2Y12 receptor (P2Y12-R) signaling is mediated through Gi, ultimately reducing cellular cAMP levels. Because cAMP is a central modulator of arginine vasopressin (AVP)-induced water transport in the renal collecting duct (CD), we hypothesized that if expressed in the CD, P2Y12-R may play a role in renal handling of water in health and in nephrogenic diabetes insipidus. We found P2Y12-R mRNA expression in rat kidney, and immunolocalized its protein and aquaporin-2 (AQP2) in CD principal cells. Administration of clopidogrel bisulfate, an irreversible inhibitor of P2Y12-R, significantly increased urine concentration and AQP2 protein in the kidneys of Sprague-Dawley rats. Notably, clopidogrel did not alter urine concentration in Brattleboro rats that lack AVP. Clopidogrel administration also significantly ameliorated lithium-induced polyuria, improved urine concentrating ability and AQP2 protein abundance, and reversed the lithium-induced increase in free-water excretion, without decreasing blood or kidney tissue lithium levels. Clopidogrel administration also augmented the lithium-induced increase in urinary AVP excretion and suppressed the lithium-induced increase in urinary nitrates/nitrites (nitric oxide production) and 8-isoprostane (oxidative stress). Furthermore, selective blockade of P2Y12-R by the reversible antagonist PSB-0739 in primary cultures of rat inner medullary CD cells potentiated the expression of AQP2 and AQP3 mRNA, and cAMP production induced by dDAVP (desmopressin). In conclusion, pharmacologic blockade of renal P2Y12-R increases urinary concentrating ability by augmenting the effect of AVP on the kidney and ameliorates lithium-induced NDI by potentiating the action of AVP on the CD. This strategy may offer a novel and effective therapy for lithium-induced NDI.

  7. P2Y12 Receptor Localizes in the Renal Collecting Duct and Its Blockade Augments Arginine Vasopressin Action and Alleviates Nephrogenic Diabetes Insipidus

    PubMed Central

    Zhang, Yue; Peti-Peterdi, Janos; Müller, Christa E.; Carlson, Noel G.; Baqi, Younis; Strasburg, David L.; Heiney, Kristina M.; Villanueva, Karie; Kohan, Donald E.

    2015-01-01

    P2Y12 receptor (P2Y12-R) signaling is mediated through Gi, ultimately reducing cellular cAMP levels. Because cAMP is a central modulator of arginine vasopressin (AVP)-induced water transport in the renal collecting duct (CD), we hypothesized that if expressed in the CD, P2Y12-R may play a role in renal handling of water in health and in nephrogenic diabetes insipidus. We found P2Y12-R mRNA expression in rat kidney, and immunolocalized its protein and aquaporin-2 (AQP2) in CD principal cells. Administration of clopidogrel bisulfate, an irreversible inhibitor of P2Y12-R, significantly increased urine concentration and AQP2 protein in the kidneys of Sprague–Dawley rats. Notably, clopidogrel did not alter urine concentration in Brattleboro rats that lack AVP. Clopidogrel administration also significantly ameliorated lithium-induced polyuria, improved urine concentrating ability and AQP2 protein abundance, and reversed the lithium-induced increase in free-water excretion, without decreasing blood or kidney tissue lithium levels. Clopidogrel administration also augmented the lithium-induced increase in urinary AVP excretion and suppressed the lithium-induced increase in urinary nitrates/nitrites (nitric oxide production) and 8-isoprostane (oxidative stress). Furthermore, selective blockade of P2Y12-R by the reversible antagonist PSB-0739 in primary cultures of rat inner medullary CD cells potentiated the expression of AQP2 and AQP3 mRNA, and cAMP production induced by dDAVP (desmopressin). In conclusion, pharmacologic blockade of renal P2Y12-R increases urinary concentrating ability by augmenting the effect of AVP on the kidney and ameliorates lithium-induced NDI by potentiating the action of AVP on the CD. This strategy may offer a novel and effective therapy for lithium-induced NDI. PMID:25855780

  8. Phase-Separation Control of KxFe2-ySe2 Superconductor through Rapid-Quenching Process

    NASA Astrophysics Data System (ADS)

    Yanagisawa, Yusuke; Tanaka, Masashi; Yamashita, Aichi; Suzuki, Kouji; Hara, Hiroshi; ElMassalami, Mohammed; Takeya, Hiroyuki; Takano, Yoshihiko

    2017-04-01

    KxFe2-ySe2 exhibits iron-vacancy ordering at Ts ˜ 270 °C and separates into two phases: a minor superconducting (iron-vacancy-disordered) phase and a major non-superconducting (iron-vacancy-ordered) phase. The microstructural and superconducting properties of this intermixture can be tuned by an appropriate control of the quenching process through Ts. A faster quenching rate leads to a finer microstructure and a suppression of formation of the non-superconducting phase by up to 50%. Nevertheless, such a faster cooling rate induces a monotonic reduction in the superconducting transition temperature (from 30.7 to 26.0 K) and, simultaneously, a decrease in the iron content within the superconducting phase such that the compositional ratio changed from K0.35Fe1.83Se2 to K0.58Fe1.71Se2.

  9. Sustained phase separation and spin glass in Co-doped KxFe2-ySe2 single crystals

    DOE PAGES

    Ryu, Hyejin; Wang, Kefeng; Opacic, M.; ...

    2015-11-19

    We describe Co substitution effects in KxFe2-y-zCozSe2 (0.06 ≤ z ≤ 1.73) single crystal alloys. By 3.5% of Co doping superconductivity is suppressed whereas phase separation of semiconducting K2Fe4Se5 and superconducting/metallic KxFe2Se2 is still present. We show that the arrangement and distribution of superconducting phase (stripe phase) is connected with the arrangement of K, Fe and Co atoms. Semiconducting spin glass is found in proximity to superconducting state, persisting for large Co concentrations. At high Co concentrations ferromagnetic metallic state emerges above the spin glass. This is coincident with changes of the unit cell, arrangement and connectivity of stripemore » conducting phase.« less

  10. Numerical simulation of ZrO2(Y2O3) ceramic plate penetration by cylindrical plunger

    NASA Astrophysics Data System (ADS)

    Bratov, V.; Kazarinov, N.; Petrov, Y.

    2015-09-01

    In this paper dynamic fracture process due to high-speed impact of steel plunger into ceramic sample is simulated. The developed numerical model is based on finite element method and a concept of incubation time criterion, which is proven to be applicable in order to predict brittle fracture under high-rate deformation. Simulations were performed for ZrO2(Y2O3) ceramic plates. To characterize fracture process quantitatively fracture surface area parameter is introduced and controlled. This parameter gives area of new surface created during dynamic fracture of a sample and is essentially connected to energetic peculiarities of fracture process. Multiple simulations with various parameters made it possible to explore dependencies of fracture area on plunger velocity and material properties. Energy required to create unit of fracture area at fracture initiation (dynamic analogue of Griffith's surface energy) was evaluated and was found to be an order of magnitude higher as comparing to its static value.

  11. Contemporary registries on P2Y12 inhibitors in patients with acute coronary syndromes in Europe: overview and methodological considerations.

    PubMed

    Jukema, J Wouter; Lettino, Maddalena; Widimský, Petr; Danchin, Nicolas; Bardaji, Alfredo; Barrabes, Jose A; Cequier, Angel; Claeys, Marc J; De Luca, Leonardo; Dörler, Jakob; Erlinge, David; Erne, Paul; Goldstein, Patrick; Koul, Sasha M; Lemesle, Gilles; Lüscher, Thomas F; Matter, Christian M; Montalescot, Gilles; Radovanovic, Dragana; Lopez-Sendón, Jose; Tousek, Petr; Weidinger, Franz; Weston, Clive F M; Zaman, Azfar; Zeymer, Uwe

    2015-10-01

    Patient registries that document real-world clinical experience play an important role in cardiology as they complement the data from randomized controlled trials, provide valuable information on drug use and clinical outcomes, and evaluate to what extent guidelines are followed in practice. The Platelet Inhibition Registry in ACS EvalUation Study (PIRAEUS) project is an initiative of registry holders who are managing national or international registries observing patients with acute coronary syndromes (ACS). The aim of PIRAEUS is to systematically compare and combine available information/insights from various European ACS registries with a focus on P2Y12 inhibitors. The present publication introduces the 17 participating registries in a narrative and tabular form, and describes which ACS groups and which dual antiplatelet therapies were investigated. It sets the basis for upcoming publications that will focus on effectiveness and safety of the antiplatelets used.

  12. Effect of Fibrinogen on Platelet Reactivity Measured by the VerifyNow P2Y12 Assay.

    PubMed

    Dobrovolsky, A B; Laguta, P S; Guskova, E V; Yarovaya, E B; Titaeva, E V; Storozhilova, A N; Panchenko, E P

    2016-05-01

    The VerifyNow assay is based upon the ability of activated platelets to cross-link beads coated with fibrinogen. However, fibrinogen is an abundant protein of blood, and therefore it may affect test results by competing with fibrinogen of beads for binding to platelets. To test this assumption, we assessed the influence of artificial alteration of fibrinogen level in blood samples obtained from donors (n = 9) and patients on clopidogrel therapy (n = 8) on the results of the VerifyNow P2Y12 assay. Fibrinogen level was altered by adding to blood samples 1/10 volume of fibrinogen solution (10.56 g/liter) or corresponding buffer. Relative to baseline, addition of buffer significantly increased platelet reactivity, whereas addition of fibrinogen decreased it. Analysis of the relationship between change in platelet reactivity values (dBase and dPRU) and change in fibrinogen concentration (dFg) revealed strong negative correlations: dBase = -63.3 × dFg - 27.1 (r = -0.924, p < 0.0005) and dPRU = -54.4 × dFg - 21.8 (r = -0.764, p < 0.0005). Thus, the results of our experiments suggest that: (i) blood fibrinogen strongly influences results of the VerifyNow P2Y12 assay, and (ii) correcting for fibrinogen effect may be needed to improve the accuracy of the test in the measuring of antiplatelet effect of clopidogrel therapy.

  13. P2Y1 purinoreceptors are fundamental to inhibitory motor control of murine colonic excitability and transit.

    PubMed

    Hwang, Sung Jin; Blair, Peter J; Durnin, Leonie; Mutafova-Yambolieva, Violeta; Sanders, Kenton M; Ward, Sean M

    2012-04-15

    Activation of enteric inhibitory motor neurons causes inhibitory junctional potentials (IJPs) and muscle relaxation in mammalian gastrointestinal (GI) muscles, including humans. IJPs in many GI muscles are bi-phasic with a fast initial hyperpolarization (fIJP) due to release of a purine neurotransmitter and a slower hyperpolarization component (sIJP) due to release of nitric oxide. We sought to characterize the nature of the post-junctional receptor(s) involved in transducing purinergic neural inputs in the murine colon using mice with genetically deactivated P2ry1. Wild-type mice had characteristic biphasic IJPs and pharmacological dissection confirmed that the fIJP was purinergic and the sIJP was nitrergic. The fIJP was completely absent in P2ry1(−/−) mice and the P2Y1 receptor antagonist MRS2500 had no effect on electrical activity or responses to electrical field stimulation of intrinsic nerves in these mice. Contractile experiments confirmed that purinergic responses were abolished in P2ry1(−/−) mice. Picospritzing of neurotransmitter candidates (ATP and its primary metabolite, ADP) and β-NAD (and its primary metabolite, ADP-ribose, ADPR) caused transient hyperpolarization responses in wild-type colons, but responses to β-NAD and ADPR were completely abolished in P2ry1(−/−) mice. Hyperpolarization and relaxation responses to ATP and ADP were retained in colons of P2ry1(−/−) mice. Video imaging revealed that transit of fecal pellets was significantly delayed in colons from P2ry1(−/−) mice. These data demonstrate the importance of purinergic neurotransmission in regulating colonic motility and confirm pharmacological experiments suggesting that purinergic neurotransmission is mediated via P2Y1 receptors.

  14. Materials Data on Al8Mo3 (SG:12) by Materials Project

    DOE Data Explorer

    Kristin Persson

    2016-02-10

    Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

  15. Etching process mills PH 14-8 Mo alloy steel to precise tolerances

    NASA Technical Reports Server (NTRS)

    Chipman, B. L.; Mulland, P. W.

    1966-01-01

    Chemical milling process, which combines an aqua regia etchant with a sulfonate wetting agent, produces finishes on PH 14-8 molybdenum alloy steel to precise tolerances. This process permits precision removal of excess metal from the steel in annealed and/or aged conditions.

  16. An X-Ray, Optical, and Radio Search for Supernova Remnants in the Nearby Sculptor Group Sd Galaxy NGC 7793

    NASA Astrophysics Data System (ADS)

    Pannuti, Thomas G.; Duric, Nebojsa; Lacey, Christina K.; Ferguson, Annette M. N.; Magnor, Marcus A.; Mendelowitz, Caylin

    2002-02-01

    This paper is the second in a series devoted to examining the multiwavelength properties of supernova remnants (SNRs) located in nearby galaxies. We consider here the resident SNRs in the nearby Sculptor group Sd galaxy NGC 7793. Using our own Very Large Array (VLA) radio observations at 6 and 20 cm, as well as archived ROSAT X-ray data, previously published optical results, and our own Hα image, we have searched for X-ray and radio counterparts to previously known optically identified SNRs and for new previously unidentified SNRs at these two wavelength regimes. Consistent with our prior results for NGC 300, only a tiny minority of the optically identified SNRs have been found at another wavelength. The most noteworthy source in our study is N7793-S26, which is the only SNR in this galaxy that is detected at all three wavelengths (X-ray, optical, and radio). It features a long (~450 pc) filamentary morphology that is clearly seen in both the optical and the radio images. N7793-S26's radio luminosity exceeds that of the Galactic SNR Cas A, and based on equipartition calculations we determine that an energy of at least 1052 ergs is required to maintain this source. Such a result argues for the source being created by multiple supernova explosions rather than by a single supernova event. A second optically identified SNR, N7793-S11, has detectable radio emission but no detectable X-ray emission. A radio-selected sample of candidate SNRs has also been prepared by searching for coincidences between nonthermal radio sources and regions of Hα emission in this galaxy. This search has produced five new candidate radio SNRs to be added to the 28 SNRs that have already been detected by optical methods. A complementary search for new candidate X-ray SNRs has also been conducted by searching for soft-spectrum sources (kT<1 keV) that are coincident with regions of Hα emission. That search has yielded a candidate X-ray SNR that is coincident with one (and possibly two) of the

  17. Variation and fractionation of lithium isotope ratios within single tourmaline crystals in the pegmatites of the Black Hills, SD

    NASA Astrophysics Data System (ADS)

    Gross, M.; Nabelek, P. I.

    2012-12-01

    Lithium isotopes are quickly becoming a valuable geochemical tool, providing insight into a broad range of studies. Li isotopes have been utilized in studies with subjects ranging from mantle processes to planetary accretion on stars. Yet, as an emerging technique, a number of uncertainties remain to be resolved. Two basic questions must be answered in order to apply isotope studies in a meaningful way: How do isotopes fractionate from each other and what do the isotope ratios mean? Previous studies on intra-crystal Li isotope signatures in tourmaline are extremely limited. One study showed roughly homogenous isotope profile using secondary ion mass spectroscopy (SIMS) analysis (Ludwig et al. 2011). If Li isotopes are in fact variable within individual crystals, however, it has implications for previous models of pegmatite formation reached using Li isotopes, as well as the root cause of Li isotope fractionation in tourmaline. For this study, tourmaline samples were collected from several texturally different pegmatite localities in the Black Hills, SD. Lithium concentrations and isotope ratios were measured along numerous points in a tourmaline crystal to discern how they change within a single crystal. The tourmaline was dissolved by an alkali fusion technique. Concentrations were determined at the University of Missouri using a Perkin-Elmer Optima 3300 Inductively Coupled Plasma Optical Emission Spectrometer (ICP-OES). Isotope measurements were performed at University of Maryland-College Park by a Nu Plasma Multi-collector ICP-MS. The procedure followed the three-column cation exchange chromatography method. Additionally, elemental mapping was performed on one sample using the JEOL JXA-8200 Superprobe at Washington University in St. Louis. Results of this research reveal that extreme fractionation of Li is possible within single tourmaline crystals. The δ7Li values measured are among the highest measured in rocks, though the average for each crystal falls

  18. Molecular Modeling of the Human P2Y2 Receptor and Design of a Selective Agonist, 2′-Amino-2′-deoxy-2-thio-UTP

    PubMed Central

    Ivanov, Andrei A.; Ko, Hyojin; Cosyn, Liesbet; Maddileti, Savitri; Besada, Pedro; Fricks, Ingrid; Costanzi, Stefano; Harden, T. Kendall; Van Calenbergh, Serge; Jacobson, Kenneth A.

    2012-01-01

    A rhodopsin-based homology model of the nucleotide-activated human P2Y2 receptor, including loops, termini, and phospholipids, was optimized with Monte Carlo Multiple Minimum. Docked UTP formed a nucleobase π–π complex with conserved Phe3.32. Selectivity-enhancing 2′-amino-2′-deoxy substitution interacted through π-hydrogen bonding with aromatic Phe6.51 and Tyr3.33. A “sequential ligand composition” approach for docking the flexible dinucleotide agonist Up4U demonstrated a shift of conserved cationic Arg3.29 from the UTP γ position to δ position of Up4U and Up4ribose. Sysnthesized nucleotides were tested as agonists at human P2Y receptors expressed in 1321N1 astrocytoma cells. 2′-Amino and 2-thio modifications synergized to enhance potency and selectivity; compound 8 (8 nM EC50) was 300-fold P2Y2-selective versus P2Y4. 2′-Amine acetylation reduced potency, and trifluoroacetylation produced intermediate potency. 5-Amino nucleobase substitution did not enhance potency through a predicted hydrophilic interaction, possibly because of destabilization of the receptor-favored (N)-ribose conformation. This detailed view of P2Y2 receptor recognition suggests mutations for model validation. PMID:17302398

  19. Anomaly in the electronic structure of the Na(x)CoO(2-y) cathode as a source of its step-like discharge curve.

    PubMed

    Molenda, Janina; Baster, Dominika; Molenda, Marcin; Świerczek, Konrad; Tobola, Janusz

    2014-07-28

    In this paper we would like to show a new approach to an explanation of the nature of the discharge-charge curve of Na/Na(+)/NaxCoO2-y batteries, which can justify the existence of the step-like characteristics. This is still an open problem, which until now had no proper description in the literature. On the basis of comprehensive experimental studies of physicochemical properties of NaxCoO2-y cathode material (XRD, electrical conductivity, thermoelectric power, electronic specific heat) supported by calculations performed using the DFT method with accounting for chemical disorder, it has been shown that the observed step-like character of the discharge curve reflects the variation of the chemical potential of electrons (Fermi level) in the density of states of NaxCoO2-y, which is anomalously perturbed by the presence of the oxygen vacancy defects and sodium ordering. Our studies of structural, electronic and thermal properties of NaxCoO2-y cathode material as a function of concentration of electrochemically intercalated sodium document strong and step-like shift of the position of the Fermi level during introduction of electrons in this process. This effect is coherently supported by the shape of calculated density of states (DOS) of NaxCoO2-y having included oxygen defects and sodium ordering.

  20. CONDENSED MATTER: ELECTRONIC STRUCTURE, ELECTRICAL, MAGNETIC, AND OPTICAL PROPERTIES Tunneling Conductance in dx2 - y2 + idxy Mixed Wave Superconductor Graphene Junctions

    NASA Astrophysics Data System (ADS)

    Li, Xiao-Wei

    2010-12-01

    Using the extended Blonder—Tinkham—Klapwijk formalism, we investigate the conductance spectra of normal metal/dx2 - y2 + idxy mixed wave superconductor graphene junctions. It is found that the conductance spectra vary strongly with the orientation of the gap and the amplitude ratio (Δ1/Δ0 of two components for dx2 - y2 + idxy mixed wave. The zero bias conductance is nearly 2 and the conductance peak vanishes in doped graphene for α = 0 and Δ1/Δ0 = 1. The conductance increases with increasing the amplitude ratio of two components for α = π/4 and Δ1/Δ0 = 1. The ZBCP becomes observable wide with 1 < EF/Δ0 < 100 for α = π/4 and Δ1/Δ0 = 1. This property is different from that in normal metal/dx2 - y2 wave superconductor graphene junctions.

  1. 4-Benzothiazole-7-hydroxyindolinyl diaryl ureas are potent P2Y1 antagonists with favorable pharmacokinetics: low clearance and small volume of distribution.

    PubMed

    Qiao, Jennifer X; Wang, Tammy C; Hiebert, Sheldon; Hu, Carol H; Schumacher, William A; Spronk, Steven A; Clark, Charles G; Han, Ying; Hua, Ji; Price, Laura A; Shen, Hong; Chacko, Silvi A; Everlof, Gerry; Bostwick, Jeffrey S; Steinbacher, Thomas E; Li, Yi-Xin; Huang, Christine S; Seiffert, Dietmar A; Rehfuss, Robert; Wexler, Ruth R; Lam, Patrick Y S

    2014-10-01

    Current antithrombotic discovery efforts target compounds that are highly efficacious in thrombus reduction with less bleeding liability than the standard of care. Preclinical data suggest that P2Y1 antagonists may have lower bleeding liabilities than P2Y12 antagonists while providing similar antithrombotic efficacy. This article describes our continuous SAR efforts in a series of 7-hydroxyindolinyl diaryl ureas. When dosed orally, 4-trifluoromethyl-7-hydroxy-3,3-dimethylindolinyl analogue 4 was highly efficacious in a model of arterial thrombosis in rats with limited bleeding. The chemically labile CF3 group in 4 was then transformed to various groups via a novel one-step synthesis, yielding a series of potent P2Y1 antagonists. Among them, the 4-benzothiazole-substituted indolines had desirable PK properties in rats, specifically, low clearance and small volume of distribution. In addition, compound 40 had high i.v. exposure and modest bioavailability, giving it the best overall profile.

  2. N-linked glycosylation of platelet P2Y12 ADP receptor is essential for signal transduction but not for ligand binding or cell surface expression.

    PubMed

    Zhong, Xiaotian; Kriz, Ron; Seehra, Jasbir; Kumar, Ravindra

    2004-03-26

    P(2)Y(12) receptor is a G(i)-coupled adenosine diphosphate (ADP) receptor with a critical role in platelet aggregation. It contains two potential N-linked glycosylation sites at its extra cellular amino-terminus, which may modulate its activity. Studies of both tunicamycin treatment and site-directed mutagenesis have revealed a dispensable role of the N-linked glycosylation in the receptor's surface expression and ligand binding activity. However, the non-glycosylated P(2)Y(12) receptor is defective in the P(2)Y(12)-mediated inhibition of the adenylyl cyclase activity. Thus the study uncovers an unexpected vital role of N-linked glycans in receptor's signal transducing step but not in surface expression or ligand binding.

  3. Radiation-induced amorphization of Ce-doped Mg2Y8(SiO4)6O2 silicate apatite

    NASA Astrophysics Data System (ADS)

    Zhou, Jianren; Yao, Tiankai; Lian, Jie; Shen, Yiqiang; Dong, Zhili; Lu, Fengyuan

    2016-07-01

    Ce-doped Mg2Y8(SiO4)6O2 silicate apatite (Ce = 0.05 and 0.5) were irradiated with 1 MeV Kr2+ ion beam irradiation at different temperatures and their radiation response and the cation composition dependence of the radiation-induced amorphization were studied by in situ TEM. The two Ce-doped Mg2Y8(SiO4)6O2 silicate apatites are sensitive to ion beam induced amorphization with a low critical dose (0.096 dpa) at room temperature, and exhibits significantly different radiation tolerance at elevated temperatures. Ce concentration at the apatite AI site plays a critical role in determining the radiation response of this silicate apatite, in which the Ce3+ rich Mg2Y7.5Ce0.5(SiO4)6O2 displays lower amorphization susceptibility than Mg2Y7.95Ce0.05(SiO4)6O2 with a lower Ce3+ occupancy at the AI sites. The critical temperature (Tc) and activation energy (Ea) change from 667.5 ± 33 K and 0.162 eV of Mg2Y7.5Ce0.5(SiO4)6O2 to 963.6 ± 64 K and 0.206 eV of Mg2Y7.95Ce0.05(SiO4)6O2. We demonstrate that the radiation tolerance can be controlled by varying the chemical composition, and enhanced radiation tolerance is achieved by increasing the Ce concentration at the AI site.

  4. Rescue of Cyclic AMP Mediated Long Term Potentiation Impairment in the Hippocampus of Mecp2 Knockout (Mecp2-/y) Mice by Rolipram

    PubMed Central

    Balakrishnan, Saju; Niebert, Marcus; Richter, Diethelm W.

    2016-01-01

    Rett syndrome (RTT) patients experience learning difficulties and memory loss. Analogous deficits of hippocampal plasticity are reported in mouse models of RTT. To elucidate the underlying pathophysiology, we studied long term potentiation (LTP) at the CA3 to CA1 synapses in the hippocampus in acute brain slices from WT and Mecp2-/y mice, by either activating cAMP dependent pathway or using high frequency stimulation, by means of patch clamp. We have observed that, the NMDA channel current characteristics remain unchanged in the Mecp2-/y mice. The adenylyl cyclase (AC) agonist forskolin evoked a long lasting potentiation of evoked EPSCs in WT CA1 neurons, but only minimally enhanced the EPSCs in the Mecp2-/y mice. This weaker potentiation in Mecp2-/y mice was ameliorated by application of phosphodiesterase 4 inhibitor rolipram. The hyperpolarization activated cyclic nucleotide gated channel current (Ih) was potentiated to similar extent by forskolin in both phenotypes. Multiple tetanus induced cAMP-dependent plasticity was also impaired in the Mecp2-/y mice, and was also partially rescued by rolipram. Western blot analysis of CA region of Mecp2-/y mice hippocampus revealed more than twofold up-regulation of protein kinase A (PKA) regulatory subunits, while the expression of the catalytic subunit remained unchanged. We hypothesize that the overexpressed PKA regulatory subunits buffer cAMP and restrict the PKA mediated phosphorylation of target proteins necessary for LTP. Blocking the degradation of cAMP, thereby saturating the regulatory subunits alleviated this defect. PMID:26869885

  5. KCa3.1 channels facilitate K+ secretion or Na+ absorption depending on apical or basolateral P2Y receptor stimulation

    PubMed Central

    Palmer, Melissa L; Peitzman, Elizabeth R; Maniak, Peter J; Sieck, Gary C; Prakash, Y S; O'Grady, Scott M

    2011-01-01

    Abstract Human mammary epithelial (HME) cells express several P2Y receptor subtypes located in both apical and basolateral membranes. Apical UTP or ATP-γ-S stimulation of monolayers mounted in Ussing chambers evoked a rapid, but transient decrease in short circuit current (Isc), consistent with activation of an apical K+ conductance. In contrast, basolateral P2Y receptor stimulation activated basolateral K+ channels and increased transepithelial Na+ absorption. Chelating intracellular Ca2+ using the membrane-permeable compound BAPTA-AM, abolished the effects of purinoceptor activation on Isc. Apical pretreatment with charybdotoxin also blocked the Isc decrease by >90% and similar magnitudes of inhibition were observed with clotrimazole and TRAM-34. In contrast, iberiotoxin and apamin did not block the effects of apical P2Y receptor stimulation. Silencing the expression of KCa3.1 produced ∼70% inhibition of mRNA expression and a similar reduction in the effects of apical purinoceptor agonists on Isc. In addition, silencing P2Y2 receptors reduced the level of P2Y2 mRNA by 75% and blocked the effects of ATP-γ-S by 65%. These results suggest that P2Y2 receptors mediate the effects of purinoceptor agonists on K+ secretion by regulating the activity of KCa3.1 channels expressed in the apical membrane of HME cells. The results also indicate that release of ATP or UTP across the apical or basolateral membrane elicits qualitatively different effects on ion transport that may ultimately determine the [Na+]/[K+] composition of fluid within the mammary ductal network. PMID:21606112

  6. P2Y12 receptor-mediated activation of spinal microglia and p38MAPK pathway contribute to cancer-induced bone pain

    PubMed Central

    Liu, Mingjuan; Yao, Ming; Wang, Hanqi; Xu, Longsheng; Zheng, Ying; Huang, Bing; Ni, Huadong; Xu, Shijie; Zhou, Xuyan; Lian, Qingquan

    2017-01-01

    Background Cancer-induced bone pain (CIBP) is one of the most challenging clinical problems due to a lack of understanding the mechanisms. Recent evidence has demonstrated that activation of microglial G-protein-coupled P2Y12 receptor (P2Y12R) and proinflammatory cytokine production play an important role in neuropathic pain generation and maintenance. However, whether P2Y12R is involved in CIBP remains unknown. Methods The purpose of this study was to investigate the role of P2Y12R in CIBP and its molecular mechanisms. Using the bone cancer model inoculated with Walker 256 tumor cells into the left tibia of Sprague Dawley rat, we blocked spinal P2Y12R through intrathecal administration of its selective antagonist MRS2395 (400 pmol/µL, 15 µL). Results We found that not only the ionized calcium-binding adapter molecule 1 (Iba-1)-positive microglia in the ipsilateral spinal cord but also mechanical allodynia was significantly inhibited. Furthermore, it decreased the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) and the production of proinflammatory cytokines interleukin-1β (IL-1β) and interleukin-6 (IL-6), whereas it increased tumor necrosis factor-α (TNF-α). Conclusion Taken together, our present results suggest that microglial P2Y12R in the spinal cord may contribute to CIBP by the activation of spinal microglia and p38MAPK pathway, thus identifying a potential therapeutic target for the treatment of CIBP. PMID:28243146

  7. IL-1ra Secreted by ATP-Induced P2Y2 Negatively Regulates MUC5AC Overproduction via PLCβ3 during Airway Inflammation.

    PubMed

    Jeong, Jee-Yeong; Kim, Jiwook; Kim, Bokyoum; Kim, Joowon; Shin, Yusom; Kim, Judeok; Ryu, Siejeong; Yang, Yu-Mi; Song, Kyoung Seob

    2016-01-01

    Mucus secretion is often uncontrolled in many airway inflammatory diseases of humans. Identifying the regulatory pathway(s) of mucus gene expression, mucus overproduction, and hypersecretion is important to alleviate airway inflammation in these diseases. However, the regulatory signaling pathway controlling mucus overproduction has not been fully identified yet. In this study, we report that the ATP/P2Y2 complex secretes many cytokines and chemokines to regulate airway inflammation, among which IL-1 receptor antagonist (IL-1ra) downregulates MUC5AC gene expression via the inhibition of Gαq-induced Ca(2+) signaling. IL-1ra inhibited IL-1α protein expression and secretion, and vice versa. Interestingly, ATP/P2Y2-induced IL-1ra and IL-1α secretion were both mediated by PLCβ3. A dominant-negative mutation in the PDZ-binding domain of PLCβ3 inhibited ATP/P2Y2-induced IL-1ra and IL-1α secretion. IL-1α in the presence of the ATP/P2Y2 complex activated the ERK1/2 pathway in a greater degree and for a longer duration than the ATP/P2Y2 complex itself, which was dramatically inhibited by IL-1ra. These findings suggest that secreted IL-1ra exhibits a regulatory effect on ATP/P2Y2-induced MUC5AC gene expression, through inhibition of IL-1α secretion, to maintain the mucus homeostasis in the airway. Therefore, IL-1ra could be an excellent modality for regulating inflamed airway microenvironments in respiratory diseases.

  8. Three-Dimensional Analysis of Retinal Layer Texture: Identification of Fluid-Filled Regions in SD-OCT of the Macula

    PubMed Central

    Lee, Kyungmoo; Dolejsi, Martin; Garvin, Mona K.; Abràmoff, Michael D.; Sonka, Milan

    2010-01-01

    Optical coherence tomography (OCT) is becoming one of the most important modalities for the noninvasive assessment of retinal eye diseases. As the number of acquired OCT volumes increases, automating the OCT image analysis is becoming increasingly relevant. In this paper, a method for automated characterization of the normal macular appearance in spectral domain OCT (SD-OCT) volumes is reported together with a general approach for local retinal abnormality detection. Ten intraretinal layers are first automatically segmented and the 3-D image dataset flattened to remove motion-based artifacts. From the flattened OCT data, 23 features are extracted in each layer locally to characterize texture and thickness properties across the macula. The normal ranges of layer-specific feature variations have been derived from 13 SD-OCT volumes depicting normal retinas. Abnormalities are then detected by classifying the local differences between the normal appearance and the retinal measures in question. This approach was applied to determine footprints of fluid-filled regions—SEADs (Symptomatic Exudate-Associated Derangements)—in 78 SD-OCT volumes from 23 repeatedly imaged patients with choroidal neovascularization (CNV), intra-, and sub-retinal fluid and pigment epithelial detachment. The automated SEAD footprint detection method was validated against an independent standard obtained using an interactive 3-D SEAD segmentation approach. An area under the receiver-operating characteristic curve of 0.961 ± 0.012 was obtained for the classification of vertical, cross-layer, macular columns. A study performed on 12 pairs of OCT volumes obtained from the same eye on the same day shows that the repeatability of the automated method is comparable to that of the human experts. This work demonstrates that useful 3-D textural information can be extracted from SD-OCT scans and—together with an anatomical atlas of normal retinas—can be used for clinically important applications

  9. The study on increasing the equivalent SNR in the certain DOI by adjusting the SD separation in near-infrared brain imaging application

    NASA Astrophysics Data System (ADS)

    Wang, Jinhai; Liu, Dongyuan; Sun, Jinggong; Zhang, Yanjun; Sun, Qiuming; Ma, Jun; Zheng, Yu; Wang, Huiquan

    2016-10-01

    Near-infrared (NIR) brain imaging is one of the most promising techniques for brain research in recent years. As a significant supplement to the clinical imaging technique, such as CT and MRI, the NIR technique can achieve a fast, non-invasive, and low cost imaging of the brain, which is widely used for the brain functional imaging and hematoma detection. NIR imaging can achieve an imaging depth up to only several centimeters due to the reduced optical attenuation. The structure of the human brain is so particularly complex, from the perspective of optical detection, the measurement light needs go through the skin, skull, cerebrospinal fluid (CSF), grey matter, and white matter, and then reverses the order reflected by the detector. The more photons from the Depth of Interest (DOI) in brain the detector capture, the better detection accuracy and stability can be obtained. In this study, the Equivalent Signal to Noise Ratio (ESNR) was defined as the proportion of the photons from the DOI to the total photons the detector evaluated the best Source and Detector (SD) separation. The Monte-Carlo (MC) simulation was used to establish a multi brain layer model to analyze the distribution of the ESNR along the radial direction for different DOIs and several basic brain optical and structure parameters. A map between the best detection SD separation, in which distance the ESNR was the highest, and the brain parameters was established for choosing the best detection point in the NIR brain imaging application. The results showed that the ESNR was very sensitivity to the SD separation. So choosing the best SD separation based on the ESNR is very significant for NIR brain imaging application. It provides an important reference and new thinking for the brain imaging in the near infrared.

  10. Surface free energy ( γsd) of active carbons determined by inverse gas chromatography: influences of the origin of precursors, the burn off level and the chemical modification

    NASA Astrophysics Data System (ADS)

    Cossarutto, L.; Vagner, C.; Finqueneisel, G.; Weber, J. V.; Zimny, T.

    2001-06-01

    The dispersive component of the surface free energies ( γsd) of commercial active carbons (AC) from various origins were determined by inverse gas chromatography at infinite dilution (IGC-ID). This method discriminates clearly the AC produced from wood (and activated/carbonised with phosphoric acid) and those from coconut-shell (carbonised and steam activated at 850°C). The values for the last AC (from coconut) are twice higher than the values for AC of wood origin. The structure and shape of the pores have to be considered to explain these values. It seems that for AC, IGC-ID globally characterises the most energetic micropores. This can be observed, in this work, by two ways: (i) washing of commercial AC (chemically activated) allows to liberate a part of the micropores blocked by soluble phosphate and consequently increases the γsd value; (ii) modifying coconuts AC by chemical treatment (formamide) results in a strong decrease of both microporosity and γsd value. On the contrary, thermal activation of the modified AC increases at the same time the microporosity and the surface free energy. Finally, we demonstrate that the IGC method is also an useful tool to monitor in situ the evolutions of the surface properties of carbonaceous materials.

  11. Effects of onion (Allium cepa L.) extract administration on intestinal α-glucosidases activities and spikes in postprandial blood glucose levels in SD rats model.

    PubMed

    Kim, Sun-Ho; Jo, Sung-Hoon; Kwon, Young-In; Hwang, Jae-Kwan

    2011-01-01

    Diets high in calories and sweetened foods with disaccharides frequently lead to exaggerated postprandial spikes in blood glucose. This state induces immediate oxidant stress and free radicals which trigger oxidative stress-linked diabetic complications. One of the therapeutic approaches for decreasing postprandial hyperglycemia is to retard absorption of glucose by the inhibition of carbohydrate hydrolyzing enzymes, α-amylase and α-glucosidases, in the digestive organs. Therefore, the inhibitory activity of Korean onion (Allium cepa L.) extract against rat intestinal α-glucosidases, such as sucrase, maltase, and porcine pancreatic α-amylase were investigated in vitro and in vivo. The content of quercetin in ethyl alcohol extract of onion skin (EOS) was 6.04 g/100 g dried weight of onion skin. The in vitro half-maximal inhibitory concentrations (IC(50)) of EOS and quercetin, a major phenolic in onion, on rat intestinal sucrase were 0.40 and 0.11 mg/mL, respectively. The postprandial blood glucose lowering effects of EOS and quercetin were compared to a known type 2 diabetes drug (Acarbose), a strong α-glucosidase inhibitor in the Sprague-Dawley (SD) rat model. In rats fed on sucrose, EOS significantly reduced the blood glucose spike after sucrose loading. The area under the blood glucose-time curve (AUC(last)) in EOS-treated SD rats (0.5 g-EOS/kg) was significantly lower than in untreated SD rats (259.6 ± 5.1 vs. 283.1 ± 19.2 h·mg/dL). The AUC(last) in quercetin-treated SD rats (0.5 g-quercetin/kg) was similar to in EOS-treated group (256.1 ± 3.2 vs. 259.6 ± 5.1 h·mg/dL). Results from this study indicates that although quercetin does have blood glucose lowering potential via α-glucosidase inhibition, there are other bioactive compounds present in onion skin. Furthermore, the effects of two weeks administration of EOS in a high carbohydrate-dietary mixture (Pico 5053) on sucrase and maltase activities in intestine were evaluated in SD rat model. Compared

  12. Preparation and magnetic properties of Ba-Co2Z and Sr-Zn2Y ferrites

    NASA Astrophysics Data System (ADS)

    Chen, In-Gann; Hsu, Shu-Hau; Chang, Y. H.

    2000-05-01

    We have prepared Ba-Co2Z and Sr-Zn2Y ferrites by mixing SrCO3 (BaCO3), Co2O3 (ZnO), and Fe2O3 and calcinating in air and O2. The effects of sintering atmosphere (O2 and Ar) and sintering temperatures (1373-1573 K) on the structural, magnetic, and electrical properties have been measured. The Ba-Co2Z sample sintered at 1573 K under a flowing O2 exhibits superior dc electrical resistivity (˜108Ω-cm), high initial permeability (u'˜21), and low loss factor (F˜1.6×10-3) at 20 MHz. The related XRD and SEM/EDS analyses of these samples have also been studied to correlate these properties. These results indicate that significant modification of magnetic properties up to 20 MHz can be achieved with the addition of the quaternary component and proper control of the processing oxygen atmosphere.

  13. P2X and P2Y Receptors—Role in the Pathophysiology of the Nervous System

    PubMed Central

    Puchałowicz, Kamila; Tarnowski, Maciej; Baranowska-Bosiacka, Irena; Chlubek, Dariusz; Dziedziejko, Violetta

    2014-01-01

    Purinergic signalling plays a crucial role in proper functioning of the nervous system. Mechanisms depending on extracellular nucleotides and their P2 receptors also underlie a number of nervous system dysfunctions. This review aims to present the role of purinergic signalling, with particular focus devoted to role of P2 family receptors, in epilepsy, depression, neuropathic pain, nervous system neoplasms, such as glioma and neuroblastoma, neurodegenerative diseases like Parkinson’s disease, Alzheimer’s disease and multiple sclerosis. The above-mentioned conditions are associated with changes in expression of extracellular ectonucleotidases, P2X and P2Y receptors in neurons and glial cells, as well as releasing considerable amounts of nucleotides from activated or damaged nervous tissue cells into the extracellular space, which contributes to disturbance in purinergic signalling. The numerous studies indicate a potential possibility of using synthetic agonists/antagonists of P2 receptors in treatment of selected nervous system diseases. This is of particular significance, since numerous available agents reveal a low effectiveness and often produce side effects. PMID:25530618

  14. Magnetic and electric behavior of praseodymium substituted CuPryFe2-yO4 ferrites

    NASA Astrophysics Data System (ADS)

    Farid, Muhammad Tahir; Ahmad, Ishtiaq; Kanwal, Muddassara; Murtaza, Ghulam; Ali, Irshad; Ashiq, Muhammad Naeem; Khan, Sajjad Ahmad

    2017-01-01

    Spinel ferrites with chemical formula CuPryFe2-yO4(y=0.0,0.02,0.04,0.06,0.08,0.10) were synthesized using sol-gel technique. The sintered powder characterized by X-ray diffraction (XRD), Scanning Electron Microscopy (SEM) and vibrating sample magnetometer (VSM). X-ray Diffraction analysis showed that the samples with concentration (y=0.0-0.06) have single spinel phase and the samples with concentration at y=0.08-0.10 have secondary phase (ortho ferrite phase) along spinel phase. The Lattice constant a increased with the substitution of Praseodymium (Pr) ions. The crystallite size calculated from Scherre's formula is found in the range of 53-37 nm. It is observed that DC resistivity and activation energy enhances with the substitution of Pr. The dc resistivity decreased with the increase in temperature. The conduction below Curie temperature (Tc) is due to hopping of electrons and holes, whereas, above Curie temperature it is due to polaron hopping. The decrease in Tc with increasing Pr constant may be due to the fact that Pr-Fe interactions on the B sites are weaker than Fe-Fe interaction. The saturation magnetization (Ms) and remanence (Mr) decreased where as coercivity (Hc) has been increased with the increase of Pr content. The measured parameters suggest that these materials are potential candidates for high frequency applications.

  15. Structural disorder in the Pb2Sr2Y1-xCaxCu3O8+δ cuprates

    NASA Astrophysics Data System (ADS)

    Staub, U.; Soderholm, L.; Skanthakumar, S.; Pattison, P.; Conder, K.

    1998-03-01

    High-resolution powder x-ray-diffraction results on Pb2Sr2Y1-xCaxCu3O8+δ are presented. Assuming an orthorhombic cell with Cmmm symmetry, the reflections that index with h and l simultaneous nonzero are observed to be distinctly broader than the other reflections. A model is presented that is able to explain quantitatively and qualitatively the relative widths of the different hkl reflections. The widths of the reflections are found to be independent of the doping level. The model employed is based on anisotropic distributions of the d spacings within the (a,c) plane, corresponding to a fluctuation of the β angle around 90° that occurs as a result of oxygen nonstoichiometry. The distortions may be related to the incommensurable modulation along the b direction in the structurally similar (Bi/Pb)2Sr2(Ca/Y)Cu2O8+δ compounds. At elevated temperatures, a disorder-order phase transition (Tdo=240 °C) is observed. At temperatures above Tdo, the structure relaxes to the undistorted average orthorhombic structure. This order-disorder transition results from oxygen diffusion, which sets in at the transition temperature.

  16. Antiplatelet efficacy of P2Y12 inhibitors (prasugrel, ticagrelor, clopidogrel) in patients treated with mild therapeutic hypothermia after cardiac arrest due to acute myocardial infarction.

    PubMed

    Bednar, Frantisek; Kroupa, Josef; Ondrakova, Martina; Osmancik, Pavel; Kopa, Milos; Motovska, Zuzana

    2016-05-01

    Survivors after cardiac arrest (CA) due to AMI undergo PCI and then receive dual antiplatelet therapy. Mild therapeutic hypothermia (MTH) is recommended for unconscious patients after CA to improve neurological outcomes. MTH can attenuate the effectiveness of P2Y12 inhibitors by reducing gastrointestinal absorption and metabolic activation. The combined effect of these conditions on the efficacy of P2Y12 inhibitors is unknown. We compared the antiplatelet efficacies of new P2Y12 inhibitors in AMI patients after CA treated with MTH. Forty patients after CA for AMI treated with MTH and received one P2Y12 inhibitor (clopidogrel, prasugrel or ticagrelor) were enrolled in a prospective observational single-center study. Platelet inhibition was measured by VASP (PRI) on days 1, 2, and 3 after drug administration. In-hospital clinical data and 1-year survival data were obtained. The proportion of patients with ineffective platelet inhibition (PRI > 50 %, high on-treatment platelet reactivity) for clopidogrel, prasugrel, and ticagrelor was 77 vs. 19 vs. 1 % on day 1; 77 vs. 17 vs. 0 % on day 2; and 85 vs. 6 vs. 0 % on day 3 (P < 0.001). The platelet inhibition was significantly worse in clopidogrel group than in prasugrel or ticagrelor group. Prasugrel and ticagrelor are very effective for platelet inhibition in patients treated with MTH after CA due to AMI, but clopidogrel is not. Using prasugrel or ticagrelor seems to be a more suitable option in this high-risk group of acute patients.

  17. X1X1X2X2/X1X2Y sex chromosome systems in the Neotropical Gymnotiformes electric fish of the genus Brachyhypopomus

    PubMed Central

    Cardoso, Adauto Lima; Pieczarka, Julio Cesar; Nagamachi, Cleusa Yoshiko

    2015-01-01

    Several types of sex chromosome systems have been recorded among Gymnotiformes, including male and female heterogamety, simple and multiple sex chromosomes, and different mechanisms of origin and evolution. The X1X1X2X2/X1X2Y systems identified in three species of this order are considered homoplasic for the group. In the genus Brachyhypopomus, only B. gauderio presented this type of system. Herein we describe the karyotypes of Brachyhypopomus pinnicaudatus and B. n. sp. FLAV, which have an X1X1X2X2/X1X2Y sex chromosome system that evolved via fusion between an autosome and the Y chromosome. The morphology of the chromosomes and the meiotic pairing suggest that the sex chromosomes of B. gauderio and B. pinnicaudatus have a common origin, whereas in B . n. sp. FLAV the sex chromosome system evolved independently. However, we cannot discard the possibility of common origin followed by distinct processes of differentiation. The identification of two new karyotypes with an X1X1X2X2/X1X2Y sex chromosome system in Gymnotiformes makes it the most common among the karyotyped species of the group. Comparisons of these karyotypes and the evolutionary history of the taxa indicate independent origins for their sex chromosomes systems. The recurrent emergence of the X1X1X2X2/X1X2Y system may represent sex chromosomes turnover events in Gymnotiformes. PMID:26273225

  18. Magnetoelectric effect in laminate composites of Tb1-xDyxFe2-y and Fe-doped BaTiO3

    NASA Astrophysics Data System (ADS)

    Zhang, Ning; Fan, Junfeng; Rong, Xiaofang; Cao, Hongxia; Wei, Jianjun

    2007-03-01

    Fe-doped BaTiO3 has been synthesized with sol-gel technique. Its transformation point of ferroelectric to paraelectric and the latent heat of the transformation were observed at 103.27 °C and 169.9 J/mol, respectively. They are a little less than those for pure BaTiO3. Bonded layered composites Tb1-xDyxFe2-y/BaTi0.99Fe0.01O3 have been fabricated. Their magnetoelectric (ME) effect has been investigated. The transverse ME voltage coefficient for the bilayer Tb1-xDyxFe2-y-BaTi0.99Fe0.01O3 and the trilayer Tb1-xDyxFe2-y-BaTi0.99Fe0.01O3-Tb1-xDyxFe2-y can reach 578 (mv Oe-1 cm-1) and 2100 (mv Oe-1 cm-1), respectively, under a bias magnetic field of 350 Oe at room temperature. Those are about 50% larger than those for the bilayer and trilayer composed by pure BaTiO3. It suggests that the doped BaTiO3 can be a new choice of piezoelectrics to compose ME composites.

  19. Emergence of superconductivity and magnetic ordering tuned by Fe-vacancy in alkali-metal Fe chalcogenides RbxFe2-ySe2

    NASA Astrophysics Data System (ADS)

    Kobayashi, Yoshiaki; Kototani, Shouhei; Itoh, Masayuki; Sato, Masatoshi

    2014-12-01

    Samples of RbxFe2-ySe2 exhibiting superconductivity [superconducting (SC) samples] undergo a phase-separation into two phases, a Fe-vacancy ordered phase with antiferromagnetic (AFM) transition at TN1~500 K (AFM1 phase) and a phase with little Fe- vacancy and SC transition at Tc~30 K (SC phase). The samples of RbxFe2-ySe2 exhibiting no SC behaviour (non-SC samples) are phase-separated into three phases, the AFM1 phase, another AFM phase with TN2 ~150 K (AFM2 phase), and a paramagnetic phase with no SC transitions (paramagnetic non-SC phase). In this paper, we present the experimental results of magnetic susceptibility, electrical resistivity, and NMR measurements on single crystals of RbxFe2-ySe2 to reveal physical properties of these co-existing phases in the SC and non-SC samples. The 87Rb and 77Se NMR spectra show that the Fe vacancy concentration is very small in the Fe planes of the SC phase, whereas the AFM2 and paramagnetic non-SC phases in non-SC samples have larger amount of Fe vacancies. The randomness induced by the Fe vacancy in the non-SC samples makes the AFM2 and paramagnetic non-SC phases insulating/semiconducting and magnetically active, resulting in the absence of the superconductivity in RbxFe2-ySe2.

  20. Band filling and correlation controlling electronic properties and magnetism in KxFe2-ySe2: a slave boson study

    NASA Astrophysics Data System (ADS)

    Liu, Da-Yong; Quan, Ya-Min; Zheng, Xiao-Jun; Yu, Xiang-Long; Zou, Liang-Jian

    2013-03-01

    We investigate the electronic and magnetic properties of KxFe2-ySe2 materials at different band fillings utilizing the multi-orbital Kotliar-Ruckenstein slave boson mean-field approach. We find that the ground state of KFe2Se2 is a paramagnetic (PM) bad metal with intermediate correlation, in contrast with the previous antiferromagnetic (AFM) results obtained by the local density approximation. Our PM metallic ground state suggests that KFe2Se2 is the parent phase of superconducting KxFe2-ySe2, supporting a recent scanning tunneling spectroscopy experiment. For pure Fe2+-based systems, the ground state is a striped AFM (SAFM) metal with a spin density wave gap partially opened near the Fermi level. In comparison, for Fe3+-based compounds, besides SAFM, a Néel AFM metal without orbital ordering is observed, and an orbital selective Mott phase (OSMP) accompanied by an intermediate-spin to high-spin transition is also found, giving a possible scenario of an OSMP in KxFe2-ySe2. These results demonstrate that the band filling and correlation control the Fermi surface topology, electronic state and magnetism in KxFe2-ySe2.

  1. P2Y1R-initiated, IP3R-dependent stimulation of astrocyte mitochondrial metabolism reduces and partially reverses ischemic neuronal damage in mouse

    PubMed Central

    Zheng, Wei; Talley Watts, Lora; Holstein, Deborah M; Wewer, Jimmy; Lechleiter, James D

    2013-01-01

    Glia-based neuroprotection strategies are emerging as promising new avenues to treat brain damage. We previously reported that activation of the glial-specific purinergic receptor, P2Y1R, reduces both astrocyte swelling and brain infarcts in a photothrombotic mouse model of stroke. These restorative effects were dependent on astrocyte mitochondrial metabolism. Here, we extend these findings and report that P2Y1R stimulation with the purinergic ligand 2-methylthioladenosine 5′ diphosphate (2MeSADP) reduces and partially reverses neuronal damage induced by photothrombosis. In vivo neuronal morphology was confocally imaged in transgenic mice expressing yellow fluorescent protein under the control of the Thy1 promoter. Astrocyte mitochondrial membrane potentials, monitored with the potential sensitive dye tetra-methyl rhodamine methyl ester, were depolarized after photothrombosis and subsequently repolarized when P2Y1Rs were stimulated. Mice deficient in the astrocyte-specific type 2 inositol 1,4,5 trisphosphate (IP3) receptor exhibited aggravated ischemic dendritic damage after photothrombosis. Treatment of these mice with 2MeSADP did not invoke an intracellular Ca2+ response, did not repolarize astrocyte mitochondria, and did not reduce or partially reverse neuronal lesions induced by photothrombotic stroke. These results demonstrate that IP3-Ca2+ signaling in astrocytes is not only critical for P2Y1R-enhanced protection, but suggest that IP3-Ca2+ signaling is also a key component of endogenous neuroprotection. PMID:23321785

  2. The effect of purinergic signaling via the P2Y11 receptor on vascular function in a rat model of acute inflammation.

    PubMed

    Dănilă, Maria D; Privistirescu, Andreea; Duicu, Oana M; Rațiu, Corina D; Angoulvant, Denis; Muntean, Danina M; Sturza, Adrian

    2017-02-17

    There is a growing body of evidence pointing to the role of purinergic signaling in the development and progression of various conditions that have inflammation as a common pathogenetic denominator. The aim of the present study was to assess the involvement of P2Y11 purinergic receptors in the regulation of vascular function in aortic segments obtained using an experimental model of acute inflammation, the lipopolysaccharide (LPS, 8 mg/kg, i.p)-treated rats. Twelve hours after LPS administration, thoracic aortas were isolated and used for studies of vascular reactivity in the organ bath and for the measurement of reactive oxygen species (ROS) generation, respectively. LPS treatment significantly increased contractility to phenylephrine and attenuated the endothelium-dependent relaxation of the vascular segments in response to acetylcholine; an increased production of hydrogen peroxide (H2O2) was also recorded. The P2Y11 activator, NF546, decreased the LPS-induced aortic H2O2 release and partially normalized the vasomotor function, namely reduced contractility and improved relaxation. The effect was abolished by co-treatment with the P2Y11 inhibitor, NF340, and also after endothelium denudation. Importantly, NF546 did not elicit an antioxidant effect by acting as a H2O2 scavenger, suggesting that the beneficial outcome of this treatment on the vasculature is the consequence of P2Y11 stimulation. In conclusion, purinergic P2Y11 receptors stimulation improves vascular function and mitigates oxidative stress in the setting of acute systemic inflammation, revealing salutary effects and therapeutic potential in pathologies associated with endothelial dysfunction.

  3. Bradykinin-induced Ca2+ signaling in human subcutaneous fibroblasts involves ATP release via hemichannels leading to P2Y12 receptors activation

    PubMed Central

    2013-01-01

    Background Chronic musculoskeletal pain involves connective tissue remodeling triggered by inflammatory mediators, such as bradykinin. Fibroblast cells signaling involve changes in intracellular Ca2+ ([Ca2+]i). ATP has been related to connective tissue mechanotransduction, remodeling and chronic inflammatory pain, via P2 purinoceptors activation. Here, we investigated the involvement of ATP in bradykinin-induced Ca2+ signals in human subcutaneous fibroblasts. Results Bradykinin, via B2 receptors, caused an abrupt rise in [Ca2+]i to a peak that declined to a plateau, which concentration remained constant until washout. The plateau phase was absent in Ca2+-free medium; [Ca2+]i signal was substantially reduced after depleting intracellular Ca2+ stores with thapsigargin. Extracellular ATP inactivation with apyrase decreased the [Ca2+]i plateau. Human subcutaneous fibroblasts respond to bradykinin by releasing ATP via connexin and pannexin hemichannels, since blockade of connexins, with 2-octanol or carbenoxolone, and pannexin-1, with 10Panx, attenuated bradykinin-induced [Ca2+]i plateau, whereas inhibitors of vesicular exocytosis, such as brefeldin A and bafilomycin A1, were inactive. The kinetics of extracellular ATP catabolism favors ADP accumulation in human fibroblast cultures. Inhibition of ectonucleotidase activity and, thus, ADP formation from released ATP with POM-1 or by Mg2+ removal from media reduced bradykinin-induced [Ca2+]i plateau. Selective blockade of the ADP-sensitive P2Y12 receptor with AR-C66096 attenuated bradykinin [Ca2+]i plateau, whereas the P2Y1 and P2Y13 receptor antagonists, respectively MRS 2179 and MRS 2211, were inactive. Human fibroblasts exhibited immunoreactivity against connexin-43, pannexin-1 and P2Y12 receptor. Conclusions Bradykinin induces ATP release from human subcutaneous fibroblasts via connexin and pannexin-1-containing hemichannels leading to [Ca2+]i mobilization through the cooperation of B2 and P2Y12 receptors. PMID

  4. Effects of pioglitazone on platelet P2Y12-mediated signalling in clopidogrel-treated patients with type 2 diabetes mellitus.

    PubMed

    Suryadevara, Siva; Ueno, Masafumi; Tello-Montoliu, Antonio; Ferreiro, Jose Luis; Desai, Bhaloo; Rollini, Fabiana; Box, Lyndon C; Zenni, Martin; Guzman, Luis A; Bass, Theodore A; Angiolillo, Dominick J

    2012-11-01

    Patients with type 2 diabetes mellitus (T2DM) have impaired clopidogrel-induced antiplatelet effects, which may be in part attributed to their reduced sensitivity to insulin and consequently, results in upregulation of the P2Y12 signalling pathway. It has been hypothesised that insulin sensitising strategies may enhance clopidogrel-mediated P2Y12 inhibitory effects. The aim of this pilot pharmacodynamics (PD) study was to assess the impact of pioglitazone on clopidogrel-mediated P2Y12 inhibitory effects in patients with T2DM. This was a prospective, randomised, double-blind, placebo-controlled, cross-over PD study. Patients with T2DM and stable coronary artery disease on maintenance aspirin and clopidogrel were randomised to receive either pioglitazone 30 mg or matching placebo daily for 14 days. PD assessments were measured at baseline, 14 days after randomisation, at the end of the wash-out period, and 14 days after cross-over. The primary endpoint measure was maximal platelet aggregation (MPA) to 20 μM adenosine diphosphate (ADP) as assessed by light transmittance aggregometry (LTA). Flow cytometric analysis of vasodilator-stimulated phosphoprotein phosphorylation (VASP-PRI), and VerifyNow P2Y12 testing were also performed. A total of 15 randomised patients completed the study. MPA to 20 μM ADP (primary endpoint) was not significantly different with pioglitazone compared with placebo (49.53 ± 4.76 vs. 52.52 ± 3.89%; p = 0.594). Similarly, other PD measures did not differ significantly between the groups. In conclusion, in patients with T2DM on maintenance aspirin and clopidogrel therapy, the adjunctive use of pioglitazone does not result in enhanced inhibition of platelet P2Y12 mediated signalling.

  5. Development of quercetin-phospholipid complex to improve the bioavailability and protection effects against carbon tetrachloride-induced hepatotoxicity in SD rats.

    PubMed

    Zhang, Kexia; Zhang, Meiyu; Liu, Ziying; Zhang, Yuanyuan; Gu, Liqiang; Hu, Gaosheng; Chen, Xiaohui; Jia, Jingming

    2016-09-01

    Quercetin (QT) is a natural flavonoid with various biological activities and pharmacological actions. However, the bioavailability of QT is relatively low due to its low solubility which severely limits its use. In this study, we intended to improve the bioavailability of QT by preparing quercetin-phospholipid complex (QT-PC) and investigate the protective effect of QT-PC against carbon tetrachloride (CCl4) induced acute liver damage in Sprague-Dawley (SD) rats. The physicochemical properties of QT-PC were characterized in terms of infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (XRPD) and water/n-octanol solubility. FTIR, DSC and XRPD data confirmed the formation of QT-PC. The water solubility of QT was improved significantly in the prepared complex, indicating its increased hydrophilicity. Oral bioavailability of QT and QT-PC was evaluated in SD rats, and the plasma QT was estimated by HPLC-MS. QT-PC exhibited higher Cmax (1.58±0.11 vs. 0.67±0.08μg/mL), increased AUC0-∞ (8.60±1.25 vs. 2.41±0.51mg/Lh) and t1/2z (7.76±1.09 vs. 4.81±0.87h) when compared to free QT. The greater absorption of QT-PC group suggested the improved bioavailability. Moreover, biochemical changes and histopathological observations revealed that QT-PC provided better protection to rat liver than free QT at the same dose. Thus, phospholipid complexation might be one of the suitable approaches to improve the oral bioavailability of QT and obtain better protective effects against CCl4 induced acute liver damage in SD rats than free QT at the same dose level.

  6. SD 1313-0019: Another Second-generation Star with [Fe/H] = -5.0, Observed with the Magellan Telescope

    NASA Astrophysics Data System (ADS)

    Frebel, Anna; Chiti, Anirudh; Ji, Alexander P.; Jacobson, Heather R.; Placco, Vinicius M.

    2015-09-01

    We present a Magellan/MIKE high-resolution (R ˜ 35,000) spectrum of the ancient star SD 1313-0019, which has an iron abundance of [Fe/H]=-5.0, paired with a carbon enhancement of [C/Fe]˜ 3.0. The star was initially identified by Allende Prieto et al. in the BOSS survey. Its medium-resolution spectrum suggested a higher metallicity of [Fe/H]=-4.3 due to the Ca II K line blending with a CH feature, which is a common issue related to the search for the most iron-poor stars. This star joins several other similar stars with [Fe/H]≲ -5.0 that all display a combination of low-iron and high-carbon abundances. Other elemental abundances of SD 1313-0019 follow that of more metal-rich halo stars. Fitting the abundance pattern with yields of Population III supernovae suggests that SD 1313-0019 had only one massive progenitor star with 20-30 M⊙ that must have undergone a mixing and fallback episode. Overall, there are now five stars known with [Fe/H]≲ -5.0 (1D local thermodynamic equilibrium abundances). This ever-increasing population of carbon-rich, iron-deficient stars can potentially constrain nucleosynthesis in Population III stars and their supernova explosions, the formation mechanisms of the first low-mass stars, and the nature of the first galaxies. This paper includes data gathered with the 6.5 m Magellan Telescopes located at Las Campanas Observatory, Chile.

  7. Reliability of manual measurements of corneal thickness obtained from healthy canine eyes using spectral-domain optical coherence tomography (SD-OCT).

    PubMed

    Alario, Anthony F; Pirie, Christopher G

    2014-07-01

    The purpose of this study was to manually measure corneal thickness in canine eyes using a spectral-domain optical coherence tomography (SD-OCT) device and to assess intra- and inter-observer reliability of this technique. Twenty healthy dogs with a mean age of 4.7 y were examined. A 6-mm corneal pachymetry protocol was carried out by 1 operator using 1 SD-OCT device in both eyes of each animal. Measurements were obtained manually and in duplicate by 2 independent investigators (> 24 h apart), using the built-in caliper function. Measurements included epithelial thickness (ET), non-epithelial thickness (NET), and central corneal thickness (CCT). The overall mean ET, NET, and CCT for all eyes examined were 72.3 ± 4.6 μm, 538.9 ± 42.5 μm, and 611.2 ± 40.3 μm, respectively. There was no significant difference in ET, NET, or CCT based on the eye examined [oculus dexter (OD) versus oculus sinister (OS)], age, or gender of the animal. There was no significant difference in replicate measurements of ET, NET, or CCT done by the same operator, although a small but significant difference was noted between operators for ET measurements only. The mean difference in ET between operators was 0.6 μm (P = 0.03). The coefficient of variation ranged from 0.5% to 9.27% and intraclass correlation coefficient ranged from 0.35 to 0.97. Based on these results, manual measurements of corneal thickness in canine eyes using a portable SD-OCT device provided ET, NET, and CCT measurements with clinically acceptable intra- and inter-observer reliability.

  8. Weak Interaction Rates of sd-SHELL Nuclei in Stellar Environments Calculated in the Proton-Neutron Quasiparticle Random-Phase Approximation

    NASA Astrophysics Data System (ADS)

    Nabi, J.-U.; Klapdor-Kleingrothaus, H. V.

    1999-03-01

    Allowed weak interaction rates for sd-shell nuclei in stellar environment are calculated using a generalized form of proton-neutron quasi-particle RPA model with separable Gamow-Teller forces. The calculated capture and decay rates take into consideration the latest experimental energy levels and ft-value compilations. Weak rates calculated are tabulated at the same points of density and temperature as those of Oda et al. [Atomic Data and Nuclear Data Tables 56, 231 (1994)]. The results are also compared with earlier works. Particle emission processes from excited states, previously ignored, are taken into account and are found to significantly affect some β decay rates.

  9. References for HNF-SD-WM-TRD-007, ``System specification for the double-shell tank system: HNF-PROs, CFRs, DOE Orders, WACs``

    SciTech Connect

    Shaw, C.P.

    1998-07-30

    HNF-SD-WM-TRD-O07, System Specification for the Double-Shell Tank System, (hereafter referred to as DST Specification), defines the requirements of the double-shell tank system at the Hanford Site for Phase 1 privatization. Many of the sections in this document reference other documents for design guidance and requirements. Referenced documents include Project Hanford Management Contract (PHMC) procedures (HNF-PROS), Codes of Federal Regulation (CFRs), DOE Orders, and Washington Administrative Codes (WACs). This document provides rationale for the selection and inclusion of HNF-PROS, CFRs, DOE Orders and WACs.

  10. Does i-T744C P2Y12 Polymorphism Modulate Clopidogrel Response among Moroccan Acute Coronary Syndromes Patients?

    PubMed Central

    Hmimech, Wiam; El Khorb, Nada; Akoudad, Hafid; Habbal, Rachida; Nadifi, Sellama

    2017-01-01

    Background. An interindividual variability in response to Clopidogrel has been widely described in patients with acute coronary syndromes (ACS). The contribution of genetics on modulating this response was widely discussed. The objective of our study was to investigate the potential effect of i-T744C P2Y12 polymorphism on Clopidogrel response in a sample of Moroccan ACS patients. We tried also to determine the frequency of this polymorphism among Moroccan ACS compared to healthy subjects. Methods and Results. 77 ACS patients versus 101 healthy controls were recruited. DNA samples were genotyped by PCR-RFLP method. The VerifyNow assay was used to evaluate platelet function among ACS patients. Our results show that the mutant allele C was more frequent among ACS ST (+) than ST (−) patients (39% versus 19.8%, resp.), when the wild-type allele was more represented in the ACS ST (−) group (80.2%). The C allele frequency was higher among resistant than nonresistant patients (30% versus 20.8%, resp.). Comparison of ACS patients and healthy controls shows higher frequency of mutant C allele among cases compared to controls (22.73% versus 19.31%, resp.); there was a statistically significant association of the recessive and additive transmission models with the ACS development risk (OR [95% CI] = 1.78 [1.58–5.05], P = 0.01 and OR [95% CI] = 1.23 [0.74–2.03], P < 0.001, resp.), increasing thus the association of this polymorphism with the pathology. Conclusion. Our results suggest that this polymorphism may have a potential effect on Clopidogrel response among our Moroccan ACS patients and also on ACS development. PMID:28261502

  11. Preparation, crystal structure and superconductivity of (C, Cu)(Sr, Ca) 2(Y, Ca, Sr)Cu 2O 7

    NASA Astrophysics Data System (ADS)

    Miyazaki, Y.; Yamane, H.; Kajitani, T.; Kobayashi, N.; Hiraga, K.; Morii, Y.; Funahashi, S.; Hirai, T.

    1994-09-01

    A series of solid solutioins containing CO 3 groups, (c ycu 1-y)(Sr 1-z/2Ca z/2) 2(Y 1-xCa x-zSr z)Cu 2 O dd with 0.30≤ x≤0.70, was prepared at 1313 K under the atmosphere of O 2-CO 2. The values of y (0.48-0.67) and z (0.14-0.28) depend on the total Ca content, x. The length of the a-axis increase from 3.8374(2) Å ( x=0.30) to 3.8591(9) Å ( x=0.70) with increasing x, while the c-axis length decreases from 11.1198(6) to 10.9410(6) Å. All the as-prepared solid solutions are semiconductors, but superconducting transition is observed for the samples with 0.35≤ × ≤0.70 after annealing at 1273 K and an oxygen pressure of 4.0 MPa. The transition temperature ( T c increases with increasing x, and the highest Tc=60 K is measured for the samples with 0.60≤ x≤0.70. All the annealed samples show appreciable expansion of the c-axis length and contraction of the a-axis length relative to the as-prepared ones. The crystal structures of the as-prepared and annealed samples with x = .50 were refined from neutron powder diffraction data by means of the Rietveld method. On the basis of the refined crystal structure data and wet chemical analysis, it is suggested that hole doping is caused, during high-pressure oxygen annealing, by the release of some CO 3 groups and by the introduction of oxygen atoms into the vacant “apical” oxygen site, where the CO 3 group is not present.

  12. Local structure and ionic conductivity in the Zr2Y2O7-Y3NbO7 system

    NASA Astrophysics Data System (ADS)

    Norberg, Stefan T.; Ahmed, Istaq; Hull, Stephen; Marrocchelli, Dario; Madden, Paul A.

    2009-05-01

    The Zr0.5-0.5xY0.5+0.25xNb0.25xO1.75 solid solution possesses an anion-deficient fluorite structure across the entire 0<=x<=1 range. The relationship between the disorder within the crystalline lattice and the preferred anion diffusion mechanism has been studied as a function of x, using impedance spectroscopy measurements of the ionic conductivity (σ), powder neutron diffraction studies, including analysis of the 'total' scattering to probe the nature of the short-range correlations between ions using reverse Monte Carlo (RMC) modelling, and molecular dynamics (MD) simulations using potentials derived with a strong ab initio basis. The highest total ionic conductivity (σ = 2.66 × 10-2 Ω-1 cm-1 at 1473 K) is measured for the Zr2Y2O7 (x = 0) end member, with a decrease in σ with increasing x, whilst the neutron diffraction studies show an increase in lattice disorder with x. This apparent contradiction can be understood by considering the local structural distortions around the various cation species, as determined from the RMC modelling and MD simulations. The addition of Nb5+ and its stronger Coulomb interaction generates a more disordered local structure and enhances the mobility of some anions. However, the influence of these pentavalent cations is outweighed by the effect of the additional Y3+ cations introduced as x increases, which effectively trap many anions and reduce the overall concentration of the mobile O2- species.

  13. The hybrid lattice of KxFe2-ySe2: why superconductivity and magnetism can coexist

    SciTech Connect

    Louca, Despina; Park, Keeseong; Li, Bing; Neuefeind, Joerg C; Yan, Jiaqiang

    2013-01-01

    It is always puzzling to observe superconductivity in atomically disordered systems as it contradicts the very nature of electronic state coherence, but nevertheless happens as in amorphous alloys1. How can superconductivity survive under conditions for strong electron localization2? To understand the effects of disorder, a family of recently discovered Fe-based superconductors3-6 is investigated, the KxFe2-ySe2 (7) where nominally, superconductivity is observed between a semi-metallic region below 0.7 < x < 0.85 insulating and antiferromagnetic region above8,9. By probing the local structure we observe that superconductivity emerges in a locally distorted Fe sublattice that accommodates two kinds of bond environments, forming a double-well distribution. Consisting of short bonds which are metallic in nature and of long ones which are insulating and antiferromagnetic, their distribution changes with x. Even though crystallographically the atomic structure changes slowly on average by adding K10, a continuous transition from the metallic (short) to the insulating (long) Fe bonds is observed across this region. What is unique to this system s superconducting state is the presence of the double-well distribution in equal proportions, in contrast to other Fe-based materials where only one kind of Fe bond is present. This suggests that in this superconducting system, superconductivity is intertwined with magnetism, appearing at the crossover from metallic to insulating conditions and is not due to phase separation. Such a hybrid state is most likely present in cuprate superconductors as well and may be more common than previously expected.

  14. Distribution of P2Y2 receptors in the guinea pig enteric nervous system and its coexistence with P2X2 and P2X3 receptors, neuropeptide Y, nitric oxide synthase and calretinin.

    PubMed

    Xiang, Zhenghua; Burnstock, Geoffrey

    2005-11-01

    The distribution of P2Y2 receptor-immunoreactive (ir) neurons and fibers and coexistence of P2Y2 with P2X2 and P2X3 receptors, neuropeptide Y (NPY), calretinin (CR), calbindin (CB) and nitric oxide synthase (NOS) was investigated with immunostaining methods. The results showed that P2Y2-ir neurons and fibers were distributed widely in myenteric and submucous plexuses of the guinea pig stomach corpus, jejunum, ileum and colon. The typical morphology of P2Y2-ir neurons was a long process with strong positive staining on the same side of the cell body. The P2Y2-ir neurons could be Dogiel type 1. About 40-60% P2X3-ir neurons were immunoreactive for P2Y2 in the myenteric plexus and all the P2X3-ir neurons expressed the P2Y2 receptor in the submucosal plexus; almost all the NPY-ir neurons and the majority of CR-ir neurons were also immunoreactive for P2Y2, especially in the myenteric plexus of the small intestine; no P2Y2-ir neurons were immunoreactive for P2X2 receptors, CB and NOS. It is shown for the first time that S type/Dogiel type 1 neurons with fast P2X and slow P2Y receptor-mediated depolarizations could be those neurons expressing both P2Y2-ir and P2X3-ir and that they are widely distributed in myenteric and submucosal plexuses of guinea pig gut.

  15. Single oral dose toxicity test of polycalcium, a mixed composition of polycan and calcium lactate-gluconate 1:9 (G/G) in SD rat.

    PubMed

    Kim, Joo-Wan; Choi, Jae-Suk; Ha, Yu-Mi; Choi, In Soon; Kim, Ki-Young; Cho, Hyung-rae; Rha, Chae-hun; Ku, Sae-Kwang

    2013-11-01

    The object of this study was to obtain acute oral toxicity information of Polycalcium, a mixed composition of Polycan and Calcium lactate-gluconate 1:9 (g/g), in Sprague-Dawely (SD) rats. In order to investigate the toxicity and identify target organs, Polycalcium were once orally administered to female and male SD rats at dose levels of 2000, 1000, 500 and 0 (control) mg/kg body weights. The mortality, changes on body weight and clinical signs were monitored during 14 days after treatment with gross observation, changes on the organ weights and histopathology of principle organs and treatment sites based on the recommendation of KFDA Guidelines [2009-116, 2009]. As the results of single oral treatment of Polycalcium, no treatment related mortalities were observed within 14 days after end of treatment up to 2000 mg/kg, the limited dosage of rodents in the both genders. In addition, no Polycalcium treatment related changes on the body and organ weights, clinical signs, necropsy and histopathological findings were detected. The results obtained in this study suggest that the Polycalcium is non-toxic in rats. The LD50 and approximate LD in rats after single oral dose of Polycalcium were considered over 2000 mg/kg in both female and male, respectively.

  16. Automated segmentation of optic disc in SD-OCT images and cup-to-disc ratios quantification by patch searching-based neural canal opening detection.

    PubMed

    Wu, Menglin; Leng, Theodore; de Sisternes, Luis; Rubin, Daniel L; Chen, Qiang

    2015-11-30

    Glaucoma is one of the most common causes of blindness worldwide. Early detection of glaucoma is traditionally based on assessment of the cup-to-disc (C/D) ratio, an important indicator of structural changes to the optic nerve head. Here, we present an automated optic disc segmentation algorithm in 3-D spectral domain optical coherence tomography (SD-OCT) volumes to quantify this ratio. The proposed algorithm utilizes a two-stage strategy. First, it detects the neural canal opening (NCO) by finding the points with maximum curvature on the retinal pigment epithelium (RPE) boundary with a spatial correlation smoothness constraint on consecutive B-scans, and it approximately locates the coarse disc margin in the projection image using convex hull fitting. Then, a patch searching procedure using a probabilistic support vector machine (SVM) classifier finds the most likely patch with the NCO in its center in order to refine the segmentation result. Thus, a reference plane can be determined to calculate the C/D radio. Experimental results on 42 SD-OCT volumes from 17 glaucoma patients demonstrate that the proposed algorithm can achieve high segmentation accuracy and a low C/D ratio evaluation error. The unsigned border error for optic disc segmentation and the evaluation error for C/D ratio comparing with manual segmentation are 2.216 ± 1.406 pixels (0.067 ± 0.042 mm) and 0.045 ± 0.033, respectively.

  17. THE ROMER DELAY AND MASS RATIO OF THE sdB+dM BINARY 2M 1938+4603 FROM KEPLER ECLIPSE TIMINGS

    SciTech Connect

    Barlow, Brad N.; Wade, Richard A.; Liss, Sandra E.

    2012-07-10

    The eclipsing binary system 2M 1938+4603 consists of a pulsating hot subdwarf B star and a cool M dwarf companion in an effectively circular three-hour orbit. The light curve shows both primary and secondary eclipses, along with a strong reflection effect from the cool companion. Here, we present constraints on the component masses and eccentricity derived from the Romer delay of the secondary eclipse. Using six months of publicly available Kepler photometry obtained in short-cadence mode, we fit model profiles to the primary and secondary eclipses to measure their centroid values. We find that the secondary eclipse arrives on average 2.06 {+-} 0.12 s after the midpoint between primary eclipses. Under the assumption of a circular orbit, we calculate from this time delay a mass ratio of q = 0.2691 {+-} 0.0018 and individual masses of M{sub sd} = 0.372 {+-} 0.024 M{sub Sun} and M{sub c} = 0.1002 {+-} 0.0065 M{sub Sun} for the sdB and M dwarf, respectively. These results differ slightly from those of a previously published light-curve modeling solution; this difference, however, may be reconciled with a very small eccentricity, ecos {omega} Almost-Equal-To 0.00004. We also report a decrease in the orbital period of P-dot = (-1.23 {+-} 0.07) Multiplication-Sign 10{sup -10}.

  18. Vibrational relaxation dynamics of SD molecules in As{sub 2}S{sub 3}: Observation of an anomalous isotope effect

    SciTech Connect

    Engholm, J.R.; Happek, U.; Rella, C.W.

    1995-12-31

    It is generally assumed that the vibrational relaxation of molecular impurities in crystals and glasses mainly depends on the order of the decay process, with lower order processes leading to more rapid relaxation (a behavior that is known under the term {open_quotes}gap-law{close_quotes}). Here we present measurements that contradict this assumption. Using high intensity psec pulses of the Stanford FEL we measured the relaxation rate of the SD vibrational stretch mode (at a frequency of 1800 cm) by applying a pump-probe technique. We find relaxation rates on the order of 2x10{sup 9} sec{sup -1}, which are a factor of 2 lower than those found for the isotope molecule SH (at a frequency of about 2500 cm{sup - 1}) in the same host{sup 1}. We recall that the relaxation of the SD vibrational stretch mode is controlled by a lower order process as compared to the SH molecule, which is due to the smaller number of host vibrational quanta to match the energy of the stretch mode; a fact we have confirmed experimentally by temperature dependent relaxation measurements. Thus our remits are in marked contrast to the so-called {open_quotes}Gap-Law{close_quotes} and emphasize the importance of the molecule - host coupling in the relaxation dynamics.

  19. Analysis of helium-rich subdwarf O stars. 1: NLTE models, methods, and fits for 21 Palomar Green survey sdOs

    NASA Technical Reports Server (NTRS)

    Thejll, P.; Bauer, F.; Saffer, R.; Liebert, J.; Kunze, D.; Shipman, H. L.

    1994-01-01

    Atmospheric parameters for 21 helium-rich hot subdwarf O stars from the Palomar Green survey are found from fits of non-local thermodynamic equilibrium (NLTE) models to optical spectra. About 250 new NLTE models in the parameter range T(sub eff) from 35,000 to 65,000 K, log (g) from 4.0 to 6.5, and epsilon(He) from 50% He to 99% He have been calculated. A fit for each object is presented. Estimated distances and luminosities are calculated, assuming a mass of 0.5 solar masses. Large distances above the Galactic plane are found, and this implies that the majority of the sdO stars belong to a different stellar population than the sdB, planetary nebulae and white dwarf stars. Possibilities may include the halo and a 'thick disk.' Kinematical data from the literature are also discussed in view of the found distances. Five of the stars have been observed, modeled, and analyzed by Dreizler et al., and significant differences exist between their results and ours for these stars. The reason for these differences is not yet known, but the problem does not alter the conclusions about population membership that we present.

  20. A dietary embryo/fetal developmental toxicity study of arruva, an R,R-monatin salt isomer, in Crl:CD(SD) rats.

    PubMed

    Brathwaite, W A; Casterton, P L; Nikiforov, A I; Rihner, M O; Sloter, E D; Hlywka, J J

    2013-12-01

    R,R-Monatin is an intensely sweet substance originally identified in the root bark of Sclerochiton ilicifolius. R,R-Monatin salt, commonly known as "arruva", has potential for use as a high-potency sweetener food ingredient. Previously, arruva was concluded to present no toxicologically relevant effects to Crl:CD(SD) rats and Crl:CD-1(ICR) mice fed up to 35,000 ppm arruva in the diet for 90 days. In the present study, groups of mated Sprague-Dawley rats (25 Crl:CD(SD) females/group) were exposed continuously to 0 (control), 15,000, 30,000, or 50,000 ppm arruva in the diet during gestation days 6-21. There were no fetal malformations or developmental variations that were attributable to arruva at any exposure level, nor were there any test article-related effects on intrauterine survival. Maternal toxicity, evidenced by lower mean body weights, body weight gains and feed efficiency, was observed at 50,000 ppm. A developmental effect, in the form of lower mean fetal body weight, was noted in the 50,000 ppm group in the presence of maternal toxicity. Therefore, the dietary no-observed-adverse-effect level (NOAEL) for maternal and embryo/fetal developmental toxicity of arruva in pregnant rats during gestation days 6-21 was 30,000 ppm (equivalent to 2564 mg/kg bw/day) based on reductions in maternal and fetal body weights.

  1. Use of 2,3,5-F3Y-β2 and 3-NH2Y-α2 to study PCET in E. coli Ribonucleotide Reductase

    PubMed Central

    Seyedsayamdost, Mohammad R.; Yee, Cyril S.; Stubbe, JoAnne

    2011-01-01

    E. coli ribonucleotide reductase is an α2β2 complex that catalyzes the conversion of nucleoside 5′-diphosphates (NDPs) to deoxynucleotides (dNDPs). The active site for NDP reduction resides in α2, and the essential diferric-tyrosyl radical (Y122•) cofactor that initiates radical transfer to the active site cysteine in α2 (C439), 35 Å removed, is in β2. The oxidation is proposed to involve a hopping mechanism through aromatic amino acids (Y122→W48→Y356 in β2 to Y731→Y730→C439 in α2) and reversible proton coupled electron transfer (PCET). Recently 2,3,5-F3Y (F3Y) was site-specifically incorporated in place of Y356 in β2, and 3-NH2Y (NH2Y) in place of Y731 and Y730 in α2. A pH rate profile with F3Y356-β2 suggested that as the pH is elevated, the rate-determining step of RNR can be altered from a conformational change to PCET and that the altered driving force for F3Y oxidation, by residues adjacent to it in the pathway, is responsible for this change. Studies with NH2Y731(730)-α2/β2/CDP/ATP resulted in detection of NH2Y radical (NH2Y•) intermediates capable of dNDP formation. In this study, the reaction of F3Y356-β2/α2/CDP/ATP has been examined by stopped flow (SF) absorption and rapid freeze quench EPR spectroscopy and has failed to reveal any radical intermediates. F3Y356-β2/CDP/ATP has also been examined with NH2Y731-α2 (or NH2Y730-α2) by stopped-flow kinetics from pH 6.5–9.2 and revealed rate constants for NH2Y• formation that support a change in rate limiting step at elevated pH. The results together with kinetic simulations provide a guide for future studies to detect radical intermediates in the pathway. PMID:21182280

  2. P2Y1 receptor modulation of Ca2+-activated K+ currents in medium-sized neurons from neonatal rat striatal slices

    PubMed Central

    Coppi, E.; Pedata, F.

    2012-01-01

    ATP signaling to neurons and glia in the nervous system occurs via activation of both P2Y and P2X receptors. Here, we investigated the effects of P2Y1 receptor stimulation in developing striatal medium-sized neurons using patch-clamp recordings from acute brain slices of 7- and 28-day-old rats. Application of the selective P2Y1 receptor agonist 2-(Methylthio) ADP trisodium salt (2-MeSADP; 250 nM) increased outward K+ currents evoked by a ramp depolarization protocol in voltage-clamp recordings. This effect was observed in 59 out of 82 cells (72%) and was blocked completely by the P2Y1 antagonist, 2′-deoxy-N6-methyl adenosine 3′,5′-diphosphate. The averaged 2-MeSADP-sensitive conductance was fitted by the sum of a linear conductance and a Boltzmann relation, giving one-half activation voltage of −14.2 mV and an equivalent charge of 2.91. The 2MeSADP-mediated effect was sensitive to submillimolar concentrations of tetraethylammonium (TEA; 200 μM), to 200 nM iberiotoxin and to 100 nM apamin, suggesting the involvement of both big and small potassium (BK and SK, respectively) calcium-activated channels. In current-clamp experiments, 2-MeSADP decreased depolarization-evoked action potential (AP) firing in all 26 cells investigated, and this effect was reversed by TEA and by apamin but not by iberiotoxin. We conclude that the stimulation of P2Y1 receptors in developing striatal neurons leads to activation of calcium-activated potassium channels [IK(Ca)] of both BK and SK subtypes, the latter responsible for decreasing the frequency of AP firing in response to current injection. Therefore, P2Y1 signaling leading to activation of IK(Ca) may be important in regulating the activity of medium-sized neurons in the striatum. PMID:22131374

  3. The rice semi-dwarf mutant sd37, caused by a mutation in CYP96B4, plays an important role in the fine-tuning of plant growth.

    PubMed

    Zhang, Jie; Liu, Xiaoqiang; Li, Shuyu; Cheng, Zhukuan; Li, Chuanyou

    2014-01-01

    Plant cytochrome P450 has diverse roles in developmental processes and in the response to environmental cues. Here, we characterized the rice (Oryza sativa L ssp. indica cultivar 3037) semi-dwarf mutant sd37, in which the gene CYP96B4 (Cytochrome P450 96B subfamily) was identified and confirmed as the target by map-based cloning and a complementation test. A point mutation in the SRS2 domain of CYP96B4 resulted in a threonine to lysine substitution in the sd37 mutant. Examination of the subcellular localization of the protein revealed that SD37 was ER-localized protein. And SD37 was predominantly expressed in the shoot apical meristem and developing leaf and root maturation zone but not in the root apical meristem. The sd37 leaves, panicles, and seeds were smaller than those of the wild type. Histological analysis further revealed that a decrease in cell number in the mutant, specifically in the shoots, was the main cause of the dwarf phenotype. Microarray analysis demonstrated that the expression of several cell division-related genes was disturbed in the sd37 mutant. In addition, mutation or strongly overexpression of SD37 results in dwarf plants but moderate overexpression increases plant height. These data suggest that CYP96B4 may be an important regulator of plant growth that affects plant height in rice.

  4. Evaluation of Global Photosynthesis and BVOC Emission Covariance with Climate in NASA ModelE2-Y

    NASA Astrophysics Data System (ADS)

    Unger, N.

    2012-12-01

    Terrestrial gross primary productivity (GPP), a measure of the total amount of CO2 removed from the atmosphere every year to fuel photosynthesis, is the largest global carbon flux. GPP is vital for human welfare as the basis for food and fiber, and provides the crucial ecosystem service of reducing the accumulation of fossil fuel CO2 in the atmosphere. Land plants emit a significant fraction of the assimilated carbon back to the atmosphere in the form of biogenic volatile organic compounds (BVOCs). Isoprene is the dominant BVOC emission with an estimated global source of 200-660 TgC/yr. Global monoterpene emission estimates range from 30-130 TgC/yr. BVOC photochemical oxidation exerts a profound impact on the distribution and variability of the short-lived climate forcers: ozone, biogenic secondary organic aerosol and methane. Here, we apply multiple observational datasets from a suite of platforms to evaluate an updated global chemistry-climate model that is coupled to a new vegetation biophysics scheme incorporating photosynthesis-dependent BVOC emissions (NASA ModelE2-Y). A fixed vegetation structure dataset based on 8 plant functional types and prescribed phenology including crop planting and harvesting gives GPP of 128 PgC/yr and a global isoprene source of 200TgC/yr. The model GPP captures 85% of the annual average zonal mean variability in a FLUXNET-derived global dataset that was generated by data orientated diagnostic upscaling. We assess model BVOC emission climatology against a comprehensive database of campaign-average above canopy flux measurements and surface concentrations of isoprene and monoterpene collected between 1995-2010 across a wide range of ecosystem types, regions and seasons (> 25 flux estimates; > 22 surface concentration values). We evaluate the diurnal, seasonal and interannual integrity of the model BVOC variability against 9 sites for isoprene and 4 sites for monoterpene. The model captures ~60% of the variability in the time

  5. ROS Production via P2Y1-PKC-NOX2 Is Triggered by Extracellular ATP after Electrical Stimulation of Skeletal Muscle Cells

    PubMed Central

    Díaz-Vegas, Alexis; Campos, Cristian A.; Contreras-Ferrat, Ariel; Casas, Mariana; Buvinic, Sonja; Jaimovich, Enrique; Espinosa, Alejandra

    2015-01-01

    During exercise, skeletal muscle produces reactive oxygen species (ROS) via NADPH oxidase (NOX2) while inducing cellular adaptations associated with contractile activity. The signals involved in this mechanism are still a matter of study. ATP is released from skeletal muscle during electrical stimulation and can autocrinely signal through purinergic receptors; we searched for an influence of this signal in ROS production. The aim of this work was to characterize ROS production induced by electrical stimulation and extracellular ATP. ROS production was measured using two alternative probes; chloromethyl-2,7- dichlorodihydrofluorescein diacetate or electroporation to express the hydrogen peroxide-sensitive protein Hyper. Electrical stimulation (ES) triggered a transient ROS increase in muscle fibers which was mimicked by extracellular ATP and was prevented by both carbenoxolone and suramin; antagonists of pannexin channel and purinergic receptors respectively. In addition, transient ROS increase was prevented by apyrase, an ecto-nucleotidase. MRS2365, a P2Y1 receptor agonist, induced a large signal while UTPyS (P2Y2 agonist) elicited a much smaller signal, similar to the one seen when using ATP plus MRS2179, an antagonist of P2Y1. Protein kinase C (PKC) inhibitors also blocked ES-induced ROS production. Our results indicate that physiological levels of electrical stimulation induce ROS production in skeletal muscle cells through release of extracellular ATP and activation of P2Y1 receptors. Use of selective NOX2 and PKC inhibitors suggests that ROS production induced by ES or extracellular ATP is mediated by NOX2 activated by PKC. PMID:26053483

  6. ROS Production via P2Y1-PKC-NOX2 Is Triggered by Extracellular ATP after Electrical Stimulation of Skeletal Muscle Cells.

    PubMed

    Díaz-Vegas, Alexis; Campos, Cristian A; Contreras-Ferrat, Ariel; Casas, Mariana; Buvinic, Sonja; Jaimovich, Enrique; Espinosa, Alejandra

    2015-01-01

    During exercise, skeletal muscle produces reactive oxygen species (ROS) via NADPH oxidase (NOX2) while inducing cellular adaptations associated with contractile activity. The signals involved in this mechanism are still a matter of study. ATP is released from skeletal muscle during electrical stimulation and can autocrinely signal through purinergic receptors; we searched for an influence of this signal in ROS production. The aim of this work was to characterize ROS production induced by electrical stimulation and extracellular ATP. ROS production was measured using two alternative probes; chloromethyl-2,7- dichlorodihydrofluorescein diacetate or electroporation to express the hydrogen peroxide-sensitive protein Hyper. Electrical stimulation (ES) triggered a transient ROS increase in muscle fibers which was mimicked by extracellular ATP and was prevented by both carbenoxolone and suramin; antagonists of pannexin channel and purinergic receptors respectively. In addition, transient ROS increase was prevented by apyrase, an ecto-nucleotidase. MRS2365, a P2Y1 receptor agonist, induced a large signal while UTPyS (P2Y2 agonist) elicited a much smaller signal, similar to the one seen when using ATP plus MRS2179, an antagonist of P2Y1. Protein kinase C (PKC) inhibitors also blocked ES-induced ROS production. Our results indicate that physiological levels of electrical stimulation induce ROS production in skeletal muscle cells through release of extracellular ATP and activation of P2Y1 receptors. Use of selective NOX2 and PKC inhibitors suggests that ROS production induced by ES or extracellular ATP is mediated by NOX2 activated by PKC.

  7. Cell density-dependent changes in intracellular Ca2+ mobilization via the P2Y2 receptor in rat bone marrow stromal cells.

    PubMed

    Ichikawa, Jun; Gemba, Hisae

    2009-05-01

    Bone marrow stromal cells (BMSCs) are an interesting subject of research because they have characteristics of mesenchymal stem cells. We investigated intracellular Ca(2+) signaling in rat BMSCs. Agonists for purinergic receptors increased intracellular Ca(2+) levels ([Ca(2+)](i)). The order of potency followed ATP = UTP > ADP = UDP. ATP-induced rise in [Ca(2+)](i) was suppressed by U73122 and suramin, but not by pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS), suggesting the functional expression of G protein-coupled P2Y(2) receptors. RT-PCR and immunohistochemical studies also showed the expression of P2Y(2) receptors. [Ca(2+)](i) response to UTP changed with cell density. The UTP-induced rise in [Ca(2+)](i) was greatest at high density. V(max) (maximum Ca(2+) response) and EC(50) (agonist concentration that evokes 50% of V(max)) suggest that the amount and property of P2Y(2) receptors were changed by cell density. Note that UTP induced Ca(2+) oscillation at only medium cell density. Pharmacological studies indicated that UTP-induced Ca(2+) oscillation required Ca(2+) influx by store-operated Ca(2+) entry. Carbenoxolone, a gap junction blocker, enhanced Ca(2+) oscillation. Immunohistochemical and quantitative real-time PCR studies revealed that proliferating cell nuclear antigen (PCNA)-positive cells declined but the mRNA expression level of the P2Y(2) receptor increased as cell density increased. Co-application of fetal calf serum with UTP induced Ca(2+) oscillation at high cell density. These results suggest that the different patterns observed for [Ca(2+)](i) mobilization with respect to cell density may be associated with cell cycle progression.

  8. Selective inhibition of beta(2)-adrenergic receptor-mediated cAMP generation by activation of the P2Y(2) receptor in mouse pineal gland tumor cells.

    PubMed

    Suh, B C; Kim, J S; Namgung, U; Han, S; Kim, K T

    2001-06-01

    Rhythmic noradrenergic signaling from the hypothalamic clock in the suprachiasmatic nucleus to the pineal gland causes an increase in intracellular cAMP which regulates the circadian fluctuation of melatonin synthesis. The activation of phospholipase C (PLC)-coupled P2Y(2) receptors upon treatment with ATP and UTP exclusively inhibited the isoproterenol-stimulated cAMP production in mouse pineal gland tumor cells. However, the activation of other PLC-coupled receptors including P2Y(1) and bombesin receptors had little or no effect on the isoproterenol-stimulated cAMP production. Also, ATP did not inhibit cAMP production caused by forskolin, prostaglandin E(2), or the adenosine analog NECA. These results suggest a selective coupling between signalings of P2Y(2) and beta(2)-adrenergic receptors. The binding of [(3)H]CGP12177 to beta(2)-adrenergic receptors was not effected by the presence of ATP or UTP. Ionomycin decreased the isoproterenol-stimulated cAMP production, whereas phorbol 12-myristate 13-acetate slightly potentiated the isoproterenol response. Chelation of intracellular Ca(2+), however, had little effect on the ATP-induced inhibition of cAMP production, while it completely reversed the ionomycin-induced inhibition. Treatment of cells with pertussis toxin almost completely blocked the inhibitory effect of nucleotides. Pertussis toxin also inhibited the nucleotide-induced increase in intracellular Ca(2+) and inositol 1,4,5-trisphosphate production by 30-40%, suggesting that the ATP-mediated inhibition of the cAMP generation and the partial activation of PLC are mediated by pertussis toxin-sensitive G(i)-protein. We conclude that one of the functions of P2Y(2) receptors on the pineal gland is the selective inhibition of beta-adrenergic receptor-mediated signaling pathways via the inhibitory G-proteins.

  9. P2Y12 Inhibitor Pre-Treatment in Non-ST-Elevation Acute Coronary Syndrome: A Decision-Analytic Model

    PubMed Central

    Gunton, James; Hartshorne, Trent; Langrish, Jeremy; Chuang, Anthony; Chew, Derek

    2016-01-01

    Current guidelines recommend initiation of a P2Y12 inhibitor for all patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) at the time of diagnosis (pre-treatment); however, there are no randomized trials directly comparing pre-treatment with initiation at the time of angiography to support this practice. We explore clinical and institutional parameters potentially associated with benefit with this strategy in a decision-analytic model based on available evidence from randomised trials. A decision analysis model was constructed comparing three P2Y12 inhibitors in addition to aspirin in patients with NSTE-ACS. Based on clinical trial data, the cumulative probability of 30 day mortality, myocardial infarction (MI) and major bleeding were determined, and used to calculate the net clinical benefit (NCB) with and without pre-treatment. Sensitivity analysis was performed to assess the relationship between NCB and baseline ischemic risk, bleeding risk, time to angiography and local surgical revascularization rates. Pre-treatment with ticagrelor and clopidogrel was associated with a greater than 50% likelihood of providing a >1% increase in 30 day NCB when baseline estimated ischemic risk exceeds 11% and 14%, respectively. Prasugrel pre-treatment did not achieve a greater than 50% probability of an increase in NCB regardless of baseline ischemic risk. Institutional surgical revascularization rates and time to coronary angiography did not correlate with the likelihood of benefit from P2Y12 pre-treatment. In conclusion, pre-treatment with P2Y12 inhibition is unlikely to be beneficial to the majority of patients presenting with NSTE-ACS. A tailored assessment of each patient’s individual ischemic and bleeding risk may identify those likely to benefit. PMID:27548237

  10. P2Y6 Receptor Antagonist MRS2578 Inhibits Neutrophil Activation and Aggregated Neutrophil Extracellular Trap Formation Induced by Gout-Associated Monosodium Urate Crystals.

    PubMed

    Sil, Payel; Hayes, Craig P; Reaves, Barbara J; Breen, Patrick; Quinn, Shannon; Sokolove, Jeremy; Rada, Balázs

    2017-01-01

    Human neutrophils (polymorphonuclear leukocytes [PMNs]) generate inflammatory responses within the joints of gout patients upon encountering monosodium urate (MSU) crystals. Neutrophil extracellular traps (NETs) are found abundantly in the synovial fluid of gout patients. The detailed mechanism of MSU crystal-induced NET formation remains unknown. Our goal was to shed light on possible roles of purinergic signaling and neutrophil migration in mediating NET formation induced by MSU crystals. Interaction of human neutrophils with MSU crystals was evaluated by high-throughput live imaging using confocal microscopy. We quantitated NET levels in gout synovial fluid supernatants and detected enzymatically active neutrophil primary granule enzymes, myeloperoxidase, and human neutrophil elastase. Suramin and PPADS, general P2Y receptor blockers, and MRS2578, an inhibitor of the purinergic P2Y6 receptor, blocked NET formation triggered by MSU crystals. AR-C25118925XX (P2Y2 antagonist) did not inhibit MSU crystal-stimulated NET release. Live imaging of PMNs showed that MRS2578 represses neutrophil migration and blocked characteristic formation of MSU crystal-NET aggregates called aggregated NETs. Interestingly, the store-operated calcium entry channel inhibitor (SK&F96365) also reduced MSU crystal-induced NET release. Our results indicate that the P2Y6/store-operated calcium entry/IL-8 axis is involved in MSU crystal-induced aggregated NET formation, but MRS2578 could have additional effects affecting PMN migration. The work presented in the present study could lead to a better understanding of gouty joint inflammation and help improve the treatment and care of gout patients.

  11. The Effect of Microstructure on Mechanical Properties of Directionally Solidified Al2O3/ZrO2(Y2O3) Eutectic

    NASA Technical Reports Server (NTRS)

    Sayir, Ali; Farmer, Serene C.

    1999-01-01

    The eutectic architecture of a continuous reinforcing phase within a higher volume fraction phase or matrix can be described as a naturally occurring in-situ composite. Here we report the results of experiments aimed at identifying the sources of high temperature creep resistance and high levels of strength in a two phase Al2O3/ZrO2(Y2O3) system. The mechanical properties of two phase Al2O3/ZrO2(Y2O3) eutectic are superior to those of either constituent alone due to strong constraining effects provided by the coherent interfaces and microstructure. The AlO3/ZrO2(Y2O3) eutectic maintains a low energy interface resulting from directional solidification and can produce strong and stable reinforcing phase/matrix bonding. The phases comprising a eutectic are thermodynamically compatible at higher homologous temperatures than man-made composites and as such offer the potential for superior high temperature properties.

  12. On the electrical properties of the Bi2-ySryIr2O7 pyrochlore solid solution: Quantum ab initio and classic calculations

    NASA Astrophysics Data System (ADS)

    de la Mora, Pablo; Cosio-Castañeda, Carlos; Martinez-Anaya, Oliver; Morales, Francisco; Tavizon, Gustavo

    2016-09-01

    In this work, a theoretical study of the electrical properties of the Bi2-ySryIr2O7 (Bi2-ySryIr2O16O2) α-pyrochlore-type solid solution is presented. Quantum ab initio DFT(WIEN2k) calculations were performed in order to understand the electrical resistivity changes associated to the Bi substitution by Sr in this system. The main crystallographic modification associated to this substitution is the x position of the 48f oxygen (x, 1/8 , 1/8 ) (O1); this substitution substantially modifies the Bi/Sr-O1 and Ir-O1 atomic distances, increasing the former and diminishing the latter. Experimentally, the Bi2-ySryIr2O7 samples are metallic and the electrical resistivity increases with the Sr content. Electronic structure calculations for Bi2Ir2O7 and BiSrIr2O7 show that, regardless of structural changes, there is only a small change of electrical conductivity with the Sr substitution, and the experimentally observed increase of the resistivity can be explained in terms of a larger impact on the electronic structure of both; the Sr 'impurities' as well as of the thermal Sr oscillations.

  13. The impact of P2Y12 promoter DNA methylation on the recurrence of ischemic events in Chinese patients with ischemic cerebrovascular disease

    PubMed Central

    Li, Xin-Gang; Ma, Ning; Wang, Bo; Li, Xiao-Qing; Mei, Sheng-Hui; Zhao, Kun; Wang, Yong-Jun; Li, Wei; Zhao, Zhi-Gang; Sun, Shu-Sen; Miao, Zhong-Rong

    2016-01-01

    The primary mechanism of clopidogrel resistance is still unclear. We aimed to investigate whether the methylation status of the P2Y12 promoter has effects on platelet function and clinical ischemic events. Patients with ischemic cerebrovascular disease were enrolled into our study. Venous blood samples were drawn for thrombelastograpy (TEG) and active metabolite assay. Patients were divided into a case- or control-group based on the occurrence of ischemic events during a one year follow-up. Two TEG parameters between the case and control groups were statistically significant [ADP inhibition rate (ADP%): P = 0.018; ADP-induced platelet-fibrin clot strength (MAADP): P = 0.030]. The concentrations of clopidogrel active metabolite had no significant difference (P = 0.281). Sixteen CpG dinucleotides on P2Y12 promoter were tested. Three CpG sites (CpG11 and CpG12 + 13) showed lower methylation status, which correlated with a strong association with increased risk of clinical events. Changes of MAADP and ADP% were also associated with methylation levels of CpG 11 and CpG 12 + 13. Hypomethylation of the P2Y12 promoter is associated with a higher platelet reactivity and increased risk of ischemic events in our patients. Methylation analysis of peripheral blood samples might be a novel molecular marker to help early identification of patients at high risk for clinical ischemic events. PMID:27686864

  14. Purinergic glio-endothelial coupling during neuronal activity: role of P2Y1 receptors and eNOS in functional hyperemia in the mouse somatosensory cortex.

    PubMed

    Toth, Peter; Tarantini, Stefano; Davila, Antonio; Valcarcel-Ares, M Noa; Tucsek, Zsuzsanna; Varamini, Behzad; Ballabh, Praveen; Sonntag, William E; Baur, Joseph A; Csiszar, Anna; Ungvari, Zoltan

    2015-12-01

    Impairment of moment-to-moment adjustment of cerebral blood flow (CBF) via neurovascular coupling is thought to play a critical role in the genesis of cognitive impairment associated with aging and pathological conditions associated with accelerated cerebromicrovascular aging (e.g., hypertension, obesity). Although previous studies demonstrate that endothelial dysfunction plays a critical role in neurovascular uncoupling in these conditions, the role of endothelial NO mediation in neurovascular coupling responses is not well understood. To establish the link between endothelial function and functional hyperemia, neurovascular coupling responses were studied in mutant mice overexpressing or deficient in endothelial NO synthase (eNOS), and the role of P2Y1 receptors in purinergic glioendothelial coupling was assessed. We found that genetic depletion of eNOS (eNOS(-/-)) and pharmacological inhibition of NO synthesis significantly decreased the CBF responses in the somatosensory cortex evoked by whisker stimulation and by administration of ATP. Overexpression of eNOS enhanced NO mediation of functional hyperemia. In control mice, the selective and potent P2Y1 receptor antagonist MRS2179 attenuated both whisker stimulation-induced and ATP-mediated CBF responses, whereas, in eNOS(-/-) mice, the inhibitory effects of MRS2179 were blunted. Collectively, our findings provide additional evidence for purinergic glio-endothelial coupling during neuronal activity, highlighting the role of ATP-mediated activation of eNOS via P2Y1 receptors in functional hyperemia.

  15. Tunneling conductance of normal metal/dx2-y2-wave superconductor junctions in the presence of broken time-reversal symmetry states near interfaces

    NASA Astrophysics Data System (ADS)

    Tanuma, Y.; Tanaka, Y.; Kashiwaya, S.

    2001-12-01

    In order to clarify the influence of (the presence of) the broken time-reversal symmetry state (BTRSS) induced near the interface, tunneling conductance spectra in normal metal/dx2-y2-wave superconductor junctions are calculated on the basis of the quasiclassical Green's function method. The spatial dependence of the pair potential in the superconductor side is determined self-consistently. We discuss two types of the symmetry on the BTRSS: (i) dx2-y2+is-wave state and (ii) dx2-y2+idxy-wave state. It is shown that the amplitude of the subdominant component (is wave or idxy wave) is quite sensitive to the transmission coefficient of the junction. As the results, the splitting of the zero-bias conductance peak due to the BTRSS inducement is detectable only at junctions with small transmission coefficients for both cases. When the transmission coefficients are relatively large, the explicit peak splitting does not occur and the difference in the two cases appears in the height of the zero-bias peaks.

  16. Fabrication and mechanical properties of continuously graded WSi{sub 2}-ZrO{sub 2}(2Y) materials using wet-molding

    SciTech Connect

    Arata, K.; Yoshinaka, M.; Hirota, K.; Yamaguchi, O.

    1998-04-01

    Continuously graded WSi{sub 2}-ZrO{sub 2}(2Y) materials with high density (99.2% of theoretical) have been fabricated by uniaxial wet-molding, followed by hot pressing (1,000 C/1h/30MPa) and hot isostatic pressing (1,500 C/2h/196MPa). A mixed solution of glycerin and ethanol with the viscosity of {approx} 6 mPa{center_dot}s has been used as a dispersion medium in the molding process. The sintered materials show a linear composition profile with a transition from WSi{sub 2}/ZrO{sub 2}(2Y) {approx} 75/25 to {approx} 5/95 mol%. Vickers hardness, Hv, for which the value is {approx} 11.2 GPa, is almost independent of the compositional change. Fracture toughness, K{sub C}, increases from 5.6 to 10.3 MPa{center_dot}m{sup 1/2} with increasing ZrO{sub 2}(2Y) composition.

  17. B{sub s(d)}-B{sub s(d)} mixing constraints on flavor changing decays of t and b quarks

    SciTech Connect

    Faessler, Amand; Gutsche, Thomas; Lyubovitskij, Valery E.; Kovalenko, Sergey; Schmidt, Ivan

    2010-10-01

    We study those dimension 6 effective operators which generate flavor-changing quark-gluon transitions of the third generation quarks, with t{yields}g+u(c) and b{yields}g+d(s), and which could be of interest for LHC experiments. We analyze the contribution of these operators to B{sub s(d)}-B{sub s(d)} mixing and derive limits on the corresponding effective couplings from the existing experimental data. The standard model gauge invariance relates these couplings to the couplings controlling t{yields}g+u(c). On this basis we derive upper limits for the branching ratios of these processes. We further show that forthcoming LHC experiments might be able to probe the studied operators and the physics beyond the standard model related to them.

  18. Multimodal Segmentation of Optic Disc and Cup from SD-OCT and Color Fundus Photographs Using a Machine-Learning Graph-Based Approach

    PubMed Central

    Miri, Mohammad Saleh; Abràmoff, Michael D.; Lee, Kyungmoo; Niemeijer, Meindert; Wang, Jui-Kai; Kwon, Young H.

    2015-01-01

    In this work, a multimodal approach is proposed to use the complementary information from fundus photographs and spectral domain optical coherence tomography (SD-OCT) volumes in order to segment the optic disc and cup boundaries. The problem is formulated as an optimization problem where the optimal solution is obtained using a machine-learning theoretical graph-based method. In particular, first the fundus photograph is registered to the 2D projection of the SD-OCT volume. Three in-region cost functions are designed using a random forest classifier corresponding to three regions of cup, rim, and background. Next, the volumes are resampled to create radial scans in which the Bruch’s Membrane Opening (BMO) endpoints are easier to detect. Similar to in-region cost function design, the disc-boundary cost function is designed using a random forest classifier for which the features are created by applying the Haar Stationary Wavelet Transform (SWT) to the radial projection image. A multisurface graph-based approach utilizes the in-region and disc-boundary cost images to segment the boundaries of optic disc and cup under feasibility constraints. The approach is evaluated on 25 multimodal image pairs from 25 subjects in a leave-one-out fashion (by subject). The performances of the graph-theoretic approach using three sets of cost functions are compared: 1) using unimodal (OCT only) in-region costs, 2) using multimodal in-region costs, and 3) using multimodal in-region and disc-boundary costs. Results show that the multimodal approaches outperform the unimodal approach in segmenting the optic disc and cup. PMID:25781623

  19. Di-(2-ethylhexyl) phthalate could disrupt the insulin signaling pathway in liver of SD rats and L02 cells via PPARγ.

    PubMed

    Zhang, Wang; Shen, Xin-Yue; Zhang, Wen-Wen; Chen, Hao; Xu, Wei-Ping; Wei, Wei

    2017-02-01

    Di-(2-ethylhexyl)-phthalate (DEHP), a ubiquitous industrial pollutant in our daily life, has been reported to cause adverse effects on glucose homeostasis and insulin sensitivity in epidemiological studies previously. Recently, it has been reported to be an endocrine disrupter and ligand to peroxisome proliferator activated receptor, which could influence the homeostasis of liver metabolic systems and contribute to the development of type-2 diabetes. However, the potential mechanisms are not known yet. This study was designed to solve these problems with male SD rats and normal human hepatocyte line, L02 cells, exposed to DEHP for toxicological experiments. Adult male SD rats were divided into four groups, normal group fed with regular diets and three DEHP-treated groups (dissolved in olive oil at doses of 0.05, 5 and 500mg/kg body weight, respectively, once daily through gastric intubations for 15weeks). L02 cells were divided into 6 groups, normal group with 5, 10, 25, 50, and 100μmol/l DEHP groups. DEHP-exposed rats exhibited significant liver damage, glucose tolerance, and insulin tolerance along with reduced expression of insulin receptor and GLUT4 proteins in the liver tissues. The results of in vitro experiments could determine that the DEHP-induced activation of peroxisome proliferator activated receptor γ (PPARγ) played a key role in the production of oxidative stress and down-regulated expression of insulin receptor and GLUT4 proteins in L02 cells. This conclusion could be supported by the results of in vitro experiments, in which the cells were exposed to DEHP with GW9662 (PPARγ inhibitor). In general, these results highlight the key role of PPARγ in the process of insulin resistance induced by DEHP.

  20. Rapid, accurate, and non-invasive measurement of zebrafish axial length and other eye dimensions using SD-OCT allows longitudinal analysis of myopia and emmetropization.

    PubMed

    Collery, Ross F; Veth, Kerry N; Dubis, Adam M; Carroll, Joseph; Link, Brian A

    2014-01-01

    Refractive errors in vision can be caused by aberrant axial length of the eye, irregular corneal shape, or lens abnormalities. Causes of eye length overgrowth include multiple genetic loci, and visual parameters. We evaluate zebrafish as a potential animal model for studies of the genetic, cellular, and signaling basis of emmetropization and myopia. Axial length and other eye dimensions of zebrafish were measured using spectral domain-optical coherence tomography (SD-OCT). We used ocular lens and body metrics to normalize and compare eye size and relative refractive error (difference between observed retinal radial length and controls) in wild-type and lrp2 zebrafish. Zebrafish were dark-reared to assess effects of visual deprivation on eye size. Two relative measurements, ocular axial length to body length and axial length to lens diameter, were found to accurately normalize comparisons of eye sizes between different sized fish (R2=0.9548, R2=0.9921). Ray-traced focal lengths of wild-type zebrafish lenses were equal to their retinal radii, while lrp2 eyes had longer retinal radii than focal lengths. Both genetic mutation (lrp2) and environmental manipulation (dark-rearing) caused elongated eye axes. lrp2 mutants had relative refractive errors of -0.327 compared to wild-types, and dark-reared wild-type fish had relative refractive errors of -0.132 compared to light-reared siblings. Therefore, zebrafish eye anatomy (axial length, lens radius, retinal radius) can be rapidly and accurately measured by SD-OCT, facilitating longitudinal studies of regulated eye growth and emmetropization. Specifically, genes homologous to human myopia candidates may be modified, inactivated or overexpressed in zebrafish, and myopia-sensitizing conditions used to probe gene-environment interactions. Our studies provide foundation for such investigations into genetic contributions that control eye size and impact refractive errors.

  1. An experimental study on use of 7T MRI for evaluation of myocardial infarction in SD rats transfected with pcDNA 3.1(+)/VEGF121 plasmid

    PubMed Central

    Zhang, Yan; Tian, Ruiqing; Shen, Xiangchun; Chen, Yushu; Chen, Wei; Gan, Lu; Shen, Guiquan; Ju, Haiyue; Yang, Li; Gao, Fabao

    2016-01-01

    This study aims to build the myocardial infarction model in SD rats transfected with pcDNA 3.1(+)/VEGF121 plasmid and study the effect of the transfection using 7T MRI. Twenty-four male SD rats were randomly divided into 2 groups, pcDNA 3.1(+)/VEGF121 plasmid transfection group (with improved coronary perfusion delivery) and myocardial infarction model group. Cardiac cine magnetic resonance imaging (Cine-MRI), T2-mapping and late gadolinium enhancement (LGE) cardiac imaging were performed at 24 h, 48 h, 72 h and 7 d after myocardial infarction, respectively. The signal intensity, area at risk (AAR), myocardium infarction core (MIC) and salvageable myocardial zone (SMZ) were compared. The hearts were harvested for anatomic characterization, which was related to pathological examination (TTC staining, HE staining, Masson staining and immunohistochemical staining). The Cine-MRI results showed that pcDNA 3.1(+)/VEGF121 plasmid transfection group had higher end-diastolic volume (EDV) with a reduction in MIC and SMZ, as compared with the myocardial infarction model group. MIC, SMZ and AAR of the plasmid transfection declined over time. At 7 d, the two groups did not differ significantly in AAR and T2 value. According to Western Blotting, VEGF was up-regulated, while CaSR and caspase-3 were downregulated in the plasmid transfection group, as compared with the model group. In conclusion, a good treatment effect was achieved by coronary perfusion of pcDNA 3.1(+)/VEGF121 plasmid. 7T CMR sequences provide a non-invasive quantification of the treatment efficacy. However, the assessment of myocardial injury using T2 value and AAR in the presence of edema is less accurate. The myocardial protection of the plasmid transfection group may be related to the inhibition of myocardial apoptosis, vascular endothelial cell (VEC) proliferation and collagen proliferation. The CaSR signaling pathway may contribute to reversing the apoptosis. PMID:27648128

  2. ELECTRON-CAPTURE AND β-DECAY RATES FOR sd-SHELL NUCLEI IN STELLAR ENVIRONMENTS RELEVANT TO HIGH-DENSITY O–NE–MG CORES

    SciTech Connect

    Suzuki, Toshio; Toki, Hiroshi; Nomoto, Ken’ichi

    2016-02-01

    Electron-capture and β-decay rates for nuclear pairs in the sd-shell are evaluated at high densities and high temperatures relevant to the final evolution of electron-degenerate O–Ne–Mg cores of stars with initial masses of 8–10 M{sub ⊙}. Electron capture induces a rapid contraction of the electron-degenerate O–Ne–Mg core. The outcome of rapid contraction depends on the evolutionary changes in the central density and temperature, which are determined by the competing processes of contraction, cooling, and heating. The fate of the stars is determined by these competitions, whether they end up with electron-capture supernovae or Fe core-collapse supernovae. Since the competing processes are induced by electron capture and β-decay, the accurate weak rates are crucially important. The rates are obtained for pairs with A = 20, 23, 24, 25, and 27 by shell-model calculations in the sd-shell with the USDB Hamiltonian. Effects of Coulomb corrections on the rates are evaluated. The rates for pairs with A = 23 and 25 are important for nuclear Urca processes that determine the cooling rate of the O–Ne–Mg core, while those for pairs with A = 20 and 24 are important for the core contraction and heat generation rates in the core. We provide these nuclear rates at stellar environments in tables with fine enough meshes at various densities and temperatures for studies of astrophysical processes sensitive to the rates. In particular, the accurate rate tables are crucially important for the final fates of not only O–Ne–Mg cores but also a wider range of stars, such as C–O cores of lower-mass stars.

  3. The involvement of P2Y12 receptors, NADPH oxidase, and lipid rafts in the action of extracellular ATP on synaptic transmission at the frog neuromuscular junction.

    PubMed

    Giniatullin, A; Petrov, A; Giniatullin, R

    2015-01-29

    Adenosine 5'-triphosphate (ATP) is the main co-transmitter accompanying the release of acetylcholine from motor nerve terminals. Previously, we revealed the direct inhibitory action of extracellular ATP on transmitter release via redox-dependent mechanism. However, the receptor mechanism of ATP action and ATP-induced sources of reactive oxygen sources (ROS) remained not fully understood. In the current study, using microelectrode recordings of synaptic currents from the frog neuromuscular junction, we analyzed the receptor subtype involved in synaptic action of ATP, receptor coupling to NADPH oxidase and potential location of ATP receptors within the lipid rafts. Using subtype-specific antagonists, we found that the P2Y13 blocker 2-[(2-chloro-5-nitrophenyl)azo]-5-hydroxy-6-methyl-3-[(phosphonooxy)methyl]-4-pyridinecarboxaldehyde did not prevent the depressant action of ATP. In contrast, the P2Y12 antagonist 2-methylthioadenosine 5'-monophosphate abolished the inhibitory action of ATP, suggesting the key role of P2Y12 receptors in ATP action. As the action of ATP is redox-dependent, we also tested potential involvement of the NADPH oxidase, known as a common inducer of ROS. The depressant action of extracellular ATP was significantly reduced by diphenyleneiodonium chloride and 4-(2-aminoethyl)-benzenesulfonyl fluoride hydrochloride, two structurally different inhibitors of NADPH oxidase, indicating that this enzyme indeed mediates the action of ATP. Since the location and activity of various receptors are often associated with lipid rafts, we next tested whether ATP-driven inhibition depends on lipid rafts. We found that the disruption of lipid rafts with methyl-beta-cyclodextrin reduced and largely delayed the action of ATP. Taken together, these data revealed key steps in the purinergic control of synaptic transmission via P2Y12 receptors associated with lipid rafts, and identified NADPH oxidase as the main source of ATP-induced inhibitory ROS at the neuromuscular

  4. Platelet reactivity after administration of third generation P2Y12-antagonists does not depend on body weight in contrast to clopidogrel.

    PubMed

    Olivier, Christoph B; Schnabel, Katharina; Weber, Susanne; Zhou, Qian; Bode, Christoph; Moser, Martin; Diehl, Philipp

    2016-07-01

    The current standard of antiplatelet therapy for patients with myocardial infarction (MI) includes the P2Y12-receptor antagonist clopidogrel, prasugrel or ticagrelor. While it has been shown that platelet reactivity after clopidogrel administration depends on factors such as body weight, it is not known if these factors have an effect on the activity of prasugrel or ticagrelor. Thus, this study aimed to analyse factors associated with high residual platelet reactivity after administration of third generation P2Y12-antagonists compared to clopidogrel. In a single centre registry the antiplatelet effect of clopidogrel, prasugrel or ticagrelor was investigated by aggregometry in patients after MI. To assess the overall capacity of platelet aggregation whole blood was induced with thrombin receptor activating peptide (TRAP; 32 µM). To specifically quantify the effect of P2Y12-antagonists, blood was stimulated with 6.4 µM adenosine diphophosphate (ADP). Relative ADP induced aggregation (r-ADP-agg) was defined as the ADP-TRAP-ratio to reflect an individual degree of P2Y12-dependent platelet inhibition. Platelet function of 238 patients was analysed [clopidogrel (n = 58), prasugrel (n = 65), ticagrelor (n = 115)]. It was found that the r-ADP-agg correlated significantly with body weight in patients after clopidogrel administration (r = 0.423; p < 0.001). In contrast, this association was not present in patients after prasugrel (r = -0.117; p = 0.354) or ticagrelor (r = -0.082; p = 0.382) administration. Comparison of the correlation coefficients showed a significant difference (p = 0.003). In contrast to clopidogrel, platelet reactivity after administration of prasugrel or ticagrelor does not depend on body weight in patients after MI. Hence, our mechanistic data support the results of large clinical trials indicating that patients with high body weight do not need to be treated with increased doses of third generation P2Y12-antagonists to achieve

  5. P2Y2 receptor activation opens pannexin-1 channels in rat carotid body type II cells: potential role in amplifying the neurotransmitter ATP

    PubMed Central

    Zhang, Min; Piskuric, Nikol A; Vollmer, Cathy; Nurse, Colin A

    2012-01-01

    Signal processing in the carotid body (CB) is initiated at receptor glomus (or type I) cells which depolarize and release the excitatory neurotransmitter ATP during chemoexcitation by hypoxia and acid hypercapnia. Glomus cell clusters (GCs) occur in intimate association with glia-like type II cells which express purinergic P2Y2 receptors (P2Y2Rs) but their function is unclear. Here we immunolocalize the gap junction-like protein channel pannexin-1 (Panx-1) in type II cells and show Panx-1 mRNA expression in the rat CB. As expected, type II cell activation within or near isolated GCs by P2Y2R agonists, ATP and UTP (100 μm), induced a rise in intracellular [Ca2+]. Moreover in perforated-patch whole cell recordings from type II cells, these agonists caused a prolonged depolarization and a concentration-dependent, delayed opening of non-selective ion channels that was prevented by Panx-1 blockers, carbenoxolone (5 μm) and 4,4′-diisothiocyano-2,2′-stilbenedisulfonic acid (DIDS; 10 μm). Because Panx-1 channels serve as conduits for ATP release, we hypothesized that paracrine, type II cell P2Y2R activation leads to ATP-induced ATP release. In proof-of-principle experiments we used co-cultured chemoafferent petrosal neurones (PNs), which express P2X2/3 purinoceptors, as sensitive biosensors of ATP released from type II cells. In several cases, UTP activation of type II cells within or near GCs led to depolarization or increased firing in nearby PNs, and the effect was reversibly abolished by the selective P2X2/3 receptor blocker, pyridoxalphosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS; 10 μm). We propose that CB type II cells may function as ATP amplifiers during chemotransduction via paracrine activation of P2Y2Rs and Panx-1 channels. PMID:22733659

  6. Investigation of global variations in the in amplitude and frequency content of the PdP, SdS and Pds phases from common upper mantle discontinuities

    NASA Astrophysics Data System (ADS)

    Ainiwaer, A.; Gurrola, H.; Zou, Z.

    2013-12-01

    The global existence of transition zone discontinuities at 410 km and 660 km depths and both almost universally observed in PdP, SdS and Pds data but the 520 and 660 are usually not observed in PdP data.. Discontinuities at approximately 220 km and 520 km depth are observed in these types of data at many regions. The discontinuities at 410, 520 and 660 km are believed to be the polymorphic phase transition zone in olivine. At 410 km discontinuity, α-olivine transforms to β-wadsleyite while γ-ringwoodite decomposes into wusite and provskite at 660 discontinuity while the 220 is usually considered to be the LAB and caused by partial melt. The contrast of elastic properties and the thickness of discontinuity can be estimated by investigating the amplitude of reflected or converted seismic waves. Recent progress in our ability to image these discontinuities in PP and SS data have made it possible to image these PdP and SdS phases to a much as 4 Hz. This will make it possible to investigate the frequency response of these phases to frequencies previously not possible; analysis of which makes it possible add new insight as to the nature of these boundaries. For example beneath the regions beneath the Line Island and the Aleutian Trench The PdP phase has amplitudes of 0.04 to 0.08, which is significantly higher than beneath Hawaii(0.02-0.04) and the region near the Nazca Plate and South American subduction zone Plate where the PdP phase has amplitudes of 0.02-0.04. We interpret that the difference of reflection amplitudes is the result of variations in the impedance between layers due to variations in the velocity and density contrast and the sharpness thereof. For example in most region investigated the P510P is not present in our data but is present in some regions such as the Line Islands. But the phase change expected for the 520 is usually considered to occur over a wide range of depths in which case it should not be visible anywhere at such high frequencies

  7. Optical and scintillation properties of ce-doped (Gd2Y1)Ga2.7Al2.3O12 single crystal grown by Czochralski method

    NASA Astrophysics Data System (ADS)

    Wang, Chao; Wu, Yuntao; Ding, Dongzhou; Li, Huanying; Chen, Xiaofeng; Shi, Jian; Ren, Guohao

    2016-06-01

    Multicomponent garnets, due to their excellent light yield and energy resolution, become one of the most promising scintillators used for homeland security and nuclear non-proliferation applications. This work focuses on the optimization of Ce-doped (Gd,Y)3(Ga,Al)5O12 scintillators using a combination strategy of pre-screening and scale-up. Ce-doped GdxY1-xGayAl5-yO12 (x=1, 2 and y=2, 2.2, 2.5, 2.7, 3) polycrystalline powders were prepared by high-temperature solid state reaction method. The desired garnet phase in all the samples was confirmed using X-ray diffraction measurement. By comparing the radioluminescence intensity, the highest scintillation efficiency was achieved at a component of Gd2Y1Ga2.7Al2.3O12:Ce powders. A (Gd2Y1)Ga2.7Al2.3O12 doped with 1% Ce single crystal with dimensions of Ø35×40 mm was grown by Czochralski method using a <111> oriented seed. Luminescence and scintillation properties were measured. An optical transmittance of 84% was achieved in the concerned wavelength from 500 to 800 nm. Its 5d-4f emission of Ce3+ is at 530 nm. The light yield of a Ce1%: Gd2Y1Ga2.7Al2.3O12 single crystal slab at a size of 5×5×1 mm3 can reach about 65,000±3000 Ph/MeV along with two decay components of 94 and 615 ns under 137Cs source irradiation.

  8. Crystal structure and luminescence properties of Bi3+activated Ca2Y8(SiO4)6O2 phosphors under near UV excitation

    NASA Astrophysics Data System (ADS)

    Sun, Zhihua; Wang, Minqiang; Yang, Zhi; Liu, Kaiping; Zhu, Feiyan

    2016-07-01

    Oxyapatite Ca2Y8-x(SiO4)6O2:xBi3+phosphor has been prepared via high temperature solid-state reaction. Its crystal structure and PL properties were investigated by X-ray diffraction, photoluminescence excitation and emission spectra. The results indicated that the Ca2Y8(SiO4)6O2 crystallizes as a hexagonal structure with a space group of P63/m and lattice constants of a=b=9.3507 Å, c=6.7899 Å, α=β=90.00°, γ=120.00°, V=514.14 Å3; The phosphor has two prominent emission bands: when excited under 320-360 nm, the phosphors emit a broad band centered at 495 nm due to the 3P1-1S0 transition of Bi3+ in 4f (C3) sites; when excited under 380 nm, the phosphors emit a broad band centered at 411 nm due to the 3P1-1S0 transition of Bi3+ in 6h (Cs) sites. The emission color varies from the greenish blue to blue as the excitation wavelength increases from 335 to 380 nm. The optimal intensity of emission band was observed when x=0.015 in the Ca2Y8-x(SiO4)6O2:xBi3+ series. The average critical distance Rc among Bi3+ ions is determined to be 20.15 Å.

  9. A model-based analysis of the clinical and economic impact of personalising P2Y12-receptor inhibition with platelet function testing in acute coronary syndrome patients.

    PubMed

    Straub, Niels; Beivers, Andreas; Lenk, Ekaterina; Aradi, Daniel; Sibbing, Dirk

    2014-02-01

    Although some observational studies reported that the measured level of P2Y12-inhibition is predictive for thrombotic events, the clinical and economic benefit of incorporating PFT to personalize P2Y12-receptor directed antiplatelet treatment is unknown. Here, we assessed the clinical impact and cost-effectiveness of selecting P2Y12-inhibitors based on platelet function testing (PFT) in acute coronary syndrome (ACS) patients undergoing PCI. A decision model was developed to analyse the health economic effects of different strategies. PFT-guided treatment was compared with the three options of general clopidogrel, prasugrel or ticagrelor treatment. In the PFT arm, low responders to clopidogrel received prasugrel, while normal responders carried on with clopidogrel. The associated endpoints in the model were cardiovascular death, stent thrombosis and major bleeding. With a simulated cohort of 10,000 patients treated for one year, there were 93 less events in the PFT arm compared to general clopidogrel. In prasugrel and ticagrelor arms, 110 and 86 events were prevented compared to clopidogrel treatment, respectively. The total expected costs (including event costs, drug costs and PFT costs) for generic clopidogrel therapy were US$ 1,059/patient. In the PFT arm, total costs were US$ 1,494, while in the prasugrel and ticagrelor branches they were US$ 3,102 and US$ 3,771, respectively. The incremental-cost-effectiveness-ratio (ICER) was US$ 46,770 for PFT-guided therapy, US$ 185,783 for prasugrel and US$ 315,360 for ticagrelor. In this model-based analysis, a PFT-guided therapy may have fewer adverse outcomes than general treatment with clopidogrel and may be more cost-effective than prasugrel or ticagrelor treatment in ACS patients undergoing PCI.

  10. Unusual Physical and Chemical Properties of Ni in Ce1-xNixO2-y Oxides: Structural Characterization and Catalytic Activity for the Water Gas Shift Reaction

    SciTech Connect

    Rodriguez, J.A.; Barrio, L.; Kubacka, A.; Zhou, G.; Estrella, M.; Martınez-Arias, A.; Hanson, J.C.; Fernandez-Garcıa, M.

    2010-07-29

    The structural and electronic properties of Ce{sub 1-x}Ni{sub x}O{sub 2-y} nanosystems prepared by a reverse microemulsion method were characterized with synchrotron-based X-ray diffraction, X-ray absorption spectroscopy, Raman spectroscopy, and density functional calculations. The Ce{sub 1-x}Ni{sub x}O{sub 2-y} systems adopt a lattice with a fluorite-type structure with an acute local order where Ni displays a strongly distorted (oxygen) nearest-neighbor coordination and the presence of Ni atoms as first cation distances, pointing to the existence of Ni-O-Ni entities embedded into the ceria lattice. A Ni {leftrightarrow} Ce exchange within the CeO{sub 2} leads to a charge redistribution and the appearance of O vacancies. The Ni?O bonds in Ce{sub 1-x}Ni{sub x}O{sub 2-y} are more difficult to reduce than the bonds in pure NiO. The specific structural configuration of Ni inside the mixed-metal oxide leads to a unique catalyst with a high activity for the water gas shift (CO + H{sub 2}O {yields} H{sub 2} + CO{sub 2}) reaction and a simultaneous reduction of the methanation activity of nickel. Characterization results indicate that small particles of metallic Ni at the interface position of a ceria network may be the key for high WGS activity and that the formate?carbonate route is operative for the production of hydrogen.

  11. Unusual Physical and Chemical Properties of Ni in Ce1-xNixO2-y Oxides: Structural Characterization and Catalytic Activity for the Water Gas Shift Reaction

    SciTech Connect

    Barrio, L.; Kubacka, A; Zhou, G; Estrella, M; Martinez-Arias, A; Hanson, J; Fernandez-Garcia, M; Rodriguez, J

    2010-01-01

    The structural and electronic properties of Ce{sub 1-x}Ni{sub x}O{sub 2-y} nanosystems prepared by a reverse microemulsion method were characterized with synchrotron-based X-ray diffraction, X-ray absorption spectroscopy, Raman spectroscopy, and density functional calculations. The Ce{sub 1-x}Ni{sub x}O{sub 2-y} systems adopt a lattice with a fluorite-type structure with an acute local order where Ni displays a strongly distorted (oxygen) nearest-neighbor coordination and the presence of Ni atoms as first cation distances, pointing to the existence of Ni-O-Ni entities embedded into the ceria lattice. A Ni {leftrightarrow} Ce exchange within the CeO{sub 2} leads to a charge redistribution and the appearance of O vacancies. The Ni-O bonds in Ce{sub 1-x}Ni{sub x}O{sub 2-y} are more difficult to reduce than the bonds in pure NiO. The specific structural configuration of Ni inside the mixed-metal oxide leads to a unique catalyst with a high activity for the water gas shift (CO + H{sub 2}O {yields} H{sub 2} + CO{sub 2}) reaction and a simultaneous reduction of the methanation activity of nickel. Characterization results indicate that small particles of metallic Ni at the interface position of a ceria network may be the key for high WGS activity and that the formate-carbonate route is operative for the production of hydrogen.

  12. P2Y2 receptor activation inhibits the expression of the sodium-chloride cotransporter NCC in distal convoluted tubule cells.

    PubMed

    Gailly, P; Szutkowska, M; Olinger, E; Debaix, H; Seghers, F; Janas, S; Vallon, V; Devuyst, O

    2014-11-01

    Luminal nucleotide stimulation is known to reduce Na(+) transport in the distal nephron. Previous studies suggest that this mechanism may involve the thiazide-sensitive Na(+)-Cl(-) cotransporter (NCC), which plays an essential role in NaCl reabsorption in the cells lining the distal convoluted tubule (DCT). Here we show that stimulation of mouse DCT (mDCT) cells with ATP or UTP promoted Ca(2+) transients and decreased the expression of NCC at both mRNA and protein levels. Specific siRNA-mediated silencing of P2Y2 receptors almost completely abolished ATP/UTP-induced Ca(2+) transients and significantly reduced ATP/UTP-induced decrease of NCC expression. To test whether local variations in the intracellular Ca(2+) concentration ([Ca(2+)]i) may control NCC transcription, we overexpressed the Ca(2+)-binding protein parvalbumin selectively in the cytosol or in the nucleus of mDCT cells. The decrease in NCC mRNA upon nucleotide stimulation was abolished in cells overexpressing cytosolic PV but not in cells overexpressing either a nuclear-targeted PV or a mutated PV unable to bind Ca(2+). Using a firefly luciferase reporter gene strategy, we observed that the activity of NCC promoter region from -1 to -2,200 bp was not regulated by changes in [Ca(2+)]i. In contrast, high cytosolic calcium level induced instability of NCC mRNA. We conclude that in mDCT cells: (1) P2Y2 receptor is essential for the intracellular Ca(2+) signaling induced by ATP/UTP stimulation; (2) P2Y2-mediated increase of cytoplasmic Ca(2+) concentration down-regulates the expression of NCC; (3) the decrease of NCC expression occurs, at least in part, via destabilization of its mRNA.

  13. A Dilatometric Study of Sintering of Composite Ceramics Manufactured from Ultrafine Zro2(Y)-Al2O3 Powders Under Different Thermal-Temporal Firing Conditions

    NASA Astrophysics Data System (ADS)

    Surzhikov, A. P.; Frangulyan, T. S.; Ghyngazov, S. A.; Vasiliev, I. P.

    2014-07-01

    Using dilatometry, kinetic principles of sintering of composite ZrO2(Y)-Al2O3 ceramic material made from ultrafine powders synthesized at the Siberian Chemical Integrated Works are investigated. It is shown that under heating conditions, sintering of the composite ceramics under study occurs within a few stages that are closely related to the structural-phase transformations taking place in the composite powder mixture. At the firing temperatures Т > 1500 С and during long isothermal times, negative phenomena develop in the ceramic material, which give rise to its undesired dilatation and cracking in the course of cooling.

  14. Synthesis and structural analysis of Bi{sub 2-y}Sr{sub y}Ir{sub 2}O{sub 7}, a new pyrochlore solid solution

    SciTech Connect

    Cosio-Castaneda, Carlos; Mora, Pablo de la; Tavizon, Gustavo

    2011-05-15

    This paper presents a study of the synthesis and structural properties of the new pyrochlore-type Bi{sub 2-y}Sr{sub y}Ir{sub 2}O{sub 7} series. Ten compositions with 0.0{<=}y{<=}0.9 were prepared by solid-state reaction with thermal treatments at 873, 1073 and 1323 K under atmospheric pressure conditions. Structural refinements from X-ray powder diffraction data by the Rietveld method show that all compounds of the Bi{sub 2-y}Sr{sub y}Ir{sub 2}O{sub 7} solid solution crystallize in a {alpha}-pyrochlore structure. The main structural difference when bismuth is substituted by strontium concerns the x position of the O1 (x, (1/8), (1/8)). This substitution significantly increases the Bi/Sr-O1 distance and diminishes the Ir-O1 distance; this implies that the Ir-O1-Ir bond angle increases. With the Sr substitution, the IrO{sub 6} local configuration goes from a flattened trigonal antiprism, y<0.5, to an elongated one, y>0.5, passing through an octahedral array, y{approx}0.5. The electrical consequences of these structural changes observed in this system are qualitatively explained with electronic structure calculations, this behavior agrees very well with those observed in other pyrochlore systems A{sub 2}M{sub 2}O{sub 7} (A=rare earth cations or Tl{sup +}, Pb{sup 2+}, or Bi{sup 3+}, and M=Ru or Ir). -- Graphical abstract: Electrical behavior of the Bi{sub 2-y}Sr{sub y}Ir{sub 2}O{sub 7} solid solution. Display Omitted Highlights: {yields} Bi{sub 2-y}Sr{sub y}Ir{sub 2}O{sub 7} crystallizes in the {alpha}-pyrochlore structure. {yields} Local geometry of Ir goes from a flattened trigonal antiprism to an elongated one. {yields} Electrical resistivity increases with the Sr content in the solid solution. {yields} Electronic structure analysis relates resistivity with Sr disorder and bond strength.

  15. Increase of intracellular Ca2+ by P2Y but not P2X receptors in cultured cortical multipolar neurons of the rat.

    PubMed

    Fischer, Wolfgang; Nörenberg, Wolfgang; Franke, Heike; Schaefer, Michael; Illes, Peter

    2009-10-10

    The expression and functionality of P2X/P2Y receptor subtypes in multipolar nonpyramidal neurons of mixed cortical cell cultures were investigated by means of immunocytochemistry and fura-2 microfluorimetry. The morphological studies revealed that most of the neurons are immunoreactive for GABA and express a range of P2X/P2Y receptors, predominantly of the P2X(2,4,6) and P2Y(1,2) subtypes. P2X(1) and P2X(7) receptor immunoreactivity (IR) was found on thin axon-like processes and presynaptic structures, respectively. Application of ATP caused a small concentration-dependent increase in intracellular Ca2+ concentration ([Ca2+]i) in most investigated neurons, whereas only about the half of these cells responded to 2',3'-O-(benzoyl-4-benzoyl)-ATP (BzATP), ADPbetaS, 2MeSADP, or 2MeSATP and even fewer cells to UTP. In contrast, alpha,beta-meATP, UDP, and UDP-glucose failed to produce any [Ca2+]i signaling. The response to ATP itself was inhibited by pyridoxal-5'-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS), Reactive Blue 2, 2'-deoxy-N(6)-methyl adenosine 3',5'-diphosphate (MRS2179), and suramin (300 microM) as well as by a cyclopiazonic acid-induced depletion of intracellular Ca2+ stores. A Ca2+-free external medium tended to decrease the ATP-induced [Ca2+]i transients, although this action did not reach statistical significance. Various blockers of voltage-sensitive Ca2+ channels and the gap junction inhibitor carbenoxolone did not interfere with the effect of ATP, whereas a combination of the ionotropic glutamate receptor antagonists D(-)-2-amino-5-phosphonopentanoic acid (AP5) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) decreased it. Cross-desensitization experiments between ADPbetaS or UTP and ATP suggested that ATP acts on the one hand via P2Y(1,2) receptors and on the other hand by additional signaling mechanisms. These mechanisms may involve the release of glutamate (which in consequence activates ionotropic glutamate receptors) and the entry of Ca2

  16. Formation of superconducting Bi sub 2-y Pb sub y Sr sub 2 Ca sub 2 Cu sub 3 O sub x from coprecipitated oxalates

    SciTech Connect

    Bernhard, K.; Gritzner, G.; Wang, Xianzhong; Baeuerle, D. )

    1990-06-01

    The conditions for the coprecipitation of Bi{sup 3+}, Pb{sup 2+}, Ca{sup 2+} as oxalates are reported. These oxalates were used as precursors for the formation of Bi{sub 2-y}Pb{sub y}Sr{sub 2}Ca{sub 2}Cu{sub 3}O{sub x} superconducting ceramics. The behavior of the oxalates upon heat treatment was studied by thermogravimetry. Both the oxalates and the superconducting oxides were analyzed and characterized by atomic absorption spectroscopy and by X-ray diffraction.

  17. Role of the extracellular loops of G protein-coupled receptors in ligand recognition: a molecular modeling study of the human P2Y1 receptor.

    PubMed

    Moro, S; Hoffmann, C; Jacobson, K A

    1999-03-23

    The P2Y1 receptor is a G protein-coupled receptor (GPCR) and is stimulated by extracellular ADP and ATP. Site-directed mutagenesis of the three extracellular loops (ELs) of the human P2Y1 receptor indicates the existence of two essential disulfide bridges (Cys124 in EL1 and Cys202 in EL2; Cys42 in the N-terminal segment and Cys296 in EL3) and several specific ionic and H-bonding interactions (involving Glu209 and Arg287). Through molecular modeling and molecular dynamics simulations, an energetically sound conformational hypothesis for the receptor has been calculated that includes transmembrane (TM) domains (using the electron density map of rhodopsin as a template), extracellular loops, and a truncated N-terminal region. ATP may be docked in the receptor, both within the previously defined TM cleft and within two other regions of the receptor, termed meta-binding sites, defined by the extracellular loops. The first meta-binding site is located outside of the TM bundle, between EL2 and EL3, and the second higher energy site is positioned immediately underneath EL2. Binding at both the principal TM binding site and the lower energy meta-binding sites potentially affects the observed ligand potency. In meta-binding site I, the side chain of Glu209 (EL2) is within hydrogen-bonding distance (2.8 A) of the ribose O3', and Arg287 (EL3) coordinates both alpha- and beta-phosphates of the triphosphate chain, consistent with the insensitivity in potency of the 5'-monophosphate agonist, HT-AMP, to mutation of Arg287 to Lys. Moreover, the selective reduction in potency of 3'NH2-ATP in activating the E209R mutant receptor is consistent with the hypothesis of direct contact between EL2 and nucleotide ligands. Our findings support ATP binding to at least two distinct domains of the P2Y1 receptor, both outside and within the TM core. The two disulfide bridges present in the human P2Y1 receptor play a major role in the structure and stability of the receptor, to constrain the

  18. P2Y6 Receptors Require an Intact Cysteinyl Leukotriene Synthetic and Signaling System to Induce Survival and Activation of Mast Cells1

    PubMed Central

    Jiang, Yongfeng; Borrelli, Laura; Bacskai, Brian J.; Kanaoka, Yoshihide; Boyce, Joshua A.

    2008-01-01

    Cysteinyl leukotrienes (cys-LTs) induce inflammatory responses through type 1 (CysLT1R) and type 2 (CysLT2R) cys-LT receptors, and activate mast cells (MCs) in vitro. We previously demonstrated that cys-LTs cross-desensitized interleukin (IL)-4-primed primary human MCs (hMCs) to stimulation with the nucleotide uridine diphosphate (UDP). We now report that hMCs, mouse bone marrow-derived mast cells (mBMMCs), and the human MC line LAD2 all express UDP-selective P2Y6 receptors that cooperate with CysLT1R to promote cell survival and chemokine generation by a pathway involving reciprocal ligand-mediated cross-talk. LTD4, the most potent CysLT1R ligand, and UDP both induced phosphorylation of extracellular signal regulated kinase (ERK) and prolonged the survival of cytokine-starved hMCs and mBMMCs. ERK activation and cytoprotection in response to either ligand were attenuated by treatment of the cells with a selective P2Y6 receptor antagonist (MRS2578), which did not interfere with signaling through recombinant CysLT1R. Surprisingly, both UDP and LTD4-mediated ERK activation and cytoprotection were absent in mBMMCs lacking CysLT1R and the biosynthetic enzyme LTC4 synthase (LTC4S), implying a requirement for a cys-LT-mediated autocrine loop. In IL-4-primed LAD2 cells, LTD4 induced the generation of macrophage inflammatory protein 1β (MIP-1β) by IL-4-primed LAD2 cells, a response blocked by short hairpin RNA (shRNA)-mediated knockdown of CysLT1R or of P2Y6 receptors, but not of CysLT2R. Thus, CysLT1R and P2Y6 receptors, which are co-expressed with on many cell types of innate immunity, reciprocally amplify one another’s function in MCs through endogenous ligands. PMID:19124756

  19. A Combination of CDF and D0 limits on the branching ratio of B0(s)(d) ---> mu+ mu- decays

    SciTech Connect

    Bernhard, R.; Glenzinski, D.; Herndon, M.; Kamon, T.; Krutelyov, V.; Landsberg, G.; Lehner, F.; Lin, C.J.; Mrenna, S.; /Zurich U. /Fermilab /Wisconsin U., Madison /Texas A-M /Brown U.

    2005-08-01

    The authors combine the results of CDF and D0 searches for the rare decays B{sub s}{sup 0} {yields} {mu}{sup +}{mu}{sup -} and B{sub d}{sup 0} {yields} {mu}{sup +}{mu}{sup -}. The experiments use 364 pb{sup -1} and 300 pb{sup -1} of data respectively. The limits on the branching ratios are obtained by normalizing the estimated sensitivity to the decay B{sup +} {yields} J/{psi}K{sup +} taking into account the fragmentation ratios f{sub u}/f{sub s(d)}. The combined results exclude branching ratios of BR(B{sub s}{sup 0} {yields} {mu}{sup +}{mu}{sup -}) > 1.5 x 10{sup -7} and BR(B{sub d}{sup 0} {yields} {mu}{sup +}{mu}{sup -}) > 4.0 x 10{sup -8} at 95% confidence level. These are the most stringent limits on these decays at the present time.

  20. Non-LTE analysis of extremely helium-rich stars. The hot sdO stars LSE 153, 259 and 263

    NASA Technical Reports Server (NTRS)

    Husfeld, D.; Butler, K.; Heber, U.; Drilling, J. S.

    1989-01-01

    Results of a non-LTE fine analysis based mainly on high-resolution CASPEC spectra for three extremely helium-rich sdO stars are discussed in order to explain hydrogen deficiency in single stars. High temperature (Teff = 70,000 to 75,000 K) and a position in the log Teff - log g diagram were found close to the Eddington limit. Various abundance estimates are derived for hydrogen (upper limits only), carbon, nitrogen, and magnesium. Hydrogen is reduced to less than 10 percent by number in LSE 153 and LSE 263, and to less than 5 percent in LSE 259. The hydrogen deficiency is accompanied by nitrogen- and carbon-enrichment in LSE 153 and LSE 259 only. In LSE 263, carbon is depleted by about 1 dex. Stellar masses obtained by assuming that a core mass-luminosity relation holds for these stars, were found to be in the range 0.6-0.9 solar mass, yielding luminosities log L/L:solar = 3.7-4.5. Two of the program stars (LSE 153 and 259) appear to be possible successors of the R CrB and helium B stars, whereas the third star (LSE 263) displays a much lower carbon content in its photosphere making it an exceptional case among the known hydrogen deficient stars.

  1. Analysis of aquifer tests conducted in boreholes USW WT-10, UE-25 WT No. 12, and USW SD-7, 1995-96, Yucca Mountain, Nevada

    SciTech Connect

    O`Brien, G.M.

    1997-09-01

    Single-borehole aquifer tests were conducted in three boreholes in the Yucca Mountain area between March 1995 and January 1996 to obtain estimates of borehole specific capacity and aquifer transmissivity. Analysis of aquifer testing in borehole USW SD-7 also resulted in an estimate of reservoir volume. Aquifer-test data were analyzed with the Cooper and Jacob straight-line method, two modified Theis nonequilibrium equation solutions, and a modified reservoir-limit solution. The highest estimates of transmissivity were in borehole USW WT-10, completed in the Topopah Spring Tuff. Mean transmissivity, based on the results of three drawdown tests, was 1,600 meters squared per day. Mean specific capacity in borehole USW WT-10 after 5 hours of pumping was 1,100 meters squared per day, and was estimated to be 740 meters squared per day after 24 hours of pumping. Aquifer testing in borehole UE-25 WT No. 12 appeared to be significantly affected by well losses. A mean transmissivity of 7 meters squared per day was obtained on the basis of analysis of three drawdown tests in borehole UE-25 WT No. 12. Mean specific capacity in borehole UE-25 WT No. 12, after 24 hours of pumping, was 7 meters squared per day. Borehole UE-25 WT No. 12 seemed to be producing water from fractures that could provide only a limited amount of water to the borehole.

  2. The Fourier transform method and the SD-bar approach for the analytical and numerical treatment of multicenter overlap-like quantum similarity integrals

    SciTech Connect

    Safouhi, Hassan . E-mail: hassan.safouhi@ualberta.ca; Berlu, Lilian

    2006-07-20

    Molecular overlap-like quantum similarity measurements imply the evaluation of overlap integrals of two molecular electronic densities related by Dirac delta function. When the electronic densities are expanded over atomic orbitals using the usual LCAO-MO approach (linear combination of atomic orbitals), overlap-like quantum similarity integrals could be expressed in terms of four-center overlap integrals. It is shown that by introducing the Fourier transform of delta Dirac function in the integrals and using the Fourier transform approach combined with the so-called B functions, one can obtain analytic expressions of the integrals under consideration. These analytic expressions involve highly oscillatory semi-infinite spherical Bessel functions, which are the principal source of severe numerical and computational difficulties. In this work, we present a highly efficient algorithm for a fast and accurate numerical evaluation of these multicenter overlap-like quantum similarity integrals over Slater type functions. This algorithm is based on the SD-bar approach due to Safouhi. Recurrence formulae are used for a better control of the degree of accuracy and for a better stability of the algorithm. The numerical result section shows the efficiency of our algorithm, compared with the alternatives using the one-center two-range expansion method, which led to very complicated analytic expressions, the epsilon algorithm and the nonlinear D-bar transformation.

  3. Spectroscopy of Ar-SH and Ar-SD. II. Determination of the three-dimensional intermolecular potential-energy surface.

    PubMed

    Sumiyoshi, Yoshihiro; Endo, Yasuki

    2005-08-01

    All the pure rotational transitions reported in the previous studies [J. Chem. Phys. 113, 10121 (2000); J. Mol. Spectrosc. 222, 22 (2003)] and newly observed rotation-vibration transitions, P = 1/2 <-- 3/2, for Ar-SH and Ar-SD [J. Chem. Phys. (2005), the preceding paper] have been simultaneously analyzed to determine a new intermolecular potential-energy surface of Ar-SH in the ground state. A Schrodinger equation considering the three-dimensional freedom of motion for an atom-diatom complex in the Jacobi coordinate, R, theta, and r, was numerically solved to obtain energies of the rovibrational levels using the discrete variable representation method. A three-dimensional potential-energy surface is determined by a least-squares fitting with initial values of the parameters for the potential obtained by ab initio calculations at the RCCSD(T)/aug-cc-pVTZ level of theory. The potential